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Moral Theory, Frameworks, and the Language of Ethics and Business Since ethics is an integral part of management, it is vital for managers to become comfortable with the language of ethics, and to understand how it is inextricable from the language of business. Students will examine key theories of ethics and how they apply to management decision making. Excerpt UVA-E-0405 Rev. Nov. 8, 2017 Moral Theory, Frameworks, and the Language of Ethics and Business The Language of Ethics Since ethics is an integral part of management, it is vital for managers to become comfortable with the language of ethics, and to understand how it is inextricable from the language of business. We will examine key theories of ethics and how they apply to management decision making. These theories provide the content of ethics as we will use it in this course, as well as the terminology we can use to describe situations in ethical termsboth to see how ethics is part of the landscape and business and to provide resources for leaders to defend their choices. There is a rich history and diverse range of ethical theory. While there are a variety of ways to frame this vast array of research, we can categorize them in terms of four different traditions we will use in this class:... |
<gh_stars>0
import * as React from "react";
import { Modal, Input } from "antd";
import {
useOpenDashServices,
useTranslation,
useDashboard,
createInternalComponent,
} from "../../..";
interface Props {
open: boolean;
close: () => void;
onSave: (id: string) => void;
}
export const DashboardCreationModal = createInternalComponent<Props>(
function DashboardCreationModal({ open, close, onSave }) {
const t = useTranslation();
const { MonitoringService } = useOpenDashServices();
const [name, setName] = React.useState(undefined);
React.useEffect(() => {
setName(undefined);
}, [open]);
return (
<Modal
visible={open}
title={t("opendash:dashboards.create_modal_title")}
okText={t("opendash:ui.create")}
onOk={() => {
// @ts-ignore
MonitoringService.createDashboard({ name: name }).then((id) => {
if (onSave) {
onSave(id);
}
});
close();
}}
cancelText={t("opendash:ui.cancel")}
onCancel={(e) => close()}
okButtonProps={{ disabled: !name }}
>
<p>{t("opendash:dashboards.create_modal_description")}</p>
<Input
value={name}
onChange={(e) => setName(e.target.value)}
placeholder={t("opendash:dashboards.create_modal_placeholder")}
></Input>
</Modal>
);
}
);
|
# -*- coding: utf-8 -*-
# Generated by Django 1.11 on 2017-07-17 20:11
from __future__ import unicode_literals
from django.db import migrations
def noop(*args):
# This migration used to add permissions,
# which is now handled by the post_migrate signal
pass
class Migration(migrations.Migration):
dependencies = [
('osf', '0077_bannerimage_scheduledbanner'),
]
operations = [
migrations.RunPython(noop, noop),
]
|
/*
* $Id$
* $URL$
*
* ====================================================================
* Ikasan Enterprise Integration Platform
*
* Distributed under the Modified BSD License.
* Copyright notice: The copyright for this software and a full listing
* of individual contributors are as shown in the packaged copyright.txt
* file.
*
* All rights reserved.
*
* Redistribution and use in source and binary forms, with or without
* modification, are permitted provided that the following conditions are met:
*
* - Redistributions of source code must retain the above copyright notice,
* this list of conditions and the following disclaimer.
*
* - Redistributions in binary form must reproduce the above copyright notice,
* this list of conditions and the following disclaimer in the documentation
* and/or other materials provided with the distribution.
*
* - Neither the name of the ORGANIZATION nor the names of its contributors may
* be used to endorse or promote products derived from this software without
* specific prior written permission.
*
* THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS "AS IS"
* AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT LIMITED TO, THE
* IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE ARE
* DISCLAIMED. IN NO EVENT SHALL THE COPYRIGHT HOLDER OR CONTRIBUTORS BE LIABLE
* FOR ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL, EXEMPLARY, OR CONSEQUENTIAL
* DAMAGES (INCLUDING, BUT NOT LIMITED TO, PROCUREMENT OF SUBSTITUTE GOODS OR
* SERVICES; LOSS OF USE, DATA, OR PROFITS; OR BUSINESS INTERRUPTION) HOWEVER
* CAUSED AND ON ANY THEORY OF LIABILITY, WHETHER IN CONTRACT, STRICT LIABILITY,
* OR TORT (INCLUDING NEGLIGENCE OR OTHERWISE) ARISING IN ANY WAY OUT OF THE
* USE OF THIS SOFTWARE, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE.
* ====================================================================
*/
package org.ikasan.ootb.scheduled.model;
import org.ikasan.harvest.HarvestEvent;
import org.ikasan.spec.scheduled.ScheduledProcessEvent;
/**
* Scheduled Process Event defines the core event managed by the Scheduler Agent
* and reports schedule fire details and process execution details.
*
* @author Ikasan Development Team
*
*/
public class ScheduledProcessEventImpl implements ScheduledProcessEvent<Outcome>, HarvestEvent
{
private Long id;
private String agentName;
private String jobName;
private String jobGroup;
private String jobDescription;
private String commandLine;
private int returnCode;
private boolean successful;
private Outcome outcome;
private String resultOutput;
private String resultError;
private long pid;
private String user;
private long fireTime;
private long nextFireTime;
private long completionTime;
private boolean harvested;
private long harvestedDateTime;
public Long getId()
{
return id;
}
private void setId(Long id)
{
this.id = id;
}
@Override
public String getAgentName() {
return agentName;
}
@Override
public void setAgentName(String agentName) {
this.agentName = agentName;
}
@Override
public String getJobName() {
return jobName;
}
@Override
public void setJobName(String jobName) {
this.jobName = jobName;
}
@Override
public String getJobGroup() {
return jobGroup;
}
@Override
public void setJobGroup(String jobGroup) {
this.jobGroup = jobGroup;
}
@Override
public String getJobDescription() {
return this.jobDescription;
}
@Override
public void setJobDescription(String jobDescription) {
this.jobDescription = jobDescription;
}
@Override
public String getCommandLine() {
return commandLine;
}
@Override
public void setCommandLine(String commandLine) {
this.commandLine = commandLine;
}
@Override
public String getResultOutput() {
return resultOutput;
}
@Override
public void setResultOutput(String resultOutput) {
this.resultOutput = resultOutput;
}
@Override
public String getResultError() {
return resultError;
}
@Override
public void setResultError(String resultError) {
this.resultError = resultError;
}
@Override
public long getPid() {
return pid;
}
@Override
public void setPid(long pid) {
this.pid = pid;
}
@Override
public String getUser() {
return user;
}
@Override
public void setUser(String user) {
this.user = user;
}
@Override
public long getFireTime() {
return fireTime;
}
@Override
public void setFireTime(long fireTime) {
this.fireTime = fireTime;
}
@Override
public long getNextFireTime() {
return nextFireTime;
}
@Override
public void setNextFireTime(long nextFireTime) {
this.nextFireTime = nextFireTime;
}
@Override
public void setHarvested(boolean harvested) {
this.harvested = harvested;
}
public boolean isHarvested() {
return harvested;
}
public long getHarvestedDateTime() {
return harvestedDateTime;
}
public void setHarvestedDateTime(long harvestedDateTime) {
this.harvestedDateTime = harvestedDateTime;
}
@Override
public int getReturnCode()
{
return returnCode;
}
@Override
public void setReturnCode(int returnCode)
{
this.returnCode = returnCode;
}
@Override
public boolean isSuccessful()
{
return successful;
}
@Override
public void setSuccessful(boolean successful)
{
this.successful = successful;
}
@Override
public Outcome getOutcome()
{
return outcome;
}
@Override
public void setOutcome(Outcome outcome)
{
this.outcome = outcome;
}
@Override
public long getCompletionTime()
{
return completionTime;
}
@Override
public void setCompletionTime(long completionTime)
{
this.completionTime = completionTime;
}
@Override
public String toString()
{
return "ScheduledProcessEventImpl{" +
"id=" + id +
", agentName='" + agentName + '\'' +
", jobName='" + jobName + '\'' +
", jobGroup='" + jobGroup + '\'' +
", jobDescription='" + jobDescription + '\'' +
", commandLine='" + commandLine + '\'' +
", returnCode=" + returnCode +
", successful=" + successful +
", outcome=" + outcome.name() +
", resultOutput='" + resultOutput + '\'' +
", resultError='" + resultError + '\'' +
", pid=" + pid +
", user='" + user + '\'' +
", fireTime=" + fireTime +
", nextFireTime=" + nextFireTime +
", completionTime=" + completionTime +
", harvested=" + harvested +
", harvestedDateTime=" + harvestedDateTime +
'}';
}
}
|
<reponame>hemendra-sharma/ComicReader
/*
* Copyright (c) 2018 <NAME>
*
* Licensed under the Apache License, Version 2.0 (the "License");
* you may not use this file except in compliance with the License.
* You may obtain a copy of the License at
*
* http://www.apache.org/licenses/LICENSE-2.0
*
* Unless required by applicable law or agreed to in writing, software
* distributed under the License is distributed on an "AS IS" BASIS,
* WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
* See the License for the specific language governing permissions and
* limitations under the License.
*/
package com.hemendra.comicreader.model.source.images.local;
import android.graphics.Bitmap;
import android.support.annotation.NonNull;
import com.hemendra.comicreader.model.utils.CustomAsyncTask;
import com.hemendra.comicreader.view.ImageAndViewHolder;
/**
* A worker thread to read from local databse and decode the data into Bitmap asynchronously.
*/
public class LocalImageLoader extends CustomAsyncTask<Void,Void,Bitmap> {
private LocalImagesDataSource dataSource;
public String imgUrl;
private ImageAndViewHolder holder;
public long startedAt = 0;
LocalImageLoader(@NonNull LocalImagesDataSource dataSource,
String imgUrl, ImageAndViewHolder holder) {
this.dataSource = dataSource;
this.imgUrl = imgUrl;
this.holder = holder;
}
@Override
protected void onPreExecute() {
startedAt = System.currentTimeMillis();
}
@Override
protected Bitmap doInBackground(Void... params) {
return dataSource.getImageFromCache(imgUrl);
}
@Override
protected void onPostExecute(Bitmap bitmap) {
if(bitmap != null) {
holder.setImage(bitmap);
dataSource.onImageDownloaded(imgUrl, bitmap, holder.isCover(), holder.isPage());
} else
dataSource.onFailedToDownloadImage(imgUrl, holder);
}
}
|
<reponame>opro1801/Interndemo-backend
/* eslint-disable prettier/prettier */
export enum TaskStatus {
IN_PROGRESSS = 'IN_PROGRESS',
COMPLETE = 'COMPLETE',
} |
package main
import (
"log"
"github.com/northvolt/norrskenunsolved19/api/neo4j"
)
func main() {
nj := neo4j.Neo4j{
Username: "neo4j",
Password: "password",
}
_, err := nj.NewSession()
if err != nil {
log.Fatal(err)
}
defer nj.Close()
if err := ImportNodes(nj); err != nil {
log.Fatal(err)
}
log.Print("import edges")
if err := ImportEdges(nj); err != nil {
log.Fatal(err)
}
}
|
Hazardous environmental factors enhance impairment of liver function in HBV and HCV hepatitis. Hepatitis B virus (HBV) and hepatitis C virus (HCV) often cause chronic liver disease. We hypothesized that environmental factors adversely impact the liver function in workers with these types of hepatitis. We used liver function tests including aspartate aminotransferase, alanine aminotransferase, and g -glutamyltransferase to evaluate whether hazardous work conditions increase the incidence of chronic liver disease among HBV and HCV infected workers. Organic solvent, night work, visual display terminals, dust, lead, vibrations, and ionizing radiation all led to increased impairment of liver function in patients with hepatitis as compared to the control group that were not exposed to such agents. Therefore, hazardous working conditions have to be carefully considered in the progress of chronic liver disease in workers infected with HBV and HCV. |
package authManager;
import auth.Auth;
import java.util.Collection;
public interface AuthManager {
void setUsers(Collection<Auth> users);
boolean checkAuth(Auth auth);
void addOnlineUser(Auth auth);
void removeOnlineUser(Auth auth);
boolean isOnline(Auth auth);
void addUser(Auth auth);
}
|
Tar Spot: An Understudied Disease Threatening Corn Production in the Americas. Tar spot of corn has been a major foliar disease in several Latin American countries since 1904. In 2015, tar spot was first documented in the United States and has led to significant yield losses of approximately 4.5 million t. Tar spot is caused by an obligate pathogen, Phyllachora maydis, and thus requires a living host to grow and reproduce. Due to its obligate nature, biological and epidemiological studies are limited and impact of disease in corn production has been understudied. Here we present the current literature and gaps in knowledge of tar spot of corn in the Americas, its etiology, distribution, impact and known management strategies as a resource for understanding the pathosystem. This will in tern guide current and future research and aid in the development of effective management strategies for this disease. |
package com.haroldstudios.infoheads.elements;
import com.haroldstudios.infoheads.InfoHeads;
import org.bukkit.entity.Player;
import org.bukkit.event.player.PlayerInteractEvent;
import org.jetbrains.annotations.NotNull;
public final class ConsoleCommandElement extends Element {
private String command;
public ConsoleCommandElement(final String command) {
this.command = command;
}
/**
* Gets command in String form
* @return Command
*/
public String getCommand() {
return command;
}
/**
* Sets the command
* @param command Command to set without /
*/
public void setCommand(String command) {
this.command = command;
}
@Override
public void performAction(@NotNull Player player, PlayerInteractEvent event) {
InfoHeads.getInstance().getServer().dispatchCommand(InfoHeads.getInstance().getServer().getConsoleSender(), removePlaceHolders(command, player, event));
}
@Override
public Object getContent() {
return command;
}
@Override
public InfoHeadType getType() {
return InfoHeadType.CONSOLE_COMMAND;
}
}
|
The SABRE experiment The dark matter interpretation of the DAMA/LIBRA annual modulation signal represents a long-standing open question in astroparticle physics. The SABRE experiment aims to test such claim, bringing the same detection technique to an unprecedented sensitivity. Based on ultra-low background NaI(Tl) scintillating crystals like DAMA, SABRE features a liquid scintillator Veto system, surrounding the main target, and it will deploy twin detectors: one in the Northern hemisphere at Laboratori Nazionali del Gran Sasso (LNGS), Italy and the other in the Stawell Underground Physics Laboratory (SUPL), Australia, first laboratory of this kind in the Southern hemisphere. The first very-high-purity crystal produced by the collaboration was shipped to LNGS in 2019 for characterization. It features a potassium contamination, measured by mass spectroscopy, of the order of 4 ppb, about three times lower than DAMA/LIBRA crystals. The first phase of the SABRE experiment is a Proof-of-Principle (PoP) detector featuring one crystal and a liquid scintillator Veto, at LNGS. This contribution will present the results of the stand-alone characterization of the first SABRE high-purity crystal, as well as the status of the PoP detector, commissioned early in the summer of 2020. |
#pragma once
#include "Base/BaseTypes.h"
#include "Reflection/Reflection.h"
#include "Scene3D/Systems/TransformSystem.h"
#include "Entity/Component.h"
#include "Scene3D/SceneFile/SerializationContext.h"
namespace DAVA
{
class Entity;
class TransformComponent : public Component
{
public:
inline Matrix4* GetWorldTransformPtr();
inline const Matrix4& GetWorldTransform();
inline const Matrix4& GetLocalTransform();
Matrix4& ModifyLocalTransform();
void SetWorldTransform(const Matrix4* transform);
void SetLocalTransform(const Matrix4* transform);
void SetParent(Entity* node);
Component* Clone(Entity* toEntity) override;
void Serialize(KeyedArchive* archive, SerializationContext* serializationContext) override;
void Deserialize(KeyedArchive* archive, SerializationContext* serializationContext) override;
private:
Matrix4 localMatrix = Matrix4::IDENTITY;
Matrix4 worldMatrix = Matrix4::IDENTITY;
Matrix4* parentMatrix = nullptr;
Entity* parent = nullptr; //Entity::parent should be removed
friend class TransformSystem;
DAVA_VIRTUAL_REFLECTION(TransformComponent, Component);
};
const Matrix4& TransformComponent::GetWorldTransform()
{
return worldMatrix;
}
const Matrix4& TransformComponent::GetLocalTransform()
{
return localMatrix;
}
Matrix4* TransformComponent::GetWorldTransformPtr()
{
return &worldMatrix;
}
}
|
If you’re looking for a prosperous European country to emulate, don’t look to the high-tax social democracies of Scandinavia. Check out Switzerland, instead.
Many leftists hail Scandinavia as a socialist haven that demonstrates the inferiority of capitalism. Presidential candidate Bernie Sanders recently declared that the United States ought to emulate Scandinavian countries because they provide education and healthcare “for free.”
There are many problems with this line of thinking. For one, it is fallacious to claim that a system that works for homogenous countries like Finland and Norway would also succeed in a massive, diverse country such as the United States. For another, it is incorrect to refer to Scandinavian countries as “socialist,” given that no Scandinavian countries nationalize their means of production.
Scandinavian countries—specifically, Norway, Sweden, Denmark, and Finland—are perceived as socialist because their citizens pay very high income taxes. However, these countries still suffer from many of the social and economic ills that socialism is supposed to prevent. Additionally, the United States taxes wealthy Americans at much higher rates than Scandinavian countries tax their similarly wealthy citizens, yet leftists such as Sanders are still displeased with how our tax system is organized. Finally, another European country defies the liberal “Scandinavian socialist success” narrative so completely that it demonstrates why capitalism is the best economic model in existence.
Scandinavian Countries Aren’t Socialist
One of the reasons it is incorrect to refer to countries like Sweden as “socialist” is that these countries were once far more progressive than they are now. The Economist says Sweden was once a “tax-and-spend” economy in which author Astrid Lindgren (of “Pippi Longstocking” fame) was required to pay more than 100 percent of her income in taxes. This heavily progressive tax rate stunted economic growth, and Sweden fell from the fourth-wealthiest country in the world to the fourteenth-wealthiest country in just 23 years.
The electoral success of moderate and conservative parties throughout Scandinavia is at once a rejection of progressive policies and an endorsement of free markets.
The government recognized the cause of the trouble and instituted several capitalist reforms to resuscitate Sweden’s economy. According to The Economist, following the success of Sweden’s relatively right-leaning Moderate party, “Swedish GDP is growing strongly, and unemployment is falling. The budget is heading into surplus next year.” The article notes that many Swedes support moderate and right-wing reforms: “The centre-right has made welfare payments less generous, cut taxes for the lower-paid and trimmed the numbers on sickness benefit. Voters seem to approve.” The electoral success of moderate and conservative parties throughout Scandinavia is at once a rejection of progressive policies and an endorsement of free markets in what some consider to be the most progressive region in the world.
In some ways, Sweden is now less progressive than the United States. Harvard professor Gregory Mankiw writes that the wealthiest decile of Swedes carries 26.7 percent of the tax burden. In The United States, the figure is a whopping 45.1 percent. Additionally, wealth inequality is more pronounced in Scandinavian countries than it is in the United States. In Sweden, Denmark, Finland, and Norway, the top decile of earners own between 65 and 69 percent of the country’s total wealth, an astonishing figure. Sanders is apparently unaware of this reality, given that one of his primary reasons for praising Scandinavia was their low levels of wealth inequality.
Scandinavia Has High Taxes and High Personal Debt
Despite their rates of wealth inequality, it is true that the citizens of Denmark, Sweden, Norway, and Finland devote more of their income to taxes than American citizens do. According to the Organization for Economic Cooperation and Development, the average American spends 9.8 percent of his income on taxes; Swedes spend 12.3 percent, Danes 26.4 percent, Norwegians 10 percent, and Finns 12.9 percent. Perhaps because of these measures, government debt is less of a problem in Scandinavia than it is in the United States.
Scandinavia’s progressive tax systems fail to protect their citizens from staggering personal debt.
However, Scandinavian rates of household debt are astronomically high. OECD figures also show the average Dane has a household debt equal to 310 percent of his disposable income; the number is 173 percent for Swedes. In America, the average is 114 percent. While America’s economic problems cannot be ignored, it is noteworthy that Scandinavia’s progressive tax systems fail to protect their citizens from staggering personal debt.
Finally, and perhaps most surprisingly, Sweden’s public education system is ranked lower than that of the United States. According to the OECD, Sweden ranks 30 of 37 in math and 24 of 37 in reading. The United States, meanwhile, is 27 of 37 in math and 25 of 37 in reading. Norway and Denmark are both ranked better than the United States, but not by much. These realities destroy the pervasive myth that “socialist” Scandinavian schools are the best in the world. Despite what Sanders might believe, educational institutions in Sweden are not superior to those in the United States. Sweden’s high tax rates have not ensured educational excellence, and many Swedes likely pay the equivalent of college tuition for their children in the form of taxes anyhow.
The Non-Socialist European Success Story: Switzerland
This evidence is quite as compelling as the success story that is Switzerland. Unlike its neighbors, Switzerland is one of the most capitalist countries in existence. Its citizens only pay 8.6 percent of their personal incomes in taxes annually, and its economic climate is particularly well-suited to entrepreneurship. The Huffington Post writes that 99 percent of Switzerland’s economy is made up of small and medium-sized enterprises, which also employ three-quarters of the country’s workforce.
Many leftists extol the limited successes of Sweden and Finland without ever acknowledging Switzerland.
Switzerland is ranked best in the world on many categories related to economic development, including “innovation, on-the-job staff training, attracting talent from elsewhere, and for government-provided training.” Ultimately, The Huffington Post claims, “Switzerland is home to one of the world’s most thriving economies and also one of the happiest populations on the globe.” Many leftists extol the limited successes of Sweden and Finland without ever acknowledging Switzerland, although it outperforms much of Europe in various economic and social metrics.
Although it is very capitalist, Switzerland boasts many of the advantages that socialist Scandinavian states are supposed to claim exclusively. Switzerland’s unemployment rate is just 4.5 percent, which is one of the lowest rates in the world. The country’s poverty rate is similarly low (XLS). Those who immigrate to Switzerland have an average employment rate of 76 percent, which is much higher than the European average of 62 percent.
Furthermore, the Swiss educational system is ranked third in the world by the OECD. Only Korea and Japan are ranked higher, which means Switzerland’s educational system is the best in the Western world. Many claim this distinction belongs to Finland, but Finnish schools are in fact ranked 10/37 in math and 4/37 in reading.
Additionally, income inequality and debt are both quite low in Switzerland. This reality persists although Switzerland’s wealthy have the lowest tax burden in the world; the richest decile in the country pays only 20.9 percent of the country’s taxes. Remarkably, even though the tax burden on the wealthy is minimal, Switzerland’s national debt as a percentage of its gross domestic product is lower than Finland’s, Sweden’s, and Denmark’s.
Switzerland is the closest to “paradise” of any European country, yet it remains one of the most capitalist economies on Earth. Its success is a powerful antidote to socialist claims about the benefits of progressive taxation, and all but destroys the assumption that Scandinavia as a bastion of socialism shows that only collectivism can produce success.
Regardless of the facts presented here, socialists like Sanders are sure to continue citing Scandinavia to support their narratives. If you happen to encounter such a person in real life, however, consider reading them this from The Economist: “Yet three deeper factors should give Social Democrats everywhere pause for thought. The first is that [Swedish] voters seem to value competent government above ideology.” Perhaps it is time for Americans to do the same.
This article originally referred to Switzerland as part of Scandinavia – it has been corrected. |
Single-dose del Nido cardioplegia used in adult minimally invasive valve surgery. Background To analyze the protective effect of single-dose del Nido cardioplegia (DNC) in adult minimally invasive valve surgery. Methods From January to December 2017, 165 consecutive adult patients who underwent minimally invasive valve surgery by the same team of surgeons were divided into two cohorts based on the type of cardioplegia administered during surgery: (I) single-dose DNC (DNC group (n=76, male 41, female 35) used in patients from May to December, 2017 and (II) intermittent standard 4:1 blood cardioplegia based on St.Thomas solution (SBC group, n=89, male 45, female 44) used in patients from January to April, 2017. Preoperative baseline demographics, preoperative comorbidities, operative variables, postoperative complications, and patient outcomes were collected and compared between the two groups. Results Preoperative characteristics were shown to be similar between the two groups before and after propensity matching. Patients in the DNC group required a significantly lower volume of cardioplegia. The volume of ultrafiltration in the DNC group was substantially higher than that in the SBC group. The spontaneous return of heartbeat rate in the DNC group was considerably higher than that in the SBC group (97.0% vs. 78.8%, P=0.006). The Euroscore II in the DNC group was markedly lower than that in the SBC group (2.00 vs. 3.00, P<0.05). The level of blood urea nitrogen (BUN) in the DNC group was significantly lower than that in the SBC group (6.20 vs. 6.95, P<0.05). There were no differences in surgery procedure, cross-clamp time, bypass time, Apache score, troponin T (cTnT), brain natriuretic peptide (BNP), liver and renal function, postoperative complications or patient outcomes between two groups. Regression analysis showed that cTnT increased with the prolongation of myocardial ischemia time, and was closely related to the type of operation, but had no significant correlation with the type of cardioplegia. Conclusions In our initial experience, single-dose DNC in adult minimally invasive valve surgery in which the cross-clamp time was mostly less than 90 min, achieved equivalent myocardial protection and clinical outcomes when compared with standard whole blood cardioplegia. In addition, single-dose DNC made the minimally invasive valve surgery procedure progress in a smoother and more convenient fashion. |
<reponame>ACS106129/toxic-gas-detector
#pragma once
#include "pitches.h"
enum Song
{
CuffinDance
};
// about notes, followed by a duration and a pitch
// prefix note durations: 4 = quarter note, 8 = eighth note, etc.:
// suffix note pitches
namespace cuda
{
static const int BLOCK_SIZE = 128;
static const uint16_t MELODY[] PROGMEM = {
4, NOTE_G4, 4, NOTE_G4, 4, NOTE_G4, 4, NOTE_G4, 4, NOTE_G4, 4, NOTE_G4, 4, NOTE_G4, 4, NOTE_G4,
4, NOTE_G4, 4, NOTE_G4, 4, NOTE_G4, 4, NOTE_G4, 4, NOTE_G4, 4, NOTE_G4, 4, NOTE_G4, 4, NOTE_G4,
4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4,
4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4,
4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_D5, 4, NOTE_D5, 4, NOTE_D5, 4, NOTE_D5,
4, NOTE_C5, 4, NOTE_C5, 4, NOTE_C5, 4, NOTE_C5, 4, NOTE_F5, 4, NOTE_F5, 4, NOTE_F5, 4, NOTE_F5,
4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5,
4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_C5, 4, NOTE_AS4, 4, NOTE_A4, 4, NOTE_F4,
4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_D5, 4, NOTE_C5, 4, REST, 4, NOTE_AS4, 4, REST,
4, NOTE_A4, 4, REST, 4, NOTE_A4, 4, NOTE_A4, 4, NOTE_C5, 4, REST, 4, NOTE_AS4, 4, NOTE_A4,
4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5,
4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5,
4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_D5, 4, NOTE_C5, 4, REST, 4, NOTE_AS4, 4, REST,
4, NOTE_A4, 4, REST, 4, NOTE_A4, 4, NOTE_A4, 4, NOTE_C5, 4, REST, 4, NOTE_AS4, 4, NOTE_A4,
4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5,
4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5,
4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_D5, 4, NOTE_C5, 4, REST, 4, NOTE_AS4, 4, REST,
4, NOTE_A4, 4, REST, 4, NOTE_A4, 4, NOTE_A4, 4, NOTE_C5, 4, REST, 4, NOTE_AS4, 4, NOTE_A4,
4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5,
4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5,
4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_D5, 4, NOTE_D5, 4, NOTE_D5, 4, NOTE_D5,
4, NOTE_C5, 4, NOTE_C5, 4, NOTE_C5, 4, NOTE_C5, 4, NOTE_F5, 4, NOTE_F5, 4, NOTE_F5, 4, NOTE_F5,
4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5,
4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_C5, 4, NOTE_AS4, 4, NOTE_A4, 4, NOTE_F4,
4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_D5, 4, NOTE_C5, 4, REST, 4, NOTE_AS4, 4, REST,
4, NOTE_A4, 4, REST, 4, NOTE_A4, 4, NOTE_A4, 4, NOTE_C5, 4, REST, 4, NOTE_AS4, 4, NOTE_A4,
4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_AS4, 4, NOTE_A5, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5,
4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_AS4, 4, NOTE_A5, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5,
4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_D5, 4, NOTE_C5, 4, REST, 4, NOTE_AS4, 4, REST,
4, NOTE_A4, 4, REST, 4, NOTE_A4, 4, NOTE_A4, 4, NOTE_C5, 4, REST, 4, NOTE_AS4, 4, NOTE_A4,
4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_AS4, 4, NOTE_A5, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5,
4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_AS4, 4, NOTE_A5, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5,
4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_D5, 4, NOTE_C5, 4, REST, 4, NOTE_AS4, 4, REST,
4, NOTE_A4, 4, REST, 4, NOTE_A4, 4, NOTE_A4, 4, NOTE_C5, 4, REST, 4, NOTE_AS4, 4, NOTE_A4,
4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_AS4, 4, NOTE_A5, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5,
4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_AS4, 4, NOTE_A5, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5,
4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_D5, 4, NOTE_D5, 4, NOTE_D5, 4, NOTE_D5,
4, NOTE_C5, 4, NOTE_C5, 4, NOTE_C5, 4, NOTE_C5, 4, NOTE_F5, 4, NOTE_F5, 4, NOTE_F5, 4, NOTE_F5,
4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5,
4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5,
32, NOTE_G5, 32, NOTE_G5, 32, NOTE_G5, 32, NOTE_G5, 4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_D5,
4, NOTE_C5, 4, REST, 4, NOTE_AS4, 4, REST, 4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_D5,
4, NOTE_C5, 4, REST, 4, NOTE_AS4, 4, REST, 4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_D5,
4, NOTE_C5, 4, REST, 4, NOTE_AS4, 4, REST, 4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_D5,
4, NOTE_C5, 4, REST, 4, NOTE_AS4, 4, REST, 4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_D5,
4, NOTE_C5, 4, REST, 4, NOTE_AS4, 4, REST, 4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_D5,
4, NOTE_C5, 4, REST, 4, NOTE_AS4, 4, REST, 4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_D5,
4, NOTE_C5, 4, REST, 4, NOTE_AS4, 4, REST, 4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_AS5,
4, NOTE_A5, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5, 32, NOTE_AS4, 32, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4,
4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4,
4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4,
4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_D5, 4, NOTE_D5, 4, NOTE_D5, 4, NOTE_D5, 4, NOTE_C5, 4, NOTE_C5,
4, NOTE_C5, 4, NOTE_C5, 4, NOTE_F5, 4, NOTE_F5, 4, NOTE_F5, 4, NOTE_F5, 4, NOTE_G5, 4, NOTE_G5,
4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5,
4, NOTE_G5, 4, NOTE_G5, 4, NOTE_C5, 4, NOTE_AS4, 4, NOTE_A4, 4, NOTE_F4, 4, NOTE_G4, 4, REST,
4, NOTE_G4, 4, NOTE_D5, 4, NOTE_C5, 4, REST, 4, NOTE_AS4, 4, REST, 4, NOTE_A4, 4, REST,
4, NOTE_A4, 4, NOTE_A4, 4, NOTE_C5, 4, REST, 4, NOTE_AS4, 4, NOTE_A4, 4, NOTE_G4, 4, REST,
4, NOTE_G4, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5, 4, NOTE_G4, 4, REST,
4, NOTE_G4, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5, 4, NOTE_G4, 4, REST,
4, NOTE_G4, 4, NOTE_D5, 4, NOTE_C5, 4, REST, 4, NOTE_AS4, 4, REST, 4, NOTE_A4, 4, REST,
4, NOTE_A4, 4, NOTE_A4, 4, NOTE_C5, 4, REST, 4, NOTE_AS4, 4, NOTE_A4, 4, NOTE_G4, 4, REST,
4, NOTE_G4, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5, 4, NOTE_G4, 4, REST,
4, NOTE_G4, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5, 4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_D5,
4, NOTE_C5, 4, REST, 4, NOTE_AS4, 4, REST, 4, NOTE_A4, 4, REST, 4, NOTE_A4, 4, NOTE_A4,
4, NOTE_C5, 4, REST, 4, NOTE_AS4, 4, NOTE_A4, 4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_AS5,
4, NOTE_A5, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5, 4, NOTE_G4, 4, REST, 4, NOTE_G4, 4, NOTE_AS5,
4, NOTE_A5, 4, NOTE_AS5, 4, NOTE_A5, 4, NOTE_AS5, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4, 4, NOTE_AS4,
4, NOTE_D5, 4, NOTE_D5, 4, NOTE_D5, 4, NOTE_D5, 4, NOTE_C5, 4, NOTE_C5, 4, NOTE_C5, 4, NOTE_C5,
4, NOTE_F5, 4, NOTE_F5, 4, NOTE_F5, 4, NOTE_F5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5,
4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5,
4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, 4, NOTE_G5, NOTE_END};
static const uint16_t MELODY_SIZE = sizeof(MELODY) / sizeof(MELODY[0]);
} // namespace cuda
|
Current perspectives on the diagnosis and management of fatigue in multiple sclerosis ABSTRACT Introduction Fatigue is a common and debilitating symptom among multiple sclerosis (MS) patients with a prevalence up to 81% and with a considerable impact on quality of life. However, its subjective nature makes it difficult to define and quantify in clinical practice. Research aimed at a more precise definition and knowledge of this construct is thus continuously growing. Areas covered This review summarizes the most relevant updates available on PubMed up to 1 July 2022 regarding: the assessment methods that aim to measure the concept of fatigue (as opposed to fatigability), the possible treatment pathways currently available to clinicians, interconnection with the pathophysiological substrates and with the common comorbidities of MS, such as depression and mood disorders. Expert opinion The in-depth study of fatigue can help to better understand its actual impact on MS patients and can stimulate clinicians toward a more valid approach, through a targeted analysis of this symptom. Considering fatigue from a multidimensional perspective allows the use of patient-tailored methods for its identification and subsequent treatment by different professional figures. Better identification of methods and treatment pathways would reduce the extremely negative impact of fatigue on MS patients quality of life. |
Focused ion beam in-situ cross sectioning and metrology in lithography We demonstrate an approach to cross-section and measure sub- 0.25 micrometer photoresist profiles in both a manual and an automated fashion. This approach includes the use of a focused ion beam (FIB) system to cut small trenches through photoresist lines, leaving a clean, vertical face to measure. We demonstrate the advantage of using this process over existing techniques in the semiconductor industry. A FIB can locally cross-section the photoresist, resulting in a side- wall that is comparable to that of a mechanical cleave. It can then measure the profile of the photoresist at multiple points using a 5 nm gallium probe. The system accomplishes the entire process inside one vacuum chamber with a limited number of steps. In contrast, when using a SEM to measure profiles, the sample must be mechanically cleaved outside of the vacuum chamber, potentially destroying the entire part and leaving a slightly distorted viewing face. Also, a SEM probe can cause swelling of the photoresist due to higher currents and penetration depths than a FIB probe and must therefore be used at low accelerating voltages. When operated at these low accelerating voltages, the SEM has degraded resolution with a spot size near 10 nm. A scanning probe microscope (SPM), on the other hand, can non-destructively measure profiles, but it is slow and less automated than the FIB or SEM. Unlike a FIB, the SPM lacks the ability to image the material transition directly beneath the photoresist. We also address concerns of sample damage, gallium contamination, and image quality. |
import asyncio
import logging
import signal
import ssl
import threading
from typing import Any, Awaitable, Callable, Coroutine, Dict, List, Optional, Set
from rap.common import event
from rap.common.asyncio_helper import Deadline
from rap.common.cache import Cache
from rap.common.collect_statistics import WindowStatistics
from rap.common.conn import CloseConnException, ServerConnection
from rap.common.exceptions import ServerError
from rap.common.signal_broadcast import add_signal_handler, remove_signal_handler
from rap.common.snowflake import async_get_snowflake_id
from rap.common.types import BASE_MSG_TYPE, READER_TYPE, WRITER_TYPE
from rap.common.utils import EventEnum, RapFunc
from rap.server.model import Request, Response
from rap.server.plugin.middleware.base import BaseConnMiddleware, BaseMiddleware
from rap.server.plugin.processor.base import BaseProcessor
from rap.server.receiver import Receiver
from rap.server.registry import FuncModel, RegistryManager
from rap.server.sender import Sender
from rap.server.types import SERVER_EVENT_FN
__all__ = ["Server"]
logger: logging.Logger = logging.getLogger(__name__)
class Server(object):
def __init__(
self,
server_name: str,
host: str = "localhost",
port: int = 9000,
send_timeout: int = 9,
keep_alive: int = 1200,
run_timeout: int = 9,
ping_fail_cnt: int = 2,
ping_sleep_time: int = 60,
backlog: int = 1024,
close_timeout: int = 9,
ssl_crt_path: Optional[str] = None,
ssl_key_path: Optional[str] = None,
pack_param: Optional[dict] = None,
unpack_param: Optional[dict] = None,
middleware_list: List[BaseMiddleware] = None,
processor_list: List[BaseProcessor] = None,
call_func_permission_fn: Optional[Callable[[Request], Awaitable[FuncModel]]] = None,
window_statistics: Optional[WindowStatistics] = None,
cache_interval: Optional[float] = None,
):
"""
:param server_name: server name
:param host: listen host
:param port: listen port
:param send_timeout: send msg timeout
:param keep_alive: conn keep_alive time
:param run_timeout: Maximum execution time per call
:param ping_fail_cnt: When ping fails continuously and exceeds this value, conn will be disconnected
:param ping_sleep_time: ping message interval time
:param backlog: server backlog
:param close_timeout: The maximum time to wait for conn to process messages when shutting down the service
:param ssl_crt_path: ssl crt path
:param ssl_key_path: ssl key path
:param pack_param: msgpack.Pack param
:param unpack_param: msgpack.UnPack param
:param middleware_list: Server middleware list
:param processor_list: Server processor list
:param call_func_permission_fn: Check the permission to call the function
:param window_statistics: Server window state
:param cache_interval: Server cache interval seconds to clean up expired data
"""
self.server_name: str = server_name
self.host: str = host
self.port: int = port
self._send_timeout: int = send_timeout
self._run_timeout: int = run_timeout
self._close_timeout: int = close_timeout
self._keep_alive: int = keep_alive
self._backlog: int = backlog
self._ping_fail_cnt: int = ping_fail_cnt
self._ping_sleep_time: int = ping_sleep_time
self._server: Optional[asyncio.AbstractServer] = None
self._connected_set: Set[ServerConnection] = set()
self._run_event: asyncio.Event = asyncio.Event()
self._run_event.set()
self._pack_param: Optional[dict] = pack_param
self._unpack_param: Optional[dict] = unpack_param
self._ssl_context: Optional[ssl.SSLContext] = None
if ssl_crt_path and ssl_key_path:
self._ssl_context = ssl.create_default_context(ssl.Purpose.CLIENT_AUTH)
self._ssl_context.check_hostname = False
self._ssl_context.load_cert_chain(ssl_crt_path, ssl_key_path)
self._middleware_list: List[BaseMiddleware] = []
self._processor_list: List[BaseProcessor] = []
self._server_event_dict: Dict[EventEnum, List[SERVER_EVENT_FN]] = {
value: [] for value in EventEnum.__members__.values()
}
self._depend_set: Set[Any] = set() # Check whether any components have been re-introduced
if middleware_list:
self.load_middleware(middleware_list)
if processor_list:
self.load_processor(processor_list)
self._call_func_permission_fn: Optional[Callable[[Request], Awaitable[FuncModel]]] = call_func_permission_fn
self.registry: RegistryManager = RegistryManager()
self.cache: Cache = Cache(interval=cache_interval)
self.window_statistics: WindowStatistics = window_statistics or WindowStatistics(interval=60)
if self.window_statistics is not None and self.window_statistics.is_closed:
self.register_server_event(EventEnum.before_start, lambda _app: self.window_statistics.statistics_data())
def register_server_event(self, event_enum: EventEnum, *event_handle_list: SERVER_EVENT_FN) -> None:
"""register server event handler
:param event_enum: server event
:param event_handle_list: event handler list
"""
for event_handle in event_handle_list:
if (event_enum, event_handle) not in self._depend_set:
self._depend_set.add((event_enum, event_handle))
self._server_event_dict[event_enum].append(event_handle)
else:
raise ImportError(f"even type:{event_enum}, handle:{event_handle} already load")
def load_middleware(self, middleware_list: List[BaseMiddleware]) -> None:
"""load server middleware
:param middleware_list: server middleware list
"""
for middleware in middleware_list:
if middleware not in self._depend_set:
self._depend_set.add(middleware)
else:
raise ImportError(f"{middleware} middleware already load")
middleware.app = self # type: ignore
if isinstance(middleware, BaseConnMiddleware):
middleware.load_sub_middleware(self._conn_handle)
setattr(self, self._conn_handle.__name__, middleware)
elif isinstance(middleware, BaseMiddleware):
self._middleware_list.append(middleware)
else:
raise RuntimeError(f"{middleware} must instance of {BaseMiddleware}")
for event_type, server_event_handle_list in middleware.server_event_dict.items():
self.register_server_event(event_type, *server_event_handle_list)
def load_processor(self, processor_list: List[BaseProcessor]) -> None:
"""load server processor
:param processor_list server load processor
"""
for processor in processor_list:
if processor not in self._depend_set:
self._depend_set.add(processor)
else:
raise ImportError(f"{processor} processor already load")
if isinstance(processor, BaseProcessor):
processor.app = self # type: ignore
self._processor_list.append(processor)
else:
raise RuntimeError(f"{processor} must instance of {BaseProcessor}")
for event_type, server_event_handle_list in processor.server_event_dict.items():
self.register_server_event(event_type, *server_event_handle_list)
def register(
self,
func: Callable,
name: Optional[str] = None,
group: Optional[str] = None,
is_private: bool = False,
doc: Optional[str] = None,
) -> None:
"""Register function with Server
:param func: function
:param name: The real name of the function in the server
:param group: The group of the function
:param is_private: Whether the function is private or not, in general,
private functions are only allowed to be called by the local client,
but rap does not impose any mandatory restrictions
:param doc: Describe what the function does
"""
if isinstance(func, RapFunc):
func = func.raw_func
self.registry.register(func, name, group=group, is_private=is_private, doc=doc)
@property
def is_closed(self) -> bool:
"""Whether the service is closed"""
return self._run_event.is_set()
async def run_event_list(self, event_type: EventEnum, is_raise: bool = False) -> None:
event_handle_list: Optional[List[SERVER_EVENT_FN]] = self._server_event_dict.get(event_type)
if not event_handle_list:
return
for callback in event_handle_list:
try:
ret: Any = callback(self) # type: ignore
if asyncio.iscoroutine(ret):
await ret
except Exception as e:
if is_raise:
raise e
else:
logger.exception(f"server event<{event_type}:{callback}> run error:{e}")
async def create_server(self) -> "Server":
"""start server"""
if not self.is_closed:
raise RuntimeError("Server status is running...")
await self.run_event_list(EventEnum.before_start, is_raise=True)
self._server = await asyncio.start_server(
self.conn_handle, self.host, self.port, ssl=self._ssl_context, backlog=self._backlog
)
logger.info(f"server running on {self.host}:{self.port}. use ssl:{bool(self._ssl_context)}")
await self.run_event_list(EventEnum.after_start)
# fix different loop event
self._run_event.clear()
self._run_event = asyncio.Event()
return self
async def run_forever(self) -> None:
"""Start the service and keep running until shutdown is called or received signal `int` or `term`"""
if self.is_closed:
await self.create_server()
def _shutdown(signum: int, frame: Any) -> None:
logger.debug("Receive signal %s, run shutdown...", signum)
asyncio.ensure_future(self.shutdown())
if threading.current_thread() is not threading.main_thread():
raise RuntimeError("Signals can only be listened to from the main thread.")
else:
for sig in [signal.SIGINT, signal.SIGTERM]:
add_signal_handler(sig, _shutdown)
await self._run_event.wait()
for sig in [signal.SIGINT, signal.SIGTERM]:
remove_signal_handler(sig, _shutdown)
async def shutdown(self) -> None:
"""Notify the client that it is about to close, and the client should not send new messages at this time.
The server no longer accepts the establishment of a new conn,
and the server officially shuts down after waiting for the established conn to be closed.
"""
if self.is_closed:
return
# Notify the client that the server is ready to shut down
async def send_shutdown_event(_conn: ServerConnection) -> None:
# conn may be closed
if not _conn.is_closed():
try:
await Sender(
self, _conn, self._send_timeout, processor_list=self._processor_list # type: ignore
).send_event(event.ShutdownEvent({"close_timeout": self._close_timeout}))
except ConnectionError:
# conn may be closed
pass
try:
with Deadline(self._close_timeout):
await self.run_event_list(EventEnum.before_end)
# Stop accepting new connections.
if self._server:
self._server.close()
await self._server.wait_closed()
task_list: List[Coroutine] = [
send_shutdown_event(conn) for conn in self._connected_set if not conn.is_closed()
]
if task_list:
logger.info("send shutdown event to client")
await asyncio.gather(*task_list)
# until connections close
logger.info(f"{self} Waiting for connections to close. (CTRL+C to force quit)")
while self._connected_set:
await asyncio.sleep(0.1)
await self.run_event_list(EventEnum.after_end, is_raise=True)
finally:
self._run_event.set()
async def conn_handle(self, reader: READER_TYPE, writer: WRITER_TYPE) -> None:
"""Handle initialization and recycling of conn"""
conn: ServerConnection = ServerConnection(
reader, writer, pack_param=self._pack_param, unpack_param=self._unpack_param
)
conn.conn_id = str(await async_get_snowflake_id())
try:
self._connected_set.add(conn)
await self._conn_handle(conn)
try:
conn.conn_future.result()
except Exception:
pass
finally:
self._connected_set.remove(conn)
async def _conn_handle(self, conn: ServerConnection) -> None:
"""Receive or send messages by conn"""
sender: Sender = Sender(self, conn, self._send_timeout, processor_list=self._processor_list) # type: ignore
receiver: Receiver = Receiver(
self, # type: ignore
conn,
self._run_timeout,
sender,
self._ping_fail_cnt,
self._ping_sleep_time,
processor_list=self._processor_list,
call_func_permission_fn=self._call_func_permission_fn,
)
recv_msg_handle_future_set: Set[asyncio.Future] = set()
async def recv_msg_handle(_request_msg: Optional[BASE_MSG_TYPE]) -> None:
if _request_msg is None:
await sender.send_event(event.CloseConnEvent("request is empty"))
return
try:
request: Request = Request.from_msg(self, _request_msg, conn) # type: ignore
except Exception as closer_e:
logger.error(f"{conn.peer_tuple} send bad msg:{_request_msg}, error:{closer_e}")
await sender.send_event(event.CloseConnEvent("protocol error"))
await conn.await_close()
return
try:
response: Optional[Response] = await receiver.dispatch(request)
await sender(response)
except Exception as closer_e:
logging.exception("raw_request handle error e")
await sender.send_exc(ServerError(str(closer_e)))
while not conn.is_closed():
try:
with Deadline(self._keep_alive):
request_msg: Optional[BASE_MSG_TYPE] = await conn.read()
# create future handle msg
future: asyncio.Future = asyncio.ensure_future(recv_msg_handle(request_msg))
future.add_done_callback(lambda f: recv_msg_handle_future_set.remove(f))
recv_msg_handle_future_set.add(future)
except asyncio.TimeoutError:
logging.error(f"recv data from {conn.peer_tuple} timeout. close conn")
await sender.send_event(event.CloseConnEvent("keep alive timeout"))
break
except (IOError, CloseConnException):
break
except Exception as e:
logging.error(f"recv data from {conn.peer_tuple} error:{e}, conn has been closed")
if recv_msg_handle_future_set:
logging.debug("wait recv msg handle future")
while len(recv_msg_handle_future_set) > 0:
await asyncio.sleep(0.1)
if not conn.is_closed():
conn.close()
logging.debug("close connection: %s", conn.peer_tuple)
|
<filename>src/test/java/com/github/kokorin/jaffree/ffprobe/FFprobeResultTest.java
package com.github.kokorin.jaffree.ffprobe;
import com.github.kokorin.jaffree.StreamType;
import com.github.kokorin.jaffree.ffprobe.data.FlatFormatParser;
import static org.junit.Assert.assertEquals;
import org.junit.Test;
import java.io.InputStream;
import java.util.List;
public class FFprobeResultTest {
@Test
public void testChaptersWithFlatFormat() throws Exception {
FFprobeResult result;
try (InputStream input = this.getClass().getResourceAsStream("./data/ffprobe_streams_and_chapters.flat")) {
result = new FFprobeResult(new FlatFormatParser().parse(input));
}
verifyChaptersFFprobeResult(result);
}
public void verifyChaptersFFprobeResult(FFprobeResult result) {
List<Stream> streams = result.getStreams();
assertEquals(8, streams.size());
Stream videoStream = streams.get(0);
assertEquals(StreamType.VIDEO, videoStream.getCodecType());
assertEquals("hevc", videoStream.getCodecName());
assertEquals(Boolean.TRUE, videoStream.getDisposition().getDefault());
Stream audioStream = streams.get(1);
assertEquals(StreamType.AUDIO, audioStream.getCodecType());
assertEquals("aac", audioStream.getCodecName());
List<Chapter> chapters = result.getChapters();
assertEquals(5, chapters.size());
Chapter chapter = chapters.get(0);
assertEquals("Chapter 01", chapter.getTag("title"));
}
@Test
public void testProgramsWithFlatFormat() throws Exception {
FFprobeResult result;
try (InputStream input = this.getClass().getResourceAsStream("./data/ffprobe_programs.flat")) {
result = new FFprobeResult(new FlatFormatParser().parse(input));
}
verifyProgramsFFprobeResult(result);
}
public void verifyProgramsFFprobeResult(FFprobeResult result) {
List<Program> programs = result.getPrograms();
assertEquals(3, programs.size());
for (int i = 0; i < 3; i++) {
Program program = programs.get(i);
assertEquals("program " + i, (Integer) (i + 1), program.getProgramId());
assertEquals("program " + i, (Integer) (i + 1), program.getProgramNum());
assertEquals("program " + i, (Integer) 2, program.getNbStreams());
assertEquals("program " + i, "FFmpeg", program.getTag("service_provider"));
List<Stream> streams = program.getStreams();
assertEquals(2, streams.size());
Stream video = streams.get(0);
assertEquals(StreamType.VIDEO, video.getCodecType());
assertEquals("mpeg2video", video.getCodecName());
Stream audio = streams.get(1);
assertEquals(StreamType.AUDIO, audio.getCodecType());
assertEquals("mp2", audio.getCodecName());
}
}
} |
<filename>src/app/module/account/history/pending-transactions/pending-transactions.component.ts<gh_stars>0
import { Component, OnInit } from '@angular/core';
import { AccountService } from '../../account.service';
import { ActivatedRoute, Router } from '@angular/router';
import { DataStoreService } from '../../../../services/data-store.service';
import { Page } from '../../../../config/page';
@Component({
selector: 'app-pending-transactions',
templateUrl: './pending-transactions.component.html',
styleUrls: ['./pending-transactions.component.scss']
})
export class PendingTransactionsComponent implements OnInit {
page = new Page();
rows = new Array<any>();
accountId = '';
accountRs = '';
constructor(
private accountService: AccountService,
private route: ActivatedRoute,
private router: Router
) {
this.page.pageNumber = 0;
this.page.size = 10;
}
ngOnInit() {
this.accountId = this.accountService.getAccountDetailsFromSession('accountId');
this.accountRs = this.accountService.getAccountDetailsFromSession('accountRs');
this.setPage({ offset: 0 });
}
setPage(pageInfo) {
this.page.pageNumber = pageInfo.offset;
this.accountService.getAccountUnconfirmedTransactions(this.accountId)
.subscribe(response => {
this.rows = response.unconfirmedTransactions;
if (this.page.pageNumber === 0 && this.rows.length < 10) {
this.page.totalElements = this.rows.length;
} else if (this.page.pageNumber > 0 && this.rows.length < 10) {
this.page.totalElements = this.page.pageNumber * 10 + this.rows.length;
this.page.totalPages = this.page.pageNumber;
}
});
}
goToDetails(row) {
DataStoreService.set('transaction-details', { id: row.transaction, type: 'onlyID', view: 'transactionDetail' });
this.router.navigate(['/account/transactions/transaction-details']); // + row.fullHash
}
accountDetail(accountID) {
// DataStoreService.set('user-details',{ id: accountID });
this.router.navigate(['/account/transactions/account-details'], { queryParams: { id: accountID } });
}
reload() {
this.setPage({ offset: 0 });
}
}
|
A high performance massive MIMO detector based on log-domain belief-propagation Massive multiple-input multiple-output (MIMO) is a promising technology in the 5G wireless communication system. In this paper, we propose a high performance and ASIC implementation friendly massive MIMO detector. An iterative belief propagation (BP) detection method is employed where the symbol message vector is transformed into log-domain to reduce the complexity. As a case study, we have designed and synthesized a pipeline degree-64 variable node for 6464 16-QAM MIMO system by using a CMOS 130 nm technology with a cell area of 6.1 mm2 and 600K logic gates. Compared with existing methods, the proposed detector has more than 10dB performance gain with even lower complexity which shows a high potential for the 5G systems. |
package org.springframework.samples.petclinic.model;
import javax.persistence.Entity;
import lombok.Getter;
import lombok.Setter;
@Getter
@Setter
@Entity
public class Laboratorio extends Cliente{
}
|
A Red Oak native has been killed in a motorcycle accident in southern Arizona.
According to the Air Force Times, Technical Sergeant Dustin Jackson died from injuries sustained in a motorcycle accident on Friday.
The 36-year-old Jackson, who recently returned from duty in Iraq, is survived by his parents and a sister.
Services for Jackson are currently pending at the Nelson-Boylan-LeRette Funeral Chapel in Red Oak. |
Fishermens perception of fisheries resources and water condition in Kretek District, Parangtritis The coastal area which located in Kretek District performed the highest production in capture fisheries of Bantul Regency. As the consequence, many people in this district earn their living on fisheries sector as a fisherman, especially people in Parangtritis Village. The existence of perception affect relation between the person and their environment. In this case, the perception between fishermen and their coastal area specifically the sea water condition. Therefore, the study was conducted to understand the perception which develop in this area. The method used was quantitative descriptive method with chi-square test to understand relation between fishermens characteristic and perception with condition in Parangtritis coast. Result showed that fishermens perception about size of capture fish results, needed for conservation of fish resources, and about capture fish result condition in Parangtritis coast is have a relation with level of education, income, and fishermens place of origin. Introduction Kretek District is in south of the Bantul Regency within area of 2,677 Ha. The climate in this district is similar as in the tropical low land areas with hot weather. The temperature in this district is ranged from 28-32 °C. The topography in this district is mostly flat to wavy areas, with small part of wavy to hilly areas (5 %). Kretek district is inhabited by 7,762 families with the total population is 30,834-14,835 people of male and 15,981 people of female. The level of population density in Kretek district is 1152 people/km 2. Based on district monograph data, it is noted that 17,215 people or 55.8 % of Kretek district residents work on the agricultural sector. The agriculture, forestry, and fisheries sectors are the second sector which generate the most contribution to GDP after the invoicing industry sector in Bantul Regency. This indicates that the large number of people are working in those sectors. Kretek district also known to be the district which performed highest contribution in capture fisheries among the districts in Bantul Regency. Consequently, many people are earning in fisheries sector, usually as fishermen in Parangtritis Village. Human response to the environment depends on how humans interpret and how the individual perceives his environment. Perception of the environment affects individual relationships with their environment. As individual, it can be observed from its participation in environment including utilizing the environment, preventing environmental damage and tackling environmental damage. Perception affects the relationship between fishermen and their environment, in this case the sea waters. Therefore, study of fishermen's perception in Parangtritis Village of water condition in Parangtritis Coast needs to be done. The concept of this perception can be adopted to coastal environment, by observing the fishermen as human and seawater as the environment. Limited data about this perception is the reason this study need to be done. Location and time The research location is in Kretek District, Bantul Regency, Special Region of Yogyakarta Province (figure 1). This research was provided on August 2018. Sampling The method used in this research is descriptive method and survey with a quantitative approach. In his book, Sugiyono stated that quantitative method is a research method used to examine a particular population or sample, the sampling technique used randomly, collecting data using research instruments, analysing statistical data aim to testing predetermined hypotheses, while survey methods are research methods who take samples in the population and use a questionnaire as a tool used to collect primary data. This study uses a questionnaire with several questions that can be answered based on the choice of answers available while some other questions can be answered according to free thinking. Data analysis In this study, the questions to the fishermen in Parangtritis coast covers some aspect. Those aspect were how their perception of the condition of the fish caught, the type of fish caught, the size of the fish caught, the condition of the waters in Parangtritis, the causes of water pollution in Parangtritis, and the need for conservation of fish resources in Parangtritis waters. This study uses a questionnaire with several questions that can be answered based on the choice of answers available while some other questions can be answered according to free thinking. While the data processing method for this research is quantitative descriptive analysis. Quantitative descriptive research methods in this study was to obtain an overview of fishermen's perception of the water conditions in Parangtritis by using SPSS (Statistical Product and Service Solutions). Characteristic of respondent The characteristics of respondent on this research based on level of education, fishermen's income seen from the socio-cultural and economic aspects are shown in figure 2. In this research, andon fishermen are fishermen who migrated from an area and have settled in the village of Parangtritis, while local fishermen are fishermen who have lived from childhood or at least 10 years in Parangtritis. Based on figure 2, most of the andon fishermens on Parangtritis coast have a level of elementary education and most of the local fishermen have a level of high school education. While the income earned by andon and local fishermen is mostly less than Rp 200,000. Perception of the fishermen Based on the results of survey, founded that most of the fishermen in Parangtritis waters felt that the condition of the cached fish increased even though not too much, then the number of fish caught and the size of capture fish in Parangtritis had not experienced an increase or decrease in the past. Most fishermen also argue that the condition of the waters in Parangtritis is relatively good, even if there is a pollution, it happens due to natural factors. Even so, most fishermen say that there is a need to conserve fish resources in Parangtritis coast. The perception of the condition of Parangtritis waters by the fishermen is not separated from the characteristics of each fisherman. Therefore, a chi-square test was conducted to see the relationship between the characteristics of fishermen -in this research include level of education, income, and place of origin -and their perception to Parangtritis water condition. Based on the results of survey, all of the variable can be seen on figure 3. Perception based on social economic characteristics of fishermen and size fish of catch Furthermore, based on data survey, data continue chi-square test. In chi-square test, there is an initial hypothesis, known that: H0 : there is no relation between fishermen's characteristic and Parangtritis water condition. H1 : there is relation between fishermen's characteristic and Parangtritis water condition. Zero hyphotesis (H0) rejected if the significance value of chi-square < 0.05. Figure 3. Map of fishermen to marine resources. Perception based on social economic characteristics of fishermen and size fish of catch Furthermore, based on data survey, data continue chi-square test. In chi-square test, there is an initial hypothesis, known that: H0 : there is no relation between fishermen's characteristic and Parangtritis water condition. H1 : there is relation between fishermen's characteristic and Parangtritis water condition. Zero hyphotesis (H0) rejected if the significance value of chi-square < 0.05. Based on the level of education and the size of the fish caught in table 1 and table 2, known that most fishermen feel that the size of the fish they catch is the same as before. Then the results of the chi-square test indicate that there was a relationship between the level of education and the perception of fishermen on the size of the fish caught, because the chi-square significance value was less than 0.050 which was 0.023. Based on fishermen's income and fishermen's perception of fish source conservation in table 3 and table 4, known that most of fishermen agree there is need to fish source conservation in Parangtritis Coast. Then the results of chi-square test indicate that there is relation between fishermen's income and fishermen's perception of fish source conservation, because the chi-square value was less than 0.050, which was 0.044. Based on fishermen's place of origin and value of fish caught condition in table 5 and 6, known that most of fishermen feel that there is an increasing fish caught in Parangtritis Coast, but not much. Then the results of chi-square test indicate that there is relation between fishermen's place of origin and fish caught condition, because the chi-square value was 0.050. Conslusion Fishermen's perception about the size of fish caught, the need for conservation of fish resources, and the condition of fish caught in coastal of Parangtritis, each has a correlation with the level of education, income, and origin of fishermen. Fishermen's perception about the size of fish caught have significant value was less than 0.050 which was 0.023. They have good perception related conservation of fish resources in Coastal of Parangtritis. The perception of fisherment have significance value was less than 0.050, which was 0.044. Then the results of perception to place of origin and fish caught condition have significant value was 0.050. |
def bbox_pred_split(self, bbox_pred, num_proposals_per_img):
bucket_cls_preds, bucket_offset_preds = bbox_pred
bucket_cls_preds = bucket_cls_preds.split(num_proposals_per_img, 0)
bucket_offset_preds = bucket_offset_preds.split(
num_proposals_per_img, 0)
bbox_pred = tuple(zip(bucket_cls_preds, bucket_offset_preds))
return bbox_pred |
The Alien will feature in Alien: Covenant according to Ridley Scott. It almost seems daft that that would need clarifying but given the Alien-less direction that was Prometheus and the fact that the new Alien film started life as Prometheus 2, there was bound to be some confusion as to just what kind of creatures we would be seeing in the coming Alien: Covenant.
In a new interview with The Wrap, Ridley Scott has confirmed that the Prometheus sequel is definitely more of an Alien film: “Well, really it’s “Alien.” They’re going to go to the planet where the engineers came from, and come across the evolving creature that they had made. Why did they make it? Why would they make such a terrifying beast? It felt bio-mechanoid, it felt like a weapon. And so the movie will explain that, and reintroduce the alien back into it.”
Ridley Scott has talked about how he considered the Alien (the creature) to be done and no longer scary. Creative Assembly proved him wrong with Alien Isolation which was praised for returning Alien to its former horror glory. But the inclusion of the traditional Alien in Alien: Covenant has been in question for sometime because of Scott’s past comments. No longer though, as Scott confirms the Alien will feature in Alien: Covenant in all stages of its life cycle:
“There was always this discussion: Is Alien, the character, the beast, played out or not? We’ll have them all: egg, face-hugger, chest-burster, then the big boy. I think maybe we can go another round or two.”
Are you relieved that the Alien will be returning in a Ridley Scott film with Alien in title? Thanks to RakaiThwei and Bloody Disgusting for the news. |
Experimental study of out-of-plane adhesion force evolution (and regression) for MEMS accelerometers The work investigates n-operation adhesion evolution in out-of-plane (OOP) test devices fabricated in an industrial surface micromachining process. The aim is to mimic the behavior of OOP MEMS accelerometers in terms of package environment (pressure of ~ 100 mbar), characteristic frequency and quality factor, so that the contact dynamics during impact events is representative of such devices. The experiments include: (i) statistical measurements of pristine adhesion forces; (ii) application of dynamic impacts at known contact velocity (~ 1 cm/s) and adhesion evolution monitoring as a function of the elapsed collisions; (iii) adhesion force monitoring within 40 days after the former test ends. With a sub-nN measurement resolution, the results show an adhesion force increase during cycles up to a few hundred nN, followed by a regression (likely due to a slow relaxation mechanism) when the device is left still. |
# Copyright 2023 The SeqIO Authors.
#
# Licensed under the Apache License, Version 2.0 (the "License");
# you may not use this file except in compliance with the License.
# You may obtain a copy of the License at
#
# http://www.apache.org/licenses/LICENSE-2.0
#
# Unless required by applicable law or agreed to in writing, software
# distributed under the License is distributed on an "AS IS" BASIS,
# WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
# See the License for the specific language governing permissions and
# limitations under the License.
"""Tests for seqio.scripts.cache_tasks_main."""
import functools
import os
from absl import flags
from absl.testing import absltest
from apache_beam.testing.test_pipeline import TestPipeline
import seqio
from seqio.scripts import cache_tasks_main
import tensorflow.compat.v2 as tf
tf.compat.v1.enable_eager_execution()
flags.FLAGS.min_shards = 0
TaskRegistry = seqio.TaskRegistry
test_utils = seqio.test_utils
class ProcessTaskBeamTest(test_utils.FakeTaskTest):
def validate_pipeline(
self,
task_name,
expected_task_dir="cached_task",
token_preprocessed=False,
ndfeatures=False,
num_shards=2,
):
self.assertTrue(TaskRegistry.get("cached_task").cache_dir)
task = TaskRegistry.get(task_name)
self.assertFalse(task.cache_dir)
with TestPipeline() as p:
output_dirs = cache_tasks_main.run_pipeline(
p, ["cached_task", task_name], cache_dir=self.test_data_dir
)
actual_task_dir = os.path.join(
self.test_data_dir, seqio.get_task_dir_from_name(task_name)
)
expected_task_dir = os.path.join(
test_utils.TEST_DATA_DIR, expected_task_dir
)
expected_tfrecord_files = [
"train.tfrecord-%05d-of-%05d" % (i, num_shards)
for i in range(num_shards)
]
expected_auxiliary_files = [
"stats.train.json",
"info.train.json",
"COMPLETED",
]
if "validation" in task.splits:
expected_tfrecord_files.append("validation.tfrecord-00000-of-00001")
expected_auxiliary_files.extend(
["stats.validation.json", "info.validation.json"]
)
self.assertEqual([actual_task_dir], output_dirs)
self.assertCountEqual(
expected_tfrecord_files + expected_auxiliary_files,
tf.io.gfile.listdir(actual_task_dir),
)
for fname in expected_auxiliary_files:
actual_content = tf.io.gfile.GFile(
os.path.join(actual_task_dir, fname)
).read()
expected_content = tf.io.gfile.GFile(
os.path.join(expected_task_dir, fname)
).read()
# Accept minor formatting difference.
actual_content = actual_content.replace(", ", ",")
# Replace with actual number of shards.
expected_content = expected_content.replace(
'"num_shards": 2', f'"num_shards": {num_shards}'
)
# Replace with actual version.
version = seqio.__version__
expected_content = expected_content.replace(
'"seqio_version": "0.0.0"', f'"seqio_version": "{version}"'
)
self.assertEqual(
expected_content, actual_content, f"Contents of {fname} mismath"
)
# Check datasets.
self.verify_task_matches_fake_datasets(
task_name,
use_cached=True,
splits=task.splits,
token_preprocessed=token_preprocessed,
ndfeatures=ndfeatures,
)
def test_tfds_pipeline(self):
self.validate_pipeline("tfds_task")
def test_new_tfds_pipeline(self):
self.validate_pipeline("t5:tfds_task")
def test_text_line_pipeline(self):
self.validate_pipeline("text_line_task")
def test_function_pipeline(self):
self.validate_pipeline("function_task", num_shards=1)
def test_tf_example_pipeline(self):
self.validate_pipeline("tf_example_task")
def test_cache_before_tokenization_ndfeatures_pipeline(self):
self.add_task(
"task_tokenized_postcache_ndfeatures",
seqio.dataset_providers.FunctionDataSource(
dataset_fn=functools.partial(
test_utils.get_fake_dataset, ndfeatures=True
),
splits=["train", "validation"],
),
output_features={
"inputs": seqio.Feature(test_utils.sentencepiece_vocab()),
"targets": seqio.Feature(test_utils.sentencepiece_vocab()),
"2d_feature": seqio.Feature(
seqio.PassThroughVocabulary(1000, eos_id=0),
add_eos=False,
rank=2,
),
"3d_feature": seqio.Feature(
seqio.PassThroughVocabulary(1000, eos_id=0),
add_eos=False,
rank=3,
),
},
preprocessors=[
test_utils.test_text_preprocessor,
seqio.CacheDatasetPlaceholder(),
seqio.preprocessors.tokenize,
test_utils.token_preprocessor_no_sequence_length,
seqio.preprocessors.append_eos_after_trim,
],
)
self.validate_pipeline(
"task_tokenized_postcache_ndfeatures",
expected_task_dir="cached_untokenized_ndfeatures_task",
num_shards=1,
token_preprocessed=True,
ndfeatures=True,
)
def test_cache_before_tokenization_pipeline(self):
self.add_task(
"task_tokenized_postcache",
self.function_source,
preprocessors=[
test_utils.test_text_preprocessor,
seqio.CacheDatasetPlaceholder(),
seqio.preprocessors.tokenize,
test_utils.token_preprocessor_no_sequence_length,
seqio.preprocessors.append_eos_after_trim,
],
)
self.validate_pipeline(
"task_tokenized_postcache",
expected_task_dir="cached_untokenized_task",
num_shards=1,
token_preprocessed=True,
)
def test_overwrite(self):
with TestPipeline() as p:
_ = cache_tasks_main.run_pipeline(
p, ["uncached_task"], cache_dir=self.test_data_dir, overwrite=True
)
actual_task_dir = os.path.join(self.test_data_dir, "uncached_task")
stat_old = tf.io.gfile.stat(
os.path.join(actual_task_dir, "train.tfrecord-00000-of-00002")
)
with TestPipeline() as p:
_ = cache_tasks_main.run_pipeline(
p, ["uncached_task"], cache_dir=self.test_data_dir, overwrite=True
)
stat_new = tf.io.gfile.stat(
os.path.join(actual_task_dir, "train.tfrecord-00000-of-00002")
)
self.assertGreater(stat_new.mtime_nsec, stat_old.mtime_nsec)
if __name__ == "__main__":
absltest.main()
|
<filename>Sources/MBDebugPanel/Headers/MBDebugPanel.h
//Copyright (c) 2014 MINDBODY, Inc. <www.mindbodyonline.com>
//
//Permission is hereby granted, free of charge, to any person obtaining a copy
//of this software and associated documentation files (the "Software"), to deal
//in the Software without restriction, including without limitation the rights
//to use, copy, modify, merge, publish, distribute, sublicense, and/or sell
//copies of the Software, and to permit persons to whom the Software is
//furnished to do so, subject to the following conditions:
//
//The above copyright notice and this permission notice shall be included in
//all copies or substantial portions of the Software.
//
//THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR
//IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY,
//FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE
//AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER
//LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM,
//OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN
//THE SOFTWARE.
//
//
// MBDebugPanel.h
// MBDebugPanel
//
// Created by <NAME> on 2/6/14.
//
//
#import <Foundation/Foundation.h>
#import <UIKit/UIKit.h>
// Expose common public headers via MBDebugPanel.h,
// so end-users only have to import <MBDebugPanel/MBDebugPanel.h>
#import "MBDebugPanelComponent.h"
#import "MBDebugPanelSimpleComponent.h"
#import "MBDebugPanelSimpleButtonComponent.h"
#import "MBDebugPanelSimpleSwitchComponent.h"
#import "MBDebugPanelSimpleTextFieldComponent.h"
@interface MBDebugPanel : UITableViewController <UITableViewDataSource, UITableViewDelegate>
/** Add a component to the panel */
+(void)addComponent:(id<MBDebugPanelComponent>)component;
/**
Add multiple components.
@param components An array of components to add to the panel
*/
+(void)addComponentsFromArray:(NSArray*)components;
/** Remove a component. */
+(void)removeComponent:(id<MBDebugPanelComponent>)component;
/**
Remove multiple components.
@param components An array of components to attempt to remove from the panel
*/
+(void)removeComponentsInArray:(NSArray*)components;
/** Remove all components */
+(void)removeAllComponents;
/** Show the panel */
+(void)show;
/** Hide the panel */
+(void)hide;
/**
Invoke "reloadData" on the panel's UITableView
@notes Call this method if you have added or removed
components while the panel is visible.
*/
+(void)reloadComponents;
/**
Whether or not the panel is currently shown
@notes Manipulation of the app window's rootViewController
could cause this to return YES unexpectedly. This method returns
true if the panel is presented inside a parent navigation controller.
However, this does not make a guarantee that the parent is still at the top of the view hierarchy.
*/
+(BOOL)isPresented;
/*
Present a view controller from the DebugPanel's parent viewcontroller
*/
+ (void)presentViewController:(UIViewController *)viewControllerToPresent
animated:(BOOL)flag
completion:(void (^)(void))completion;
/*
Expose the ability to set the DebugPanel's modal title
*/
+ (void)setTitle:(NSString*)title;
@end
|
Nuclear activation in dual-durotaxing cells on a matrix with cell-scale stiffness-heterogeneity Living organisms are typically composed of various tissues with microscopic cell-scale stiffness-heterogeneity, in which some cells receive dynamically fluctuating mechanical stimuli from the heterogeneous extracellular milieu during long-term movement. Although intracellular stress dynamics (ISD), which are closely related to the regulation of cell functions such as proliferation and differentiation, can be characteristically modulated in cells migrating on a matrix with stiffness-heterogeneity, it has been unclear how the mode of fluctuation of ISD affects cell functions. In the present study, we demonstrate that mesenchymal stem cells (MSCs) dual-durotaxing (i.e., both forward and reverse durotaxis) on microelastically-patterned gels with stiff triangular domains markedly amplify the fluctuation of ISD, nuclear shape, and the spatial distribution of chromatins, which makes the cells remain far from tensional equilibrium. We provide evidence that amplified chromatin fluctuation in the dual-durotaxing MSCs can cause activation of cellular vigor and maintenance of the stemness. |
A Neurophysiological Perspective on a Preventive Treatment against Schizophrenia Using Transcranial Electric Stimulation of the Corticothalamic Pathway Schizophrenia patients are waiting for a treatment free of detrimental effects. Psychotic disorders are devastating mental illnesses associated with dysfunctional brain networks. Ongoing brain network gamma frequency (3080 Hz) oscillations, naturally implicated in integrative function, are excessively amplified during hallucinations, in at-risk mental states for psychosis and first-episode psychosis. So, gamma oscillations represent a bioelectrical marker for cerebral network disorders with prognostic and therapeutic potential. They accompany sensorimotor and cognitive deficits already present in prodromal schizophrenia. Abnormally amplified gamma oscillations are reproduced in the corticothalamic systems of healthy humans and rodents after a single systemic administration, at a psychotomimetic dose, of the glutamate N-methyl-d-aspartate receptor antagonist ketamine. These translational ketamine models of prodromal schizophrenia are thus promising to work out a preventive noninvasive treatment against first-episode psychosis and chronic schizophrenia. In the present essay, transcranial electric stimulation (TES) is considered an appropriate preventive therapeutic modality because it can influence cognitive performance and neural oscillations. Here, I highlight clinical and experimental findings showing that, together, the corticothalamic pathway, the thalamus, and the glutamatergic synaptic transmission form an etiopathophysiological backbone for schizophrenia and represent a potential therapeutic target for preventive TES of dysfunctional brain networks in at-risk mental state patients against psychotic disorders. Introduction Neurobiological disorders of the brain are an immense burden with a rising cost in our societies. In the European Union, about a third of the total population suffers from mental disorders, and we are still missing effective treatments, free of side-effects, against complex neuropsychiatric illnesses such as schizophrenia. Most of the patients suffering from schizophrenia are treated with a combination of non-biological therapies (cognitive remediation, psychotherapies) and antipsychotic medications. These drugs are more effective against the positive than the negative symptoms of schizophrenia, and they induce serious adverse effects. Because schizophrenia is characterized by multiple etiopathophysiological factors, does it make sense to have a treatment based principally on a "single receptor"? There is increasing evidence that the psychiatric disorders and the cognitive deficits of patients with schizophrenia are associated with and may be caused by dysfunction of highly-distributed systems displaying disturbed spatiotemporal activity patterns. Moreover, a recent meta-analysis demonstrated significant changes in whole brain network architecture associated with schizophrenia. This supports the notion of functional interactions between multiple molecular, cellular and system pathways, which contribute to the multiple symptoms and cognitive deficits in schizophrenia. So, would it not be more promising to use a therapeutic means that non-specifically modulates the ongoing global brain activity such as to re-establish normal brain function? The rationale behind the use of a non-specific therapeutic means in patients with schizophrenia is that the return to their normal brain function may especially alleviate the psychiatric disorders and dampen their emotion, sensorimotor and cognitive deficits. Deep brain stimulation (DBS) may be a promising alternative. The challenge is immense given the complex symptomatology and pathophysiological mechanisms of schizophrenia (see below). Davidson and colleagues wrote: "To achieve the best therapeutic results in schizophrenia-like most other disorders-primary prevention is preferable to early and prompt treatment, which, in turn, is preferable to treatment of chronically established illness". This raises the questions when to apply the preventive treatment and what could be the appropriate treatment modality? Ideally, assuming that schizophrenia is caused by an aggressive agent (microbe, virus, parasite) during pregnancy, it would be great to have the infection type identified to proceed to the appropriate preventive asymptomatic treatment. Moreover, there is increasing evidence suggesting that maternal immune stimulation during pregnancy can increase the risk of neurodevelopmental disorders such as schizophrenia. Prenatal infection may lead to a developmental neuroinflammation, which would contribute to the disruption of the normal brain development leading to dysfunctional networks and abnormal behavior relevant to schizophrenia. The corresponding neuroimmune and behavioral abnormalities might occur in response to stress in puberty. Rodent models of maternal immune activation mimic both behavioral and neurobiological abnormalities, which are relevant to schizophrenia. Interestingly, an early presymptomatic anti-inflammatory intervention during peripubertal stress exposure can prevent the schizophrenia-relevant behavioral and neurobiological abnormalities. Nevertheless, there is a real need to treat high-risk patients for whom the causes of their mental state remain unknown. That is why in the present review, I will present a neurophysiological perspective on a preventive symptomatic treatment in patients with premorbid and/or prodromal manifestations and bioelectrical markers of latent schizophrenia. A universal property of brain networks is to produce electric currents, conveyed by the movement of ions across cellular membranes, whatever the pathophysiological context may be. Moreover, both the normal and the unhealthy brain can generate normal and abnormal brain rhythms. Importantly, almost every cognitive task is associated with event-related electroencephalographic (EEG) oscillations. We will see that disturbances in brain rhythms are common in patients with schizophrenia. So, can exogenous electricity correct or re-normalize abnormal brain oscillations and, in parallel or as a result, the related mental, emotional, sensorimotor and cognitive disorders? Numerous clinical interventions have demonstrated the benefits of brain electrical stimulation methods in patients with neurobiological disorders resistant to available pharmacological treatments. There is increasing evidence that exogenous electric currents can modulate not only brain electrical activity but also behavioral and cognitive performance, giving hope for treating complex neuropsychiatric illnesses. Moreover, schizophrenia patients with auditory hallucinations that are unresponsive to antipsychotic medications can be treated with transcranial magnetic stimulation (TMS) or transcranial electric stimulation (TES). Ongoing research aims to develop such noninvasive neurophysiological therapies as a routine therapy, which may be more promising than DBS (see below). The exponents of noninvasive technologies now face a huge challenge to develop and refine an efficient therapeutic, free of side-effects, neurophysiological method that treats schizophrenia in its entirety, that is, to treat all its core features, including positive, negative and mood symptoms, and the decline in cognitive abilities (memory and thinking skills). Although there is accumulating evidence that TES techniques are reliable and versatile therapeutic options, a certain number of questions remains open regarding their anatomical targets and the neural mechanisms underlying their clinical impact. The development of the chronic character of schizophrenia takes years following the occurrence of prodromal symptoms with cognitive declines and first-episode psychosis. Longitudinal studies in at-risk mental state individuals and the duration of untreated psychosis offer a time window to identify predictive biomarkers, to better understand the etiopathophysiology of schizophrenia and to develop innovative therapies. It would be ideal to have a therapeutic neurophysiological modality, for instance, a weak TES (see below) applied in at-risk individuals, capable of stopping the occurrence of first-episode psychosis and chronic schizophrenia. This exciting idea has already received increasing interest during at least the last two decades [43,. Electro-and magneto-encephalographic oscillations are natural bioelectrical markers of the functional and dysfunctional state of brain networks. Spontaneously-occurring gamma frequency (30-80 Hz) oscillations (GFO) of cortical origin, naturally implicated in attention and integration processes, are excessively amplified not only during hallucinations but also in first-episode psychosis and in at-risk mental states for psychosis. Such abnormally amplified GFO can be reproduced after a single systemic administration, at a psychotomimetic dose, of the glutamate N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine in the corticothalamic (CT) systems of healthy humans and rodents. These translational models of first-episode psychosis highlight one important factor, glutamate synaptic transmission, which may be altered in individuals at high risk of developing psychotic disorders. Also, disturbances in sleep and reductions in EEG sleep spindles in first-episode psychosis and early-onset schizophrenia [3, support the hypothesis that the thalamus plays a critical role in the pathogenesis of schizophrenia. Therefore, in the present essay, I put forward the notion that the CT pathway, the thalamus, and glutamate synaptic transmission might together represent the backbone etiopathophysiological mechanism of chronic psychotic disorders. This mainstay mechanism may be a prime target for early therapeutic intervention using TES techniques, more specifically targeting the CT pathway. First of all, I will start with a discussion about possible anatomical targets for late therapeutic electrical stimulation in patients with advanced schizophrenia. Then, I will provide an overview of therapeutic neurophysiological procedures and will develop a theoretical proposal on how we may understand the mechanisms underlying the effects of TES of the cerebral cortex with a focus on the CT pathway. It is worth specifying that, in the present survey, the rodent is our predilection animal since its neural networks share common anatomo-functional properties with those of humans. Is There an Anatomical Target for Advanced Schizophrenia? It is extremely challenging to find the correct or best anatomical target(s) for the use of invasive or non-invasive electrical stimulation of brain networks as last resort treatment of complex mental-health disorders, such as schizophrenia. For instance, low-frequency TMS of the left temporoparietal cortex can reduce positive symptoms, especially self-reported auditory hallucinations. Although there is evidence that TMS can enhance cortical synchrony, improve cognitive performance, and is safe and free of cognitive side-effects, further investigations are however required to identify both the anatomical target(s) and the stimulation settings that would lead to an efficient treatment against both positive and negative symptoms of schizophrenia. In contrast, applying DBS at the seemingly best anatomical target might not be free of side-effects. For instance, it is well known that DBS treatment in the subthalamic nucleus can not only alleviate essential and Parkinson disease tremors but also reduce symptoms in patients suffering from severe forms of obsessive compulsive disorders, providing encouraging findings that are corroborated by animal studies. Even if the subthalamic nucleus might be an effective target for the treatment of behavioral disorders that include emotional, cognitive, and motor impairments, its use in patients experiencing severe psychiatric disorders with limited therapeutic options remains questionable. Patients who severely suffer from advanced psychiatric disorders, and who are refractory to medication, must benefit from a new efficient therapeutic approach, and DBS may be a promising alternative. Goodman and Insel recently put emphasis on the fact that the pace of DBS being used against seriously advanced neuropsychiatric disorders is accelerating, giving the incentive both basic and clinical researchers need to concentrate their efforts on the road ahead. However, are we actually ready to use DBS against severe and ultra-complex mental-health disorders? Schizophrenia, as a typical example, is a multidimensional and multifactorial illness, raising an important question as to whether or not DBS could alleviate both the negative and the positive symptoms in all schizophrenic patients who urgently need a new effective therapy. Could both the anatomical target and the DBS settings used in any specific patient be also generally applied to other very problematic patients? The challenge is immense because of the existence of several types of schizophrenia. Finding a unique effective therapy against all types of schizophrenia presupposes that they all share common etiopathophysiological mechanisms. In psychiatry, DBS may be effective in combination with commendable clinical practices. Therefore, the use of non-human animal and network models remain a versatile means to develop therapeutic concepts and to understand the neural mechanisms of electrical neuromodulation used in diverse interventions. Reliable and reproducible non-human animal models of schizophrenia do not exist, and any model for schizophrenia remains questionable with its strengths and limitations. Indeed, schizophrenia belongs to a group of hyper-complex mental-health disorders. So, how to model the heterogeneity of the causes, the progression, the multiple clinical symptoms of chronic schizophrenia, and of the changes elicited by years of medication? The critical problem in finding an efficient treatment of schizophrenia is due to the challenge in modeling psychiatric disorders, which depends on the lack of information about their etiology and pathophysiology. So, what would be a "good" model of or for advanced schizophrenia (untreatable using the currently available therapeutic means) suitable to develop a therapeutic concept based on the use of invasive or noninvasive electrical stimulation of the appropriate neural networks? In theory, one may believe that an animal model that is not validated as being a good model for schizophrenia but that is validated as being a good model for a measurable, singular pathophysiological behavioral trait (e.g., violent behavior, catatonia) similar to that observed in advanced schizophrenic patients and that often makes it to the headlines of newspapers, may have an added value to investigate the efficacy of a therapeutic treatment using DBS in clinical trials. Again, validation of such a concept (reversal of the behavioral/pathophysiological trait by DBS) should rest on well identified anatomo-pathophysiological mechanisms, and they should be conducted along with appropriate ethical guidelines. Animal models are, however, all potentially useful as long as they are precisely described, and as the related working hypotheses are clearly formulated. This critical view is still a matter of discussion. So, along these lines, any model can be a versatile tool to explore the multiple facets concealed by healthy and sick brains. The challenge is indeed to find convergences across models and patients, at least in terms of symptoms and neural dysfunction. Then comes the question of how animal models can be used to discover the appropriate therapy? Neurodevelopmental rodent models, based on prenatal immune activation, which present at the adult stage schizophrenia-relevant behavioral and neurobiological abnormalities, may be promising. Indeed, it was recently demonstrated that a preventive, presymptomatic anti-inflammatory treatment during peripubertal stress exposure can prevent the abnormal behavior and the biomarkers of the neuroimmune abnormality. However, there is a real need to find an appropriate treatment of psychosis for high-risk patients for whom the causes of their mental state remain unknown. Also, if we have known the etiological cause(s) of a given patient suffering from schizophrenia for many years, would we be able to find the appropriate treatment that alleviates simultaneously the positive and negative symptoms and the cognitive and emotional disorders? For the time being, we face the absolute necessity to understand the etiology and pathophysiology of schizophrenia at the molecular, cellular and systems levels, with the dream to find an effective, asymptomatic or symptomatic treatment free of side-effects. Overview of Therapeutic Neurophysiological Procedures: DBS versus TES Since the middle of the 20th century, invasive and noninvasive neurophysiological approaches have been attracting increasing interest as means of last resort treatments against advanced neurological and mental illnesses that are resistant to currently available therapies. Deep brain electrical stimulation has evolved as an invasive, stereotaxic-guided and neuroimaging-guided neurophysiological treatment when drug therapy no longer provides relief from symptoms accompanying severe neurological and psychiatric disorders. It is now used to treat other severe brain disorders in patients resistant to pharmacological mono-and polytherapy, including Parkinson's disease epilepsy, dystonia, obsessive-compulsive disorders, pain, multiple sclerosis, depression and Tourette syndrome. It is also used in brain-injured patients in vegetative and minimally conscious states. Although therapeutic DBS is applied along with the rules of the art and ethics, its use can be accompanied by psychiatric complications. The neural mechanisms underlying the effects of DBS are complex and little known. Since the end of the 20th century, TMS has emerged as a tool to study the human brain and an efficient noninvasive therapeutic means against depression, schizophrenia, addiction and other neurological and psychiatric disorders. However, there is a need to optimize the TMS protocols for routine clinical practice. TMS excites or inhibits the activity of cortical nerve cells and the dynamics and plastic properties of neural networks through the influence of electric currents that are induced by changing magnetic fields. Repetitive TMS modulates in a frequency-dependent manner the excitability of the cortical circuits. Regarding schizophrenia, although TMS is efficient in treating auditory hallucinations, a major issue is to find the anatomical target and the TMS settings that allow treating the disease in its entirety, that is, to alleviate all the negative and positive symptoms, mood disorders and cognitive deficits. Since the beginning of the 21st century, three principal TES techniques, forms of noninvasive and less aggressive neurophysiological modulation, have been increasingly used in cognitive neurosciences and interventional approaches : transcranial direct current stimulation (tDCS), alternating current stimulation (tACS), and random noise stimulation (tRNS). Transcranial electrical stimulations safely apply, via scalp electrodes, a weak electrical current to modulate the physiological or pathological cortical and subcortical activities of healthy subjects or patients suffering from severe mental disorders. Such TES techniques can modulate synaptic plasticity and related genes. It seems not yet clear whether the application of TES on the frontal cortex of patients with schizophrenia can bring significant beneficial effects. However, tDCS applied over the left frontotemporal cortex of schizophrenia patients with disabling treatment-resistant symptoms reduces both the auditory verbal hallucinations (~30%) and the abnormal resting-state hyperactivity between the left temporoparietal junction and the anterior insula. When applied to the temporoparietal cortex of schizophrenia patients with medication-refractory auditory verbal hallucination, tDCS can not only decrease the severity of the hallucinations but also ameliorate some negative and positive symptoms. tDCS is a static current that polarizes the membrane potential of the neuronal elements of the target cortical volume whereas tACS modulates, in a frequency specific manner (within the EEG frequency range), ongoing cortical neural oscillations. There is increasing evidence that tDCS can induce memory enhancement in healthy subjects, in patients with psychiatric and neurological disorders, and in animal models. In contrast to tDCS, tACS can modulate, more directly, not only the firing of the nerve cells but also their oscillations and synchrony. In a subpopulation of patients with schizophrenia, tDCS can be efficient in the reduction of refractory verbal hallucinations but also of positive and negative symptoms. Interestingly, an imperceptible alternating current (peak-to-peak: 750 A) applied at the gamma frequency (40 Hz) to the frontal cortex can enhance cognitive performance during logical reasoning. Also, gamma frequency (25-40 Hz) tACS applied on the frontotemporal cortex of subjects during REM sleep influences ongoing brain activity and induces conscious awareness, making it possible for the dreamer to be lucid of his or her dream and to have control of its content. Gamma frequency oscillations are well known to be prevalent during REM sleep. It was recently shown that gamma tACS of the human motor cortex increases motor performance during a visuomotor task. Concurrent functional magnetic resonance imaging has revealed neural activity changes underneath the stimulation electrode and in related brain networks, including the prefrontal cortex. On the other hand, alpha frequency (10 Hz) tACS applied over the occipitoparietal cortex reduced cognitive performance in a visual task. The effects of tACS on brain network oscillations and on behavior are critically discussed in a comprehensive review article. tRNS is an alternating current stimulation technique with a wide-band stimulation frequency (up to 640 Hz). It has been shown to increase neuroplasticity during perceptual learning. In summary, TES techniques appear promising for clinical interventions. They are safer than DBS techniques and less expensive than TMS. TES is also more appropriate than DBS as a preventive treatment modality against schizophrenia because it is noninvasive and almost free of side-effects. In addition, the efficacy of TES techniques to modulate brain activities and to influence cognitive performance have been demonstrated. The mechanisms underlying their effects, however, remain still elusive. Also, more research and clinical trials are necessary to attain, during routine clinical practice, consistent benefits for patients suffering from debilitating mental illnesses. Importantly, emerging clinical interventions have shown that TES therapeutic modalities can reduce essential tremors in patients suffering from Parkinson's disease. So, one can easily imagine that the noninvasive and low-cost TES techniques might supplant invasive DBS methods. Three Candidates for Preventive TES As mentioned above, it is extremely challenging to make a decision for a late therapeutic neurophysiological intervention in treatment-resistant advanced schizophrenia. The development of chronic forms of schizophrenia takes years after the occurrence of prodromal symptoms, cognitive declines and first-episode psychosis [45,. So, would it be possible to prevent or to delay the progressive development of chronic schizophrenia? Early therapeutic intervention is a notion that has been around with increasing interest during the last two decades. Indeed, the complex symptomatology of schizophrenia results from progressive abnormalities of brain networks, including the thalamus with its reciprocal connections with the cerebral cortex [11,. Even if cognitive impairments are relatively modest during the prodromal phase of schizophrenia, efficient early therapeutic intervention could stop or delay the onset of psychotic disorders, which might otherwise lead to further cognitive damage and impaired daily functioning. A preventive treatment against schizophrenia of course requires a better understanding of the evolution of the clinical disorganization and of the cognitive changes that can be observed from premorbid to first-episode psychosis. The great challenge is to identify the time window when the very first clinical symptoms and cognitive declines start to occur in individuals who will actually develop schizophrenia. The "primary" factor(s) responsible for the progressive neural changes leading to chronic forms of schizophrenia remain to be identified. Whatever the preventive neurophysiological therapy implies, it should target an etiopathophysiological mechanism that is at the root of the mental disorders. Multiple diverse (genetic, epigenetic, neurodevelopmental, immunological, environmental, socio-cultural) factors are thought to be (either in isolation or through interactions), the cause of schizophrenia [14,. This is a long-standing debate that is not discussed in the present essay. Here, I highlight recent findings supporting the glutamate neurotransmission hypothesis of schizophrenia, which implicates critical etiopathophysiological mechanisms that appear early during its progressive development. Here, it is assumed that these processes are common to several types of chronic schizophrenia during the prodromal phase. Glutamate is one of the main neurotransmitters of the thalamus, an essential subcortical structure involved in sensory discrimination, motor and cognitive processes. It is worth mentioning that more than 80% of the thalamic neurons are glutamatergic and they are massively innervated by the CT neurons, which are also glutamatergic. Importantly, there is compelling evidence that multiple and diverse abnormalities (glutamate receptors, transporters and associated proteins; NMDAR-associated intracellular signaling proteins, and glutamatergic enzymes) related to the glutamate transmission have been found in the thalamus of patients with schizophrenia. Furthermore, in the following, we describe compelling evidence that the pathogenesis of first-episode psychosis can be better modeled translationally than chronic forms of schizophrenia. Therefore, we will also demonstrate that the thalamus might be an interesting target for TES, directly and indirectly via the glutamatergic CT pathway, designed for early therapeutic intervention against first-episode psychosis and chronic forms of schizophrenia. The Corticothalamic Pathway and the Thalamus The thalamus, located around the third ventricle, is reciprocally connected with the cerebral cortex and it receives inputs from the cerebellum, the basal ganglia, the brainstem and basal forebrain. The thalamus is an essential relay and plays an integrative role for ongoing and function-related cortical activities. It relays information to multiple regions of the cerebral cortex in a bottom-up (from the external world via the sensory receptors) and a top-down (from the cerebral cortex) fashion. During sensory discrimination, sensorimotor integration and cognitive processes, the information circulates along the glutamatergic CT and thalamocortical (TC) pathways. The thalamus is implicated in multiple functions: sensory perception (visual, somatosensory, auditory), sleep, wakefulness (through the ascending activating system), pain, attention and consciousness. It is also implicated in many neurological and psychiatric diseases, including Alzheimer's disease, Parkinson disease, epilepsy, schizophrenia, autism, bipolar disorders, chronic pain and major depression. Damage to the thalamus can cause very long-lasting (>3 years) or permanent coma. The thalamus is also the anatomical target of therapeutic DBS methods. The specific prethalamic (or peripheral) inputs of the sensory systems innervate both the specific or first-order (primary sensory) and the non-specific or higher-order (associative and cognitive) thalamic nuclei. First-and higher-order thalamic nuclei relay information to the granular and the supra-and infragranular layers of the neocortex, respectively. TC neurons, the principal neurons of the thalamus, are glutamatergic and their axon relays thalamically processed signals to the cerebral cortex ( Figure 1A). In contrast to the CT pyramidal neurons, the TC neurons do not communicate with each other. The TC axons give rise to en passant collaterals in the GABAergic thalamic reticular nucleus (TRN)-a thin layer that covers the lateral walls of the dorsal thalamus-which is the principal source of GABA receptor-mediated inhibition of TC neurons. The TC-related information is also computed in vertical (within the cortical column) and horizontal (between columns) cortical networks, linked with other cortical (distant areas) and subcortical structures (e.g., striatum, amygdala, and hippocampus; Figure 1B). Intracortically-computed information reaches the thalamus via CT axons. Thereby, both the thalamus and the cerebral cortex work together in concert through their topographically organized reciprocal connections, which form intermingled feed-forward and closed-loop CT-TC circuits. The CT pathways are of two types, one originating in layer V and the other in layer VI. The GABAergic TRN is an inhibitory interface strategically located between the thalamus and the neocortex. It is innervated by glutamatergic TC and layer VI CT inputs (Figures 1 and 2). TRN cells have dendro-dendritic synapses to communicate among each other ( Figure 2). The TRN is also characterized by an important intrinsic network of chemical (GABAergic) and electrical synapses, which can effectively be influenced by the layer VI CT pathway. The hodology and the innervation pattern of the CT-TRN-TC circuit strongly indicate that the GABAergic TRN neurons are implicated in both top-down and bottom-up processing, suggesting that the TRN might play a central role in attentional processes. Moreover, lesions of the TRN lead to attentional deficit. Their axonal projections are topographically organized and form open-loop connections with the related TC neurons, the anatomical substrate of lateral inhibition in the thalamus. Thereby, TRN neurons can modulate, in a coordinated fashion, the TC activities that are relevant for attention and integration processes. In schizophrenia, disorders of thalamic lateral inhibition are thought to disturb the pattern of TC activity on the way to the cerebral cortex. Importantly, GABAergic TRN neurons are endowed with powerful oscillatory properties (see below). The layer V CT pathway selectively innervates the higher-order thalamic nuclei in a focal manner (like a driver input). Like the peripheral inputs, it does not innervate the TRN, in contrast to the layer VI CT pathway. This layer V CT pathway is an essential element in cortico-cortical (or transthalamic) circuits, which parallel direct cortico-cortical connections. The principal axon of layer V CT neurons also innervates motor centers in the brainstem and spinal cord. The axonal branch that innervates the thalamus conveys corollary discharges used to modulate imminent sensorimotor processing. In fact, corollary discharges might be disturbed in schizophrenia. Both layer V and VI CT pathways are assumed to work together in synergy from the very first stages of sensorimotor processing up to subsequent higher cognitive and motor processes. system. This is the principal CT-TRN-TC system that is common to first-and higher-order thalamic nuclei. (A) Mounting of reconstructed juxtacellularly-labelled neurons of the rat primary somatosensory system. Both the CT (in green) and the TC (in blue) neurons are glutamatergic (glu) and their principal axon crosses the TRN where it gives rise to axon collaterals. The TRN neuron is GABAergic (gaba) and innervates only the TC neurons of the dorsal thalamus principally through lateral inhibition. (B) In this schematic drawing of this 3-neuron circuit, the principal afferents (bg, basal ganglia; cb, cerebellar; sens, sensory) and efferents of the dorsal thalamus are indicated, the TRN being part of the ventral thalamus. The GABAergic TRN is an inhibitory interface strategically located between the thalamus and the neocortex. It is innervated by glutamatergic TC and layer VI CT inputs (Figures 1 and 2). TRN cells have dendro-dendritic synapses to communicate among each other (Figure 2). The TRN is also characterized by an important intrinsic network of chemical (GABAergic) and electrical synapses, which can effectively be influenced by the layer VI CT pathway. The hodology and the innervation pattern of the CT-TRN-TC circuit strongly indicate that the GABAergic TRN neurons are implicated in both top-down and bottom-up processing, suggesting that the TRN might play a central role in attentional processes. Moreover, lesions of the TRN lead to attentional deficit. Their axonal projections are topographically organized and form open-loop connections with the related TC neurons, the anatomical substrate of lateral inhibition in the thalamus. Thereby, TRN neurons can modulate, in a coordinated fashion, the TC activities that are relevant for attention and integration processes. In schizophrenia, disorders of thalamic lateral inhibition are thought to disturb the pattern of TC activity on the way to the cerebral cortex. Importantly, GABAergic TRN neurons are endowed with powerful oscillatory properties (see below). The layer V CT pathway selectively innervates the higher-order thalamic nuclei in a focal manner (like a driver input). Like the peripheral inputs, it does not innervate the TRN, in contrast to the layer VI CT pathway. This layer V CT pathway is an essential element in cortico-cortical (or transthalamic) circuits, which parallel direct cortico-cortical connections. The principal axon of layer V CT neurons also innervates motor centers in the brainstem and spinal cord. The axonal branch that innervates the thalamus conveys corollary discharges used to modulate imminent sensorimotor processing. In fact, corollary discharges might be disturbed in schizophrenia. Both layer V and VI CT pathways are assumed to work together in synergy from the very first stages of sensorimotor processing up to subsequent higher cognitive and motor processes. The layer VI CT pathway plays an essential role in attentional and integrative processes [8,. This CT pathway innervates the TRN and the related first-and higher-order thalamic nuclei. This pathway exerts a massive (about ten-fold stronger than the corresponding TC pathway) and regional innervation within large thalamic territories ( Figure 2). Cortical layer VI contains a heterogeneous population of neurons. The layer VI CT pathway is the major glutamatergic output, which is reciprocally connected with TC neurons. Layer VI CT apical dendrites and axon collaterals terminate in layer III-IV. Their axon collaterals are implicated in both excitatory and inhibitory feedback mechanisms in layer IV. Layer VI CT axons innervate other layer VI CT neurons. Their apical dendrites can perform active integration of synaptic inputs via dendritic spiking. There is anatomical evidence that some dendritic spines of neocortical pyramidal neurons are simultaneously innervated by GABAergic and glutamatergic inputs from local-circuit cells and TC neurons, respectively. Thereby these GABAergic inputs can gate the synaptic impact of the incoming TC inputs on the pyramidal neurons. Layer VI CT neurons mediate most of their excitatory neuronal transmissions through the activation of ionotropic (NMDA and AMPA) and metabotropic glutamate receptors in both the cortex and the thalamus. Interestingly, Layer VI CT neurons innervate not only the thalamus but also cortical layer IV, suggesting that layer VI CT neurons exert a dual, intrathalamic and intracortical, feedback control of incoming TC activities. Such a cortical feedback would have a facilitatory effect on the thalamus. Thereby, the spatiotemporal dynamics of intracortical synaptic and intrinsic processes, especially in layer VI dendrites, are under the influence of the dialogue between the corresponding CT and TC neurons. The layer VI CT pathway plays an essential role in attentional and integrative processes [8,. This CT pathway innervates the TRN and the related first-and higher-order thalamic nuclei. This pathway exerts a massive (about ten-fold stronger than the corresponding TC pathway) and regional innervation within large thalamic territories ( Figure 2). Cortical layer VI contains a heterogeneous population of neurons. The layer VI CT pathway is the major glutamatergic output, which is reciprocally connected with TC neurons. Layer VI CT apical dendrites and axon collaterals terminate in layer III-IV. Their axon collaterals are implicated in both excitatory and inhibitory feedback mechanisms in layer IV. Layer VI CT axons innervate other layer VI CT neurons. Their apical dendrites can perform active integration of synaptic inputs via dendritic spiking. There is anatomical evidence that some dendritic spines of neocortical pyramidal neurons are simultaneously innervated by GABAergic and glutamatergic inputs from local-circuit cells and TC neurons, respectively. Thereby these GABAergic inputs can gate the synaptic impact of the incoming TC inputs on the pyramidal neurons. Layer VI CT neurons mediate most of their excitatory neuronal transmissions through the activation of ionotropic (NMDA and AMPA) and metabotropic glutamate receptors in both the cortex and the thalamus. Interestingly, Layer VI CT neurons innervate not only the thalamus but also cortical layer IV, suggesting that layer VI CT neurons exert a dual, intrathalamic and intracortical, feedback control of incoming TC activities. Such a cortical feedback would have a facilitatory effect on the thalamus. Thereby, the spatiotemporal dynamics of intracortical synaptic and intrinsic processes, especially in layer VI dendrites, are under the influence of the dialogue between the corresponding CT and TC neurons. In the thalamus, NMDAR-mediated excitatory postsynaptic currents are much larger in CT than in prethalamic (sensory inputs) synapses. Importantly, the corresponding NMDAR-related response is antagonized by the NMDAR antagonist ketamine or MK-801, which significantly increases the power, and the synchrony, of ongoing GFO in the highly-distributed CT-TC systems. Moreover, the CT pathway significantly contributes to thalamic GFO. The layer VI CT pathway also exerts a great influence on the state of the membrane potential of the TC neurons, as well as on ongoing and function-related thalamic activities. More specifically, the CT neurons shape the spatiotemporal receptive fields of TC cells and play an essential role in the coordination of widespread coherent oscillations. Importantly, the CT innervation, mediated by both NMDA and non-NMDA receptors, is more effective to the TRN than to TC neurons. In the TRN, the CT pathway involves not only monosynaptic excitations but also disynaptic and polysynaptic GABA(A)-mediated inhibitions. Thereby, the layer VI CT pathway and the TRN work together as an attentional searchlight (focused attention) to salient sensory stimuli [165,. There is a large body of comprehensive anatomo-functional studies showing that CT neurons exert a simultaneous effect on both the center (excitation) and the surround (suppressive) of receptive fields [189,. The CT synapses would thus exert a crucial role in sharpening the thalamic receptive field via intensifying both the center and the surround mechanisms. The CT influence is dynamic with an excitation-inhibition balance changing in an activity-dependent manner. Sustained cortical activity enhances thalamic activities, such as during states of focused attention. Finally, CT neurons are thought to function similarly across species and across sensory modalities. Thalamic rhythms: The thalamus plays a crucial role in the generation of brain rhythms and it is implicated in a wide range of brain oscillations. Indeed, the thalamic neurons are endowed with state-, time-and voltage-dependent properties, under the control of synaptic inputs, which allow them to fire a single action potential or a high-frequency (up to 600 Hz) burst of two to seven action potentials. The firing mode, tonic or bursting, is determined by low-threshold T-type calcium channels. They are inactivated at a membrane potential more positive than −60 mV and de-inactivated below for more negative values. This means that for a membrane potential hyperpolarized below −60 mV, any intrinsic depolarization or depolarizing input, including a reversed inhibitory postsynaptic potential, can trigger a low-threshold potential crowned by a high-frequency burst of action potentials. In short, when the T channels are inactive, the thalamic neurons fire in a tonic manner; they fire in the burst mode when the T channels are de-inactivated. These electrophysiological properties have been characterized in detail in a countless number of publications (for review see, e.g., ). The GABAergic TRN cells are also endowed with state-and voltage-dependent pacemaker properties not only at the spindle frequency (7-12 Hz) but also at the gamma frequency oscillations. Indeed, the membrane of the GABAergic TRN neurons can generate intrinsic subthreshold and threshold GFO, which result in rhythmic GABA(A) receptor-mediated inhibitory postsynaptic potentials in related TC neurons. The oscillating properties of TRN and TC neurons are influenced by the CT pathway. Therefore, the TRN plays a key role in the state-dependent generation of thalamic GFO, which are under the powerful control of large populations of layer VI CT neurons. In schizophrenia, the thalamus and its related networks present diverse (structural, chemical, physiological and metabolic) abnormalities [5,7,11,140,. Volumetric and structural studies using imaging have revealed a reduction in the volume of the thalamus not only in chronic schizophrenia but also in first-episode psychosis and in antipsychotic-naive high-risk individuals for psychosis. These structural changes may be linked to a functional dysconnectivity between the thalamus and the cerebral cortex in both early and chronic stages of psychosis, which is associated with cognitive impairment [10,135,. A decrease of the thalamic glutamate level has also been measured, and almost all molecules implicated in the glutamate transmission pathway are altered in the thalamus of patients with schizophrenia (changes in the expression of glutamate receptors, transporters and associated proteins). The thalamic glutamate level, measured with the use of proton magnetic resonance spectroscopy, might also be a predictor of psychosis. In first-episode and early-onset schizophrenia patients, disturbances in sleep represent a core pathophysiological feature. Cortical EEG studies conducted in such patients have revealed a significant deficit in sleep spindles, a marker of functional dysconnectivity. This might be due to a reduced function of NMDAR, as an in vitro study, conducted in thalamic slices, demonstrated that a selective blockade of NMDAR or a diminished extracellular magnesium concentration significantly shortens spindle-like oscillations. However, we do not know whether the reduction in sleep spindles in patients with schizophrenia is due to a presynaptic and/or postsynaptic dysfunction of TC or TRN neurons. It is tempting to speculate that the functional dysconnectivity recorded in schizophrenia also involves a reduction of NMDAR activity. This hypothesis is supported by the fact that, in rodents, the NMDAR antagonist ketamine, at a psychotomimetic dose, disrupts the functional state of the CT pathway. In summary, the thalamic volume and glutamate level, sleep spindles and ongoing GFO are potentially useful biomarkers for the clinician to diagnose the prodromal phase of psychosis. Therefore, the thalamus with its structural, neurochemical and electrophysiological properties seems an essential structure in the etiopathophysiology of schizophrenia, as well as a prime target structure for preventive TES, directly and indirectly via the CT pathway. Glutamatergic Transmission In the light of our current knowledge, the term "glutamate hypothesis" mean that schizophrenia is caused by multiple variables and a stream of pathophysiological processes related to NMDAR-related synaptic functions. NMDAR are well known to play, by means of synaptic plasticity, an essential role in the adequate neurodevelopment of cognitive abilities. Here, the glutamate hypothesis does not negate the dopamine hypothesis and the other pathophysiological hypotheses of schizophrenia. Moreover, the disturbed dopaminergic and glutamatergic neurotransmissions might be causally related [44,. Glutamate is the predominant neurotransmitter in the brain. It is the precursor of GABA, the most prevalent inhibitory neurotransmitter that balances glutamate's actions. Glutamate works with ion channel-associated (ionotropic) or G protein-coupled (metabotropic) receptors. It is also well known that NMDARs play, by means of synaptic plasticity, an essential role in the adequate neurodevelopment of cognitive abilities. Since 1980, there have been increasing lines of evidence suggesting that glutamate-based synaptic neurotransmission is altered in schizophrenia. Kim and colleagues measured a decrease of glutamate in the cerebrospinal fluid of an untreated patient with schizophrenia. Then, studies performed on postmortem human brain samples demonstrated changes in glutamate receptor binding, transcription and subunit protein expression in the prefrontal cortex and subcortical structures, including the thalamus and hippocampus. They also showed altered levels of the amino acids N-acetyl aspartate (NAA) and N-acetyl aspartyl glutamate (NAAG) and of the activity of the enzyme that cleaves NAA to NAAG and glutamate in the cerebral spinal fluid and postmortem tissues from patients suffering from schizophrenia. Also, genetic studies have revealed that a majority of genes associated with schizophrenia are linked to the glutamatergic system [248,. Interestingly, an imaging study (SPECT tracer for the NMDAR) revealed a reduction in NMDAR binding in the hippocampus of medication-free patients. Even when considering the possibility that schizophrenia is caused by an immune dysfunction due to infectious agents, a link is identified between immune alterations and disturbances of glutamate NMDA receptors. Interestingly, there is a growing body of findings indicating that glutamate synaptic transmission is significantly altered in schizophrenia since the premorbid phase [244,245,254,. In summary, disturbances in glutamate synaptic transmission, involving a reduced function of NMDAR with multiple functional consequences, start to appear early during the development of schizophrenia. This may cause the dysfunctional neural plasticity in schizophrenia. A certain number of genes (DISC-1, dysbindin, SHANK, and NRG-1) are well-known to modulate NMDAR-mediated glutamate transmission. This notion is supported by patients with an autoimmune encephalitis because they produce antibodies against NMDAR and have a clinical disorganization that is similar to that of patients with schizophrenia. Therefore, glutamate transmission appears a potential "primary" target for an early therapeutic intervention. Of importance, the psychosis-relevant abnormal amplification of GFO is reliably reproduced in healthy humans and rodents under the acute influence of the NMDAR antagonist ketamine at a psychotomimetic dose. So, these translational acute pharmacological models seem appropriate to develop an innovative preventive treatment against the development of chronic psychotic disorders. It is well recognized that reduced function of NMDAR is a crucial factor for the progression and symptoms of schizophrenia. It is tempting to posit that an appropriate preventive treatment would correct the dysfunctional brain network plasticity. Gamma Frequency (30-80 Hz) Oscillations, a Potential Pathophysiological and Therapeutic Bioelectrical Marker In the present essay, I put emphasis on GFO because there is compelling evidence of functional links between GFO, NMDAR hypofunction and a reduction in the number and the function of cortical GABAergic interneurons in schizophrenia. This implies that GFO are considered a common denominator of the above-presented three facets (CT pathway, thalamus, and glutamate transmission), which represent the etiopathophysiological backbone for premorbid, acute and chronic psychotic disorders. Indeed, (i) coherent GFO are recorded not only in the neocortex but also in the related thalamus; (ii) the layer VI CT pathway contributes to thalamic GFO; and (iii) GFO increase in amplitude and power not only during hallucinations, in at-risk individuals for psychosis, but also after the administration, at a psychotomimetic dose, of the NMDAR antagonist ketamine. It is worth remembering that, in humans, GFO start to emerge several months after birth. It was demonstrated that, during rodent neural development, thalamic GFO play a crucial role in the mapping of the functional TC modules. Both in humans and rodents, GFO are simultaneously present in cortex and thalamus. In the following, we will see that GFO are also potential bioelectrical markers of psychosis, which could be used for the development of therapeutic interventions. Coherent synchronized GFO emerge in large-scale cortical-subcortical networks spontaneously or during global brain operations such as attention, perception, and memory. They are thought to play an essential role in synaptic plasticity, spatiotemporal coding (binding by synchronization), storage and recall of information. Network GFO are ubiquitous and operate in combination with other brain rhythms. Extracellular field GFO principally result from subthreshold, synaptic and intrinsic membrane potential oscillations that trigger action potentials at a precise phase during the oscillatory period. Their functions and mechanisms are still a matter of debate. The functional interactions between GABAergic and glutamatergic neurons are thought to be responsible for the generation of GFO during attention and integration processes. There is accumulating evidence that, in schizophrenia, the dysfunctional network connectivity between cerebral cortex and thalamus is accompanied by disturbances in GFO and by deficits in sensorimotor and cognitive performance [4,53,. There is also evidence of a correlation between schizophrenia-related symptoms and in particular cognitive and perceptual deficits with disturbances in cortical GFO, also in first-episode schizophrenia. Gamma oscillations may be considered not only as neurophysiological markers of the functional state of brain networks but also as trait markers in schizophrenia. Of importance, abnormally increased GFO are recorded in patients with first-episode schizophrenia and in at-risk mental state patients for psychosis. Gamma oscillations are also abnormally excessive in amplitude during hallucinations. Increased GFO are associated more with positive (such as hallucinations) than negative symptoms. Therefore, hypersynchronized GFO look like a predictive bioelectrical marker for both psychosis and treatment outcome. As reported above, such abnormally amplified GFO can consistently be reproduced in healthy humans and rodents following the systemic administration at a psychotomimetic dose of the NMDAR antagonist ketamine. These translational acute ketamine models, which model the prodromal phase of psychotic disorders and first-episode psychosis, are thus appealing to work out a preventive treatment against the occurrence of chronic forms of schizophrenia. It may be worth specifying that a single low-dose (<10 mg/kg) application of ketamine in rats increases hyperfrontality, which can also be observed in first-episode schizophrenia. In contrast, hypofrontality is diagnosed in patients with chronic schizophrenia. Therefore, the acute ketamine model may be more appropriate to mimic the pathogenesis of acute psychotic states in humans. Abnormally amplified GFO in neural networks may contribute to the disruption of the integration of task-relevant information, which is part of psychotic symptoms. Moreover, in rodents, a single systemic administration (at a subanesthetic dose) of ketamine disturbs the functional state of the somatosensory CT-TRN-TC circuit (Figure 3). Ketamine reliably increases the amplitude and power of spontaneously-occurring GFO and decreases the amplitude of the sensory-evoked potential and its related evoked GFO in both the thalamus and the neocortex. In other words, the NMDAR antagonist ketamine generates persistent and generalized hypersynchrony in GFO, which act as an aberrant diffuse network noise under these conditions, and represent a potential electrophysiological correlate of a psychosis-relevant state. Such a generalized network gamma hypersynchrony thought to create a hyper-attentional state (see discussion in ), might be the force that disrupts the flow of sensorimotor and cognitive processes as observed in schizophrenia. Thereby, ketamine reduces the ability of the somatosensory CT-TRN-TC system to encode and integrate incoming information, perhaps by disrupting the center-surround receptive field properties in thalamic neurons. The electrophysiological signals (ongoing and sensory-related potentials and GFO) appear as valuable neurophysiological markers to test the functional state of neural networks. Such quantifiable bioelectrical markers might thus be a promising translational tool to develop innovative therapies designed to prevent the occurrence of psychotic disorders. In short, ketamine decreases the signal-to-noise ratio at least in the CT-TRN-TC system. Ketamine also transiently disrupts the expression of long-term potentiation in the TC system, disorganizes action potential firing in rat prefrontal cortex, increases the firing in fast-spiking neurons and decreases it in regular spiking neurons and disturbs sensory-related cortical and thalamic GFO. Dizocilpine (MK-801) is, like its derivative ketamine, a well-known non-competitive NMDAR antagonist with psychotomimetic properties leading to similar but more sustained effects than ketamine. It addition, dizocilpine modulates the expression of numerous genes in cortical and subcortical structures. In summary, neural GFO represent a translational bioelectric marker. It may be considered a potential prognostic and therapeutic hallmark for cerebral network disorders underlying psychotic symptoms. Such a quantifiable marker might be a promising translational tool for understanding the etiopathophysiological mechanisms of psychotic disorders and for developing innovative therapies. These include, for instance, noninvasive neurophysiological modalities such as TES, applied in at-risk mental state individuals to prevent the occurrence of first-episode psychosis and chronic forms of psychotic disorders. Layer VI CT neurons innervate the thalamic relay (TC) and reticular (TRN) neurons through the activation of glutamate ionotropic (NMDA and AMPA) and metabotropic receptors. Ketamine is expected to decrease the NMDA/AMPA ratio at least at CT synapses. Thereby, ketamine disturbs the mental state and decreases the gamma signal-to-noise ratio in the CT-TRN-TC system. The sensoryevoked potential (SEP) can be considered as an index of the sensory-related signal. Adapted from and from. Potential Mechanisms of TES Little is known about the mechanisms underlying the clinical, acute and chronic effects of TES techniques, which are expected to re-establish the normal functional state in dysfunctional corticalsubcortical networks and/or to recruit compensatory networks. Whatever the technique and specific setting considered, it is difficult to perceive an integrated view of the mechanisms that are responsible for and contribute to the expected and the observed clinical effects. The possible mechanisms include genetic, molecular, cellular and systems pathways as well as long-lasting processes involving plasticity. The nerve cells are embedded in a conductive medium, the extracellular space, an important interface between the exogenous and endogenous electric currents and the excitable and non-excitable elements involved in information processing. In addition, before reaching the excitable cellular and subcellular elements, the TES-induced electric currents cross several types of barriers, including the cranium, the meninges, the vascular network and the glial tissue. Also, the Figure 3. The NMDAR antagonist ketamine decreases the ability of the cortico-reticulo-thalamocortical (CT-TRN-TC) system to integrate incoming information. A single systemic administration of ketamine disturbs the functional state of the three-neuron circuit (layer VI CT-TRN-TC). Ketamine increases the amplitude of spontaneously occurring gamma frequency oscillations and decreases the amplitude of the sensory-evoked potential in both the thalamus and the neocortex. Layer VI CT neurons innervate the thalamic relay (TC) and reticular (TRN) neurons through the activation of glutamate ionotropic (NMDA and AMPA) and metabotropic receptors. Ketamine is expected to decrease the NMDA/AMPA ratio at least at CT synapses. Thereby, ketamine disturbs the mental state and decreases the gamma signal-to-noise ratio in the CT-TRN-TC system. The sensory-evoked potential (SEP) can be considered as an index of the sensory-related signal. Adapted from and from. Potential Mechanisms of TES Little is known about the mechanisms underlying the clinical, acute and chronic effects of TES techniques, which are expected to re-establish the normal functional state in dysfunctional cortical-subcortical networks and/or to recruit compensatory networks. Whatever the technique and specific setting considered, it is difficult to perceive an integrated view of the mechanisms that are responsible for and contribute to the expected and the observed clinical effects. The possible mechanisms include genetic, molecular, cellular and systems pathways as well as long-lasting processes involving plasticity. The nerve cells are embedded in a conductive medium, the extracellular space, an important interface between the exogenous and endogenous electric currents and the excitable and non-excitable elements involved in information processing. In addition, before reaching the excitable cellular and subcellular elements, the TES-induced electric currents cross several types of barriers, including the cranium, the meninges, the vascular network and the glial tissue. Also, the applied electric field has two components, one parallel and the other one perpendicular to the brain surface. The strength of these two components determines the relative influence of TES on the excitability of the neural and non-neuronal elements. All these barriers, as well as the ongoing changes in the brain state, are a source of interferences with the electric field. Taken together, TES is expected to target a large number of neuronal and glial elements over large cortical and subcortical regions. The clinical effects of TES and the underlying short-and long-term mechanisms principally rely on the electrode type and stimulation parameters (stimulus location, intensity, duration, polarity). The TES effects on brain structures are non-selective, state-dependent, and the strongest impact is not necessarily exerted in neural structures that are located below the electrodes. The TES effects on the cellular and subcellular excitable elements depend on their geometry and on their spatial orientation in the electric field. Both the TES effects and the underlying mechanisms lie on a continuum of effects ranging from the stimulation settings to the ongoing genetic, molecular, cellular and network dynamics. The mechanisms underlying the effects of TES are the subject of intensive research (for a review see: [33,119,). Our current knowledge remains fragmented with multiple and diverse proposed mechanisms: conduction block, synaptic potentiation or depression, network resonance, modulation of brain oscillations [127,337,, of ongoing cellular firing and subthreshold membrane potential oscillations, of dendritic inhibition, of the astrocytic Ca 2+ /IP3 signaling and of the synaptic efficacy in excitatory and inhibitory pathways. It is reasonable to assume that multiple mechanisms are likely to operate in combination. The combination of these multiple mechanisms over time can be viewed as "meta-mechanisms" at the brain-network level. In the following, I speculate on a few possible mechanisms that may, depending on the TES modality, be involved in the modulation of the layer VI CT pathway, which massively innervates both the dorsal thalamus and the TRN. As mentioned above, this glutamatergic pathway may be one of the prime targets for preventive TES in at-risk mental state individuals for psychotic disorders. In the present discussion, I take fundamental principles of neurophysiology into consideration. As the electrical field spreads at the speed of light, all neural and non-neural elements will be affected at the same time. The TES effects are expected to be attenuated with distance, obeying to the rule that the amount of current delivered by the electrode is proportional to the square of the distance between the brain elements and the stimulation electrode. Figure 4 illustrates some of the anatomo-functional elements of the CT-TRN-TC system, which may somehow be impacted by TES electric fields. TES entrains neuronal populations: Nerve cells operate on the basis of electrical charges, which makes them also responsive to weak electric currents. Importantly, it was demonstrated that, in the rat, TES can directly entrain neurons in multiple neocortical areas and sub-neocortical structures, including the hippocampus. Indeed, some of the cortical and hippocampal neurons were affected at similar phases of the TES oscillations, suggesting the contribution of non-synaptic mechanisms in the TES-induced direct entrainment of cortical and subcortical neurons. Of course, the directly activated neurons become a source for subsequent polysynaptic mechanisms, which represent a significant contribution in TES-induced entrainment over large cortical territories and the related subcortical structures. The percentage of TES phase-locked neurons depends on the state of brain networks and increases with TES intensity. Furthermore, intracellular recordings revealed that both the firing and the underlying subthreshold and suprathreshold membrane potential oscillations are under the combined influence, through amplification, attenuation or interference, of TES fields and global network activities. The mechanisms underlying the TES direct effects on ongoing neuronal activity are not well understood.. Potential mechanistic targets in the cortico-reticulo-thalamocortical (CT-TRN-TC) system for transcranial electrical stimulation. This model includes three parts, which are assumed to work together: (i) The innervation of the intracortical circuitry by both the descending axonal branches (topdown process) of the axons running within the molecular layer and the ascending TC inputs (bottomup process); (ii) functional interactions between glutamatergic and GABAergic neurons of the intracortical circuitry, which includes feedback and feedforward excitations (from CT and TC axon collaterals, respectively); and (iii) the layer VI CT pathway, one of the outputs of the intracortical circuitry, which innervates simultaneously the thalamic GABAergic reticular (TRN) and glutamatergic relay (TC) neurons. In this model, the TRN cells generate more lateral than feedback inhibition in the dorsal thalamus, which contains only TC neurons. The layer VI CT axonal projections are about ten-fold higher in number than the TC projections, thereby generating a great excitatory pressure on TRN and TC neurons. Furthermore, the apical dendrites of layer VI pyramidal neurons terminate in layers III-IV. Each neuron exhibits its own firing pattern that is state-, voltage-, synapticand time-dependent. The action potentials (APs) are drawn like a code bar. Under physiological condition, it is assumed that the APs are initiated at the axon hillock, the initial segment of the axon. The axon can also transmit, in addition to APs, analog signals (generated in the somatodendritic domain and represented by sinusoidal waves) along the axon (at least several hundreds of micrometers away from the soma) and can modulate AP-evoked transmitter release at the corresponding synapses. In this model, it is assumed that axodendritic (chemical synapses) and dendrodentritic electrical (via gap junctions) coupling exist between the two types (basket and chandelier) of GABAergic parvalbumin (PV) expressing cells. 5-HT, 5-HT3A receptor; CT, corticothalamic; SOM, somatostatin; ssc, spiny stellate cells; TC, thalamocortical; TRN, thalamic reticular nucleus.. Potential mechanistic targets in the cortico-reticulo-thalamocortical (CT-TRN-TC) system for transcranial electrical stimulation. This model includes three parts, which are assumed to work together: (i) The innervation of the intracortical circuitry by both the descending axonal branches (top-down process) of the axons running within the molecular layer and the ascending TC inputs (bottom-up process); (ii) functional interactions between glutamatergic and GABAergic neurons of the intracortical circuitry, which includes feedback and feedforward excitations (from CT and TC axon collaterals, respectively); and (iii) the layer VI CT pathway, one of the outputs of the intracortical circuitry, which innervates simultaneously the thalamic GABAergic reticular (TRN) and glutamatergic relay (TC) neurons. In this model, the TRN cells generate more lateral than feedback inhibition in the dorsal thalamus, which contains only TC neurons. The layer VI CT axonal projections are about ten-fold higher in number than the TC projections, thereby generating a great excitatory pressure on TRN and TC neurons. Furthermore, the apical dendrites of layer VI pyramidal neurons terminate in layers III-IV. Each neuron exhibits its own firing pattern that is state-, voltage-, synaptic-and time-dependent. The action potentials (APs) are drawn like a code bar. Under physiological condition, it is assumed that the APs are initiated at the axon hillock, the initial segment of the axon. The axon can also transmit, in addition to APs, analog signals (generated in the somatodendritic domain and represented by sinusoidal waves) along the axon (at least several hundreds of micrometers away from the soma) and can modulate AP-evoked transmitter release at the corresponding synapses. In this model, it is assumed that axodendritic (chemical synapses) and dendrodentritic electrical (via gap junctions) coupling exist between the two types (basket and chandelier) of GABAergic parvalbumin (PV) expressing cells. 5-HT, 5-HT3A receptor; CT, corticothalamic; SOM, somatostatin; ssc, spiny stellate cells; TC, thalamocortical; TRN, thalamic reticular nucleus. The axonal membrane, the more excitable element: The axonal membrane is generally more excitable than the somatic and dendritic membranes. There is increasing evidence supporting the hypothesis that distal parts of the axon, remote from the axon initial segment, can autonomously integrate and generate action potentials, which could contribute to the emergence of field GFO involving synchronized GABAergic rhythmic activities. So, it is predictable that the TES-induced electric field would create regional conditions in cortical tissue favorable for activating axons. Also, the number and the location of the activated axonal areas depend on both the neural tissue architecture and geometry, in relation to the direction of the electric field. The pattern of activated axons depends on the direction of the electric field and of the state of the cortical region being stimulated. The more numerous intersecting axons within an axonal bundle, the more numerous the axonal couplings. An axon curvature would be as excitable as the initial segment. Because the axonal membrane is more excitable than the somatodendritic membrane and is endowed with integrative properties, the TES-induced field may activate intracortical axons and axonal endings, where action potentials may be initiated. Dopamine and kainate can generate axon membrane depolarization leading to action potential initiation. Also, oligodendrocytes, in addition to regulating myelination, would play a promoting role in synchronizing firing through axons. Axo-axonal interactions can also involve glial cells. Once triggered, ectopic axonal action potentials would run along the axons simultaneously both orthodromically up to the axon terminals and antidromically up to the parent somatodendritic domains. The orthodromically conducted action potentials would then activate local and distant postsynaptic neurons. A single orthodromically conducted action potential can even itself generate, for a while (a few tens of ms), a sequence of excitatory and inhibitory synaptic events in a subpopulation of interconnected glutamatergic and GABAergic neurons. On the other hand, the antidromically conducted action potentials can activate directly the parent somatodendritic complex. Moreover, TC neurons can spontaneously generate ectopic axonal action potentials, which subsequently modulate the parent soma's excitability. Cortical neurons are excited when the electric field is directed from the dendrites toward the axon. The impedance mismatch between the dendritic arbor and the principal axon represents a likely mechanism for TES-induced cortical excitation. Moreover, low-intensity electric fields concurrent to suprathreshold synaptic inputs can modulate the timing of action potential initiation. Therefore, TES has the potential to influence the functional input-output balance in neurons. Electrical couplings: Couplings between neurons in the central nervous system can occur through electrical synapses, that is, gap junctions. They represent another potential target for the TES electric field. An important feature of these synapses is that they are bidirectional. Axo-axonal electric coupling via gap junctions is thought to contribute to the oscillating and integrative properties of neural networks. This is a possible mechanism through which periodic TES can entrain oscillating neural networks. Sparse electrical couplings through axo-axonal gap junctions play a key role in the initiation and spreading of network gamma and higher (>100 Hz) frequency oscillations. The coupling action potentials occur in the axon prior to invading the parent somatodendritic tree. Such a mechanism represents a fast device for signal transmission directly between the outputs of neurons, thereby leading to temporally precise firing during fast network synchrony. This supports the notion that the axon and its branches are not only reliable transmission cables for action potentials but also functional entities with integrative properties. In the presented CT-TRN-TC system (Figure 4), it is shown that intracortical GABAergic parvalbumin-expressing interneurons communicate with each other through electrical and chemical synapses, which are functional modalities of tight couplings that contribute to the generation of synchronized oscillations in cortical structures. Such couplings may also be influenced by TES. Electrical couplings between central nervous system neurons can also occur through direct electrical (or ephaptic: touch phenomenon through ion exchanges between two adjacent excitable membranes) coupling. Electrical couplings could also be mediated by the electric field generated jointly by many parallel axons. Such couplings might significantly be influenced not only by endogenous but also by exogenous electric fields independently of electrical and chemical synapses. Therefore, ephaptic couplings may be one important target for TES. Ephaptic couplings between axons might be involved in the synchronization and the timing of action potentials as well. Endogenous or exogenous oscillating electric fields impose temporal windows, during which periodic ephaptically-induced membrane polarization can become the source of enhanced excitability in the corresponding neurons. Thereby, ephaptic coupling leads to coordinated spiking activity among nearby neurons. Ephaptic coupling influences the synchronization and timing of firing in neurons receiving suprathreshold synaptic inputs. Combined digital and analog coding: It is usually taught that excitatory and inhibitory synaptic inputs modulate the integrative properties of the somatodendritic membrane areas, which lead to local voltage fluctuations (synaptic activity) that propagates up to the axon hillock, the non-myelinated segment of the principal axon, which will initiate a firing pattern (barcode) subsequently transmitted to the downstream synapses. Once initiated, the action potentials simultaneously propagate orthodromically along the principal axon up to the presynaptic terminals, where they cause Ca 2+ influx and transmitter release, and antidromically into the somatodendritic arbor, preventing the activation of the trigger zone at a proper time and/or triggering dendritic activities. In vitro studies have demonstrated that, in the cerebral cortex and the hippocampus, somatodendritic voltage fluctuations can propagate over significant distances along the axon, change the amplitude and duration of the axonal action potential and, through a Ca 2+ -dependent mechanism, change the amplitude of the corresponding postsynaptic potentials. In short, axons can transmit analog signals in addition to action potentials (Figure 4). Such a combined digital and analog coding represents an additional mechanism for information processing in neural networks. This dual coding must be a functional target for TES. It can be predicted that a TES-induced field can, for instance, modulate (via amplification, attenuation or interference) the amplitude of the voltage fluctuations running along the axon with subsequent impact on the action potential-evoked transmitter release at the corresponding synapses. Top-down control: The first neural elements that are intensely impacted by any TES technique are, by all likelihood, first located in the more superficial layers of the cerebral cortex. The layer I or molecular layer, which is situated just underneath the pial surface, contains dense bundles of axons and dendrites and a paucity of sparsely distributed cell bodies. Some of these axons give rise to descending axonal branches that innervate cortical neurons, thereby exerting a top-down control on the cortical and subcortical networks. For instance, it was demonstrated that the electric current generated by TMS can activate a network of GABAergic interneurons that innervate, in the upper cortical layers, the apical dendrites of layer V pyramidal neurons. This GABAergic inhibition would be mediated by GABA(B) receptors, and their activation would decrease or suppress dendritic Ca 2+ currents implicated in the synaptically-mediated dendritic excitation, which is involved in the integration of information. Even if such a scenario could also apply to the dendrites of layer VI CT neurons, it remains a challenge to predict, from the inspection of individual mechanisms, the actual activity pattern of the CT neurons. Assuming that TES inhibits their somatodendritic activity and firing, reduced firing of layer VI CT neurons, which exert a massive excitatory pressure on both TC and TRN neurons (Figure 2), would lead to a disfacilitation of the thalamic activity. So, the proposed TES-induced CT disfacilitation would reduce first the monosynaptic excitation of the glutamatergic TC and GABAergic TRN neurons and, secondly, the disynaptic inhibition of the TC neurons ( Figure 4). Furthermore, because of the presence of dendrodendritic synapses between TRN neurons and because of their pacemaker properties for GFO, TES-induced disfacilitation would also reduce the multisynaptic intra-TRN inhibitions, a possible brake for the generation of thalamic GFO. It is thus tempting to hypothesize that such TES-induced intracortical dendritic inhibition can reduce the power of GFO in cortical and subcortical structures. Bottom-up effect from the thalamus: So far, TES has been presented as a noninvasive therapeutic means exerting top-down effects from the current source. Such effects can be categorized into at least two principal types of mutual interactions: local type with top-down controls, for instance the one discussed above, and a highly-distributed type, which involves interconnected cortical and subcortical networks. Indeed, it was well demonstrated that TES can directly, likely through non-synaptic mechanisms, entrain/modulate subcortical neurons. The TES-induced electric fields would act as endogenous electric fields, which are known to guide network activity, to modulate the timing of action potentials, and to enhance stochastic resonance. This is valid for both tDCS (static electric field) and tACS (alternating electric field) with effects on brain function. The TES-induced field effects would modulate the amplitude of subthreshold and suprathreshold membrane potential oscillations of the target neurons. Because of a large number of variables mentioned above, it is difficult to provide a precise picture of the direct effects of TES field on both GABAergic TRN and glutamatergic TC neurons. Whatever the differential effects, both types of neurons work together and mutually influence each other. TES would affect their threshold mechanisms equivalent to an integrate-and-fire model, which depends on a certain number of factors, including the ion channel kinetics, the weight of excitatory and inhibitory synaptic inputs and the shape of the membrane potential distribution near threshold. However, as mentioned above, we should keep in mind that both TRN and TC neurons generate action potentials during sustained membrane potential depolarization and hyperpolarization. The GABAergic TRN neurons can be considered a privileged cell-to-network target for TES indirectly through the CT pathway, as mentioned above, and directly. In the following, I will speculate on possible mechanisms underlying eventual direct effects at the thalamic level, more specifically in the GABAergic TRN cells. It is first important to know that, at a sufficiently hyperpolarized membrane potential, TRN cells are more excitable and electro-responsive than TC neurons. Indeed, high-frequency bursts of action potentials generated by excitatory inputs require a higher degree of convergence of excitatory inputs than TRN neurons. Furthermore, TRN cells are endowed with low-threshold T-type calcium currents of longer duration than TC neurons. These anatomofunctional properties suggest that TRN cells may be more electro-responsive to TES than TC neurons. Gap junctions-mediated electrical synapses is another important characteristic of GABAergic TRN neurons. Such electrical synapses are implicated in diverse forms of cell-to-network signaling. Using a novel dye-coupling technique, Connors and colleagues further demonstrated that, in the rodent, electrically coupled TRN cells form clusters with distinctive patterns and axonal projections. Unpredictably, TES would facilitate the synchronized generation and spread of electrically-and chemically-induced synaptic activities within TRN clusters. The presumed TES-induced TRN activity patterns would strongly influence network oscillations, which would generate inhibitory activities (principally lateral inhibition ) in the related populations of TC neurons. To sum up, alternating TES (or tACS) is expected to influence directly the thalamus, which is a well-known oscillator. Here, in the present conceptual context, the thalamus is a reference. This means that the proposed mechanisms underlying direct subcortical effects could apply to other sub-neocortical structures, such as the hippocampus, along with their respective anatomofunctional properties. Another direct influence relies on the fact that, as above mentioned, the axonal membrane is more excitable than the somatodendritic membrane. So, assuming that the ongoing state of the cortex allows TES-mediated triggering of action potentials on axonal terminations of TC neurons, the corresponding ectopically-generated axonal action potentials would backpropagate up to the parent somatodendritic complex of these TC neurons. Such antidromically conducted axonal action potentials would influence the somatodendritic excitability of the corresponding TC neurons. If true, such an effect may, under suitable circumstances regarding the network state, short-circuit the CT-mediated thalamic multisynaptic effects. In theory, such an effect would be more efficient when the somatodendritic field is hyperpolarized (see Figure 35 in ). In short, TES would not only generate action potentials on ectopic axonal membrane but also modulate the timing of action potential initiation in the axonal and somatodendritic membrane, thereby influencing the dynamics and plasticity of neural networks. In summary, regarding its multiple and diverse mechanisms, TES would exert local and highly distributed influences on the ongoing thalamic activities through at least three principal ways. They would, over time, occur individually or in combination leading to polysynaptic effects ( Figure 4): Direct, intracortical synaptic and non-synaptic (especially electrical) mechanisms, thereby modulating the excitability of the CT axon (from the hillock to the ascending ramifying axon collaterals) and the integrative properties of the CT neurons' somatodendritic arbor; direct, intracortical modulation of the excitability of TC axon terminals, which could initiate antidromic firing along the principal axon of TC neurons with subsequent effects on the TC neurons' somatodendritic membrane state-dependent excitability and a monosynaptic excitation of TRN cells; direct forced TES field effect on thalamic neurons, especially on the GABAergic TRN cells because they are endowed with more "explosive" electrophysiological properties than TC neurons, leading for instance to phase-biased cellular firing. Whatever the TES-induced top-down and bottom-up (from presumed direct effect on thalamic neurons) mechanisms, the effect on the excitability and integrative properties of all the elements (including non-neuronal) that make up the CT-TRN-TC system would depend on its ongoing functional state. At any rate, TES-elicited modulation of the CT pathway should influence the thalamic neurons' spatiotemporal properties, which are related to the center-surround receptive field. The predictions and hypotheses presented in the present essay need to be validated through appropriate experiments. Conclusions and Perspectives In the present essay, I began with a neurophysiological perspective on early therapeutic intervention (TES) in at-risk mental state individuals against the occurrence of FE psychosis, chronic psychotic disorders, and schizophrenia. Because of their noninvasiveness, low-cost and safety, the use of TES therapeutic modalities, which are almost free of side-effects, is increasing over years with encouraging and promising clinical outcomes. Furthermore, there is accumulating evidence that static (DC field) or alternating (AC field) TES exerts an effect on brain function. On the other hand, the underlying mechanisms still remain elusive. There is accumulating evidence that exogenous electric currents can modulate not only brain electrical activity but also behavioral and cognitive performance. All the proposed mechanisms belong to a continuum that can be considered "meta-mechanisms" at the brain-network level. The use of TES may be seen as a "natural" treatment as it can influence, like endogenous electric fields, the excitability and the integrative properties of the brain nerve cells and subcellular elements. TES can, through the extensive CT and cortico-cortical systems, nonselectively affect, directly and through multisynaptic pathways, global brain activity. This is not surprising since electrical modulation of a single neuron can modify not only the global brain state but also motor behavior, and that a single action potential can itself generate sequences of excitatory and inhibitory synaptic events in subnetworks. On the basis of our current knowledge, it is tempting to put forward that noninvasive therapeutic interventions using TES might turn out to be very promising in the future as there is emerging evidence that TES might supplant surgical DBS therapy against neurobiological disorders, including Parkinson's disease. This might also be the case for epilepsy, dystonia, obsessive compulsive disorders, pain, multiple sclerosis, addiction, depression, Tourette syndrome, and in brain-injured patients in vegetative and minimally conscious states. That TES (with settings adjusted on the basis of cortical-subcortical oscillations) can be applied to treat any neurobiological disorder rests on the notion that TES would set into action highly-distributed networks, which would help the brain, in case of dysfunctional networks associated with disturbed oscillations, to retrieve its fundamental capability to self-organize, self-calibrate and self-correct. In the present essay, there is a bias toward rodent models merely because the CT-TRN-TC system of rodents and humans share common anatomo-functional properties. The CT-TRN-TC system was put on the stage since the widespread CT pathway, the thalamus and the glutamatergic synaptic transmission together form an etiopathophysiological backbone for schizophrenia and, therefore, may represent a prime therapeutic target for preventive TES of dysfunctional brain networks in at-risk mental state individuals against the occurrence of first-episode psychosis and schizophrenia. Importantly, the one common denominator is cortical GFO, which are amplified not only during hallucinations but also in at-risk individuals for psychosis and during first-episode psychosis. Furthermore, abnormal network gamma hypersynchrony is likewise recorded in the CT systems of healthy humans and rodents after a single systemic administration, at a psychotomimetic dose, of the NMDAR antagonist ketamine. These translational ketamine models of prodromal to first-episode psychosis are thus promising means not only to work out a preventive treatment against the occurrence of chronic schizophrenia but also to investigate the TES mechanisms. An important question remains open as to whether TES is capable of replacing the generalized cortical-to-subcortical ongoing gamma hypersynchrony for normal gamma synchrony. Importantly, alpha frequency (10 Hz) tACS can reduce the power of cortical GFO. This is interesting since ongoing alpha oscillations are often associated to cortical idling whereas GFO are associated to an attentional state. Because of its activity-dependent dynamic properties, the CT pathway is expected to play a crucial role in the modulation of the ongoing activity in the CT-TRN-TC system. Indeed, a comprehensive in vitro study performed in rodent CT-TRN-TC slices demonstrated that a low-frequency optogenetic stimulation (≤10 Hz) exerts a suppressive effect on TC neurons' activity. In other words, we predict that TES of the extensive CT pathway can re-normalize/improve its key attentional role to generate in the dysfunctional CT-TRN-TC circuits, more specifically in at-risk mental state individuals, "normal" prediction models that guide the flow and sequences of sensorimotor and cognitive processes. Such mechanisms would operate in combination with the TRN, strategically located at the interface between the dorsal thalamus and the neocortex, through the modulation of the excitatory and suppressive components of the receptive fields in the appropriate and related cortical and thalamic territories. Thereby, principally under the influence of the TC pathway, the TRN may fine-tune the responsiveness of sensory, motor and cognitive TC neurons, depending on the ongoing functional brain state and on the relative timing of the multiple and diverse thalamic inputs. Now, if TES were able to suppress the psychosis-relevant CT-TRN-TC gamma hypersynchrony, thought to be the electrophysiological correlate of a hyper-attentional state, would it stop the occurrence of the schizophrenia-relevant clinical disorganization and the emotional, sensorimotor and cognitive abnormalities? This is a fundamental issue that certainly needs further investigation. Also, should TES be systematically applied, along with ethical guidelines, in a standard fashion to all at-risk mental state patients for psychotic disorders? Probably not. This is an important issue because its efficiency depends on multiple variables, more specifically on the brain state and longitudinal outcomes. Also, in an attempt to effectively apply TES at the right time, it might be necessary to use a closed-loop feedback system able to trigger the stimulation on the basis of the pattern of the ongoing brain activity. On the other hand, TES may be supplanted by, or combined with, other non-pharmacological therapies, for instance, with cognitive remediation and psychotherapies. These latter therapies are promising when it comes to helping individuals with impaired cognitive performance [146,. Mindfulness-based therapy may also be an interesting alternative or complement to TES. All these alternatives mean that a good quality of life prevails for at-risk mental state and first-episode psychosis patients with or without a rational use of TES in the frame of a personalized medicine. |
/*
A Broadcaster with few garantees.
Uses reliable links.
Author: <NAME>
Date: 11.10.20
*/
package cs451.Broadcasters;
import cs451.*;
import cs451.Links.*;
import cs451.Messages.*;
public class BestEffortBroadcaster extends Broadcaster {
private Link link;
private Observer observer;
public BestEffortBroadcaster(Observer observer){
link = new ReliableLink(this);
// other alternative that may not be functional
//link = new ReliableLink(this);
//link = new ThreadedReliableLink(this);
//link = new DirectedReliableLink(this);
this.observer = observer;
}
public void broadcast(Message m){
Main.hosts.forEach( dest -> link.send(m, dest));
}
public void receive(Message m){
observer.receive(m);
}
public Link link(){ return link;}
}
|
for i in range(5):
a = map(int , raw_input().split())
if sum(a) == 1:
r = i+1
for p in a:
if p == 1:
c = (a.index(p) + 1)
print abs(3-r) + abs(3-c) |
//<NAME> 279079
#include "utils.h"
#include "receiving.h"
#include "sending.h"
size_t vector_size = 0;
size_t neighbour_size = 0;
struct routing_record routing_vector[MAX_VECTOR_SIZE];
struct neighbour_record neighbour_vector[MAX_VECTOR_SIZE];
int sockfd;
int main()
{
if( scanf("%lu\n", &neighbour_size ) != 1 ) return EXIT_FAILURE;
vector_size = neighbour_size;
// struct routing_record * routing_vector;
// if( (neighbour_vector = (struct neighbour_record *) malloc(sizeof(struct neighbour_record)*neighbour_size)) == NULL )
// {
// printf("ERROR:NOT ENOUGH MEM FOR neighbour_vector\n" );
// return EXIT_FAILURE;
// }
// if((routing_vector = (struct routing_record *)malloc(sizeof(struct routing_record)*MAX_VECTOR_SIZE)) == NULL)
// {
// printf("ERROR:NOT ENOUGH MEM FOR routing_vector\n");
// return EXIT_FAILURE;
// }
struct neighbour_record a;
for(size_t i=0; i<neighbour_size; i++)
{
memset(&a, 0, sizeof(a));
unsigned int net,dist;
scanf("%[^/]", a.my_ip );
scanf("/%u",&net );
scanf(" distance %u\n",&dist );
a.netmask = net;
a.distance = dist;
gen_net_ip(a.my_ip, a.net_ip, a.netmask);
neighbour_vector[i] = a;
copy_neighbour_rec( &a, &routing_vector[i]);
}
//if(TESTING)
//{
// printf("TABLICA SIECI\n" );
// for(size_t i=0; i<neighbour_size; i++)
// {
// show_record_neighbour(neighbour_vector[i]);
// }
//}
if(configure_in_socket() )
{
return EXIT_FAILURE;
}
struct timeval my_time;
my_time.tv_sec = ROUND_LENGTH /SHOWS_PER_ROUND;
my_time.tv_usec = 0;
int parts_of_round=0;
while(1)
{
fd_set descriptors;
FD_ZERO(&descriptors);
FD_SET(sockfd, &descriptors);
int ready = select(sockfd+1, &descriptors, NULL,NULL, &my_time);
if( ready < 0 )
{
fprintf(stderr, "select error: %s\n",strerror(errno) );
return EXIT_FAILURE;
}
if(ready == 0)
{
show_vector(routing_vector);
if(parts_of_round != 2)
{
parts_of_round++;
//show_vector(routing_vector);
}
else
{
if(TESTING) printf("ROUND!!!\n" );
parts_of_round =0;
increase_freezd_counter(routing_vector);
mark_unactive_nets(routing_vector);
if( send_routing_table(routing_vector) )
{
if (TESTING) printf("ERROR: Sending routing table\n" );
}
}
my_time.tv_sec = ROUND_LENGTH /3;
}
else
{
struct routing_record temp;
memset(&temp, 0, sizeof(temp));
if( recive_packet(&temp) )
{
if(TESTING) printf("ERROR:REFUSED PACKET\n" );
continue;
}
//printf(" recived packet: " );show_record_routing(temp);
update_vector(routing_vector, &temp);
}
//printf("TAK%lu\n",my_time.tv_sec );
}
//send_record(&routing_vector[0], "127.0.0.1");
return 0;
}
|
import lldb
from lldbsuite.test.lldbtest import *
from lldbsuite.test.decorators import *
import lldbsuite.test.lldbutil as lldbutil
import json
import unittest2
class TestSimulatorPlatformLaunching(TestBase):
mydir = TestBase.compute_mydir(__file__)
NO_DEBUG_INFO_TESTCASE = True
def check_load_commands(self, expected_load_command):
"""sanity check the built binary for the expected number of load commands"""
load_cmds = subprocess.check_output(
['otool', '-l', self.getBuildArtifact()]
).decode("utf-8")
found = 0
for line in load_cmds.split('\n'):
if expected_load_command in line:
found += 1
self.assertEquals(
found, 1, "wrong number of load commands for {}".format(
expected_load_command))
def check_debugserver(self, log, expected_platform, expected_version):
"""scan the debugserver packet log"""
process_info = lldbutil.packetlog_get_process_info(log)
self.assertIn('ostype', process_info)
self.assertEquals(process_info['ostype'], expected_platform)
dylib_info = lldbutil.packetlog_get_dylib_info(log)
self.assertTrue(dylib_info)
aout_info = None
for image in dylib_info['images']:
if image['pathname'].endswith('a.out'):
aout_info = image
self.assertTrue(aout_info)
self.assertEquals(aout_info['min_version_os_name'], expected_platform)
if expected_version:
self.assertEquals(aout_info['min_version_os_sdk'], expected_version)
@skipIf(bugnumber="rdar://76995109")
def run_with(self, arch, os, vers, env, expected_load_command):
env_list = [env] if env else []
triple = '-'.join([arch, 'apple', os + vers] + env_list)
sdk = lldbutil.get_xcode_sdk(os, env)
version_min = ''
if not vers:
vers = lldbutil.get_xcode_sdk_version(sdk)
if env == 'simulator':
version_min = '-m{}-simulator-version-min={}'.format(os, vers)
elif os == 'macosx':
version_min = '-m{}-version-min={}'.format(os, vers)
sdk_root = lldbutil.get_xcode_sdk_root(sdk)
clang = lldbutil.get_xcode_clang(sdk)
self.build(
dictionary={
'ARCH': arch,
'CC': clang,
'ARCH_CFLAGS': '-target {} {}'.format(triple, version_min),
'SDKROOT': sdk_root
})
self.check_load_commands(expected_load_command)
log = self.getBuildArtifact('packets.log')
self.expect("log enable gdb-remote packets -f "+log)
lldbutil.run_to_source_breakpoint(self, "break here",
lldb.SBFileSpec("hello.c"))
triple_re = '-'.join([arch, 'apple', os + vers+'.*'] + env_list)
self.expect('image list -b -t', patterns=['a\.out '+triple_re])
self.check_debugserver(log, os+env, vers)
@skipIfAsan
@skipUnlessDarwin
@skipIfDarwinEmbedded
@apple_simulator_test('iphone')
@skipIfOutOfTreeDebugserver
def test_ios(self):
"""Test running an iOS simulator binary"""
self.run_with(arch=self.getArchitecture(),
os='ios', vers='', env='simulator',
expected_load_command='LC_BUILD_VERSION')
@skipIfAsan
@skipUnlessDarwin
@skipIfDarwinEmbedded
@apple_simulator_test('appletv')
@skipIfOutOfTreeDebugserver
def test_tvos(self):
"""Test running an tvOS simulator binary"""
self.run_with(arch=self.getArchitecture(),
os='tvos', vers='', env='simulator',
expected_load_command='LC_BUILD_VERSION')
@skipIfAsan
@skipUnlessDarwin
@skipIfDarwinEmbedded
@apple_simulator_test('watch')
@skipIfDarwin # rdar://problem/64552748
@skipIf(archs=['arm64','arm64e'])
@skipIfOutOfTreeDebugserver
def test_watchos_i386(self):
"""Test running a 32-bit watchOS simulator binary"""
self.run_with(arch='i386',
os='watchos', vers='', env='simulator',
expected_load_command='LC_BUILD_VERSION')
@skipIfAsan
@skipUnlessDarwin
@skipIfDarwinEmbedded
@apple_simulator_test('watch')
@skipIfDarwin # rdar://problem/64552748
@skipIf(archs=['i386','x86_64'])
@skipIfOutOfTreeDebugserver
def test_watchos_armv7k(self):
"""Test running a 32-bit watchOS simulator binary"""
self.run_with(arch='armv7k',
os='watchos', vers='', env='simulator',
expected_load_command='LC_BUILD_VERSION')
#
# Back-deployment tests.
#
# Older Mach-O versions used less expressive load commands, such
# as LC_VERSION_MIN_IPHONEOS that wouldn't distinguish between ios
# and ios-simulator. When targeting a simulator on Apple Silicon
# macOS, however, these legacy load commands are never generated.
#
@skipUnlessDarwin
@skipIfDarwinEmbedded
@skipIfOutOfTreeDebugserver
def test_lc_version_min_macosx(self):
"""Test running a back-deploying non-simulator MacOS X binary"""
self.run_with(arch=self.getArchitecture(),
os='macosx', vers='10.9', env='',
expected_load_command='LC_VERSION_MIN_MACOSX')
@skipIfAsan
@skipUnlessDarwin
@skipIfDarwinEmbedded
@apple_simulator_test('iphone')
@skipIf(archs=['arm64','arm64e'])
@skipIfOutOfTreeDebugserver
def test_lc_version_min_iphoneos(self):
"""Test running a back-deploying iOS simulator binary
with a legacy iOS load command"""
self.run_with(arch=self.getArchitecture(),
os='ios', vers='11.0', env='simulator',
expected_load_command='LC_VERSION_MIN_IPHONEOS')
@skipIfAsan
@skipUnlessDarwin
@skipIfDarwinEmbedded
@apple_simulator_test('iphone')
@skipIf(archs=['arm64','arm64e'])
@skipIfOutOfTreeDebugserver
def test_ios_backdeploy_x86(self):
"""Test running a back-deploying iOS simulator binary
with a legacy iOS load command"""
self.run_with(arch=self.getArchitecture(),
os='ios', vers='13.0', env='simulator',
expected_load_command='LC_BUILD_VERSION')
@skipIfAsan
@skipUnlessDarwin
@skipIfDarwinEmbedded
@apple_simulator_test('iphone')
@skipIf(archs=['i386','x86_64'])
@skipIfOutOfTreeDebugserver
def test_ios_backdeploy_apple_silicon(self):
"""Test running a back-deploying iOS simulator binary"""
self.run_with(arch=self.getArchitecture(),
os='ios', vers='11.0', env='simulator',
expected_load_command='LC_BUILD_VERSION')
@skipIfAsan
@skipUnlessDarwin
@skipIfDarwinEmbedded
@apple_simulator_test('appletv')
@skipIf(archs=['arm64','arm64e'])
@skipIfOutOfTreeDebugserver
def test_lc_version_min_tvos(self):
"""Test running a back-deploying tvOS simulator binary
with a legacy tvOS load command"""
self.run_with(arch=self.getArchitecture(),
os='tvos', vers='11.0', env='simulator',
expected_load_command='LC_VERSION_MIN_TVOS')
@skipIfAsan
@skipUnlessDarwin
@skipIfDarwinEmbedded
@apple_simulator_test('appletv')
@skipIf(archs=['i386','x86_64'])
@skipIfOutOfTreeDebugserver
def test_tvos_backdeploy_apple_silicon(self):
"""Test running a back-deploying tvOS simulator binary"""
self.run_with(arch=self.getArchitecture(),
os='tvos', vers='11.0', env='simulator',
expected_load_command='LC_BUILD_VERSION')
@skipIfAsan
@skipUnlessDarwin
@skipIfDarwinEmbedded
@apple_simulator_test('watch')
@skipIf(archs=['arm64','arm64e'])
@skipIfDarwin # rdar://problem/64552748
@skipIfOutOfTreeDebugserver
def test_lc_version_min_watchos(self):
"""Test running a back-deploying watchOS simulator binary
with a legacy watchOS load command"""
self.run_with(arch='i386',
os='watchos', vers='4.0', env='simulator',
expected_load_command='LC_VERSION_MIN_WATCHOS')
@skipIfAsan
@skipUnlessDarwin
@skipIfDarwinEmbedded
@apple_simulator_test('watch')
@skipIf(archs=['arm64','arm64e'])
@skipIfDarwin # rdar://problem/64552748
@skipIfOutOfTreeDebugserver
def test_watchos_backdeploy_apple_silicon(self):
"""Test running a back-deploying watchOS simulator binary"""
self.run_with(arch='armv7k',
os='watchos', vers='4.0', env='simulator',
expected_load_command='LC_BUILD_VERSION')
|
def generate_combinations(urls: List[str], params: List[dict]) -> List[tuple]:
return list(itertools.product(urls, params)) |
DNR in the OR? I also understand that the Ambulance may have been called and there are situations in which conflicting directives may be given by family and others resulting in attempts being made to resuscitate me. In consideration of utilizing this DNR request I, on behalf of myself and my heirs release any claim for damages resulting from such attempted resuscitation I may have against any emergency response personnel, the Williston Ambulance Service, the City of Williston, and the 911 system. |
Identification of Differential Drought Response Mechanisms in Medicago sativa subsp. sativa and falcata through Comparative Assessments at the Physiological, Biochemical, and Transcriptional Levels Alfalfa (Medicago sativa L.) is an extensively grown perennial forage legume, and although it is relatively drought tolerant, it consumes high amounts of water and depends upon irrigation in many regions. Given the progressive decline in water available for irrigation, as well as an escalation in climate change-related droughts, there is a critical need to develop alfalfa cultivars with improved drought resilience. M. sativa subsp. falcata is a close relative of the predominantly cultivated M. sativa subsp. sativa, and certain accessions have been demonstrated to exhibit superior performance under drought. As such, we endeavoured to carry out comparative physiological, biochemical, and transcriptomic evaluations of an as of yet unstudied drought-tolerant M. sativa subsp. falcata accession (PI 641381) and a relatively drought-susceptible M. sativa subsp. sativa cultivar (Beaver) to increase our understanding of the molecular mechanisms behind the enhanced ability of falcata to withstand water deficiency. Our findings indicate that unlike the small number of falcata genotypes assessed previously, falcata PI 641381 may exploit smaller, thicker leaves, as well as an increase in the baseline transcriptional levels of genes encoding particular transcription factors, protective proteins, and enzymes involved in the biosynthesis of stress-related compounds. These findings imply that different falcata accessions/genotypes may employ distinct drought response mechanisms, and the study provides a suite of candidate genes to facilitate the breeding of alfalfa with enhanced drought resilience in the future. Introduction Alfalfa (Medicago sativa L.) is one of the most widely grown and valuable perennial forage legumes, with an estimated global cropping area of over 30 million hectares. This popularity stems from the high nutritional value, palatability, environmental adaptability, and biomass yield of alfalfa, as well as its low fertilizer requirements due to its ability to fix nitrogen through symbiosis with rhizobia. The demand for ruminant products such as meat and milk is expected to grow substantially in coming years due to our expanding population and affluence, and high levels of forage crop production will therefore be a necessity. While alfalfa is relatively drought tolerant compared to many other crop species as a result of the typical presence of a deep tap root, its production depends upon irrigation in many growing regions, and it consumes a particularly high amount of water due to its long growing season and dense canopy. Unfortunately, there is a progressively limited supply of water for irrigation, as well as an escalation in the severity and frequency of drought events due to climate change, which will negatively impact alfalfa productivity. As such, there is a vital need to develop alfalfa cultivars that use water more efficiently and/or exhibit improved drought resilience compared to current varieties in a timely manner. Plants respond to drought stress using a variety of physiological, cellular, and molecular processes, with the aim of enhancing their ability to withstand or recover from such challenging conditions. At the molecular level, drought stress leads to an increase in the production of reactive oxygen species (ROS) that act as important signaling molecules in the abiotic stress response. However, when present at levels above a particular threshold, they can be detrimental to plant cells due to resulting lipid peroxidation, as well as the degradation of nucleic acids and proteins. In order to minimize such damage, plants tend to enhance the production/activity of various enzymatic and non-enzymatic antioxidants under water deficit as a means of scavenging ROS and maintaining redox homeostasis. ROS can also influence the production of certain phytohormones, which then often function through an interplay with the ROS signaling cascade. Abscisic acid (ABA) in particular is known to be a key signaling hormone under drought stress in plants, where its accumulation leads to stomatal closure and the regulation of numerous transcription factors. The differential activity of these ABA-responsive transcription factors, as well as the transcriptional regulation of many genes that are modulated in ABA-independent pathways, then leads to an increased accumulation of various products that contribute to stress tolerance, including protective proteins such as late embryogenesis abundant (LEA) proteins, osmoprotectants such as proline, glycine betaine, and trehalose, and the aforementioned antioxidant system components. Although this general framework for the cascade of events that occurs following plant exposure to drought stress has been elucidated, the complex regulatory processes that coordinate these responses have yet to be established in full at the genetic level, and precise mechanisms can differ between plant species and genotypes. Above and beyond drought tolerance mechanisms, plants can also make use of drought avoidance, which typically entails a short life cycle and/or developmental plasticity, and drought escape, which tends to involve enhanced water uptake and/or reduced water loss. Until fairly recently, the enhancement of drought resilience has not been a major focus of alfalfa breeding efforts, and the scope of genetic variation and mechanisms responsible for this trait are not fully known. While conventional breeding programs have begun to focus on the improvement of this trait in alfalfa, and a growing number of studies are dedicated towards the enhancement of drought tolerance in alfalfa using a transgenic approach, such efforts are complicated by a lack of understanding of the exact mechanisms by which alfalfa senses, reacts, and adapts to water deficit. Medicago sativa subsp. falcata, which can be found in diploid or tetraploid form, is a close relative of tetraploid M. sativa subsp. sativa. While the sativa subspecies is the most commonly cultivated subspecies of alfalfa, current-day varieties have been bred using introgressions from, and hybridization with, other subspecies, including falcata, and thus the delineation between subspecies is not necessarily quite so obvious. In any case, M. sativa subsp. falcata is well known to exhibit superior cold tolerance compared to the sativa subspecies, and a small number of studies have also shown it to be more resilient to other abiotic stresses such as drought. While M. sativa subsp. falcata germplasm has been used for many years in alfalfa breeding programs as a means of harnessing its enhanced abiotic stress tolerance, it typically exhibits relatively low productivity and persistence, which has made its use in this context challenging. The drought resilience of the falcata subspecies has been suggested to result from several physiological and biochemical characteristics, including reduced stomatal density and conductance, delayed leaf senescence, increased root length, and a greater accumulation of carbohydrate osmoprotectants (raffinose, myo-inositol, and galactinol) and flavonoid antioxidants. In addition, various studies have demonstrated that the heterologous expression of certain genes from M. sativa subsp. falcata genotypes, including those encoding Universal Stress Protein 1 (MfUSP1), galactinol synthase (MfGolS1), myo-inositol phosphate synthase (MfMIPS1), and late embryogenesis abundant protein 3 (MfLEA3), in tobacco led to enhanced tolerance to osmotic or dehydration stress in transgenic lines. Although comparative transcriptional responses between a droughtsensitive sativa (Chilean) and a drought-tolerant falcata (Wisfal) variety have been assessed under drought stress using microarray analysis previously, this type of evaluation has not been extended to other accessions/genotypes as of yet. Therefore, we sought to carry out further physiological, biochemical, and transcriptomic comparisons of distinct falcata and sativa accessions exhibiting differential levels of drought tolerance to provide new insight into the molecular mechanisms driving the resilience of falcata to water-deficient environmental conditions. The 'Falcata' Genotype Exhibits an Enhanced Ability to Withstand Drought Conditions Compared to 'Sativa' To assess the extent of differential drought responses between M. sativa subsp. falcata accession PI 641381 (hereafter referred to as 'falcata') and sativa cultivar Beaver (hereafter referred to as 'sativa'), water was withheld from plants, volumetric soil moisture contents were measured daily, and symptoms of stress were monitored. 'Sativa' plants typically began to wilt when volumetric soil moisture levels reached between 7-9%, while 'falcata' plants did not exhibit any signs of drought stress at this point (Figure 1a,b) and instead only began to show symptoms at between 3% and 4% soil moisture levels, which was significantly lower than 'sativa' (Figure 1b). In line with this, while leaf relative water content (RWC) declined significantly in both 'sativa' and 'falcata' genotypes under drought conditions (soil moisture level of approximately 7%) compared to well-watered conditions, only 'sativa' exhibited a significant reduction in RWC under moderate drought conditions (soil moisture level of approximately 20%) compared to control growth conditions ( Figure 1c). In addition, RWC was significantly higher in 'falcata' than 'sativa' under more severe drought conditions (soil moisture level of 7%; Figure 1c). Similarly, 'falcata' plants also consistently exhibited fewer detrimental effects from severe drought stress than 'sativa', and even at soil moisture levels of 0.5-1.5%, when 'sativa' plants were severely desiccated, 'falcata' plants retained some level of turgidity (Figure 1d). We also evaluated the number of days from the commencement of drought treatment for soil moisture levels to reach approximately 1.5%, and found that 'falcata' took significantly longer to reach a low soil moisture level than 'sativa' (Figure 1e). Finally, subsequent to having re-watered plants for 2-3 weeks after they reached a soil moisture level of approximately 1%, only 10% of 'sativa' plants survived, while 100% of 'falcata' plants regenerated (Figure 1f,g). Taken together, these results suggest that not only is the 'falcata' genotype more resilient to drought stress than 'sativa', but that this genotype also may use water at a lower rate. Response of 'sativa' and 'falcata' genotypes to drought stress conditions. (a) Representative images of 'sativa' and 'falcata' after withholding water until volumetric soil moisture levels reached approximately 7%. (b) Soil moisture level at which 'sativa' and 'falcata' began to wilt. (c) Relative water content (RWC) of first fully expanded trifoliate leaves assessed when soil moisture contents were at~50% (C, control),~20% (MD, mild drought), and~7% (D, drought). (d) Representative images of 'sativa' and 'falcata' after withholding water until soil moisture levels reached 1.5% and 0.5%, respectively. (e) Number of days from the initiation of drought treatment at which soil moisture levels in pots reached approximately 1.5%. (f) Proportion of plants that survived following 2-3 weeks of re-watering after allowing soil moisture contents to reach 1%. (g) Representative images of 'sativa' and 'falcata' plants following 2-3 weeks of re-watering once plants reached 1% soil moisture content. Blocks in each graph consist of the mean value of 10 (e) or 11 (b,c,f) biological replicates derived from vegetative stem cuttings, with black denoting 'sativa' and gray denoting 'falcata'. Bars denote standard errors. Scale bars = 5 cm. Lowercase letters indicate statistically significant differences between groups in each graph (p ≤ 0.05), while asterisks denote means that are statistically different in 'falcata' compared to 'sativa' (p ≤ 0.01). 'Falcata' Plants Exhibit Differences in Growth Characteristics Compared to 'Sativa' under Well-Watered Conditions and Following Drought Recovery To determine whether 'sativa' and 'falcata' genotypes exhibited differential growth responses, plant growth characteristics were first assessed under well-watered conditions (approximately 50% soil moisture content). Under such non-limiting conditions, 'sativa' and 'falcata' plants appeared morphologically similar overall ( Figure 2a); however, quanti-tative differences were apparent between the two genotypes. Flowering was significantly delayed in 'falcata' compared to 'sativa' under well-watered conditions (Figure 2b), with the first open flowers noted in 'sativa' and 'falcata' on average 35 and 45 days following cutting, respectively. Leaf size was also substantially smaller in 'falcata' than 'sativa' (Figure 2c), with a significant reduction in leaflet area (43.3% relative decrease compared to 'sativa'; Figure 2d) and specific leaf area (SLA; 37.0% relative decrease compared to 'sativa'; Figure 2e) compared to 'sativa' under control growth conditions. While no significant differences were noted between genotypes in terms of plant height (Figure 2f) or aboveground biomass (Figure 2g,h) under well-watered conditions, the 'falcata' genotype exhibited significantly fewer shoots ( Figure 2i) and reduced internode length (Figure 2j). In terms of root characteristics, there was no significant difference in root length in 'falcata' compared to 'sativa' under control conditions (Figure 2k,l); however, a significant decrease in root dry weight (DW) was noted in 'falcata' compared to 'sativa' (Figure 2m). Plant growth characteristics were also assessed following drought recovery (2-3 weeks of re-watering subsequent to drought treatment) as a means of distinguishing possible differences in biomass yield penalties between genotypes. Both 'falcata' and 'sativa' displayed significant reductions in plant height (Figure 2f), internode length (Figure 2j), and aboveground fresh weight (FW) and DW biomass (Figure 2g,h) after recovery from drought treatment. However, reductions were less substantial in 'falcata' than 'sativa' in every case. Similarly, while 'sativa' exhibited a significant reduction in shoot number following drought recovery compared to plants that had been well-watered, no statistically significant change was noted in 'falcata' between conditions (Figure 2i). In terms of root growth, while significant decreases in both root length (39.4% relative decrease) and root DW (82.0% relative decrease) were observed in 'sativa' plants that were re-watered following drought treatment compared to unstressed plants, no significant differences were observed in 'falcata' plants between treatments for either trait. This corresponded with significant increases in both root length and DW in 'falcata' compared to 'sativa' following re-watering (Figure 2l,m). Taken together, these results suggest that shoot and root growth penalties were less severe following drought in 'falcata' than 'sativa'. Stomatal Density and Size, but Not Photosynthesis-Related Traits or Detached Leaf Water Loss, Differ between 'Sativa' and 'Falcata' Genotypes To gain further insight into the physiological differences between the 'sativa' and 'falcata' genotypes assessed in this study, stomatal-and photosynthesis-related traits were evaluated, and detached leaf water loss assays were carried out. No significant differences were found between 'sativa' and 'falcata' in detached leaf water loss assays at any time point ( Figure S1a), or between genotypes or growth conditions (approximately 50% (control) and 8% (drought) soil moisture contents) with respect to leaf chlorophyll content ( Figure S1b). In terms of stomatal traits under well-watered conditions, the 'falcata' genotype exhibited a significant 40.2% relative increase in abaxial stomatal density compared to 'sativa' (Figure S1c,d). Conversely, while no significant difference in stomatal length was noted between genotypes under well-watered conditions in this study (Figure S1e), stomatal width and area were significantly reduced in 'falcata' compared to 'sativa' (15.8% and 17.7% relative decreases, respectively; Figure S1f,g). Light-saturated photosynthetic rate (Asat), stomatal conductance (g s ), and transpiration rate (E) were all found to decrease significantly under drought conditions (volumetric soil moisture content of approximately 7%) compared to well-watered conditions in both 'sativa' and 'falcata'. However, no significant differences were noted between genotypes (Figure S1h-j), which indicates that these traits were not a main driver for the observed differences in drought tolerance. approximately 50% soil moisture content) and following drought recovery (DR, 2 weeks of re-watering after allowing soil moisture levels to reach approximately 4%). Measurements were taken 35 (f-h) or 37 (i,j) days following cutting. (k) Representative images of 'sativa' and 'falcata' roots 54 days following cutting under control conditions (approximately 50% soil moisture content) and following drought recovery (3 weeks of re-watering after allowing soil moisture levels to reach approximately 1%). Scale bars = 5 cm. (l-m) Length of the longest root and root DW in 'sativa' and 'falcata' plants under control conditions (C, approximately 50% soil moisture content) and following drought recovery (DR, approximately 3 weeks of re-watering after allowing soil moisture levels to reach approximately 1% soil moisture content). Measurements were taken 54 days following cutting. For all graphs, blocks consist of the mean value of 5 (d,e) or 11 (f-j,l-m) biological replicates derived from stem cuttings, with black denoting 'sativa' and gray denoting 'falcata'. Bars denote standard errors. Lowercase letters indicate statistically significant differences between groups in each graph (p ≤ 0.05), while asterisks denote means that are statistically different in 'falcata' compared to 'sativa' (p ≤ 0.01). 'Sativa' and 'falcata' Genotypes Exhibit Differential Soluble Carbohydrate Levels and Antioxidant Activities Levels of osmoprotectants, including proline and soluble carbohydrates, and antioxidant activities were assessed in leaf tissues from plants grown under well-watered and drought conditions (volumetric soil moisture contents of approximately 7%) to gain a further understanding of possible mechanisms driving the superior drought tolerance observed in 'falcata' compared to 'sativa' in this study. Proline concentrations increased significantly under drought compared to control conditions in both genotypes (25.4% and 19.9% relative increases in 'sativa' and 'falcata', respectively); however, no significant differences were noted between genotypes under either growth condition ( Figure S2a). Both 'sativa' and 'falcata' also exhibited significant enhancements in soluble carbohydrate levels under drought compared to the control treatment (47.2% and 47.0% relative increases in 'sativa' and 'falcata', respectively); however, in this case, levels were significantly lower in 'falcata' than 'sativa' under both growth conditions ( Figure S2b). In terms of antioxidant activity, superoxide dismutase (SOD) activity was found to be significantly lower in 'falcata' than 'sativa' under both well-watered and drought conditions ( Figure S2c). Conversely, no significant differences in ascorbate peroxidase (APX) activity were noted between growth conditions or genotypes in this study ( Figure S2d). In the case of catalase (CAT) activity, while no significant differences were observed between genotypes under well-watered or drought conditions, 'sativa', but not 'falcata', exhibited a significant increase in activity under drought conditions compared to control conditions (36.4% relative increase; Figure S2e). RNA-Seq Analysis of 'Sativa' and 'Falcata' Leaf Tissue under Control and Drought Conditions To determine whether the 'sativa' and 'falcata' accessions assessed here exhibited differential gene expression under control and drought conditions, we carried out comparative RNA-Seq analysis using RNA derived from the leaves of a 'sativa' and 'falcata' genotype, respectively, under both well-watered and drought conditions (at an average volumetric soil moisture content of approximately 7%; four biological replicates of each) for a total of 16 samples. Between 79,873,614 and 178,252,170 reads, with an average of 100,797,720 reads, were obtained per sample, leading to a mean coverage of 20,361,139,390 bases per sample (Table S1). The resulting reads were mapped to the M. truncatula reference genome (v4.0), with an average of approximately 36,074 and 36,716 transcripts identified under well-watered conditions in 'sativa' and 'falcata', respectively, and 38,149 and 38,041 transcripts identified under drought in 'sativa' and 'falcata', respectively (Table S1). Two of the test groups ('sativa' control and 'falcata' drought) formed distinct groups after principal component analysis (PCA) of fragments per kilobase of transcript per million mapped reads (FPKM), which confirmed the similarity of biological replicates within each group. Conversely, 'sativa' drought and 'falcata' control groups both included three biological replicates that formed distinct groups following PCA analysis, while one biological replicate of each was outlying to some degree ( Figure S3). Some variability among biological replicates may be expected due to minor differences in microclimate or developmental stage, and overall there was a clear separation among groups of samples in this study. We first aimed to assess transcriptional discrepancies in both 'sativa' and 'falcata' genotypes, respectively, between control and drought conditions (File S1). A comparison between 'sativa' plants grown under well-watered and drought conditions led to the identification of 6520 differentially expressed genes (DEGs), with 3104 exhibiting significant up-regulation under drought conditions compared to control conditions, and 3416 DEGs displaying significant down-regulation under drought. Similarly, a comparison of 'falcata' plants under well-watered and drought conditions led to the identification of 4354 DEGs, with 1574 DEGs exhibiting significant up-regulation under drought compared to control conditions, and 2780 DEGs displaying significant down-regulation under drought. Of these, 3494 DEGs were unique to 'sativa', 1328 DEGs were unique to 'falcata', and 3026 DEGs were present in both 'sativa' and 'falcata' between control vs. drought conditions ( Figure S4a). These results suggest that the more drought-sensitive 'sativa' genotype was affected to a greater degree transcriptionally than the drought-tolerant 'falcata' genotype under drought stress compared to control conditions. We also assessed differential gene expression between 'sativa' and 'falcata' genotypes under both control and drought conditions (File S1). A cross-comparison of 'sativa' and 'falcata' plants grown under well-watered conditions led to the identification of 490 DEGs between the two subspecies, with 373 genes displaying significantly increased transcript abundance, and 117 exhibiting significantly decreased transcript abundance in 'falcata' compared to 'sativa'. Conversely, a comparison between 'sativa' and 'falcata' plants grown under drought conditions led to the identification of 4304 DEGs, with 1991 being significantly up-regulated and 2313 being significantly down-regulated in 'falcata' compared to 'sativa'. Of these, 238 DEGs were specific to control conditions, 4052 were specific to drought conditions, and 252 were present under both control and drought conditions ( Figure S4b). These results indicate that greater transcriptional differences were apparent between 'sativa' and 'falcata' under drought stress than under control conditions. Comparison of quantitative real-time RT-PCR (qRT-PCR) and RNA-Seq log2 foldchange values for ten genes identified as DEGs in our RNA-Seq analyses revealed a high level of correlation between the results ( Figure S4c,d). Correlation coefficients of 0.99 and 0.97 were observed across RNA-Seq and qRT-PCR log2 fold-change values between control and drought conditions in 'sativa' and 'falcata' genotypes for these ten genes, which confirms the validity of the RNA-Seq data in this study. Differential Gene Ontology (GO) Term Enrichment in 'Sativa' and 'Falcata' under Drought Compared to Control Conditions In order to assess 'sativa' and 'falcata' in terms of their transcriptional response to drought, we carried out singular enrichment analysis (SEA) and subsequent cross comparison of SEA (SEACOMPARE) of both 'sativa' and 'falcata' DEGs, respectively, that were observed under drought compared to control conditions. For genes that were upregulated under drought compared to well-watered conditions in the biological process GO term category, no significantly enriched terms were observed in 'sativa', while 33 terms were significantly enriched in 'falcata' ( Figure S5). In the molecular function GO term category, significant enrichment of 13 and 7 GO terms were observed in 'sativa' and 'falcata' genotypes, respectively ( Figure S6). No significantly enriched GO terms derived from genes that were up-regulated in drought vs. control conditions were identified in either genotype in the cellular component category. For genes that were down-regulated in drought compared to well-watered conditions, far more GO terms were enriched in 'sativa' and 'falcata' in the biological process, molecular function, and cellular compartment categories than for up-regulated genes. In addition, substantially more GO terms were enriched overall for down-regulated genes in 'sativa' than 'falcata'. In the case of the biological process category, 102 GO terms were significantly enriched in 'sativa', whereas only 43 were identified in 'falcata'. While 39 terms were enriched in both 'sativa' and 'falcata', enrichment was typically more significant in 'sativa' than 'falcata' ( Figure S7). In the molecular function category, 25 significantly enriched GO terms were identified in 'sativa' and 'falcata' genotypes. Of these, 11 were significantly enriched in 'sativa' but not 'falcata', while 8 were significantly enriched in 'falcata' but not 'sativa' ( Figure S8). Within the cellular component category, of 19 significantly enriched GO terms in 'sativa' and 'falcata' genotypes, 10 were unique to 'sativa', while only 5 were significantly enriched in 'falcata' but not 'sativa' ( Figure S9). Differential GO Term Enrichment between 'Sativa' and 'Falcata' under Drought Conditions To further assess transcriptional differences between 'sativa' and 'falcata' genotypes, parametric analysis of gene set enrichment (PAGE), which takes into consideration both gene ID and log2 fold-changes, was carried out using DEGs derived from comparisons between 'sativa' and 'falcata' genotypes, under both well-watered and drought conditions. In the case of well-watered plants, no significant alterations in GO terms were observed between the two genotypes. Conversely, substantial differences in GO term enrichment were noted between 'sativa' and 'falcata' genotypes under drought conditions ( Figure 3). In the case of the biological process category, there was a significant enrichment of four up-regulated GO terms in 'falcata' compared to 'sativa' genotypes, including response to stimulus (GO:0050896), response to stress (GO:0006950), and defense response (GO:0006952) (Figure 3a). With respect to GO terms in the molecular function category, there was a significant enrichment of two up-regulated and four down-regulated GO terms in 'falcata' compared to 'sativa' (Figure 3b). Within the cellular component category, 10 significantly enriched GO terms were identified, all of which were up-regulated in 'falcata' compared to 'sativa' (Figure 3c). Differential Transcriptional Responses in Abiotic Stress Response-Related Pathways between 'Sativa' and 'Falcata' in Response to Drought In order to gain a further understanding of the differential response of 'sativa' and 'falcata' genotypes to drought stress, we also carried out MapMan pathway analysis of DEGs between control and drought conditions in both 'sativa' and 'falcata', as well as between 'sativa' and 'falcata' plants under both control and drought conditions. Between control and drought conditions, more DEGs were observed in 'sativa' than 'falcata' in most categories (Figures 4, S10 and S11), including the 'drought/salt' and 'miscellaneous abiotic stress' categories ( Figure S10, File S2). Between 'sativa' and 'falcata', a greater number of DEGs were observed under drought than control conditions in the vast majority of selected pathways with putative functions in abiotic stress response ( Figures 5 and S12). Under drought stress, 12 of 16 DEGs were up-regulated in 'falcata' compared to 'sativa' in the 'drought/salt stress' category ( Figure 5a, File S2). Furthermore, there was a striking abundance of genes that were up-regulated in 'falcata' compared to 'sativa' overall under well-watered conditions, with all DEGs in the 'drought/salt' and 'miscellaneous abiotic stress' categories being up-regulated in 'falcata' compared to 'sativa' in this treatment (Figure 5a, File S2). Categories of a selection of differentially expressed stress response-associated genes are described below. Transcriptional alterations in abiotic stress-related metabolic pathways and transcription factor families between 'sativa' and 'falcata' under both control and drought conditions. Pathway analysis was conducted using MapMan, with blue boxes indicating down-regulated genes and red boxes denoting up-regulated genes. Pathways shown include those related to (a) abiotic stress response, (b) the metabolism of various osmoprotectants, (c) the metabolism of non-tocopherol and non-carotenoid terpenoids, and (d) a selection of transcription factor families. Osmoprotectants To decipher any putative role of osmoprotectants in the drought tolerance of 'falcata', we examined the expression of genes involved in their metabolism. Since proline accumulation does not appear to drive the enhancement in drought tolerance observed in 'falcata' compared to 'sativa' in the current study, we focused on the differential expression of genes involved in the metabolism of glycine betaine and minor carbohydrates such as myo-inositol, raffinose, and trehalose between treatments and genotypes. In 'sativa', a single betaine aldehyde dehydrogenase (Medtr3g078550) was up-regulated in response to drought, while no genes within this pathway exhibited differential expression between conditions in 'falcata' (Figure S10c,d, File S2). However, this same gene was significantly up-regulated in 'falcata' compared to 'sativa' under well-watered conditions (1.26081 log2 fold-change; Figure 5b, File S2). Taken together, this indicates that although 'falcata' did not significantly up-regulate the expression of this gene in response to drought, it was expressed at higher baseline levels compared to 'sativa'. With regard to genes involved in the metabolism of minor carbohydrates, 'sativa' exhibited a higher number of DEGs than 'falcata' between drought and control conditions in most categories (Figure 4, File S2). Of these, genes involved in myo-inositol metabolism were largely down-regulated, and those involved in raffinose metabolism were mostly upregulated, under drought conditions in both genotypes. Conversely, while genes involved in trehalose metabolism were largely up-regulated under drought conditions in 'sativa', DEGs in this category were fairly evenly distributed between up-and down-regulated genes in 'falcata' (Figure 4; File S2). However, comparisons of DEGs between the two genotypes indicated that a single putative trehalose phosphatase/synthase (Medtr4g129270) was significantly up-regulated in 'falcata' compared to 'sativa' under well-watered conditions (Figure 5b, File S2). Numerous other genes involved in trehalose, myo-inositol, and raffinose metabolism were also found to be differentially expressed between 'falcata' and 'sativa' under drought conditions (Figure 5b, File S2). Of particular note, GolS1 (Medtr1g084670), which has been previously implicated in raffinose series oligosaccharide (RSO) biosynthesis, was found to be up-regulated (2.22634 log2 fold-change) in 'falcata' compared to 'sativa' under drought conditions. Redox-Related Pathways Due to the importance of scavenging and detoxifying ROS in plants under abiotic stress, we also surveyed DEGs with putative roles in this context. With respect to enzymatic antioxidants, a higher number of DEGs were observed overall in 'sativa' than 'falcata' in response to drought (Figures S10a,b and S12a, File S2). With respect to molecular antioxidants, the majority of DEGs encoding enzymes involved in tocopherol metabolism, and all DEGs involved in carotenoid metabolism, were down-regulated under drought compared to well-watered conditions in both genotypes ( Figure S10c,d, File S2). In the case of other terpenoids, the majority were down-regulated under drought compared to well-watered conditions in both genotypes ( Figure S10c,d, File S2). However, eight DEGs (Medtr5g024880, Medtr2g064425, Medtr2g089120, Medtr3g052120, Medtr4g045810, Medtr4g081460, Medtr6g039440, and Medtr6g093180) involved in terpenoid metabolism or the mevalonate pathway were expressed at significantly higher levels in 'falcata' compared to 'sativa' under control conditions, with no down-regulated genes observed. Four of these genes (Medtr5g024880, Medtr3g052120, Medtr4g045810, and Medtr4g081460) were also expressed at significantly higher levels in 'falcata' compared to 'sativa' under drought conditions (Figure 5c, File S2). Many genes involved in flavonoid metabolism were also differentially expressed between treatments in both genotypes (Figure 4), as well as between genotypes under both conditions ( Figure S12a). The majority of these were expressed at lower levels in 'falcata' compared to 'sativa' in both growth conditions (File S2). Hormone Metabolism Between control and drought conditions, the 'sativa' genotype yielded a higher number of DEGs in the ABA, ethylene, brassinosteroid, and IAA metabolism categories than 'falcata', while 'falcata' displayed a greater number of DEGs in the salicylic acid, jasmonic acid, and gibberellin metabolism categories ( Figure S10a,b, File S2). A 9-cis-epoxycarotenoid dioxygenase-encoding gene (Medtr2g070460), which typically functions as a rate-limiting enzyme in ABA and strigolactone biosynthesis (Ellison 2016), was up-regulated to a similar degree in both 'sativa' (log2 fold-change of 6.33952) and 'falcata' (log2 fold-change of 6.77675) under drought compared to well-watered conditions (File S2). In contrast, while a gene encoding an adenine nucleotide alpha hydrolase-like superfamily protein (Medtr1g054765), which was previously termed MfUSP1 in M. sativa subsp. falcata and falls within the ethylene-induced-regulated-responsive-activated bin in MapMan, was only up-regulated under drought conditions in 'sativa' (log2 fold-change of 1.57089; File S2), this gene was significantly up-regulated in 'falcata' compared to 'sativa' under both well-watered (3.43631 log2 fold-change) and drought (2.56688 log2 fold-change) conditions ( Figure S12b, File S2). Transcription Factors As was the case for most categories, increased numbers of transcription-factor-encoding DEGs were observed between control and drought conditions in 'sativa' than 'falcata' ( Figure S11, File S2). Similarly, higher numbers of DEGs were observed between 'sativa' and 'falcata' under drought stress compared to well-watered conditions for all transcription factor categories assessed in this study (AP2/ERF, bZIP, WRKY, MYB, MYB-related, NAC, DOF, and bHLH) (Figure 5d, File S2). With the exception of AP2/ERF transcription factors, there was a predominance of genes that were down-regulated in 'falcata' compared to 'sativa' under drought conditions. Conversely, under well-watered conditions, all DEGs in these transcription factor categories were up-regulated in 'falcata' compared to 'sativa' (Figure 5d). For example, while NAC3 (Medtr8g059170) was significantly up-regulated in both 'sativa' (log2 fold-change of 8.2973) and 'falcata' (log2 fold-change of 3.3731) under drought compared to well-watered conditions, this gene was significantly up-regulated in 'falcata' compared to 'sativa' under control conditions, while no differential expression was noted between the two genotypes under drought stress (File S2). Protective Proteins In the current study, we found that a large number of genes belonging to three major classes of proteins with protective functions during drought response (heat shock proteins, LEAs (including dehydrins), and aquaporins) were differentially expressed in both 'sativa' and 'falcata' under drought compared to well-watered conditions ( Figure S13). In the case of heat shock proteins, 'sativa' exhibited a higher number of DEGs than 'falcata' under drought compared to well-watered conditions, and an elevated number of DEGs were also noted between genotypes under drought than control conditions ( Figure S13a). In the case of dehydrins, which are one class of LEA protein, three genes (Medtr3g117290, Medtr6g084640, and Medtr7g086340) were found to be significantly up-regulated under drought stress in both 'sativa' and 'falcata' ( Figure S13b). Interestingly, one of these genes (Medtr6g084640) was significantly up-regulated in 'falcata' compared to 'sativa' under both growth treatments. In the case of other LEAs, most DEGs were up-regulated in both genotypes under drought compared to control conditions. Furthermore, a gene encoding LEA3 (Medtr4g123950), which was previously reported to be responsive to dehydration in M. sativa subsp. falcata, was found to be significantly up-regulated (2.596 log2 fold-change) in 'falcata' compared to 'sativa' under control conditions ( Figure S13b). With respect to aquaporin-encoding genes, the vast majority were down-regulated in both genotypes under drought compared to control conditions ( Figure S13c). While no differential expression was observed in these genes between genotypes under control conditions, several were differentially expressed under drought ( Figure S13c). Discussion Previously, several falcata accessions were shown to exhibit superior drought tolerance or water use efficiency compared to the sativa subspecies; a phenomenon that has been suggested to be related to characteristics such as differences in root morphology, reduced stomatal density and conductance, delayed leaf senescence under drought, and increased RSO and (iso)flavonoid accumulation [22,. However, relatively few falcata accessions have been examined in-depth in terms of drought tolerance, and only a single falcata accession (Wisfal) has been comparatively assessed at the transcriptional level in this context thus far. As such, we sought to compare various physiological, biochemical, and transcriptional characteristics in 'sativa' (Beaver) and 'falcata' (PI 641381) genotypes as a means of furthering our knowledge regarding the mechanisms driving improved resilience to water deficit in alfalfa. In the current study, 'falcata' was found to exhibit superior drought tolerance compared to 'sativa', as evidenced by a significant reduction in the soil moisture level at which plants began to wilt (Figure 1a-b), and enhanced survival following severe drought ( Figure 1f-g). In addition, while both 'sativa' and 'falcata' exhibited decreases in growth following drought recovery, which is a typical response of alfalfa, reductions were far more substantial in 'sativa' (Figure 2f-h). Given the mounting limitations in water resources, minimizing yield loss under drought conditions will be a crucial component of attaining both agricultural and environmental sustainability in alfalfa production. Drought-induced senescence is commonplace among drought-sensitive plants and is typically correlated with a reduction in leaf chlorophyll content, which can lead to a decrease in photosynthetic capacity and eventually the death of the plant. Indeed, the ability to retain chlorophyll, and thus photosynthesis, under water deficit has been suggested to be a key contributor to drought tolerance in falcata genotypes assessed previously. In the present study, we did not note any changes in leaf chlorophyll content between drought and well-watered conditions in either genotype ( Figure S1b), and light-saturated photosynthetic rates declined under water deficit to a similar extent in both genotypes ( Figure S1h), which was consistent with the down-regulation of a multitude of genes involved in the photosynthetic process ( Figure 4). This implies that unlike previously studied falcata genotypes, chlorophyll content was not correlated with photosynthetic rate in this study, and neither trait appeared to contribute to the improvement of drought tolerance in 'falcata'. The fact that 'falcata' plants wilted at a lower volumetric soil moisture content than 'sativa' and leaves retained a higher level of turgidity under severe drought stress ( Figure 1) suggests that 'falcata' is better able to maintain a high water status under stress, thus avoiding dehydration and allowing for the continuation of metabolic function for a longer period of time. This corresponds with our finding that 'sativa' leaves exhibited a greater number of DEGs under drought compared to well-watered conditions than 'falcata' (Figure S4a), which resembles the outcome of a previous comparative microarray assessment of droughttolerant Wisfal falcata and drought-sensitive Chilean sativa shoots. However, PAGE analysis of our RNA-Seq data also indicated that up-regulated genes within the 'response to stress' category were significantly enriched in 'falcata' compared to 'sativa' under drought (Figure 3a). This signifies that while 'sativa' may have undergone an overall greater transcriptional response under drought than 'falcata', the latter exhibited the preferential regulation of genes known to be specifically involved in stress response. One way in which plants can avoid cellular dehydration under drought stress is through the superior capture of soil moisture, at least under certain water deficit scenarios. Accordingly, several falcata genotypes have been shown previously to exhibit higher root-to-shoot ratios under drought conditions than their sativa counterparts. In the current study, root DW was lower in 'falcata' than 'sativa' under well-watered conditions. However, only 'sativa' exhibited a significant reduction in root length and DW following drought recovery (Figure 2k-m), which corresponds with the greater overall growth penalties incurred in this genotype. Therefore, although we did not examine root morphology in fine detail in this study, root size did not appear to be a main component of the improved drought tolerance in 'falcata'. Another manner in which plant water status can be maintained under water-limited conditions is through a reduction in water loss. Given that 'falcata' took approximately 2 days longer to reach a soil moisture level of 1.5% (from approximately 50% soil moisture) than 'sativa' following drought treatment (Figure 1e), it is possible that this characteristic played a greater role in maintaining cellular hydration than enhanced soil moisture capture through the roots. Reductions in stomatal density and conductance are traits that have been associated with reduced water loss and are often linked to increased drought tolerance in many plant species, including alfalfa. In the present study, we observed an increase in stomatal density in 'falcata' compared to 'sativa', but a decrease in stomatal width and area ( Figure S1c-g), which corresponds with the lack of difference in stomatal conductance and transpiration rate on a per area basis between genotypes ( Figure S1i-j). This is in stark contrast to a selection of falcata genotypes assessed previously, whereby they were found to exhibit decreases in stomatal density and/or stomatal conductance compared to sativa genotypes. Although ABA levels, which can contribute to drought resilience in part through stomatal-related changes, were not examined in the current study, few differences were noted between genotypes with respect to the expression of ABA biosynthetic genes (File S2). Taken together, this implies that ABA-independent pathways and non-stomatal traits may be more important than ABA-dependent pathways in terms of eliciting superior drought tolerance in 'falcata'. Water loss can also be curtailed through non-stomatal leaf characteristics, such as a small leaf size and low SLA, and these traits are thus also associated with superior drought tolerance in plants. In line with this, 'falcata' plants bore leaves with a significantly lower area and SLA than 'sativa' under well-watered conditions (Figure 2c-e). While we did not observe any difference between genotypes in detached leaf water loss assays ( Figure S1a), which suggests that 'falcata' leaves were not inherently better at minimizing water loss than 'sativa' on a per weight basis, it is possible that the leaf characteristics of 'falcata' may be contributing to an overall improvement in transpiration efficiency on a whole-plant level. Such a phenomenon could also feasibly have been a factor in the slower rate of soil moisture utilization observed in these plants. An increase in the production of compatible solutes, such as proline, glycine betaine, and certain soluble sugars including trehalose and raffinose, within a plant under drought conditions can also have a positive impact on cellular hydration by augmenting osmotic pressure in the cytoplasm of plant cells, thus protecting enzymes and cell membranes under drought stress. Proline accumulation did not appear to be a differentiating factor in drought resilience between 'falcata' and 'sativa' (Figures 4, 5b and S2a), which is consistent with previous findings in Wisfal falcata and Chilean sativa. However, single genes involved in glycine betaine and trehalose biosynthesis, respectively, were up-regulated in 'falcata' compared to 'sativa' under well-watered conditions (Figure 5b, File S2). Similarly, GolS1, which encodes a galactinol synthase that catalyzes the production of galactinol that is utilized for the subsequent biosynthesis of RSO and elicits enhanced tolerance to drought, salinity, and cold tolerance when over-expressed in tobacco, was also up-regulated in 'falcata' compared to 'sativa' under drought conditions (File S2). Wisfal falcata was found previously to possess increased levels of several minor carbohydrates with known functions as osmoprotectants, including raffinose and myo-inositol, compared to Chilean sativa under both well-watered and water-limited conditions. Together, these findings hint at the possibility that the accumulation of particular carbohydrates may be a general drought response mechanism across multiple falcata genotypes. Although total soluble carbohydrate levels were found to increase similarly under drought conditions in both 'sativa' and 'falcata' in the current study ( Figure S2b), these changes do not necessarily reflect alterations in specific types of soluble carbohydrate, and it is thus feasible that an increase in the levels of these, and potentially other osmoprotectants may be a contributing factor to the enhanced ability of 'falcata' to maintain cell turgor under drought conditions. In addition to a reduction in cellular hydration, drought stress also typically leads to an increase in the production of ROS such as superoxide (O 2 -) and hydrogen peroxide (H 2 O 2 ). These ROS have important signaling functions in drought response, particularly through their function as secondary messengers that contribute to the coordination of specific physiological, molecular, and metabolic events. However, above a certain threshold they have detrimental effects on cells and their components, and as such, plants typically increase the transcriptional levels/enzymatic activities of various enzymatic and non-enzymatic antioxidant systems under stress as a means of scavenging and detoxifying ROS. The enzymatic antioxidant activity of SOD, APX, and CAT did not appear to contribute to the increased drought resilience of 'falcata' in this study ( Figure S2c-e), and instead, both SOD and CAT activity increased to a greater extent in 'sativa' than 'falcata' under drought treatment. This implies that in line with the fact that 'falcata' was able to maintain a higher RWC than 'sativa' under the same intensity of water deficit, ROS levels may have been less impacted in the former genotype and there was thus less of a need to increase enzymatic antioxidant activity under these conditions. Interestingly, the transcriptional changes in genes encoding enzymatic antioxidants did not appear to follow this same pattern overall ( Figures S10a,b and S12a, File S2). This was not wholly unexpected since the expression patterns of genes encoding antioxidant enzymes have not always been found to be congruent with fluctuations in enzyme activity under drought stress, which may be related to post-translational regulatory mechanisms that have yet to be fully elucidated. Non-enzymatic antioxidants, such as flavonoids () and isoprenoids including carotenoids, tocopherols, and a variety of other terpenoids, also function to reduce ROS levels during abiotic stress. In line with this, shoot flavonoids were found previously to be elevated in Wisfal falcata compared to Chilean sativa under both control and water-deficient conditions, with a concomitant increase in the propensity for the up-regulation of genes involved in their biosynthesis in the falcata genotype under drought compared to well-watered conditions. However, a similar trend was not observed in the present study (Figure 4, File S2), and instead, a relatively large proportion of genes involved in the flavonoid biosynthetic pathway were expressed at lower levels in 'falcata' than 'sativa' under drought stress ( Figure S12a). In agreement with our findings, a drought-tolerant alfalfa genotype was shown previously to exhibit a reduction in flavonoid levels under drought stress, whereas levels were not altered significantly in a droughtsensitive cultivar. As such, it is possible that the role of these metabolites in the abiotic stress response may differ between species/genotypes, and that different alfalfa genotypes may employ distinct mechanisms to withstand drought stress. In the case of terpenoids, no obvious distinction was noted in the differential expression of genes involved in the metabolism of carotenoids or tocopherols between 'sativa' and 'falcata' (File S2). In contrast, we noted the significant up-regulation of eight genes involved in the metabolism of other terpenoids in 'falcata' compared to 'sativa' under well-watered conditions, while no down-regulated genes in this category were present (Figure 5c). Higher levels of metabolites involved in terpenoid biosynthesis were found in a drought-tolerant alfalfa genotype relative to a sensitive genotype under well-watered conditions previously, which is analogous to what we observed in the current study. As there has been a relative paucity of research attempting to unravel the role of noncarotenoid and non-tocopherol terpenoids in plants, it is possible that these specialized metabolites may provide an as of yet undeciphered mechanism contributing to drought tolerance in alfalfa. Therefore, while carotenoids and tocopherols do not likely contribute to the differential drought response observed between genotypes in the present study, further examination will be necessary to definitively determine whether baseline terpenoid levels/composition are involved. Differential levels of heat shock proteins, LEAs, and aquaporins have also been found to contribute to drought tolerance in plants. Aquaporins function to regulate the movement of water across cellular membranes, and at least certain members of this family tend to be down-regulated in response to drought in plants, which may reduce water loss during dehydration. In contrast, heat shock proteins and LEAs (including dehydrins), which function, at least in part, as molecular chaperones to maintain protein stability and cellular homeostasis, are both typically up-regulated in response to drought stress. Genes encoding all three types of protein have been shown to follow this trend at the transcriptional level in Wisfal falcata and Chilean sativa, with many being more responsive to drought in sativa than falcata. While we observed a similar pattern in the current study, there were several exceptions ( Figure S13). Of particular note was a gene encoding LEA3, which was significantly up-regulated in 'falcata' compared to 'sativa' under control, but not drought, conditions ( Figure S13b). Previously, the over-expression of MfLEA3 (derived from a falcata accession) in tobacco enhanced tolerance to drought, cold, and high light, possibly due in part to a concomitant decrease in ROS accumulation. Therefore, it is possible that higher levels of baseline expression of this gene may play a role in the superior drought tolerance observed in 'falcata' compared to 'sativa' via a protective effect on as of yet unidentified proteins. Alterations in the expression of genes encoding particular transcription factors have also been shown to be important for the regulation of drought stress response. In the present study, we found that overall, genes encoding transcription factors were more highly regulated in 'sativa' than 'falcata' under drought compared to control conditions ( Figure S11). Intriguingly, we also found that despite the greater overall response of 'sativa' under drought in this context, all differentially expressed genes encoding abiotic stress-related transcription factors assessed in this study were up-regulated in 'falcata' compared to 'sativa' under well-watered conditions (Figure 5d), which implies that 'falcata' might possess higher baseline levels of these transcription factors than 'sativa'. It is noteworthy that, in certain cases, drought tolerance can be attributed to the enhanced expression of genes, including a subset of transcription factors, prior to the onset of drought, thus rendering the plant quicker to respond. Accordingly, NAC3, which was shown previously to positively regulate cold tolerance in M. truncatula, was up-regulated in 'falcata' compared to 'sativa' under control but not drought conditions (File S2). Finally, we also found that the expression of USP1 was significantly higher in 'falcata' than 'sativa' under both well-watered and drought conditions (File S2). The heterologous expression of a falcata homolog of this gene in tobacco was previously shown to enhance tolerance to various types of abiotic stress, including osmotic stress, at least in part by lowering ROS accumulation. Although the precise mechanism by which this gene elicits improvements in abiotic stress tolerance remains to be determined, it is possible that its increased expression may also influence drought response in 'falcata'. In conclusion, unlike the small number of falcata genotypes assessed previously, 'falcata' PI 641381 did not appear to elicit its superior drought resilience through alterations in stomatal-related traits, root size, or delayed senescence under drought. While 'falcata' may make use of increased RSO accumulation, as evidenced by the up-regulation of GolS1 in 'falcata' compared to 'sativa' under drought conditions, which resembles one possible factor behind improved drought tolerance in the Wisfal falcata genotype, it also appears to utilize a unique suite of additional mechanisms to achieve drought resilience. These putative mechanisms include the presence of smaller, thicker leaves and an increase in baseline transcriptional levels of a number of genes under well-watered conditions, which could feasibly allow a more rapid response to drought. This suggests that different falcata accessions/genotypes may make use of distinct mechanisms to enhance their ability to thrive under drought conditions. While the majority of studies to date have focused on common drought response mechanisms in particular alfalfa accessions/cultivars, little effort has been directed towards elucidating differences between drought-tolerant genotypes thus far. However, such discrepancies have been found to occur in other plant species, highlighting the complexity of drought tolerance mechanisms in general. As such, deciphering the molecular and regulatory processes driving the superior ability of falcata genotypes to withstand adverse conditions will provide knowledge and molecular tools to improve alfalfa, and potentially also other crops, in the future. Plant Growth Conditions Seeds of tetraploid M. sativa subsp. falcata accession PI 641381 ('falcata'; determined to exhibit superior resilience to drought stress in preliminary experiments) were obtained from the United States Department of Agriculture-Agricultural Research Service Germplasm Resources Information Network (https://www.ars-grin.gov/Pages/Collections; accessed on 16 October 2017). This accession was derived from a population grown in Russia at a latitude of 56. Seeds of M. sativa subsp. sativa cv. Beaver ('sativa'), which is relatively susceptible to drought and is typically grown under irrigation, were provided by Dr. Surya Acharya (Agriculture and Agri-Food Canada, Lethbridge Research and Development Centre, Lethbridge, Canada). Due to the outcrossing nature of M. sativa, all assessments were carried out using biological replicates (details are provided in specific subsections below, as well as in figure legends) of a single genotype of each accession/cultivar derived from vegetative stem cuttings for each treatment, respectively. All plants were grown in Cornell mix in 4" pots under greenhouse conditions with supplemental light with a 16 h/8 h photoperiod, and a day/night temperature of approximately 20/15 C. Pots were rotated daily to prevent microclimate effects and plants were cut back to approximately 5 cm at least twice prior to assessments. Drought treatment involved withholding water and daily monitoring of volumetric soil moisture content using a ML3 ThetaKit soil moisture meter (Hoskin Scientific Ltd., Burnaby, Canada), as well as stress symptoms, such as dry shoots and wilted leaves. All pots were adjusted to a soil moisture content of 50% prior to the experiment. All physiological, biochemical, and transcriptomic analyses were carried out at volumetric soil moisture contents of approximately 50% (control treatment) and 7-8% (drought treatment; when 'sativa' plants first began exhibiting signs of dehydration stress). All growth measurements were carried out using well-watered plants (approximately 50% volumetric soil moisture content) and in certain cases also following drought recovery (2-3 weeks of re-watering after allowing volumetric soil moisture contents to reach approximately 4% (aboveground measurements) or 1% (root measurements)). Assessment of Growth Characteristics Between ten and eleven vegetative stem cuttings for each treatment (drought recovery and control) were generated from a single genotype of 'sativa' and 'falcata', respectively, in order to assess growth characteristics and penalties in each case. Flowering time was defined as the number of days following cutting to the appearance of the first open flower in well-watered plants. To evaluate growth penalties following drought recovery, aboveground and belowground plant growth characteristics were assessed. For aboveground evaluations, measurements were carried out 35-37 days after cutting under well-watered control conditions (soil moisture levels were maintained at approximately 50%) and following drought recovery (soil moisture content was allowed to reach approximately 4%, after which time plants were re-watered for 2 weeks). Plant height was derived from the length of the longest shoot, internode length consisted of the mean value of the longest internode on the three longest shoots of each plant, and the number of shoots comprised the total number of primary, secondary, and tertiary shoots per plant. Aboveground FW was evaluated by weighing all aboveground tissue immediately following harvest, while DW was determined following drying at 65 C for at least 1 week. Root assessments were carried out 54 days after cutting under well-watered conditions (control) and following drought recovery, which comprised allowing soil moisture content to reach approximately 1%, followed by re-watering for 3 weeks. At the time of evaluation, plants were removed from their pots and the roots were washed thoroughly. Root length was determined from the longest root on each plant. Root DW measurements were determined by drying at 65 C for at least 1 week prior to weighing. For evaluation of survival following drought treatment, water was withheld until volumetric soil water content reached approximately 1%, after which time plants were re-watered normally for 2-3 weeks and plant survival was assessed by determining the percentage of plants that regenerated. Leaf Characteristics and Stomatal Measurements Leaf length, leaf width, leaf area, and SLA were measured 21 days after cutting on five biological replicate plants of each genotype, with three leaves assessed per plant, using the middle leaflet of the third fully expanded trifoliate leaf from the shoot tip. Leaf area was resolved using the Petiole plant leaf area meter app (version 2.0.1; https://play.google. com/store/apps/details?id=com.petioleapp.petiole&hl=en_CA&gl=US; accessed on 29 April 2019) and leaf dry weight was then determined after drying at 80 C for 24 h. Specific leaf area was established by dividing leaf area by dry weight in each case. Stomatal density, length, width, and area were measured using middle leaflets of third trifoliate leaves (from the shoot tip) from three biological replicate 35-day-old plants. Stomatal density was determined by applying clear nail polish to the abaxial side of leaflets (four to five leaflets from each of the three biological replicate plants), which were then allowed to dry for 10-15 min. The leaf imprints were then peeled off with the help of transparent tape, and slides were prepared. The resulting slides were visualized with an EVOS FL Auto Imaging System (Thermo Fisher Scientific, Waltham, MA, USA) under 20 magnification and stomata were counted. Values were then converted to the number of stomata per mm 2 in each case. Stomatal length, width, and area were assessed on six to seven randomly selected stomata from each of the three biological replicate plants (twenty stomata total for each genotype) using the EVOS FL Auto Cell Imaging System software (Thermo Fisher Scientific, Waltham, MA, USA). Measurement of Relative Water Content and Detached Leaf Water Loss Water deficit was estimated by measuring the RWC of first fully expanded trifoliate leaves from ten biological replicates of each genotype, as described previously, when soil moisture content reached approximately 50% (well-watered), 20% (mild drought), and 7% (drought). In brief, the fresh weight (FW) of trifoliate leaves was recorded immediately after harvesting, turgid weights (TW) were resolved after submersing petioles in water in an enclosed Eppendorf tube for 3-4 h, and dry weights (DW) were established by drying turgid leaves at 80 C overnight. RWC (%) was then calculated as 100. Detached leaf water loss assays were carried out on five biological replicate plants of 'sativa' and 'falcata' by weighing a fully expanded trifoliate leaf from each plant immediately upon harvest (W initial ), placing the leaf in the open air on a benchtop, and then weighing every 30 min for 180 min. The rate of water loss as a percentage was calculated as (W initial − W at particular time /W initial ) 100. Biochemical Assessments All biochemical assessments were conducted using first fully expanded trifoliate leaves from nine to ten biological replicates of each genotype in each treatment. In all instances, leaf tissue was freeze-dried prior to carrying out assays. The control treatment comprised plants with soil moisture levels maintained at approximately 50%, while drought-treated samples were harvested when soil moisture levels reached approximately 7% (when 'sativa' plants were beginning to show signs of drought stress). Total soluble sugar content was assessed using the Plant Soluble Sugar Content Assay Kit according to the manufacturer's instructions (MyBioSource Inc., San Diego, CA, USA). Two technical replicates were carried out for each sample. Proline content was determined as described previously with minor modifications. In brief, approximately 50 mg (FW) leaf tissue was freeze dried and ground using a TissueLyzer II (Qiagen Inc., Toronto, ON, Canada), after which time 1 mL 3% aqueous sulphosalicylic acid was added to each tube. The tissue was further homogenized and incubated at room temperature for 3 h, and then centrifuged at 1500 g for 10 min. Following centrifugation, 600 L of sample supernatant (or various concentrations of L-proline standard) was added to 600 L glacial acetic acid and 600 L ninhydrin reagent (0.025 g/mL ninhydrin, 0.6 mL/mL glacial acetic acid, 2.4 M H 3 PO 4 ). Reactions were incubated at 100 C for 45 min, then cooled on ice for 30 min. To each tube, 1.2 mL toluene was added, and reactions were vortexed and then centrifuged at 1000 g for 5 min. Proline content was determined in triplicate in microplate format using toluene as a blank in a Synergy Mx Multi-Mode Microplate Reader spectrophotometer (BioTek Instruments Inc., Winooski, VT, USA) at 520 nm. Evaluation of Antioxidant Activity Antioxidant assays were carried out using a single first fully expanded trifoliate leaf from nine to ten biological replicates of 'sativa' and 'falcata' plants under well-watered (approximately 50% soil water content) and drought (approximately 7% soil water content) conditions. Tissue was immediately frozen in liquid nitrogen, ground in a TissueLyzer for 1 min at 30 Hz, and placed back in liquid nitrogen. To each sample, 1.5 mL extraction buffer (0.15 M potassium phosphate buffer, pH 7.8 and 1 mM EDTA) was added and samples were vortexed for 30 s. Subsequently, the samples were centrifuged at 12,000 g at 4 C for 20 min, and the supernatant was transferred to a fresh tube. Extracts were used for all subsequent assays, which were carried out in triplicate. Protein concentration was determined using a Bradford assay, with 4 L extract and the Quickstart Protein Assay according to the manufacturer's microassay protocol, with bovine serum albumin as a standard (Bio-Rad Laboratories Ltd., Hercules, CA, USA). CAT activity was evaluated as described previously with minor modifications. Initially, the spectrophotometer (SmartSpec Plus; Bio-Rad Laboratories Ltd., Hercules, CA, USA) was blanked at 240 nm with 50 mM potassium phosphate buffer (pH 7.0). For each assay, 33 L sample extract was added to 967 L CAT reaction mixture (50 mM potassium phosphate buffer, pH 7.0, 10 mM H 2 0 2 ) in a 1 mL cuvette and the absorbance was immediately measured at 240 nm (A sampleT0 ). A second reading was carried out after precisely 3 min (A sampleT3 ). CAT activity (nM H 2 0 2 min −1 mg protein −1 ) was calculated as (A sampleT0 − A sampleT3 )/(e d t C), where e corresponds to 39.4 M −1 (extinction coefficient of H 2 0 2 ), d corresponds to 1 cm (cuvette path length), t corresponds to 3 min (incubation time), and C corresponds to the amount of protein (mg) within the 33 L of extract used for analysis. APX activity was determined as described previously with minor modifications. To a 1 mL cuvette, 967 L APX reaction mixture (50 mM potassium phosphate buffer, pH 7.0, 0.5 mM ascorbic acid, 0.1 mM EDTA) was mixed with 33 L sample extract and 5 L 200 mM H 2 0 2. APX reaction buffer was used in place of sample extract for blanks. Absorbances were read immediately at 290 nm (A sampleT0 ), and a second reading was taken after precisely 3 min (A sampleT3 ). APX activity (M ascorbatemin −1 mg protein −1 ) was calculated as (A sampleT0 − A sampleT3 )/(e d t C), where e corresponds to 2.8 mM −1 cm −1 (extinction coefficient of H 2 0 2 ), d corresponds to 1 cm (cuvette path length), t corresponds to 3 min (incubation time), and C corresponds to the amount of protein (mg) within the 33 L of extract used for analysis. SOD activity was assessed as described previously with minor modifications to allow for microplate format. Briefly, each reaction consisted of 5 L of sample extract and 195 L SOD reaction mixture (50 mM potassium phosphate buffer, pH 7.8, 2 mM EDTA, 9.9 mM L-methionine, 55 M nitroblue tetrazolium, 0.025% Triton X-100 and 1 M riboflavin). Every reaction was replicated under light (approximately 80 mol m −2 s −1 ) and dark conditions, and was incubated for 10 min at room temperature in each case. Absorbance was then measured with a microplate spectrophotometer (Synergy Mx Multi-Mode Microplate Reader; BioTek Instruments Inc., Winooski, VT, USA) at 560 nm with extraction buffer as a blank (A blank ). Sample absorbance (A sample ) was calculated as absorbance in the dark subtracted from absorbance in the light. SOD activity (SOD units/mg protein) was calculated as /mg protein. Chlorophyll-and Photosynthesis-Related Measurements Chlorophyll content in the leaves of ten to eleven biological replicates of 'sativa' and 'falcata' genotypes was determined using a CCM-200 Chlorophyll Content Meter (Hoskin Scientific Ltd., Burlington, ON, Canada). The middle leaflet of third fully expanded trifoliate leaves was used for measurements in each case, with the values obtained from three leaves averaged for each biological replicate. Leaves were assessed under wellwatered conditions (approximately 50% soil moisture content) and when drought-treated 'sativa' plants were just beginning to display symptoms of stress (soil moisture content of approximately 8%). Stomatal conductance (g s ), transpiration rate (E), and light-saturated photosynthetic rate (Asat) were measured with an LI-6800 (LI-COR Inc., Lincoln, NE, USA). The centre leaflet of a first fully expanded dark green trifoliate leaf was used for measurements, and all observations were carried out between 12:45 pm and 3:45 pm in the greenhouse. Leaves were evaluated under well-watered conditions (approximately 50% soil moisture content) and under drought treatment (average soil moisture content of approximately 7%). Four biological replicates were utilized for 'sativa' under drought conditions and eleven biological replicates were used for the remaining groups. The number of 'sativa' drought-treated plants assessed was lower than other groups due to the lack of viable tissue in a proportion of plants as a result of drought stress on the day testing was carried out. Within the chamber, light intensity was maintained at 1500 mol m −2 s −1, relative humidity at 65%, air temperature at 22 C, and CO 2 level at 410 mol CO 2 /mol air. Each leaflet was allowed 3 min to stabilize within the chamber prior to assessment. All three measurements were adjusted for leaf area, which was determined using the Petiole app (version 2.0.1) as described in a previous section. Leaf tissue was harvested from control (soil moisture content of approximately 50%) and drought-treated plants (soil moisture content of approximately 7%), flash frozen in liquid nitrogen, and stored at −80 C. Tissue was harvested from four biological replicates of 'sativa' and 'falcata' under each treatment, respectively. Total RNA was extracted from ground tissue using the Spectrum Plant Total RNA Kit according to the manufacturer's instructions (Sigma-Aldrich Corp., St. Louis, MO, USA). RNA integrity was confirmed by resolving a small aliquot on a 1% agarose gel and using a 2100 BioAnalyzer (Agilent Technologies, Santa Clara, CA, USA). A stranded mRNA library was prepared using 250 ng of total RNA and the NEBNext®system (New England Biolabs Ltd., Whitby, ON, Canada), and sequencing was carried out using an Illumina NovaSeq 6000 platform (Illumina Inc., San Diego, CA, USA) with 100 bp paired-end reads by a third party (Genome Qubec Centre d'Expertise et de Services, Montreal, QC, Canada). The resulting raw RNA-Seq data was analyzed as described previously with minor modifications. Briefly, raw reads were trimmed using the 'sickle' script in Linux with default parameters, and read quality was assessed using the FASTQC tool (https://www.bioinformatics.babraham.ac. uk/projects/fastqc/; accessed on 30 May 2020). High-quality filtered reads were mapped to the Medicago truncatula genome (Mt4.0 v2; http://www.medicagogenome.org/downloads; accessed on 31 May 2020; a close diploid relative of alfalfa with a well-annotated genome sequence) using Tophat2. DEGs were identified and normalized to FPKM using Cuffdiff. Genes with a false discovery rate (FDR) of less than 0.05 were considered DEGs (File S1). PCA was performed using total exon read counts, which were obtained using the featureCounts program, followed by analysis using freely available R-software (v4.0). Venn diagrams were generated using freely available software (http://bioinformatics.psb.ugent. be/webtools/Venn/; accessed on 15 June 2021). The sequence data generated in this study are available at the National Center for Biotechnology Information (NCBI) Sequence Read Archive (BioProject accession number PRJNA765383). GO Term Enrichment and Pathway Analysis SEA of either up-regulated or down-regulated DEGs observed between control and drought conditions for both 'sativa' and 'falcata' were carried out using AgriGO v2.0 (http://systemsbiology.cau.edu.cn/agriGOv2/; accessed on 13 January 2021) with M. truncatula as the reference species. In both cases, the hypergeometric statistical test was used, along with the Yekutieli (FDR under dependency) multi-test adjustment method, with a significance level of 0.05. SEACOMPARE was conducted by inputting SEA results. PAGE was carried out by inputting all up-regulated and down-regulated DEGs observed between 'sativa' and 'falcata' when grown either under control or drought conditions, along with log2 fold-change expression values (expression values of 0 were artificially set to 0.001 in order to provide numerical log2 fold-changes), using the same program with the Hochberg (FDR) multi-test adjustment method and a significance level of 0.05. Heat maps were generated using the freely available Morpheus tool (https://software. broadinstitute.org/morpheus/; accessed on 20 May 2021). Visualization of DEG-associated pathways between 'sativa' and 'falcata' under both well-watered and control conditions was performed using MapMan V3.6 software (https://mapman.gabipd.org/) with the M. truncatula genome as a reference sequence (Mt4.0 v2). Validation of RNA-Seq Results Total RNA that was extracted from leaf tissues for RNA-Seq analysis was utilized for qRT-PCR validation. First-strand cDNA synthesis was carried out using the SuperScript VILO cDNA synthesis kit (Thermo Fisher Scientific, Waltham, MA, USA) and quantitative real-time RT-PCR assays were conducted using an appropriate dilution of each cDNA template along with PerfeCTa SYBR Green Supermix (VWR International LLC, Mississauga, ON, Canada) in a final reaction volume of 10 L. Assays were accomplished on a Quantstudio 6 Flex Real-Time PCR System (Thermo Fisher Scientific, Waltham, MA, USA) using primers designed to anneal to a region of coding sequence for ten genes selected based on their up-or down-regulation in RNA-Seq analyses (see Table S2 for primer sequences used for qRT-PCR assays). A 183 nt region of the constitutively expressed actin-depolymerizing factor (ADF) gene, which has been shown previously to act as a highly stable reference gene for qRT-PCR across developmental stages and environmental conditions (including water stress) in alfalfa, was amplified as an internal control. Thermal parameters for amplification were as follows: initial denaturation at 95 C for 3 min, followed by 40 cycles of 95 C for 15 s and 60 C for 45 s. Dissociation curves were generated to confirm the presence of a single amplification product in each case. Levels of gene expression were established using the standard curve method and Applied Biosystems TM analysis software v4.0 (Thermo Fisher Scientific, Waltham, MA, USA), with the expression of each target gene comprising mean values of four biological replicates (three technical replicates each) normalized to that of the internal control. Log2 fold-change values between control and drought samples were calculated for comparison to RNA-Seq values. Statistical Analyses For the majority of multi-variate comparisons, the observed response variables were modeled using the GLIMMIX procedure in SAS (SAS version 9.4, SAS Institute Inc., Cary, NC, USA) with one-thousand iterations at multiple levels of iteration (MAXOPT = 1000 and NLOPTIONS MAXITER = 1000). The normal distribution of the response was not assumed and therefore the models were "generalized." The best-fitting distribution from the exponential family of distributions (e.g., gamma, inverse Gaussian, lognormal, shifted-t, normal, and exponential) was selected for each variable, based on the model fit statistics, that is, the Bayesian information criterion (BIC). The models were "mixed" due to the inclusion of fixed factors (Genotype, Growth_conditions, and Genotype Growth_conditions) and random factors (Biological_replicate). Variance homogeneity was not assumed and models of variance heterogeneity were tested and selected based on the BIC of the models. Bonferroni's method was used to adjust for multiple comparisons. For assessments that involved comparisons between genotypes under a single treatment, as well as for evaluations of photosynthetic rate, stomatal conductance, and transpiration rate, 2-tailed Student's t-tests assuming unequal variance were used for statistical analysis. Differences were considered significant at p ≤ 0.05. Supplementary Materials: The following are available online at https://www.mdpi.com/article/ 10.3390/plants10102107/s1, Figure S1: Stomatal, photosynthetic, and water loss-related traits in 'sativa' and 'falcata' plants, Figure S2: Biochemical and antioxidant response of 'sativa' and 'falcata' genotypes to drought stress conditions, Figure S3: Principal component analysis of FPKM expression values, Figure S4: Identification of DEGs between genotypes and conditions and validation of RNA-Seq results, Figure S5: SEACOMPARE analysis of up-regulated DEGs observed in 'sativa' control vs. drought and 'falcata' control vs. drought in the biological process GO grouping, Figure S6: SEACOMPARE analysis of up-regulated DEGs observed in 'sativa' control vs. drought and 'falcata' control vs. drought in the molecular function GO grouping, Figure S7: SEACOMPARE analysis of down-regulated DEGs observed in 'sativa' control vs. drought and 'falcata' control vs. drought in the biological process GO grouping, Figure S8: SEACOMPARE analysis of downregulated DEGs observed in 'sativa' control vs. drought and 'falcata' control vs. drought in the molecular function GO grouping, Figure S9: SEACOMPARE analysis of down-regulated DEGs observed in 'sativa' control vs. drought and 'falcata' control vs. drought in the cellular compartment GO grouping, Figure S10: Transcriptional alterations in the abiotic stress response, as well as phytohormone-, redox-, and secondary-metabolism-related pathways in 'sativa' (a and c) and 'falcata' (b and d) plants under control vs. drought conditions, Figure S11: Transcriptional alterations in genes involved in transcriptional regulation in 'sativa' (a) and 'falcata' (b) plants under control vs. drought conditions, Figure S12: Transcriptional alterations in redox-related pathways, as well as hormone metabolism, between 'sativa' vs. 'falcata' under control and drought conditions, Figure S13: Differential expression of genes encoding heat shock factors, LEAs, and aquaporins between conditions and genotypes, Table S1: RNA-Seq read and alignment data for 'sativa' and 'falcata' under well-watered (control) and drought conditions, Table S2: Primers used for qRT-PCR validation of RNA-Seq results, File S1: Differentially expressed genes between genotypes and growth conditions, File S2: Information regarding differentially expressed genes between treatments and genotypes falling into a selection of MapMan categories with putative functions in abiotic stress response. |
ABCA1-dependent serum cholesterol efflux capacity inversely correlates with pulse wave velocity in healthy subjects. The capacity of HDL to induce cell cholesterol efflux is considered one of its main antiatherogenic properties. Little is known about the impact of such HDL function on vascular physiology. We investigated the relationship between ABCA1-dependent serum cholesterol efflux capacity (CEC), an HDL functionality indicator, and pulse wave velocity (PWV), an indicator of arterial stiffness. Serum of 167 healthy subjects was used to conduct CEC measurement, and carotid-femoral PWV was measured with a high-fidelity tonometer. J774 macrophages, labeled with cholesterol and stimulated to express ABCA1, were exposed to sera; the difference between cholesterol efflux from stimulated and unstimulated cells provided specific ABCA1-mediated CEC. PWV is inversely correlated with ABCA1-dependent CEC (r = −0.183; P = 0.018). Moreover, controlling for age, sex, body mass index, mean arterial pressure, serum LDL, HDL-cholesterol, and fasting plasma glucose, PWV displays a significant negative regression on ABCA1-dependent CEC ( = −0.204; 95% confidence interval, −0.371 to −0.037). The finding that ABCA1-dependent CEC, but not serum HDL cholesterol level (r = −0.002; P = 0.985), is a significant predictor of PWV in healthy subjects points to the relevance of HDL function in vascular physiology and arterial stiffness prevention. The PWV, the vessel vasodilative function ( 23 ), and endothelial function ( 24 ) are interrelated through a complex network of cellular and biochemical factors, including PGI-2 and NO ( 13 ). Because HDL function determination could be a useful tool to better defi ne vessel health and preclinical vascular risk, the aim of this study was to evaluate the relationship between serum CEC, as a metabolic parameter refl ecting HDL function, and PWV, as an index of arterial stiffness, in a population of healthy subjects in the absence of pharmacological treatment. The inverse correlation that we found between ABCA1-mediated CEC and PWV in a healthy population provides insights into the mechanisms of early atherosclerotic process and HDL atheroprotection. Study design Healthy subjects were selected among those enrolled in the Brisighella Heart Study (BHS) ( 25 ). The general protocol of the BHS and of its substudies have been approved by the Ethical Committee of the University of Bologna and conform to the principles outlined in the Helsinki Declaration. Written informed consent was obtained from all study participants. The BHS is a prospective, population-based, longitudinal, epidemiological investigation started in 1972 and involving randomly selected subjects, aged 14 to 84 years and free of CVD at enrolment, all resident in the rural town of Brisighella, an area characterized by life-style homogeneity and a very low migration rate from other countries ( 26 ). Participants were clinically evaluated at baseline and every 4 years thereafter by extensively assessing clinical and laboratory profi les according to a standardized protocol that has been described in detail elsewhere ( 27,28 ). Subjects The fi nal enrolled population sample consisted of 167 subjects (54 male and 113 female) who were nonsmokers; nondiabetics; untreated with antihypertensive, antihyperlipidaemic, or antidiabetic drugs; and free from echographically detectable atherosclerotic plaques ( Table 1 ). Beyond the standard procedures enlisted in the BHS protocol, these subjects underwent serum cholesterol effl ux capacity determination and carotid-femoral PWV measurement. role in cardioprotection ( 11 ). The interaction between HDL and ABCA1 is followed by the activation of distinct intracellular signaling pathways in macrophages and in endothelial cells, resulting in preservation of vessel health ( 13 ). Isolated aortic endothelial cells from transgenic mice overexpressing hABCA1 show enhanced cholesterol effl ux and elevated levels of eNOS mRNA ( 14 ). Moreover, a more recent study demonstrated that binding of apoA-I to ABCA1 increases prostaglandin I-2 (PGI-2) secretion in endothelial cells, resulting in atheroprotection through vasodilation as well as the inhibition of platelet aggregation and monocyte adhesion ( 13,15 ). Pulse wave velocity (PWV), the propagation speed of the pulse pressure wave, is one of the major determinants of pulse pressure and is widely used as an index of arterial stiffness. Arterial stiffness is determined by several structural and functional factors, including the cross-sectional arrangement of cells and interstitial components (particularly collagen and elastin) in the vessel wall, the characteristics and number of smooth muscle cells, endothelium-mediated vasodilation, hormones, and electrolyte balance. The correlation between arterial stiffness and end-organ damage in cardiovascular diseases is widely accepted on the basis of clinical studies and pathophysiology mechanisms ( 16,17 ). In particular, PWV has been demonstrated to be a predictor for adverse cardiovascular events in hypertension and CVD in many patient populations ( 18 ) and has been indicated as a useful diagnostic tool for increased cardiovascular risk by international guidelines ( 19,20 ). The relevance of PWV derives not only from the fact that it refl ects the structure of elastic arteries (i.e., the composition and organization of vessel wall) but also from its involvement in the evolution of heart and vessel function in time. In fact, if PWV increases, the backward pressure wave refl ections return from the distal arterial compartment earlier than normal, during systole instead of diastole, increasing ventricular and aortic systolic pressure and decreasing aortic pressure during diastole. These changes augment left ventricular afterload and myocardial oxygen demand, reduce coronary perfusion, and cause mismatch between ventricle emptying and arterial pulse wave transmission, leading to ventricular hypertrophy ( 21,22 ). Statistical analysis Statistical analyses were performed with STATA 11.0, Version for Windows. Mean and standard deviation were used to describe the studied variables except for lipoprotein(a), which was summarized by means of median and interquartile range due to its natural asymmetric distribution. A multiple linear regression analysis with nested design was then performed to investigate the relationship between PWV and CEC. A nested design allowed us to assess the effect of each variable and potential confounder and to evaluate the improvement in model fi t produced by the introduction of such variable (or set of variables). This latter statistical element informs how well the model predicts the outcome. All the variables included in the models are continuous. Because age has a non-normal distribution, as emerged from application of the Shapiro-Wilk test for normality, all the models were estimated with Huber-White sandwich robust estimator of standard errors, which limits the effects of non-normality of explanatory variables. In the nested design, model 1 estimates the effect of individual characteristics (age and sex) on PWV, model 2 checks for the infl uence of cardio-circulatory risk factors (body mass index, mean arterial pressure, LDL-cholesterol, fasting plasma glucose), and models 3 and 4 assess, respectively, the effect of HDL-C and ABCA1 once controlled for the previous variables. A further CEC We quantifi ed serum CEC by using a validated ex vivo system that involves incubation of macrophages with whole serum from the study participants ( 4,8,9 ). Effl ux studies were performed using macrophages labeled with cholesterol in the presence of an ACAT inhibitor (Sandoz 58035) used at 2 g/ml. Aqueous diffusion-dependent process was evaluated in J774 murine macrophages, which, under basal conditions, express low levels of ABCA1, ABCG1, and SR-BI and release membrane cholesterol to extracellular acceptors mainly by aqueous diffusion ( 4,29 ). Stimulation of J774 murine macrophages with cAMP (0.3 mM) for 18 h up-regulates the ABCA1 protein ( 30,31 ). In such conditions, total release of cholesterol occurs mainly by ABCA1 and aqueous diffusion ( 4,32 ). ABCA1-mediated CEC was calculated as the difference in effl ux between ABCA1 expressing J774 and J774 in basal conditions ( 33 ). The effl ux was promoted for 4 h to 2% (v/v) serum samples. CEC was expressed as a percentage of the radioactivity released to the medium over the total radioactivity incorporated by cells ( 33 ). Whole serum was used to measure ABCA1-mediated CEC because the specifi c acceptor for ABCA1 is lipid free or lipid poor apoA-I, which characterizes nascent HDL ( 8,34,35 ); thus, the presence of apoB lipoprotein during the procedure does not affect the fi nal result ( 29 ). To minimize the intra-assay variability, every serum sample was run in triplicate, and average values and standard deviations were calculated for each percentage of effl ux obtained ( 29 ). cAMPinduced ABCA1 expression was verifi ed by the increase in effl ux to 10 g/ml apoA-I used as ABCA1 specifi c extracellular acceptor ( 31,32 ). A pool of human sera as reference standard 1 (St1) was tested in each assay, and its effl ux capacity was used to normalize the patient sample values from different experiments to correct for the interassay variability. A second pool of human sera as reference standard 2 (St2) was tested in each assay, and its effl ux capacity, after normalization, was the index of the intra-assay variability ( 32 ). Calculated mean intra-and interassay coeffi cients of variation were 5.95% and 9.53%, respectively. To prevent HDL remodeling at room temperature, all serum samples were immediately stored at 80°C after drawing, and the aliquots were defrosted in ice just before use. All sera used in the study underwent one cycle of freezing and thawing. Vascular investigations Carotid-femoral PWV was measured using the PulsePen device (DiaTecne srl, Milan, Italy), which is a validated, easy-to-use, high-fi delity tonometer that has been described in detail previously ( 36 ). PWV is determined by a single probe at two intervals in a highly rapid succession, using the electrocardiogram trace as reference: the detector is fi rst positioned at the common carotid artery, the central detection site, simultaneously performing electrocardiogram and tonometry, and then on the femoral artery. When the difference between heart rate recorded during the carotid measurement and that recorded during the femoral measurement is 10%, the PWV evaluation is repeated (the difference in heart rate is indicated in the PulsePen software). The PWV is calculated as the distance between the measurement sites divided by transit time delay between femoral and carotid pulse wave. The distance of the pulse wave transit is the difference between the distance from suprasternal notch to femoral point of application of the tonometer and the distance from carotid point of tonometer application and the suprasternal notch. The time delay is measured between the foot of the femoral artery and carotid waveforms. The wave foot is defi ned at the end of diastole, when the steep rise of the waveform begins. To avoid methodological bias, a single senior investigator performed all of the PWV measurements. The intraobserver coeffi cient Finally, ABCA1-mediated CEC shows a signifi cant negative relationship with PWV. Once controlled for the previous factors, a one-unit change in ABCA1 produces a significant decrease of 0.179 m/s in PWV (95% CI, 0.363 to 0.006) and a 0.015 increase in adjusted R 2 with respect to model 3. The VIF statistic does not support the hypothetic existence of multicollinearity issues ( Table 3 ). DISCUSSION The main fi ndings of this work are that serum ABCA1mediated CEC inversely correlates with PWV independently of total HDL-C serum concentration and is a strong independent predictor of arterial stiffness in a healthy population not receiving pharmacological therapy. These fi ndings point to the relevance of HDL function in the maintenance of vessel health. Our new observation that ABCA1-dependent serum CEC is the fi rst strong parameter that follows those well known to be predictive of PWV (age, blood pressure, and BMI) ( 38,39 ) is consistent with the idea that functionally conserved HDL, infl uencing cholesterol traffi cking in the arterial wall, may contribute to limit vessel stiffness. A very recent work showed that arterial stiffness, evaluated as PWV, correlates with circulating oxidized LDL in healthy subjects, pointing to the importance of lipid metabolism on this parameter ( 40 ). Our fi ndings support the emerging concept that HDL-mediated atheroprotection is dependent on its function rather than quantity and, most importantly, is relevant in clinically healthy subjects. Indeed, only ABCA1-dependent serum CEC, an index of HDL functionality ( 8 ), and not aqueous diffusion-dependent CEC, which refl ects a bidirectional nonspecifi c effl ux with variable impact on cellular cholesterol content ( 31 ), is a good indicator of arterial compliance in our study. The (model 5), including an interaction between ABCA1 and sex, was estimated. The improvement in model fi t after the estimation of every model was assessed by means of adjusted R 2 and a likelihood ratio test. Finally, a postestimation analysis was carried out to check for the presence of multicollinearity among variables using the variance infl ation factor (VIF) statistic. Multicollinearity is a statistical problem that arises when two predictor variables are highly correlated and might bias the coeffi cient estimates of the variables involved. This statistic indicates the existence of multicollinearity for VIF 5. All reported P values are two-tailed, with a P value of 0.05 indicating statistical signifi cance. In the nested linear regression ( Table 2 ), all the models show a signifi cant improvement in model fi t except models 3 and 5 (likelihood ratio test returns P values of 0.475 and 0.441, respectively). This means that HDL-C and the interaction term do not increase the explanatory power of the model. On the other hand, model 4 has the best fi t (adjusted R 2 = 0.440). In this model, as expected, age is the only signifi cant individual characteristics, with PWV increasing by 0.042 m/s (95% confi dence interval , 0.026-0.058) per year of age. Regarding risk factors, BMI (  = 0.052; 95% CI, 0.019-0.085) and mean arterial pressure (  = 0.056; 95% CI 0.039-0.074) show a signifi cant impact on PWV. All these effects are robust across models. variables that could interfere with PWV, such as smoking habit and diabetes, or controlled through a specifi c statistical analysis. The main limitation of this study is the relatively low number of subjects enrolled. This was mainly due to the strict defi nition of "healthy subject" that we applied and to the search for a representative sample of a general population cohort. In conclusion, we have shown for the fi rst time that ABCA1-dependent serum CEC is inversely related to PWV in pharmacologically untreated healthy subjects, independently of total HDL-C serum levels, and is a powerful predictor of arterial stiffness. This fi nding points to the relevance of HDL function in vascular physiology and arterial stiffness prevention. measurement of ABCA1-mediated CEC is a direct index of HDL functionality strictly dependent on serum pre  HDL content, as widely demonstrated ( 8,34,35,41 ), so it renders redundant HDL composition analyses such as HDL pre  content measurement in the present study. The relationship between HDL composition/function and arterial stiffness seems to be underlined also by the recent observation that reduction of paraoxonase-1, an atheroprotective HDL antioxidant component, predicts PWV in renal transplant recipients ( 42 ). The demonstration that PWV in adulthood is infl uenced by atherogenic lifestyle factors in childhood ( 43,44 ) confi rms the existence of a large number of determinants, other than blood pressure and age, able to modify arterial wall over time in asymptomatic subjects. The idea that HDL promotion of cholesterol effl ux may be an important determinant of vessel health is supported by increasing evidence that cholesterol effl ux mediated by ABCA1 and other ABC transporters, particularly ABCG1, are associated with intracellular signaling resulting, for example, in endothelial eNOS activation, PGI-2 secretion, and inhibition of various proinfl ammatory molecules ( 13 ). The absence of a signifi cant correlation between PWV and HDL cholesterol levels in our population supports the idea that HDL serum concentration does not always refl ect HDL function. The discrepancy between our data and previous reports could be related to the type of population analyzed. Our observation adds to the recently reported correlation between serum CEC and IMT as a marker of early atherosclerosis ( 4 ). However, the data presented in our work represent new information because IMT and PWV are considered different entities of vascular damage, with IMT believed to refl ect more advanced structural atherosclerotic changes in the arterial wall compared with PWV ( 48 ). Moreover, PWV has been recently demonstrated to inversely correlate with fl ow-mediated dilation, a sensitive parameter for endothelial function ( 24 ). Our results support the idea that the predictive power of ABCA1mediated CEC with respect to arterial stiffness may be an adjunctive tool to understand and detect early functional and structural vascular derangement. One of the strengths of our study is the accurate selection of pharmacologically untreated subjects with a known clinical history. Moreover, the role of other confounding factors was minimized through the careful exclusion of |
Voters head to the polls Tuesday in New York state, where 247 Democratic delegates are at stake--and it's yet another state where Vermont Sen. Bernie Sanders is outspending former secretary of state Hillary Clinton heavily on the airwaves.
Sanders has spent $6.64 million on television and radio buys in New York since April 5, a Democratic source who tracks media buys told CBS News. Clinton, by contrast, has spent $3.93 million on television and radio during that same two-week period.
This is not the first time Sanders has dropped more on TV ads than Clinton, and with varying results. In Wisconsin, his team spent $2.4 million on TV and radio ads in the two weeks before primary day, compared with $1.43 million for Clinton--and Sanders ended up winning the state by 13 points. The same dynamic was true in New Hampshire, where Sanders spent more and had a big win.
But in Arizona, where Clinton won by 18 points, NBC News reported that Sanders spent $1.3 million to Clinton's $600,000. He also spent heavily that same week in Utah, Washington, Idaho and Hawaii--all states he won by large margins, but into which Clinton put no ad money at all.
Sanders still isn't running any ads that go after Clinton by name--but in New York, where the tone of the Democratic primary has become much more contentious, he's getting a bit closer. After repeatedly hitting her for accepting speaking fees on Wall Street in excess of $200,000 per hour and her position on the federal minimum wage, his campaign put out an ad in New York that focuses on how "Wall Street banks shower Washington politicians with campaign contributions and speaking fees."
"$200,000 an hour for them, but not even 15 bucks an hour for all Americans," the ad's narrator says. "Enough is enough."
Clinton's campaign nodded to the spending discrepancy in an email to supporters Monday morning.
"The New York primary is in just one day, and Bernie's team has outspent us by more than TWO MILLION DOLLARS in TV ads," campaign manager Robby Mook writes in the email. "If we want to bring home a big win, we need to close that gap in these crucial final 24 hours."
A CBS News Battleground Tracker poll released Sunday found Clinton with a 10-point lead over Sanders in New York, 53 percent to 43 percent. |
n=int(input())
l=[int(i) for i in input().split()]
s=l[-1]
for i in range(1,n):
if(l[-i]<=l[-1-i]):
l[-i-1]=l[-i]-1
if l[-1-i]<0:
l[-1-i]=0
s+=l[-i-1]
#print("s",s)
else:
#print(l[-1-i])
#print("ssss",s)
s+=l[-1-i]
print(s) |
Design Approach with Higher Levels of Abstraction: Implementing Heterogeneous Multiplication Server Farms In order to reuse a register transfer level (RTL)-based IP block, it takes another architectural exploration in which the RTL will be put, and it also takes virtual platforms to develop the driver and applications software. Due to the increasing demands of new technology, the hardware and software complexity of organizing embedded systems is growing rapidly. Accordingly, the traditional design methodology cannot stand up forever to designing complex devices. In this paper, I introduce an electronic system level (ESL)-based approach to designing complex hardware with a derivative of SystemVerilog. I adopted the concept of reuse with higher levels of abstraction of the ESL language than traditional HDLs to design multiplication server farms. Using the concept of ESL, I successfully implemented server farms as well as a test bench in one simulation environment. It would have cost a number of Verilog/C simulations if I had followed the traditional way, which would have required much more time and effort. |
How valuable is Jameis Winston to the Buccaneers? Most Bucs fans understand that he is incredibly valuable, but few realize just how valuable Jameis is.
When you think about young quarterbacks that start in the NFL the first two that come to mind might be Carson Wentz and Dak Prescott. They are rookies right out of college so they are the youngest, right? Surprisingly this is simply not correct.
Who are the two youngest quarterbacks starting in the NFL? The answer is pretty exciting. The youngest is Marcus Mariotta at 22 years old with Jameis just behind him also at 22 years old. After that at 23 years old are Carson Wentz followed by Dak Prescott and then Cody Kessler.
Carson Wentz and Dak Prescott started out looking invincible, but let’s discuss these two compared to Jameis. Let me warn you in advance though that this will not be a homer article, but rather it will be as impartial a view that a fan like me can offer.
When a young quarterback starts their first season they are an unknown commodity. There is no real film for a defense to study on this quarterback. They are a new player on a team that is obviously making changes. This is one reason that young starting quarterbacks can look fantastic and then they fall to the dreaded “sophomore jinx”. It isn’t a jinx at all. It is simply that defenses now have a year of film to study and they know a little bit how to prepare for that quarterback.
For some quarterbacks like Carson Wentz this reality does not take a complete year. Reality begins setting in after a few games and that great streak of never turning the ball over crumbles when the opposition, which is filled with talented players, has the opportunity to prepare.
Dak Prescott is in a unique situation. He is on a team with a fantastic (possibly best in the NFL) offensive line. He is not asked to carry the team on his back. He has a great rookie running back right next to him. He is in an idea situation.
Cody Kessler? Well…Cleveland. Enough said.
Jameis is younger than both of these quarterbacks. Jameis has great fan appeal with both young and old and it is growing. He has been asked to shoulder a much greater load and has been asked to perform at a much higher level. Teams have a full year of film on him to study. His top RB, Doug Martin, is out injured. He lost his supposed top tight end in ASJ. What has he done with that situation? He positioned the team, at .500, to compete with the division leading falcons.
I learned years ago about “Perceived Value”.
Perceived value is the worth that a product or service has in the mind of the consumer. For the most part, consumers are unaware of the true cost of production for the products they buy; instead, they simply have an internal feeling for how much certain products are worth to them.
This certainly applies to Jameis. Does Jameis ACTUAL value match the PERCEIVED value that many fans have for him?
In one year Jameis will be as old as Wentz and Prestcott. He will have two full seasons under his belt and the team that was to be built around him will be well on its way to fruition. Complete? Probably not. He will be miles ahead of Wentz and Prestcott when it comes to knowledge of the game.
Jameis is a special commodity. In one year he will have the future of Wentz and Prestcott with a solid history behind him.
Marcus Mariotta is younger. He too will be in the same situation as Jameis, but things don’t look quite as bright in Tennessee. He seems like a solid, maybe even good, quarterback.
That feeling you have as a Tampa fan…what is it? It’s called “hope”. It’s been a while since we have had reasonable hope for a future of success. Right now we have that hope. We have it simply because we have a great quarterback…and we have him for a very VERY long time.
At least that is how I see it from the cheap seats.
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Eccentric former basketball star Dennis Rodman may not have brought imprisoned American Kenneth Bae back with him from North Korea, but he did emerge with something that set tongues wagging: the purported name of Kim Jong Un's baby daughter.
Rodman, who calls North Korea's young ruler his friend, returned this weekend from his second trip to the reclusive, nuclear-armed nation this year.
As he passed through Beijing airport on Saturday, he remained tight-lipped about what went on during his latest visit.
But he appears to have been more candid in an interview Sunday with the Guardian, a British newspaper, in which he described the "relaxing time by the sea" he spent with Kim and his family. And he also let slip the baby's name.
The people of Colcord, Oklahoma, might need something a little stronger than Brita filters to remove the impurities from their drinking water.
Blood worms - small, red insect larvae - have been appearing in water glasses and filters in the rural town.
Authorities have warned Colcord's 800 residents not to drink, cook with or brush their teeth with the worm-infested tap water.
Filed under: Oklahoma • U.S.
Philippine navy divers retrieved bodies Monday from inside a ferry that sank last week after colliding with a cargo ship.
The discovery of more victims' remains brought the number of people confirmed dead from the disaster in the southern Philippines to 52, the Philippine Coast Guard said. Another 68 people remain missing and 750 have been rescued, it said.
Rescue workers in northern India are scrambling to save tens of thousands of people left stranded by devastating floods that have killed as many as 150 people in the region.
Triggered by unusually heavy monsoon rains, the floods have swept away buildings, roads and vehicles in the mountainous state of Uttarakhand, which borders Nepal and China.
The Oxford English Dictionary has finally gotten around to acknowledging that tweeting isn't just for the birds.
In its latest update, the dictionary that describes itself as "the accepted authority on the evolution of the English language over the last millennium" has revamped the entry for "tweet" to include its social networking usage.
A North Korean court has sentenced a U.S. citizen to 15 years of hard labor, saying he committed "hostile acts" against the secretive state.
The country's Supreme Court delivered the sentence against Pae Jun Ho, known as Kenneth Bae by U.S. authorities, on Tuesday, the North's state-run Korean Central News Agency (KCNA) reported Thursday.
The KCNA article said Bae a Korean-American, was arrested November 3 after arriving as a tourist in Rason City, a port in the northeastern corner of North Korea. It didn't provide any details about the "hostile acts" he is alleged to have committed.
N. Korea sets tough terms for talks with U.S.
North Korea on Thursday set out demanding conditions for any talks with Washington and Seoul, calling for the withdrawal of U.N. sanctions against it and a permanent end to joint U.S.-South Korean military exercises.
The United States and South Korea "should immediately stop all their provocative acts against the DPRK and apologize for all of them," the North's National Defense Commission said in a statement carried by state-run media, using the shortened version of North Korea's official name, the Democratic People's Republic of Korea.
Filed under: Kim Jong Un • North Korea • South Korea • U.S. |
package main
import (
"gopkg.in/AlecAivazis/survey.v1"
"gopkg.in/AlecAivazis/survey.v1/tests/util"
)
var answer = []string{}
var table = []TestUtil.TestTableEntry{
{
"standard", &survey.MultiSelect{
Message: "What days do you prefer:",
Options: []string{"Sunday", "Monday", "Tuesday", "Wednesday", "Thursday", "Friday", "Saturday"},
}, &answer,
},
{
"default (sunday, tuesday)", &survey.MultiSelect{
Message: "What days do you prefer:",
Options: []string{"Sunday", "Monday", "Tuesday", "Wednesday", "Thursday", "Friday", "Saturday"},
Default: []string{"Sunday", "Tuesday"},
}, &answer,
},
{
"default not found", &survey.MultiSelect{
Message: "What days do you prefer:",
Options: []string{"Sunday", "Monday", "Tuesday", "Wednesday", "Thursday", "Friday", "Saturday"},
Default: []string{"Sundayaa"},
}, &answer,
},
{
"no help - type ?", &survey.MultiSelect{
Message: "What days do you prefer:",
Options: []string{"Sunday", "Monday", "Tuesday", "Wednesday", "Thursday", "Friday", "Saturday"},
Default: []string{"Sundayaa"},
}, &answer,
},
}
func main() {
TestUtil.RunTable(table)
}
|
/**
* Creates a JmsTracer using factory with the given name and any relevant configuration
* properties set on the given remote URI.
*
* @param remoteURI
* The connection uri.
* @param name
* The name that describes the desired tracer factory.
* @return a tracer instance matching the name.
*
* @throws Exception if an error occurs while creating the tracer.
*/
public static JmsTracer create(URI remoteURI, String name) throws Exception {
JmsTracerFactory factory = findTracerFactory(name);
return factory.createTracer(remoteURI, name);
} |
<reponame>NCHUSC/FootballLeague
package com.example.web;
import com.example.model.League;
import com.example.model.MatchInformation;
import com.example.model.MatchResult;
import com.example.model.Team;
import com.example.repository.LeagueRepository;
import com.example.service.MatchInformationService;
import com.example.service.MatchNewsService;
import com.example.service.PlayerService;
import com.example.service.TeamService;
import org.springframework.beans.factory.annotation.Autowired;
import org.springframework.stereotype.Controller;
import org.springframework.ui.Model;
import org.springframework.web.bind.annotation.GetMapping;
import org.springframework.web.bind.annotation.PostMapping;
import java.util.ArrayList;
import java.util.Collection;
import java.util.List;
@Controller
public class MatchController {
@Autowired
MatchNewsService matchNewsService;
@Autowired
MatchInformationService matchInformationService;
@Autowired
TeamService teamService;
@Autowired
LeagueRepository leagueRepository;
@Autowired
PlayerService playerService;
/**
* 跳转至添加比赛页面
*
* @param model
* @return
*/
@GetMapping("/selectLeague")
public String selectLeague(Model model) {
List<League> leagues = leagueRepository.findAll();
model.addAttribute("leagues", leagues);
return "match/selectLeague";
}
@PostMapping("/matchInformation")
public String matchInformation(League league, Model model) {
System.out.println(league);
System.out.println("所选联赛：" + league.getLeagueName());
List<Team> teams = teamService.getTeamByLeague(league.getLeagueName());
System.out.println("参加该联赛球队数：" + teams.size());
String mr;
int j = 1;
List<String> matchRounds = new ArrayList<>();
for (int i = 0; i < teams.size() - 1; i++) {
mr = "第" + j + "轮";
System.out.println(mr);
j++;
matchRounds.add(mr);
}
//System.out.println(matchRounds.get(0)+matchRounds.get(1));
model.addAttribute("league", league);
model.addAttribute("teams", teams);
model.addAttribute("matchRounds", matchRounds);
return "match/addMatchInformation";
}
@PostMapping("/addMatchInformationFinish")
public String addMatchFinish(MatchInformation matchInformation) {
matchInformationService.saveMatchInformation(matchInformation);
return "redirect:/matches";
}
/**
* 跳转至查询比赛页面
*
* @param model
* @return
*/
@GetMapping("/queryMatch")
public String toQueryPage(Model model) {
Collection<Team> teams = playerService.selectAllTeam();
model.addAttribute("teams", teams);
return "match/queryMatch";
}
/**
* 跳转至比赛信息页面
*
* @param model
* @return
*/
@GetMapping("/matches")
public String toMatchesPage(Model model) {
List<MatchInformation> matchInformations = matchInformationService.getAllMatchInformation();
model.addAttribute("matchInformations", matchInformations);
return "match/matches";
}
@GetMapping("/displayMatchInformation")
public String displayMatchInformation(Integer id, Model model) {
MatchInformation matchInformation = matchInformationService.getMatchInformationById(id);
model.addAttribute("matchInformation", matchInformation);
MatchResult matchResult = matchNewsService.getMatchResultByMatchId(id);
if (matchResult == null) {
matchResult = new MatchResult();
matchResult.setHomeGoals(-1);
matchResult.setGuestGoals(-1);
matchResult.setScore("比赛未结束，比分未知！");
matchResult.setWinner("比赛未结束，胜者未知！");
}
model.addAttribute("matchResult", matchResult);
//System.out.println(matchResult.toString());
return "match/displayMatchInformation";
}
}
|
// SPDX-License-Identifier: GPL-2.0-only
/*
* soc-acpi-intel-hsw-bdw-match.c - tables and support for ACPI enumeration.
*
* Copyright (c) 2017, Intel Corporation.
*/
#include <linux/dmi.h>
#include <sound/soc-acpi.h>
#include <sound/soc-acpi-intel-match.h>
struct snd_soc_acpi_mach snd_soc_acpi_intel_haswell_machines[] = {
{
.id = "INT33CA",
.drv_name = "haswell-audio",
.fw_filename = "intel/IntcSST1.bin",
.sof_fw_filename = "sof-hsw.ri",
.sof_tplg_filename = "sof-hsw.tplg",
},
{}
};
EXPORT_SYMBOL_GPL(snd_soc_acpi_intel_haswell_machines);
struct snd_soc_acpi_mach snd_soc_acpi_intel_broadwell_machines[] = {
{
.id = "INT343A",
.drv_name = "broadwell-audio",
.fw_filename = "intel/IntcSST2.bin",
.sof_fw_filename = "sof-bdw.ri",
.sof_tplg_filename = "sof-bdw-rt286.tplg",
},
{
.id = "10EC5650",
.drv_name = "bdw-rt5650",
.fw_filename = "intel/IntcSST2.bin",
.sof_fw_filename = "sof-bdw.ri",
.sof_tplg_filename = "sof-bdw-rt5650.tplg",
},
{
.id = "RT5677CE",
.drv_name = "bdw-rt5677",
.fw_filename = "intel/IntcSST2.bin",
.sof_fw_filename = "sof-bdw.ri",
.sof_tplg_filename = "sof-bdw-rt5677.tplg",
},
{
.id = "INT33CA",
.drv_name = "haswell-audio",
.fw_filename = "intel/IntcSST2.bin",
.sof_fw_filename = "sof-bdw.ri",
.sof_tplg_filename = "sof-bdw-rt5640.tplg",
},
{}
};
EXPORT_SYMBOL_GPL(snd_soc_acpi_intel_broadwell_machines);
|
<gh_stars>0
package org.jakubczyk.dbtesting.domain;
import org.jakubczyk.dbtesting.domain.repository.datasource.RequeryTodoDatasource;
import org.jakubczyk.dbtesting.domain.repository.datasource.TodoDatasource;
import javax.inject.Singleton;
import dagger.Binds;
import dagger.Module;
@Module
public abstract class RepositoryModule {
@Binds
@Singleton
abstract TodoDatasource provideTodoDatasource(RequeryTodoDatasource todoDatasource);
}
|
package core
import (
"context"
v1 "k8s.io/api/core/v1"
metav1 "k8s.io/apimachinery/pkg/apis/meta/v1"
"k8s.io/apimachinery/pkg/types"
"k8s.io/apimachinery/pkg/watch"
v12 "k8s.io/client-go/applyconfigurations/core/v1"
clientset "k8s.io/client-go/kubernetes"
)
type Nodes struct {
ps *StateManager
client clientset.Interface
}
func (n Nodes) Create(ctx context.Context, node *v1.Node, opts metav1.CreateOptions) (*v1.Node, error) {
err := n.ps.AddNode(node)
return node, err
}
func (Nodes) Update(ctx context.Context, node *v1.Node, opts metav1.UpdateOptions) (*v1.Node, error) {
//TODO implement me
panic("implement me")
}
func (Nodes) UpdateStatus(ctx context.Context, node *v1.Node, opts metav1.UpdateOptions) (*v1.Node, error) {
//TODO implement me
panic("implement me")
}
func (n Nodes) Delete(ctx context.Context, name string, opts metav1.DeleteOptions) error {
err := n.ps.RemoveNode(name)
return err
}
func (Nodes) DeleteCollection(ctx context.Context, opts metav1.DeleteOptions, listOpts metav1.ListOptions) error {
//TODO implement me
panic("implement me")
}
func (n Nodes) Get(ctx context.Context, name string, opts metav1.GetOptions) (*v1.Node, error) {
node, err := n.ps.GetNode(name)
return node, err
}
func (Nodes) List(ctx context.Context, opts metav1.ListOptions) (*v1.NodeList, error) {
//TODO implement me
panic("implement me")
}
func (Nodes) Watch(ctx context.Context, opts metav1.ListOptions) (watch.Interface, error) {
//TODO implement me
panic("implement me")
}
func (Nodes) Patch(ctx context.Context, name string, pt types.PatchType, data []byte, opts metav1.PatchOptions, subresources ...string) (result *v1.Node, err error) {
//TODO implement me
panic("implement me")
}
func (Nodes) Apply(ctx context.Context, node *v12.NodeApplyConfiguration, opts metav1.ApplyOptions) (result *v1.Node, err error) {
//TODO implement me
panic("implement me")
}
func (Nodes) ApplyStatus(ctx context.Context, node *v12.NodeApplyConfiguration, opts metav1.ApplyOptions) (result *v1.Node, err error) {
//TODO implement me
panic("implement me")
}
func (Nodes) PatchStatus(ctx context.Context, nodeName string, data []byte) (*v1.Node, error) {
//TODO implement me
panic("implement me")
}
func NewNodes(ps *StateManager) *Nodes {
return &Nodes{
ps: ps,
}
}
|
The way people breathe is known to affect their emotional and/or physiological state. For example, breathing more slowly and gently can help to calm and relax, can reduce tension and anxiety, and can improve concentration and memory. Shallow and fast breathing can contribute to anxiety, muscular tension, panic attacks, headaches, and fatigue. Yogic techniques that teach control of various aspects of the breathing offer many advantages in both treating undesired conditions and reaching new desired mental and physical conditions. However, it is usually difficult for people to become aware of their breathing, and gaining such awareness often requires years of practice.
Biofeedback is a technique that teaches self-regulation of various physiological processes through a feedback provided to the user. Biofeedback involves the measurement of the user and providing the user a feedback indicative of the measured physiological activity. The feedback enables the user to improve awareness and control of the activity. Current methods for monitoring breathing typically require uncomfortable setup (e.g., chest straps), which makes it impractical to use in real-world environments on a daily basis, and is often unavailable on demand when a person needs it. Additionally, current breathing monitoring techniques monitor only certain breathing parameters (e.g., breathing rate and volume), and do not monitor many other parameters that may affect the emotional and/or physiological state. Thus, there is a need for a comfortable wearable breathing biofeedback device. |
Light and Confocal Microscopic Studies of Evolutionary Changes in Neurofilament Proteins Following Cortical Impact Injury in the Rat Previous studies have shown that traumatic brain injury (TBI) produces progressive degradation of cytoskeletal proteins including neurofilaments (e.g., neurofilament 68 and neurofilament 200 ) within the first 24 h after injury. Thus, we employed immunofluorescence (light and confocal microscopy) to study the histopathological correlates of progressive neurofilament protein loss observed at 15 min, 3 h, and 24 h following unilateral cortical injury in rats. TBI produced significant alterations in NF68 and NF200 immunolabeling in dendrites and cell bodies at contusion sites ipsilateral to injury, as well as in the noncontused contralateral cortex. Changes in immunolabeling were associated with, but not exclusively restricted to, regions previously shown to contain dark shrunken neurons labeled by hematoxylin and eosin staining, a morphopathological response to injury suggesting impending cell death. Immunofluorescence microscopic studies of neurofilament proteins in the ipsilateral cerebral cortex detected prominent fragmentation of apical dendrites of pyramidal neurons in layers 3-5 and loss of fine dendritic arborization within layer 1. While modest changes were observed 15 min following injury, more pronounced loss of dendritic neurofilament immunofluorescence was detected 3 and 24 h following injury. Confocal microscopy also revealed progressive alterations in NF68 immunoreactivity in dendrites following TBI. While some evidence of structural alterations was observed 15 min following TBI, dendritic breaks were readily detected in confocal micrographs from 3 to 24 h following injury. However, disturbances in axonal NF68 by immunofluorescence microscopy in the corpus callosum were not detected until 24 h after injury. These studies confirmed that derangements in dendritic neurofilament cytoskeletal proteins are not exclusively restricted to sites of impact contusion. Moreover, changes in dendritic cytoskeletal proteins are progressive and not fully expressed within the first 15 min following impact injury. These progressive dendritic disruptions are characterized by disturbances in the morphology of neurofilament proteins, resulting in fragmentation and focal loss of NF68 immunofluorescence within apical dendrites. In contrast, alterations in axonal cytoskeletal proteins are more restricted and delayed with no pronounced changes until 24 h after injury. |
Feature based indoor mapping using a bat-type UWB radar A system for building a feature-based map of an unknown indoor environment is proposed. We consider emergency scenarios where smoke and dust block the vision so that camera-based systems and laser range finders are not operable. In this kind of situation, ultra-wideband (UWB) radar is a good alternative. We use a bat-type UWB radar system composed of one transmitter and two receivers arranged in a fixed linear array. Time-of-flight measurements are taken between the transmitter and the receivers. The environment is reconstructed from impulse responses by extracting information on different features like walls, edges and corners. These features can be used as landmarks to navigate. The solution we present works by dividing the problem into three different parts and solving them: Tracking of the bat pose and localization of already detected landmarks; data association to single out measurements originating from the detected landmarks; and detection of new landmarks from the remaining measurements. By combining solutions to these three subtasks, a computationally cheap, precise algorithm for feature-based indoor mapping is obtained. Tests using real life data were performed to confirm the feasibility of the approach. |
Negative activation enthalpies in the kinetics of protein folding. Although the rates of chemical reactions become faster with increasing temperature, the converse may be observed with protein-folding reactions. The rate constant for folding initially increases with temperature, goes through a maximum, and then decreases. The activation enthalpy is thus highly temperature dependent because of a large change in specific heat (delta Cp). Such a delta Cp term is usually presumed to be a consequence of a large decrease in exposure of hydrophobic surfaces to water as the reaction proceeds from the denatured state to the transition state for folding: the hydrophobic side chains are surrounded by "icebergs" of water that melt with increasing temperature, thus making a large contribution to the Cp of the denatured state and a smaller one to the more compact transition state. The rate could also be affected by temperature-induced changes in the conformational population of the ground state: the heat required for the progressive melting of residual structure in the denatured state will contribute to delta Cp. By examining two proteins with different refolding mechanisms, we are able to find both of these two processes; barley chymotrypsin inhibitor 2, which refolds from a highly unfolded state, fits well to a hydrophobic interaction model with a constant delta Cp of activation, whereas barnase, which refolds from a more structured denatured state, deviates from this ideal behavior. |
Most of the news you hear about the state of the labor movement these days is either bad…or worse. Falling union membership, losing organizing campaigns, passage right-to-work (for less) bills and on and on.
But yesterday we saw some very different headlines coming out of Iowa: “In biggest vote since new law, Iowa public unions overwhelmingly choose to recertify.”
Background
Republicans, who took over both houses of Iowa’s legislature last year, and Governor Terry Branstad, sought to emulate the union-busting campaign of Scott Walker in Wisconsin who had declared war on public employees in 2011. Most of the law affected “non-safety” public employees, leaving firefighters and police relatively unscathed. Non public safety related employees, however, will now be limited to just bargaining over wages. No longer would they be allowed to bargain over such items as health insurance, vacation time and seniority perks, holidays, leaves of absence, shift differentials, overtime compensation,supplemental pay, seniority, transfer procedures, job classifications, health and safety matters, evaluation procedures, procedures for staff reduction, in-service training or grievance procedures.
“There’s not one Republican in this state that could win an election under the rules they gave us.” — AFSCME Council 61 President Danny Homan
The legislation also requires public employees to re-certify their unions with each new contract — which means once every two to three years. To re-certify, a majority of workers in a bargaining unit have to vote in favor of the union, not just the majority of those voting. What that means is that members not voting count as “no” votes. As my old AFSCME buddy, Danny Homan, who leads the 40,000 members of AFSCME Council 61 in Iowa, said, “There’s not one Republican in this state that could win an election under the rules they gave us.”
All Iowa Democrats voted against the legislation. Six Republicans also opposed, with the rest voting in favor.
The Results
But never underestimate the power of strong unions. Turns out that despite the Republicans’ best efforts, Iowa public sector unions won an overwhelming victory in this week’s elections. 436 out of 468 public-sector bargaining units voted to recertify their unions. 88 percent of members voted. Homan proudly boasted that “100% of AFSCME-covered employees voted to retain their union.” AFSCME only lost one 4-person unit because of a voided ballot. Other unions, like the Iowa State Education Association also did well, winning 216 out of 220 bargaining units.
28,448 people voted to maintain their union affiliations in this round of voting and only 624 people voted against. 4,043 people did not vote.
Homan summed it up:
This sweeping victory confirms what we’ve known since the gutting of collective bargaining rights in February: that unionized employees, both members and non-members, value their voice in the workplace and reject the actions of … Republicans who turned their backs on working Iowans in February.
And Republicans won’t be able to sleep easily from now on, according to Homan: “I am confident that workers will once again claim victory in the November 2018 election when those politicians who stabbed them in the back are sent packing.”
Might be a fun election.
And appropriately, we’ll let Billy Bragg take us out tonight: |
0 'Farm living' in the city: Urban farming on the rise
BOSTON - Above the hustle and bustle of Watertown, don't be surprised if you hear the cluck of chickens.
In that city, a hot pink chicken coop sits in an unusual space and it marks a trend that's bringing "farm living" into the heart of urban areas.
"It's not just a matter of watering. They're learning about crop cycles, we're learning about how to compost," James Miner said.
Miner isn't a professional farmer though. the plants where he works are located just beyond a parking lot, planted in about a hundred milk crates -- just outside the offices of Sasaki and Associates.
There are also chickens.
"The agricultural initiative at work, worked so well that we really wanted to build on that," Sasaki and Associates employee Philip Dugdale said.
Dugdale is known as "the chicken man."
"They're really easy to care for," he said.
Dugdale says his hot pink chicken coop is the only one of its kind located at a business property. But he won't be surprised if others get in the game.
Gretl, Gretchen and Heidi -- all chickens -- are part of a trend building for almost three years, when Boston passed a zoning order that allowed urban farming. Since then, city residences, colleges, even Fenway Park, have begun to install patches for growing crops.
Sasaki is part of a small, but increasing number of companies adding them as well.
"I know in Boston, there's 15 or 20 that I'm aware of," Miner said.
Miner says the trend is growing because people want to know where their food comes from, cities want to shed their "food desert" labels and businesses want to offer a better work/life balance.
"Fundamentally, there's a source of pride around all of this," Miner said. "This has been a place with a culture of 'no' and now it's becoming more of a culture of 'Why not? Let's try stuff. Let's experiment.'"
Miner told FOX25 where there are chickens today, there could be honeybees tomorrow.
He believes that as interest in urban farming builds, many of these simple growing spots will expand to meet the food and environmental needs of city dwellers.
© 2019 Cox Media Group. |
<gh_stars>1-10
import tool
from pymel.core import *
from AdditionalFeatures import * |
Sacred Heart Cathedral, Sacred Heart School and Christian Brothers Home
History
The buildings belonged to the first Roman Catholic parish in Duluth, founded by Rev. John Chebul in 1870. The parish originally occupied a small wooden building, but it burned down in 1892. A new building was started in 1894 and completed in 1896. The church had a 1,493-pipe pipe organ installed in 1898, built by Felgemaker Organ Company, of Erie, Pennsylvania. The organ has been listed by the Organ Historical Society for its "exceptional historic merit, worthy of preservation."
In 1985 the Diocese of Duluth announced that the congregation would be merging with the congregation of Saint Mary, Star of the Sea, and that the building would be closed. Joan Connolly, who had started playing the Sacred Heart organ in 1930 when she was a sophomore in high school, wanted to preserve the building and keep the organ in its original space. She recruited volunteers, and bought the church from the diocese for $1. The church building now serves as a performance space for live music, and is also a venue for weddings, receptions, meetings, and other potential uses. |
Long-term tacrine treatment in three mild Alzheimer patients: effects on nicotinic receptors, cerebral blood flow, glucose metabolism, EEG, and cognitive abilities. The effect of long-term treatment with tacrine (tetrahydroaminoacridine) was studied in three Alzheimer patients (aged 57, 64, and 68 years) with mild dementia. All three patients had a Mini-Mental State Examination score of 24/30 and carried at least one apolipoprotein E (ApoE) epsilon4 allele. Tacrine was given in doses between 80 and to 160 mg daily for 13-31 months. A lower tacrine concentration was observed generally in cerebrospinal fluid (CSF) compared with plasma. The acetylcholinesterase activity in CSF tended to be increased following longer periods of tacrine treatment, whereas the butyrylcholinesterase activity was decreased. The three patients repeatedly underwent positron emission tomography investigation of cerebral blood flow, nicotinic receptors, cerebral glucose metabolism, and electroencephalogram (EEG) and cognitive tests. Positive influences on these parameters were observed following both short-term and long-term treatment with tacrine. Improvement of nicotinic receptors (measured as 11C-nicotine binding), cerebral blood flow, EEG, and some cognitive tests (trail making test, block design test) occurred earlier after initiation of tacrine treatment compared with the glucose metabolism, which was increased after several months of tacrine treatment. An improvement in attention (trail making test) was observed following tacrine as sign for frontal lobe activation (EEG). The functional effects of tacrine in Alzheimer patients appeared to be related to both dose and length of cholinesterase inhibitor treatment. |
<filename>source/nawindow.cpp
#include <Beep.h>
#include <Debug.h>
#include <LayoutBuilder.h>
#include <String.h>
#include "nawindow.h"
#include "commandconstants.h"
#include "guistrings.h"
PatternWindow::PatternWindow(BMessenger * messenger)
: BWindow(BRect(300,300,600,385), "New filename pattern", B_TITLED_WINDOW, B_NOT_V_RESIZABLE|B_NOT_ZOOMABLE|B_NOT_MINIMIZABLE),
m_text_control (NULL),
m_add_button (NULL),
m_cancel_button (NULL),
m_parent_messenger (messenger)
{
m_text_control = new BTextControl("m_text_control","","",NULL);
m_add_button = new BButton("m_add_button", ADD_BUTTON, new BMessage(MSG_PATTERN_CREATED));
m_add_button->MakeDefault(true);
m_cancel_button = new BButton("m_cancel_button", CANCEL_BUTTON, new BMessage(B_QUIT_REQUESTED));
BLayoutBuilder::Group<>(this, B_VERTICAL)
.SetInsets(B_USE_WINDOW_INSETS)
.Add(m_text_control)
.AddGroup(B_HORIZONTAL)
.AddGlue()
.Add(m_add_button)
.Add(m_cancel_button);
m_text_control->MakeFocus();
}
PatternWindow::~PatternWindow()
{
delete m_parent_messenger;
}
void
PatternWindow::MessageReceived(BMessage* message)
{
// PRINT(("PatternWindow::MessageReceived()\n"));
switch(message->what)
{
case MSG_PATTERN_CREATED:
{
BString string = m_text_control->Text();
if (string.FindFirst("/") < 0)
{
// XXX -- show BAlert and explain some
beep();
break;
}
message->AddString("pattern", m_text_control->Text());
m_parent_messenger->SendMessage(message);
PostMessage(B_QUIT_REQUESTED);
}
break;
default:
BWindow::MessageReceived(message);
}
}
|
<filename>include/TacoGL/Sampler.h
#ifndef __TACOGL_SAMPLER__
#define __TACOGL_SAMPLER__
#include <TacoGL/OpenGL.h>
#include <TacoGL/Error.h>
#include <TacoGL/algebra.h>
#include <TacoGL/Object.h>
namespace TacoGL
{
class Sampler : public Object
{
public:
Sampler();
virtual ~Sampler();
void bind(size_t unit);
gl::GLenum getMagFilter() const;
gl::GLenum getMinFilter() const;
size_t getMinLOD() const;
size_t getMaxLOD() const;
// TODO:TEXTURE_WRAP, Vector or scalar ?
Vector4 getBorderColor() const;
// TODO: TEXTURE_COMPARE_MODE
gl::GLenum getCompareFunction() const;
void setMagFilter(gl::GLenum value);
void setMinFilter(gl::GLenum value);
void setMinLOD(size_t value);
void setMaxLOD(size_t value);
// TODO:TEXTURE_WRAP, Vector or scalar ?
void setBorderColor(const Vector4 &value);
// TODO: TEXTURE_COMPARE_MODE
void setCompareFunction(gl::GLenum value);
};
} // end namespace GL
#endif |
Financial Executives in U.S. Clubs Private clubs in the United States require not only the leadership of a strong general manager, but of an excellent chief financial officer. Traditionally club CFOs have been expected to be strong in technical skills. This study finds that the essential leadership qualities of private-club financial executives include strong communication skills, maintaining trust in their employees, developing a vision, and being consistent and firm in decision making. In this particular sample, slightly more than half the responding financial officers were women. While the respondents stressed the importance of strong leadership from a general manager, the financial officers also made clear the importance of their own leadership, particularly in human resources, for which many of them had responsibility (in addition to their financial duties). |
<reponame>andresryes/POS
export class Product {
idProduct: string;
stock: string;
price: string;
category: any;
image: string;
name: string;
description: string;
}
|
A Tale of Two Houses: Tracing Transitory Changes to Two Jamaican Social Classes through their Micro-cultures of Sewing in the Independence Period (19601970) Abstract This paper asks how changes to the way that dressmaking was practiced in two separate communities exemplified post-independence changes to Jamaican national identity. It was first written in 2013, from research conducted in and around two Jamaican residences: one in the beach-front, tourist hot spot of Montego Bay and the other in rural Elgin in Clarendon, at the islands mountainous heart. At the time of Jamaican independence, these geographically and socio-economically different locations were nuclei for dressmaking practice, although for different purposes. Through them, the paper identifies two separate, classed and racialized worlds on a relatively small island, examining a social, political, architectural and creative landscape formed by the legacy of the transatlantic slave trade and European colonialism. It considers how, and how effectively these landscapes were changing in the post-independence period of decolonial struggle, in which a new Jamaicanness was being formed. To do so, it focuses on three individuals who engaged in sewing within these houses at the time: Sewing school leader Dee Davis, fashion designer Trevor C. Owen, and peripatetic seamstress Miss Aslyn. Research methods combined Oral History interviews with surviving individuals connected to the two houses, analysis of the houses themselves, and archival research conducted in Jamaica. |
Cheezburger Network, publisher of I Can Has Cheezburger? and other blogs, has raised $30 million in funding. The money will go toward hiring and growth initiatives, which is good because the internet is running dangerously low on funny cat pictures. |
/*
* Copyright 2020 <NAME>
*
* Licensed under the Apache License, Version 2.0 (the "License");
* you may not use this file except in compliance with the License.
* You may obtain a copy of the License at
*
* http://www.apache.org/licenses/LICENSE-2.0
*
* Unless required by applicable law or agreed to in writing, software
* distributed under the License is distributed on an "AS IS" BASIS,
* WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
*
* See the License for the specific language governing permissions and
* limitations under the License.
*/
use std::fs;
use iced::{button, scrollable, text_input, Button, Column, Element, Row, Scrollable, Text, TextInput};
use crate::gradescope;
#[derive(Debug, Clone)]
pub enum Message {
RetrieveResults,
PathChanged(String)
}
#[derive(Default)]
pub struct Visualizer {
// The result pulled from
grader_result: Option<gradescope::GraderResult>,
// Where to grab the results
retrieve_path: String,
// The state of the GUI
retrieve_button: button::State,
retrieve_path_state: text_input::State,
scrollable_state: scrollable::State
}
impl Visualizer {
pub fn update(&mut self, message: Message) {
match message {
Message::RetrieveResults => {
self.grader_result = match fs::read(fs::canonicalize(&self.retrieve_path).unwrap()) {
Ok(vec) => {
serde_json::from_slice(vec.as_slice()).ok()
}
Err(_) => {
None
}
}
}
Message::PathChanged(path) => {
self.retrieve_path = path;
}
}
}
pub fn view_result(result: &gradescope::GraderResult) -> Element<Message> {
let score = result.score
.unwrap_or_else(
|| result.tests
.as_ref()
.unwrap()
.iter()
.fold(
0.0,
|full_score, test_score| full_score + test_score.score.unwrap()
)
);
let test_output = match result.tests.as_ref() {
Some(tests) => {
tests.iter().fold(Column::new().spacing(15), |column, test| {
column.push(Self::view_test(test))
})
}
None => {
Column::new()
.push(Text::new(String::from("No Tests")))
}
};
Column::new().padding(15)
.push(
Row::new()
.push(
Text::new(String::from("Score: "))
)
.push(
Text::new(score.to_string())
)
)
.push(
test_output
)
.into()
}
pub fn view(&mut self) -> Element<Message> {
Column::new()
.spacing(10)
.padding(10)
.push(
Row::new()
.push(
TextInput::new(
&mut self.retrieve_path_state,
"Enter the path to Gradescope's output",
&self.retrieve_path,
Message::PathChanged
)
.on_submit(Message::RetrieveResults)
)
.push(
Button::new(
&mut self.retrieve_button,
Text::new("Retrieve Result")
)
.on_press(Message::RetrieveResults)
)
)
.push(
Scrollable::new(&mut self.scrollable_state)
.push(
self.grader_result
.as_ref()
.map(Self::view_result)
.unwrap_or(
Column::new()
.push(Text::new(String::from("No Results Loaded")))
.into()
)
)
)
.into()
}
fn view_test(test: &gradescope::TestResult) -> Element<Message> {
Column::new().spacing(10)
.push(Text::new(Self::create_test_header(test)))
.push(Text::new(test.output.as_ref().unwrap()))
.into()
}
fn create_test_header(test: &gradescope::TestResult) -> String {
test.number.as_ref().unwrap().to_owned() + ") " + test.name.as_ref().unwrap_or(&String::from("")) + "(" +
&test.score.as_ref().unwrap().to_string() + " / " + &test.max_score.as_ref().unwrap().to_string() + ")"
}
}
|
/*
* CDDL HEADER START
*
* The contents of this file are subject to the terms of the
* Common Development and Distribution License (the "License").
* You may not use this file except in compliance with the License.
*
* You can obtain a copy of the license at usr/src/OPENSOLARIS.LICENSE
* or http://www.opensolaris.org/os/licensing.
* See the License for the specific language governing permissions
* and limitations under the License.
*
* When distributing Covered Code, include this CDDL HEADER in each
* file and include the License file at usr/src/OPENSOLARIS.LICENSE.
* If applicable, add the following below this CDDL HEADER, with the
* fields enclosed by brackets "[]" replaced with your own identifying
* information: Portions Copyright [yyyy] [name of copyright owner]
*
* CDDL HEADER END
*/
/* Copyright (c) 1984, 1986, 1987, 1988, 1989 AT&T */
/* All Rights Reserved */
/*
* Copyright 2007 Sun Microsystems, Inc. All rights reserved.
* Use is subject to license terms.
*/
/*
* Copyright 2010 Nexenta Systems, Inc. All rights reserved.
*/
/*LINTLIBRARY*/
/* 5-20-92 newroot support added */
#include <stdio.h>
#include <limits.h>
#include <ctype.h>
#include <errno.h>
#include <string.h>
#include <sys/types.h>
#include <pkgstrct.h>
#include <pkginfo.h>
#include <pkglocs.h>
#include <stdlib.h>
#include <unistd.h>
#include "libadm.h"
#define VALSIZ 128
#define NEWLINE '\n'
#define ESCAPE '\\'
static char sepset[] = ":=\n";
static char qset[] = "'\"";
static char *pkg_inst_root = NULL;
char *pkgdir = NULL;
char *pkgfile = NULL;
static char Adm_pkgloc[PATH_MAX] = { 0 }; /* added for newroot */
static char Adm_pkgadm[PATH_MAX] = { 0 }; /* added for newroot */
/*
* This looks in a directory that might be the top level directory of a
* package. It tests a temporary install directory first and then for a
* standard directory. This looks a little confusing, so here's what's
* happening. If this pkginfo is being openned in a script during a pkgadd
* which is updating an existing package, the original pkginfo file is in a
* directory that has been renamed from <pkginst> to .save.<pkginst>. If the
* pkgadd fails it will be renamed back to <pkginst>. We are always interested
* in the OLD pkginfo data because the new pkginfo data is already in our
* environment. For that reason, we try to open the backup first - that has
* the old data. This returns the first accessible path in "path" and a "1"
* if an appropriate pkginfo file was found. It returns a 0 if no type of
* pkginfo was located.
*/
int
pkginfofind(char *path, char *pkg_dir, char *pkginst)
{
int len = 0;
/* Construct the temporary pkginfo file name. */
len = snprintf(path, PATH_MAX, "%s/.save.%s/pkginfo", pkg_dir,
pkginst);
if (len > PATH_MAX)
return (0);
if (access(path, 0)) {
/*
* This isn't a temporary directory, so we look for a
* regular one.
*/
len = snprintf(path, PATH_MAX, "%s/%s/pkginfo", pkg_dir,
pkginst);
if (len > PATH_MAX)
return (0);
if (access(path, 0))
return (0); /* doesn't appear to be a package */
}
return (1);
}
/*
* This opens the appropriate pkginfo file for a particular package.
*/
FILE *
pkginfopen(char *pkg_dir, char *pkginst)
{
FILE *fp = NULL;
char temp[PATH_MAX];
if (pkginfofind(temp, pkg_dir, pkginst))
fp = fopen(temp, "r");
return (fp);
}
char *
fpkgparam(FILE *fp, char *param)
{
char ch, buffer[VALSIZ];
char *mempt, *copy;
int c, n;
boolean_t check_end_quote = B_FALSE;
boolean_t begline, quoted, escape;
int idx = 0;
if (param == NULL) {
errno = ENOENT;
return (NULL);
}
mempt = NULL;
for (;;) { /* For each entry in the file fp */
copy = buffer;
n = 0;
/* Get the next token. */
while ((c = getc(fp)) != EOF) {
ch = (char)c;
if (strchr(sepset, ch))
break;
if (++n < VALSIZ)
*copy++ = ch;
}
/* If it's the end of the file, exit the for() loop */
if (c == EOF) {
errno = EINVAL;
return (NULL); /* No more entries left */
/* If it's end of line, look for the next parameter. */
} else if (c == NEWLINE)
continue;
/* At this point copy points to the end of a valid parameter. */
*copy = '\0'; /* Terminate the string. */
if (buffer[0] == '#') /* If it's a comment, drop thru. */
copy = NULL; /* Comments don't get buffered. */
else {
/* If parameter is NULL, we return whatever we got. */
if (param[0] == '\0') {
(void) strcpy(param, buffer);
copy = buffer;
/* If this doesn't match the parameter, drop thru. */
} else if (strcmp(param, buffer))
copy = NULL;
/* Otherwise, this is our boy. */
else
copy = buffer;
}
n = 0;
quoted = escape = B_FALSE;
begline = B_TRUE; /* Value's line begins */
/* Now read the parameter value. */
while ((c = getc(fp)) != EOF) {
ch = (char)c;
if (begline && ((ch == ' ') || (ch == '\t')))
continue; /* Ignore leading white space */
/*
* Take last end quote 'verbatim' if anything
* other than space, newline and escape.
* Example:
* PARAM1="zonename="test-zone""
* Here in this example the letter 't' inside
* the value is followed by '"', this makes
* the previous end quote candidate '"',
* a part of value and the end quote
* disqualfies. Reset check_end_quote.
* PARAM2="value"<== newline here
* PARAM3="value"\
* "continued"<== newline here.
* Check for end quote continues.
*/
if (ch != NEWLINE && ch != ' ' && ch != ESCAPE &&
ch != '\t' && check_end_quote)
check_end_quote = B_FALSE;
if (ch == NEWLINE) {
if (!escape) {
/*
* The end quote candidate qualifies.
* Eat any trailing spaces.
*/
if (check_end_quote) {
copy -= n - idx;
n = idx;
check_end_quote = B_FALSE;
quoted = B_FALSE;
}
break; /* End of entry */
}
/*
* The end quote if exists, doesn't qualify.
* Eat end quote and trailing spaces if any.
* Value spans to next line.
*/
if (check_end_quote) {
copy -= n - idx;
n = idx;
check_end_quote = B_FALSE;
} else if (copy) {
copy--; /* Eat previous esc */
n--;
}
escape = B_FALSE;
begline = B_TRUE; /* New input line */
continue;
} else {
if (!escape && strchr(qset, ch)) {
/* Handle quotes */
if (begline) {
/* Starting quote */
quoted = B_TRUE;
begline = B_FALSE;
continue;
} else if (quoted) {
/*
* This is the candidate
* for end quote. Check
* to see it qualifies.
*/
check_end_quote = B_TRUE;
idx = n;
}
}
if (ch == ESCAPE)
escape = B_TRUE;
else if (escape)
escape = B_FALSE;
if (copy) *copy++ = ch;
begline = B_FALSE;
}
if (copy && ((++n % VALSIZ) == 0)) {
if (mempt) {
mempt = realloc(mempt,
(n+VALSIZ)*sizeof (char));
if (!mempt)
return (NULL);
} else {
mempt = calloc((size_t)(2*VALSIZ),
sizeof (char));
if (!mempt)
return (NULL);
(void) strncpy(mempt, buffer, n);
}
copy = &mempt[n];
}
}
/*
* Don't allow trailing white space.
* NOTE : White space in the middle is OK, since this may
* be a list. At some point it would be a good idea to let
* this function know how to validate such a list. -- JST
*
* Now while there's a parametric value and it ends in a
* space and the actual remaining string length is still
* greater than 0, back over the space.
*/
while (copy && isspace((unsigned char)*(copy - 1)) && n-- > 0)
copy--;
if (quoted) {
if (mempt)
(void) free(mempt);
errno = EFAULT; /* missing closing quote */
return (NULL);
}
if (copy) {
*copy = '\0';
break;
}
if (c == EOF) {
errno = EINVAL; /* parameter not found */
return (NULL);
}
}
if (!mempt)
mempt = strdup(buffer);
else
mempt = realloc(mempt, (strlen(mempt)+1)*sizeof (char));
return (mempt);
}
char *
pkgparam(char *pkg, char *param)
{
static char lastfname[PATH_MAX];
static FILE *fp = NULL;
char *pt, *copy, *value, line[PATH_MAX];
if (!pkgdir)
pkgdir = get_PKGLOC();
if (!pkg) {
/* request to close file */
if (fp) {
(void) fclose(fp);
fp = NULL;
}
return (NULL);
}
if (!param) {
errno = ENOENT;
return (NULL);
}
if (pkgfile)
(void) strcpy(line, pkgfile); /* filename was passed */
else
(void) pkginfofind(line, pkgdir, pkg);
if (fp && strcmp(line, lastfname)) {
/* different filename implies need for different fp */
(void) fclose(fp);
fp = NULL;
}
if (!fp) {
(void) strcpy(lastfname, line);
if ((fp = fopen(lastfname, "r")) == NULL)
return (NULL);
}
/*
* if parameter is a null string, then the user is requesting us
* to find the value of the next available parameter for this
* package and to copy the parameter name into the provided string;
* if it is not, then it is a request for a specified parameter, in
* which case we rewind the file to start search from beginning
*/
if (param[0]) {
/* new parameter request, so reset file position */
if (fseek(fp, 0L, 0))
return (NULL);
}
if (pt = fpkgparam(fp, param)) {
if (strcmp(param, "ARCH") == 0 ||
strcmp(param, "CATEGORY") == 0) {
/* remove all whitespace from value */
value = copy = pt;
while (*value) {
if (!isspace((unsigned char)*value))
*copy++ = *value;
value++;
}
*copy = '\0';
}
return (pt);
}
return (NULL);
}
/*
* This routine sets adm_pkgloc and adm_pkgadm which are the
* replacement location for PKGLOC and PKGADM.
*/
static void canonize_name(char *);
void
set_PKGpaths(char *path)
{
if (path && *path) {
(void) snprintf(Adm_pkgloc, sizeof (Adm_pkgloc),
"%s%s", path, PKGLOC);
(void) snprintf(Adm_pkgadm, sizeof (Adm_pkgadm),
"%s%s", path, PKGADM);
set_install_root(path);
} else {
(void) snprintf(Adm_pkgloc, sizeof (Adm_pkgloc), "%s", PKGLOC);
(void) snprintf(Adm_pkgadm, sizeof (Adm_pkgadm), "%s", PKGADM);
}
canonize_name(Adm_pkgloc);
canonize_name(Adm_pkgadm);
pkgdir = Adm_pkgloc;
}
char *
get_PKGLOC(void)
{
if (Adm_pkgloc[0] == '\0')
return (PKGLOC);
else
return (Adm_pkgloc);
}
char *
get_PKGADM(void)
{
if (Adm_pkgadm[0] == '\0')
return (PKGADM);
else
return (Adm_pkgadm);
}
void
set_PKGADM(char *newpath)
{
(void) strcpy(Adm_pkgadm, newpath);
}
void
set_PKGLOC(char *newpath)
{
(void) strcpy(Adm_pkgloc, newpath);
}
#define isdot(x) ((x[0] == '.')&&(!x[1]||(x[1] == '/')))
#define isdotdot(x) ((x[0] == '.')&&(x[1] == '.')&&(!x[2]||(x[2] == '/')))
static void
canonize_name(char *file)
{
char *pt, *last;
int level;
/* Remove references such as "./" and "../" and "//" */
for (pt = file; *pt; ) {
if (isdot(pt))
(void) strcpy(pt, pt[1] ? pt+2 : pt+1);
else if (isdotdot(pt)) {
level = 0;
last = pt;
do {
level++;
last += 2;
if (*last)
last++;
} while (isdotdot(last));
--pt; /* point to previous '/' */
while (level--) {
if (pt <= file)
return;
while ((*--pt != '/') && (pt > file))
;
}
if (*pt == '/')
pt++;
(void) strcpy(pt, last);
} else {
while (*pt && (*pt != '/'))
pt++;
if (*pt == '/') {
while (pt[1] == '/')
(void) strcpy(pt, pt+1);
pt++;
}
}
}
if ((--pt > file) && (*pt == '/'))
*pt = '\0';
}
void
set_install_root(char *path)
{
pkg_inst_root = strdup(path);
}
char *
get_install_root()
{
return (pkg_inst_root);
}
|
1. Field of the Invention
The present invention relates to an ink jet recording head for use in an ink jet recording device which ejects drops of ink to thereby form an image and, more particularly, to an ink jet recording head having a mechanism for precisely positioning the respective components of the head.
2. Description of the Related Art
There has been known, from Japanese Patent Unexamined Publication No. Sho 58-119870, etc., an ink jet recording head employing a piezoelectric vibrator which moves in the longitudinal direction to apply pressure to ink stored within a pressure chamber, and the pressurized ink is then jetted out from a nozzle as droplets of ink onto a recording medium.
In the recording head of the above-mentioned type, a large number of piezoelectric vibrators are inserted into guide holes formed in the upper and lower portions of a support member to thereby position and support the respective base end portions and leading end portions thereof. However, in this structure, the piezoelectric vibrators cannot be disposed in a high density arrangement. Also, they may be unevenly in the longitudinal direction thereof, and may be inclined with respect to each other, which makes it impossible to provide a uniform ink jet characteristic. |
import { Injectable } from '@angular/core';
import {AngularFireAuth} from '@Angular/Fire/Auth'
@Injectable({
providedIn: 'root'
})
export class FirebaseService {
isLoggedIn = false
constructor(public firebaseAuth : AngularFireAuth) { }
async signin(email: string, password: string){
await this.firebaseAuth.signInWithEmailAndPassword(email,password)
.then(res=>{
this.isLoggedIn = true
localStorage.setItem('user',JSON.stringify(res.user))
})
}
async signup(email: string, password: string){
await this.firebaseAuth.createUserWithEmailAndPassword(email,password)
.then(res=>{
this.isLoggedIn = true
localStorage.setItem('user',JSON.stringify(res.user))
})
}
logout(){
this.firebaseAuth.signOut()
localStorage.removeItem('user')
}
}
|
Data assimilation of GPS-ZTD into the RAMS model through 3D-Var: preliminary results at the regional scale The knowledge of water vapour distribution is a key element in atmospheric modeling and considerable information, also at the local scale, can be derived from the GPS-ZTD (global positioning system-Zenith total delay) data. This paper shows the assimilation of GPS-ZTD data into the RAMS@ISAC (Regional Atmospheric Modeling System at Institute of Atmospheric Sciences and Climate of the National Research Council) to improve the representation of the water vapour in the meteorological model. The data assimilation system is based on 3D-Var (three-dimensional variational assimilation system) and it is applied to a network of 29 receivers located within the Lazio Region, Central Italy. All collected data are processed using the PPP (precise point positioning) method through RTKLIB, an open source program package for GNSS (Global Navigation Satellite Systems) Positioning. Among the GPS receivers, three are single frequency receivers, able to acquire L1 frequency only, so that it is necessary a preliminary reconstruction of L2 synthetic observations, which is achieved by a new original ground-based augmentation strategy. Results show remarkably that the single frequency receivers can be used the same way as geodetic receivers. The RAMS@ISAC is run at 4 km horizontal resolution over central Italy and is nested, using one-way nesting, into a 10 km horizontal resolution run of the same model. The experiment was performed along to two months, from 28 July to 28 September 2017. Results show that the GPS-ZTD data, assimilated by 3D-Var, have an important impact on the analysis of the water vapour field and the RMSE of ZTD and IWV (vertically integrated water vapour) is roughly halved for the analysis compared to the background. The impact of the GPS-ZTD data assimilation is also evaluated for the very short term (VSF) forecast (13h), obtaining an improvement of the ZTD and IWV RMSE for all three hours of forecast. |
Maria Tănase
Legacy
In 1939, after meeting Tănase for the first time, Constantin Brâncuși told her: "When I hear you singing, Maria, I would be able to carve for each song of ours a Bird in Space!" He regarded her as a "symbol of all Romanians".
Famous Russian soprano Lydia Lipkowska was also fascinated by her artistry: "No one managed to impress me so deeply with the interpretation of traditional songs and pop music pieces in the way she did. Her voice penetrates me, stirs me, disturbs me so strongly that I always leave as if I tasted a miraculous potion; I feel like I don't have control over my own feelings!"
Nicolae Iorga famously called her "Pasărea măiastră" ("The Magic Bird").
Mihail Sadoveanu considered her "the first authentic rhapsodist" of the Romanians.
The character of Florica in the first novel of Olivia Manning's Fortunes of War trilogy is supposed to have been based upon Maria Tănase.
British musician Nigel Kennedy with Polish Kroke band celebrated her legacy with a recording titled "Tribute to Maria Tănase", which was included on his 2003 album East Meets East. The musical themes of this track are Maria Tănase's song Luncă, luncă (Meadow, Meadow) and Gheorghe Zamfir's Sârba bătrânească.
The 2009 Laureate of the Nobel Prize in Literature, Herta Müller, has spoken many times about the influence that Maria Tănase had on her: "When I first heard Maria Tănase she sounded incredible to me, it was for the first time that I really felt what folklore meant. Romanian folk music is connected to existence in a very meaningful way. However, German folklore was not at all inspiring for me."
In 2013, musical group Pink Martini named Maria Tănase one of their greatest inspirations and covered the song Până când nu te iubeam.
In 2013 Romanian singer Oana Cătălina Chiţu who lives in Berlin, published album Divine with songs from the repertoire of Maria Tănase.
On 25 September 2013, Google Romania celebrated Maria Tănase's legacy with a doodle, which marked what would have been her 100th birthday. |
def tn_is_same(cp):
photo_stem = Path(cp.photo.file.name).stem
tn_stem = Path(cp.thumbnail.file.name).stem
return tn_stem.startswith(f"tn_{photo_stem}") |
Researchers charged with helping defend U.S. nuclear assets and other complex federal systems are looking into how data mined from high-profile, big-money jewel and bank heists can inform their work.
"There are many insights to be gained from studying high-value heists and related crimes that could be applied to Sandia's work in physical security," Sandia National Labs systems analyst Jarret Lafleur said in an Aug. 19 statement. "Our work focuses on securing nuclear materials and other assets. Those kinds of attacks and threats are extremely rare, which is good, but give us very little historical information to draw upon."
A team of researchers that includes LaFluer, published research in a report, "The Perfect Heist: Recipes from Around the World," that leverages details from 23 craftily executed crimes, including the 2003 Antwerp diamond heist in Belgium that saw thieves sneak past a ring of police, into a secured building, and past motion sensors to break into a supposedly impregnable vault and make off with hundreds of millions of dollars in diamonds. Data points from other audacious, high-end crimes, like the 1999 Isabella Stewart Gardner Museum art heist in Boston, in which burglars posed as police officers to fool and subdue museum guards, were also used by the researchers to compile the Heist Methods and Characteristics Database.
The Sandia researchers analyzed the results qualitatively and quantitatively to describe the range and diversity of criminal methods and identify characteristics that are common or uncommon in such high-value heists. The analysis, said the lab, focused on seven areas: defeated security measures and devices; deception methods; timing and target selection; weapons employed; resources and risk acceptance; insiders; and failures and mistakes.
"I learned from this study that these thieves have a lot of patience. Most spent months and even years planning. They were very deliberate in how they defeated security measures and those methods were often very low-tech, like using hair spray to disable infrared sensors," said Lafleur. "In most of these heists, multiple security measures were defeated."
The National Intelligence Council is working on the sixth edition of the Global Trends report, forecasting social, economic and political trends through 2035. Written for the incoming president, and due to be released in 2016, the document stands to influence high-level thinking about global demographics, governance, the impact of technology, the distribution of natural resources and the influence of the United States on the international stage.
Naturally, the intelligence community is seeking input from only the most knowledgeable sources ... like the audience at the annual South by Southwest Interactive conference, to be held in Austin next March.
Suzanne Fry of the National Intelligence Council will be co-hosting a discussion with University of California-Berkeley professor Steve Weber, and they're seeking input now on possible topics, including questions of how robotics and manufacturing automation will affect employment, how technology will alter relationships with between governments and citizens, and steps governments can take to better understand the forces of change in play across different societies.
Click here to upvote the panel at the SXSW site, and to contribute ideas in the comments.
SelectUSA, a Commerce Department effort to encourage business investment in the United States, wants to build a database of business incentives offered by states, GCN reports.
A request for information on FedBizOpps describes the State Business Incentives Database as a comprehensive, searchable and regularly updated web-based database of all business incentives offered by states.
Computers at the Nuclear Regulatory Commission were hacked twice by foreigners in the last three years, Nextgov reports, citing an IG report from the commission. The IG report did not specifying the nationality or nationalities of the hackers.
The NRC is the country's regulator of commercial nuclear power. |
def intersection(self, hashes):
for chunk in lchunks(999, hashes):
cmd = "SELECT checksum FROM {} WHERE checksum IN ({})".format(
self.INDEX_TABLE, ",".join("?" for hash_ in chunk)
)
for (hash_,) in self._execute(cmd, chunk):
yield hash_ |
package com.example.vulndashboard.repository;
import com.example.vulndashboard.entities.VirtualMachine;
import com.example.vulndashboard.entities.WindowsVm;
import org.springframework.data.mongodb.repository.MongoRepository;
import java.util.Optional;
public interface VirtualMachineRepository extends MongoRepository<VirtualMachine, Long> {
Optional<WindowsVm> findByHostName(String hostName);
Optional<WindowsVm> findByOSName(String OSName);
Optional<WindowsVm> findByOSVersion(String OSVersion);
Optional<WindowsVm> findByProcessorType(String processorType);
Optional<WindowsVm> findByIpAddress(String ipAddress);
String deleteByOSName(String OSName);
}
|
Insiders Views of the Valley of Death: Behavioral and Institutional Perspectives Valley of death describes the metaphorical depths to which promising science and technology too often plunge, never to emerge and reach their full potential. Behavioral and institutional perspectives help in understanding the implications of choices that inadvertently lead into rather than over the valley of death. A workshop conducted among a diverse set of scientists, managers, and technology transfer staff at a U.S. national laboratory is a point of departure for discussing behavioral and institutional elements that promote or impede the pathway from research toward use, and for suggesting actionable measures that can facilitate the flow of information and products from research toward use. In the complex systems that comprise research institutions, where competing pressures can create barriers to information or technology transfer, one recommendation is to re-frame the process as a more active ushering toward use. |
Technical Field
Embodiments of the present disclosure relate generally to power inverters. More specifically, embodiments relate to systems and methods for determining inverter output current without the use of current transformers.
Background Discussion
Inverters are used to convert Direct Current (DC), the form of electricity produced by solar panels and batteries, to Alternating Current (AC). Inverters are used in a variety of different power systems. For example, inverters are commonly used in uninterruptible power supplies (UPSs) to provide regulated, uninterrupted power for sensitive and/or critical loads, such as computer systems and other data processing systems
Current Transformers (CT) are commonly used to monitor current at the output of an inverter. A CT typically includes a coil with a number of windings and a resistive element. A CT may be used to measure the output current by producing a reduced current signal, proportionate to the output current, which may be further manipulated and measured. The reduced current AC signal may then either be measured directly or converted to a DC signal and then measured. An inverter may use the measured current to regulate output power. |
/**
* Section of code shared between the two recalibration walkers which uses the command line arguments to adjust attributes of the read such as quals or platform string
*
* @param read The read to adjust
* @param RAC The list of shared command line arguments
*/
public static void parsePlatformForRead(final GATKSAMRecord read, final RecalibrationArgumentCollection RAC) {
GATKSAMReadGroupRecord readGroup = read.getReadGroup();
if (RAC.FORCE_PLATFORM != null && (readGroup.getPlatform() == null || !readGroup.getPlatform().equals(RAC.FORCE_PLATFORM))) {
readGroup.setPlatform(RAC.FORCE_PLATFORM);
}
if (readGroup.getPlatform() == null) {
if (RAC.DEFAULT_PLATFORM != null) {
if (!warnUserNullPlatform) {
Utils.warnUser("The input .bam file contains reads with no platform information. " +
"Defaulting to platform = " + RAC.DEFAULT_PLATFORM + ". " +
"First observed at read with name = " + read.getReadName());
warnUserNullPlatform = true;
}
readGroup.setPlatform(RAC.DEFAULT_PLATFORM);
}
else {
throw new UserException.MalformedBAM(read, "The input .bam file contains reads with no platform information. First observed at read with name = " + read.getReadName());
}
}
} |
def plot_polygon_lines(poly_y, poly_left_x, poly_right_x, out_img, color=[255,0,0]):
if not any(0 > poly_left_x) and not any( poly_left_x > out_img.shape[1]-1):
out_img[poly_y.astype(int), poly_left_x.astype(int)-1] = color
out_img[poly_y.astype(int), poly_left_x.astype(int)] = color
out_img[poly_y.astype(int), poly_left_x.astype(int)+1] = color
if not any(0 > poly_right_x) and not any( poly_right_x > out_img.shape[1]-1):
out_img[poly_y.astype(int), poly_right_x.astype(int)-1] = color
out_img[poly_y.astype(int), poly_right_x.astype(int)] = color
out_img[poly_y.astype(int), poly_right_x.astype(int)+1] = color
return out_img |
<filename>src/main/java/ru/task/clickerapplication/service/ClickService.java
package ru.task.clickerapplication.service;
import com.sun.istack.NotNull;
public interface ClickService {
@NotNull
String getCounter();
@NotNull String increment();
}
|
/*
author : oloop
*/
public class PercolationProbability
{
public static double estimate(int n, double p, int trials)
{
// Generate trials random n by n systems; return
// empirical percolation probability estimate
int count = 0;
for( int t = 0; t < trials; t++)
{
boolean[][] isOpen = Percolation.random( n, p );
// if ( Percolation.percolates(isOpen) && (!PercolationDirected.percolates(isOpen)))
// {
// count++;
// }
if ( Percolation.percolates(isOpen) count++;
}
return (double) count / trials;
}
public static double estimate_new(double x)
{
return 0.5 * (Math.sin(x) + Math.cos(10 * x));
}
public static double estimate_depth(int n, double p, int trials)
{
// Generate trials random n by n systems; return
// empirical percolation probability estimate
int count = 0;
for( int t = 0; t < trials; t++)
{
boolean[][] isOpen = Percolation.random( n, p );
count += Percolation.depth(isOpen);
}
return (double) count / (trials);
}
public static double estimate_bernoulli(int n, double p, int trials)
{
// Generate trials random n by n systems; return
// empirical percolation probability estimate
int count = 0;
for( int t = 0; t < trials; t++)
{
int heads = 0;
for ( int i = 0; i < n; i++)
if (StdRandom.bernoulli(0.5)) heads++;
if (heads == (int) (p*n) ) count++;
}
return (double) count / (trials);
}
public static void main(String[] args)
{
int n = Integer.parseInt(args[0]);
double p = Double.parseDouble(args[1]);
int trials = Integer.parseInt(args[2]);
double q = estimate( n, p, trials);
StdOut.println(q);
}
} |
Comparative Life Cycle Assessment on City Quarter Level A Case Study of Redensification The German and European climate action programs and the ongoing discussion of resource efficiency require an in-depth analysis of the building sector, especially with the background of the German refurbishment backlog and high energy demands of the German building stock. A Life Cycle Assessment (LCA) on the city quarter level allows fast and efficient evaluation of environmental impacts, emissions, and energy demands of densification in urban areas. This study presents LCA results for a specific urban city quarter. Thereby environmental and energetic values for specific building ages are developed and used to conduct LCA for the building construction and technical building services components. A 3D city model in CityGML-format of residential buildings serves as the basis for assessment. The results can be used to identify decisive drivers of energy demands and emissions and the saving potentials of different building development scenarios. Introduction The German and European climate action programs and the ongoing discussion of resource efficiency require an in-depth analysis of the building sector. The buildings sector and the construction industry are responsible for 38% of all energy related CO2-emissions. However, these numbers do not include the energy demands and emissions of the whole building life cycle. Due to the building refurbishment backlog in Germany and the need to densify neighbourhoods in urban areas, there is a need for methods which allow for fast and efficient comparative LCAs of large building stocks in order to identify environmental saving potentials in early planning phases and to derive recommendations for sustainable development of existing city quarters. In this context the connection of geo-referenced, spatial 3D city models and environmental values of building components show great potential. Semantic 3D city models in CityGML-standard provide data about building geometries and areas of large building stocks up to the national level, including roof types, when Level of Detail (LoD) 2 is chosen. These data can be linked with further external databases, like environmental values for different building components or energy demands. Using this method, LCA studies of large building stocks can be executed in a fraction of the time required for manual and project-specific calculations. Up to now, 3D city models have been used to analyse the energy demand and environmental impacts of large building stocks. The focus of these studies has, however, been on the operational energy demands or the embodied energies and emissions of the building constructions (BC), rather than on technical building service components (TBSC). A framework for performing LCAs for BC is integrated in umi 2.0, but before LCAs can be performed, BC and LCA parameters must first be defined. In our approach, typical BC and TBSC are defined for each building age class and LCA parameters are stored for them. These can then be linked to the building-specific information (year of construction, areas of the building components, etc.) from the 3D city models (CityGML format) to calculate the LCA automatically. The building stock chosen is an urban quarter with 105 linear buildings located in Munich, Germany. The buildings were constructed between 1949 and 1968 and were intended to be renovated and densified by adding one more storey or have to be replaced by new and larger buildings. Figure 2 shows the workflow to identify the current and future life cycle based energy demands, emissions, and potentials for improvements to the case study. The 3D city model provides exterior wall areas, shared wall areas, the ground area, the roof area, the roof type (pitched or flat roof), the number of storeys above ground and the volume of each building. Additionally, it provides information about the use of the buildings (residential or non-residential) and their year of construction. These specifications are combined with other specific user defined parameters in step 1. By analysing the building size and geometry, the building type can be specified as single family/semi-detached houses (SFH) or multi-family houses (MFH). To define window areas, a factor for the window-to-wall ratio is defined (SFH: 0.12; MFH: 0.15) according to. To define areas for interior walls and foundation, other factors for interior-wall-to-exterior-wall-per-floor (0.2) and foundation-to-ground-floor (0.27) are inserted according to. By defining one storey below ground, areas for exterior cellar walls and shared cellar walls are generated based on exterior wall and shared wall areas above ground. Methodology In total, we defined five main development scenarios (one renovation scenario and four replacement scenarios), which are further divided into subscenarios (see table 1). We assume that all the existing buildings have an unheated basement and, when there is a pitched roof, an unheated top floor. After renovation or replacement with new buildings, the top floor is assumed to be heated and the cellar floor to be unheated. In the course of the renovation, all components of the TBSC under consideration will be replaced. For heating and domestic hot water, this includes in particular the heat generators and storage tanks, heat transfer system, pipelines and their insulation. In step 2 the data given by the 3D city model and expert definitions are used to calculate the current and future operational energy demand for heating and cooling with umi with simulation boundaries based on German DIN 4108-2:2013-02 (step 3) and U-values in table 2. In step 4, the specific heating and cooling demands are imported from umi into the 3D city models. In step 5 and 6 all data given by the 3D city model is joined with energetic and environmental values of specific BC and TBSC (see figure 2). Therefore, the decisive construction components and energy systems before and after renovation are defined together with the City of Munich, which opened a competitive bidding process for the design of the district development. The environmental and energy related impacts of all defined building age specific components (exterior walls, interior walls, shared walls, roofs, ceilings, windows, baseplates, foundations) and systems (energy systems for heating and hot water preparation as well as Net energy demand and indoor comfort We determined the energy demand for heating and cooling for the current state (buildings from 1949-1968) and for KfW-55 and passive house standard. The majority of residential buildings in Germany are not equipped with active cooling. However, the cooling demand was simulated in order to evaluate the potential of overheating and an indirect assessment of the thermal comfort. In summary, we discovered that the heating demand of the city quarter in life cycle stage B6 can be significantly reduced from the range of 113.9-173.7 to 22.3-39.8 kWh/(myr) (KfW-55 standard) or to 7.4-17.0 kWh/(myr) (passive house standard). This is an average improvement of 78%. In addition, the potential cooling demand plays a decisive role in near zero energy standards with values from 7.6-20.5 (KfW-55 standard) or 9.9-27.0 kWh/(myr). Consequently, the potential cooling demand must be reduced by passive measures. Here, green infrastructure, especially big trees can prevent overheating via shading. Figure 3 shows the GWP of each considered scenario (see section 2). Based on scenario 1a the influences of different construction types regarding the GWP are shown. Considering the life cycle stages A1-A3, B4, and C3/C4 (black bars), the renovation scenario has the lowest GWP of all scenarios. Comparing the renovation (scenario 1a) with the demolition and replacement (scenarios 2.1a to 2.4a, the saving potential of GWP is up to 71%. If all known benefits and loads beyond the life cycle (stage D) are considered (scenarios 2.1b to 2.4b; see grey bars of figure 3), the demolition and replacement in massive timber construction has the lowest GWP per m living area and year. The tendencies of GWP for each scenario are, in summary, equivalent to the tendencies of PENRT. Here the values are between 1.63 and 18.89 kWh/(myr) Scenario 1a and 1b also have the lowest values of PET with 7.80 and 6.25 kWh/(myr), but the proportions in the replacement scenarios are slightly different from the proportions of GWP and PENRT. Here the massive timber construction has the highest PET with 28.29 kWh/(myr), without considering stage D (scenario 2.2a). Scenario 2.4a has the lowest PET of the replacement scenarios, without stage D, with 24.53 kWh/myr. However, it has to be considered whether the percentage of primary renewable energy of timber constructions (Sc. 2.1a: 35%; Sc. 2.2a: 37%) is higher than the percentage of massive constructions (Sc. 2.3a: 25%; Sc. 2.4a: 25%). LCA of technical building service components To determine the dimensions and consequently the life cycle based environmental and energetic impacts of the TBSC, the heating load of each building has to be calculated first. We assumed that every current component is deconstructed and replaced regarding the requirements of the KfW-55 or the passive house standard. Due to the higher energetic standard after renovation or new construction, the total heating load is reduced by -76% or -77% compared to the status quo. This has a significant influence on the dimensions of the new TBSCs. In addition, the selected district heating network and solar heating system for drinking water result in a marginal percentage of TBSC for life cycle stage A1-A3, B4 and C3/C4. In sum, the TBSC are responsible for a GWP of 0.32 kg CO2-eq./(myr) (scenario 1 to 2.4), a PENRT of 1.11 (scenario 1) or 1.08 kWh/(myr) (scenario 2.1 to 2.4) and a PET of 1.34 (scenario 1) or 1.32 kWh/(myr) (scenario 2.1 to 2.4). The heating demand (see section 3.1) is responsible for the environmental and energetic impacts during phase B6 with a GWP of 3.51 kg CO2-eq./(myr) (scenario 1) or 2.39 kg CO2-eq./(myr) (scenario 2.1 to 2.4), a PENRT of 7.92 (scenario 1) or 5.39 kWh/(myr) (scenario 2.1 to 2.4) and a PET of 11.46 (scenario 1) or 7.79 kWh/(myr) (scenario 2.1 to 2.4). The grid emission factors for these calculations are also sourced from the kobaudat (e.g., average of 0.162 kg CO2-eq./kWh of district heating). Discussion Recommendations for the sustainable development of the existing city quarter for a study period of 50 years can be derived from the results in section 3. By renovating all existing buildings or replacing the city quarter with new buildings with a near zero energy standard, the operational energy use for heating can be reduced significantly. The prospective cooling demand should be reduced by passive ventilation and shading measures to minimize the life cycle based energy demand and emissions. With the focus on BC the renovation scenario has the lowest GWP and PENRT, followed by replacement and new construction in timber. The PET of timber constructions is higher than the PET of massive constructions, but it should be considered that the percentage of renewable primary energy demand is also higher for timber constructions. Finally, we found that for low energy buildings, such as near zero energy houses, the percentage of the environmental and energy related impacts of the BC during the whole building life cycle increases significantly, while the operational energy demand decreases to a minimum. An increase in the share of renewable resources in energy supply over 50 years was taken into account and calculated by specifying the share in the starting and target year. The increase is distributed evenly over all years. While the GWP of stage B6 has a percentage of 61% and the BC 33% in the renovation scenario, this changes in the scenario 'replacement with reinforced concrete construction'. Here, stage B6 has a percentage of only 25% and the BC of 71%. The impacts of the TBSC play a marginal role with a percentage of 3-6%. Conclusion The results of this study show the necessity of conducting LCA to improve the environmental quality of large building stocks over the whole building life cycle. The methodology developed here can be applied to other city quarters or even whole cities for which CityGML-data is available. The generated environmental values of building components (see section 2) can also be used to assess other city quarter development scenarios, wherein the parameters chosen here can be replaced with other national or international building typologies, and user assumptions. Further research is necessary to translate the methodology into an automated and user friendly simulation tool. In addition, the database of environmental and energetic values of the building components should be published for use in other LCA studies and building models, potentially in combination with building information modelling (BIM). Acknowledgement This study was conducted within the scope of the research project "Green City of the Future -climate change-resilient neighbourhoods in a growing city". The project is funded by the German Federal Ministry of Education and Research -funding number 01LR1727A. Many thanks go to our project partners, especially the City of Munich, who provided us with the building data and all necessary information about the case study. |
Lunar module pilot Charles M. Duke Jr. explored moon’s rugged Descartes region with John Young during the Apollo 16 mission in April 1972. He speaks April 7 at Texas State University.
Astronaut Charles M. Duke Jr., the youngest of only 12 astronauts to walk on the moon, will speak on “The Adventure of the Apollo Moon Landings” at 6:30 p.m. Tuesday, April 7, in Taylor-Murphy 101 on the Texas State University campus.
The lecture, sponsored by the Department of History and Phi Alpha Theta, is made possible by an award from the University Lectures Committee. The lecture is free and open to the public, and refreshments will be served afterward.
Duke, retired USAF Brigadier General, was the 10th person to walk on the Moon. He served as lunar module pilot of Apollo 16 in 1972, when he and John W. Young made the first landing in the rough Descartes Highlands region and conducted three extravehicular activities.
During a record-setting stay on the lunar surface of 71 hours and 14 minutes, Duke and Young placed and activated scientific equipment and experiments, collected nearly 213 pounds of rock and soil samples, and evaluated the use of Rover-2 over the roughest surface yet encountered on the moon.
In 1969, Duke was a member of the astronaut support crew for Apollo 10. He then served as capcom (capsule communicator) for Apollo 11, the first landing on the Moon, where his distinctive southern drawl became familiar to viewers around the world. As capcom, he was the voice of a Mission Control made nervous by a long landing that almost expended all of the lunar module Eagle’s fuel.
Duke was backup Lunar Module pilot on Apollo 13. Two days after the launch, an electrical fault caused an explosion, resulting in a loss of oxygen and electrical power in the Command Module. The crew shut down the Command Module and used the Lunar Module as a “lifeboat” for the return to earth.
Duke also served as backup lunar module pilot for Apollo 17. He has logged 265 hours in space, plus 21 hours and 28 minutes of extra vehicular activity. In December 1975, he retired from the Astronaut program to enter private business. He is owner of Duke Investments and is President of Charlie Duke Enterprises.
He and his wife Dorothy, who live in New Braunfels, have two sons and nine grandchildren. Duke is an Eagle Scout and recipient of the Distinguished Eagle Scout Award from the Boy Scouts of America. After his Apollo 16 experience, he became a Christian, and he is active in prison ministry. He is also author of the book Moonwalker.
For information, contact the Texas State Department of History at (512) 245-2142.
CORRECTION: The article’s headline originally identified Duke as an Apollo 13 astronaut. He was the backup lunar module pilot on that mission but was not aboard to the fated spacecraft.
Mark, you may want to change your headline. General Duke was lunar module pilot, and explored the northern reaches of the Descartes Formation with John Young, on Apollo 16.
He was also the first man to talk with another person on the Moon, when he acknowledged Dr. Armstrong’s confirmation that “the Eagle has landed,” with..
He has to have been among the most cheerful people among the Apollo moonwalkers. He and Dr. Schmitt on Apollo 17 were clearly the most delighted of the astronauts to be on the Moon, if you don’t count Pete Conrad of Apollo 12.
The Descartes Formation, and the landing site between North Ray and South Ray craters are very easy to locate through a telescope, and I would ask him, if I could be there, if he still holds any interest in the Descartes swirl and the value placed on the Apollo 16 samples still setting the standard for scientists like the Japanese controllers of the Kaguya (SELENE 1) probe.
I envy you, if you are going. He’s a national treasure.
It still amazes me, decades after the last American on the moon, the majesty of it all — truly one of the greatest triumphs of humanity. I’ll be at this lecture with bells on my heels.
Texas State also needs to get John Herrington to come and speak, First Native American Astronaut !
Phillip, as great as Mr. Herrington is, he’s not the first Native American astronaut.
NASA astronaut Bill Pogue is. |
Preheat the oven to 200 C degrees.
Dust the bench with flour, roll the pastry into a 22 x 32cm rectangle, approx 4mm thin, rest in the fridge for half an hour. Place the pastry on a non stick baking sheet, trim the edges with a large sharp knife to form a 20 x 30cm rectangle.
Lightly cut the pastry, almost to the bottom 2 cm in from the edge all the way round, use a fork to prick the pastry - this is known as docking - to make lots of holes through the pastry, don't go on the edge! This is to prevent it from rising up in the centre.
Bake until golden, approx 15 minutes. Remove the pastry from the oven and press the centre part down, then sprinkle with half the blue cheese. Trim the bottom 3 - 5 cms off the asparagus spears so that they fit neatly across the inside of the tart shell.
Place them in a single layer arranging them alternate top to tail. Brush them with the olive oil, sprinkle the remaining blue cheese over and season with salt and pepper. Brush a little egg wash (made with 1 whisked whole egg and a good pinch of salt) around the edge of the pastry.
Bake for a further 15 - 20 minutes or until the spears are tender.
I like to enjoy eating this tart with a fresh bowl of crisp salad leaves and my all time favourite classic Kiwi mayonnaise dressing. |
<filename>app/src/main/java/ru/dimaarts/universaladapter/interfaces/ListActivity.java
package ru.dimaarts.universaladapter.interfaces;
import android.support.v7.widget.RecyclerView;
import android.widget.Adapter;
/**
* Created by gorshunovdv on 5/22/2017.
*/
public interface ListActivity {
RecyclerView.Adapter getAdapter();
}
|
You occasionally see very pretty photos of contrails, like this one:
Very pretty. But what is it? It’s clearly not a regular exhaust contrail, as the trail seems to start actually ON the wing, and it has a weird rainbow effect you don’t often find in exhaust contrails.
It’s actually an aerodynamic contrail. It’s formed by the reduction of pressure in the air as it moves over the wing. When the pressure of a gas falls, then its temperature also falls (the same principle as is used by your refrigerator). The reduced temperature cause small drops of water to condense, which then may freeze. The (frozen) drops get larger as more water condenses on them. The different sized drops (or ice crystals) have different optical properties, which affect different wavelengths of light, which accounts for the “rainbow” effect.
A rather more scientific explanation (also explaining the exact colors) can be found here:
http://contrailscience.com/files/Gierens_Aerodynamic_poster_060625.pdf
The interesting thing about this type of contrail is that they are actually more common in warm weather. They need a lot of moisture, and cold air is generally dry, so they are more common in the summer months, and in warmer climes. See Aerodynamic Contrails Phenomenology and flow physics – Gierens, et al.
As aerodynamic contrails are independent of the formation conditions of jet contrails, they form an additional class of contrails which might be complementary because they form in predominantly in layers that are too warm for jet contrail formation.
(They are not entirely complementary however, as you can get both types of contrail simultaneously from the same plane, see below.)
There is actually surprisingly little work being done on the formation of aerodynamic contrails. A lot of the time they only show up as wingtip contrails (which you can see are very dense in the above photo). Conditions need to be just right for the full wing to generate a contrail, and it typically does not last very long at all.
You’ve probably seen aerodynamic contrails on landing planes, like:
Here you can see the wing contrails vanish almost immediately. The long persisting contrails (which won’t persist very long) are from the outer end of the lowered flaps – where air is compressed and then expanded very rapidly, causing a lot of moisture to condense. You can also see there’s a lot of moisture in the air, it’s quite misty looking.
If the aerodynamic contrail is thick enough, then it forms like a solid sheet, and can curl up at the sides as it is drawn into the wingtip vortices:
http://www.airliners.net/photo/Cathay-Pacific-Airways/Boeing-777-267/2213426/L/&sid=0b512dfe498efba828a2189aca22fac6
This fantastic photo set on Flickr has some nice photos of both exhaust and aerodynamic contrails, you can clearly see the difference:
http://www.flickr.com/photos/jpro747/
In this shot, you can see the jet seems to be underneath a layer of clouds, suggesting it’s at a low altitude, where exhaust contrails would not normally form. Although with this image, it’s little hard to see what is in front of what. I suspect that the shadow you see near the tail is actually the shadow of the plane on the clouds, meaning the plane is just above them, or in them – in a region of high humidity, either way.
From the same set, we can see that the two types of contrail are not mutually exclusive. You can have both at the same time:
Note you have the thick white contrails coming from the engine, and the aerodynamic contrails coming from the wings.
(side note here: most of the photos in jpro747’s set were taken FROM THE GROUND with a Canon 350D ($400) attached to a 1200mm 6-inch Dobsonian telescope ($300-$1000, depending on quality). In most of the shots, you can clearly see the type of plane, and usually the airline markings. Now, why has NOBODY in the supposed 2 Million “chemtrail” community managed to take a closeup photo of a jet spraying chemicals. Considering you can do it with $700 worth of equipment, it seems rather odd).
This video shows an aerodynamic contrail forming in patchy air:
Aerodynamic Contrail in patchy air
You can see the trail looks very similar to the photos, especially in the final segment of the video. There are few wide shots, so it’s hard to tell how long the trails is lasting for, but at 0:50, the camera pulls back, and the provious trail is either off screen, or has already evaporated. Note this video was shot in Torino (Turin), Italy,on August 16th 2008 – during the summer. That’s when these type of contrails are more likely, as they need very humid air.
(Update 9/24/2010)
Here’s a similar phenomenon. This is taken at a lower altitude, with the the sun just right. This is a bit different as it’s not really a trail – or rather it’s a very short non persistent trail that only exists because of the extreme changes in air pressure from the F-22’s high power maneuvering.
Original source:
http://www.fencecheck.com/forums/index.php/topic,12042.msg203579.html#msg203579
And here’s an early photo, from LIFE magazine, October 4 1954
You can also get contrails from the tips of propellors
Here’s what it looks like from close up, following a KC_10:
Reference:
Aerodynamic Contrails Phenomenology and flow physics – Gierens, et al.
Aerodynamic contrails Microphysics and optical Properties – Gierens, at al. |
const NODE_ENV = process.env.NODE_ENV || 'development'
const env = require(`./config/env.${NODE_ENV}.ts`)
export default {
mode: 'spa',
srcDir: 'src/',
/*
** Headers of the page
*/
env,
head: {
title: process.env.npm_package_name || '',
meta: [
{ charset: 'utf-8' },
{ name: 'viewport', content: 'width=device-width, initial-scale=1' },
{
hid: 'description',
name: 'description',
content: process.env.npm_package_description || ''
}
],
link: [{ rel: 'icon', type: 'image/x-icon', href: '/favicon.ico' }]
},
/*
** Customize the progress-bar color
*/
loading: { color: '#3B8070' },
/*
** Global CSS
*/
css: [
'element-ui/lib/theme-chalk/index.css',
'@fortawesome/fontawesome-free/css/all.css',
'@/assets/scss/main.scss'
],
/*
** Plugins to load before mounting the App
*/
plugins: [
{ src: '~plugins/element-ui' },
'~/plugins/nuxt-i18n',
'~/plugins/axios-accessor',
'~/plugins/axios',
'~/plugins/favorite-filter'
],
/*
** Nuxt.js dev-modules
*/
buildModules: [
// Doc: https://github.com/nuxt-community/eslint-module
'@nuxtjs/eslint-module',
'@nuxt/typescript-build'
],
/*
** Nuxt.js modules
*/
modules: [
// Doc: https://axios.nuxtjs.org/usage
'@nuxtjs/axios',
'@nuxtjs/pwa',
'@nuxtjs/style-resources'
],
styleResources: {
scss: ['~/assets/scss/_variables.scss']
},
/*
** Axios module configuration
** See https://axios.nuxtjs.org/options
*/
axios: { baseURL: env.apiBaseUrl, proxy: false },
typescript: {
typeCheck: true,
ignoreNotFoundWarnings: true
},
/*
** Build configuration
*/
build: {
transpile: [/^element-ui/],
/*
** You can extend webpack config here
*/
extend(config: any, _ctx: any) {
config.devtool = 'inline-cheap-module-source-map'
}
}
}
|
The Correlation of Platelet Lymphocyte Ratio (PLR) as 28 Days Sepsis Mortality Predictor in Intensive Care Unit RSMH Palembang Introduction. Inflammatory and anti-inflammatory response are important in pathophysiology and mortality of sepsis. Platelet as first line inflammatory marker was found increasing during early phase of infection. Decrease in lymphocyte was caused by disrupted balance between inflammatory and anti-inflammatory response. Platelet-to-lymphocyte ratio (PLR) is a cheap and accessible biomarker of sepsis mortality. This study aims to find the sensitivity and specificity of PLR as mortality predictor of sepsis in 28 days. Method. This observational analytic study with retrospective cohort design was conducted to 91 sepsis patients in intensive care unit of Dr. Mohammad Hoesin Palembang Central Hospital between January and December 2019. Samples were secondarily collected from medical record during June-July 2020. Data was analyzed using chi-square test, cog regression test, and ROC curve analysis. Results. The result found 50 patients (54,9%) died in 28 days. Morbidity score (Charlson) was the only statistically significant mortality parameter (p=0,009). The study reported PLR cut-off point of >272,22. The sensitivity and specificity of PLR as 28-days sepsis mortality predictor are 84% and 80,49% respectively. Conclusion. PLR is alternatively reliable mortality predictor in sepsis patient, accounted to its relatively high sensitivity and specificity. |
Is there an additional effect on the risk of entry into out-of-home care from having parent(s) born outside of Europe in cases of alleged physical child abuse? findings from Sweden ABSTRACT Children to immigrants are over-represented in Swedens out-of-home care (OHC) population. The driving forces behind this over-representation have not been sufficiently researched. This studys objective was to investigate if having parent(s) born outside of Europe has an additional effect on the risk of entry into OHC in cases of alleged parental physical violence against children, and to discuss potential empirical support for the risk model and the bias model for explaining the over-representation. The data for this study consisted of case-file data abstracted from 132 child-welfare investigations concluded with some form of intervention by Stockholm City in 2014. By using an interaction term in a logistic regression model, it was estimated that having parent(s) born outside of Europe had no additional effect on the risk of entry into OHC in these cases, i.e. the interaction effect was insignificant, OR = 1.302, 95% CI . The result was adjusted for sex, age, poverty, and lone parenting. Hence, discrimination in these cases does not seem to be a substantial driving force behind the over-representation. Instead, it may be driven by disparities in exposures to common risk factors for child abuse and neglect. Poverty, poor housing conditions are of high relevance for Stockholm City. Policymakers are advised to close the gap in living conditions between Swedish and foreign-born people in the country. |
/**
* Test for {@link InformationTable#discard(int[], boolean)} method.
* Tests if {@link IndexOutOfBoundsException} is thrown if discarded object's index is out of range.
*/
@Test
public void testDiscardIntArrayBoolean03() {
InformationTable informationTable = configuration02.getInformationTable(false);
int[] discardedObjectIndices = new int[] {0, 3, 4, 7};
try {
informationTable.discard(discardedObjectIndices, true);
fail("Should throw an exception if discarded object's index is out of range.");
} catch (IndexOutOfBoundsException exception) {
}
} |
def check_badge(badge_id):
try:
if (User.verify_role(current_user.id)):
return redirect(url_for('admin'))
login_manager.current_user = User.get_user_by_username(current_user.username)
badges = Badge.get_all_badges()
badge = Badge.get_badge_by_id(badge_id)
user_id = current_user.id
unearned_stamps = [row.stamp_name for row in Stamp.get_unearned_stamps_of_badge(user_id, badge.badge_id)]
earned_stamps = [row for row in UserStamp.get_earned_stamps_of_badge(user_id, badge.badge_id)]
if not unearned_stamps:
unearned_stamps = ['All stamps earned']
badge_progress = User.get_badge_progress(user_id, badge.badge_id)
if badge_progress:
points = badge_progress[0]
current_level = badge_progress[1]
to_next_lv = badge_progress[2]
else:
points = 0
current_level = 0
to_next_lv = 0
if request.method == 'POST':
stamp_id = request.form.get('stamp_id')
time_finished = datetime.strptime(request.form.get('time_finished'), '%Y-%m-%d').date()
log_date = datetime.strptime(request.form.get('log_date'), '%Y-%m-%d %H:%M:%S')
if stamp_id and time_finished and log_date:
if UserStamp.delete_stamp(user_id, stamp_id, time_finished, log_date):
print('deleted:\nid: ' + str(stamp_id) + '\ntime finished: ' + str(time_finished) + '\nlog_date: ' + str(log_date))
else:
print('error when deleting user earned stamp')
return redirect('/badges' + str(badge_id))
events = get_event_list()
mesa_days = searchEvents(events, ['Mesa','Day'])
demo_days = searchEvents(events, ['Demo','Day'])
future_events = [event for event in events if event['remain_days'] < 15]
upcoming_events = [event for event in events if event['remain_days'] < 8]
current_events = [event for event in events if event['remain_days'] < 3]
mesa_events = get_mesa_events(future_events)
close_session()
return render_template('badges.html',
badges=badges,
badge=badge,
unearned=unearned_stamps,
earned=earned_stamps,
pt=points,
lv=current_level,
to_next_lv=to_next_lv,
events=events,
number_upcoming=len(upcoming_events),
upcoming_events=upcoming_events,
number_current=len(current_events),
current_events=current_events,
mesa_days=mesa_days,
demo_days=demo_days,
mesa_events=mesa_events)
except:
return redirect(url_for('error')) |
class Solution {
public int shortestDistance(int[][] maze, int[] start, int[] destination) {
int m = maze.length;
int n = maze[0].length;
int[][] dist = new int[m][n];
for (int i = 0; i < m; ++i) {
Arrays.fill(dist[i], Integer.MAX_VALUE);
}
dist[start[0]][start[1]] = 0;
Deque<int[]> q = new LinkedList<>();
q.offer(start);
int[] dirs = {-1, 0, 1, 0, -1};
while (!q.isEmpty()) {
int[] p = q.poll();
int i = p[0], j = p[1];
for (int k = 0; k < 4; ++k) {
int x = i, y = j, step = dist[i][j];
int a = dirs[k], b = dirs[k + 1];
while (
x + a >= 0 && x + a < m && y + b >= 0 && y + b < n && maze[x + a][y + b] == 0) {
x += a;
y += b;
++step;
}
if (step < dist[x][y]) {
dist[x][y] = step;
q.offer(new int[] {x, y});
}
}
}
return dist[destination[0]][destination[1]] == Integer.MAX_VALUE
? -1
: dist[destination[0]][destination[1]];
}
} |
Enhanced Sensitivity to Afferent Stimulation and Impact of Overactive Bladder Therapies in the Conscious, Spontaneously Hypertensive Rat The spontaneously hypertensive rat (SHR) has been proposed as an overactive bladder model, driven, at least partially, by alterations in bladder innervation. To assess the functional role of sensory bladder afferents we evaluated the conscious cystometric response to prostaglandin E2 (PGE2) or acetic acid (AA) bladder infusion. SHR demonstrated a hypersensitivity to PGE2 and AA, as indicated by a greater reduction in both void volume (VV) and micturition interval (MI) compared with Sprague-Dawley controls. The heightened PGE2 and AA responses in the SHR were inhibited by capsaicin desensitization, supporting a role for bladder afferents in facilitating the hypersensitivity. Furthermore, we characterized the SHR pharmacologically using overactive bladder therapeutic agents. In the SHR, both darifenacin and oxybutynin (M3-selective and nonselective muscarinic antagonists, respectively) reduced micturition pressure (MP) and functional bladder capacity (VV and MI). In sharp contrast, functional bladder capacity was significantly enhanced by 3-adrenoceptor agonism [5-[(2R)-2-[amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL316243)], and by gabapentin, without effect on MP. These data provide the first functional evidence for hypersensitive bladder afferents in the SHR and provide a pharmacological benchmark in this model for overactive bladder therapeutics. These data also support the idea that 3-adrenoceptor agonism and gabapentin may provide a more effective overactive bladder therapy than muscarinic antagonism. |
ROBERTO MARTINEZ has told Wigan to get tough against Chelsea, blaming a psychological problem for his side’s woeful record against the Premier League’s Big Four.
The Latics have lost 30 of 34 games against Chelsea, Manchester United, Liverpool and Arsenal and entertain Carlo Ancelotti’s leaders on the back of a 4-0 hammering at Arsenal.
Martinez, who also saw his side crushed 5-0 at home to United last month, said it was time they stopped rolling over against the big clubs.
“We gave Arsenal too much respect. That probably explains why we haven’t beaten one of the big four clubs in 34 attempts,” he said.
“When you look at a stat like it, it’s quite clear. Psychologically we haven’t approached these games in the right manner. |
Investigating the ranksize relationship of urban areas using land cover maps We investigated the possibility that the ranksize rule can be applied to the relationship between urban size and rank order. Accordingly, using a global land cover data set, we clustered contiguous urban grid cells, calculated the area in each cluster, and ranked urban areas in each of the countries studied. This research revealed that Zipf's law can be applied to the relationship between urban area and rank order as well as to city populations. Comparisons were made in some countries, and it was shown that the urban area ranksize rule was free from administrative boundaries. Finally, in Japan, using landuse maps for several times in recent history, changes in ranksize were investigated. As a result, it was found that the slopes for urban areas did not change visvis their rank in a double logarithmic graph and that only the x and y interception changed. |
/**
* @author auto create
* @version
*/
public class GetHotlineServiceStatisticsRequest extends RpcAcsRequest<GetHotlineServiceStatisticsResponse> {
private List<Long> depIds;
private List<Long> agentIds;
private String timeLatitudeType;
private Integer currentPage;
private Long startDate;
private String instanceId;
private Long endDate;
private Boolean existDepartmentGrouping;
private List<Long> groupIds;
private Integer pageSize;
private Boolean existSkillGroupGrouping;
private Boolean existAgentGrouping;
public GetHotlineServiceStatisticsRequest() {
super("aiccs", "2019-10-15", "GetHotlineServiceStatistics");
setMethod(MethodType.GET);
try {
com.aliyuncs.AcsRequest.class.getDeclaredField("productEndpointMap").set(this, Endpoint.endpointMap);
com.aliyuncs.AcsRequest.class.getDeclaredField("productEndpointRegional").set(this, Endpoint.endpointRegionalType);
} catch (Exception e) {}
}
public List<Long> getDepIds() {
return this.depIds;
}
public void setDepIds(List<Long> depIds) {
this.depIds = depIds;
if (depIds != null) {
for (int depth1 = 0; depth1 < depIds.size(); depth1++) {
putQueryParameter("DepIds." + (depth1 + 1) , depIds.get(depth1));
}
}
}
public List<Long> getAgentIds() {
return this.agentIds;
}
public void setAgentIds(List<Long> agentIds) {
this.agentIds = agentIds;
if (agentIds != null) {
for (int depth1 = 0; depth1 < agentIds.size(); depth1++) {
putQueryParameter("AgentIds." + (depth1 + 1) , agentIds.get(depth1));
}
}
}
public String getTimeLatitudeType() {
return this.timeLatitudeType;
}
public void setTimeLatitudeType(String timeLatitudeType) {
this.timeLatitudeType = timeLatitudeType;
if(timeLatitudeType != null){
putQueryParameter("TimeLatitudeType", timeLatitudeType);
}
}
public Integer getCurrentPage() {
return this.currentPage;
}
public void setCurrentPage(Integer currentPage) {
this.currentPage = currentPage;
if(currentPage != null){
putQueryParameter("CurrentPage", currentPage.toString());
}
}
public Long getStartDate() {
return this.startDate;
}
public void setStartDate(Long startDate) {
this.startDate = startDate;
if(startDate != null){
putQueryParameter("StartDate", startDate.toString());
}
}
public String getInstanceId() {
return this.instanceId;
}
public void setInstanceId(String instanceId) {
this.instanceId = instanceId;
if(instanceId != null){
putQueryParameter("InstanceId", instanceId);
}
}
public Long getEndDate() {
return this.endDate;
}
public void setEndDate(Long endDate) {
this.endDate = endDate;
if(endDate != null){
putQueryParameter("EndDate", endDate.toString());
}
}
public Boolean getExistDepartmentGrouping() {
return this.existDepartmentGrouping;
}
public void setExistDepartmentGrouping(Boolean existDepartmentGrouping) {
this.existDepartmentGrouping = existDepartmentGrouping;
if(existDepartmentGrouping != null){
putQueryParameter("ExistDepartmentGrouping", existDepartmentGrouping.toString());
}
}
public List<Long> getGroupIds() {
return this.groupIds;
}
public void setGroupIds(List<Long> groupIds) {
this.groupIds = groupIds;
if (groupIds != null) {
for (int depth1 = 0; depth1 < groupIds.size(); depth1++) {
putQueryParameter("GroupIds." + (depth1 + 1) , groupIds.get(depth1));
}
}
}
public Integer getPageSize() {
return this.pageSize;
}
public void setPageSize(Integer pageSize) {
this.pageSize = pageSize;
if(pageSize != null){
putQueryParameter("PageSize", pageSize.toString());
}
}
public Boolean getExistSkillGroupGrouping() {
return this.existSkillGroupGrouping;
}
public void setExistSkillGroupGrouping(Boolean existSkillGroupGrouping) {
this.existSkillGroupGrouping = existSkillGroupGrouping;
if(existSkillGroupGrouping != null){
putQueryParameter("ExistSkillGroupGrouping", existSkillGroupGrouping.toString());
}
}
public Boolean getExistAgentGrouping() {
return this.existAgentGrouping;
}
public void setExistAgentGrouping(Boolean existAgentGrouping) {
this.existAgentGrouping = existAgentGrouping;
if(existAgentGrouping != null){
putQueryParameter("ExistAgentGrouping", existAgentGrouping.toString());
}
}
@Override
public Class<GetHotlineServiceStatisticsResponse> getResponseClass() {
return GetHotlineServiceStatisticsResponse.class;
}
} |
/**
* Base of all chart factories.
*
* <p>
* Responsible to build the charts' tool bars and to create charts (including building their models).
* </p>
*
* @author Andras Belicza
*/
public class ChartFactory {
/** Reference to the charts component that created us. */
protected final ChartsComp chartsComp;
/** Reference to the replay processor. */
protected final RepProcessor repProc;
/**
* Creates a new {@link ChartFactory}.
*
* @param chartsComp reference to the charts component that created us
*/
public ChartFactory( final ChartsComp chartsComp ) {
this.chartsComp = chartsComp;
repProc = chartsComp.getRepProcessor();
}
/**
* Adds the option components of the chart to the specified tool bar.
*
* <p>
* This implementation does not add any components.
* </p>
*
* @param toolBar tool bar to add the option components to
*/
public void addChartOptions( final XToolBar toolBar ) {
// Subclasses will optionally add options.
}
/**
* Creates the charts.
*
* <p>
* This implementation sets an "unimplemented" message to the charts canvas and returns an empty list.
* </p>
*
* @return the charts
*/
public List< ? extends Chart< ? > > createCharts() {
chartsComp.getChartsCanvas().setMessage( "This chart is not yet implemented." );
return Collections.emptyList();
}
/**
* Reconfigures the charts canvas with chart specific parameters (does not repaint).
*
* <p>
* This implementation does nothing.
* </p>
*/
public void reconfigureChartCanvas() {
// Subclasses will optionally reconfigure chart canvas.
}
} |
The Marine Fisheries Council will make decisions on regulations for the upcoming fluke and sea bass seasons at their meeting on Thursday at 4 p.m. in the Toms River Township Municipal Building at 33 Washington St.
Five alternatives for fluke have been provided, most of which provide a longer season than last year’s May 7 to Sept. 25. By staying at 18 inches and eight fluke, we could have a spring to fall season lasting as long as to Oct. 28. Opting for a 17.5-inch minimum would drop the season to just May 5 to Sept. 28 with five fish — and with a 17-inch minimum the season would be only from May 29 to Sept. 1 with three fish.
Rich Johnson, of the Fishing Line, reports the New York Department of Environmental Conservation is favoring four fluke at a 19½-inch monimum for their waters in order to get a season from May 3 to Sept. 30. Dropping back to 19 inches would considerably shorten that season.
Check my blog entry at nj.com/shore/blogs/fishing for all the New Jersey summer flounder and sea bass alternatives, as well as Mid-Atlantic Council quotas on bluefish that must be commented upon by Thursday. The Council doesn't appear to be aware of how poor last year's bluefishing was in New York/New Jersey Bight, and supports a transfer of recreational quota to commercial interests.
In the case of sea bass, we have only two options, with B providing a few more days (210) of a split season running May 19 to Oct. 14 and resuming from Nov. 1 to Dec. 31 with the same 25 sea bass at a 12.5-inch minimum as last year. The winter season would also remain open from Jan.1 to Feb. 28, 2013, with a 15-fish bag, under proposed federal waters regulations.
Only a few $99 tickets remain for Saturday's Canyon Runner Seminar at the Huntington Hilton in nearby Long Island. Call Adam La Rosa at (732) 842-6825 for reservations, or e-mail [email protected].
The New Jersey Boat Sale & Expo, sponsored by the Marine Trades Association of New Jersey, opened Thursday at the New Jersey Convention and Exposition Center in Raritan Center Edison, and runs through Sunday. Today's hours are from noon to 8 p.m.; Saturday's from 10 a.m. to 9 p.m., and Sunday's from 11 a.m. to 5 p.m. Admission is $6 for adults, those under 16 are admitted free with an accompanying adult. Seminars will be provided by On the Water magazine. For information e-mail [email protected] or call (732) 292-1041.
The World Fishing & Outdoor Expo is coming up Thursday to March 4 at SUNY Rockland Community College Field House in Suffern, N.Y. — and the Somerset Saltwater Expo from March 16 to 18. Underwater photographer Mike Laptew, captain Pete Meyers, and Rich Johnson will be speaking at Suffern, and I’ll be among those doing seminars at Somerset. A free ticket for either show may be obtained courtesy of Rich Johnson by sending a self-addressed business (10) envelope to Suffern (or Somerset) Free Tix Giveaway, The Fishing Line, 24 Troy Ave., E. Atlantic Beach, NY 11561. Only one ticket for either show may be requested, and duplicates will be rejected.
The Miami International Boat Show was its usual big success. I ran into many N.J. anglers at that massive show, including Paul Regula of Bounty Hunter from Point Pleasant. The most innovative product I spotted was AFTCO’s Reel Drag Technology (ARDT) — a rod handle incorporating sensors and an LCD digital scale that provides a readout of reel drag as you’re fighting a fish. It will work on any trolling or spinning rod, and with roller or ring guides.
Capt. Harry’s Fishing Supply is a must for anglers visiting Miami, and it’s now a lot easier to find in the new location at 8501 NW 7th Ave. — with a sign alongside Interstate 95.
During every trip to Miami I’m amazed by how beautiful and productive the waters of Biscayne Bay are just a few miles from downtown. During a few hours fishing Sunday evening with Adrian Gray of the International Game Fish Association (IGFA) in his 16-foot IPB skiff at Key Biscayne, we had hits from a variety of small fish on Gulp Minnows under a popping cork on 5-foot grass flats in the harbor (spotted sea trout were the target, but Gray even jumped a 50-pound tarpon), before trolling four short gag groupers at dusk on small Bomber diving plugs. Tarpon weren’t showing at the bridge on the ebb tide after dark, but a blind hit on a live shrimp drifted under the bridge provided me with a 40-pound release on a Shimano Sustain 8000 one-handed spinning rig when the silver king responded to the pressure and swam into the current instead of cutting me off in the pilings.
The targeted species didn’t cooperate Wednesday morning during the couple of hours I had to fish with friend and former Montauk skipper Steve Horowitz on his skiff. Clouds on an otherwise beautiful morning prevented us from spotting bonefish on the flats, though I hooked a barracuda casting a tube — and had a shot at a reluctant lemon shark. There’s never any worry about getting skunked with Horowitz (561) 271-6006 as casting a jig tipped with shrimp in the channels produces hits almost every cast from a variety of small fish ranging from jacks to snappers and groupers. I even upheld my trash fish reputation by jigging a puffer among our nine species. There’s always something to catch at any time of day in crystal clear waters virtually under Miami’s skyscrapers. Upon our return to the Key Biscayne ramp we saw a huge manatee that looked like a misplaced whale as it cruised slowly around the skiff.
Ling fishing has remained excellent in local waters, though there's only been a pick of cod in mild winter waters. Some blackfish are still being caught fairly close to shore, but that season closes in March. Anglers plugging the tips of northern jetties at night continue to catch stripers. There have been no bass reports from the beach, but Betty & Nick's in Seaside Park heard of a winter flounder being released in the surf– and a party boat mate mentioned stripers being spotted on the way in from the Mud Hole. Betty & Nick's will try to have salted clams ready for those seeking a striper this weekend. Though the ocean is open year-round, bay fishing for stripers remains closed until March 1.
Windy weather has held back the mackerel boats this week, but mackerel were still within range last Saturday.
The Jamaica from Brielle sails at 11 p.m. for cod and pollock on offshore wrecks. Call (732) 528-5014 for reservations. Wrecks closer to shore will be fished at 4 a.m. Sunday plus the upcoming Wednesday, Friday, Saturday and Sunday.
Wednesday’s trip produced catches of from 20 ling up to 51 by Dave Thomas of Paterson, who also had the pool winner at 3 pounds. Robert Rushnak of Point Pleasant Beach boated 65 ling on Gulp strips.
Russ Binns has Coast Boating School safety courses set for Monday and Tuesday, 6 to 9:30 p.m. at West Marine on Route 37 in Toms River; on March 5 and 6 at Brick Elks Club on Old Hooper Avenue in Brick, 7 to 10:30 p.m.; and on March 10 and 11 at West Marine at Route 35 in Eatontown, 9 a.m. to 12:30 p.m. Call (732) 279-0562. |
It's not every day you get an email from a former director of the U.S. Mint (unless you're married to one, probably) — but it's also not every day that you write about the very real possibility that the U.S. Treasury might mint a platinum coin worth one trillion dollars. Either way, it was an excellent surprise to hear from Philip Diehl, the former Mint director and Treasury chief of staff who drafted Sec. 5112 of title 31, United States Code with Rep. Mike Castle — in other words, the guy who wrote the "trillion-dollar coin" law. His take? Not only does the law clearly allow for the coin to be minted, it also would have "no negative macroeconomic effects."
I'm the former Mint director and Treasury chief of staff who, with Rep. Mike Castle, wrote the platinum coin law (Sec. 5112 of title 31, United States Code) and oversaw minting of the original coin authorized by the law, so I'm in a unique position to address some confusion I've seen in the media about the $1 trillion platinum coin proposal.
In minting the $1 trillion platinum coin, the Treasury Secretary would be exercising authority which Congress has granted routinely for more than 220 years. The Secretary's authority is derived from an Act of Congress (in fact, a GOP Congress) under power expressly granted to Congress in the Constitution (Article 1, Section 8). What is unusual about the law is that it gives the Secretary discretion regarding all specifications of the coin, including denominations.
The accounting treatment of the coin is identical to the treatment of all other coins. The Mint strikes the coin, ships it to the Fed, books $1 trillion, and transfers $1 trillion to the treasury's general fund where it is available to finance government operations just like with proceeds of bond sales or additional tax revenues. The same applies for a quarter dollar.
Once the debt limit is raised, the Fed could ship the coin back to the Mint where the accounting treatment would be reversed and the coin melted. The coin would never be "issued" or circulated and bonds would not be needed to back the coin.
There are no negative macroeconomic effects. This works just like additional tax revenue or borrowing under a higher debt limit. In fact, when the debt limit is raised, Treasury would sell more bonds, the $1 trillion dollars would be taken off the books, and the coin would be melted.
This does not raise the debt limit so it can't be characterized as circumventing congressional authority over the debt limit. Rather, it delays when the debt limit is reached. Those who claim otherwise are misinformed or pursuing an agenda.
This preserves congressional authority over the debt limit in a way that reliance on the 14th Amendment would not. It also avoids the protracted court battles the 14th Amendment option would entail and avoids another confrontation with the Roberts Court.
Any court challenge is likely to be quickly dismissed since (1) authority to mint the coin is firmly rooted in law that itself is grounded in the expressed constitutional powers of Congress, (2) Treasury has routinely exercised this authority since the birth of the republic, and (3) the accounting treatment of the coin is entirely routine.
Yes, this is an unintended consequence of the platinum coin bill, but how many other laws have had unintended consequences? Most, I'd guess. The fact that this use of the authority granted by Congress is unintended has no bearing on its legality or constitutionality. |
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