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<reponame>agdturner/agdt-java-generic-data-web-SEA
/*
* Copyright 2018 geoagdt.
*
* Licensed under the Apache License, Version 2.0 (the "License");
* you may not use this file except in compliance with the License.
* You may obtain a copy of the License at
*
* http://www.apache.org/licenses/LICENSE-2.0
*
* Unless required by applicable law or agreed to in writing, software
* distributed under the License is distributed on an "AS IS" BASIS,
* WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
* See the License for the specific language governing permissions and
* limitations under the License.
*/
package uk.ac.leeds.ccg.web.seag;
import com.gargoylesoftware.htmlunit.BrowserVersion;
import com.gargoylesoftware.htmlunit.Page;
import com.gargoylesoftware.htmlunit.ScriptResult;
import com.gargoylesoftware.htmlunit.WebClient;
import com.gargoylesoftware.htmlunit.html.HtmlPage;
import java.io.File;
import java.io.IOException;
import java.io.PrintWriter;
import java.nio.file.Files;
import java.nio.file.Paths;
import java.util.HashSet;
import uk.ac.leeds.ccg.data.core.Data_Environment;
import uk.ac.leeds.ccg.generic.core.Generic_Environment;
import uk.ac.leeds.ccg.generic.io.Generic_Defaults;
import uk.ac.leeds.ccg.web.io.Web_Scraper;
import uk.ac.leeds.ccg.web.core.Web_Environment;
/**
* @author <NAME>
* @version 1.0.0
*/
public class Anna extends Web_Scraper {
public Anna(Web_Environment e) {
super(e);
}
/**
* Main method
*
* @param args
*/
public static void main(String[] args) {
try {
new Anna(new Web_Environment(new Data_Environment(
new Generic_Environment(new Generic_Defaults())))).run(args);
} catch (Exception ex) {
ex.printStackTrace(System.err);
}
}
public void run(String[] args) throws IOException {
run();
}
public void run() throws IOException {
url = "http://www.gov.scot/seag/publicsearch.aspx";
dir = Paths.get(System.getProperty("user.dir"), "data", "seag", "anna");
Files.createDirectories(dir);
recs = new HashSet<>();
parse(url);
}
HashSet<String> recs;
public void parse(String url) throws IOException {
// ArrayList<String> lines;
File f;
PrintWriter outputPW;
outputPW = getPrintWriter(url + ".html");
// lines = getHTML(10, 1, url, outputPW);
// Iterator<String> ite;
// ite = lines.iterator();
// while (ite.hasNext()) {
// System.out.println(ite.next());
// }
// outputPW.close();
// Map<String, String> allFields = new HashMap<>();
// allFields.put("search1$GridView1", "Page$2");
// try {
//// Document doc = Jsoup.connect(url).get();
// Document doc = Jsoup.connect(url)
// .followRedirects(true)
// .userAgent("netscape")
// .data(allFields)
// .post();
// System.out.println(doc.html());
// } catch (IOException ex) {
// Logger.getLogger(Anna.class.getName()).log(Level.SEVERE, null, ex);
// }
// Initialise webClient
WebClient webClient = new WebClient(BrowserVersion.FIREFOX_45);
String START_URL = url;
try {
HtmlPage page = webClient.getPage(START_URL);
printPage(page, outputPW);
webClient.getOptions().setJavaScriptEnabled(true);
webClient.waitForBackgroundJavaScript(3000);
int totalPages = 212;
for (int i = 2; i < totalPages; i++) {
ScriptResult sr = page.executeJavaScript("javascript:__doPostBack('search1$GridView1','Page$" + i + "')");
Page page2 = sr.getNewPage();
if (page2.isHtmlPage()) {
HtmlPage page2h = (HtmlPage) page2;
printPage(page2h, outputPW);
}
}
//http://www.gov.scot/seag/details.aspx?id=PRE\00844&sid=2
} catch (IOException ex) {
ex.printStackTrace();
}
outputPW.close();
}
protected void printPage(HtmlPage page2h, PrintWriter outputPW) {
String txt = page2h.asText();
// System.out.println(txt);
// String xml = page2h.asXml();
// System.out.println(xml);
String[] txts = txt.split("Date Last Modified");
for (int j = 1; j < txts.length; j++) {
String[] txts2 = txts[j].split("\\r|\\n");
String s;
for (int k = 0; k < txts2.length; k++) {
if (txts2[k].startsWith("SEA") || txts2[k].startsWith("UK")
|| txts2[k].startsWith("EU") || txts2[k].startsWith("PRE")) {
String[] s2 = txts2[k].split("\t");
s = "\"" + s2[0] + "\",\"http://www.gov.scot/seag/details.aspx?id=" + txts2[k].replaceAll("\t", "\",\"") + "\"";
if (recs.contains(s)) {
System.out.println("Duplicate" + s);
} else {
//System.out.println(s);
outputPW.println(s);
recs.add(s);
}
} else {
if (!txts2[k].isEmpty()) {
if (txts2[k].equalsIgnoreCase("1\t2\t3\t4\t5\t6\t7\t8\t9\t10...")) {
System.out.println(txts2[k]);
}
}
}
}
// s = s.replaceAll("(\\r|\\n)", "") + "\"";
// System.out.println(s);
// outputPW.println(s);
// for (int k = 1; k < txts2.length; k++) {
// String s2;
// s2 = "\"http://www.gov.scot/seag/details.aspx?id=" + txts2[k].replaceAll("\t", "\",\"");
// //s2 = s2.replaceAll("(\\r|\\n)", "") + "\"";
// System.out.println(s2);
// outputPW.println(s2);
// }
// System.out.println(txts[j]);
// outputPW.println(txts[j]);
}
outputPW.flush();
}
}
|
The U.S. Department of Education moved Tuesday to cut off access to federal financial aid for Globe University and the Minnesota School of Business, an action that could force the troubled chain of for-profit colleges to close.
Letters from the federal education department to Jeffrey Myhre, president of the Woodbury-based colleges, cited a September court ruling that the schools defrauded students enrolled in criminal justice programs as reason to not recertify the schools for the federal aid programs. The letters also said the schools misled students about whether credits they earned could be transferred to other institutions.
Globe and the Minnesota School of Business will no longer be able to participate in the federal student loan program after Dec. 31, the letters said. The school is able to appeal the ruling by offering evidence to refute the department’s findings.
Losing access to student loans could have serious financial consequences for the schools, where most students rely on financial aid and the majority receive federal loans and grants. Similar actions led to the closure of ITT Technical Institute and the sale of the Corinthian chain of colleges.
“This is a sad day for two long-standing private institutions,” Myhre said in a statement noting both colleges were founded in the late 19th century. “Today’s decision continues the destructive actions taken by Minnesota Attorney General Lori Swanson and the Obama Administration against career-focused institutions.”
Myhre added that the court found only a fraction of the colleges’ students were “unintentionally misled” and that the criminal justice program was ended in 2014.
“It’s unfortunate that the Attorney General and the Department of Education decided to sanction the schools in their entirety,” Myhre said. “Instead of helping students in one program, their actions will eliminate options and tarnish the degrees of thousands of graduates.”
Related Articles October 11, 2016 Globe, Minnesota School of Business ordered to stop enrolling students
September 23, 2016 Globe U, Minnesota School of Business students could get refund under state plan
September 8, 2016 Fraud ruling threatens Globe U, Minnesota School of Business with closure The move to deny access to federal student loans is the latest in a string of trouble for the two colleges.
Swanson filed a lawsuit against the schools in 2014 alleging fraud and other misconduct after hundreds of students filed complaints with her office. In September, a Hennepin County District Court judge found the schools defrauded students in its criminal justice program by leading them to believe the program would help them become police or probation officers.
Shortly after September’s fraud ruling, the Minnesota Office of Higher Education said it was revoking the schools’ authority to operate in Minnesota. The federal education department has also restricted the schools’ ability to enroll new students.
The schools are also in need of a new oversight agency after the Accrediting Council for Independent Colleges and Schools, or ACICS, asked school officials to make a case for keeping the schools open. The U.S. Department of Education is also in the process of revoking ACICS’ accrediting powers.
Federal data from 2015 show the schools had 19 campuses in Minnesota, Wisconsin and South Dakota that enrolled more than 4,500 students. After the fraud trial began in April, the schools said they were closing several Minnesota campuses and consolidating others.
About 1,700 Minnesotans were enrolled in the schools as of September, state officials said.
|
<reponame>markdoliner/thrift-typescript<filename>src/main/render/thrift-server/union/create.ts
import * as ts from 'typescript'
import { FieldDefinition, UnionDefinition } from '@creditkarma/thrift-parser'
import { COMMON_IDENTIFIERS } from '../identifiers'
import { thriftTypeForFieldType } from '../types'
import { createFunctionParameter } from '../utils'
import { createEqualsCheck, throwProtocolException } from '../utils'
import { IRenderState } from '../../../types'
import { createSkipBlock, readValueForFieldType } from '../struct/decode'
import { createReturnForFields, endReadForField } from './decode'
import { strictNameForStruct } from '../struct/utils'
import { unionTypeName } from './union-fields'
import {
createFieldAssignment,
createFieldIncrementer,
createFieldValidation,
createReturnVariable,
fieldWithDefault,
incrementFieldsSet,
throwBlockForFieldValidation,
} from './utils'
import { renderValue } from '../../apache/values'
function createArgsParameter(
node: UnionDefinition,
state: IRenderState,
): ts.ParameterDeclaration {
return createFunctionParameter(
'args', // param name
ts.createTypeReferenceNode(
ts.createIdentifier(unionTypeName(node.name.value, state, false)),
undefined,
),
)
}
export function createCreateMethod(
node: UnionDefinition,
state: IRenderState,
): ts.MethodDeclaration {
const inputParameter: ts.ParameterDeclaration = createArgsParameter(
node,
state,
)
const returnVariable: ts.VariableStatement = createReturnVariable()
const fieldsSet: ts.VariableStatement = createFieldIncrementer()
const fieldAssignments: Array<ts.IfStatement> = node.fields.map(
(next: FieldDefinition) => {
return createFieldAssignment(next, state)
},
)
return ts.createMethod(
undefined,
undefined,
undefined,
COMMON_IDENTIFIERS.create,
undefined,
undefined,
[inputParameter],
ts.createTypeReferenceNode(
ts.createIdentifier(strictNameForStruct(node, state)),
undefined,
), // return type
ts.createBlock(
[
fieldsSet,
returnVariable,
...fieldAssignments,
createFieldValidation(thenBlockForFieldValidation(node, state)),
ts.createIf(
ts.createBinary(
COMMON_IDENTIFIERS._returnValue,
ts.SyntaxKind.ExclamationEqualsEqualsToken,
ts.createNull(),
),
ts.createBlock(
[createReturnForFields(node, node.fields, state)],
true,
),
ts.createBlock(
[
throwProtocolException(
'UNKNOWN',
'Unable to read data for TUnion',
),
],
true,
),
),
],
true,
),
)
}
function thenBlockForFieldValidation(
node: UnionDefinition,
state: IRenderState,
): ts.Block {
const defaultField: FieldDefinition | null = fieldWithDefault(node)
if (defaultField !== null) {
return ts.createBlock(
[
ts.createStatement(
ts.createAssignment(
COMMON_IDENTIFIERS._returnValue,
ts.createObjectLiteral([
ts.createPropertyAssignment(
defaultField.name.value,
renderValue(
defaultField.fieldType,
defaultField.defaultValue!,
state,
),
),
]),
),
),
],
true,
)
} else {
return throwBlockForFieldValidation()
}
}
/**
* EXAMPLE
*
* case 1: {
* if (fieldType === Thrift.Type.I32) {
* this.id = input.readI32();
* }
* else {
* input.skip(fieldType);
* }
* break;
* }
*/
export function createCaseForField(
node: UnionDefinition,
field: FieldDefinition,
state: IRenderState,
): ts.CaseClause {
const fieldAlias: ts.Identifier = ts.createUniqueName('value')
const checkType: ts.IfStatement = ts.createIf(
createEqualsCheck(
COMMON_IDENTIFIERS.fieldType,
thriftTypeForFieldType(field.fieldType, state),
),
ts.createBlock(
[
incrementFieldsSet(),
...readValueForFieldType(field.fieldType, fieldAlias, state),
...endReadForField(fieldAlias, field),
],
true,
),
createSkipBlock(),
)
if (field.fieldID !== null) {
return ts.createCaseClause(ts.createLiteral(field.fieldID.value), [
checkType,
ts.createBreak(),
])
} else {
throw new Error(`FieldID on line ${field.loc.start.line} is null`)
}
}
|
The Porsche 964 has become highly sought after in recent years and prices have risen as a result. There are some great examples of this generation of the 911 available if you have the right budget, but there are also some potential money pits around, so it pays to know what to look out for.
When it launched in 1989, the 964 represented one of the biggest advances in Porsche history and the carmaker’s engineers estimated that 85% of it differed from its predecessor, the 911 Classic. With its improved aerodynamics, ABS brakes, integrated bumper, 3.6-litre 247bhp engine, redesigned suspension, automatic electric spoiler and air conditioning system that actually worked, it was not hard for drivers to spot where the key changes had been made.
At first, the Porsche 964 was only available as the all-wheel drive Carrera 4, but a much lighter rear-wheel drive Carrera 2 arrived in 1990 – and the C2 soon became the biggest seller. Targa and Cabriolet versions of the C2 and C4 followed, along with 3.3 and 3.6 Turbo models and the highly desirable RS and rare Speedster.
Porsche 964 values have risen in recent years.
All models are great to drive and boast classic styling, which partly explains why demand is growing and values are going up. A C2 or C4 will cost you somewhere between £25,000 and £60,000, but you are likely to need a six-figure budget for a good Turbo or any RS.
The good news is that as even the latest 964s are more than 20 years old (production stopped in 1994), any car that is still in working order is likely to be fundamentally sound. However, there are some potentially expensive problems that are known to occur on the 964, so it is a good idea to organise a Pre Purchase Inspection at a Porsche specialist before handing over a large cheque to the seller.
Mileage and service history
Try not to worry about the mileage too much. Yes, almost all buyers would prefer a low mileage 964, but you are likely to need a lot of patience and an extremely healthy bank balance to find one. If you are buying the car to drive and enjoy rather than purely as an investment, why fret about it?
Having well over 100,000 miles on the clock is hardly exceptional for a car that is more than 20 years old and, as long as there is plenty of evidence that it has been properly maintained, it shouldn’t be a major concern. Many high-mileage models will have been very well cared for by Porsche enthusiasts and you may even find that they have had major jobs, such as engine rebuilds, done.
A full service history is something you should look for when buying any used car, but it is particularly important when purchasing a Porsche of this vintage. A history that demonstrates that the 964 has been serviced and repaired exclusively by OPCs and/or reputable independent Porsche specialists would indicate that it has been well looked after throughout its entire life.
Don’t be afraid to ask questions about gaps in the service history, as you will want some kind of reassurance that previous owners didn’t look to cut ownership costs by skipping services or taking the 964 to non-specialist garages. If you have any concerns about the car’s history (or if it is missing completely), arrange for an independent Porsche specialist to undertake a full Pre Purchase Inspection and prepare a condition report before making an offer.
Don’t worry too much about high-mileage Porsche 964s
We usually recommend that the service book is accompanied by invoices for all work undertaken, as this demonstrates that the right parts and fluids have been used. For a car over 20 years old though, an invoice for a wear and tear job carried out in 1997 is probably of little relevance, as the parts will almost certainly have been replaced again since then.
Invoices for work undertaken in the last few years and, in particular, the last service (which will allow you to check whether any advisories have been dealt with) should be sufficient, if the full file isn’t available.
Oil leaks
Any car of this age can be susceptible to oil leaks, so it is well worth having all the likely problem areas checked before buying to get an idea of whether any crucial or costly repairs are imminent. Two areas need particularly close attention.
The early Porsche 964s were infamous for oil leaks from around the cylinder base, in part because the original design did not include a cylinder head gasket. In 1991, Porsche redesigned the cylinder head base and added a gasket in an attempt to solve the problem. The change was largely successful, but it is not unknown for later 964s to suffer leaks here as well.
Another common source of leaks are the pipes between the dry sump oil tank and the engine. Typically the cause is corrosion and the issue can usually be fixed by replacing the pipes.
Dual Mass Flywheel
Perhaps the most notorious issue to have afflicted the Porsche 964 is dual mass flywheel (DMF) failure. Early 964s were fitted with a Freudenberg DMF, which proved to be highly unreliable, and in 1992 Porsche switched to an LUK-manufactured unit that has lasted well.
The telltale sign of DMF failure is heavy vibrations at low revs but, while it is worth checking for, you are unlikely to find a 964 with the problem these days. Most of the problematic Freudenberg units in the early cars will have been replaced by the higher-quality LUK part by now.
Bodywork
Carry out a thorough inspection of the bodywork before agreeing to buy a Porsche 964 and not only for signs of accident damage. While it would be an exaggeration to say that corrosion is a major issue with the cars – in fact, some 964s reached their 20th birthdays without even a hint of rust – it is far from unknown.
The most common areas to find rust are around the wheel arches, under the lights, around the windscreen and window seals and on the door bottoms. It can usually be treated effectively, but you should make sure the repair costs are reflected in the price.
If you are unsure about the extent of a corrosion problem, ask a Porsche specialist to assess it and give you some advice.
Look closely for signs of rust around the windscreen seals when buying a Porsche 964.
Suspension
The suspension in the 964 was among the best available when it was launched in 1989 and helped provide great ride quality (for the time, although not so great when compared to modern family cars). A 964 should still be comfortable enough for everyday use, as long as the standard suspension maintenance has been carried out.
The most common problem affecting the ride is perished front suspension bushes. Replacing them is a simple and relatively inexpensive repair that has a very noticeable effect.
Brakes
The 964 was the first version of the Porsche 911 to come with ABS as standard and while that improved performance, it can mean that repairs are expensive. It is sensible to get a Porsche expert to inspect a 964’s brakes before you agree to buy – and not only to spot signs of imminent big bills.
The brake system varies between the different 964 models and there are a number of issues that can easily be misinterpreted by non-specialists who aren’t familiar with them. To give just one example, a problem with the C4 that appears to require a replacement ABS pump (a four-figure bill) can sometimes be solved by cleaning the accelerometer (a one-hour job).
It is also well worth getting the 964 you are considering buying up on a lift for an assessment of the condition of the pads and discs. As wear and tear items they will have to be replaced from time to time, but if they are nearing the end of their life, you will want it to be reflected in the purchase price.
While checking for wear there, take a look at the callipers. As the callipers are aluminium but fixed to steel, corrosion is common and you should consider how likely they are to need replacement in the near future.
Engine rebuilds
Don’t immediately be put off if a Porsche 964 has had an engine rebuild – it is likely to be a good thing. Many owners noticed a drop off in power and a rise in oil consumption as their 964 headed towards 90,000 miles and a partial engine overhaul was required, complete with new valves and piston rings.
Before parting with your cash for a 964 it is well worth asking an expert to inspect the condition of the engine and assess 1) If it hasn’t had a rebuild, will it need one soon? 2) If it has been rebuilt, was the work done to a high standard? As a rebuild costs thousands, it really pays to know this before agreeing a purchase price.
Distributor vent kit
A design fault on the 964 resulted in the rubber distributor belt perishing due to a build up of ozone within the distributor housing; a failure that could cause serious engine damage. A relatively inexpensive vent kit can be retrofitted to prevent the problem and it is worth having this done if the current owner hasn’t already taken the safety first approach.
All-wheel drive
Not so much a technical problem, as a question of personal preference, but some drivers really dislike the Porsche 964 C4’s all-wheel drive system. It does feel very different to those on later 911s and can suffer badly from understeer, so a long-ish test drive is recommended to check you can live with it.
The Porsche 964 Carrera 4’s all-wheel drive system isn’t to everyone’s taste.
Performance modifications
Many Porsche enthusiasts love to modify their 911s in an attempt to maximise the performance, and 964 owners were no exception. Popular work included remapping the ECU for additional horsepower, exhaust upgrades and lowered suspensions.
Given the age of the 964, there shouldn’t be any issues with mods preventing an MOT being passed, but extensive upgrades may be an indication that the car has been thrashed on the track. Make sure you obtain full details of the work from the seller, as it may affect how the 964 needs to be maintained and you will probably need to inform insurers about them.
Think carefully about whether you can live with the extra power or noise for how you intend to use the car; an exhaust that sounds great while speeding round the track may be less appealing when setting off on the daily commute at 7am. If you need any advice about the modifications, give us a call and we’ll help if we can.
If you are interested in buying a Porsche 964, Revolution Porsche can help you to make sure you pick a good example or, at the very least, ensure you go into the deal with your eyes open about the extent of the work that needs doing. Book the 964 you are considering into our Brighouse workshop for a Pre-Purchase Inspection and our experienced Porsche technicians will undertake a full visual and diagnostic check, which will be used to compile a comprehensive car condition report.
The inspection costs £150+VAT, with a borescope inspection also available for a further £99+VAT. Call Revolution Porsche on 01484 717342 or contact us via the website to find out more or to book a car in.
|
Binding of ATP at the active site of human pancreatic glucokinase nucleotide-induced conformational changes with possible implications for its kinetic cooperativity Glucokinase (GK) is the central player in glucose-stimulated insulin release from pancreatic -cells, and catalytic activation by -d-glucose binding has a key regulatory function. Whereas the mechanism of this activation is well understood, on the basis of crystal structures of human GK, there are no similar structural data on ATP binding to the ligand-free enzyme and how it affects its conformation. Here, we report on a conformational change induced by the binding of adenine nucleotides to human pancreatic GK, as determined by intrinsic tryptophan fluorescence, using the catalytically inactive mutant form T228M to correct for the inner filter effect. Adenosine-5-(,-imido)triphosphate and ATP bind to the wild-type enzyme with apparent 0.5 (ligand concentration at half-maximal effect) values of 0.27 ± 0.02 mm and 0.78 ± 0.14 mm, respectively. The change in protein conformation was further supported by ATP inhibition of the binding of the fluorescent probe 8-anilino-1-naphthalenesulfonate and limited proteolysis by trypsin, and by molecular dynamic simulations. The simulations provide a first insight into the dynamics of the binary complex with ATP, including motion of the flexible surface/active site loop and partial closure of the active site cleft. In the complex, the adenosine moiety is packed between two -helices and stabilized by hydrogen bonds (with Thr228, Thr332, and Ser336) and hydrophobic interactions (with Val412 and Leu415). Combined with enzyme kinetic analyses, our data indicate that the ATP-induced changes in protein conformation may have implications for the kinetic cooperativity of the enzyme. Glucokinase (GK) is the central player in glucose-stimulated insulin release from pancreatic b-cells, and catalytic activation by a-D-glucose binding has a key regulatory function. Whereas the mechanism of this activation is well understood, on the basis of crystal structures of human GK, there are no similar structural data on ATP binding to the ligand-free enzyme and how it affects its conformation. Here, we report on a conformational change induced by the binding of adenine nucleotides to human pancreatic GK, as determined by intrinsic tryptophan fluorescence, using the catalytically inactive mutant form T228M to correct for the inner filter effect. Adenosine-5¢-(b,c-imido)triphosphate and ATP bind to the wild-type enzyme with apparent 0.5 (ligand concentration at half-maximal effect) values of 0.27 ± 0.02 mM and 0.78 ± 0.14 mM, respectively. The change in protein conformation was further supported by ATP inhibition of the binding of the fluorescent probe 8-anilino-1-naphthalenesulfonate and limited proteolysis by trypsin, and by molecular dynamic simulations. The simulations provide a first insight into the dynamics of the binary complex with ATP, including motion of the flexible surface active site loop and partial closure of the active site cleft. In the complex, the adenosine moiety is packed between two a-helices and stabilized by hydrogen bonds (with Thr228, Thr332, and Ser336) and hydrophobic interactions (with Val412 and Leu415). Combined with enzyme kinetic analyses, our data indicate that the ATP-induced changes in protein conformation may have implications for the kinetic cooperativity of the enzyme. of insulin secretion, and is therefore termed the pancreatic b-cell glucose sensor. In humans, more than 600 different mutations in the glucokinase gene (GCK) have been detected in patients suffering from familial, mild fasting hyperglycaemia [GCK maturity onset diabetes of the young (GCK-MODY), GCK permanent neonatal diabetes mellitus, and GCK congenital hyperinsulinism of infancy. Some of the mutations greatly reduce the binding affinity of MgATP 2), which is compatible with a direct interaction of these residues with the nucleotide at the active site. The catalytic mechanism of GK has been the subject of several detailed analyses, and is still a partly unresolved issue. Although some theoretical evidence has been presented in support of a random order mechanism, in which the enzyme interacts with the substrate and cosubstrate in a random fashion, enzyme kinetic studies support an ordered mechanism in which Glc binds to the enzyme before the cosubstrate. The discussion is reminiscent of that related to the catalytic mechanism of yeast hexokinase. For both enzymes, part of the discussion has been related to the question of whether ATP binds to the Glc-free enzyme and the possibility of a nucleotide-triggered change in protein conformation. In this work, we have studied the interaction of ATP and analogues with the human pancreatic enzyme with the aims of: (a) presenting experimental evidence for equilibrium binding to the ligand-free super-open conformation; (b) demonstrating possible conformational changes associated with ATP binding; (c) obtaining insights into the active site contact residues involved in ATP binding; and (d) relating this information to steady-state enzyme kinetic data. To achieve these aims, we used a combined experimental approach including intrinsic tryptophan fluorescence (ITF), extrinsic 8-anilino-1-naphthalenesulfonate (ANS) fluorescence, limited proteolysis, and molecular dynamic (MD) simulations. Additionally, enzyme kinetic analyses were performed to evaluate the functional implications of the structural data. The different approaches provide new insights into the interaction of ATP with hGK, with possible implications for the positive kinetic cooperativity with respect to Glc. Recombinant proteins The average yields of soluble recombinant pancreatic glutathione-S-transferase (GST)-hGK fusion proteins were 4.0 mg L )1 (wild type and T228M) and 2.0 mg L )1 (L146R). As the recombinant wild-type (WT) hGK and WT GST-hGK enzymes demonstrate similar steady-state kinetic parameters and the same apparent K d for Glc in the ITF equilibrium binding assay, the fusion proteins were used in kinetic studies and ITF equilibrium binding analyses with Glc. In the adenine nucleotide (AdN) equilibrium binding studies, we compared nontagged and GST-tagged GK. In all other experiments, only the nontagged proteins were used. Characterization of the T228M mutant reference enzyme The T228M mutant form, causing GCK-MODY in the heterozygous state and GCK permanent neonatal diabetes mellitus in the homozygous state, was selected as a non-ATP-binding reference enzyme on the basis of its previously described kinetic properties. Here, equilibrium binding of Glc, as determined by ITF, demonstrated an increased affinity (K d = 3.1 ± 0.1 mm) in comparison with WT GST-hGK (K d = 4.3 ± 0.1 mm), and a fluorescence enhancement signal response similar to that of the wild type (Table 1). Steady-state kinetic analyses demonstrated a 9000-fold reduced catalytic activity (k cat 7 10 )3 s )1 ) ( Table 1). Thr228 is a highly conserved residue at the active site of the hexokinase family of enzymes, positioned in the phosphate-binding loop and part of a classical ATPbinding motif (phosphate 2 site) in hexokinases and homologous proteins. In the crystal structures of human and yeast hexokinases, the hydroxyl group of this conserved Thr interacts with the a-phosphate of ATP, and a Thr fi Met substitution in hGK is inferred to eliminate this important contact (see the in silico studies below). According to the coordinates of the closed (Glc-bound) conformation of WT hGK , the T228M mutation is predicted to be destabilizing, as measured by the free energy of thermal unfolding (DDG = )4.07 kcalAEmol )1 ) and the free energy of folding (DDG = 0.85 kcalAEmol )1 ). However, the far-UV CD spectrum was very similar, if not identical, to that of WT hGK (Fig. S1), and no significant differences in the apparent T m values (on thermal unfolding) of WT hGK ( Fig. 1) and the mutant protein (data not shown) were observed. Thus, the Thr fi Met substitution has little impact on the protein fold. Equilibrium binding of adenosine-5¢-(b,c-imido) triphosphate (AMP-PNP), ATP and MgATP to the ligand-free enzyme To study binding of AdNs to the ligand-free nontagged enzyme, we first measured the change in ITF at 25°C as a function of the AdN concentration. In contrast to the enhancement of the ITF signal observed with Glc, the ATP analogue AMP-PNP resulted in quenching of the fluorescence (Fig. 2), consistent with a previous report. However, the inner filter effect resulting from nucleotide absorbance at the excitation wavelength (295 nm), which was not considered in that report, made a significant contribution to the quenching. To correct for this effect, a similar titration was performed with the non-ATP-binding mutant T228M and with free Trp ( Fig. 2A,C). Of the two reference titrations, the T228M mutant gave the preferred correction ( Fig. 2A), as the mutant also demonstrated quenching of the ITF at low concentrations (£ 0.1 mm). From the fluorescence difference data (Fig. 2B), an apparent 0.5 (ligand concentration at half-maximal effect) value of 0.27 ± 0.02 mm (25°C) was estimated by nonlinear regression analysis. The net (specific) fluorescence quenching observed for AMP-PNP was modest, but significant , suggesting that one or more of the three Trp residues (Trp99, Trp167, and Trp257) undergo small changes in quantum yield, but without any significant spectral shift. A similar result was obtained with the respective GST-hGK fusion proteins (Fig. 2C,D), with an 0.5 value of 0.16 ± 0.04 mm and D(DF eq F 0 )max 100 = )2.2% ± 0.2%. In the ITF titrations of the wild type and the T228M mutant (control) with increasing concentrations of ATP (Fig. 2E), a net decrease in fluorescence intensity similar to the AMP-PNP response was observed. The differential binding data ( Fig. 2E) were fitted to a hyperbolic binding isotherm by nonlinear regression (r 2 > 0.97), giving a halfmaximal effect ( 0.5 ) at 0.78± 0.14 mm and D(DF eq F 0 ) max 100 = )1.5% ± 0.1%. Similar titrations with MgATP gave comparable maximal quenching of ITF of D(DF eq F 0 ) max 100= )2.2% ± 0.3%. Fig. 1. Thermal refolding-unfolding and aggregation of WT hGK. The experiments were performed as described in Experimental procedures. (A) The thermal refolding-unfolding profile of WT hGK (23 lM) in the absence of Glc was determined by following the change in ellipticity at 222 nm at a constant heating rate of 40°CAEh )1. An apparent transition temperature (T m ) of 42.4 ± 0.2°C was determined from the first derivative of the smoothed denaturation curve. No significant difference in the profile was observed in the presence of Glc (data not shown). The observed optical activity is expressed as the mean residue molar ellipticity ( MR ). (B) The pseudo-absorbance data were obtained at the same time as the CD data in (A), reporting on the biphasic heat-induced increase in absorbance. The regression lines, based on data points in the temperature interval 24-79°C, indicate an inflection point at 42°C and increasing aggregation of the protein above this temperature; above 80°C, the absorbance decreased, probably owing to precipitation of the protein. Thermal refolding and unfolding As previously demonstrated by ITF, ligand-free WT hGK senses temperature shifts from 4 to 39°C directly by a slow (seconds to minutes) conformational change (hysteresis), with a biphasic time course in temperature jump (4-39°C) experiments. The far-UV CD spectroscopy at 222 nm confirmed this conformational change by an apparent change in the secondary structure in the same temperature range (Fig. 1A). At higher temperatures, the enzyme demonstrated relatively low global thermodynamic stability, with an apparent T m of 42.4 ± 0.2°C and increasing aggregation at temperatures 42°C, as measured from the associated high-voltage (pseudo-absorbance) curve obtained at the same time (Fig. 1B). Similarly, the isothermal (25°C) chemical unfolding caused by guanidine chloride also resulted in aggregation of the protein (data not shown). This instability of the protein precluded an estimate of equilibrium thermodynamic parameters, and thus also measurement of the effect of ligands on such conformational equilibria. Effect of ATP and Glc on extrinsic ANS fluorescence and limited proteolysis ANS is an extrinsic fluorophore with affinity for hydrophobic clusters in proteins that are not tightly packed in a fully folded structure or become exposed in partially unfolded structures. The weak fluorescence of ANS was greatly enhanced upon binding to ligand-free WT hGK (Fig. 3A), with a maximum at 480 nm (blue shift), indicative of ANS binding to exposed hydrophobic clusters. As seen from Fig. 3B, both ATP and Glc significantly reduced the ANS fluorescence signal , compatible with a decrease in accessible hydrophobic clusters as compared with the ligand-free enzyme. In our studies on mutant forms of hGK, their susceptibilities to limited proteolysis by trypsin have proved to be a valuable conformational probe (unpublished data). Here, it was demonstrated (Fig. 3C) that the ligand-free WT hGK (at 25°C) is partly stabilized by its association with ATP and Glc (Glc > ATP). Effect of nonhydrolysable ATP analogues on the equilibrium binding of Glc The equilibrium binding of Glc to the ligand-free WT hGK and its binary AdN complexes was determined by its enhancement of the ITF signal (Table 2). In the absence of AdNs, a hyperbolic binding isotherm for Glc was observed, with a K d value of 4.2 ± 0.1 mm at 25°C. Titration with Glc in the presence of Mg-adenosine-5¢-O-(3-thiotriphosphate) (ATPcS) and MgAMP-PNP also gave hyperbolic binding isotherms; however, the apparent affinity for Glc increased (Table 2), i.e. about two-fold with 5 mm MgAMP-PNP (P = 0.002). A similar effect was observed for the GCK-MODY L146R mutant in the presence of 2.5 mm ATPcS; that is, the apparent K d decreased from 19.3 ± 3.8 mm to 14.0 ± 1.4 mm (Fig. 4), and there was a 25% increase in the fluorescence signal response . The mutant demonstrated a 100-fold reduction in k cat and a 40-fold increase in the 0.5 (substrate concentration at half-maximal activity) value for Glc ( Table 1). The positive kinetic cooperativity with respect to Glc was partly lost in the mutant (n H = 1.29 ± 0.04), and in contrast to previous findings, the K m for ATP (0.24 ± 0.04 mm) was only slightly increased. In silico dynamic and conformational effects of ATP binding In the MD simulations, the starting crystal structure (PDB ID 1v4t) of the ligand-free super-open conformation was modified to include the 23 missing residues (Glu157-Asn179) in a surface loop structure (see Experimental procedures). The C a rmsd value for the modelled structure and the crystal structure was 2.3 when the Glu157-Asn179 loop residues were not included. From the computed B-factor values (Figs 5A and S2B), the region that fluctuates the most is Glu157-Asn179, consistent with the observed disorder in the crystal structure. MD simulations of the modelled binary GK-ATP complex revealed that the global rmsd of the structure converged at the end of the 2-ns simulation period (Fig. S2A). The dynamic changes in the active site cleft opening over the 2-ns equilibration period (Fig. 5C), as defined by the residues Lys169-Gly223 ('hinge')-Gly229, suggest partial closure of the interdomain cleft ( 15°). These defining residues were previously used to monitor the opening of the cleft ( 50°) on MD simulations of Glc dissociation from the binary hGK-Glc complex. A molecular motion was further indicated by the dyndom algorithm, with the coordinates obtained for the ligand-free form and the hGK-ATP complex at the end of the simulations (Figs 6B,C and S3; Table S2), also indicating partial closure of the cleft ( 33°) and an apparent domain motion, which were less dramatic than for the Glc-induced conformational transition (Table S2). In the final structure of the binary complex ( Fig. 6A; Table S1), the adenosine moiety is packed between helices 12 and 15 in the L-domain and stabilized by hydrogen bonds (with Thr332 and Ser336 in helix 12) and hydrophobic interactions (with Val412 and Leu415 in helix 15). A conformational change was also indicated by the MD simulations of the modelled ternary hGK-Glc-ATP complex. In the final structure of the simulations, the interactions of the adenosine moiety were similar to those observed in the binary ATP complex, with the a-phosphate and b-phosphate oxygen atoms forming hydrogen bonds with Thr228 and Ser411 in the L-domain (data not shown). For comparison, when the MD simulations were performed with Glc in the super-open conformation (Fig. 5C), no significant change in the interdomain cleft was observed. The substrate was found to be positioned at the active site, as expected, including the interactions with the primary contact residues Asn204 and Asn231 (data not shown). However, no interactions with Thr168 and Lys169 were seen, as the Ser151-Val181 surface loop was not displaced in the direction of Glc, and there was no measurable closure of the active site cleft during the 2-ns MD simulations (Fig. 5C), as observed in the crystal structures of the binary GK-Glc complex. Thus, in this case, the simulation time (2 ns) was too short to demonstrate the large global conformational transition observed by ITF upon Glc binding, which has a millisecond to minute time scale, characteristic of this hysteretic enzyme, and thus out of reach of nanosecondscale MD simulations. Steady-state kinetics The steady-state kinetic properties of WT GST-hGK were determined with Glc as the variable substrate at high or low concentrations of MgATP (Table 3). Positive cooperativity was observed with respect to Glc at 5 mm (saturating) MgATP (n H = 1.95 ± 0.10) (Fig. 7A) with an 0.5 value of 8.2 ± 0.3 mm. However, at 0.05 mm MgATP, the cooperativity was reduced to n H = 1.07 ± 0.07 (Fig. 7B) Table S1. For helix nomenclature, see. (B, C) The domain motion induced by ATP binding to the apoenzyme with partial closure of the active site cleft and a rotation angle of 33°. The coordinates were those obtained for (B) the modelled super-open conformation, including the Glu157-Asn179 loop, and (C) the modelled open conformation with inserted ATP (GK-ATP). The C a rmsd values were 4.01 for the whole protein, 2.09 for the fixed domain (349 residues), and 3.91 for the moving domain (87 residues). The dynamic domains were identified with the DYNDOM program. The C a backbone structures, shown in line presentation, were colour-coded as follows: blue, fixed domain; red, moving domain; and green, connecting residues. For comparison, the corresponding data for the domain motion induced by Glc binding to the apoenzyme are shown in Table S2. **ATP. increased to 14.3 ± 1.7 mm. The fact that the kinetic cooperativity is dependent on the MgATP concentration is consistent with previous data reported for the rat liver isoform. With MgATP as the variable substrate, a hyperbolic curve was obtained at a high Glc concentration (60 mm), with a K m of 0.16 ± 0.01 mm (Table 3; Fig. 7C). However, at a low Glc concentration (0.5 mm), negative cooperativity was observed with respect to MgATP (n H = 0.87 ± 0.06) (Fig. 7D), consistent with a previous report on the rat liver isoform, and the K m was reduced to 0.04 ± 0.003 mm. Interestingly, the L146R mutant, with a severely reduced affinity for Glc (Table 1), demonstrated similar negative kinetic cooperativity with respect to MgATP as the variable substrate (n H = 0.73 ± 0.04). Discussion The bisubstrate reaction catalysed by monomeric GK is mechanistically characterized by diffusion-controlled binding of Glc to thermodynamically favoured ligandfree conformations of the enzyme (Scheme 1), followed by global hysteretic isomerization of the enzyme to a closed conformation. From crystallographic, biophysical and kinetic studies on GK, it is known that both substrate binding and catalysis require substantial conformational changes in the enzyme. Ligand-free hGK is structurally dominated by a super-open conformation, which, in the crystal structure, is locked in an inactive state by electrostatic and hydrophobic interactions between the C-terminal helix (helix 17) and helix 6. Three residues (Asn204, Asn231, and Glu256) in the large domain function as primary contact residues in the binding of Glc. Pre-steady-state analyses of Glc binding to WT hGK have provided evidence that the ligand-free enzyme in solution is in a pre-existing equilibrium between at least two conformers (marked as GK and GK " in Scheme 1), i.e. the super-open conformation ( 80-95%) and an alternative (presumably less open) con-formation ( 5-20%) with a higher affinity for Glc, which adds to the kinetic complexity of this reaction. Recent high-resolution NMR analyses and pre-steady-state Glc binding experiments also suggest that GK is capable of sampling multiple conformational states, both in the absence and the presence of Glc. The global conformational changes triggered by Glc binding have been defined crystallographically. In the closed conformation (marked as GK* in Scheme 1), precise alignment of additional substrate contact residues (notably Thr168 and Lys169 in the flexible surface active site loop) and the subsequent higher affinity for Glc efficiently accelerate the chemical reaction (k 3 ) on binding of the cosubstrate MgATP. The overall binding constant K 1 for Glc and the values for the forward (k 2 ) and reverse (k )2 ) rates of the conformational transition, which probably includes intermediates, have been estimated by stopped-flow fluorescence spectroscopy. In that study, the GK-Glc M GK*-Glc interconversion was found to be slow, with k 2 = 0.45 s )1 and k )2 = 0.28 s )1 (K 2 = 1.6), favouring the forward rate and isomerization, whereas the isomerization was unfavourable with 2-deoxyglucose as the substrate (K 2 = 0.8). Here, we present experimental evidence that ATP binds to the ligand-free form, and that this also results in changes in the protein conformation. ATP binds to the ligand-free open conformation of hGK Previous attempts to demonstrate direct binding of ATP to the ligand-free form of rat GK by ITF Reaction scheme for mammalian glucokinase. spectroscopy and hGK by differential scanning calorimetry were reported to be unsuccessful. The topic was more recently readdressed with a nonhydrolysable ATP analogue (AMP-PNP) and ITF, and relatively large quenching of the fluorescence signal was demonstrated, interpreted as a nucleotideinduced conformational change. However, as no corrections were made for a large inner filter effect, owing to the significant absorbance of the nucleotide at the excitation wavelength (285 nm), we have corrected for this effect here (at k ex = 295 nm) as well as for any effect of nonspecific binding to the enzyme (i.e. not in the active site), with the non-ATP-binding mutant form T228M (Table 1) as a reference enzyme. Our analyses revealed that AMP-PNP and ATP do indeed bind to hGK (Fig. 2) in the ligand-free open conformation, and the MD simulations (Fig. 6) further support this conclusion and also show the residues (including the mutated residue Thr228) directly contacting ATP at the active site of WT hGK. The partial quenching effect of AMP-PNP on the T228M reference enzyme with disrupted ATP binding at the active site ( Fig. 2A,C) suggests a contribution of nonspecific binding of that nucleotide (i.e. not in the active site) in addition to its inner filter effect, as observed for free Trp. The idea that AMP, in contrast to MgADP ) MgATP 2), can bind to more than one site has been suggested for the rat liver isoform. Binding of ATP to ligand-free hGK results in a conformational change High-resolution NMR analyses have revealed that GK is an intrinsically mobile enzyme whose structure and dynamics are modulated by temperature and ligand binding. Here, we provide the first experimental evidence of ATP-dependent structural changes in WT hGK. Specifically, our ITF quenching (Fig. 2) and MD simulations (Figs 5 and 6) indicate a significant conformational change upon ATP binding, including motion of the flexible surface active site loop and partial closure of the active site cleft (Figs 5C, 6B,C and S3). A change in conformation is further supported by the significant protective effect of ATP on binding of the extrinsic fluorescence probe ANS (Fig. 3A,B) and on the limited proteolysis by trypsin (Fig. 3C). In both assay systems, Glc showed more potent inhibition than ATP, which may be related to the larger conformational change and more effective closure of Table 3. Kinetic cooperativity with respect to Glc In general, the mechanism for cooperativity observed in enzyme kinetic studies represents an experimental challenge. For monomeric GK, several models have been considered to explain the positive kinetic cooperativity with respect to Glc, including: (a) a random order mechanism of substrate (Glc and MgATP 2) ) addition ; and (b) a sequential order mechanism, in which the binding of Glc as the first substrate induces a slow, concentration-dependent conformational transition characteristic of a hysteretic enzyme (Scheme 1). The Glc-induced multiphasic ITF enhancement (millisecond to minute time scale) of WT and mutant forms of GK strongly favours the second mechanism, and support the idea that the cooperativity can be explained by an equilibrium between conformational states with different affinities for Glc. However, little experimental effort has been made to include or exclude any contribution of (Mg)ATP binding to the kinetic cooperativity. The ligand-free and the binary GK-Glc complex are dynamic entities, and binding of (Mg)ATP may shift the equilibrium between different enzyme conformations, as shown for Glc. In this study, the binding of ATP to the ligand-free enzyme was found, by four independent criteria, to trigger conformational changes, including partial closure of the active site cleft (Figs 5B, 6B,C and S3). Moreover, previous and present (Table 1) steady-state kinetic analyses are also compatible with conformational control of GK catalytic activity by the binding of (Mg)ATP, with possible implications for kinetic cooperativity with respect to Glc. Thus, the cooperativity is largely reduced (n H = 1.07 ± 0.07) at low concentrations of MgATP ( Fig. 7B; Table 1) and when MgATP is replaced by MgITP, a poor phosphoryl donor ATP analogue. In most previous steady-state kinetic analyses, rat GK (liver) was observed to be noncooperative with respect to (Mg)ATP. However, Neet et al. reported negative kinetic cooperativity (n H = 0.84) when measurements were made in the presence of 30% glycerol at a low Glc concentration (0.5 mm), and this was also observed here for the recombinant pancreatic hGK in the absence of glycerol (n H = 0.87 ± 0.06). However, when hGK activity was measured at high glucose concentrations, the Hill coefficient for (Mg)ATP approached 1.0 (Fig. 7C), as expected from studies on rat liver GK. Negative cooperativity (n H = 0.73 ± 0.04) was also observed for the GCK-MODY mutant L146R, which has severely reduced affinity for Glc (Table 1). Moreover, our studies on this mutant revealed that the analogue ATPcS (at 2.5 mm) increases the mutant's low equilibrium binding affinity for Glc (K d decreases from 19.3 ± 3.8 mm to 14.0 ± 1.4 mm), as well as the Glc-induced fluorescence enhancement (by 25%) (Fig. 4). These effects may be related to partial catalytic activation following (Mg)ATP binding at physiological concentrations of Glc. Similar or possibly larger effects of ATP in promoting a catalytically competent state may occur in other mutations associated with GCK-MODY. Conclusions Using biochemical and biophysical methods, we have obtained experimental evidence in support of binding of ATP to the ligand-free hGK, resulting in a change of protein conformation. The MD simulations indicate that the binding triggers molecular motion of the flexible surface active site loop and partial closure of the interdomain active site cleft. The modelled structure of the hGK-ATP binary complex shows the residue contacts involved in ATP binding at the active site. Our findings further support conformational regulation of GK by ATP binding, with possible implications for kinetic cooperativity with respect to Glc. Further mutational studies, notably of GCK-MODY-associated mutations, may contribute to a better understanding of the mechanistic and functional implications of the multiple conformational equilibria and the conformational transitions induced by both Glc and (Mg)ATP, with possible future clinical implications. Materials The oligonucleotide primers used for site-directed mutagenesis were from Invitrogen (Carlsbad, CA, USA). The QuickChange XL Site-directed Mutagenesis Kit was from Stratagene (La Jolla, CA, USA). Glutathione Sepharose 4B was from Amersham Biosciences (GE Healthcare Europe GMBH, Oslo, Norway). Glc was from Calbiochem (San Diego, CA, USA). Magnesium chloride, magnesium acetate, guanidine hydrochloride, trypsin (bovine pancreas), trypsin inhibitor (soybean), pyruvate kinase (rabbit muscle), phospho(enol)pyruvate, ATP, ANS and AMP-PNP were from Sigma-Aldrich (St Louis, MO, USA). ATPcS was obtained from Roche Diagnostics Corporation (Indianapolis, IN, USA). All chemicals and buffers used for fluorescence measurements were of the highest analytical grade. Site-directed mutagenesis The mutations T228M and L146R were introduced into the cDNA of the pancreatic (isoform 1) WT hGK with the QuikChange XL Site-directed Mutagenesis Kit. The pGEX-3X vector (kindly provided by F. M. Matschinsky, University of Pennsylvania, PA, USA), containing a protease factor Xa cleavage site, was used as the template. The following specific oligonucleotide primers were used for mutagenesis (mutated nucleotides are underlined): T228M forward, 5¢-GC ATG ATC GTG GGC ATG GGC TG C AAT GCC TGC 3¢; T228 reverse, 5¢-GCA GGC ATT GCA GCC CAT GCC CAC GAT CAT GC-3¢; L146R forward, 5¢-CAC AAG AAG CTG CCC CGG GGC TTC AC C TTC TCC-3¢; and L146R reverse, 5¢-GGA GAA GGT GAA GCC CCG GGG CAG CTT CTT GTG-3¢. Mutations were confirmed by DNA sequencing. Expression and purification of hGK The WT and mutant recombinant proteins were generated and expressed in the form of GST fusion proteins in Escherichia coli BL21 cells, as previously described. For the CD and guanidine hydrochloride unfolding experiments, the WT hGK was isolated by removing the GST fusion protein as previously described. Purified protein was stored in liquid nitrogen in the absence of glucose (10 mm glutathione, 50 mm Tris HCl, pH 8.0). The protein concentration was determined with the following absorption coefficients: A 280 nm (1 mgAEmL )1 AEcm )1 ) = 1.05 (fusion protein); and A 280 nm = 0.65 (isolated protein). Steady-state kinetics The catalytic activity of GST-hGK was measured spectrophotometrically (A 340 nm ) at 37°C by an NAD + -coupled assay with glucose-6-phosphate dehydrogenase, as previously described. Kinetic studies were performed with 10-12 dilutions of Glc or ATP. The protocol with Glc as the variable substrate was carried out with 5 mm ATP (2.5 mm excess of Mg 2+ ), whereas in the assay with MgATP as variable substrate (2.5 mm excess of Mg 2+ ), saturating amounts of Glc were used. In the case of the severely inactivating mutation T228M, an ATP concentration of 10 mm was used. For determination of Hill coefficients of WT hGK, assays were performed with 12 different Glc concentrations (range: 0-60 mm) or with 11 or 12 concentrations of MgATP (range: 0-3 mm). In the assays with a low ATP concentration, an ATP-regenerating system was used, including 2 mm phospho(enol)pyruvate and 10 U of pyruvate kinase, to ensure a constant ATP level. Steady-state kinetic parameters were calculated by nonlinear regression analyses with the Hill and Michaelis-Menten equations. The reaction rates were measured from the linear part of the initial time-course. GST-hGK fluorescence measurements ITF measurements were performed on a Perkin-Elmer LS-50B spectrometer (1-cm pathlength) at 25°C in a buffer containing 20 mm Hepes, 100 mm NaCl, and 1 mm dithiothreitol (pH 7.0), and a protein concentration of 0.03 mgAEmL )1 (a concentration of 0.04 mgAEmL )1 was used for the mutant L146R GST-hGK). ATP titration experiments were performed in the same buffer containing 1 mm EDTA to complex trace amounts of Mg 2+. The excitation and emission wavelengths used were 295 nm and 340 nm, respectively. Steady-state emission spectra were recorded from 305 nm to 500 nm, and slit widths for excitation and emission were set at 3 nm and 7 nm, respectively. All spectra represent an average of four scans. The binding isotherms and the apparent equilibrium dissociation constants (K d for Glc and 0.5 for ATP) were determined by titration experiments; small aliquots of concentrated ligand (Glc (Mg)ATP AMP-PNP) were successively added to the enzyme solution every time that equilibrium was achieved after the previous addition (150-200 s). The change in intrinsic fluorescence intensity at k max (340 nm) was recorded as a function of the concentration of added ligand, with slit widths for excitation and emission set at 4 nm and 7 nm, respectively. The concentrations used were 0-60 mm Glc, 0-5 mm (Mg)ATP, and 0-450 lm AMP-PNP. To correct for the inner filter effect, caused by nucleotide absorbance at the excitation wavelength, the mutant T228M hGK, which is unable to bind ATP at the active site, was used as a reference enzyme. The specific WT hGK fluorescence response to added nucleotide was determined by subtracting the mutant T228M fluorescence response (inner filter effect) to added nucleotide. Titrations in the presence of free Trp (at a concentration giving the same F 0 value as the enzyme) were performed as an additional control. The fluorescence intensity was adjusted for dilutions of protein, and baseline corrections were obtained with buffer without protein. Linear and nonlinear regression analyses of the data were performed as described previously, with sigmaplot technical graphing software (Systat Software, San Jose, CA, USA). ANS fluorescence measurements Binding of ANS was performed at 38°C on a Perkin-Elmer LS50B spectrometer (1-cm pathlength), with an excitation wavelength of 385 nm and excitation emission slit widths of 6 nm. The cuvette, containing 60 lm ANS in 20 mm Hepes, 100 mm NaCl, and 1 mm dithiothreitol (pH 7.0), was pre-equilibrated to 38°C before the reaction was started by the addition of hGK (0.75 lm). Five minutes later, the stable fluorescence emission spectra were recorded (400-600 nm). All spectra represent an average of four scans. When the effect of Glc (30 mm) or ATP (2 mm) on ANS binding was investigated, the ligand was added to the buffer in the cuvette and pre-equilibrated at the appropriate temperature before addition of enzyme. Prior to addition, the enzyme was preincubated for 7 min in the presence of the same concentration of ligand. CD spectroscopy Far-UV CD spectra (185-260 nm, light path 1 mm) were recorded at 20°C on a Jasco J-810 spectropolarimeter. The isolated WT and T228M proteins were diluted in 20 mm sodium phosphate buffer (pH 7.2) with 0.7 mm dithiothreitol to a final concentration of 23 lm. The proteins were analysed in the absence and presence of 40 mm Glc. The spectra obtained represent an average of four scans (scan rate of 50 nmAEmin )1 ), all background-corrected and smoothed. Secondary structure analyses were performed with the CD Neural Network algorithm. Thermal unfolding (20-90°C) was determined by following the change in ellipticity at 222 nm at a constant heating rate of 40°CAEh )1. The midpoint of the transition (T m ) was determined from the first derivative of the smoothed denaturation curve. The associated high-voltage (pseudoabsorbance) increase was recorded at the same time as the CD data; this was found to be important for monitoring the quality and validity of the data (Fig. 1). Limited proteolysis with trypsin WT GST-hGK was cleaved with factor Xa for 2 h at 4°C, and the rate of limited proteolysis by trypsin was subsequently measured at 25°C in a 100-lL reaction mixture containing 20 mm Hepes, 50 mm NaCl, and 2 mm dithiothreitol (pH 7.0), at a final GST-hGK concentration of 0.5 lgAElL )1 and a GST-hGK trypsin ratio of 400 : 1 (by mass). The effect of preincubation with the substrates Glc (40 mm) or MgATP (2 mm ATP 4 mm MgAc) on the extent of proteolysis of WT hGK was studied. At timed intervals (0, 5, 10, 20 and 30 min), aliquots of 15 lL were taken from the proteolytic reaction, quenched with 14 lL of SDS sample buffer containing soybean trypsin inhibitor , heated for 15 min at 56°C, and subjected to 10% SDS PAGE analyses. Bands were visualized by Coomassie Blue staining, and the band corresponding to full-length hGK was quantified with quantity one 1-d analysis software from Bio-Rad (Hercules, CA, USA). The data were fitted by nonlinear regression analysis with sigmaplot technical graphing software. Modelling of the hGK apoenzyme in the super-open conformation The initial coordinates of the hGK apoenzyme were taken from the X-ray crystal structure solved at 3.4 resolution (PDB ID 1v4t). As the coordinates of a highly flexible loop structure, comprising residues Glu157-Asn179, were not fully resolved, we refined this crystal structure computationally. Initial coordinates for the 23 missing amino acids were taken from the structure of the binary glucose-hGK complex (PDB ID 1v4s) . The dihedral angle of the peptide bond of Gly170 was adjusted so that the terminal amino acids were in an optimal position for filling the gap in the apoenzyme. Insertion of the missing residues was followed by energy minimization and 3-ns MD simulation (allowing only the inserted residues to move). The first 2 ns of simulation were performed in an implicit water environment (generalized Born model) to allow fast relaxation of the inserted peptide (avoiding friction with explicit water molecules). The resulting model was then solvated in explicit water in a periodic box, and simulated for another nanosecond to further relax the model. Structure modelling and MD simulations The binary hGK-Glc complex (PDB ID 1v4s) was structurally aligned with the modelled structure of the complete hGK apoenzyme by applying the combinatorial extension method as implemented in the ce software. Coordinates for glucose were extracted from the binary complex, and saved together with the hGK apoenzyme coordinates to construct an initial model of glucose bound to the super-open conformation. Furthermore, the coordinates of human hexokinase type I in complex with AMP-PNP (PDB ID 1qha) were aligned with our model to build the initial model for ATPbound super-open hGK, and with the coordinates of the binary complex with Glc (PDB ID 1v4s) to generate starting coordinates for the ternary complex. These procedures provided us with the following four structural models: Coordinates for all four models were relaxed by MD simulation in explicit water. The changes in rmsd values during the 2-ns MD simulations, relative to the starting structures, are given in Fig. S2A. Mg was not included in the initial simulation of the ternary complex. Software and hardware MD simulations were performed with amber10 software. The four models were all simulated in a truncated octahedral periodic box with TIP3P water, keeping bonds involving hydrogen atoms fixed, allowing a 2-fs time step between calculations of forces acting on the atoms. The temperature was increased from 0 K to 300 K under constant volume during the first 20 ps of the simulation, keeping the protein coordinates fixed with weak restraints. The systems were further equilibrated at 300 K for 200 ps before restraints were removed, and the models were allowed to relax for 2 ns under constant pressure and temperature. Coordinates were saved every 10th picosecond from the 2-ns simulations, and trajectories were analysed with the ambertools suite of programs (http://ambermd.org/#AmberTools). All simulations were performed on an HP BL 460c Linux cluster equipped with Xeon 2.66-GHz quad-core processors. Each job was distributed over 32 CPUs, and the average computation time was 11.5 hAEns )1. By use of the crystal structure of the super-open (PDB ID 1v4t) and the closed (Glc and GKA-bound) (PDB ID 1v4s) forms, two structure-based methods were used for the estimation of the free energy of thermal unfolding and the folding free energy of hGK mutants. The dyndom program was used to determine dynamic domains and connecting residues involved in hinge bending motions on binding of Glc and ATP to the superopen conformation of hGK. Structural images were generated with pymol, version 1.0. icm-pro was used to analyse the resulting complexes after MD simulations and to calculate the contact area of residues interacting with Glc and ATP presented in Table S1. Supporting information The following supplementary material is available: Fig. S1. Far-UV CD spectra of WT and T228M hGK. Table S1. Contact area in percentage of exposed area for residues interacting with Glc and ATP in the binary complex. Table S2. Domain motions in the conformational transitions induced by Glc and ATP binding to the apoenzyme. This supplementary material can be found in the online version of this article. Please note: As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer-reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.
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1. Field of the Invention
This invention relates generally to rod rolling mills, and is concerned in particular with an improvement in the laying heads used to form the rods exiting from such mills into helical formations of so called "rings".
2. Description of the Prior Art
Referring initially to FIGS. 1 and 2, the typical delivery end of a rod mill is depicted schematically as including the last roll stand of a finishing block 10, several water boxes 12, 14, a pinch roll unit 16, a laying head 18, a cooling conveyor 20 and a reforming tub 22. The finished rod exits from finishing block 10 at an elevated temperature in the range of 650.degree. to 950.degree. C. The rod is quenched in the water boxes 12, 14 before passing through the pinch roll unit 16 into the laying head 18. The laying head forms the product into a helical formation of rings 24 which are received on and transported along the length of the conveyor 20 towards the reforming tub 22. While on the conveyor, the rings are arranged in a Spencerian formation and subjected to various heat treatments, e.g., controlled cooling at selected rates to achieve selected metallurgical properties. The rings drop from the delivery end of the conveyor into the reforming tub 22 where they are gathered around a vertical mandrel 26 into upstanding cylindrical coils. Other devices (not shown) remove the coils from the tub for transport to other locations.
It is important to maintain a uniform ring pattern on the conveyor 20, with the diameters of the rings being such that they will drop smoothly into the reforming tub without being caught up on either the outer tub circumference or the central mandrel 26. Either of such occurrences will foul the equipment, necessitating a costly interruption in production.
While a segment of the rod is being rolled in the mill and another segment of the rod is passing through the laying head where it is being formed into rings that are being deposited on the conveyor, operating conditions remain substantially steady. Thus, a uniform ring pattern can be maintained by synchronizing the operating speed of the laying head with the speed at which the rod is being delivered from the mill.
When the tail end of the rod leaves the mill, the pinch roll unit 16 comes into play and serves to continue stabilizing operating conditions. Thus, when smaller diameter products on the order of 5.5 mm are being rolled at higher speeds in the range of 100 m/sec, the pinch roll unit will act as a brake resisting the tendency of the product to speed up after the tail end drops out of the finishing block. By the same token, when larger diameter products on the order of 12-20 mm are being rolled at slower speeds ranging from 11 to 30 m/sec, the pinch roll unit will serve to continue propelling the product through the laying head after the tail end drops out of the finishing block.
A problem arises, however, when the tail end of the product leaves the pinch roll unit 16. The distance "d" between the pinch roll unit and the delivery end of the laying head 18 is typically about 4 meters, which is equal to or slightly greater than the circumference of one ring being deposited on the conveyor. Under high speed operating conditions, when the tail end clears the pinch roll unit, that relatively short product length tends to speed up, causing buckling and/or an increase in the diameter of the last ring. This in turn can hinder passage of the last ring downwardly into the reforming tub.
A related although somewhat different problem can be experienced with the front end of the product as it leaves the laying head and before it contacts the conveyor. During this brief interval, conditions are again unsteady, and consequently the shape of the lead ring may be deformed or hooked. This can result in the lead end becoming snarled on the reforming tub's mandrel 26.
Attempts have been made at resolving the above-described problems by varying the operating speed of the laying head to suit changing operating conditions. However, at mill delivery speeds of 100 m/sec. and higher, laying head inertia is difficult if not impossible to overcome during the narrow time frame within which front and tail ends are travelling in an unsteady state.
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# pragma once
# include "AMI_stlconfig.h"
# include "AMI_stddef.h"
# include "../AMI_functional.hpp"
# include "AMI_iterator.h"
__ASTL_NAMESPACE_START
template <class random_iterator,
class _cmp = AMI_std::less<typename __iterator_traits<random_iterator>::value_type>>
inline void push_heap(random_iterator begin, random_iterator end) {
return __push_heap(begin, end, end - begin, *begin, _cmp());
}
template <class random_iterator, class _cmp, class distance, class value_type>
inline void __push_heap(random_iterator begin, random_iterator end, distance, value_type, _cmp) {
return __percolate_up(begin, distance((end - begin) - 1), *(end - 1), _cmp());
}
template <class random_iterator, class _cmp, class distance, class value_type>
inline void __percolate_up(random_iterator begin, distance insert_loca,
value_type insert_value, _cmp) {
auto father_index = [](distance loca) { return (loca - 1) / 2; };
_cmp compare;
distance current = insert_loca;
for (current = insert_loca; current > 0; current = father_index(current)) {
if (compare(*(begin + father_index(current)), insert_value)) break;
*(begin + current) = *(begin + father_index(current));
}
*(begin + current) = insert_value;
}
template <class random_iterator,
class _cmp = AMI_std::less<typename __iterator_traits<random_iterator>::value_type>>
inline void pop_heap(random_iterator begin, random_iterator end) {
return __pop_heap(begin, end, end - begin, *begin, _cmp());
}
template <class random_iterator, class _cmp, class distance, class value_type>
inline void __pop_heap(random_iterator begin, random_iterator end, distance, value_type, _cmp) {
return __percolate_down(begin, distance((end - begin) - 1), *(begin), _cmp());
}
template <class random_iterator, class _cmp, class distance, class value_type>
inline void __percolate_down(random_iterator begin, distance end_loca,
value_type root_value, _cmp) {
_cmp compare;
auto left_child = [](distance root) { return (root + 1) * 2 - 1; };
auto right_child = [](distance root) { return (root + 1) * 2; };
distance current = 0;
while (1) {
if (left_child(current) >= end_loca) break;
if (right_child(current) >= end_loca) {
if (!compare(*(begin + left_child(current)), *(begin + end_loca))) break;
*(begin + current) = *(begin + left_child(current));
current = right_child(current);
} else {
if (compare(*(begin + left_child(current)), *(begin + right_child(current)))) {
if (!compare(*(begin + left_child(current)), *(begin + end_loca))) break;
*(begin + current) = *(begin + left_child(current));
current = left_child(current);
} else {
if (!compare(*(begin + right_child(current)), *(begin + end_loca))) break;
*(begin + current) = *(begin + right_child(current));
current = right_child(current);
}
}
}
*(begin + current) = *(begin + end_loca);
*(begin + end_loca) = root_value;
}
template <class random_iterator,
class _cmp = AMI_std::less<typename __iterator_traits<random_iterator>::value_type>>
inline void build_heap(random_iterator begin, random_iterator end) {
random_iterator current = begin + 1;
for (current; current != end; current++) {
push_heap<random_iterator, _cmp>(begin, current);
}
push_heap<random_iterator, _cmp>(begin, end);
}
__ASTL_NAMESPACE_END
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Crewmember interactions during a Mir space station simulation. BACKGROUND Interpersonal problems may negatively affect crews on long-duration space missions. These problems stem from crewmember tension and its displacement to the outside monitoring personnel and from disruptions in crew cohesion and unclear leadership roles. HYPOTHESES We hypothesized that crew tension and dysphoria would transiently increase following stressful events and be greater in the second half of a mission; that cohesion would be less during the second half of a mission; that tension and dysphoria would be displaced to the outside monitoring personnel; and that high levels of leader support and control would produce high levels of cohesion. METHODS We tested these hypotheses during a 135-d Mir space station simulation study in Moscow. At weekly intervals, the three crewmembers completed items from two group climate questionnaires, a mood questionnaire, and a log of stressful events. RESULTS Contrary to expectations, there was significantly (p < 0.05) more total mood disturbance and tension during the first 9 wks than during the subsequent 10 wks of the simulation. Although levels of cohesion remained the same over time, cohesion scores dropped at a significantly greater rate during the last third of the seclusion. There was evidence for the displacement of tension and dysphoria to the outside monitoring personnel. There were significant correlations in the predicted direction between leader support and control and crew cohesion, as well as evidence of status leveling in the mission commander. CONCLUSIONS Crewmember tension, cohesion, and leadership are important issues affecting people working in secluded environments, and they need to be studied further in space.
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Pattern of care of prostate cancer patients across the Martinique: results of a population-based study in the Caribbean Background The French West-Indies rank first for both prostate cancer incidence and mortality rates. Analyzing diagnostic and therapeutic procedures among patients with prostate cancer, using data from a population-based cancer registry, is essential for cancer surveillance and research strategies. Methods This retrospective observational cohort study was based on data from the Martinique Cancer Registry. Records of 452 patients diagnosed with prostate cancer in 2013 were retrieved from the registry. Data extracted were: socio-demographic and clinical characteristics, circumstances of diagnosis, PSA level at diagnosis, Gleason score and risk of disease progression. Stage at diagnosis and patterns of care among prostate cancer patients were analyzed. Results Mean age at diagnosis was 67±8years; 103 (28.5%) were symptomatic at diagnosis. Digital rectal exam was performed in 406 (93.8%). Clinical stage was available in 385 (85.2%); tumours were localized in 322/385 (83.6%). Overall, 17.9% were at low risk, 36.4% at intermediate and 31.9% at high risk; 13.8% were regional/metastatic cancers. Median PSA level at diagnosis was 8.16ng/mL (range 1.45000ng/mL). A total of 373 patients (82.5%) received at least one treatment, while 79 (17.5%) had active surveillance or watchful waiting. Among patients treated with more than one therapeutic strategy, the most frequent combination was external radiotherapy with androgen deprivation (n=102, 22.6%). Conclusions This study provides detailed data regarding the quality of diagnosis and management of patients with prostate cancer in Martinique. Providing data on prostate cancer is essential for the development of high-priority public health measures for the Caribbean. Background In 2012, prostate cancer (PCa) was the second most common cancer in men worldwide, with wide variation in incidence rates, which can be explained by differences in detection practices, treatment availability, lifestyle, environmental and genetic factors. PCa incidence and mortality rates are high in the Caribbean, with an estimated 79.8 and 29.0 cases per 100,000 men respectively in this predominantly black population, and PCa is the leading cause of cancer deaths. In the Caribbean, the French West-Indies rank first for both PCa incidence and mortality rates, which have been suggested to be partially related to the high prevalence of some gene polymorphisms and environmental endocrine disruptors. Higher tumor grade is also reported in African-Caribbean populations and a higher risk of metastatic progression among black men; studies on PCa management are a huge challenge in our region to investigate and explain the observed higher incidence. The Martinique Cancer Registry (MCR) is a population based cancer registry that collects population data in Martinique, an overseas region of France with a population of 386,486 inhabitants. The MCR is one of the only two French population-based cancer registries (PBCR) among the 30 nations and territories of the Caribbean. Between 2010 and 2014, the MCR reported 535 new cases of PCa per year with an incidence rate of 161 per 100,000 men, placing Martinique among the regions with the highest PCa rates in the world. For men diagnosed during this period, 5-year survival was 97.5% with a world-standardized mortality rate of 23.5 per 100,000. In Martinique, there is no screening program for PCa, treatments can vary according to health care providers, patients, organizational resources and facilities. The manner in which these factors interact greatly shape the patient's care plan. The burden of PCa will increase in the future, due to the known association between older age and cancer. The management of elderly prostate cancer patients requires the assessment of overall health status and life expectancy based on the combination of age and comorbidity, to take into account the risk of dying from prostate cancer or another cause, the risks of treatment, and patient preferences. Although national and international guidelines for PCa management exist, large-scale surveys are needed in the Caribbean, in view of the high incidence of this cancer and the predisposition of its populations to PCa. In this regard, accurate data from PBCRs is important to evaluate the burden of disease, and, when complemented with detailed assessment of care and management, can provide important information on the health system organisation. To date, few studies have investigated the clinical stage at diagnosis and the management patterns of PCa in the Caribbean zone based on data from population-based cancer registries [1,. The aim of this study was therefore to analyze diagnostic and therapeutic procedures among patients with PCa and the clinical characteristics according to age, in Martinique in 2013, using data from the MCR. Study population Population-based cancer registries perform continuous and exhaustive recording of all new cancer cases occurring in the population resident in a given area, regardless of where the diagnosis or the treatment takes place. The registries meet a twofold objective, namely description and surveillance of cancer risk, and secondly, research based on the analysis of the data thus collected, or by means of cross-sectional surveys. Observation and follow-up of cancer cohorts are a complement to surveillance of cancer incidence, and make it possible to describe incidence and prognosis in greater detail. This was a population-based study based on data from the MCR. We included data from all patients who were diagnosed with PCa (ICD10: C61) in 2013 in private and public hospitals. Patients with a history of, or recurrence of PCa, or those treated for another cancer were excluded from the study. Data collection Data were recorded in the PBCR database of Martinique in strict conformity with the international standards laid down by the International Agency for Research on Cancer, the French FRANCIM network, and the European Network of Cancer Registries. Quality control of all recorded cases in the MCR was performed in accordance with international guidelines for cancer registries. The following variables were recorded and retrieved for all cases: date of diagnosis, patient's age, symptoms at diagnosis and complementary imaging exams performed. Radiological diagnostic tests and treatment within 24 months of diagnosis were included in the analysis. Radiotherapy, brachytherapy, prostatectomy, androgen deprivation therapy, active surveillance/watchful waiting (no active treatment) received by each patient were retrieved from the database and medical records. Statistical analysis Patient characteristics are described as mean ± standard deviation for quantitative variables, and number (percentage) for qualitative variables. Comparisons were performed using the Student t and Chi square or Fisher's exact tests, as appropriate. Missing data were analysed for each variable. We analyzed socio-demographic characteristics (age at diagnosis and area of residence at the time of diagnosis) and clinical factors such as symptoms at diagnosis, diagnostic procedures, clinical stage at diagnosis and therapeutic management. Patients were classified into three age groups (< 65 years, 65-74 years and ≥ 75 years) to enable analysis of variations in clinical characteristics according to age. All analyses were performed using SAS version 9.2. (SAS Institute Inc., Cary, NC, USA). For all analyses, a p value < 0.05 was considered statistically significant. Demographic and diagnostic characteristics In total, 473 new cases of PCa were diagnosed in Martinique in 2013. We excluded 21 patients because they were multiple tumour cases. Finally, 452 patients were included in the final analysis of this paper. Table 1 presents the baseline characteristics of the study population. Almost 60% (n = 269) were aged 65 years and older (median 67, range 45 to 86 years). In total, 103 patients (28.5%) presented clinical symptoms at diagnosis, mainly urinary or genital (87.4% of those with symptoms). Digital rectal exam (DRE) was performed in 406 patients (93.8%) by urologists or family physicians, and led to suspicion of cancer in 54.6% of cases. Patients in the oldest age group (75+) more often presented with symptoms as compared to younger patients. Analysis of symptoms according to age showed a statistically significant difference in the rate of symptoms across age groups (p = 0.024). Clinical stage at diagnosis was available for analysis in 385 patients (85.2%). The tumors were localized in 322 (83.6%), and locally advanced in 10 patients (2.6%). A total of 53 (13.8%) had node positive and distant metastases at diagnosis. We found that 79.2% of patients with localized disease were at intermediate or high risk (263 / 332). There was an increasing proportion of advanced tumours with increasing age, although this association was not statistically significant. We observed a statistically significant increase in Gleason score and in the risk of disease progression for the oldest patients (≥ 65 years). For example, among those aged 75 years and older, 37.8% were in the highest risk group, as compared to only 30.8% among those younger than 65 years (p = 0.0129). Finally, we observed that PSA level at diagnosis was significantly higher in patients with advanced cancer (p < 0.0001) ( Table 1). Similar findings were observed for Gleason score, i.e., increasing PSA levels at diagnosis were associated with increasing Gleason score ( Fig. 1, Table 2). Treatment characteristics The different treatment combinations according to age groups and risk of disease progression are detailed in Table 3 and Fig. 2. Overall, 373 patients (82.5%) received at least one treatment, while 79 (17.5%) had noninvasive treatment, active surveillance or watchful waiting. Among patients treated with more than one therapeutic strategy, the most frequent combination was external radiotherapy with androgen deprivation (n = 102, 22.6%). There was a significant difference in treatment types according to age and prostate cancer risk group (p < 0.0001), with prostatectomy more frequently performed in patients aged < 75 years with localized cancer and at low or intermediate risk. Brachytherapy was more frequently used in patients aged < 65 years with localized cancer and at low risk. Androgen deprivation therapy was more frequent in high risk patients aged 75 and over, with advanced disease. No patient at low risk received androgen deprivation therapy. The different treatment combinations used in the study population are presented in Fig. 3. For the year 2013, according to the data from our PBCR, it is estimated that less than 5% left Martinique to undergo treatment. The vast majority of patients with a de novo diagnosis were managed and treated by the cancer care teams on site in Martinique. Only 9 patients (2%) travelled to mainland France for therapy; the remaining 98% were managed on site. Overall, 75% of all patients had a prostate MRI, 80.1% had a CT bone scan, and 60.8% had an abdominal CT scan. Prostate MRI was most frequently performed among patients aged < 65 years (p = 0.036) and at low risk (p = 0.017). CT bone scan was most frequently performed in patients at intermediate and high risk (p < 0.0001). Discussion This is the first population-based study performed in the Caribbean on PCa management and treatment patterns in the French West-indies. Most PCa research studies in the Caribbean have evaluated cohorts from single referral institutions or were performed in highly selected patient groups, with limitations regarding the generalization of results, despite statistical quality control. Studies from population-based cancer registries represent a meaningful standard of comparison for the Caribbean zone, and may help to limit selection biases that could affect the results obtained. In our study, three quarters of the patients had localized disease, and overall, a total of 79.2% were at intermediate (42.2%) or high risk (37.0%) suggesting that more than three quarters of patients diagnosed with localized disease may nonetheless have poor prognosis. Regarding the population of older subjects, a total of 59.5% of patients in our study were aged 65 years and over. The main characteristics of these patients were a significantly higher proportion of patients with clinical symptoms (urinary or genital) at diagnosis, a higher risk of recurrence, and an increasing Gleason score with increasing age. Radical prostatectomy was less frequent in this group, which is understandable considering the life expectancy of the patients and the invasive nature of this treatment strategy. Elderly patients aged ≥75 years were observed to be more often diagnosed with higher Gleason score and a higher risk of disease progression (37.8%). We also observed a significant difference in the treatment strategies according to age, stage and risk class. For example, radical prostatectomy was significantly more frequent in patients aged < 75 years, in those with localized cancer, and in those at low or intermediate risk. On the other hand, older patients (75+) were more likely to receive. The choice of therapy should not be based on chronological age only, but also on biological age and overall health status. The stage distribution of PCa patients observed in our study is in line with those observed in mainland France, in Europe, and elsewhere in the Caribbean. One study, covering 11 French counties in 2001, showed that the proportion of localized PCa (T1 or T2) was 86.6%. The rate of use of invasive curative treatment (radical prostatectomy and radiotherapy) was 58.4% for localized cancers. African-Caribbean studies on urological management of PCa in Trinidad and Tobago showed that most cases were found to be high risk (63.1%) followed by intermediate risk (29.6%) and low risk (7.3%). In this latter study, intermediate and high risk groups represented 92% of all cases diagnosed. This suggests that cases in Martinique are diagnosed at the same rate as these other countries, probably partly reflecting similar levels of population awareness, and health system infrastructure. In our study, we observed that the treatments were in line with the recommendations of the French Urology Association, which stipulates the need for appropriate management in light of the risk of recurrence, as well as taking account of comorbidities, stage at diagnosis, age and patient preferences. Patients at low risk of disease progression can benefit from watchful waiting or curative treatment for localized cancers, whereas in patients at intermediate risk, prostatectomy and radiotherapy are recommended as standard. Other studies, based on clinical series in Martinique, have shown a similar distribution of treatment approaches. Other studies have been performed in Guadeloupe in the framework of cohort studies or patient series. Radiotherapy with androgen deprivation in high-risk PCa was studied among 59 consecutive patients and was found to be effective, as observed in other populations. We found a significant difference in the treatment strategies according to age, stage and risk of disease progression. Indeed PCa management should be chosen in light of the risk of recurrence, comorbidity, stage, age and patient's preference. Yet, reports to date suggest that active surveillance should be considered as the appropriate treatment for PCa surveillance for men at low-risk. A study in France showed that watchful waiting was proposed to 17.5% of the patients who were mostly young patients with localized disease and low risk. This choice is also an option in patients at low risk for whom invasive treatments can be reduced to a minimum.. However, careful selection of patients who may be amenable to this strategy is indispensable in order to distinguish those who require active surveillance from those in whom it is possible to forego treatment. In our study, prostate magnetic resonance imaging (MRI) was performed in 75% of patients, while computerized tomography (CT) bone scan was frequently performed in patients at intermediate to high risk, since it is the reference exam for the detection of bone metastasis. The diagnostic performance of MRI depends on the extent of disease and the tumour volume, with good sensitivity for Gleason scores ≥7. In case of a visible lesion, the tumour mapping Unknown achieved with MRI also makes it possible to adapt the treatment strategy. MRI is indeed the recommended imaging technique for assessing the extent of disease in PCa, suggesting that in our population this diagnostic recommendation was generally followed. Unfortunately, Martinique does not yet dispose of a Positron Emission Tomography -Computed Tomography (PET-CT) device. An ongoing project planning to build a PET center in Martinique will be very useful in the future for PCa management in the whole Caribbean area. Nuclear medicine imaging procedures and particularly PET-CT are useful in PCa management strategies. PET-CT using several radio-tracers such as 18F-Choline or recently 68Ga PSMA demonstrated a higher diagnostic efficacy compared with conventional imaging. In particular, 68Ga-PSMA PET/CT seems to be a promising tool for staging of primary prostate cancer and restaging after recurrence. In biochemical relapse, 68Ga-PSMA PET imaging can increase detection of metastatic sites, even at low serum PSA levels. The strength of this study is the fact that this is a population-based study including all patients diagnosed in Martinique in 2013. Only 21 cases were excluded, in order to avoid bias in the analysis linked to the presence of multiple tumours. Among the limitations of our study, it should be noted that we had difficulty accessing data about the stage of disease at the time of diagnosis. Indeed, the cancer registrars may have difficulty extracting the full TNM code from clinical records, if this has not been explicitly recorded by the clinicians or pathologists. Furthermore, regarding access to data concerning the treatment administered or dispensed, treatment administered in-hospital can be identified from data sources already used in the registry (e.g. medical informatics databases from the national social security system). However, in our study, we did not have data regarding treatment performed more than 2 years after diagnosis, and this represents a potential limitation. For patients who travel outside of Martinique for treatment, data on treatment were reported in the medical records. In our study, only 9 patients (2%) travelled to mainland France for therapy; the remaining 98% were managed on site. Due to the fact that the data was derived from the integrated national informatics system for the French social security system, we were able to confirm the rate of patients who travel outside Martinique for treatment. This study adds valuable information on prostate cancer patterns of diagnosis in the Caribbean region. This is especially important considering the high incidence and mortality of the disease in the region. Unlike our study, most PCa research studies in the Caribbean have evaluated cohorts from single referral institutions or were performed in highly selected patient groups, with limitations regarding the generalization of results, despite statistical quality control. In view of the paucity of data from the Caribbean region on this topic, comparisons with other countries from the Caribbean area are limited by the accuracy and quality of data from the countries that are not covered by population-based cancer registries. Our study is descriptive by nature and does not serve to draw causal relations; nonetheless, it can serve as a benchmark for future analyses of overall and net survival according to the diagnostic and therapeutic strategies. In order to better coordinate public health policy, the Regional Health Agencies (Agence Regionale de Sant, ARS) need epidemiological data, with a view to implementing appropriate anti-cancer programmes, with suitable oversight and indicators for evaluating success. Our study will help to meet the needs of the ARS in the French overseas territories, in particular by proposing and describing indicators that are adapted to local and regional needs in terms of healthcare, for use in future public health policies for this region. This work will contribute to identifying public health challenges in our geographical region, especially to assess the adequacy of the healthcare opportunities offered to our populations. Conclusions This study from the Martinique Cancer Registry provides the most comprehensive clinical data regarding the quality of diagnosis and management of patients with PCa in Martinique. The diagnostic and therapeutic management was found to be in line with international recommendations, except for PET CT imaging. These findings will contribute to identifying public health challenges in the management of PCa in this geographic area. Genomic studies on PCa patients could help to better understand clinical factors associated with high incidence of prostate cancer in Martinique and help develop better treatment strategies. The future installation of a PET-CT scan in Martinique will enable better staging of prostate cancers and optimized therapeutic follow-up of this disease. Finally, the results of our study will contribute to improving epidemiological knowledge of cancer patterns in ultraperipheral geographic regions, and help to develop surveillance tools and raise awareness of health states in these populations. Funding Not applicable. Availability of data and materials The individual patient data that support the findings of this study are not publicly released. Data are however available from the corresponding author upon request and with permission of the Martinique Cancer Registry. Authors' contributions CJ was a major contributor in writing the manuscript, made substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data; and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. JVB, SUG, OPL, KF, TA and JM revising it critically for important intellectual content. PE revising it critically for important intellectual content. VVH, LG, MD and JLN made substantial contributions to conception and design; been involved in drafting the manuscript and revising it critically for important intellectual content. All authors read and approved the final manuscript. Ethics approval and consent to participate According to French legislation, cancer data were rendered anonymous prior to analysis with codes. The Martinique cancer registry database was approved by the French National authority for the protection of privacy and personal data (Commission Nationale Informatique et Liberts, CNIL N°987,001). Additional approval from ethical committees was not required since our study did not involve direct patient contact. Consent for publication Consent for publication was not required since our study did not involve direct patient contact. Competing interests The authors declare that they have no competing interests. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Author details 1 CHU Martinique, UF1441 Registre des cancers de la Martinique, Ple de
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Zincated Nanoclay Polymer Composites (ZNCPCs): Synthesis, Characterization, Biodegradation and Controlled Release Behaviour in Soil ABSTRACT Novel zincated nanoclay polymer composites (ZNCPCs) with variable percentage of commercial bentonite and nanobentonite (8%, 10% and 12% of monomer for each case) were synthesized. Polyacrylic acid-Polyacrylamide copolymer was synthesized using N, N-Methylene bisacrylamide as crosslinker and ammonium persulfate as initiator. Clays as well as ZNCPCs were characterized by XRD, SEM, TEM and FTIR. 12% nanoclay containing formulation showed slowest release rate. ZNCPCs containing 8% clay recorded highest Zn content as well as highest equilibrium water absorbency. Biodegradation study revealed that Aspergillus spp was more effective as compared with Trichoderma spp in degradation of ZNCPCs. GRAPHICAL ABSTRACT
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1. Field of the Invention
The present invention relates to a beauty-treatment method in which massaging is done in the direction in which the blood flows or massaging is done while the dermal blood flow is in a stimulated state as opposed to a resting state, allowing short periods of massaging to result in considerable massaging effects and thus in pronounced cosmetic effects related to improved skin color or the like.
The present invention also relates to a cosmetic method for rapidly restoring the moisture components of skin which have been washed away when the skin is washed with a cleanser or a detergent.
2. Description of the Related Art
Beauty soaps and other detergents containing surfactants as their principal components are commonly used to wash the skin.
Detergents designed to remove soil through the action of surfactants, while effective in removing perspiration, dirt, dust and other contaminants from the skin, fail to satisfactorily remove sebum, cosmetics and other types of oily soil. In particular, contemporary foundations and other cosmetics are resistant against perspiration or water and adhere firmly to the skin, and thus cannot be adequately removed by detergents containing surfactants as their principal components. Consequently, cleansers consisting primarily of components for dissolving oily soil, such as liquid paraffin, squalane, and isopropyl myristate, are used to remove such oily soil. In such cases, the skin is washed by so-called double washing, in which oily soil is first washed away with a cleanser, and aqueous soil is then washed off with a detergent containing surfactants as its principal components.
Detergents containing both surfactants and components for dissolving oily soil have been developed recently, making it possible to remove both oily soil such as foundations and common soil such as perspiration and dust in a single washing cycle.
Washing the skin with a cleanser and a detergent, however, tends to remove the sebaceous membrane, intercellular sebum (ceramide), NMF (natural moisturizing factors), and other moisture components of the skin along with the soil.
When the sebaceous membrane is removed as a result of washing, it takes several hours to be regenerated, and no intercellular sebum or NMF is formed until the corneal layer is formed again. The skin meanwhile has lower moisture retention capacity, less defensive capacity against external stimulation, and is less soft.
After the skin has been washed with cleanser or detergents, skincare has thus been undertaken with the use of skincare cosmetics such as skin lotions, emulsions, and cremes in order to enhance the moisture retention capacity of the corneal layer of the skin, enhance dermal blood flow, promote the regeneration of the moist components of the skin, and improve skin softness.
However, despite the use of skincare cosmetics, skin tightness or luster is often lost as a result of changes in physical constitution, environment, or the like, and tightness or luster is not readily restored once it is lost.
Massaging is also sometimes attempted to address this, but massaging is known to cause wrinkling or slackness, depending on the method used. It is thus usually done by experts such as beauticians. Experts are entrusted in the direction in which massaging is done at certain massaging locations, the time needed for massaging, and the sequence of the massaging locations or the like. The massages given by experts are difficult for ordinary people to manage on their own and are hard work, which is rarely done at home.
Massages are generally done not only after the use of cleansers or detergents as described above, but also to promote blood circulation and to obtain the cosmetic effect of providing the skin with tightness or luster. Massaging is known to cause wrinkling or slackness, depending on the method used. It is thus usually done by experts such as beauticians. Experts are entrusted in the direction in which massaging is done at certain massaging locations, the time needed for massaging, and the sequence of the massaging locations or the like. The massages given by experts are difficult for ordinary people to manage on their own and are hard work, which is rarely done at home.
Because massaging promotes blood circulation and thus affords a variety of substantial beneficial effects, however, it would be desirable if ordinary people were able to manage simple massaging on their own.
A first object of the present invention is to provide a novel beauty-treatment method which resolves the aforementioned drawbacks of the prior art, which can be easily managed by ordinary people, and which affords considerable massaging effects as well as pronounced cosmetic effects.
A second object of the present invention is to achieve effective skincare by incorporating massaging that is easily managed by ordinary people in a cosmetic method comprising washing the skin and subsequent skincare.
|
import {NgModule} from '@angular/core';
import {CommonModule} from '@angular/common';
import {WorkoutEntryComponent} from './workout-entry.component';
import {WorkoutsOverviewComponent} from './workouts-overview.component';
import {RouterModule} from '@angular/router';
import {WorkoutsOverviewRoutingModule} from './workouts-overview-routing.module';
@NgModule({
declarations: [
WorkoutEntryComponent,
WorkoutsOverviewComponent
],
imports: [
CommonModule,
RouterModule,
WorkoutsOverviewRoutingModule
]
})
export class WorkoutsOverviewModule {
}
|
PROVO, Utah
New mission presidents and their wives — 127 couples from 24 countries — gathered at the Provo Missionary Training Center June 24 through June 28 for the 2017 Seminar for New Mission Presidents.
The couples, who will serve in 61 different countries, received training and instruction from senior Church leaders.
Sharing the gospel and the love of the Lord is a call all Latter-day Saints receive at baptism, taught President Henry B. Eyring, first counselor in the First Presidency.
“We are in His service, called by Him to help take His gospel, and His love, to Heavenly Father's children,” said President Eyring.
President Dieter F. Uchtdorf, second counselor in the First Presidency, told the new mission presidents, “You will not only have a positive influence on the spreading of the word of God worldwide, but you will also impact the lives of individuals and families,” he said. “You will be remembered for years and generations to come.”
Of the 127 couples entering missionary service, 82 couples came from the United States, 10 from Brazil, and four couples were called from Argentina, from Mexico and from the Philippines. The remaining mission presidents represent 19 additional countries.
The youngest of the 2017 mission president class is 40 years old and the oldest is 66 years old. Of the 127 mission presidents, 35 are converts, with 34 of their wives being converts, and 113 mission presidents served full-time missions in their youth with 19 mission president’s wives having served full-time missions.
More than 50 of the new mission presidents work in business or finance and more than 25 are Church employees; 11 work in the legal profession.
Regarding languages, 94 couples are native English speakers, 18 are native Spanish speakers, 10 are native Portuguese speakers and four are native Tagalog speakers.
Elder Brent H. Nielson, General Authority Seventy and executive director of the Missionary Department, thanked the new mission presidents and their wives — who begin service July 1 — for their courage to “accept a call you did not seek, to an area you did not choose, to be with people you do not know.”
Following are summaries of selected talks given during the seminar:
Women’s Auxiliary presidents: Sister Jean B. Bingham, Sister Bonnie L. Oscarson, and Joy D. Jones Sister
President Henry B. Eyring
President Dieter F. Uchtdorf
President Russell M. Nelson
Elder Dallin H. Oaks opening address
Elder Dallin H. Oaks closing address
Elder M. Russell Ballard
Elder Jeffrey R. Holland
Elder Quentin L. Cook
Elder D. Todd Christofferson
Elder Neil L. Andersen
Elder Ronald A. Rasband and Sister Melanie Rasband
Elder Gary E. Stevenson and Sister Lesa Stevenson
Elder Dale G. Renlund
Bishop W. Christopher Waddell
|
#ifndef __CAMERA_H__
#define __CAMERA_H__
/*******************************************************************************
*
* Graphene::Camera
*
******************************************************************************/
class Graphene::Camera : public Graphene::Object
{
public:
class Targeted;
const enum Graphene::CameraType Type = Graphene::CameraType::Free;
protected:
float m_AspectRatio;
float m_FOV;
fvec3 m_Head = { 0, 1, 0 };
static constexpr fvec3 s_Base = glm::fvec3( 0, 0, 1 );
public:
Camera(const fvec3 position = {0, 0, 2}, const fquat rotation = {0, 0, 0, 0}, const float aspectRatio = 1.25, const float FOV = M_PI_4)
: Object(position, rotation), m_AspectRatio(aspectRatio), m_FOV(FOV) {};
virtual ~Camera() = default;
virtual float aspectRatio() const;
virtual void aspectRatio(const float aspectRatio);
virtual float FOV() const;
virtual void FOV(const float angle);
virtual fmat4 view() const;
virtual fmat4 projection() const;
virtual void orbit(const fvec3 angle);
virtual void rotate(const fvec3 angle);
virtual void dolly(const float offset);
virtual void zoom(const float angle);
};
/*******************************************************************************
*
* Graphene::Camera::Targeted
*
******************************************************************************/
class Graphene::Camera::Targeted : public Graphene::Camera
{
public:
const enum Graphene::CameraType Type = Graphene::CameraType::Targeted;
protected:
fvec3 m_Target;
public:
Targeted(const fvec3 position = {0, 0, 2}, const fvec3 target = {0, 0, 0}, const float aspectRatio = 1.25, const float FOV = M_PI_4);
virtual ~Targeted() = default;
virtual fmat4 view() const override;
virtual void rotation(const fquat rotation) override;
virtual void orbit(const fvec3 angle);
virtual void rotate(const fvec3 angle);
};
#endif // __CAMERA_H__
|
Bovine Herpesvirus 1 Can Infect CD4+ T Lymphocytes and Induce Programmed Cell Death during Acute Infection of Cattle ABSTRACT Acute infection of cattle with bovine herpesvirus 1 (BHV-1) represses cell-mediated immunity, which can lead to secondary bacterial infections. Since BHV-1 can induce apoptosis of cultured lymphocytes, we hypothesized that these virus-host interactions occur in cattle. To test this hypothesis, we analyzed lymph nodes and peripheral blood mononuclear cells (PBMC) after calves were infected with BHV-1. In situ terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling (TUNEL) staining of lymphoid tissues (pharyngeal tonsil, cervical, retropharyngeal, and inguinal) was used to detect apoptotic cells. Calves infected with BHV-1 for 7 days revealed increased apoptotic cells near the corticomedullary junction in lymphoid follicles and in the subcapsular region. Increased frequency of apoptotic cells was also observed in the mucosa-associated lymphoid tissue lining the trachea and turbinate. Immunohistochemistry of consecutive sections from pharyngeal tonsil revealed that CD2+ T lymphocytes were positive for the BHV-1 envelope glycoprotein gD. The location of these CD2+ T lymphocytes in the germinal center suggested that they were CD4+ T cells. Electron microscopy and TUNEL also revealed apoptotic and herpesvirus-infected lymphocytes from this area. Fluorescence-activated cell sorting analyses demonstrated that CD4+ and CD8+ T cells decreased in lymph nodes and PBMC after infection. The decrease in CD4+ T cells correlated with an increase in apoptosis. CD4+ but not CD8+ lymphocytes were infected by BHV-1 as judged by in situ hybridization and PCR, respectively. Immediate-early (bovine ICP0) and early (ribonucleotide reductase) transcripts were detected in PBMC and CD4+ lymphocytes prepared from infected calves. In contrast, a late transcript (glycoprotein C) was not consistently detected suggesting productive infection was not efficient. Taken together, these results indicate that BHV-1 can infect CD4+T cells in cattle, leading to apoptosis and suppression of cell-mediated immunity.
|
WASHINGTON ― Senate Minority Leader Harry Reid (D-Nev.) slammed FBI Director James Comey over his handling of the investigation into Democratic presidential nominee Hillary Clinton, accusing Comey of applying a double standard to Clinton while letting her GOP opponent get away with breaking the law.
Reid, in a Sunday letter to Comey, accused the bureau director of “tarring Secretary Clinton with thin innuendo” when he disclosed to Congress that the FBI had found emails that may or may not impact the bureau’s decision to not charge Clinton for her handling of emails while she was secretary of state.
Comey’s decision to reveal the information with just over a week until Election Day “appears to be a clear intent to aid one political party over another,” Reid wrote.
Reid argued that Comey’s “partisan actions... may have broken the law,” citing the Hatch Act, which, however, requires someone to act with the intent of interfering with an election.
Reid also said Comey’s actions showed “a disturbing double standard for the treatment of sensitive information.” He wrote that he believes the FBI possesses “explosive information about close ties and coordination between Donald Trump, his top advisors, and the Russian government,” although he offered no proof.
|
// Decompiled by Jad v1.5.8g. Copyright 2001 <NAME>.
// Jad home page: http://www.kpdus.com/jad.html
// Decompiler options: packimports(3) braces deadcode fieldsfirst
package net.minecraft.src;
class RedstoneUpdateInfo {
int x;
int y;
int z;
long updateTime;
public RedstoneUpdateInfo(int i, int j, int k, long l) {
x = i;
y = j;
z = k;
updateTime = l;
}
}
|
IoT Device Implementation for Evaluation of Electronics and Software Design Skills The use of specific hardware and the Application Programing Interface (API) are incorporated into a methodology for the study of the Internet of Things (IoT) from the point of view of electronic, computing, communication and data base design. Selected courses in one semester of the curricula of the student career are grouped and create a task force is created to achieve a final project. Topics covered in this semester are: sensors and actuators, microcontrollers architecture, analog electronic design, and social entrepreneurship. The proposed final project implements the knowledge of each course and incorporates some specific elements of the IoT environment. The final project is always supervised by the professors of the semester and by a guest company that collaborates in the observations of details in the implementation of the final product during the design and development time. The guest company designates two or three specific engineers in their area of information technology or logistics to join the students for three specific weeks of the semester. The results observed in the application of this methodology shows a high impact in the understanding of the theory and improvement in the circuit design capabilities from the conceptual description to final product.
|
/**
* @author Igor Antropov
* @version $Id$
* @since 0.1
*/
public class Exit implements UserCommand {
@Override
public String keyWord() {
return "exit";
}
@Override
public void executeAction() {
Chat.setExit(false);
Chat.setOutStreamOn(false);
}
@Override
public String logInfo(final Logger log) {
log.info("Command: EXIT");
log.info("Chat-bot is terminated");
return "Chat-bot is terminated";
}
}
|
#include<cstdio>
#include<algorithm>
#include<vector>
#include<deque>
#include<stack>
#include<queue>
#include<string>
#include<iostream>
//#include<tuple>
#include<utility>
#include<set>
#include<queue>
#include<iomanip>
#include<iterator>
//#include<chrono>
//cout<<setprecision(12)
//fixed
//#include<random>
using namespace std;
typedef long long int llint;
typedef long double lldo;
const llint big=1e15+100000;
const int mod=1e9+7;
const lldo eps=1e-9;
const long double pai=3.141592653589793238462643;
#define mt make_tuple
#define mp make_pair
#define fir first
#define sec second
#define pub push_back
#define puf push_front
#define pob pop_back
#define pof pop_front
#define res resize
#define ins insert
#define era erase
#define dme(in) cout<<in<<endl;return 0
template <class T,class U>void mineq(T& a,U b){if(a>b){a=b;}}
template <class T,class U>void maxeq(T& a,U b){if(a<b){a=b;}}
int main(void){
int i,j,k,n,p;cin>>n>>p;
static llint dp[1001][1001]={0};
vector<int>dag;//0,3,1,2,5,4,6
vector<int>zi(n);
queue<int>kra;kra.push(n-1);
vector<vector<pair<int,pair<int,int> > > > mti(n);//??\??????
for(i=0;i<n;i++){
for(j=0;j<n;j++){dp[i][j]=big;}
}
dp[0][0]=0;
for(i=0;i<p;i++){
int s,e,t1,t2;cin>>s>>e>>t1>>t2;s--;e--;
zi[s]++;
mti[e].pub(mp(s,mp(t1,t1+t2)));
}
while(!kra.empty()){
int ba=kra.front();kra.pop();
dag.pub(ba);
for(i=0;i<mti[ba].size();i++){
zi[mti[ba][i].fir]--;
if(zi[mti[ba][i].fir]==0){kra.push(mti[ba][i].fir);}
}
}
reverse(dag.begin(),dag.end());
for(i=1;i<dag.size();i++){
int no=dag[i];
for(j=0;j<mti[no].size();j++){
int mae=mti[no][j].fir;
mineq(dp[no][no],dp[mae][mae]+mti[no][j].sec.sec);//????????¨?????????2????????????
int ti=mti[no][j].sec.fir;//?????£???????????????
for(k=0;k<i;k++){
mineq(dp[dag[k]][no],dp[dag[k]][mae]+ti);//1??????????????????
mineq(dp[no][dag[k]],dp[dag[k]][mae]+ti);//1??????????????????
}
for(k=0;k<mti[no].size();k++){
int mak=mti[no][k].fir;
if(mae==mak){continue;}
int tk=mti[no][k].sec.fir;//?????£???????????????
mineq(dp[no][no],dp[mae][mak]+ti+tk);
}
}
}
cout<<dp[n-1][n-1]<<endl;
return 0;
}
|
Randomized comparison of bipolar vs unipolar plus bipolar recordings during atrioventricular junction ablation: importance and efficacy of unipolar recording. BACKGROUND No prior studies have clarified the utility and efficacy of unipolar recording for identifying successful sites for atrioventricular junction (AVJ) ablation. METHODS AND RESULTS Thirty-six patients underwent radiofrequency (RF) AVJ ablation for drug-resistant atrial fibrillation (AF) or AF/flutter. AVJ ablation was performed with either bipolar (Bi-group; n=18) or unipolar plus bipolar recording (Uni-group; n=18). In the Uni-group, the primary parameter used to select ablation sites was a QS or rS morphology of the His bundle unipolar recording. There was no significant difference between the 2 groups for the bipolar electrogram characteristics at the successful ablation site. However, in the Uni-group, the procedure time and fluoroscopy duration were shorter (both p<0.05), and the total number of RF energy applications less (p<0.05) than in the Bi-group. In the Uni-group, unipolar His bundle recordings could be assessed in 26 (76%) of 34 RF energy applications: Complete atrioventricular block was obtained at 15 (83%) of 18 sites with QS morphology and in 3 (37%) of 8 sites with rS morphology on the unipolar His bundle recording. CONCLUSIONS AVJ ablation can be achieved more efficiently and with fewer RF energy applications when guided by unipolar recordings than by bipolar recordings alone.
|
First Eagle Investment Management
History
The company formerly known as Arnhold and S. Bleichroeder, traces its heritage to a predecessor firm S. Bleichroeder that was founded in 1803 in Berlin, Germany. In 1937, the firm's activities moved to New York City. First Eagle was established in 1967 at Arnhold and S. Bleichroeder by its chairman, Henry H. Arnhold and its vice president, George Soros. In 1987, the firm established its first U.S. registered mutual fund, the First Eagle Fund of America.
In 1999, First Eagle Investment Management, LLC acquired the majority share of Société Générale Asset Management, a subsidiary of the French bank Société Générale whose investment team managed global value equity strategies. At that time, the Firm became the investment adviser to the First Eagle Funds, including the SocGen International Fund, later named the First Eagle Global Fund. The team managing these strategies became First Eagle's Global Value Team.
Funds
The team manages five mutual funds: First Eagle Global Fund, First Eagle Overseas Fund, First Eagle U.S. Value Fund, First Eagle Gold Fund, and First Eagle Global Income Builder Fund.
First Eagle Investment Management also offers two additional funds: First Eagle High Yield Fund and First Eagle Fund of America.
|
def _setup_default_server_props(self, properties, annotators, output_format):
self.server_start_info = {}
if properties is None or (not isinstance(properties, str) and not isinstance(properties, dict)):
if properties is not None:
print('Warning: properties passed invalid value (not a str or dict), setting properties = {}')
properties = {}
if isinstance(properties, str):
if properties.lower() in CoreNLPClient.PIPELINE_LANGUAGES:
lang_name = properties.lower()
if lang_name in LANGUAGE_SHORTHANDS_TO_FULL:
lang_name = LANGUAGE_SHORTHANDS_TO_FULL[lang_name]
if lang_name in ['en', 'english']:
self.server_props_file['path'] = f'StanfordCoreNLP.properties'
else:
self.server_props_file['path'] = f'StanfordCoreNLP-{lang_name}.properties'
self.server_start_info['preload_annotators'] = LANGUAGE_DEFAULT_ANNOTATORS[lang_name]
print(f"Using Stanford CoreNLP default properties for: {lang_name}. Make sure to have {lang_name} "
f"models jar (available for download here: https://stanfordnlp.github.io/CoreNLP/) in CLASSPATH")
else:
self.server_props_file['path'] = properties
if os.path.isfile(properties):
props_from_file = read_corenlp_props(properties)
self.server_start_info['props'] = props_from_file
self.server_start_info['preload_annotators'] = props_from_file.get('annotators')
else:
print(f"Warning: {properties} does not correspond to a file path.")
print(f"Setting server defaults from: {self.server_props_file['path']}")
self.server_start_info['props_file'] = self.server_props_file['path']
self.server_start_info['server_side'] = True
if annotators is not None:
print(f"Warning: Server defaults being set server side, ignoring annotators={annotators}")
if output_format is not None:
print(f"Warning: Server defaults being set server side, ignoring output_format={output_format}")
else:
client_side_properties = {
'annotators': CoreNLPClient.DEFAULT_ANNOTATORS,
'outputFormat': CoreNLPClient.DEFAULT_OUTPUT_FORMAT,
'serializer': CoreNLPClient.DEFAULT_SERIALIZER
}
client_side_properties.update(properties)
if annotators:
client_side_properties['annotators'] = \
",".join(annotators) if isinstance(annotators, list) else annotators
if output_format is not None and isinstance(output_format, str):
client_side_properties['outputFormat'] = output_format
self.server_props_file['path'] = write_corenlp_props(client_side_properties)
self.server_props_file['is_temp'] = True
self.server_start_info['client_side'] = True
self.server_start_info['props'] = client_side_properties
self.server_start_info['props_file'] = self.server_props_file['path']
self.server_start_info['preload_annotators'] = client_side_properties['annotators']
|
<gh_stars>1-10
package com.matteobattilana.almi.message;
import io.netty.channel.ChannelHandlerContext;
public interface MessageInterpreter<T>
{
T interpret(MethodCallResponse methodCallResponse, ChannelHandlerContext ctx)
throws Exception;
T interpret(MethodCallRequest methodCallRequest, ChannelHandlerContext ctx)
throws Exception;
T interpret(ErrorMessage errorMessage, ChannelHandlerContext ctx);
}
|
<filename>dialog/yesno_dialog.go
// Copyright 2020, <NAME>
// Licensed under the terms of the MIT. See LICENSE file in project root for terms.
package dialog
import (
"io"
"github.com/theparanoids/aterm/fancy"
"github.com/manifoldco/promptui"
)
type booleanOption struct {
Label string
Value bool
Icon string
ActiveStyle func(interface{}) string
SelectedStyle func(interface{}) string
}
var yes = booleanOption{
Label: " Yes ",
Icon: fancy.GreenCheck(),
Value: true,
ActiveStyle: promptui.Styler(promptui.BGGreen, promptui.FGBold, promptui.FGBlack),
SelectedStyle: promptui.Styler(promptui.FGGreen),
}
var no = booleanOption{
Label: " No ",
Icon: fancy.RedCross(),
Value: false,
ActiveStyle: promptui.Styler(promptui.BGRed, promptui.FGBold, promptui.FGWhite),
SelectedStyle: promptui.Styler(promptui.FGRed),
}
var yesNo = []booleanOption{yes, no}
// YesNoPrompt spans a "Select" dialog, where a given user will be propted with a
// yes/no question (plus, optional details, if details is not the empty string)
// will return (true, nil) if the user selected "Yes", (false, nil) if the user selected "No"
// (false, <error>) if some error occurred.
func YesNoPrompt(label, details string, inputStream io.ReadCloser) (bool, error) {
yesNoAsStringSlice := make([]string, len(yesNo))
for i := range yesNo {
yesNoAsStringSlice[i] = yesNo[i].Label
}
templates := &promptui.SelectTemplates{
Label: "{{ . }}",
Active: "{{ .Label | call .ActiveStyle }}",
Inactive: "{{ .Label }}",
Selected: "{{ (print .Icon (.Label | call .SelectedStyle)) }}",
}
if details != "" {
templates.Details = details
}
p := MkBasicSelect(inputStream)
p.Items = yesNo
p.Label = label
p.Searcher = SearcherContainsCI(yesNoAsStringSlice)
p.Templates = templates
selectedIndex, _, err := p.Run()
return yesNo[selectedIndex].Value, err
}
|
import java.awt.Graphics2D;
import java.awt.Image;
import java.util.ArrayList;
import javax.swing.ImageIcon;
/** This class is the foundation for all the players and monsters. */
public class Person
{
private String name;
private int strength;
private int dexterity;
private int intelligence;
private int constitution;
private int cash;
private String race;
private int x;
private int y;
private int maxHealth;
private int health;
private boolean visible;
private Image srcImage;
private ArrayList<Thing> inventory = new ArrayList<Thing>();
public Person()
{
this.setName("Joe");
this.setStrength(10);
this.setDexterity(10);
this.setIntelligence(10);
this.setConstitution(10);
this.setCash(0);
this.setRace("CYKBOT");
this.setX(0);
this.setY(0);
this.updateMaxHealth();
this.setHealth(this.getMaxHealth());
this.setVisible(true);
this.setSrcImage(this.getRace());
}
public Person(String name, int s, int d, int i, int c, int cash, String race, int x, int y)
{
this.setName(name);
this.setStrength(s);
this.setDexterity(d);
this.setIntelligence(i);
this.setConstitution(c);
this.setCash(cash);
this.setRace(race);
this.setX(x);
this.setY(y);
this.updateMaxHealth();
this.setHealth(this.getMaxHealth());
this.setVisible(true);
this.setSrcImage(this.getRace());
}
public Person(Person other)
{
this.setName(other.getName());
this.setStrength(other.getStrength());
this.setDexterity(other.getDexterity());
this.setIntelligence(other.getIntelligence());
this.updateMaxHealth();
this.setRace(other.getRace());
this.setX(other.getX());
this.setY(other.getY());
this.setHealth(this.getMaxHealth());
this.setCash(other.getCash());
this.setVisible(other.isVisible());
this.setSrcImage(other.getSrcImage());
}
public void setName(String name)
{
this.name = name;
}
public String getName()
{
return name;
}
public void setHealth(int health)
{
this.health = health;
}
public int getHealth()
{
return health;
}
public void updateMaxHealth()
{
this.maxHealth = this.getConstitution() + (this.getStrength() / 3);
}
public int getMaxHealth()
{
return maxHealth;
}
public void setCash(int cash)
{
this.cash = cash;
}
public int getCash()
{
return cash;
}
public void setStrength(int strength)
{
this.strength = strength;
}
public int getStrength()
{
return strength;
}
public void setDexterity(int dexterity)
{
this.dexterity = dexterity;
}
public int getDexterity()
{
return dexterity;
}
public void setIntelligence(int intelligence)
{
this.intelligence = intelligence;
}
public int getIntelligence()
{
return intelligence;
}
public void setConstitution(int constitution)
{
this.constitution = constitution;
}
public int getConstitution()
{
return constitution;
}
public void changeHealth(int health)
{
if(this.health + health >= this.maxHealth)
{
this.health = maxHealth;
}
else if(this.health + health <= 0)
{
this.health = 0;
}
else
{
this.health += health;
}
}
public void setX(int x)
{
this.x = x;
}
public int getX()
{
return x;
}
public void setY(int y)
{
this.y = y;
}
public int getY()
{
return y;
}
public void setVisible(boolean visible)
{
this.visible = visible;
}
public boolean isVisible()
{
return visible;
}
public void setRace(String race)
{
this.race = race;
}
public String getRace()
{
return race;
}
public void setSrcImage(Image srcImage)
{
this.srcImage = srcImage;
}
public void setSrcImage(String fileName)
{
this.srcImage = new ImageIcon(this.getClass().getResource(fileName + ".png")).getImage();
}
public Image getSrcImage()
{
return srcImage;
}
public ArrayList<Thing> getInventory()
{
return this.inventory;
}
/** @return Whether the person is dead or not. */
public boolean isDead()
{
boolean isDead = false;
if(this.health == 0)
{
isDead = true;
}
return isDead;
}
public void driver()
{
if(this.isDead())
{
//TODO: Drop stuff.
//Remove the person.
Game.map[this.getX()][this.getY()].setOccupant(null);
}
}
/** @return A string representation of the person. TODO: Make this more complete. Is it needed? */
public String toString()
{
String output;
output = "Name: " + this.name + "\n";
output += "Health: " + this.health + "/" + this.maxHealth + "\n";
output += "Cash: " + this.cash + "\n";
return output;
}
/** This checks to see if the location the person wants to move to is
* indeed a valid place to move. If so, it moves the person there.
* This function should be provided with the exact coordinates.
* @param newX The new X position.
* @param newY The new Y position. */
public void move(int newX, int newY)
{ //Make sure the target location is inside the map.
if(newX >= 0 && newX < Game.map.length && newY >= 0 && newY < Game.map.length)
{ //Make sure the new location is passable and without another occupant.
if(Game.map[newX][newY].isPassable() && !Game.map[newX][newY].hasOccupant())
{
Game.map[newX][newY].setOccupant(Game.map[this.getX()][this.getY()].getOccupant());
Game.map[this.getX()][this.getY()].setOccupant(null);
this.setX(newX);
this.setY(newY);
}
else if(Game.map[newX][newY].hasOccupant())
{
this.attack(newX, newY);
}
}
}
/** This checks to see if the location the person wants to move to is
* indeed a valid place to move. If so, it moves the person there.
* This function should be provided with a relative position.
* @param deltaX The change in X position.
* @param deltaY The change in Y position. */
public void moveRelative(int deltaX, int deltaY)
{
deltaX += this.getX();
deltaY += this.getY();
if(deltaX >= 0 && deltaX < Game.map.length && deltaY >= 0 && deltaY < Game.map.length)
{
if(Game.map[deltaX][deltaY].isPassable() && !Game.map[deltaX][deltaY].hasOccupant())
{
Game.map[deltaX][deltaY].setOccupant(Game.map[this.getX()][this.getY()].getOccupant());
Game.map[this.getX()][this.getY()].setOccupant(null);
this.setX(deltaX);
this.setY(deltaY);
}
else if(Game.map[deltaX][deltaY].hasOccupant())
{
this.attack(deltaX, deltaY);
}
}
}
public void attack(int x, int y)
{
if(Game.map[x][y].hasOccupant())
{
int damage = 0;
damage = (int) (this.getStrength() + (Math.random() * this.getDexterity()));
Game.map[x][y].getOccupant().changeHealth(-1 * damage);
}
}
/** This method is used to draw the person.
* @param dx The x coordinate of where to draw on the JPanel.
* @param dy The y coordinate of where to draw on the JPanel.
* @param pose The "Action" being performed (Walk, Attack, Die, etc.)
* @param g2d The Graphics2D object used to draw. */
public void draw(int dx, int dy, String pose, Graphics2D g2d)
{
int sx = 0;
int sy = 0;
if(pose.equalsIgnoreCase("walk"))
{
sx = 0;
sy = 0;
}
else if(pose.equalsIgnoreCase("attack"))
{
sx = 0;
sy = 1 * Game.TILE_SIZE;
}
else if(pose.equalsIgnoreCase("death"))
{
sx = 0;
sy = 2 * Game.TILE_SIZE;
}
g2d.drawImage(this.getSrcImage(), dx, dy, dx + Game.TILE_SIZE, dy + Game.TILE_SIZE,
sx, sy, sx + Game.TILE_SIZE, sy + Game.TILE_SIZE, null);
}
}
|
import { mount } from "@vue/test-utils";
import OwnHeader from "@/components/OwnHeader/OwnHeader.vue";
import router from "@/router";
import state from "../../../tests/mockedState";
describe("Given an OwnMenu component", () => {
describe("When it is rendered", () => {
test("Then it should render a heading with 'own.' text", async () => {
const title = "own.";
const wrapper = await mount(OwnHeader, {
global: {
plugins: [router],
mocks: {
$store: {
state,
},
},
},
});
expect(wrapper.text()).toContain(title);
});
test("Then it should render 2 li elements with 'Login' & 'Register", async () => {
const registerText =
'<li class="nav__element nav__element--register">Register</li>';
const logoutText =
'<li class="nav__element nav__element--logout"> Logout </li>';
const wrapper = await mount(OwnHeader, {
global: {
plugins: [router],
mocks: {
$store: {
state,
},
},
},
});
expect(wrapper.html()).toContain(logoutText);
});
});
});
|
Electrophysiological responses of angiotensin peptides on the rat isolated nodose ganglion. Previous autoradiographic studies have identified angiotensin II (AII) binding sites over the nodose ganglion and along the vagal afferent neurons. In the present study, we examined whether these binding sites are functional receptors by measuring d.c. potential changes by extracellular recording techniques in the rat isolated nodose ganglion preparation in response to superfusion of angiotensin peptides. It was found that AII, as well as AI and AIII elicited concentration-dependent depolarisation of the nodose ganglion. However, the amino terminal angiotensin heptapeptide, A, failed to evoke any significant response. The AII receptor antagonist, saralasin had no intrinsic activity, but caused a concentration-dependent blockade of AII-induced depolarisation. This study provides evidence for direct neuronal effects of angiotensin peptides on rat vagal afferent neurons. Moreover, this preparation is a relatively convenient one in which to study functional neuronal AII receptor mechanisms on central or peripheral terminals of vagal sensory neurons.
|
My mom handed me an envelope today, Christmas Eve. CLEARLY something to do with Reddit - it had Snoo on the front! There was also a totally charming flower decoration and some writing on the back.
This envelope...it was thick....did I accidentally sign up for secret santa again?
I took out the card and still couldn't quite tell. But this is what I can tell you: I will be taking this card with me back to my dorm. It's so beautiful. Subtle. Tactile. My favorite color. How does my Santa have such good taste? I'm already smitten.
I opened the card up. Oh my gosh! As my friends would say, I'd be the one to survive on a deserted island the longest because of how much I know about plants. Not true, but maybe you can tell how much I like nature. Nurturing. Seeing things grow. I love the sun and the earth.
So I was co-president of the gardening club in high school and I grew up planting things in the yard with my dad. I once went on a field trip to a farm and the owner challenged us to survive for two days on just food we got from our land. With all these seeds, I think I can finally do it! I can't wait until it gets warmer. I have that much more to look forward to now.
Santa, thank you so much for your generosity. You don't know me, but somehow you know this part of me so well. Merry Christmas. ❤️
|
#ifndef SESSION_H
#define SESSION_H
#include "AbstractNetworkOps.h"
using namespace std;
class Session : public AbstractNetworkOps {
typedef boost::asio::ssl::stream<boost::asio::ip::tcp::socket> ssl_socket;
public:
Session(boost::asio::io_service& io_service, boost::asio::ssl::context& context);
virtual ~Session();
void start();
void handle_handshake(const boost::system::error_code& error);
};
#endif
|
Crosssensitivity within the neomycin group of antibiotics Neomycin sensitive patients were tested for hypersensitivity to kanamycin, gentamycin, tobramycin, spectinomycin and to the new, not yet registered sisomycin and netilmicin. Cross-sensitivity occured in a considerable part of the patients, except for spectinomycin, the structure of which is basically different from that of the other aminoglycosides tested. The common occurence of cross-sensitivity between neomycin and other aminoglycoside antibiotics shows that it is possible to predict cross-sensitivity between a new drug and an old sensitizing one before clinical reactions from the new drug have occured. Such an investigation should be performed before adopting new antibiotics.
|
<reponame>zmyml/parking_labeler
'''
最后一行是最后图片加1s,全部出车,且保留车辆pos信息
'''
import cv2
import numpy as np
import os
import json
from detect_utils import parking_line
from detect_utils import show_parking_line
from create import create_json_record
path_img = r'E:\home_label\2000_02_02\DDT2G1907ZMY00040SY' # 路径
parking_space = 5 # 停车位个数 #需要手动改
# #################不标车牌的IP##################
no_plate_list = ['test_177', 'test_211', 'test_212', 'test_221', 'test_222', 'test_231',
'test_232', 'test_241', 'test_242', 'test_251', 'test_252', 'test_261', 'test_262']
# #################创建参数和初始化##################
path_txt = os.path.dirname(path_img) + '\\' + path_img.split('\\')[-1] + '_label.txt'
path_json = os.path.dirname(path_img) + '\\' + path_img.split('\\')[-1] + '_label_v2.json'
font = cv2.FONT_HERSHEY_SIMPLEX # 使用默认字体
change_parking_state = 0
show_parking_num = 1
change_parking_num = 2
frame_car_use_left_button = 3
state_mouse_init = 0
drag_start = None
sel = (0, 0, 0, 0) # 鼠标用
state_num_key = change_parking_state
state_mouse = state_mouse_init
parking_num_block = [] # 车位数据集合(选择跨车位停车时使用),是车位列表中的数字"0,1"
parking_num = [] # 各停车空间的所占的停车位号,parking_num[idx]的内容是parking_num_block中的数字
state_loc = [] # 停车状态
pos_show = [] # 显示位置坐标
pos_show_bias = [] # 显示位置偏移后的坐标
color_parking_num = [] # 停车状态颜色
color_parking_space_num = []
car_frame_point = []
car_frame_point_abs = []
act = 0 # 控制是否连续播放
state_time_label_overwrite = 0
time_label = ''
# 为各项数值初始化
for idx, i in enumerate(range(parking_space)):
parking_num.append([idx])
state_loc.append(0)
pos_show.append([0, 0])
pos_show_bias.append([0, 0])
color_parking_num.append((255, 0, 255))
color_parking_space_num.append((255, 0, 0))
car_frame_point.append([]) # 车辆框架点初始为空
car_frame_point_abs.append([])
# list_img = os.listdir(path_img)
# for filename in list_img:
# if not filename.endswith('jpg'):
# list_img.remove(filename)
# list_img.sort() # 排序
file_list = os.listdir(path_img)
list_img = [file for file in file_list if file.endswith('jpg')]
list_img.sort() # 排序
imgs_list_only_time = ['_'.join(i.split('_')[:3]) + '.jpg' for i in list_img] # 以防文件名后为电压等
os.chdir(path_img)
im_data = cv2.imread(list_img[0])
# ##############得到图像参数##################
h, w = im_data.shape[0:2]
# ##############字体大小和位置参数##################
x_panel = int(w * 0.83)
y_panel = int(h * 0.10)
y_panel_bias = y_panel - int(0.05 * h)
font_size = w // 1000
bias = int(w * 0.025) # 车位与状态标记在图片上的偏移
bias_y = int(h * -0.05) # 车位idx号位置的偏移
font_width = int((h + w) / 1000)
# ##################得到IP地址并人为规定显示位置##################
img_dir_name = os.path.basename(path_img)
ip_name = img_dir_name
if ip_name in parking_line:
parking_list_np = np.array(parking_line[ip_name]).astype(int) # 获得车位线
else:
blank_list = []
for i in range(parking_space):
blank_list.append([[0, 0], [0, 0], [0, 0], [0, 0]]) # 待修改
parking_list_np = np.array(blank_list)
if ip_name == 'test_177':
h_h = 600
h_l = 1400
elif ip_name == 'test_175':
h_h = 700
h_l = 1700
elif ip_name == 'test_176':
h_h = 500
h_l = 1400
elif ip_name == 'test_178':
h_h = 250
h_l = 1050
elif ip_name == 'test_170':
h_h = 250
h_l = 1300
elif ip_name == 'test_211':
h_h = 350
h_l = 850
elif ip_name == 'test_212':
h_h = 350
h_l = 850
elif ip_name == 'test_221':
h_h = 350
h_l = 850
elif ip_name == 'DDZ2G1907ZMY00002SY':
h_h = 200 # 显示的最上边界
h_l = 1300 # 显示的最下边界
elif ip_name == 'DDT2G1907ZMY00008SY':
h_h = 300 # 显示的最上边界
h_l = 1400 # 显示的最下边界
elif ip_name == 'DDT2G1907ZMY00016SY':
h_h = 600 # 显示的最上边界
h_l = 1450 # 显示的最下边界
else:
h_h = 1000 # 显示的最上边界
h_l = 1800 # 显示的最下边界
# 标记窗口大小设置
# 待修改
if ip_name == 'test_177':
# w_w = w//3
# w_h = (h_l - h_h)//3
w_w = (w // 7) * 3
w_h = ((h_l - h_h) // 7) * 3
elif ip_name == 'test_170':
w_w = (w // 7) * 3
w_h = ((h_l - h_h) // 7) * 3
elif ip_name in ['test_211', 'test_212', 'test_221']:
w_w = (w // 3) * 3
w_h = ((h_l - h_h) // 3) * 3
else:
w_w = (w // 5) * 2
w_h = ((h_l - h_h) // 5) * 2
img_len = len(list_img)
idx = 0
h_0, m_0, s_0 = os.path.splitext(list_img[0])[0].split('_')[:3] # 排序后第一个时间
h_1, m_1, s_1 = os.path.splitext(list_img[1])[0].split('_')[:3]
# 两幅图片时间间隔
# 如果时间间隔不确定,这个就对程序没意义了
gap_sec = (int(h_1) - int(h_0)) * 3600 + (int(m_1) - int(m_0)) * 60 + (int(s_1) - int(s_0))
one_min = 60 // gap_sec
three_mins = 180 // gap_sec
five_mins = 300 // gap_sec
if one_min == 0:
one_min = 2
if three_mins == 0:
three_mins = 6
if five_mins == 0:
five_mins = 10
# 得到初始时间秒值
initial_time_sec = int(h_0) * 3600 + int(m_0) * 60 + int(s_0)
# 全部图片时间秒
h_f, m_f, s_f = os.path.splitext(list_img[-1])[0].split('_')[:3]
h_sum = int(h_f) - int(h_0)
m_sum = int(m_f) - int(m_0)
s_sum = int(s_f) - int(s_0)
sec_sum = h_sum * 3600 + m_sum * 60 + s_sum
# 计算图片最后一张加一秒的时_分_秒表达
sec_all = int(h_f) * 3600 + int(m_f) * 60 + int(s_f)
sec_all_plus_one_sec = sec_all + 1
h_last = sec_all_plus_one_sec // 3600 # 时
m_last = sec_all_plus_one_sec % 3600 // 60 # 分
s_last = sec_all_plus_one_sec % 60 # 秒
last_time = str(h_last).zfill(2) + '_' + str(m_last).zfill(2) + '_' + str(s_last).zfill(2)
imgs_last_time_plus_one = last_time # 为了减少改动
img_data = cv2.imread(list_img[0])
# global record_list
record_list = []
click_time = 0
def onmouse(event, x, y, flags, param):
global drag_start, sel
global click_time
global pos_show
global pos_show_bias
if state_mouse == state_mouse_init:
if event == cv2.EVENT_LBUTTONDOWN:
if click_time < parking_space:
pos_show[click_time] = [x, y]
pos_show_bias[click_time] = [x + bias, y]
click_time += 1
print(x, y)
if state_mouse == frame_car_use_left_button:
if event == cv2.EVENT_LBUTTONDOWN:
drag_start = x, y
sel = 0, 0, 0, 0
elif event == cv2.EVENT_LBUTTONUP:
drag_start = None
car_frame_point[id_parking_num_change] = [(sel[0], sel[1]), (sel[2], sel[3])]
car_frame_point_abs[id_parking_num_change] = [(sel[0], sel[1] + h_h), (sel[2], sel[3] + h_h)]
print('是否保留该边框?是:点击回车确认;否:直接重画')
# state_mouse = frame_car_use_left_button
elif drag_start:
if flags & cv2.EVENT_FLAG_LBUTTON:
minpos = min(drag_start[0], x), min(drag_start[1], y)
maxpos = max(drag_start[0], x), max(drag_start[1], y)
sel = minpos[0], minpos[1], maxpos[0], maxpos[1]
img = img_data.copy()
cv2.rectangle(img, (sel[0], sel[1]), (sel[2], sel[3]), (0, 255, 255), 4)
cv2.imshow("label", img)
else:
print("selection is complete")
drag_start = None
# 在数字键用来改变停车状态下的简单显示
def tmp_print(state_loc):
for idx_state_loc, i in enumerate(state_loc):
if idx_state_loc < parking_space - 1:
print(i, end='\t')
else:
print(i)
# 加减一秒数值状态简单显示
def tmp_print_time_label(state_loc, time_label):
for i in state_loc:
print(i, end='\t')
print(time_label)
# 加减一秒数值状态删除显示
def tmp_print_for_delete(tmp_np_array):
for i in tmp_np_array:
print(i, end='')
print('<--X')
# 加车牌函数
def add_plate_2_label_v2(data_raw): # 待修改
parking_state_txt_record_state = []
for i in range(parking_space):
parking_state_txt_record_state.append('0') # 初始状态为0
data_updata = [] # 第一行处理方法,见2加车牌
for i in data_raw:
data_updata.append(i[0])
for idx_0 in range(parking_space):
if (i[idx_0 + 1].split(':')[1] == '2') and (parking_state_txt_record_state[idx_0] == '0'):
data_updata.append(i[idx_0 + 1] + ':蓝辽Axxxxx')
else:
data_updata.append(i[idx_0 + 1])
if i[idx_0 + 1].split(':')[1] != '1': # 若无此判断,则012的2显示不了车牌
parking_state_txt_record_state[idx_0] = i[idx_0 + 1].split(':')[1]
data_updata = np.array(data_updata)
data_updata = data_updata.reshape((-1, parking_space + 1))
return data_updata
def save_json_label(record_list, parking_space, path_json, imgs_last_time_plus_one, imgs_list_only_time):
record_for_json = create_json_record(record_list, parking_space, imgs_last_time_plus_one, imgs_list_only_time)
file = open(path_json, 'w', encoding='utf-8')
json.dump(record_for_json, file, ensure_ascii=False)
file.close()
print(f'save json at:{path_json}')
# 补全记录(在记录的最后一条补全出车)
def complement_record_list(record_list, last_time, parking_space): # 这里的last_time就是最后图片加1s的时间
record_list_tmp = np.array(record_list) # 得到记录
record_list_tmp = record_list_tmp.reshape((-1, parking_space + 1)) # 排版
record_list_last = record_list_tmp[-1] # 得到最后一行
for i in range(parking_space + 1):
if i == 0:
info = last_time
else:
info_splits = record_list_last[i].split(':')
if len(info_splits) == 2:
info = info_splits[0] + ':' + '0'
elif len(info_splits) == 3:
info = info_splits[0] + ':' + '0' + ':' + info_splits[2]
record_list.append(info)
return record_list
def save_label_and_print(record_list, path_txt, parking_space):
print('============原始数据如下===============')
record_list = np.array(record_list)
record_list = record_list.reshape((-1, parking_space + 1))
for i in record_list:
for idx_i, j in enumerate(i):
if idx_i < parking_space:
print(j, end=' ') # 原始数据加制表
else:
print(j) # 最后一个数据加回车
# 对所有结果按时间由小到大排序
tmp = record_list.T # np排序方法
record_list_order = tmp[0].argsort() # 得出比较结果
record_list_new_order = record_list[record_list_order] # 排序完毕
# 去掉重复行
tmp_f = record_list_new_order[0] # 为了去掉重复行
data_raw = []
for idx_i, j in enumerate(tmp_f): # 第一行的写法
if idx_i < parking_space:
data_raw.append(j)
else:
data_raw.append(j)
for i in record_list_new_order[1:]: # 后面的写法
if (i != tmp_f).any():
for idx_i, j in enumerate(i):
if idx_i < parking_space:
data_raw.append(j)
else:
data_raw.append(j)
tmp_f = i
data_raw = np.array(data_raw)
data_raw = data_raw.reshape((-1, parking_space + 1))
if ip_name in no_plate_list: # ['177']
record_list_new_order = data_raw
else:
record_list_new_order = add_plate_2_label_v2(data_raw)
# 输出到txt
path_txt = path_txt
file = open(path_txt, 'a+', encoding='UTF-8')
for i in record_list_new_order:
for idx_i, j in enumerate(i):
if idx_i < parking_space:
file.write(j + ' ')
else:
file.write(j + '\n')
file.close()
print('save txt at :{}'.format(path_txt))
# 删除一行
def modify_record_list(record_list, list_img, idx):
# 1.先找当前图片是否存在记录,无则显示无需修改,有则显示列表的idx
# 2.取出相应记录,使用remove删除该图片名称下全部记录
# if record_list is None:
# record_list = []
# print('记录里啥也没有,没东西可删')
# return record_list
# #return要返回值,否则就会把record变成none
if len(record_list) == 0:
print('记录里啥也没有,没东西可删')
else:
tmp_np_array = np.array(record_list)
tmp_np_array = tmp_np_array.reshape(-1, parking_space + 1)
delete_time = '_'.join(os.path.splitext(list_img[idx])[0].split('_')[:3])
if (tmp_np_array.T[0] == delete_time).any(): # any:不加括号是bug
idx_for_delete = [idx for idx, i in enumerate(tmp_np_array.T[0]) if i == delete_time] # 得到索引值
idx_for_delete = idx_for_delete[::-1] # 从后往前删除,否则idx失效
tmp_np_array_for_print = tmp_np_array[idx_for_delete] # 先取出要删除的
for i in idx_for_delete:
tmp_np_array = np.delete(tmp_np_array, i, 0) # 将要删除的删除
tmp_print_for_delete(tmp_np_array_for_print) # 显示出已经删除的条目
tmp_np_array = tmp_np_array.reshape(-1) # 恢复record
record_list = tmp_np_array.tolist() # 恢复record
else:
print('记录中无当前时间条目')
return record_list
def str_space_remove(content):
temp = ''
for letter in content:
if letter != ' ':
temp += letter
return temp
cv2.namedWindow('label', 0)
cv2.namedWindow('next', 0)
cv2.startWindowThread()
cv2.resizeWindow('label', w_w, w_h) # 宽,高
cv2.resizeWindow('next', w_w, w_h) # 宽,高
while idx < img_len - 1:
idx_next = idx + 1
img_data = cv2.imread(list_img[idx])
img_data_next = cv2.imread(list_img[idx_next])
if img_data is None:
idx += 1
continue
if img_data_next is None:
if img_data is None:
idx += 1
continue
else:
idx_next += 1
continue
img_data = show_parking_line(img_data, parking_list_np, 4) # 画停车线
img_data = img_data[h_h:h_l, ...]
img_data_next = img_data_next[h_h:h_l, ...]
h, m, s = os.path.splitext(list_img[idx])[0].split('_')[:3]
h_p = int(h) - int(h_0)
m_p = int(m) - int(m_0)
s_p = int(s) - int(s_0)
sec_pass = h_p * 3600 + m_p * 60 + s_p
# 显示的是当前时间(使用图片文件名)
img_data = cv2.putText(img_data, '_'.join([h.zfill(2), m.zfill(2), s.zfill(2)]), (x_panel, y_panel),
font, font_size, (0, 0, 255), font_width) # 添加文字，字体大小，初始位置，颜色，粗细
# 显示剩余时间
img_data = cv2.putText(img_data, str(int(sec_sum - sec_pass) // 60) + 'm' + str(int(sec_sum - sec_pass) % 60) + 's', (x_panel, y_panel_bias),
font, font_size, (0, 255, 0), font_width) # 添加文字，字体大小，初始位置，颜色，粗细
if state_num_key == change_parking_num:
if len(parking_num_block) > 1: # 车位数据集合(选择跨车位停车时使用)
parking_num_block.sort()
parking_num[id_parking_num_change] = parking_num_block # 写进去使命就完成了
for i in range(parking_space):
if len(car_frame_point[i]) == 0:
pass
else:
# 画图时只使用当前的两点坐标,但是在记入label时,使用绝对值坐标
img_data = cv2.rectangle(img_data, car_frame_point[i][0], car_frame_point[i][1], (0, 255, 255), 4)
for i in range(parking_space):
if state_num_key == show_parking_num:
color_parking_space_num[i] = (0, 255, 255)
elif state_num_key == change_parking_state:
color_parking_space_num[i] = (255, 0, 0)
elif state_num_key == change_parking_num:
color_parking_space_num[i] = (255, 0, 0)
if state_num_key == show_parking_num:
color_parking_num[i] = (255, 0, 255)
elif state_num_key == change_parking_state:
color_parking_num[i] = (255, 0, 255)
elif state_num_key == change_parking_num:
color_parking_num[i] = (255, 0, 255)
color_parking_num[id_parking_num_change] = (0, 255, 255)
# 车位idx
img_data = cv2.putText(img_data, str(i),
(pos_show[i][0], pos_show[i][1] + bias_y), font, font_size, color_parking_space_num[i], font_width)
# 车位
img_data = cv2.putText(img_data, str(parking_num[i]),
(pos_show[i][0], pos_show[i][1]), font, font_size, color_parking_num[i], font_width)
# 状态标记
img_data = cv2.putText(img_data, str(int(state_loc[i])),
(pos_show_bias[i][0], pos_show_bias[i][1] + bias_y), font, font_size + 1, (0, 0, 255), font_width)
# cv2.namedWindow('label',0)
# cv2.resizeWindow('label',w_w ,w_h) #宽,高
cv2.setMouseCallback('label', onmouse, 0) # 鼠标操作回调函数
# cv2.startWindowThread()
cv2.imshow('label', img_data)
# cv2.namedWindow('next',0)
# cv2.resizeWindow('next',w_w ,w_h) #宽,高
cv2.imshow('next', img_data_next)
key = cv2.waitKeyEx(1) # 等待按键
if act == 1:
idx += 1
if key == 27: # ESC
break
elif key == ord(' '): # 空格控制act
if act:
act = 0
else:
act = 1
elif key == ord('s') or key == ord('S'): # s 前进3min
idx += three_mins
elif key == ord('d') or key == ord('D'): # d前进5min
idx += five_mins
elif key == ord('a') or key == ord('A'): # a后退5min
if idx > 0:
idx -= five_mins
else:
idx = 0
elif key == ord('w') or key == ord('W'): # w 后退3min
if idx > 0:
idx -= three_mins
else:
idx = 0
elif key == 2490368: # 上
if idx > 0:
idx -= 1
else:
idx = 0
elif key == 2621440: # 下
idx += 1
elif key == 2424832: # 左
if idx > 10:
idx -= one_min # 1min
else:
idx = 0
elif key == 2555904: # 右
idx += one_min # 1min
elif key == 13: # p或回车
if state_mouse == frame_car_use_left_button:
# 待改进
print(f'两点当前坐标为({sel[0]}, {sel[1]}), ({sel[2]}, {sel[3]})')
print(f'两点绝对坐标为({sel[0]}, {sel[1]+h_h}), ({sel[2]}, {sel[3]+h_h})')
state_mouse = state_mouse_init # 将状态返回为初始化
continue
if state_num_key == change_parking_num:
if len(parking_num_block) == 0:
parking_num_block = [] # 为其复位,归空
print('请赋值')
elif len(parking_num_block) == 1: # 列表里只有一个值
state_num_key = change_parking_state
# car_frame_point[parking_num_block[0]] = [] # 取出唯一的值作为索引,并将里面的值去掉,成为[],这样不对
car_frame_point[id_parking_num_change] = [] # 取出唯一的值作为索引,并将里面的值去掉,成为[]
parking_num_block = [] # 为其复位,归空
print('赋值已完成,不需要画框了')
elif len(parking_num_block) > 1:
state_num_key = change_parking_state
state_mouse = frame_car_use_left_button
parking_num_block = [] # 为其复位,归空
print("\n赋值结束,请用鼠标左键为车画框")
elif state_num_key == change_parking_state:
if state_time_label_overwrite == 0: # 如果秒数没有被改写
# record_list.append(os.path.splitext(list_img[idx])[0]) # 先记录时间
record_list.append('_'.join([h.zfill(2), m.zfill(2), s.zfill(2)])) # 先记录时间
for idx_state_loc, i in enumerate(state_loc): # 再记录数据
parking_num_str = str_space_remove(str(parking_num[idx_state_loc]))
if len(car_frame_point[idx_state_loc]) == 0:
record_list.append(parking_num_str + ':' + str(i))
else:
car_frame_point_abs_str = str_space_remove(str(car_frame_point_abs[idx_state_loc]))
record_list.append(parking_num_str + ':' + str(i) + ':' + car_frame_point_abs_str)
for i in state_loc:
print(i, end='\t')
# print(os.path.splitext(list_img[idx])[0], end=' ')
print('_'.join([h.zfill(2), m.zfill(2), s.zfill(2)]), end=' ')
print('<---')
else:
record_list.append(time_label) # 先记录时间
for idx_state_loc, i in enumerate(state_loc): # 再记录数据
parking_num_str = str_space_remove(str(parking_num[idx_state_loc]))
if len(car_frame_point[idx_state_loc]) == 0:
record_list.append(parking_num_str + ':' + str(i))
else:
car_frame_point_abs_str = str_space_remove(str(car_frame_point_abs[idx_state_loc]))
record_list.append(parking_num_str + ':' + str(i) + ':' + car_frame_point_abs_str)
for i in state_loc:
print(i, end='\t')
print(time_label, end=' ')
print('<---')
state_time_label_overwrite = 0 # 更改状态
elif (key == ord('p')) or key == ord('P'): # p
if state_num_key == change_parking_state:
print("点击数字选择一个要更改的停车区域,从零开始", end=' ')
state_num_key = show_parking_num
elif (key == ord('o')) or key == ord('O'): # o或O
if state_num_key == show_parking_num:
print("\n状态恢复")
state_num_key = change_parking_state
elif key == ord('f') or key == ord('F'): # f 时间标签增加1s
tmp = sec_pass + initial_time_sec
tmp += 1
time_label = f'{tmp//3600:02d}_{tmp%3600//60:02d}_{tmp%60:02d}' # 上下都行
state_time_label_overwrite = 1
tmp_print_time_label(state_loc, time_label)
elif key == ord('r') or key == ord('R'): # r 时间标签减少1s
tmp = sec_pass + initial_time_sec
tmp -= 1
time_label = f'{tmp//3600:02d}_{tmp%3600//60:02d}_{tmp%60:02d}' # 上下都行
state_time_label_overwrite = 1
tmp_print_time_label(state_loc, time_label)
elif key == ord('m') or key == ord('M'): # m 减去当前图片名下的一条数据
record_list = modify_record_list(record_list, list_img, idx)
elif key == ord('l') or key == ord('L'): # l leave 离开需要马上打印
if len(record_list) != 0:
record_list = complement_record_list(record_list, last_time, parking_space)
save_label_and_print(record_list, path_txt, parking_space)
else:
print('there are no records to record !!!')
# save_json_label(record_list, parking_space, path_json)
elif key == 48 and parking_space > 0: # 0
if state_num_key == change_parking_state:
if state_loc[0] == 2:
state_loc[0] = 0
else:
state_loc[0] += 1
tmp_print(state_loc)
elif state_num_key == show_parking_num:
id_parking_num_change = 0
print('0')
print('按数字选择该空间所占车位,按回车确定', end=' ')
state_num_key = change_parking_num
elif state_num_key == change_parking_num:
parking_num_block.append(0)
print('0', end=' ')
elif key == 49 and parking_space > 1: # 1
if state_num_key == change_parking_state: # 若数字键用来改变停车位状态
if state_loc[1] == 2: # 修改的状态位置是0-1-2
state_loc[1] = 0
else:
state_loc[1] += 1
tmp_print(state_loc)
elif state_num_key == show_parking_num: # 若数字键用来选择车位索引
id_parking_num_change = 1 # 先确定索引的位置,若不同车在相同车位,这个索引也是不同的
print('1')
print('按数字选择该空间所占车位,按回车确定', end=' ')
state_num_key = change_parking_num
elif state_num_key == change_parking_num: # 若数字键用来标记车位
parking_num_block.append(1)
print('1', end=' ')
elif key == 50 and parking_space > 2: # 2
if state_num_key == change_parking_state:
if state_loc[2] == 2:
state_loc[2] = 0
else:
state_loc[2] += 1
tmp_print(state_loc)
elif state_num_key == show_parking_num:
id_parking_num_change = 2
print('2')
print('按数字选择该空间所占车位,按回车确定', end=' ')
state_num_key = change_parking_num
elif state_num_key == change_parking_num:
parking_num_block.append(2)
print('2', end=' ')
elif key == 51 and parking_space > 3: # 3
if state_num_key == change_parking_state:
if state_loc[3] == 2:
state_loc[3] = 0
else:
state_loc[3] += 1
tmp_print(state_loc)
elif state_num_key == show_parking_num:
id_parking_num_change = 3
print('3')
print('按数字选择该空间所占车位,按回车确定', end=' ')
state_num_key = change_parking_num
elif state_num_key == change_parking_num:
parking_num_block.append(3)
print('3', end=' ')
elif key == 52 and parking_space > 4: # 4
if state_num_key == change_parking_state:
if state_loc[4] == 2:
state_loc[4] = 0
else:
state_loc[4] += 1
tmp_print(state_loc)
elif state_num_key == show_parking_num:
id_parking_num_change = 4
print('4')
print('按数字选择该空间所占车位,按回车确定', end=' ')
state_num_key = change_parking_num
elif state_num_key == change_parking_num:
parking_num_block.append(4)
print('4', end=' ')
elif key == 53 and parking_space > 5: # 5
if state_num_key == change_parking_state:
if state_loc[5] == 2:
state_loc[5] = 0
else:
state_loc[5] += 1
tmp_print(state_loc)
elif state_num_key == show_parking_num:
id_parking_num_change = 5
print('5')
print('按数字选择该空间所占车位,按回车确定', end=' ')
state_num_key = change_parking_num
elif state_num_key == change_parking_num:
parking_num_block.append(5)
print('5', end=' ')
elif key == 54 and parking_space > 6: # 6
if state_num_key == change_parking_state:
if state_loc[6] == 2:
state_loc[6] = 0
else:
state_loc[6] += 1
tmp_print(state_loc)
elif state_num_key == show_parking_num:
id_parking_num_change = 6
print('6')
print('按数字选择该空间所占车位,按回车确定', end=' ')
state_num_key = change_parking_num
elif state_num_key == change_parking_num:
parking_num_block.append(6)
print('6', end=' ')
elif key == 55 and parking_space > 7: # 7
if state_num_key == change_parking_state:
if state_loc[7] == 2:
state_loc[7] = 0
else:
state_loc[7] += 1
tmp_print(state_loc)
elif state_num_key == show_parking_num:
id_parking_num_change = 7
print('7')
print('按数字选择该空间所占车位,按回车确定', end=' ')
state_num_key = change_parking_num
elif state_num_key == change_parking_num:
parking_num_block.append(7)
print('7', end=' ')
elif key == 56 and parking_space > 8: # 8
if state_num_key == change_parking_state:
if state_loc[8] == 2:
state_loc[8] = 0
else:
state_loc[8] += 1
tmp_print(state_loc)
elif state_num_key == show_parking_num:
id_parking_num_change = 8
print('8')
print('按数字选择该空间所占车位,按回车确定', end=' ')
state_num_key = change_parking_num
elif state_num_key == change_parking_num:
parking_num_block.append(8)
print('8', end=' ')
elif key == 57 and parking_space > 9: # 9
if state_num_key == change_parking_state:
if state_loc[9] == 2:
state_loc[9] = 0
else:
state_loc[9] += 1
tmp_print(state_loc)
elif state_num_key == show_parking_num:
id_parking_num_change = 9
print('9')
print('按数字选择该空间所占车位,按回车确定', end=' ')
state_num_key = change_parking_num
elif state_num_key == change_parking_num:
parking_num_block.append(9)
print('9', end=' ')
elif key == 57: # 9
record_list = complement_record_list(record_list, last_time, parking_space)
save_label_and_print(record_list, path_txt, parking_space)
# save_json_label(record_list, parking_space, path_json, imgs_last_time_plus_one, imgs_list_only_time)
if key != 27: # ESC没按输出结果到txt
record_list = complement_record_list(record_list, last_time, parking_space)
save_label_and_print(record_list, path_txt, parking_space)
# save_json_label(record_list, parking_space, path_json, imgs_last_time_plus_one, imgs_list_only_time)
cv2.destroyAllWindows()
print('程序结束')
|
Genome-wide identification and expression analysis of the VQ gene family in Cicer arietinum and Medicago truncatula Valine-glutamine (VQ) proteins are plant-specific proteins that play crucial roles in plant development as well as biotic and abiotic stress responses. VQ genes have been identified in various plants; however, there are no systematic reports in Cicer arietinum or Medicago truncatula. Herein, we identified 19 and 32 VQ genes in C. arietinum and M. truncatula, respectively. A total of these VQ genes were divided into eight groups (IVIII) based on phylogenetic analysis. Gene structure analyses and motif patterns revealed that these VQ genes might have originated from a common ancestor. In silico analyses demonstrated that these VQ genes were expressed in different tissues. qRT-PCR analysis indicated that the VQ genes were differentially regulated during multiple abiotic stresses. This report presents the first systematic analysis of VQ genes from C. arietinum and M. truncatula and provides a solid foundation for further research of the specific functions of VQ proteins. The VQ proteins have multiple functions at different stages of plant growth (Jiang, Sevugan & Ramachandran, 2018). For example, the AtVQ8 mutation causes a yellowishgreen leaf phenotype and growth retardation throughout the entire developmental period (). Over-expression of AtVQ29 reduces the hypocotyl growth of seedlings under special light conditions (). VQ proteins are also involved in plant responses to biotic and abiotic stresses (). AtVQ21 (MKS1)-overexpressing transgenic plants exhibit decreased resistance to Botrytis cinerea but significantly increased resistance to Pseudomonas syringae (), and AtVQ15 (AtCaMBP25)-overexpressing transgenic plants exhibit sensitivity to osmotic stress during seed germination and seedling growth (). In addition, the transcript levels of some VQ genes in rice are affected by exposure to drought (a). Most studies have indicated that many VQ proteins interact with WRKY transcription factors, which are not only involved in plant growth but also participate in multiple regulatory pathways ;Lei, Ma & Yu, 2018;;;). For instance, AtVQ14 interacts with AtWRKY10 to regulate endosperm growth and seed size (), and AtVQ9 acts antagonistically with AtWRKY8 to mediate responses to salt stress (). AtVQ22 could negatively control mediated JA defense through interact with AtWRKY28 and AtWRKY51 (). Moreover, MaWRKY26 could physically interact with MaVQ5, restricting the transactivation of the genes which control the JA biosynthetic, indicating that MaVQ5 might act as a repressor of MaWRKY26 in activating the JA biosynthesis in banana (). Legumes represent the third largest family of seed plants and one of the most important sources of food and nutrition for humans and animals (a;b). Cicer arietinum and Medicago truncatula are common legumes and model plants that have been used to study legume genomics (a). However, VQ genes have not been comprehensively evaluated in C. arietinum or M. truncatula. In this study, we identified 19 and 32 VQ genes in C. arietinum and M. truncatula, respectively. We conducted a comprehensive analysis to examine their phylogenetic relationship, gene structure, protein motifs, chromosome locations, promoters and collinearity, used silico expression analysis of VQ genes to show expression patterns of VQ genes in different tissues, and a qRT-PCR analysis to explore their responses to multiple abiotic stresses. This report provides a theoretical basis for the evolutionary relationship and function of the VQ genes in C. arietinum and M. truncatula. Identification of VQ genes The current genome sequence and annotation files of C. arietinum and M. truncatula were downloaded from Phytozome v12.1 (https://phytozome.jgi.doe.gov/pz/portal.html). The most updated Hidden Markov Model (HMM) for the VQ gene family (PF05678) was downloaded from the Pfam database (http://pfam.xfam.org) (). We conducted a BLAST search against the entire protein dataset of C. arietinum and M. truncatula with a cut-off E-value of 0.1. Subsequently, all hit protein sequences were extracted using custom Perl scripts. Then, the integrity of the VQ domain was evaluated using SMART tools with an e-value <0.1 (Ivica, Tobias & Peer, 2012), and candidate CaVQ and MtVQ proteins composed of a truncated VQ domain were identified. Peptide length, molecular weight (MW), and isoelectric point (pI) of each VQ protein were calculated using the online ExPASy program (https://www.expasy.org/) (). Detailed information of CaVQ and MtVQ proteins can be found in Table S1. Motif prediction and gene structure analysis of VQ genes The online MEME analysis was performed to identify unknown conserved motifs (http://meme.ebi.edu.au/) using the following parameters: site distribution: zero or one occurrence (of a contributing motif site) per sequence; maximum number of motifs: 20; and optimum motif width: ≥6 and ≤200 (). A gene structure displaying server program (http://gsds.cbi.pku.edu.cn/index.php) was used to display the structures of the CaVQ and MtVQ genes. Chromosomal distribution, gene duplication and collinearity analysis Physical positions of CaVQ and MtVQ genes were retrieved from the GFF3 annotation file using a Perl script, and diagrams of their chromosomal locations and duplication events were drawn using MG2C website (http://mg2c.iask.in/mg2c_v2.0/). In addition, gene duplication information was also identified based on public data in the Plant Genome Duplication Data base (PGDD, http://chibba.agtec.uga.edu/duplication/) (). If two homologous genes were separated by five or fewer genes, they were identified as tandem duplications, while if two genes were separated by more than five genes or distributed in different chromosomes, they were referred to as segmental duplications. BLASTP, OrthoMCL (http://orthomcl.org/orthomcl/about.do#release) and Multiple collinear scanning toolkits (MCScanX) with the default parameters were used to analyze the gene replication events (E <1 e −5, top 5 matches) (Li, Stoeckert & Roos, 2003;. Calculating Ka and Ks of the homologous VQ gene pairs Ka and Ks were used to assess the selection history and divergence time of gene families (Li, Gojobori & Nei, 1981). The number of synonymous (Ks) and nonsynonymous (Ka) substitutions of paralogous MtVQ gene pairs and orthologous VQ gene pairs between C. arietinum and M. truncatula were computed using the KaKs_Calculator 2.0 with the NG method (b)). Divergence time (T ) was calculated using the formula T = Ks/ (2 6. 1 10 −9 ) 10 −6 million years ago (MYA) (a). Analysis of cis-elements in VQ promoters The cis-elements of CaVQ and MtVQ promoters were analysed to further understand the VQ gene family. The 1,500 bp upstream sequences of the CaVQs and MtVQs promoter regions were downloaded FASTA format from the Phytozome database and used to identify the putative cis-elements in PlantCARE (http://bioinformatics.psb.ugent.be/ webtools/plantcare/html/) (). In silico expression analysis of VQ genes The transcriptome data in different tissues of C. arietinum and M. truncatula were available in the NCBI SRA (http://www.ncbi.nlm.nih.gov) with accession numbers PRJNA413872 and PRJNA80163, respectively. The quality-filtered reads were mapped to the respective C. arietinum and M. truncatula genomes with the spliced read mapper. Clean reads from all samples were mapped to the genome sequence using SAM (). TopHat v2.1.0 (Trapnell, Pachter & Salzberg, 2009). Cufflinks v2.1.1 and cuffcompare () were used to estimate the abundance of reads mapped to genes by calculating the fragments per kilobase of transcript per million (FPKM) values. Transcriptome data of the C. arietinum, including the nodule, leaf, flower, root, pod and bud; nodule, blade, flower, root, seedpod and bud in M. truncatula were obtained. The FPKM (fragment per kilobase per million mapped reads) representing the gene expression level of each CaVQ and MtVQ was extracted with custom Perl scripts. The heatmaps showing expression profiles were generated using log10-transformed FPKM values. The heatmaps and k-means clustering were generated using R 3.2.2 software (). Plant material, treatments, RNA extraction and quantitative real-time PCR (qRT-PCR) C. arietinum (ICC4958) and M. truncatula (Jemalong A17) were used in this study. ICC4958 is drought tolerant, and Jemalong A17 is salt-sensitive and drought-tolerant. In the greenhouse, seeds were planted in a 3:1 (w/w) mixture of soil and sand, germinated, and irrigated with half-strength Hoagland solution once every 2 days. Seedlings were grown at a night temperature of 18 C, day temperature of 24 C, relative humidity of 60%, and 14/10 h photoperiod (daytime: 06:00-20:00). Seedlings that germinated after 8 weeks were subjected to the following environmental conditions: temperatures of 4 (cold) or −8 C (freezing) and treatment with 300 mM mannitol (drought) and 200 mM NaCl solution (salt). The control (untreated) and treated seedlings were harvested at 1 h, 6 h, 12 h, and 24 h after treatment. All samples were frozen in liquid nitrogen and stored at −80 C until further use. Primers were designed to amplify 19 CaVQ and 32 MtVQ CDS using Primer Express 3.0 software, and the primer pairs are listed in Table S1. Total RNA was extracted from the root of C. arietinum and M. truncatula using the RNA Prep Pure Plant Kit (Tiangen, Beijing, China). The RNA quality was checked using 1.0% (w/v) agarose gel stained with ethidium bromide (EB) and spectrophotometer analysis and then DNase I treatment was conducted to remove the DNA contaminations (Takara, Shiga-ken, Japan). cDNA was synthesized from total RNA using the ReverTra Ace qPCR RT Kit (Toyobo Life Science, Shanghai, China). Quantitative real-time PCR (qRT-PCR) was performed using SYBR Green and monitored on an ABI 7300 Real-Time PCR system (Applied Biosystems, CA, USA). The PCR conditions were set as follows: 95 C for 10 min; 40 cycles at 95 C for 15 s, 55 C for 30 s, and 72 C for 30 s, a final step to preparation of DNA melting curve at 95 C for 15 s, and then one cycle at 60 C for 20 s and one cycle at 95 C for 15 s. Rapid detection expression levels of CaVQ and MtVQ genes using the qRT-PCR with DNA melting curve analysis. The gene -actin was used as a reference gene. The relative expression levels of each gene were analysed using the 2 − Ct method (Livak & Schmittgen, 2000). All samples were tested with three technical replicates and three independent biological replicates. Identification and phylogenetic analysis of VQ genes in two legumes A total of 19 and 32 genes putatively encoding VQ domains were identified in C. arietinum and M. truncatula, respectively. We designated the 19 VQ genes in C. arietinum as CaVQ1 to CaVQ19 and 32 VQ genes in M. truncatula as MtVQ1 to MtVQ32 according to their physical locations on the chromosomes (Table 1). The lengths of these VQ proteins ranged from 82 (MtVQ9) to 419 (MtVQ22) amino acids (aa), with an average of 206 aa. Their molecular weights varied from 9.3 (MtVQ9) to 45.8 (CaVQ17/CaVQ19) kDa, and the theoretical isoelectric points (pI) extended from 4.06 (CaVQ4) to 10.68 (MtVQ21). Among them, MtVQ30 and MtVQ31 as well as CaVQ17 and CaVQ19 were highly similar. We constructed a NJ phylogenetic tree to explore the evolutionary relationship between VQ genes in C. arietinum, M. truncatula, A. thaliana and O. Sativa (Fig. 1). As shown in Fig. 1, VQ proteins were classified into eight groups. Groups II and III contained 10 proteins, respectively. While Group V only contained 3 VQ proteins. We also found that CaVQs and MtVQs were clustered together, suggesting that they might have originated from a common ancestor. Conservative motifs and structural analysis To analyse the sequence characteristics of the CaVQ and MtVQ proteins, we used the MEME tool to predict their conserved motifs (Fig. 2). A total of 20 motifs describing details of CaVQ and MtVQ proteins were predicted and termed motifs 1-20 (Fig. 2B, Fig. S1). Motif 1 contained the VQ domain, which is an essential motif in these proteins. In addition, the VQ proteins in the same group possessed the same conserved motifs, which supported the results of the phylogenetic analysis. For instance, motifs 12 and 16 were especially prominent in Group V, motifs 2 and 9 were observed in Group IV, while motifs 3, 6, and 15 were present only in Groups VIII, IV and III, respectively. Multiple sequence alignment was constructed based on the types of VQ domain proteins (Fig. S2). In this study, four types of VQ motifs, including FxxxVQxLTG (39/51), FxxxVQxFTG (6/51), FxxxVQxLTC (4/51), FxxxVQxVTG (2/57) were identified in CaVQ and MtVQ proteins. We created exon/intron organizational maps based on the coding sequences of each CaVQ and MtVQ gene (Fig. S3) and found that only 4 VQ genes (CaVQ1, CaVQ15, MtVQ21 and MtVQ32) had introns. Among them, two VQ genes belonged to Group VII. The majority of VQ genes in C. arietinum and M. truncatula lacked introns. Furthermore, Group V members had longer coding regions than the others, and Group I members had shorter coding regions than the others. Chromosomal locations and gene duplication The locations of the VQ genes revealed that they were unevenly distributed on their corresponding chromosomes (Table 1, Figs. 3 and 4). VQ genes were identified in 7 of 8 C. arietinum chromosomes and in all M. truncatula chromosomes. In C. arietinum, four genes (CaVQ16, CaVQ17, CaVQ18 and CaVQ19) could not be mapped on any chromosome. In M. truncatula, there were four gene clusters (MtVQ1-MtVQ2, MtVQ17 -MtVQ18-MtVQ19, MtVQ23-MtVQ24 and MtVQ30-MtVQ31) located on chromosomes 1, 4, 6 and 8, respectively. The gene duplication analysis (Figs. 3 and 4) revealed that there were 4 and 6 gene pairs originating in tandem duplication and segment duplication events in M. truncatula; however, there was no gene duplication event in C. arietinum. Three gene clusters were formed by tandem duplication located on chromosomes 1, 4, and 8 in M. truncatula. Synteny analysis of VQ genes We analysed collinearity diagrams between the VQ genes in C. arietinum, M. truncatula, and other model plants, such as A. thaliana, O. sativa and G. max (Fig. 5). We found that the VQ genes in C. arietinum had the most homologous gene pairs with VQ genes in G. max, followed by A. thaliana (Figs. 5A-5C). Similarly, the VQ genes in M. truncatula had the most homologous gene pairs with VQ genes in G. max, followed by A. thaliana and O. sativa (Figs. 5D-5E). However, no homologous gene pairs were observed between C. arietinum and O. sativa (Fig. 5F). Ten homologous gene pairs were observed between the CaVQ and MtVQ genes (Fig. 5G). In addition, one VQ gene in C. arietinum and M. truncatula matched more than one VQ gene in other plants. Ka/Ks of VQ genes To better understand the selection pressure acting on paralogous MtVQ gene pairs and orthologous VQ gene pairs between C. arietinum and M. truncatula, we calculated their Ka/Ks substitution ratios (Table 2). Our results suggest that the Ka/Ks values of most gene pairs were <1; the Ka/Ks value of only one gene pair (MtVQ19/MtVQ17 ) was >1, indicating that they had primarily evolved under purifying selection. We also found that the differentiation time of VQ genes in C. arietinum and M. truncatula was between 110 and 190 MYA and that the differentiation time of paralogous VQ gene pairs in M. truncatula was primarily between 3 and 11 MYA. Cis-element analysis of VQ genes To investigate gene function and regulation, we analyzed cis-elements in the promoters of CaVQs and MtVQs (Table S2, Fig. S4). The multiple light responsive elements were observed in the VQ genes (e.g., G-Box, GT1-motif, 3-AF1 binding site and TCT-motif) (Table S2). Furthermore, some cis-elements participated in plant growth and development (e.g., circadian, RY-element, and CAT-box) (Fig. S4). Other cis-elements could be classified into two major groups: hormone responsive and abotic stress. Ten cis-elements are involved in hormone responses, including ABRE, P-box, TATC-box and AuxRR-core, and five cis-elements are related to stress, i.e., ARE, LTR, MBS, TC-rich repeats and GC-motif. In addition, we found that several VQ genes contained W-box motifs, which are binding sites for WRKY transcription factors (a). In silico analysis of VQ genes in different tissues We investigated the expression profiles of CaVQ and MtVQ genes in various tissues using high-throughput sequencing data from NCBI, including leaf, bud, flower, root, pod, nodule in C. arietinum and nodule, blade, flower, root, seedpod, bud in M. truncatula. As shown in Fig. 6, most CaVQ genes exhibited tissue-specific expression patterns. Seven CaVQ genes (CaVQ13,5,16,7,12,10 and 15) were highly expressed in the root and nodule; four CaVQ genes (CaVQ18, 4 and 6 ) were highly expressed in leaf and root; CaVQ14 was expressed only in the bud; CaVQ8 was highly expressed in the six tissues; and six CaVQ genes (CaVQ2,1,11,9,17 and 19) were expressed at low levels in all tissues. Most CaVQ genes exhibited tissue-specific expression patterns. In M. truncatula (Fig. 7), six genes (MtVQ12,29,3,7,4 and 20) were highly expressed in the nodule and root; four MtVQ genes (MtVQ23, 16, 11 and 32) were expressed only in the blade; eight MtVQ genes (MtVQ27,10,5,14,15,26,13 and 21) were highly expressed in all detected tissues; and the other MtVQ genes were expressed at low levels in six tissues. To explore the stress-specific distribution of the VQ gene family under four abiotic stresses (drought, salt, cold and freezing), we compared the gene expression similarly between C. arietinum and M. truncatula under a combination of all stresses, and the results are shown in Fig. S5. Some VQ genes were exclusively induced, and certain VQ genes were exclusively inhibited. Under four stresses, three CaVQ genes (CaVQ2, 7 and 8) were upregulated at all the time points; only CaVQ17 was downregulated at early time point but no gene was downregulated at late time point. six MtVQ genes (MtVQ12, 13, 14, 15, 21 and 26 ) were upregulated and six MtVQ genes (MtVQ8,18,19,28,31 and 32) were downregulated genes under all four stresses at early time points. At the same time, five MtVQ genes (MtVQ15,16,20,21 and 23) were exclusively induced and two MtVQ genes (MtVQ21 and 28) were repressed under all stresses at later time points. Expression patterns of homologous genes under abiotic stresses We found that most homologous genes between MtVQ and CaVQ genes showed the same expression patterns under abiotic stresses (Fig. S6) DISCUSSION VQ proteins are plant-specific proteins involved in the regulation of plant growth, development and responses to various environmental stresses in plants (;;;). VQ genes have been identified in various plants, such as A. thaliana, O. sativa, Z. mays, G. max and V. vinifera (a;;;). Legumes, such as C. arietinum and M. truncatula, are widely cultivated and have high nutritional and economic value (b;;;). However, systematic analyses of VQ genes in C. arietinum and M. truncatula are lacking. Herein, a total of 19 and 32 VQ genes were identified in C. arietinum and M. truncatula, respectively. Although the genome size of C. arietinum is twice larger than that of M. truncatula, the number of VQ genes in M. truncatula is much larger than that in C. arietinum, indicating that a large number of CaVQ genes have been lost during evolution (a). We systematically analysed the structural and functional characteristics of the CaVQ genes and MtVQ genes to explore their evolutionary relationships and provide a theoretical basis for further research. CaVQ genes and MtVQ genes were closely related, based on the phylogenetic analyse, we found that the CaVQs and MtVQs were always clustered together. The gene structure analysis suggested that 94.74% (18/19 genes) of CaVQ genes and 90.63% (29/32 genes) of MtVQ genes did not contain introns. These results are consistent with the previous studies that reported the VQ genes in Z. mays (54, 88.5%) (), O. sativa (37, 92.5%) (a), and A. thaliana (30, 88.2%) () without introns. While, a smaller number of moss VQ motif-containing genes (7/25, 28%) are not possess introns (Jing & ). Comparative these plants (higher plants C. arietinum, M. truncatula, A. thaliana, Z. mays, O. sativa, and lower plants, moss) indicate that most VQ genes have lost introns during the long evolutionary period. Based on the multiple sequence alignment, we found that there are four types in VQ domain of CaVQ and MtVQ proteins (LTG, FTG, LTC, VTG), however, there are six types of AtVQ proteins (LTG, LTS, LTD, FTG, VTG, YTG) () and four types of OsVQ proteins (ITG, LTG, VTG, FTG) (a) in previous studies. Except these, we found that a unique and conserved sequence. The conserved motif analysis showed that CaVQ genes and MtVQ genes were very closely related. Both CaVQ genes and MtVQ genes showed similar motif patterns in the same groups, such as motif 2 and motif 7 were specifically exist in all members of group IV and II, respectively. These results suggest that CaVQ and MtVQ genes may originate from a common ancestor. Segmental and tandem duplication events are major expansion methods in the plant genome (Storz, 2009;Kaltenegger, Leng & Heyl, 2018). In the MtVQ gene family, 6 gene pairs originated from segmental duplication and 4 gene pairs were involved in tandem duplication. These results are similar to those found in Brassica rapa and pears (;), suggesting that segmental duplication events are a common expansion mechanism in the VQ gene family. For gene pairs originating from tandem duplication, they all formed gene clusters on M. truncatula chromosomes. However, we did not identify gene duplication event in CaVQ genes. Furthermore, we noticed that there were a large number of orthologous gene pairs in CaVQ and MtVQ genes, which is consistent with the results that C. arietinum and M. truncatula were closely related based on the phylogenetic analysis. The substitution rates of Ka and Ks are the basis for analysing the selection pressure in gene duplication events (b). We found that the Ka/Ks values of most gene pairs were <1, suggested that they had primarily evolved under purifying selection. During evolution, C. arietinum and M. truncatula common experienced whole genome triplication ( event) at 130 MYA and whole genome duplication (-event) at 59 MYA, and the differentiation time between them was approximately 30-54 MYA (a). However, the differentiation time of the VQ gene pairs in C. arietinum and M. truncatula was approximately 110-190 MYA. These results indicate that the time of gene differentiation is earlier than that of C. arietinum and M. truncatula differentiation, the VQ gene show high intraspecific polymorphism. Except these, the differentiation time of paralogous gene pairs in M. truncatula was about 3-25 MYA, which were later than the time of species differentiation (a). In higher plants, the VQ gene family has critical functions in the process of plant growth, development and response to multiple stresses. In the whole period of pear fruit development, most PbrVQ genes are expressed and can play critical roles in pear fruit development (). In bamboo, 11 VQ genes are highly express in leaf, early panicle, advanced panicle, root and rhizome tissue, and they are lowly express in shoot (b). In this study, based on silico analysis, the VQ genes exhibited tissue-specific expression in both C. arietinum and M. truncatula. We found that six MtVQ genes and four CaVQ genes were specifically highly expressed in root and nodule, these results are similar to that in soybean: nine and ten GmVQ genes are specifically express in root and nodule, respectively (). We speculate that they may be involve in root and nodule formation and development. There were six VQ genes (CaVQ8, CaVQ18, MtVQ10, MtVQ5, MtVQ14, MtVQ26 ) were highly expressed in flowers, GmVQ43 and GmVQ62 affect flowering time of plants, we speculate that these VQ genes may involve in regulate flowering time and flower development (). Some orthologous gene pairs showed similar expression patterns in different tissues. For instance, CaVQ3/MtVQ7 was highly expressed in the nodule and root and CaVQ8/MtVQ26 was highly expressed in all examined tissues. However, the CaVQ5/MtVQ3 gene pair had different expression patterns, with CaVQ5 highly expressed in six tissues and MtVQ3 expressed only in the root. These results suggest that some gene pairs retained similar functions while others produced functional differentiation during the process of evolution (). In previous study, the VQ gene family is found to be involve in responses to multiple stresses (). Certain PbrVQ genes were shown to be highly expressed under GA (Gibberellic acid, GA), salt and black spot disease stresses (). In this study, five CaVQ genes (CaVQ2,4,7,9,and 15) and eight MtVQ genes (MtVQ4,5,9,12,14,17,27,and 29) significantly upregulated during drought stress, which results are similar to the OsVQ genes that twenty-two OsVQ genes are upregulated under drought stress (a). Under salt stress, eight CaVQ genes (CaVQ3,7,8,10,13,14,17 and 19) and four MtVQ genes (MtVQ7, 10, 14 and 21) were significantly induced. In the A. thaliana, similar expression changes among VQ genes were also observed, including the expression of AtVQ9 and AtVQ15 that changed significantly under salt stress (). In addition, the VQ genes are also sensitive to temperature changes. Seven CaVQ genes (CaVQ7,8,9,11,12,13 and 15) and eleven MtVQ genes (MtVQ1,4,6,9,12,13,15,20,21,22 and 25) were rapidly upregulated at early time point under cold treatment. Six CaVQ genes (CaVQ2,7,13,14,18 and 19) and five MtVQ genes (MtVQ12,16,20,21 and 30) were upregulated at early time point (1 h or 6h) for the case of freezing treatment. Similar results have been reported in Chinese cabbage that VQ genes are quickly responsive to heat and cold stresses (). We speculate that VQ genes can respond to various abiotic stresses both in C. arietinum and M. truncatula. By combining promoter analysis with qRT-PCR analysis, we found that VQ genes were responses to multiple abiotic that might be closely related to their promoters. For example, CaVQ13 and MtVQ26 which contained cis-elements (LTR) involved in low temperature responsiveness, all of them showed upregulated expression both under cold and freezing stresses. Oppositely, four VQ genes (CaVQ3, CaVQ4, CaVQ8 and CaVQ9) contained LTR elements and they were downregulated during cold and freezing stresses. Furthermore, CaVQ5, MtVQ18, MtVQ22 and MtVQ25, which have TC-rich repeats that can participate in response defence and stress, they were showed downregulated expression patterns in drought and salt stresses. The expression patterns of most orthologous gene pairs are similar while others are different. For instance, three gene pairs (CaVQ3/MtVQ7, CaVQ10/MtVQ14 and CaVQ13/MtVQ20) showed similar expression patterns in C. arietinum and M. truncatula, while other gene pairs (CaVQ1/MtVQ10, CaVQ7/MtVQ12, CaVQ9/MtVQ5 and CaVQ12/MtVQ17 ) exhibited opposing expression patterns during the salt stress. These results indicate that the orthologous gene pairs in different plants may undergo functional differentiation in the long-term evolution process that they may have distinct regulatory mechanisms under various abiotic stresses (Jiang, Sevugan & Ramachandran, 2018). Hence, the expression of most CaVQ and MtVQ orthologous gene pairs have undergone functional divergence, indicating that these gene pairs originate from a common ancestor and they are involve in functional redundancy, while other gene pairs are involve in neo-functionalization or sub-functionalization (Sandve, Rohlfs & Hvidsten, 2018). Taken together, our study suggests that a system analysis of the evolutionary relationship, structure and response to various abiotic stresses may help to elucidate the CaVQ and MtVQ genes for further functional characterization. CONCLUSIONS In conclusion, this study provides the first comprehensive and systematic analysis of the VQ gene family in two legumes (C. arietinum and M. truncatula). A total of 19 and 32 VQ genes were identified in C. arietinum and M. truncatula, respectively. All VQ genes fell into eight groups (I-VIII). The VQ genes from the same evolutionary branches shared similar motifs and structures, these results suggested that the VQ genes of C. arietinum and M. truncatula might originate from a common ancestor. The selection pressure analysis showed that most homologous pairs were under strong purifying selection by the VQ genes. In silico analyses revealed that most VQ genes exhibited tissue-specific expression patterns, indicating that they might play crucial roles in different tissues. Finally, qRT-PCR analysis showed that the VQ gene family was responsive to abiotic stresses. The results indicating that the VQ genes not only participates in regulating plant growth and development, but also responds to abiotic stresses. Our results provide a theoretical basis for the further study of VQ gene functions.
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Specialized Search Engines for E-learning Italian National Research Council - Institute for Educational Technology - Via Ugo la Malfa, 153 - 90146 Palermo, ITALY The web provides an enormous amount of information and the diffusion of search engines has made this information accessible. Without the use of search engines the web would not have been so successful. The most common search engines are keyword-based, but in general they present various limits related to the quality of the search results. To overcome these limits many authors suggest the use of a specialized search engine. In this paper we propose the use of a specialized search engine to assist students in their learning tasks. We introduce an iterative technique to build a taxonomy which is used to classify docu-ments regarding a specific topic, and a tool that assists users in the taxonomy building process. Finally, we present an application example that by means of a search engine, GPS and mobile learning technolo-gies allows students to access relevant information related to the cultural site they are visiting.
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Field dependence of emission and capture rates of DX-related centers in AlxGa1-xAs. The emission and capture rates of DX-related centers have been studied by junction space-charge techniques at various reverse biases in silicon-doped ${\mathrm{Al}}_{\mathit{x}}$${\mathrm{Ga}}_{1\mathrm{\ensuremath{-}}\mathit{x}}$As alloys for six different values of x. It is shown that for modest changes in the reverse bias, the thermal-emission rate decreases by more than an order of magntiude and the enthalpy increases by more than a factor of 2. Possible explanations for these observations are discussed.
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Cervical Exenteration - Guidelines and Surgical Technique Principles. Introduction: Neoplastic invasion of the structures of the cervical region originating from a malignant tumour developed in one of the viscera of the throat may benefit from cervical exenteration. Defined as resection of the hypopharynx, cervical oesophagus, larynx and cervical trachea, exenteration has limited indications and is mandatorily accompanied by digestive tube reconstruction. The aim of this article is to highlight the indication, surgical strategy and important surgical stages illustrated by images from personal professional experience. MATERIALS AND METHOD Pharyngo-laryngo-oesophageal en bloc resection and radical cervical lymphadenectomy were followed by reconstruction via free jejunal transfer or colic pedicle grafting. Between 2000 and 2018 we have performed cervical exenteration in 25 patients with tumours originating in the pharynx, larynx or cervical oesophagus. In the cases of 5 patients in whom we did not obtain the oncological safety margin for oesophageal cancer we performed transhiatal pharyngo-laryngo-oesophagectomy. In these patients, we performed reconstruction of the oesophagus with colonic graft. In 20 cases we performed jejunal autotransplant. Results: We recorded 4 perioperative deaths, due to major arterial vessel haemorrhage (1 case), after jejunal necrosis (2 cases), and mediastinitis after oesophageal striping and colonic graft necrosis (1 case). One patient presented tumour recurrence at the level of the tracheal stump. Survival rate varied between 6 months and 4 years for the group of patients who presented for postoperative follow-ups. Conclusions: Cervical exenteration remains an option for tumour recurrence after radiochemotherapy or for obstructive airway or digestive tract tumours. It can be burdened by complications difficult to treat. The surgical team has to adapt its initial surgical strategy to the reality of the surgical field, both in terms of exeresis and in terms of types of pharyngo-oesophageal reconstruction.
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/**
* toXML returns XML document equivalent
* to the informations this class carries.
*
* @return XML document in a String equivalent
* to the informations this class carries.
*/
public String toXML()
{
StringBuilder bldr = new StringBuilder();
bldr.append("<"+ SsrcProvider.ELEMENT_NAME +" xmlns=\""+getNamespace()+"\"");
bldr.append(" cname=\""+ this.cname +"\"");
bldr.append(" msid=\""+ this.msid +"\"");
bldr.append(" mslabel=\""+ this.mslabel +"\"");
bldr.append(" label=\""+ this.label +"\"");
bldr.append(" ssrc=\""+ this.ssrc +"\"");
bldr.append("/>");
return bldr.toString();
}
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Mobile computing executives are gathering in Barcelona this week as they do each year at this time to hold symposia about the telephone business and to show off their latest handsets. Alphabet Inc.'s (GOOGL - Get Report) Google unit, which makes over half its advertising revenue from paid search on mobile devices, faces a new challenge to maintain its advertising empire.
In addition to making money on devices running its Android operating system and on Apple Inc.'s (AAPL - Get Report) iPhone, Google sells the "Pixel" line of smartphones for which it is responsible for all the costs and earns the revenue, just like any other smartphone maker. The Mobile World Congress meeting in Barcelona this year will be the first time since Google debuted Pixel that the company faces a major shift in the marketplace for those devices.
Dozens of vendors of Android-based phones will be unveiling their first models that use faster 5G cellular connections -- networks that can have upward of two billion bits-per-second download speeds, and, as important, dramatically faster upload speeds than what's commonly available. Samsung Electronics (SSNLF , the world's largest maker of phones, pushed up the announcement of its own device, the "Galaxy S10," hosting an event in San Francisco this past week, rather than its usual gathering in Barcelona, to get ahead of the wave of news from competitors.
Google doesn't have a 5G phone, and it's unclear if they will when the next model of Pixel arrives, presumably this fall. That is noteworthy, because Google faces a marketplace that is increasingly looking to supplant some of the functionality that Android affords and, perhaps, give Android device makers, including Samsung, a new degree of control over the mobile operating system.
Samsung, for example, has its own camera app that it built for the Galaxy S10, which can be used instead of the built-in, stock, camera app Google provides with Android. That Samsung app has the ability to send short-form video directly to Facebook's Instagram service, a new level of integration between the device maker and the social network.
A variety of services are placing deeper hooks into the device over and above what Google offers. Samsung positions its "Bixby" voice-controlled intelligent assistant as an alternative to Google's own Assistant software. One imagines that Amazon.com Inc.'s (AMZN - Get Report) Alexa software will similarly gain greater prominence on Android devices over time, thereby threatening Google's position as the primary interface to the phone. Losing that preeminence would threaten Google's advertising revenue stream from the phone.
The Pixel has been one way for Google not to lose control of its own platform, by maintaining a new level of control over the services the average user consumes. If Google's delay in offering a 5G version hinders its sales of new devices, the risk is not merely lost device sales, it is a loss of prominence on its own platform.
The results for Pixel in the market have been decent so far. Although the Google phones don't crack the top five of devices by unit shipments, Pixel was the top-selling smartphone in the U.S. in the December-ending quarter, according to market research firm Strategy Analytics. Pixel unit sales rose by 43%, the firm estimates, which is a fine number. It's also made even more impressive because the market overall dove by 23% as sales by Samsung and Apple and other top vendors failed to live up to expectations.
It remains to be seen whether being late to the 5G party will slow Pixel's advance. It may as yet be so early in the deployment of the new network that it won't make much difference this year and Google can catch up with a 5G model later this year or in 2020.
But Android will remain a challenging market approach for Google. The company must keep Android partners such as Samsung happy by helping them to make sure their devices are desirable. At the same time, Google must continue to build the competitive position of its own Pixel offerings to hedge against a future in which other parties - Samsung, Facebook, Amazon, Apple - dominate mobile with their own applications.
For the moment, Google seems to believe it can strike that balance, advancing Android generally as a platform and still assembling a decent offering of its own. Time will tell if all that is enough.
Alphabet, Apple and Amazon are holdings in Jim Cramer's Action Alerts PLUS member club. Want to be alerted before Jim Cramer buys or sells the stocks? Learn more now.
Tiernan Ray neither owns nor trades any shares of companies mentioned in this article.
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The combustion of hydrocarbon fuels involves the chemical combination of oxygen with the carbon and with the hydrogen, producing water vapor and oxides of carbon. The nitrogen content of the air will frequently enter into the reaction to form various oxides of nitrogen as pollutants. Incomplete combustion can be expected to produce percentages of carbon monoxide, rather than exclusively carbon dioxide, primarily as a result of the impossibility of assuring a perfect mixture of the fuel and air, and the optimum combustion temperature. The classic assumption has always been that the oxygen would have a preference for the hydrogen in cases of incomplete combustion, and this would result in certain percentages of carbon monoxide in the exhaust gases, even where the theoretically quantity of air for proper combustion was present. This gas is not only an undesirable pollutant, but represents a loss of a considerable quantity of the available heat in the fuel.
It has been recognized for at least 50 years that the presence of moisture in the combustion space will significantly modify the combustion process. the injection of water spray into the cylinders of high-output air craft engines has been used as a means of supressing detonation, by the absorption of the heat of vaporization, which would otherwise peak to a point at which the fuel charge would detonate, rather than burn at a uniform rate. Another phenomenon, which has been less well recognized, has been the effects of minute quantities of water vapor in the combustion air. It has been known that the performance of internal combustion engines was frequently improved under conditions of increased humidity. It has also been observed that it was much more difficult to ignite a hydrocarbon fuel-air mixture at all under conditions of extremely low humidity. It was suspected that the water vapor was somehow entering into the combustion process and modifying it, but the nature of this interaction has not been general knowledge. It has, however, been known to specialists in this field for many years. One would normally expect that any dissociation of water vapor into its component oxygen and hydrogen would simply be a passive reaction, as it should re-combine to restore the energy of dissociation. The actual reaction involved, however, is far different. At a particular temperature level related to selected conditions of pressure, the dissociation of the water vapor into oxygen and hydrogen leaves these components in the nascent state, which places them in this condition in the company of the oxygen and hydrogen of the fuel in essentially the same state. Under these conditions, the usual valence laws establishing a preference of the carbon for hydrogen are reversed, with the oxygen then exhibiting a preference for the carbon. The carbon is then completely burned, and the remaining hydrogen is subsequently burned very easily after the oxidation of the carbon, whenever sufficient oxygen is present. This rather surprising behavior has also been observed for many years in a totally different setting. Firemen are very much aware that a coal pile burning from spontaneous combustion cannot be quenched by turning a hose on it. Such a procedure simply results in the migration of enough water vapor into the interior to enter into the dissociation phenomenon, resulting in very efficient burning of all the carbon, and then the subsequent burning of the hydrogen nearer the surface of the coal pile.
The dissociation phenomenon has been incorporated in internal combustion engines and in various forms of heatgenerating devices, frequently without a specific understanding of what was happening. The intake manifold of internal combustion engines provided with carburetors has frequently been supplied with vapor injectors of one form or another, as shown in the U.S. Pat. Nos. 3,724,429; 3,790,139; and 3,107,657. The Wentworth, Jr. U.S. Pat. No. 3,862,819 shows an example of the application of this principle to boilers and furnaces. In this patent, the disclosed system involves a bypass of the air of the primary combustion blower such that a reduced pressure in a container of water induces an inflow of air through a conduit extending to a point below water level. The resulting moisture-ladened air bubbling up through the liquid is removed by the blower, and is intermixed with the main stream of the intake air. Arrangements have also been proposed and used involving a continuous recirculation of the major portion of the air bubbling up through the liquid, which may conceivably increase the vapor content of the resulting air. The recirculation, however, complicates the problem of controlling the amount of vapor actually delivered to the combustion chamber. The quantities of water vapor that are administered to the combustion system in this manner must necessarily be very minute. Excessive moistur will tend to supress the combustion temperature, and interfere with the combustion process rather than improve it. It appears that the amount of water vapor should be closely related to the combustion conditions in a particular installation, so that the degree of incompleteness of combustion in the absence of water vapor can be compensated for by appropriate adjustment of the vapor-injection equipment.
|
<reponame>alirezamirian/ngx-panes
import {AfterViewInit, Directive, ElementRef, Inject, Input, NgZone, OnDestroy, Renderer2} from '@angular/core';
import {CoerceBoolean} from '../utils/decorators';
import {DOCUMENT} from '@angular/common';
import {fromEvent} from 'rxjs/observable/fromEvent';
import {debounceTime, merge} from 'rxjs/operators';
import {Subscription} from 'rxjs/Subscription';
/**
* Makes `pane-area` fill entire remaining window height. The more preferred way to achieve this is with pure
* css (with flexbox or other approaches). However css solution might not be available in some cases or it may
* require a lot of `height: 100%` styles on all descendants back to body.
*
* @usage
* <ngx-pane-area ngxFullHeight>
* ...
* </ngx-pane-area>
*
* @experimental
*/
@Directive({
selector: 'ngx-pane-area[ngxFullHeight]'
})
export class FullHeightDirective implements AfterViewInit, OnDestroy {
/**
* Whether directive is active or not.
* @type {boolean}
*/
@Input('ngxFullHeight')
@CoerceBoolean
enabled = true;
// low priority TODO: react to changes. setup and tear down event handling when active is false.
/**
* Offset to consider when sizing pane-area. The offset is subtracted from the calculated height
* @type {number}
*/
@Input('ngxFullHeightOffset')
offsetHeight = 1;
private subscription: Subscription;
constructor(private elementRef: ElementRef,
private renderer: Renderer2,
private ngZone: NgZone,
@Inject(DOCUMENT) private document: Document) {
}
ngAfterViewInit(): void {
this.ngZone.runOutsideAngular(() => {
this.update();
if (this.document && typeof window !== 'undefined') {
const resize$ = fromEvent(window, 'resize');
const transitionEnd$ = fromEvent(this.document, 'transitionend');
this.subscription = resize$.pipe(
merge(transitionEnd$),
debounceTime(100)
).subscribe(() => this.update());
}
});
}
ngOnDestroy(): void {
if (this.subscription) {
this.subscription.unsubscribe();
}
}
private update() {
if (this.enabled) {
const el: HTMLElement = this.elementRef.nativeElement;
// const offsetParent = <HTMLElement> el.offsetParent;
let height;
if (typeof window !== 'undefined') {
const top = el.getBoundingClientRect().top;
if (top >= 0) {
height = window.innerHeight - top;
}
}
// if (offsetParent && el.offsetTop !== null) {
// height = offsetParent.offsetHeight - el.offsetTop;
// }
if (height) {
height -= this.offsetHeight;
}
if (height > 50) {
this.renderer.setStyle(el, 'height', `${height}px`);
}
}
}
}
|
// Make the userdata as a dict-like map.
func Map(in io.Reader) *UdMap {
lines := getLines(in)
envmap := makeMap(lines)
u := &UdMap{envmap}
return u
}
|
package com.mizhousoft.weixin.miniapp.service;
import com.mizhousoft.weixin.common.WXException;
import com.mizhousoft.weixin.miniapp.model.WxJscode2SessionResult;
/**
* 微信小程序服务
*
* @version
*/
public interface WxMiniAppService
{
// auth.code2Session
String JSCODE_TO_SESSION_URL = "https://api.weixin.qq.com/sns/jscode2session?appid=%s&secret=%s&js_code=%s&grant_type=authorization_code";
/**
* 获取微信APP ID
*
* @return
*/
String getAppId();
/**
* 获取登录后的session信息
*
* @param jsCode
* @return
* @throws WXException
*/
WxJscode2SessionResult jsCode2Session(String jsCode) throws WXException;
}
|
<reponame>cadeli/CdlUI<filename>CdlUIg/src/com/cadeli/ui/controls/CdlKnob.java
/*
Copyright 2013 Cadeli
Contact the authors at <EMAIL>
See updates at http://github.com/cadeli/CdlUI
Licensed under the Apache License, Version 2.0 (the "License");
you may not use this file except in compliance with the License.
You may obtain a copy of the License at
http://www.apache.org/licenses/LICENSE-2.0
Unless required by applicable law or agreed to in writing, software
distributed under the License is distributed on an "AS IS" BASIS,
WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
See the License for the specific language governing permissions and
limitations under the License.
*/
package com.cadeli.ui.controls;
import android.graphics.Canvas;
import android.graphics.Color;
import android.graphics.RectF;
import android.view.MotionEvent;
import com.cadeli.ui.CdlBaseButton;
import com.cadeli.ui.CdlPalette;
import com.cadeli.ui.CdlUtils;
public class CdlKnob extends CdlBaseButton {
private static final String TAG = "CdlKnob";
private CdlValue valueControler;
private boolean clickOnIncr=false;
public CdlKnob(String label) {
super();
setLabel(label);
valueControler = new CdlValue(label);
setHilightColor(Color.rgb(255, 0, 0));
}
public void draw(Canvas canvas) {
if (isVisible() ) {
//super.draw(canvas);
CdlPalette.getKnobPaintLarge().setStrokeWidth(CdlPalette.computeStrockWidth(1,rect.width(),rect.height()));
int wl = (int) CdlPalette.getKnobPaintLarge().getStrokeWidth();
double dispVal = valueControler.getValue();
if (valueControler.isNormalized()) {
dispVal *= 100;
}
String text = "" + (int) dispVal;
// XmlUtil.myLog(TAG," drawFader " + frameCursorRect);
RectF oval2 = new RectF(rect.left + wl, rect.top + wl, rect.right - wl, rect.bottom - wl);
float maxAngle = 300f;
float minAngle = 120f;
float alpha = (float) getValueControler().computeAlphaFromVal((int) dispVal, (int) maxAngle, 0);
CdlPalette.getKnobPaintLarge().setColor(CdlPalette.computeLowColor(getHilightColor()));
canvas.drawArc(oval2, minAngle, maxAngle, false, CdlPalette.getKnobPaintLarge());
CdlPalette.getKnobPaintLarge().setColor(getHilightColor());
canvas.drawArc(oval2, minAngle, alpha, false, CdlPalette.getKnobPaintLarge());
if (isEnable()) {
drawCenterText(canvas, text, CdlPalette.getTxtPaint(text.length(),w - 2 * padding, h - 2 * padding));
}
if (getLabel()!=null) {
drawBottomText(canvas, getLabel(), CdlPalette.getTxtPaint(getLabel().length(),w/2 - 2 * padding, h/2 - 2 * padding));
}
}
}
public void scroll(MotionEvent e1, MotionEvent e2, float distanceX, float distanceY) {
if (!isEnable())
return;
valueControler.setValueFromDistance(distanceY, rect.height(), 2);
super.scroll(e1, e2, distanceX, distanceY);
}
public CdlValue getValueControler() {
return valueControler;
}
public void longPress(MotionEvent e) {
CdlUtils.cdlLog(TAG, "longpress" + e);
if (!isEnable())
return;
valueControler.setValuesToMiddle();
super.longPress(e);
}
public void singleTapUp(MotionEvent e){
if (e.getX() < rect.centerX()) {
clickOnIncr=false;
} else {
clickOnIncr=true;
}
super.singleTapUp(e);
}
public boolean isClickOnIncr() {
return clickOnIncr;
}
}
|
The Rebound of the Capitalist State: The Rearticulation of the StateCapital Nexus in the Global Crisis With the financial crisis and the shockwaves it has sent through the global system many argue that we are witnessing the end of an era: a simultaneous crisis of neoliberal globalization and a crisis of US hegemony in the context of a power shift towards the East and attendant new geopolitical rivalries. The economic crisis has raised the question of whether we are witnessing the transition to a new phase of global capitalism. Many observers have interpreted the turn of events over the past decade as the death struggle of the neoliberal project, and as signaling a return of the state and of statist regulation to the center stage of global capitalism. Indeed, in recent years we have been able to observe two trends that appear to lend support to this notion. First, in the crisis-ridden core of the global economy, a full-blown depression was only averted by the state taking over the reins of capital, saving the hypertrophied financial sector from collapse by huge bail-outs or even outright nationalization, and subsequently by unprecedented stimulus programs sustaining overall demand where the market was unable to. Subsequently, the financial crisis has morphed into a sovereign debt crisis enveloping nearly all of the developed capitalist countries. In the Eurozone in particular, the crisis is raising the question of the relationship between capital and the state with ever more clarity: who is the real sovereign? So far, European politics has been unable and/or unwilling to challenge the sovereignty of capital: financial markets rule, politics kowtows to this sovereign in fearful reverence. But the voters in Europe seem to be on the verge of challenging the sovereignty of capital, thus also again putting the nature of the statecapital nexus on the political agenda. Second, countries outside the core, such as Brazil, India, and especially China, appear to have escaped relatively unscathed from the crisis, or at least have continued their economic and political rise arguably challenging the hegemony of the West. The role of the state in steering these economies through the crisis and forward onto their developmental path has been unmistakable. Moreover, these and other rising Southern states are the home to often state-owned or
|
<reponame>thecoblack/CompilerGym
# Copyright (c) Facebook, Inc. and its affiliates.
#
# This source code is licensed under the MIT license found in the
# LICENSE file in the root directory of this source tree.
"""Tests for the Csmith dataset."""
from itertools import islice
from pathlib import Path
import gym
import numpy as np
import pytest
from compiler_gym.envs.gcc.datasets import CsmithBenchmark
from tests.pytest_plugins.common import is_ci
from tests.pytest_plugins.gcc import with_gcc_support
from tests.test_main import main
pytest_plugins = ["tests.pytest_plugins.common", "tests.pytest_plugins.gcc"]
@pytest.mark.xfail(
reason="github.com/facebookresearch/CompilerGym/issues/459",
)
@with_gcc_support
def test_csmith_size(gcc_bin: str):
with gym.make("gcc-v0", gcc_bin=gcc_bin) as env:
csmith_dataset = env.datasets["generator://csmith-v0"]
assert csmith_dataset.size == 0
assert len(csmith_dataset) == 0
@pytest.mark.xfail(
reason="github.com/facebookresearch/CompilerGym/issues/459",
)
@with_gcc_support
@pytest.mark.parametrize("index", range(3) if is_ci() else range(10))
def test_csmith_random_select(gcc_bin: str, index: int, tmpwd: Path):
with gym.make("gcc-v0", gcc_bin=gcc_bin) as env:
csmith_dataset = env.datasets["generator://csmith-v0"]
uri = next(islice(csmith_dataset.benchmark_uris(), index, None))
benchmark = csmith_dataset.benchmark(uri)
assert isinstance(benchmark, CsmithBenchmark)
env.reset(benchmark=benchmark)
assert benchmark.source
benchmark.write_sources_to_directory(tmpwd)
assert (tmpwd / "source.c").is_file()
@pytest.mark.xfail(
reason="github.com/facebookresearch/CompilerGym/issues/459",
)
@with_gcc_support
def test_random_benchmark(gcc_bin: str):
with gym.make("gcc-v0", gcc_bin=gcc_bin) as env:
csmith_dataset = env.datasets["generator://csmith-v0"]
num_benchmarks = 5
rng = np.random.default_rng(0)
random_benchmarks = {
b.uri
for b in (
csmith_dataset.random_benchmark(rng) for _ in range(num_benchmarks)
)
}
assert len(random_benchmarks) == num_benchmarks
@pytest.mark.xfail(
reason="github.com/facebookresearch/CompilerGym/issues/459",
)
@with_gcc_support
def test_csmith_from_seed_retry_count_exceeded(gcc_bin: str):
with gym.make("gcc-v0", gcc_bin=gcc_bin) as env:
csmith_dataset = env.datasets["generator://csmith-v0"]
with pytest.raises(OSError, match="Csmith failed after 5 attempts with seed 1"):
csmith_dataset.benchmark_from_seed(seed=1, max_retries=3, retry_count=5)
if __name__ == "__main__":
main()
|
Temperature Robust Active-Compensated Sound Field Reproduction Using Impulse Response Shaping Spatial audio may be performed in rooms using active-compensated sound field reproduction (AC-SFR), to cancel the reverberant reflections. Reproduction of a sound field may be performed using precalculated loudspeaker filters. However the robustness can be poor due to the temperature-induced perturbation of the room impulse responses (RIR). To compensate for reverberation, filters with significant non-causal components are designed. It is known that the requirements on the loudspeaker filters for room equalization may be reduced by applying the method of impulse response shaping (IRS). In this paper, we show that actively compensating paths with a long propagation distance are more heavily influenced by temperature than short paths. We hence impose a shaping penalty on the non-causal components of designed loudspeaker filters, to reduce the error caused by a change in temperature. We obtain AC-SFR designs that are more robust to changes in temperature.
|
def least_common_subsumer(self, concept1, concept2):
for concept_x in self.parent_path(concept1):
for concept_y in self.parent_path(concept2):
if concept_x == concept_y:
return concept_x
return None
|
/**
* The main Damage Calculator of the PokeJava program. This method is
* vital in setting the changing values of health of the Pokemon
* throught the game. It uses {@link me.pavva.pokejava.Type#doStabCheck doStabCheck} method
* and {@link me.pavva.pokejava.Type#doEffectCheck doEffectCheck} method to realistically
* change the values of the health of the Pokemon.
*
* @param attacker The Pokemon which is attacking. Its attack value is used in determining the damage done.
* @param defender The Pokemon which is receiving damage. Its defense value is used in determing the damage done. Its health value is changed at the end of the method
* @param attackerMove The Move which the attacking Pokemon is using. Its power and type are used to determine the damage, STAB, and effectivity.
*/
public static void attack(Pokemon attacker, Pokemon defender, Move attackerMove) {
int level = 100;
int a = attacker.getAttack();
int d = defender.getDefense();
int power = attackerMove.getPower();
double stab = Type.doStabCheck(attackerMove, attacker);
double effectivity = Type.doEffectCheck(attackerMove, defender);
double modifier = (stab * effectivity);
double damage = (((((((((2 * level) / 5) + 2) * power) * (a / d))) / 50) + 2) * modifier);
defender.setHealth(defender.getHealth() - damage);
attackerMove.points--;
}
|
Electric Vehicle Deployment - Where Should We Be Today?
Electric vehicles (EVs) have come under siege in the media in the past two years, with several observers pointing to shortcomings like driving range, performance in cold weather and resale value as indicators of their imminent demise. Do we know for sure that EVs will overcome all these challenges? No. But we are seeing impressive year-on-year sales, declining battery costs, a decarbonizing power sector, and cities around the world committed to reducing congestion and local air pollution. For these reasons, EVs should not be dismissed and are among the best options to decarbonize the transport sector while boosting a flagging automotive sector, creating jobs, and reducing local air pollution.
The real question asked by few is this: where should EVs be today? The answer should probably be framed in terms of technological development and a close proxy for measuring development would be another vehicle such as the hybrid electric vehicle (HEV). In Figure 1, you can see new vehicle sales versus over time since the vehicle’s initial market launch (date of introduction in parentheses). This figure shows that all major battery electric vehicles (BEV) and plug-in hybrid electric vehicles (PHEV) are on track or doing better than what the Prius HEV was doing at a similar time. Of course, this is not strictly an apples-to-apples comparison (it does not take overall vehicle market into account, nor potential subsidy effects, for example), but does help us evaluate a true answer, beyond the press eager for a fail-or-victory message.
The truth is, given that EVs were only released in 2011 to a full range of consumers worldwide, a doubling of sales (approximately 120,000 in 2012 vs. 45,000 in 2011) is not bad growth. Of course, the key is to keep this momentum to hit intermediate-to-long-term targets, but still; perhaps the death of EVs is greatly exaggerated?
The simple truth is that EVs are coming along, but they are going through a delicate phase that most new technologies experience in the early years when only so-called “Early Adopters” begin buying the product, being less sensitive to a higher price point. Consider the MP3 player in the late 1990s, before Apple introduced the iPod in 2001. Another parallel “product” launch was the Internet, which transcended product state and spurred a systematic reinvention of information sharing in a revolution that took years, not days. EVs similarly have the potential to integrate into the power grid and do much more than get you from Point A to Point B.
Bottom line – EVs are a new or (depending on your perspective) revived technology – and as such must pass through several stages of technological development, optimization, and scale-up. Today’s EVs are far better than the models sold a decade ago, but the costs are still high and infrastructure is still being developed. In the next two or three years, there may only be a few tens of thousands of EVs produced and sold around the world, but this period will allow for a much bigger expansion of markets toward the middle of the decade. By 2015, there is a good chance of EVs and plug-in hybrids becoming cost-competitive (or nearly so if including subsidies) with conventional gasoline and diesel vehicles.
The reason EVs (or fuel-cell vehicles for that matter) get lambasted or unequivocally praised is that we are tempted to look for a silver bullet to our energy security, economic, and environmental problems. Yet there is no need for a zero-sum game. Whichever advanced vehicle technology we pursue, at some point we cannot get better efficiencies or lower CO2 emissions from conventional gasoline and diesel cars. Even hybrids will have trouble reaching below 90 grams of CO2/km. In contrast, plug-in hybrids could go under 90 grams of CO2/km and full electric vehicles could reach well below 50 grams of CO2/km in areas with clean electricity. Either way, we need to make a sound investment, and electric vehicles are a far sounder investment than the cost of doing nothing.
The widespread deployment of EVs will take time. The Electric Vehicles Initiative, a coalition of 15 key countries, together has set a target of over 20 million EVs on the road by 2020. This is achievable, but even this will just be a small share (about 2%) of the world’s cars at that point. But it will set the stage for EVs to play an increasingly important role after 2020, and especially by 2030. The International Energy Agency (IEA) projects that EVs could account for 15% of the world’s vehicle fleet by 2030 and over one half by 2050. But we have to start somewhere.
Besides EVs, there are other promising alternative vehicle configurations, but what is clear is that EVs offer promise by virtue of their energy efficiency, relying on existing infrastructure, and can be considered desirable high-tech consumer products, all of which together makes these vehicles one of the likeliest technological solutions to lowering CO2 emissions in the transport sector in the next 40 years. However, improving conventional fuel economy and better urban planning and public transit options should be higher near-term priorities in the next 10 to 20 years. These parallel challenges can and need to be achieved, but not at the expense of the broader goal: ensuring reliable, affordable, low-carbon transport.
The promise of an EV is beyond replacing one vehicle type with another; rather EVs offer a clean solution in the near-term as cities try to understand how to best reduce congestion and local air pollution. Car sharing, two-way interactions with the electricity grid, and fleet economies are but three reasons for why the value proposition of EVs is greater than that of yet another hyped vehicle technology.
Tali Trigg is an international energy and transport analyst whose expertise is in transportation issues and technologies, with an emphasis on smart growth policies, bus rapid transit (BRT), and electric vehicles (EVs). Mr. Trigg can be found on twitter @talitrigg. He was invited to contribute this guest post by Plugged In’s Melissa C. Lott.
Disclaimer: The opinions expressed in this post are the responsibility of its authors and do not in any way reflect those of another organization.
1. Photo of two Chevy Volts and a Nissan Leaf charging in parking lot by rudisillart and used under this Creative Commons License.
|
import { PedidosPage } from './../pedidos/pedidos';
import { LojaService } from './../../providers/loja/loja.service';
import { HomePage } from './../home/home';
import { Component } from '@angular/core';
import { IonicPage, NavController, NavParams } from 'ionic-angular';
import { paginaInterface } from '../../app/app.component';
import { LojaPerfilPage } from '../loja-perfil/loja-perfil';
import { LojaProdutosPage } from '../loja-produtos/loja-produtos';
import { Loja } from '../../models/loja.model';
@IonicPage()
@Component({
selector: 'page-loja',
templateUrl: 'loja.html',
})
export class LojaPage {
paginas: paginaInterface[] = [
{ titulo: "Perfil da Loja", nome: "PerfilPage", componente: LojaPerfilPage, icone: "basket" },
{ titulo: "Pedidos", nome: "PedidosPage", componente: PedidosPage, icone: "cube" },
{ titulo: "Produtos", nome: "CatalogoPage", componente: LojaProdutosPage, icone: "cart" }
]
lojaId: string;
lojaAtiva: Loja;
constructor(
public navCtrl: NavController,
public navParams: NavParams,
public lojaService: LojaService) {
this.lojaId = navParams.get("lojaId");
}
ionViewDidLoad() {
this.lojaService.buscarLojaAtiva(this.lojaId).then(async loja => {
this.lojaAtiva = await loja.data() as Loja;
console.log(this.lojaAtiva);
})
}
abrirPagina(pagina: paginaInterface) {
this.navCtrl.push(pagina.componente, { loja: this.lojaAtiva, isLoja: true });
}
backMenu() {
this.navCtrl.setRoot(HomePage);
}
}
|
The Salary Trap The pay gap between men and women and for nonminority and minority workers has persisted for decades despite federal and state legislation and substantial enforcement efforts. While much of the pay differential can be traced to factors other than gender or race, such as occupational choice, union membership, anddifferent industry characteristics, the strong inference remains that unlawful wage discrimination is a contributing cause. The fact is that there is something embedded in the employment process itself that conspires to keep the pay of women and minorities low. Under current laws, a hiring company may ask job applicants for information 0on salary history and then use that information to set the salary for a newly hired employee. It's time to put the negotiation of salary offers on a level playing field by ensuring that a person's salary history is not used to unfairly eliminate them from consideration for a job or to perpetuate past wage discrimination. Until this situation is corrected, discriminatory wage inequities will continue.
|
Effects of perinatal stress and drug abuse on maternal behavior and sensorimotor development of affected progeny. Methamphetamine (MA) is an addictive psychostimulant with significant potential for abuse. Previous rat studies have demonstrated that MA use during pregnancy impairs maternal behavior and induced delayed development of affected pups. The offspring of drug-addictive mothers were often neglected and exposed to neonatal stressors. The present study therefore examines the effect of perinatal stressors combined with exposure to prenatal MA on the development of pups and maternal behavior. Dams were divided into three groups according to drug treatment during pregnancy: controls (C); saline (SA, s.c., 1 ml/kg); MA (s.c., 5 mg/ml/kg). Litters were divided into four groups according to postnatal stressors: controls (N); maternal separation (S); maternal cold-water stress (W); maternal separation plus cold-water stress (SW). The pup-retrieval test showed differences among postnatally stressed mothers and non-stressed controls. The righting reflex on a surface revealed delayed development of pups prenatally exposed to MA/SA and postnatal stress. Negative geotaxis and Rotarod results confirmed that the MA group was the most affected. Overall, our data suggests that a combination of perinatal stress and prenatal MA can have a detrimental effect on maternal behavior as well as on the sensorimotor development of pups. However, MA exposure during pregnancy seems to be the decisive factor for impairment.
|
//Get get value of key
//if not exist return nil interface
func (s *SimpleCache) Get(key string) interface{} {
var result interface{}
value, ok := s.cache.Load(key)
if ok && value != nil {
entry := value.(CacheEntry)
if entry.timestamp > time.Now().Unix() {
result = entry.value
}
}
return result
}
|
What types of COVID-19 conspiracies are populated by Twitter bots? With people moving out of physical public spaces due to containment measures to tackle the novel coronavirus (COVID-19) pandemic, online platforms become even more prominent tools to understand social discussion. Studying social media can be informative to assess how we are collectively coping with this unprecedented global crisis. However, social media platforms are also populated by bots, automated accounts that can amplify certain topics of discussion at the expense of others. In this paper, we study 43.3M English tweets about COVID-19 and provide early evidence of the use of bots to promote political conspiracies in the United States, in stark contrast with humans who focus on public health concerns.
|
<reponame>minimouli/website
/**
* Copyright (c) Minimouli
*
* This source code is licensed under the MIT license found in the
* LICENSE file in the root directory of this source tree.
*/
import { ReactElement } from 'react'
import { Hints, Syntheses } from '@minimouli/types'
import ChipCounter from './ChipCounter'
import Divider from './Divider'
import FailTest from './FailTest'
import IndicatorLarge from './IndicatorLarge'
import SuccessTest from './SuccessTest'
import LightSuiteSynthesis from '../types/LightSuiteSynthesis'
import styles from '../styles/SuiteCard.module.scss'
interface SuiteCardProps {
suite: LightSuiteSynthesis
}
const isDividerNeeded = (suite: LightSuiteSynthesis, current: Syntheses.TestSynthesis, index: number): boolean => {
const next: Syntheses.TestSynthesis | undefined = suite.tests[index + 1]
const containsFailures: boolean = suite.score !== 1
if (!containsFailures)
return false
const isLast: boolean = index === suite.tests.length - 1
const isCurrentAFailure: boolean = current.status === Syntheses.TestStatus.FAILURE
const isNextAFailure: boolean = next?.status === Syntheses.TestStatus.FAILURE || false
if (isLast)
return false
if (isCurrentAFailure)
return true
if (isNextAFailure)
return true
return false
}
const countCategory = (tests: Syntheses.TestSynthesis[], category: Hints.HintCategory): number => {
return tests.reduce((previous: number, test: Syntheses.TestSynthesis) => {
if (!test.hint)
return previous
if (test.hint.category === category)
return previous + 1
return previous
}, 0)
}
const SuiteCard = ({suite}: SuiteCardProps) => {
const categorizedTests: Syntheses.TestSynthesis[] = suite.tests.filter((test: Syntheses.TestSynthesis) => !!test.hint?.category)
const chips = {
output: countCategory(categorizedTests, Hints.HintCategory.OUTPUT),
exitCode: countCategory(categorizedTests, Hints.HintCategory.EXIT_CODE),
timeout: countCategory(categorizedTests, Hints.HintCategory.TIMEOUT)
}
return (
<section className={styles.container} >
<div className={styles.head} >
<div className={styles.headline} >
<div className={styles.title} >
<h2>{suite.name}</h2>
</div>
{categorizedTests.length > 0 && (
<div className={styles.chips} >
{chips.output > 0 && <ChipCounter category={Hints.HintCategory.OUTPUT} value={chips.output} />}
{chips.exitCode > 0 && <ChipCounter category={Hints.HintCategory.EXIT_CODE} value={chips.exitCode} />}
{chips.timeout > 0 && <ChipCounter category={Hints.HintCategory.TIMEOUT} value={chips.timeout} />}
</div>
)}
</div>
<div className={styles.indicator} >
<IndicatorLarge value={suite.score} />
</div>
</div>
<Divider />
<div className={styles.tests} >
{suite.tests.map((test: Syntheses.TestSynthesis, index: number) => {
const showDivider: boolean = isDividerNeeded(suite, test, index)
if (test.status === Syntheses.TestStatus.SUCCESS) {
return (
<div className={styles.item} key={index} >
<SuccessTest test={test} />
{showDivider && <Divider/>}
</div>
)
}
return (
<div className={styles.item} key={index} >
<FailTest test={test} />
{showDivider && <Divider/>}
</div>
)
})}
</div>
</section>
)
}
export default SuiteCard
|
from datetime import datetime
from collections import OrderedDict
import pytest
from cidc_api.models import (
ClinicalTrial,
Cohort,
CollectionEvent,
insert_record_batch,
Sample,
Shipment,
TrialMetadata,
)
from cidc_api.models.models import UploadJobStatus, UploadJobs
from cidc_api.models.templates.csms_api import *
from cidc_api.models.templates.file_metadata import Upload
from cidc_api.models.templates.trial_metadata import Participant
from tests.csms.data import manifests
from tests.csms.utils import validate_json_blob, validate_relational
from ...resources.test_trial_metadata import setup_user
def manifest_change_setup(cidc_api, monkeypatch):
setup_user(cidc_api, monkeypatch)
# prepare relational db
ordered_records = OrderedDict()
ordered_records[ClinicalTrial] = [
ClinicalTrial(protocol_identifier="test_trial"),
ClinicalTrial(protocol_identifier="foo"), # need a second valid trial
]
ordered_records[CollectionEvent] = [
CollectionEvent(trial_id="test_trial", event_name="Baseline"),
CollectionEvent(trial_id="test_trial", event_name="Pre_Day_1_Cycle_2"),
CollectionEvent(trial_id="test_trial", event_name="On_Treatment"),
]
ordered_records[Cohort] = [
Cohort(trial_id="test_trial", cohort_name="Arm_A"),
Cohort(trial_id="test_trial", cohort_name="Arm_Z"),
]
errs = insert_record_batch(ordered_records)
assert len(errs) == 0
# also checks for trial existence in JSON blobs
metadata_json = {
"protocol_identifier": "test_trial",
"participants": [],
"shipments": [],
"allowed_cohort_names": [],
"allowed_collection_event_names": [],
}
TrialMetadata(trial_id="test_trial", metadata_json=metadata_json).insert()
# need a second valid trial
metadata_json["protocol_identifier"] = "foo"
TrialMetadata(trial_id="foo", metadata_json=metadata_json).insert()
for manifest in manifests:
if manifest.get("status") not in (None, "qc_complete"):
continue
# insert manifest before we check for changes
insert_manifest_from_json(manifest, uploader_email="<EMAIL>")
# should check out, but let's make sure
validate_relational("test_trial")
def test_change_protocol_identifier_error(cidc_api, clean_db, monkeypatch):
with cidc_api.app_context():
manifest_change_setup(cidc_api, monkeypatch)
for manifest in manifests:
if manifest.get("status") not in (None, "qc_complete"):
continue
# Test critical changes throws Exception on samples
# Change trial_id or manifest_id is adding a new Shipment
## but this means they'll conflict on the sample
# a bad ID raises a no trial found like insert_manifest_...
with pytest.raises(Exception, match="No trial found with id"):
new_manifest = {k: v for k, v in manifest.items() if k != "samples"}
new_manifest["samples"] = [
{
k: v if k != "protocol_identifier" else "bar"
for k, v in sample.items()
}
for sample in manifest["samples"]
]
detect_manifest_changes(new_manifest, uploader_email="<EMAIL>")
# this is why we needed a second valid trial to test this check
with pytest.raises(Exception, match="Change in critical field for"):
# CIDC trial_id = CSMS protocol_identifier
# stored on samples, not manifest
new_manifest = {k: v for k, v in manifest.items() if k != "samples"}
new_manifest["samples"] = [
{
k: v if k != "protocol_identifier" else "foo"
for k, v in sample.items()
}
for sample in manifest["samples"]
]
detect_manifest_changes(new_manifest, uploader_email="<EMAIL>")
def test_change_manifest_id_error(cidc_api, clean_db, monkeypatch):
with cidc_api.app_context():
manifest_change_setup(cidc_api, monkeypatch)
for manifest in manifests:
if manifest.get("status") not in (None, "qc_complete"):
continue
# manifest_id has no such complication, but is also on the samples
# changing the manifest_id makes it new
with pytest.raises(NewManifestError):
new_manifest = {
k: v if k != "manifest_id" else "foo" for k, v in manifest.items()
}
new_manifest["samples"] = [
{k: v if k != "manifest_id" else "foo" for k, v in sample.items()}
for sample in new_manifest["samples"]
]
detect_manifest_changes(new_manifest, uploader_email="<EMAIL>")
def test_change_cimac_id_error(cidc_api, clean_db, monkeypatch):
with cidc_api.app_context():
manifest_change_setup(cidc_api, monkeypatch)
for manifest in manifests:
if manifest.get("status") not in (None, "qc_complete"):
continue
# Changing a cimac_id is adding/removing a Sample
## so this is a different error
with pytest.raises(Exception, match="Malformatted cimac_id"):
new_manifest = {k: v for k, v in manifest.items()}
new_manifest["samples"] = [
{k: v if k != "cimac_id" else "foo" for k, v in sample.items()}
if n == 0
else sample
for n, sample in enumerate(manifest["samples"])
]
detect_manifest_changes(new_manifest, uploader_email="<EMAIL>")
# need to use an actually valid cimac_id
with pytest.raises(Exception, match="Missing sample"):
new_manifest = {k: v for k, v in manifest.items() if k != "samples"}
new_manifest["samples"] = [
{
k: v if k != "cimac_id" else "CXXXP0555.00"
for k, v in sample.items()
}
if n == 0
else sample
for n, sample in enumerate(manifest["samples"])
]
detect_manifest_changes(new_manifest, uploader_email="<EMAIL>")
def test_manifest_non_critical_changes(cidc_api, clean_db, monkeypatch):
with cidc_api.app_context():
manifest_change_setup(cidc_api, monkeypatch)
# grab a completed manifest
for manifest in manifests:
if manifest.get("status") not in (None, "qc_complete"):
continue
# Test non-critical changes on the manifest itself
for key in manifest.keys():
# ignore list from calc_diff + criticals
if key in [
"barcode",
"biobank_id",
"manifest_id",
"modified_time",
"modified_timestamp",
"samples",
"status",
"submitter",
]:
continue
new_manifest = {
k: v if k != key else "foo" for k, v in manifest.items()
}
records, changes = detect_manifest_changes(
new_manifest, uploader_email="<EMAIL>"
)
assert (
len(records) == 1
and Shipment in records
and len(records[Shipment]) == 1
), f"{records}\n{changes}"
assert getattr(records[Shipment][0], key) == "foo", (
str(records) + "\n" + str(changes)
)
assert len(changes) == 1 and changes[0] == Change(
entity_type="shipment",
manifest_id=manifest["manifest_id"],
trial_id=manifest["samples"][0]["protocol_identifier"],
changes={
key: (
datetime.strptime(manifest[key], "%Y-%m-%d %H:%M:%S").date()
if key.startswith("date")
else manifest[key],
"foo",
),
},
), str(changes)
def test_manifest_non_critical_changes_on_samples(cidc_api, clean_db, monkeypatch):
with cidc_api.app_context():
manifest_change_setup(cidc_api, monkeypatch)
# grab a completed manifest
for manifest in manifests:
if manifest.get("status") not in (None, "qc_complete"):
continue
# Test non-critical changes for the manifest but stored on the samples
for key in [
"assay_priority",
"assay_type",
"sample_manifest_type",
]:
# ignore list from calc_diff + criticals
if key in [
"barcode",
"biobank_id",
"manifest_id",
"modified_time",
"modified_timestamp",
"samples",
"status",
"submitter",
]:
continue
new_manifest = {k: v for k, v in manifest.items() if k != "samples"}
if key == "sample_manifest_type":
new_manifest["samples"] = [
{k: v for k, v in sample.items()}
for sample in manifest["samples"]
]
for n in range(len(new_manifest["samples"])):
new_manifest["samples"][n].update(
{
"processed_sample_type": "foo",
"sample_manifest_type": "Tissue Scroll",
"processed_sample_derivative": "Germline DNA",
}
)
else:
new_manifest["samples"] = [
{k: v if k != key else "foo" for k, v in sample.items()}
for sample in manifest["samples"]
]
records, changes = detect_manifest_changes(
new_manifest, uploader_email="<EMAIL>"
)
if key == "sample_manifest_type":
assert (
len(records) == 2
and Sample in records
and Upload in records
and len(records[Upload]) == 1
), f"{records}\n{changes}"
else:
assert (
len(records) == 1
and Shipment in records
and len(records[Shipment]) == 1
), f"{records}\n{changes}"
assert getattr(records[Shipment][0], key) == "foo", (
str(records) + "\n" + str(changes)
)
assert len(changes) == 1 and changes[0] == Change(
entity_type="shipment",
manifest_id=manifest["manifest_id"],
trial_id=manifest["samples"][0]["protocol_identifier"],
changes={key: (manifest["samples"][0][key], "foo"),},
), str(changes)
def test_sample_non_critical_changes(cidc_api, clean_db, monkeypatch):
with cidc_api.app_context():
manifest_change_setup(cidc_api, monkeypatch)
# grab a completed manifest
for manifest in manifests:
if manifest.get("status") not in (None, "qc_complete"):
continue
# Test non-critical changes on the samples
for key in manifest["samples"][0].keys():
# ignore list from calc_diff + criticals
if key in [
"assay_priority",
"assay_type",
"barcode",
"biobank_id",
"cimac_id",
"collection_event_name",
"entry_number",
"manifest_id",
"modified_time",
"modified_timestamp",
"processed_sample_derivative",
"processed_sample_type",
"protocol_identifier",
"qc_comments",
"recorded_collection_event_name",
"sample_approved",
"sample_key",
"sample_manifest_type",
"samples",
"status",
"submitter",
"trial_participant_id",
"type_of_sample",
]:
continue
else:
print(key)
new_manifest = {k: v for k, v in manifest.items() if k != "samples"}
if key in ["sample_derivative_concentration"]:
new_manifest["samples"] = [
{k: v if k != key else 10 for k, v in sample.items()}
if n == 0
else sample
for n, sample in enumerate(manifest["samples"])
]
else:
new_manifest["samples"] = [
{k: v if k != key else "foo" for k, v in sample.items()}
if n == 0
else sample
for n, sample in enumerate(manifest["samples"])
]
records, changes = detect_manifest_changes(
new_manifest, uploader_email="<EMAIL>"
)
# name change for when we're looking below
if key == "standardized_collection_event_name":
key = "collection_event_name"
if key not in ["cohort_name", "participant_id"]:
assert (
len(records) == 1
and Sample in records
and len(records[Sample]) == 1
), f"{records}\n{changes}"
assert (
getattr(records[Sample][0], key)
== new_manifest["samples"][0][key]
), f"{records}\n{changes}"
elif key == "cohort_name":
assert (
len(records) == 1
and Participant in records
and len(records[Participant]) == 1
), f"{records}\n{changes}"
assert (
getattr(records[Participant][0], key)
== new_manifest["samples"][0][key]
), f"{records}\n{changes}"
else: # key == "participant_id":
assert (
len(records) == 1
and Participant in records
and len(records[Participant]) == 1
), f"{records}\n{changes}"
assert (
getattr(records[Participant][0], "trial_participant_id")
== new_manifest["samples"][0][key]
), f"{records}\n{changes}"
assert len(changes) == 1 and changes[0] == Change(
entity_type="sample",
manifest_id=manifest["manifest_id"],
cimac_id=manifest["samples"][0]["cimac_id"],
trial_id=manifest["samples"][0]["protocol_identifier"],
changes={
key: (
manifest["samples"][0][key],
new_manifest["samples"][0][key],
),
},
), str(changes)
def test_insert_manifest_into_blob(cidc_api, clean_db, monkeypatch):
"""test that insertion of manifest into blob works as expected"""
# grab a completed manifest
manifest = [m for m in manifests if m.get("status") in [None, "qc_complete"]][0]
with cidc_api.app_context():
setup_user(cidc_api, monkeypatch)
# blank db throws error
with pytest.raises(Exception, match="No trial found with id"):
insert_manifest_into_blob(manifest, uploader_email="<EMAIL>")
# also checks for trial existence in relational
errs = insert_record_batch(
{ClinicalTrial: [ClinicalTrial(protocol_identifier="test_trial",)]}
)
assert len(errs) == 0
metadata_json = {
"protocol_identifier": "test_trial",
"participants": [],
"shipments": [],
"allowed_cohort_names": [],
"allowed_collection_event_names": [],
}
TrialMetadata(trial_id="test_trial", metadata_json=metadata_json,).insert()
with pytest.raises(Exception, match="not found within '/allowed_cohort_names/"):
insert_manifest_into_blob(manifest, uploader_email="<EMAIL>")
metadata_json["allowed_cohort_names"] = ["Arm_A", "Arm_Z"]
TrialMetadata.select_for_update_by_trial_id("test_trial").update(
changes={"metadata_json": metadata_json}
)
with pytest.raises(
Exception, match="not found within '/allowed_collection_event_names/"
):
insert_manifest_into_blob(manifest, uploader_email="<EMAIL>")
metadata_json["allowed_collection_event_names"] = [
"Baseline",
"Pre_Day_1_Cycle_2",
]
TrialMetadata.select_for_update_by_trial_id("test_trial").update(
changes={"metadata_json": metadata_json}
)
insert_manifest_into_blob(manifest, uploader_email="<EMAIL>")
md_json = TrialMetadata.select_for_update_by_trial_id(
"test_trial"
).metadata_json
validate_json_blob(md_json)
for other_manifest in [
m
for m in manifests
if m.get("status") in [None, "qc_complete"]
if m != manifest
]:
insert_manifest_into_blob(other_manifest, uploader_email="<EMAIL>")
md_json = TrialMetadata.select_for_update_by_trial_id(
"test_trial"
).metadata_json
validate_json_blob(md_json)
with pytest.raises(Exception, match="already exists for trial"):
insert_manifest_into_blob(manifest, uploader_email="<EMAIL>")
def test_insert_manifest_from_json(cidc_api, clean_db, monkeypatch):
"""test that insertion of manifest from json works as expected"""
# grab a completed manifest
manifest = [m for m in manifests if m.get("status") in [None, "qc_complete"]][0]
with cidc_api.app_context():
setup_user(cidc_api, monkeypatch)
# blank db throws error
with pytest.raises(Exception, match="No trial found with id"):
insert_manifest_from_json(manifest, uploader_email="<EMAIL>")
errs = insert_record_batch(
{ClinicalTrial: [ClinicalTrial(protocol_identifier="test_trial",)]}
)
assert len(errs) == 0
# also checks for trial existence in JSON blobs
metadata_json = {
"protocol_identifier": "test_trial",
"participants": [],
"shipments": [],
"allowed_cohort_names": [],
"allowed_collection_event_names": [],
}
TrialMetadata(trial_id="test_trial", metadata_json=metadata_json,).insert()
with pytest.raises(
Exception, match="No Collection event with trial_id, event_name"
):
insert_manifest_from_json(manifest, uploader_email="<EMAIL>")
errs = insert_record_batch(
{
CollectionEvent: [
CollectionEvent(trial_id="test_trial", event_name="Baseline"),
CollectionEvent(
trial_id="test_trial", event_name="Pre_Day_1_Cycle_2"
),
CollectionEvent(trial_id="test_trial", event_name="On_Treatment"),
]
}
)
assert len(errs) == 0, errs
with pytest.raises(Exception, match="no Cohort with trial_id, cohort_name"):
insert_manifest_from_json(manifest, uploader_email="<EMAIL>")
errs = insert_record_batch(
{
Cohort: [
Cohort(trial_id="test_trial", cohort_name="Arm_A"),
Cohort(trial_id="test_trial", cohort_name="Arm_Z"),
]
}
)
assert len(errs) == 0
insert_manifest_from_json(manifest, uploader_email="<EMAIL>")
validate_relational("test_trial")
for other_manifest in [
m
for m in manifests
if m.get("status") in [None, "qc_complete"] and m != manifest
]:
insert_manifest_from_json(other_manifest, uploader_email="<EMAIL>")
validate_relational("test_trial")
with pytest.raises(Exception, match="already exists for trial"):
insert_manifest_from_json(manifest, uploader_email="<EMAIL>")
|
#!/usr/bin/env python
import os
from setuptools import setup, find_packages
execfile(os.path.join(os.path.dirname(__file__), "src/fileseq/__version__.py"))
descript = 'A Python library for parsing frame ranges and file ' \
'sequences based on a similar library found in Katana.'
setup(name='Fileseq',
version=__version__,
package_dir = {'': 'src'},
packages=find_packages('src'),
test_suite="test.run",
author='<NAME>',
author_email='<EMAIL>',
url='https://github.com/sqlboy/fileseq',
description=descript
)
|
A review on radiomics and the future of theranostics for patient selection in precision medicine. The growing complexity and volume of clinical data and the associated decision-making processes in oncology promote the advent of precision medicine. Precision (or personalised) medicine describes preventive and/or treatment procedures that take individual patient variability into account when proscribing treatment, and has been hindered in the past by the strict requirements of accurate, robust, repeatable and preferably non-invasive biomarkers to stratify both the patient and the disease. In oncology, tumour subtypes are traditionally measured through repeated invasive biopsies, which are taxing for the patient and are cost and labour intensive. Quantitative analysis of routine clinical imaging provides an opportunity to capture tumour heterogeneity non-invasively, cost-effectively and on large scale. In current clinical practice radiological images are qualitatively analysed by expert radiologists whose interpretation is known to suffer from inter- and intra-operator variability. Radiomics, the high-throughput mining of image features from medical images, provides a quantitative and robust method to assess tumour heterogeneity, and radiomics-based signatures provide a powerful tool for precision medicine in cancer treatment. This study aims to provide an overview of the current state of radiomics as a precision medicine decision support tool. We first provide an overview of the requirements and challenges radiomics currently faces in being incorporated as a tool for precision medicine, followed by an outline of radiomics' current applications in the treatment of various types of cancer. We finish with a discussion of possible future advances that can further develop radiomics as a precision medicine tool.
|
Rapid DNA fingerprinting of pathogens by flow cytometry. BACKGROUND A new method for rapid discrimination among bacterial strains based on DNA fragment sizing by flow cytometry is presented. This revolutionary approach combines the reproducibility and reliability of restriction fragment length polymorphism (RFLP) analysis with the speed and sensitivity of flow cytometry. METHODS Bacterial genomic DNA was isolated and digested with a rare-cutting restriction endonuclease. The resulting fragments were stained stoichiometrically with PicoGreen dye and introduced into an ultrasensitive flow cytometer. A histogram of burst sizes from the restriction fragments (linearly related to fragment length in base pairs) resulted in a DNA fingerprint that was used to distinguish among different bacterial strains. RESULTS Five different strains of gram-negative Escherichia coli and six different strains of gram-positive Staphylococcus aureus were distinguished by analyzing their restriction fragments with DNA fragment sizing by flow cytometry. Fragment distribution analyses of extracted DNA were approximately 100 times faster and approximately 200,000 times more sensitive than pulsed-field gel electrophoresis (PFGE). When sample preparation time is included, the total DNA fragment analysis time was approximately 8 h by flow cytometry and approximately 24 h by PFGE. CONCLUSIONS DNA fragment sizing by flow cytometry is a fast and reliable technique that can be applied to the discrimination among species and strains of human pathogens. Unlike some polymerase chain reaction (PCR)-based methods, sequence information about the bacterial strains is not required, allowing the detection of unknown, newly emerged, or unanticipated strains.
|
Structural studies of fibrinolysis by electron microscopy. Fibrin is degraded by the fibrinolytic system in which a plasminogen activator converts plasminogen to plasmin, a serine protease that cleaves specific bonds in fibrin leading to solubilization. To elucidate further the biophysical processes involved in conversion of insoluble fibers to soluble fragments, fibrin was treated with either plasmin or the combination of plasminogen and plasminogen activator, and morphologic changes were observed using scanning electron microscopy. These changes were correlated with biochemical analysis and with characterization of released, soluble fragments by transmission electron microscopy. Initial changes in the fibrin matrix included creation of many free fiber ends and gaps in the continuity of fibers. With more extensive digestion, free fiber segments associated laterally, resulting in formation of thick fiber bundles. Supernatants of digesting clots, containing soluble derivatives, were negatively contrasted and examined by transmission electron microscopy. Large, complex fragments containing portions of multiple fibers were observed, as were pieces of individual fibers and smaller fragments previously identified. Some large fragments had sharply defined ends, indicating that they had been cleaved perpendicularly to the fiber direction. Other fibers showed splayed ends or a lacy meshwork of surrounding protofibrils. Longer times generated more small fragments whose molecular composition could be inferred from their appearance. These results indicate that fibrinolytic degradation results in larger pieces than previously identified and that plasmin digestion proceeds locally by transverse cutting across fibers rather than by progressive cleavage uniformly around the fiber.
|
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|
Back to Basics: Culturally Relevant Pedagogy in Special Education While the student population in public education is becoming more diverse, the representation of teachers of color remains low. With over half the student population in the United States considered as non-white, and only 20% of teachers identifying as teachers of color, it is imperative to examine the ways in which education professionals are addressing teaching and learning in a way that is inclusive of culturally diverse populations. Gloria Ladson-Billings developed her culturally relevant pedagogy framework nearly 30 years ago, and though rarely discussed in special education, her approach is critically important to the field. This article calls on teacher educators to engage future special education teachers in ways that support their implementation of CRP as an ongoing framework. In order to achieve this, we focus on the effective characteristics of culturally relevant special education teachers, and on creating culturally relevant special education teacher programs in higher education.
|
Mindfulness and Coping Skills as Predictors of Competitive Anxiety amongst Athletes in Indonesia Competitive anxiety is one of the psychological factors which greatly affect athletes' performances. Competitive anxiety is divided into somatic anxiety and cognitive anxiety. This study was conducted to look at mindfulness and coping skills as predictors of competitive anxiety. Through purposive sampling techniques, some (N = 159) senior athletes, representatives of various sports from various provinces in Indonesia, with an age range of 18-40 years were included in this study. This non-experimental research method design used three questionnaires, consisting of AAQ-II (mindfulness), ACSI (coping skills), and CSAI-2R (competitive anxiety) as measurement tools. Statistical analysis, using multiple regression, showed that mindfulness and coping skills simultaneously have a linear relationship to competitive anxiety, and significantly predict a competitive anxiety level of 29%. This means that mindfulness and coping skills can decrease competitive anxiety in athletes. Further analysis found that mindfulness plays a greater role in reducing competitive anxiety than coping skills.
|
Probing Toluene and Ethylbenzene Stable Glass Formation Using Inert Gas Permeation. Inert gas permeation is used to investigate the formation of stable glasses of toluene and ethylbenzene. The effect of deposition temperature (T(dep)) on the kinetic stability of the vapor deposited glasses is determined using Kr desorption spectra from within sandwich layers of either toluene or ethylbenzene. The results for toluene show that the most stable glass is formed at T(dep) = 0.92 T(g), although glasses with a kinetic stability within 50% of the most stable glass were found with deposition temperatures from 0.85 to 0.95 T(g). Similar results were found for ethylbenzene, which formed its most stable glass at 0.91 T(g) and formed stable glasses from 0.81 to 0.96 T(g). These results are consistent with recent calorimetric studies and demonstrate that the inert gas permeation technique provides a direct method to observe the onset of molecular translation motion that accompanies the glass to supercooled liquid transition.
|
import argparse
def example():
return 42
|
Cystic fibrosis--a single locus disease? Results of a population genetics study. In a population genetics study of cystic fibrosis (CF), we investigated the state of health of 1276 first cousins of CF index patients. Six hundred seventy-five married aunts and uncles (siblings of CF index patients' mothers and fathers) who had at least one child were interviewed. In only 1 of these 675 families, three children of a total of eight had died of CF. If CF occurs more frequently than in 1 in 3000 newborn babies in our population, our investigation supports the hypothesis that CF is caused by mutations at more than one locus. We also determined that the evidence furnished by such a study of other, more uncommon autosomal recessive disorders is limited.
|
<reponame>1tgr/rust-calc-graph<gh_stars>1-10
extern crate calc_graph;
use std::collections::HashMap;
use std::sync::Arc;
use std::time::{Duration, SystemTime};
use calc_graph::{Calc, Graph, Node, SharedNode, Source};
type BSNode<T> = SharedNode<Box<Calc<Value = T> + Send>>;
fn timed<T>(name: &str, f: impl FnOnce() -> T) -> T {
let start_time = SystemTime::now();
let result = f();
let duration = start_time.elapsed().unwrap_or(Duration::default());
println!(
"{} took {}µs",
name,
duration.as_secs() as u64 * 1_000_000 + duration.subsec_micros() as u64
);
result
}
fn node(
nodes: &mut HashMap<(u32, u32), BSNode<Arc<[u64; 32]>>>,
n: u32,
k: u32,
) -> BSNode<Arc<[u64; 32]>> {
if let Some(node) = nodes.get(&(n, k)) {
return node.clone();
}
if k == 0 || k >= n {
return node(nodes, 0, 0);
}
assert!(n >= 1, "n = {} k = {}", n, k);
assert!(k >= 1, "n = {} k = {}", n, k);
let node = Node::zip_update(
node(nodes, n - 1, k - 1),
node(nodes, n - 1, k),
Arc::new([0; 32]),
|sum, x, y| {
let sum = Arc::make_mut(sum);
for i in 0..32 {
sum[i] = x[i] + y[i];
}
true
},
).boxed()
.shared();
nodes.insert((n, k), node.clone());
node
}
fn setup() -> (
Node<Source<Arc<[u64; 32]>>>,
BSNode<Arc<[u64; 32]>>,
HashMap<(u32, u32), BSNode<Arc<[u64; 32]>>>,
) {
let graph = Graph::new();
let n1 = graph.source(Arc::new([1; 32]));
let mut nodes = HashMap::new();
nodes.insert((0, 0), n1.clone().boxed().shared());
(n1, node(&mut nodes, 80, 20), nodes)
}
fn main() {
setup();
let (n1, last, nodes) = timed("setup", || setup());
assert_eq!(1201, nodes.len());
assert_eq!(3_535_316_142_212_174_320, timed("calc", || last.get())[0]);
assert_eq!(
3_535_316_142_212_174_320,
timed("cached 1", || last.get())[0]
);
timed("dirty", || {
n1.update(|mut prev| {
*Arc::make_mut(&mut prev) = [2; 32];
true
})
});
assert_eq!(7_070_632_284_424_348_640, timed("recalc", || last.get())[0]);
assert_eq!(
7_070_632_284_424_348_640,
timed("cached 2", || last.get())[0]
);
}
|
<reponame>hackshieldteam/guardedbox
package com.guardedbox.controller;
import static com.guardedbox.constants.Constraints.EMAIL_MAX_LENGTH;
import static com.guardedbox.constants.Constraints.EMAIL_MIN_LENGTH;
import static com.guardedbox.constants.Constraints.EMAIL_PATTERN;
import javax.validation.Valid;
import javax.validation.constraints.Email;
import javax.validation.constraints.NotBlank;
import javax.validation.constraints.Size;
import org.springframework.beans.factory.annotation.Autowired;
import org.springframework.validation.annotation.Validated;
import org.springframework.web.bind.annotation.GetMapping;
import org.springframework.web.bind.annotation.PostMapping;
import org.springframework.web.bind.annotation.RequestBody;
import org.springframework.web.bind.annotation.RequestMapping;
import org.springframework.web.bind.annotation.RequestParam;
import org.springframework.web.bind.annotation.RestController;
import com.guardedbox.dto.AccountWithEncryptionPublicKeyDto;
import com.guardedbox.dto.AccountWithSaltDto;
import com.guardedbox.dto.CreateAccountDto;
import com.guardedbox.dto.RegistrationDto;
import com.guardedbox.dto.SuccessDto;
import com.guardedbox.service.CryptoCaptchaService;
import com.guardedbox.service.transactional.AccountsService;
import com.guardedbox.service.transactional.RegistrationsService;
/**
* Controller: Accounts.
*
* @author <EMAIL>
*
*/
@RestController
@RequestMapping("/api/accounts")
@Validated
public class AccountsController {
/** AccountsService. */
private final AccountsService accountsService;
/** RegistrationsService. */
private final RegistrationsService registrationsService;
/** CryptoCaptchaService. */
private final CryptoCaptchaService cryptoCaptchaService;
/**
* Constructor with Attributes.
*
* @param accountsService AccountsService.
* @param registrationsService RegistrationsService.
* @param cryptoCaptchaService CryptoCaptchaService.
*/
public AccountsController(
@Autowired AccountsService accountsService,
@Autowired RegistrationsService registrationsService,
@Autowired CryptoCaptchaService cryptoCaptchaService) {
this.accountsService = accountsService;
this.registrationsService = registrationsService;
this.cryptoCaptchaService = cryptoCaptchaService;
}
/**
* @param email An email.
* @return The salt of the account corresponding to the introduced email.
*/
@GetMapping("/salt")
public AccountWithSaltDto getAccountSalt(
@RequestParam(name = "email", required = true) @NotBlank @Email(regexp = EMAIL_PATTERN) @Size(min = EMAIL_MIN_LENGTH, max = EMAIL_MAX_LENGTH) String email) {
return accountsService.getAndCheckAccountWithSaltByEmail(email);
}
/**
* @param email An email.
* @return The encryption public key of the account corresponding to the introduced email.
*/
@GetMapping("/encryption-public-key")
public AccountWithEncryptionPublicKeyDto getAccountEncryptionPublicKey(
@RequestParam(name = "email", required = true) @NotBlank @Email(regexp = EMAIL_PATTERN) @Size(min = EMAIL_MIN_LENGTH, max = EMAIL_MAX_LENGTH) String email) {
return accountsService.getAndCheckAccountWithEncryptionPublicKeyByEmail(email);
}
/**
* Creates an Account.
*
* @param createAccountDto Object with the necessary data to create an Account.
* @return Object indicating if the execution was successful.
*/
@PostMapping()
public SuccessDto createAccount(
@RequestBody(required = true) @Valid CreateAccountDto createAccountDto) {
// Verify the crypto-captcha.
cryptoCaptchaService.verify(createAccountDto);
// Get the registration, checking if it exists and is not expired.
RegistrationDto registrationDto = registrationsService.getAndCheckRegistrationByToken(createAccountDto.getRegistrationToken());
// Create the account.
createAccountDto.setEmail(registrationDto.getEmail());
accountsService.createAccount(createAccountDto);
// Delete the registration.
registrationsService.deleteRegistration(registrationDto.getRegistrationId());
// Successful result.
return new SuccessDto(true);
}
}
|
/**
* Created by Javiera.
*/
public class AppCliente{
public static void main(String[] args){
ConexionServidor c;
System.out.println("Conectando\n=======================================");
switch (args.length) {
case 0:
c = new ConexionServidor();
c.peticion();
break;
case 1:
c = new ConexionServidor(args[0]);
c.peticion();
break;
case 2:
int puerto = 0;
try {
puerto = Integer.parseInt(args[1]);
} catch (NumberFormatException e) {
e.printStackTrace();
System.out.println("El segundo argumento tiene que ser un numero.");
System.exit(-1);
}
c = new ConexionServidor(args[0],puerto);
c.peticion();
break;
}
}
}
|
<filename>core/src/main/java/com/ottoszika/sokoban/screens/PlayScreen.java
package com.ottoszika.sokoban.screens;
import com.badlogic.gdx.Gdx;
import com.badlogic.gdx.graphics.GL20;
import com.ottoszika.sokoban.Sokoban;
import com.ottoszika.sokoban.engine.GameEngine;
public class PlayScreen extends AbstractScreen {
/**
* Game reference.
*/
private Sokoban game;
/**
* Game engine.
*/
private GameEngine gameEngine;
/**
* Play screen constructor.
*
* @param game the game instance.
* @param gameEngine the game flow.
*/
public PlayScreen(Sokoban game, GameEngine gameEngine) {
this.game = game;
this.gameEngine = gameEngine;
}
/**
* Render callback.
*
* @param delta the amount of time from the last rendered frame.
*/
@Override
public void render(float delta) {
Gdx.gl.glClear(GL20.GL_COLOR_BUFFER_BIT);
this.game.getSpriteBatch().begin();
gameEngine.draw(game.getSpriteBatch());
this.game.getSpriteBatch().end();
}
}
|
MANCHESTER UNITED are likely to push for deals for Antoine Griezmann and Gareth Bale if Ed Woodward oversees the club’s recruitment this summer, according to reports.
But, on numerous occasions, the Red Devils have seen both players snub moves to Old Trafford to stay at their respective clubs.
Manchester United are expected to splash the cash when the transfer window reopens this summer, regardless of who is in charge.
Ole Gunnar Solskjaer looks likely to be given the job on a permanent basis - but links to Mauricio Pochettino also still remain.
Woodward is, though, hoping to appoint a director of football.
Jose Mourinho was against such a role during his time in charge - contrary to claims made as a pundit - which meant United holding fire.
Woodward instead oversaw transfer activity during the 56-year-old’s time in charge.
And the Manchester Evening News say that the United mastermind will likely chase Griezmann and Bale transfers this summer if a director of football appointment does not happen.
That is, partly, down to his desire to sign marquee names.
Woodward rejected Mourinho over Toby Alderweireld, Harry Maguire, Jerome Boateng, Willian and Ivan Perisic last summer.
He had happily signed Alexis Sanchez mere months previously, however, with the Chilean’s blockbuster appeal one of the reasons why.
Sanchez also sold plenty of shirts - particularly during his first few months at the club.
So too have fellow marquee arrivals Paul Pogba, Romelu Lukaku, Angel Di Maria and Radamel Falcao in recent times.
And, if Woodward stays at the helm, more Galacticos could be on their way to United.
- Solskjaer’s transfer advice to Woodward has emerged.
- Real Madrid hatch a plan to sign Paul Pogba.
- Fabio Da Silva reveals what Sir Alex Ferguson was often worried about.
Meanwhile, Bale is facing an uncertain future at Real Madrid following Zinedine Zidane’s return.
Zidane clashed with the Wales international during his first stint at the Bernabeu and that rocky relationship may lead to a transfer.
Griezmann, over at Atletico, is supposedly disillusioned with life in the capital.
And United have been heavily linked with previous suitors Barcelona now looking elsewhere.
|
(Corrects grammar in first paragraph)
JAKARTA, March 6 (Reuters) - Indonesia plans to stop further declines in its oil output this year and hold it at 830,000 barrels per day, but still hopes to raise production to 1 million bpd by end-2014, the head of the energy regulator said on Wednesday.
Indonesia’s state budget for 2013 sets an oil output target of 900,000 bpd, up from 2012 output of crude and condensate at 860,000 bpd. The 2012 target had been set at 930,000 bpd.
“As of March we had already reached around 830 (thousand barrels per day). Hopefully we can maintain this,” Rudi Rubiandini, head of SKKMigas, told Reuters in an interview.
That target for the year would be just over the output seen in December at 826,000 bpd.
The country plans to stop the 10-15 percent natural decline in output at existing wells with new drilling and well workovers, he said, labelling 2013 “the year of drilling.”
The former OPEC member and net importer of oil has often fallen short of production targets, with crude and condensate output declining at an annual rate of 3.8 percent between 1998 and 2011.
Rubiandini also said that additional output of 150,000 bpd from ExxonMobil’s Cepu block — currently producing at 24,000 bpd — should help to put Indonesia’s oil output over the 1 million bpd mark in 2014. (Reporting by Fergus Jensen and Andjarsari Paramaditha; Editing By Tom Hogue)
|
An unusual case of a well-differentiated neuroendocrine tumour of the ileum with peritoneal carcinomatosis: a case report Neuroendocrine tumours (NETs) are a family of neoplasms that come from neuroendocrine cells and express neural markers, such as synaptophysin or chromogranin A. The current classifications of these tumours are presented by the WHO 2000 classification, based on histological parameters, and the WHO 2010 classification, based on the proliferative index, that divides the NETs into a neuroendocrine tumour of a low grade, neuroendocrine tumour of a intermediate grade and neuroendocrine carcinoma (NEC) of a high grade. We are reporting a very rare case of a G1 low-grade neuroendocrine tumour (NET) of the ileum with a peritoneal carcinomatosis. This case is challenging because the tumour expresses low proliferative index as G1 tumours, but it has an aggressive clinical behaviour such as node metastasis and peritoneal carcinomatosis. The peritoneal carcinomatosis is not actually considered by the current classifications of NETs, so it is difficult to predict the prognosis of this patient. Background This article represents the original observation of a lowgrade neuroendocrine tumour of the ileum debuting with a bowel obstruction and peritoneal carcinomatosis. Neuroendocrine tumours (NETs) are a family of neoplasms that arise from neuroendocrine cells and express neural markers, such as synaptophysin or chromogranin A. They are mainly distributed in the gastrointestinal tract. Pancreatic neuroendocrine tumours are included in this category (gastrointestinal-pancreatic neuroendocrine tumours (GPNETs). The behaviour of NETs differs by anatomic site, so it is important to define the tumour localization for prognostic stratification. Current classifications of NETs are the 2000 WHO and the 2010 WHO classifications. The first is based on histological parameters such as size, depth of invasion, angiolymphatic invasion and metastases, and it divides the tumours into well-differentiated neuroendocrine tumour (WDNT), well-differentiated neuroendocrine carcinoma (WDNC) and poorly differentiated neuroendocrine carcinoma (PDNC). The 2010 WHO classification, instead, considers the proliferative activity of the tumours on the basis of their expression of the Ki-67 index or the mitotic count, and it divides the tumours into neuroendocrine tumour (NET) of low grade, neuroendocrine tumour of intermediate grade and neuroendocrine carcinoma (NEC -high grade). So the two classifications consider different aspects of these tumours and use different nomenclature. Well/moderately differentiated NETs are relatively low-aggressive tumours, with a rather indolent disease course and good prognosis in most patients. The lymph nodes and the liver are the prevalent metastatic sites. Peritoneal carcinomatosis is a frequent complication of high-grade aggressive tumours, but to our knowledge, it has never been described in patients with low-grade NETs. The aim of our work is to report the case of low-grade NET of the ileum with peritoneal carcinomatosis at the first diagnosis of the disease. Case presentation We describe the case of a 64-year-old man admitted to our hospital for an intestinal obstruction caused by a tumour of the ileum associated with pelvic peritoneal carcinomatosis. A preoperative CT scan showed an ileal solid mass of 4 cm in diameter with peritoneal fluid in Douglas and radiologic signs of intestinal obstruction. No liver nor thoracic focal lesions were found. We performed an urgent surgical operation. At the opening of the peritoneal cavity, we found a stenotic ileal tumour, about 40 cm from the ileocecal valve, with a mesenteric adenopathy of 4 cm and pelvic peritoneal carcinomatosis. Ileal tract of 30 cm was resected and a manual L-L anastomosis performed. Pathologic evaluation of the resected specimen confirmed the diagnosis of a neuroendocrine tumour 2.7 2 cm in size, with a metastatic node mass of 4 cm in diameter. Only one node was positive for cancer localization. The tumour presented serosa and perivisceral fat infiltrations, perineural and lymphatic vessels invasion and mesenteric implants (Figure 1a, b). Our diagnosis was pT4N1 according to the 2010 American Joint Committee on Cancer (AJCC) classification (Table 1). The case was discussed in a multidisciplinary team, consisting of oncologists, surgeons, radiation oncologists and radiologists. To our knowledge, this is the first case reported in literature of a low-grade NET with concomitant peritoneal carcinomatosis. To exclude the presence of another primitive tumour, we performed a positron emission tomography with gallium-labeled somatostatine analogues (DOTA-NOC PET) and a second look in a Poorly indifferentiated >20 >20 laparoscopy way (Figure 2a, b), with the aim to achieve a complete systemic and peritoneal staging. During the second surgical operation, multiple biopsies of the metastatic nodules and parietal peritoneum were done (left and right pelvic peritoneum, left and right diaphragmatic peritoneum) and a peritoneal cytology was performed. The exploration revealed no other tumours. According to the classification of peritoneal carcinomatosis, the laparoscopic staging showed a peritonial cancer index (PCI) of 4. Peritoneal cytology was negative for malignancy. At the histological examination, carcinomatosis nodules showed the same features of the primary tumour. So the final diagnosis was ileal G1 NET with peritoneal carcinomatosis T4N1M1, stage IV (Figures 3a, b, 4a, b, and 5a, b). The patient is currently under treatment with somatostatine analogue and in follow-up with biannual DOTA-NOC PET; at present, he is disease free. Discussion The gastropancreatic neuroendocrine neoplasms (GEP-NEN) are a heterogeneous group of tumours characterized by the expression of the neural antigens such as chromogranin A or synaptophysin. They are relatively rare but with an increasing incidence rate in the last years. The term carcinoid was proposed for the first time in 1907 by S. Oberndorfer, and it is nowadays traditionally used although it is not mentioned in the current classification of the neuroendocrine neoplasms (NEN). In 2000, the WHO revised the previous classification system of 1980. Neuroendocrine tumours were divided into three groups, considering various histological parameters, such as size, depth of invasion, angiolymphatic invasion and metastases: WDNT or carcinoid; WDNC or malignant carcinoid; PDNC. In 2010, a revised version of the previous WHO classification appeared (Table 2), not based on histological parameters, but on proliferation rate, expression of Ki-67 index, or on mitotic count, calculated by the number of mitosis/10 HPF. The category of well-differentiated neuroendocrine carcinoma of WHO 2000 does not exist anymore in this new classification, and all tumours are evaluated malignant with the potential to metastasize. In a recent study of Yamaguchi T. et al., considering a group of 45 patients with diagnosis of G1 and G2-NET, metastases were observed also in the G1-NET. In the metastatic group of seven patients, four showed a Ki-67 ≤ 2. Metastasis was observed in the liver, lungs and lymph nodes, and one patient presented a local recurrence. Clinical behaviour of the NEN is very heterogeneous: NEC are considered extremely aggressive, with a bad prognosis, instead of NET-G1, that are relatively indolent. Miller HC et al. analyzed the metastatic rate in a cohort of 161 patients with NEN and found out that metastasized tumours were noted in 46.1% of the G1 cases, 77.8% of the G2 cases and 100% of the G3 cases. In spite of this, relatively high incidence of metastasis also in G1 tumour; 87% of G1 cases are alive after 3 years. So it is mandatory in the pathology report to specify the grade or differentiation of the tumour. Indeed, the terms neuroendocrine carcinoma and neuroendocrine tumour, without reference to these parameters, are considered inadequate for prognosis or therapy. The proliferative rate can be assessed as the number of mitosis per unit area of tumour or as the percentage of proliferation marker Ki-67. Despite the new classification of NET, WHO 2010, many works are based on the old WHO 2000 classification, making an analytic comparison of the data very difficult. Some studies that compared the histological features of the WHO 2000 classification to proliferative index of the WHO 2010 classification in predicting metastasis have shown that the Ki-67 index is the best parameter. Metastasis is more frequent in the liver, lymph nodes, lungs, bones and other organs. A rare case of a solitary atrial myocardial metastasis is reported. Liver metastasis were found between 20% and 60% of the NETs. In literature, some cases of small bowel NETsperitoneal carcinomatosis are reported [12,13,, but at our knowledge, a case of well-differentiated neuroendocrine tumour of ileum with single node metastasis and peritoneal carcinomatosis has never been described. Metastatic G1 well-differentiated NETs are described in literature, and the liver is the most frequent site of neoplastic spreading, but there are no reports about peritoneal carcinomatosis in G1 NET. G1 NETs are considered relatively indolent. Strosberg J et al. reported a survival rate at 2 and 5 years of 100% and 85%, respectively, for G1 NETs, and considering the time between diagnosis of metastasis and death from any cause, median survival was not reached in the well-differentiated NETs. In spite of this benign behaviour of G1 NETs, we report a case of potentially aggressive well-differentiated G1 NET. Although the low proliferative index and mitotic rate (Ki-67 < 1% and mitotic count 2x10 HPF), the tumour showed lymphatic metastasis, serosa and perivisceral fat infiltrations, perineural and lymphatic vessels invasion, mesenteric implants and above all peritoneal carcinomatosis. We decided to perform a second surgical operation for PCI staging in a laparoscopic way because some studies demonstrated that laparoscopy is a safe and accurate technique for peritoneal carcinomatosis staging. We started with adhesiolysis procedure, and after, the peritoneal cavity was totally explored for the allocation of PCI using the Sugarbaker scoring system ( Figure 6). Such as for ovarian cancer, we accomplished a peritoneal washing for cytology examination and multiple random peritoneal biopsies of normal surfaces and neoplastic implants. We think that, during surgery, a complete peritoneal cavity exploration should be always performed for these tumours to avoid a wrong staging of the disease, and laparoscopy could be, in selected cases, a useful technique. In some cases metastasis have a more aggressive behaviour in relation to primary tumours. A recent study compared the expression of the Ki-67 index between primary tumours and liver metastasis in 30 patients with NETs. Actually, in one third of the patients with well-differentiated NETs, liver metastasis had an elevated Ki-67 index. Four cases were small bowel NETs and three of these were upgraded from G1 to G2 (two cases) or from G2 to G3 (one case). In our, case both the ileal tumour and the carcinomatosis nodules showed the same Ki-67 index and a well differentiation grade. This means that the tumour has an unusual behaviour because it shows immunohistochemical markers of low malignancy, such as other indolent G1 NET, but histological features of high aggressiveness. The work of Pape UF et al., comparing the prognostic relevance of the TNM classification system to the grading system, reports a 5-year survival rate of 55.4% for stage IV NETs, according to the TNM classification system and of 95.7% for G1 NETs, according to the grading system. In a recent study, the 5-year probability of survival of 458 patients with stage IV midgut NETs is reported around 70% against 100% of stage I, and the 5-year probability of survival of 499 patients with low-grade midgut NETs is near 100%. The prognosis of the well-differentiated NET with peritoneal carcinomatosis could not be established since neither the WHO 2010 classification nor the TNM classification system could be useful for prognostic stratification. Conclusions GPNETs are rare tumours, and large case series are difficult to collect and analyze, although their incidence is increasing. For these reasons, it is crucial for scientists to employ a universally accepted diagnostic system with a common language. Both histological parameters (such as tumour dimensions, lymphatic and vascular invasion, nodes involvement, metastasis, etc.) and proliferative index (such as Ki-67 or mitotic count) are important in prognostic stratification. Our case is challenging because the tumour expresses low proliferative index such as G1 tumours, but it has an aggressive clinical behaviour such as node metastasis and peritoneal carcinomatosis. The peritoneal carcinomatosis is actually not considered by the current classifications of NETs, so it is difficult to predict the prognosis of this patient.
|
Vitiligo Treatment in Childhood: A State of the Art Review Abstract: Vitiligo is a common depigmenting disorder affecting about 12% of the world population. Approximately half of the affected individuals develop the disease before adulthood. Etiologic hypotheses for vitiligo include biochemical, neural and autoimmune mechanisms. The most compelling of these suggests a combination of genetic and immunologic factors that result in an autoimmune melanocyte destruction. We reviewed studies carried out on various treatment modalities used in childhood vitiligo. Topical corticosteroids were found to have excellent repigmentation rates, whereas calcineurin inhibitors have comparable efficacy and a better safety profile compared with topical corticosteroids. These two groups of topical medications are good firstline treatment modalities for localized vitiligo. For the treatment of generalized vitiligo, phototherapy has excellent efficacy. Narrowband ultraviolet B (UVB) has better overall repigmentation rates and safety profile than either topical or oral psoralens and ultraviolet A (PUVA). Other treatment modalities may be considered depending on a patients specific condition, such as surgical options and depigmentation. With adequate sun protection, the option of no treatment with or without corrective camouflage, is an innocuous alternative to any of these treatment modalities.
|
. The authors present three patients, one female and two males, with special forms of non-Hodgkin's lymphoma, the so called T-cell rich B-cell lymphoma (TCRBCL). This is a relatively new entity which has not yet been described in our literature. The first diagnosis in our female patient was Hodgkin's disease. However, the revision of old and new lymph node samples and use of immunohistochemical analysis helped the establishing of diagnosis--TCRBCL. In the other two patients the diagnosis of TCRBCL was established on the basis of immunohistochemical analysis of the lymph node which indicated the dominating T-lymphocytes, positive to pan-T antigen (CD45 RO+), with considerably lower count of B-lymphocyte elements positive to CD20+. The female patient survived 33 months from the time of diagnosis. The other two patients experienced complete remission lasting 10 and 12 months after the end of therapy.
|
1 In Caesarea there lived a Roman army officer named Cornelius, who was a captain of the Italian Regiment. 2 He was a devout, God-fearing man, as was everyone in his household. He gave generously to the poor and prayed regularly to God. 3 One afternoon about three o'clock, he had a vision in which he saw an angel of God coming toward him. "Cornelius!" the angel said.
4 Cornelius stared at him in terror. "What is it, sir?" he asked the angel. And the angel replied, "Your prayers and gifts to the poor have been received by God as an offering!" 5 Now send some men to Joppa, and summon a man named Simon Peter. 6 He is staying with Simon, a tanner who lives near the seashore."
7 As soon as the angel was gone, Cornelius called two of his household servants and a devout soldier, one of his personal attendants. 8 He told them what had happened and sent them off to Joppa.
9 The next day as Cornelius's messengers were nearing the town, Peter went up on the flat roof to pray. It was about noon, 10 and he was hungry. But while a meal was being prepared, he fell into a trance. 11 He saw the sky open, and something like a large sheet was let down by its four corners. 12 In the sheet were all sorts of animals, reptiles, and birds. 13 Then a voice said to him, "Get up, Peter; kill and eat them."
14 "No, Lord," Peter declared. "I have never eaten anything that our Jewish laws have declared impure and unclean. "
15 But the voice spoke again: "Do not call something unclean if God has made it clean." 16 The same vision was repeated three times. Then the sheet was suddenly pulled up to heaven.
17 Peter was very perplexed. What could the vision mean? Just then the men sent by Cornelius found Simon's house. Standing outside the gate, 18 they asked if a man named Simon Peter was staying there.
19 Meanwhile, as Peter was puzzling over the vision, the Holy Spirit said to him, "Three men have come looking for you. 20 Get up, go downstairs, and go with them without hesitation. Don't worry, for I have sent them."
21 So Peter went down and said, "I'm the man you are looking for. Why have you come?"
22 They said, "We were sent by Cornelius, a Roman officer. He is a devout and God-fearing man, well respected by all the Jews. A holy angel instructed him to summon you to his house so that he can hear your message." 23 So Peter invited the men to stay for the night. The next day he went with them, accompanied by some of the brothers from Joppa.
24 They arrived in Caesarea the following day. Cornelius was waiting for them and had called together his relatives and close friends. 25 As Peter entered his home, Cornelius fell at his feet and worshiped him. 26 But Peter pulled him up and said, "Stand up! I'm a human being just like you!" 27 So they talked together and went inside, where many others were assembled.
28 Peter told them, "You know it is against our laws for a Jewish man to enter a Gentile home like this or to associate with you. But God has shown me that I should no longer think of anyone as impure or unclean. 29 So I came without objection as soon as I was sent for. Now tell me why you sent for me."
30 Cornelius replied, "Four days ago I was praying in my house about this same time, three o'clock in the afternoon. Suddenly, a man in dazzling clothes was standing in front of me. 31 He told me, `Cornelius, your prayer has been heard, and your gifts to the poor have been noticed by God! 32 Now send messengers to Joppa, and summon a man named Simon Peter. He is staying in the home of Simon, a tanner who lives near the seashore.' 33 So I sent for you at once, and it was good of you to come. Now we are all here, waiting before God to hear the message the Lord has given you."
34 Then Peter replied, "I see very clearly that God shows no favoritism. 35 In every nation he accepts those who fear him and do what is right. 36 This is the message of Good News for the people of Israel—that there is peace with God through Jesus Christ, who is Lord of all. 37 You know what happened throughout Judea, beginning in Galilee, after John began preaching his message of baptism. 38 And you know that God anointed Jesus of Nazareth with the Holy Spirit and with power. Then Jesus went around doing good and healing all who were oppressed by the devil, for God was with him.
39 "And we apostles are witnesses of all he did throughout Judea and in Jerusalem. They put him to death by hanging him on a cross, 40 but God raised him to life on the third day. Then God allowed him to appear, 41 not to the general public, but to us whom God had chosen in advance to be his witnesses. We were those who ate and drank with him after he rose from the dead. 42 And he ordered us to preach everywhere and to testify that Jesus is the one appointed by God to be the judge of all - the living and the dead. 43 He is the one all the prophets testified about, saying that everyone who believes in him will have their sins forgiven through his name."
44 Even as Peter was saying these things, the Holy Spirit fell upon all who were listening to the message. 45 The Jewish believers who came with Peter were amazed that the gift of the Holy Spirit had been poured out on the Gentiles, too. 46 For they heard them speaking in other tongues and praising God.
Then Peter asked, 47 "Can anyone object to their being baptized, now that they have received the Holy Spirit just as we did?" 48 So he gave orders for them to be baptized in the name of Jesus Christ. Afterward Cornelius asked him to stay with them for several days.
<< 10:1 Greek a centurion; similarly in 10:22.
<< 10:14 Greek anything common and unclean.
<< 10:39 Greek on a tree.
<< 10:41 Greek the people.
<< 10:45 Greek The faithful ones of the circumcision.
<< 10:46 Or in other languages.
|
#include "vcc2.h"
typedef unsigned int CHUNK;
usebitvectors
unsigned Bitcount (CHUNK Target)
requires (Target <= 0xFFFFFFFF) //FFFFFFFF)
/*++
Routine Description:
This procedure counts and returns the number of set bits within
a the chunk.
Arguments:
Target - The integer containing the bits to be counted.
Return Value:
UINT32 - The total number of set bits in Target.
--*/
{
spec(
unsigned T0 = (Target & 1);
unsigned T1 = (Target & (1 << 1)) >> 1;
unsigned T2 = (Target & (1 << 2)) >> 2;
unsigned T3 = (Target & (1 << 3)) >> 3;
unsigned T4 = (Target & (1 << 4)) >> 4;
unsigned T5 = (Target & (1 << 5)) >> 5;
unsigned T6 = (Target & (1 << 6)) >> 6;
unsigned T7 = (Target & (1 << 7)) >> 7;
unsigned T8 = (Target & (1 << 8)) >> 8;
unsigned T9 = (Target & (1 << 9)) >> 9;
unsigned T10 = (Target & (1 << 10)) >> 10;
unsigned T11 = (Target & (1 << 11)) >> 11;
unsigned T12 = (Target & (1 << 12)) >> 12;
unsigned T13 = (Target & (1 << 13)) >> 13;
unsigned T14 = (Target & (1 << 14)) >> 14;
unsigned T15 = (Target & (1 << 15)) >> 15;
unsigned T16 = (Target & (1 << 16)) >> 16;
unsigned T17 = (Target & (1 << 17)) >> 17;
unsigned T18 = (Target & (1 << 18)) >> 18;
unsigned T19 = (Target & (1 << 19)) >> 19;
unsigned T20 = (Target & (1 << 20)) >> 20;
unsigned T21 = (Target & (1 << 21)) >> 21;
unsigned T22 = (Target & (1 << 22)) >> 22;
unsigned T23 = (Target & (1 << 23)) >> 23;
unsigned T24 = (Target & (1 << 24)) >> 24;
unsigned T25 = (Target & (1 << 25)) >> 25;
unsigned T26 = (Target & (1 << 26)) >> 26;
unsigned T27 = (Target & (1 << 27)) >> 27;
unsigned T28 = (Target & (1 << 28)) >> 28;
unsigned T29 = (Target & (1 << 29)) >> 29;
unsigned T30 = (Target & (1 << 30)) >> 30;
unsigned T31 = (Target & (unsigned)(1 << 31)) >> 31;
)
assert(Target ==
(unsigned)(1 << 31) * T31 +
(1 << 30) * T30 +
(1 << 29) * T29 +
(1 << 28) * T28 +
(1 << 27) * T27 +
(1 << 26) * T26 +
(1 << 25) * T25 +
(1 << 24) * T24 +
(1 << 23) * T23 +
(1 << 22) * T22 +
(1 << 21) * T21 +
(1 << 20) * T20 +
(1 << 19) * T19 +
(1 << 18) * T18 +
(1 << 17) * T17 +
(1 << 16) * T16 +
(1 << 15) * T15 +
(1 << 14) * T14 +
(1 << 13) * T13 +
(1 << 12) * T12 +
(1 << 11) * T11 +
(1 << 10) * T10 +
(1 << 9) * T9 +
(1 << 8) * T8
+ 128 * T7 + 64 * T6 + 32 * T5 + 16 * T4
+ 8 * T3 + 4 * T2 + 2 * T1 + T0
);
//
// The following algorithm was taken from the AMD publication
// "Software Opimization Guide for the AMD Hammer Processor",
// revision 1.19, section 8.6.
//
//
// First break the chunk up into a set of two-bit fields, each
// field representing the count of set bits. Each field undergoes
// the following transformation:
//
// 00b -> 00b
// 01b -> 01b
// 10b -> 01b
// 11b -> 10b
//
// Target -= (Target >> 1) & 0x5555555555555555;
Target -= (Target >> 1) & 0x55555555;
assert(Target ==
(1 << 30) * (T31 + T30) +
(1 << 28) * (T29 + T28) +
(1 << 26) * (T27 + T26) +
(1 << 24) * (T25 + T24) +
(1 << 22) * (T23 + T22) +
(1 << 20) * (T21 + T20) +
(1 << 18) * (T19 + T18) +
(1 << 16) * (T17 + T16) +
(1 << 14) * (T15 + T14) +
(1 << 12) * (T13 + T12) +
(1 << 10) * (T11 + T10) +
(1 << 8) * (T9 + T8) +
(1 << 6) * (T7 + T6) +
(1 << 4) * (T5 + T4) +
(1 << 2) * (T3 + T2) +
T1 + T0
);
//
// Next, combine the totals in adjacent two-bit fields into a four-bit
// field.
//
//Target = (Target & 0x3333333333333333) +
// ((Target >> 2) & 0x3333333333333333);
Target = (Target & 0x33333333) +
((Target >> 2) & 0x33333333);
assert(Target ==
(1 << 28) * (T31 + T30 + T29 + T28) +
(1 << 24) * (T27 + T26 + T25 + T24) +
(1 << 20) * (T23 + T22 + T21 + T20) +
(1 << 16) * (T19 + T18 + T17 + T16) +
(1 << 12) * (T15 + T14 + T13 + T12) +
(1 << 8) * (T11 + T10 + T9 + T8) +
(1 << 4) * (T7 + T6 + T5 + T4) +
T3 + T2 + T1 + T0);
//
// Now, combine adjacent four-bit fields to end up with a set of 8-bit
// totals.
//
Target = (Target + (Target >> 4)) & 0x0F0F0F0F;
assert(Target ==
(1 << 24) * (T31 + T30 + T29 + T28 + T27 + T26 + T25 + T24) +
(1 << 16) * (T23 + T22 + T21 + T20 + T19 + T18 + T17 + T16) +
(1 << 8) * (T15 + T14 + T13 + T12 + T11 + T10 + T9 + T8) +
T7 + T6 + T5 + T4 + T3 + T2 + T1 + T0);
//
// Finally, sum all of the 8-bit totals. The result will be the
// number of bits that were set in Target.
//
//Target = (Target * 0x0101010101010101) >> 56;
assert(Target <= 0x08080808);
Target = ((Target * 0x01010101) & 0xFFFFFFFF) >> 24;
assert(Target ==
T31 + T30 + T29 + T28 + T27 + T26 + T25 + T24 +
T23 + T22 + T21 + T20 + T19 + T18 + T17 + T16 +
T15 + T14 + T13 + T12 + T11 + T10 + T9 + T8 +
T7 + T6 + T5 + T4 + T3 + T2 + T1 + T0);
return Target;
}
|
ORDER, DISORDER, AND PHASE TRANSITION IN CONDENSED SYSTEM Nonmonotonic Behavior of Magnetoresistance, R(H) Hysteresis, and LowTemperature Heat Capacity of the BaPb 0.75 Bi 0.25 O 3 Superconductor in a Magnetic Field: Possible Manifestations of Phase Separation The transport properties (R(T) and R(H) dependences at various values of the transport current in magnetic fields up to 65 kOe) and lowtemperature heat capacity in magnetic fields up to 90 kOe of the BaPb0.75 Bi 0.25 O 3 superconductor (T C ≈ 11.3 K) are investigated with the goal of clarifying the mechanisms determining the nonmonotonic behavior and hysteresis of its magnetoresistance R(H). The type of R(H) hys� teretic dependences for BaPb0.75Bi0.25O3 is analogous to that observed in granular highTc superconductors (HTSCs); however, unlike classical HTSC systems, the field width of the magnetoresistance hysteresis loop for polycrystalline BaPb0.75Bi0.25O3 depends on the transport current. This means that although the mecha� nisms responsible for the magnetoresistance hysteresis (the influence of the magnetic flux trapped in super� conducting regions on the effective field in Josephson interlayers) are identical in these objects, the transport current in BaPb0.75Bi0.25O3 may considerably affect the diamagnetic response of the superconductor. A con� siderable effect of transport current on the field in which the R(H) dependences have a peak and exhibit hys� terestic properties is observed. Such a behavior can be adequately interpreted using the model of the spatially inhomogeneous superconductor-insulator state proposed by Gorbatsevich et al. (JETP Lett. 52, 95 ). The nonmonotonic dependence of quantity C/T (C is the heat capacity) on the magnetic field discovered in the present study also agrees with the conclusions based on this model.
|
import { NgModule } from '@angular/core';
import { PreloadAllModules, RouterModule, Routes } from '@angular/router';
const routes: Routes = [
{
path: '',
redirectTo: 'login',
pathMatch: 'full'
},
{
path: 'folder/:id',
loadChildren: () => import('./folder/folder.module').then( m => m.FolderPageModule)
},
{
path: 'unica-respuesta',
loadChildren: () => import('./unica-respuesta/unica-respuesta.module').then( m => m.UnicaRespuestaPageModule)
},
{
path: 'mensaje-respuesta-modal',
loadChildren: () => import('./mensaje-respuesta-modal/mensaje-respuesta-modal.module').then( m => m.MensajeRespuestaModalPageModule)
},
{
path: 'login',
loadChildren: () => import('./pages/login/login.module').then( m => m.LoginPageModule)
},
{
path: 'lecciones-select',
loadChildren: () => import('./pages/lecciones/lecciones-select/lecciones-select.module').then( m => m.LeccionesSelectPageModule)
},
{
path: 'leccion-ejecucion/:id',
loadChildren: () => import('./pages/lecciones/leccion-ejecucion/leccion-ejecucion.module').then( m => m.LeccionEjecucionPageModule)
},
{
path: 'grupos-admin',
loadChildren: () => import('./pages/grupos/grupos-admin/grupos-admin.module').then( m => m.GruposAdminPageModule)
},
{
path: 'resultado-admin',
loadChildren: () => import('./pages/resultados/resultado-admin/resultado-admin.module').then( m => m.ResultadoAdminPageModule)
},
{
path: 'perfil-edit',
loadChildren: () => import('./pages/perfil/perfil-edit/perfil-edit.module').then( m => m.PerfilEditPageModule)
}
];
@NgModule({
imports: [
RouterModule.forRoot(routes, { preloadingStrategy: PreloadAllModules })
],
exports: [RouterModule]
})
export class AppRoutingModule {}
|
Enhancing our clinical links and credibility: nurse lecturers in clinical practice. INTRODUCTION As changes in health care continue, the role of nurse lecturer is expected to increase in terms of scope, responsibility and recognition. The nurse lecturers are expected to maintain clinical credibility and competence in addition to teaching and research. They should have educational background and the clinical expertise to organize and coordinate services and resources to meet the clients nursing care needs in a cost-effective and efficient manner. As the workload increases, many lecturers have difficulty obtaining time to update their clinical experience. Although it is recommended that lecturers spend 20% of their time in practice education, many nurse lecturers find this difficult to achieve. The aim of this paper is to suggest pragmatic approaches to enhance credibility and competence, which in turn should result in closing gap between theory and realities of clinical practice. The approaches include working clinically, developing learning environment, getting involved in practice development, developing links with the local trust, involving clinicians in teaching and running a staff support group. This paper focuses on the need for nurse lecturers to develop an individualized practice-based role that will enable them to keep in touch with current clinical developments.
|
. Special method of complex diagnosis of mandibular injury is under consideration. It is based on the informational technologies. The study of the mechanisms of the injury's formation has been made on 109 patients of the skull-jaw-facial surgery department of the hospital were under investigation. Two main types of jaw-facial injuries have been revealed. The first type: falling down from the height of one's own size (stature). The second type: blow (stroke) of a blunt object. The decrease of the number of the inflammatory complications of the broken jaw due to the usage of new algorithms on the basis of informational technologies has been noted.
|
APS kinase from Arabidopsis thaliana: genomic organization, expression, and kinetic analysis of the recombinant enzyme. The gene encoding 5'-adenylylsulfate (APS) kinase (EC 2.7.1.25) (APK) was cloned from Arabidopsis thaliana. There is a single APK locus in A. thaliana. The coding sequence of the gene is composed of 7 exons, interrupted by 6 introns. A transcriptional initiation site was detected 120 bp 5' of the initiation codon. APK mRNA is slightly more abundant in leaves than in roots of A. thaliana and its level does not change in response to sulfur starvation. The APK protein, synthesized in vitro, is able to enter isolated intact chloroplasts. Recombinant APS kinase shows maximal activity at 10 microM APS with 5 mM ATP, but it is inhibited at APS concentrations above 10 microM. The inhibition is alleviated at higher ATP concentrations. Reciprocal plot analysis showed that the theoretical Vmax is approximately 1.2 mumol min-1 mg-1 at 25 degrees C, pH 8.0; the K(m) values are 3.6 microM APS and 1.8 mM ATP.
|
On behalf of the entire University at Buffalo community, my thoughts and deepest sympathies are with the families and friends of the shooting victims at the Tree of Life synagogue in Pittsburgh. As well, I would like to offer my deepest condolences to the victims’ extended family among our Jewish students, faculty, staff and community members. Our hearts are very much with you as we mourn—along with the nation and world—this terrible and senseless loss.
Bigotry, racism, intolerance and discrimination have no place on our campus or in our society. As a campus community, we must denounce such vile sentiments and actions in the most unambiguous terms.
Whether you are a student, faculty or staff member, know that there are campus resources available to you if you are struggling through this tragedy. These include University Counseling Services and the Employee Assistance Program (EAP).
As I have always said, UB’s shared values of inclusiveness, diversity and mutual respect for all form the bedrock of our university. Today, and every day, tolerance, acceptance, compassion and generosity of spirit must be cherished and upheld. As president of the University at Buffalo, I pledge to uphold these values in the strongest of terms. I encourage our entire university community to stand with me in solidarity to reaffirm these values, and in support of the victims of this unconscionable crime – and all hate crimes.
|
/// `Candle`s are the default data item. They may be used as an input to any indicator, as they
/// implement `Open`, `Close`, `High`, `Low`, and `Volume`
impl Candle {
pub fn new(open: f64, close: f64, high: f64, low: f64, volume: u64) -> Result<Candle, Error> {
if [open, close, low].into_iter().all(|x| x <= high) && [open, close].into_iter().all(|x| x >= low) {
Ok(Candle {
open,
close,
high,
low,
volume,
})
} else {
Err(anyhow!(
"Unclean candle! Open: {}, Close: {}, High: {}, Low: {}, Volume: {}",
open,
close,
low,
high,
volume,
))
}
}
}
|
Story highlights Evgeny Nikitin was due to appear at the Bayreuth Festival this week
He got a Nazi swastika tattoo as a young man in a heavy metal band, the festival says
The festival performs the works of Richard Wagner, a favorite of Adolf Hitler's
Russian singer Evgeny Nikitin has pulled out of one of the world's best-known opera events, the Bayreuth Festival in Germany, because he has a Nazi tattoo, organizers said Sunday.
Nikitin was in a heavy metal band as a young man, and got the swastika tattoo then, said festival spokesman Gunther Philipowski.
"That is a problem in Bayreuth," Philipowski said. "Bayreuth has a bad history with the Nazis. It's clear that Bayreuth has to be careful about this terrible part of history and has to take a position against it."
The festival is dedicated to the works of Richard Wagner, one of Nazi dictator Adolf Hitler's favorite composers.
Hitler attended the Bayreuth Festival regularly, according to the Holocaust Encyclopedia, which describes Wagner as "an artist long associated with anti-Semitism" and the racist-nationalist volkisch tradition "from which the Nazis drew much of their ideology."
Nikitin, 38, a bass-baritone, has "painted over" his Nazi tattoo, and it would not have been visible during his performance in "The Flying Dutchman," Philipowski said.
But there are videos of him online where the tattoo is visible, he said.
"I had the tattoos made when I was young. It was a big mistake in my life and I wish I had never done it," Nikitin said in a statement released by the festival.
Nikitin canceled his appearance after discussions with Bayreuth management, the spokesman said.
He had already been in Germany rehearsing for his premiere on Wednesday, Philipowski said.
Nikitin's agent did not immediately respond to CNN questions about the cancellation.
|
def gradient_descent(func, x0=None, func_grad=None):
params = inspect.getfullargspec(func)[0]
if x0 == None:
a = [0 for p in params]
else:
a = list(x0)
s = 0.001
n = len(a)
a_1 = a.copy()
n_iter = 10000
precision = 0.01
for k in range(n_iter):
for i in range(n):
grad = [0]*n
for j in range(n):
grad[j] = func_grad[j](*tuple(a))
a[i] = a[i] - s*grad[i]
if func(*tuple(a)) - func(*tuple(a_1)) > 0:
print('function increases.')
return func(*tuple(a_1))
a_1 = a.copy()
print('a = ', a)
return func(*tuple(a))
|
Bridging the gap: spectral distortions meet gravitational waves Gravitational waves (GWs) have the potential to probe the entirety of cosmological history due to their nearly perfect decoupling from the thermal bath and any intervening matter after emission. In recent years, GW cosmology has evolved from merely being an exciting prospect to an actively pursued avenue for discovery, and the early results are very promising. As we highlight in this paper, spectral distortions (SDs) of the cosmic microwave background (CMB) uniquely probe GWs over six decades in frequency, bridging the gap between astrophysical high- and cosmological low-frequency measurements. This means SDs will not only complement other GW observations, but will be the sole probe of physical processes at certain scales. To illustrate this point, we explore the constraining power of various proposed SD missions on a number of phenomenological scenarios: early-universe phase transitions (PTs), GW production via the dynamics of SU and ultra-light U axions, and cosmic string (CS) network collapse. We highlight how some regions of parameter space were already excluded with data from COBE/FIRAS, taken over two decades ago. To facilitate the implementation of SD constraints in arbitrary models we provide GW2SD. This tool calculates the window function, which easily maps a GW spectrum to a SD amplitude, thus opening another portal for GW cosmology with SDs, with wide reaching implications for particle physics phenomenology. INTRODUCTION Gravitational wave (GW) astronomy has become a reality. The now routine detection of compact object mergers by the LIGO/Virgo collaboration () has made, for good reasons, the study of GWs one of the most active and current topics in cosmology and astrophysics. Ongoing and planned observations of the tensor perturbation power spectrum currently span some 21 orders of magnitudes of frequency: From cosmic microwave background (CMB) upper limits on primordial B-modes (;) measurements at the lowest frequencies, to interferometry detections of GWs (e.g., b,a) and Pulsar Timing Array (PTA) measurements (e.g., ;) at higher frequencies. In the next few years, a plethora of experiments will test different scales between these extremes (e.g.,, for overview). How do CMB SDs constrain tensor perturbations at the scales that they do? Spectral distortions are created by mechanisms that lead to energy release into the photon-baryon fluid at redshifts z 2 10 6, when thermalization processes cease to be efficient (Zeldovich & Sunyaev 1969;Illarionov & Sunyaev 1975;Danese & de Zotti 1982;;Hu & Silk 1993;Chluba & Sunyaev 2012). Many sources of distortions exist within standard CDM cosmology as well as scenarios invoking new physics (see b, for broad overview), and innovative experimental concepts ((Kogut et al., 2019a) have now reached critical thresholds to significantly advance the long-standing distortion constraints from COBE/FIRAS (;). A particular source of SDs is due to the dissipation of ten-sor modes while they travel almost unimpeded through the cosmic plasma (;a). How do tensor perturbations distort the CMB spectrum? In general, perturbations in the photon fluid dissipate through electron scattering and free-streaming effects. Dissipation of scalar perturbations provides one of the guaranteed sources of SDs in the early Universe within the standard thermal history (e.g., Daly 1991;;b,a). Similarly, tensor modes lose a small fraction of their energy by continuously sourcing perturbations in the photon fluid which then also distort the CMB spectrum. In contrast to scalar modes, however, the dissipation is mainly mediated by free-streaming effects. As shown in detail by Chluba et al. (2015a), this leads to dissipation of perturbations over a vast range of scales, extending far beyond those relevant to scalar perturbations. Thus, although the tensor dissipation rate is suppressed relative to scalar dissipation (tensor modes are not significantly damped by interactions with the photons), this opens new avenues for model constraints from SDs. Building on Chluba et al. (2015a), we translate the relations between -distortions and primordial tensor perturbation into quantities commonly used for GW searches. This makes it easier to compare SD limits to those from other probes. As examples we consider several inflationary models which source GWs beyond vacuum fluctuations, early-universe phase transitions (PTs) and cosmic string (CS) networks, all of which demonstrate how SD measurements are and will be important for excluding portions of their respective parameter spaces. Indeed we highlight that several of the widely discussed models could have already constrained some regions of their respective parameter spaces with SD limits from COBE/FIRAS, taken over a quarter-century ago. Future spectrometer concepts like PIXIE () and its enhanced versions (e.g., PRISM ;) could, through their increased sensitivity, significantly increase the range of scales and parameter space covered. This could give CMB spectral distortions an important role in this highly-synergistic multi-messenger campaign, providing unique scientific opportunities for the next generation of cosmologists and particle phenomenologists alike. GWS IN THE EXPANDING UNIVERSE A GW can be represented as a transverse traceless tensor perturbation of the metric's spatial component, h i j, and the energy density it carries is GW = h i j h i j /(32G), where the prime denotes conformal time derivatives 1. If these GWs were produced primordially 2, we can define the GW fractional energy density per decade of wavelengths as (e.g., Watanabe & Komatsu 2006) where c is the critical density, and in the second equality we factored the primordial tensor power spectrum P T and the deterministic GW transfer function T GW. In Watanabe & Komatsu, several analytical approximations of the GW transfer function were developed. During radiation domination (RD) we have 1 We adopt the normalization conventions of Watanabe & Komatsu. 2 We consider the case of sub-horizon generation further on. whereas during matter domination (MD), one finds Here, k eq is the comoving wavenumber entering the horizon at the time of matter-radiation equality eq, and j and y are the spherical Bessel functions of first and second kind. For wavelengths much smaller than those entering the horizon today (k 0 1) we can expand the GW transfer function derivatives at leading order in k. Additionally, since we always observe quantities that involve (T GW ) 2 integrated over some range of k, we can average over one period to obtain (e.g., Caprini & Figueroa 2018) which is a smooth function of k valid during MD. Similarly, during RD we can apply the same procedure to Eq., and obtain For later use we point out that during RD, where Eq. is valid, a ∝, while during MD relevant to Eq. we have a ∝ 2. Together with Eq., this means that the GW energy density at a given scale evolves as GW ∝ a −4 H −2 ∝ const during RD and GW ∝ a −4 H −2 ∝ (1 + z) in the MD era. As pointed out in Watanabe & Komatsu, the approximations given above neglect some important details. One of these is the process of neutrino damping, which has its greatest effects on scales important to SD physics. The damping is effective during RD but only after neutrino decoupling (T 2MeV), which taken together almost exactly coincides with the SD regime. This damping occurs since free streaming neutrinos correspond to a nonnegligible fraction of the energy density of the Universe during RD and generate significant anisotropic stresses that result in the damping of tensor perturbations. The magnitude of the effect is a 35.6% decrease of the power available in GW (Weinberg 2004). To include this effect the transfer function given in Dicus & Repko is used: T GW = 1 n even a n n j n (k) − k j n+1 (k), with the coefficients a 0 = 1, a 2 = 0.243807, a 4 = 5.28424 10 −2 and a 6 = 6.1354510 −3. This is valid for the range of scales needed in the following section. It is clear from Eqs., and that the exact transfer functions are important quantities for comparing the effects of the GW background in the early and late Universe. In this paper, we compare the SD sensitivity (↔ early Universe) to PTA and interferometry (↔ late Universe). Even CMB temperature anisotropies, although sourced early on, mostly probe the Universe after the RD-MD transition. Because of this it is essential to get the exact dynamics of this transition right for any comparison to be meaningful. To study the evolution of the GW background in detail we numerically solved for the wave evolution through the RD-MD transition, which gave results agreeing with Watanabe & Komatsu and Dicus & Repko in the appropriate limits, while allowing us to more carefully model the GW background for a realistic cosmology involving neutrino and dark energy densities. Since gravitational wave upper limits are usually quoted as function of frequencies rather than wavelengths, we will use the relation k/Mpc −1 = 6.5 10 14 f /Hz to change units. -DISTORTIONS FROM TENSOR PERTURBATIONS Much like scalar perturbations, tensor perturbations dissipate over time, both transferring energy to neutrinos and (in smaller proportion) to photons. Primordial tensor perturbations entering the horizon during or slightly before the -era (5 10 4 z 2 10 6 ), when dissipating, generate -distortions of the CMB that will be observable today (;a). The average value of -distortions today is related to the primordial tensor power spectrum via a window function W (k) which already averages oscillations by integrating over a transfer function's evolution throughout the -era, achieving the usual factor of 1/2 implicitly. We calculate W (k) numerically according to Chluba et al. (2015a). The window function is shown in Fig. 1. In comparison to the corresponding k-space window function of scalar perturbations (e.g., aChluba et al., 2015b, the dissipation efficiency of tensors is about five orders of magnitude smaller, highlighting how weakly tensor modes couple to the photon fluid. Offsetting this loss, we can see that tensor modes contribute to the generation of -distortions over a vast range of scales, with a power-law decay of contributions at k 10 6 Mpc −1 (Fig. 1). This is in stark contrast to the dissipation of scalar perturbations, which are limited to scales k 50 − 10, 000 Mpc −1, with a strong exponential decay of contributions from k 10, 000 Mpc −1 (e.g., a). Scalar modes damp by photon diffusion, which virtually erases all perturbations once the dissipation scale is crossed. For tensors, the photon damping is minute and photon perturbations are continuously sourced by the driving tensor force, explaining this significant difference (a). This makes SDs a potentially unique probe of GWs from early-universe physics. Time-dependent injection Equation determines the SD signal from primordial perturbations that were created during inflation and only later enter the horizon to dissipate their energy. Another possibility is to have perturbations created on sub-horizon scales at later times. This requires a generalisation of the window function formalism to account for the new time dependence. An immediate difference for sub-horizon injection is that neutrino damping will not occur, as this only matters for GWs that cross the horizon between neutrino decoupling and the start of MD. The solid curve is the result for power injection before the era, while the other curves suffer from some reduced visibility at higher k. The faded line shows the results without neutrino damping, leading to a 30% increase across the window function. This means one can use the simpler versions of the transfer function, valid in RD, given in Eqs. and. The time dependence -which before was included in the physics underlying the window function -has to be made more explicit. Using redshift z to better match Chluba et al. (2015a), Eq. can be generalized to where we introduced the GW--distortion window primitive W (k, z), which captures the physics behind the damping of GWs. Note that with P T (k, z) = P T (k) we recover Eq. by defining ∞ 0 W dz = W. The explicit form of the window primitive is 4. and for convenience we summarize here the quantities which are relevant to calculate the window function (for their derivation and further explanation we refer to a): is the time derivative of the Thomson optical depth. The terms T e − * contain the physics of how the GW transfer function T GW couples to the photon fluid. These terms can be reliably approximated as with = k/. The final term J () is the energy branching ratio, which gives the fraction of total energy injected into the photon fluid that contributes to the distortion. We use the simple analytic approximation of the branching ratio ('method B' in Chluba 2016): with z th = 1.98 10 6 denoting the redshift where thermalisation becomes inefficient (see also Hu & Silk 1993). We employ one further approximation in assuming the injection happens instantaneously across all scales at a time *. Therefore, the tensor perturbations are uncorrelated (P T (k, < * ) = 0) up to * when their power spectrum abruptly jumps to some value that we will now determine. The spectrum is found at all times after * by redshifting GW from the present-day value where we used a −4 /E 2 ∝ GW / c. We will only consider power injection in the RD era, hence the tensor power spectrum is then obtained using Eq. together with Eq., and reads Notice that if not for the fact that the tensor perturbations appear at *, the power spectrum would always be time-independent: it is in fact the equivalent of the primordial one in the "standard" scenario described in Chluba et al. (2015a). Using that Eq. is independent of time during RD and inserting this into Eq., we can remove the time dependence in the integrand, leaving only changes in the upper limit of integration. It is therefore sufficient to study a series of window functions W zmax Fig. 1. We can observe that even modes originating from z 2 10 6 contribute to the generation of distortions. The flat plateau of the window function at k 0.1−10 3 Mpc −1 is not affected until z max 5 10 5, and will rapidly approach W zmax 0 as z max approaches 5 10 4. For numerical applications, it is convenient to pre-tabulate the tensor window function W zmax across k and injection redshift z max. Since the background cosmology is fixed to high precision (Planck ), this procedure avoids additional approximations. 5 However, a few comments are in place: we can further improve the treatment of the transition between the and y-distortion eras, which here we modelled as a step-function . Including the more gradual transition (e.g., see discussion in Chluba 2016), enhances the contributions from the largest scales (k 10 −2 Mpc −1 ), however, a more accurate treatment of transfer effects is also required and left to future work. With the procedure outlined in this section we can calculate the tensor dissipation contribution to the present day value of distortions. However, other processes, such as dissipation of acoustic modes and Compton cooling also source -distortions, henceforth referred to as other. Any non-detection of an enhanced level of SD would straightforwardly constrain models that generate a large GW, comparable to or greater than other. However, things are more delicate when GW becomes much smaller than the value of other expected in the standard cosmological model, other 2 10 −8 (e.g., Chluba 2016). In this regime, any actual analysis would require a marginalization of other sources, that we do not take into account here. However, assuming standard slow-roll inflation, we can in principle accurately predict the expected standard contribution given the power spectrum parameters measured at large angular scales (b;Khatri & Sunyaev 2013;Chluba & Jeong 2014;;Chluba 2016). For simplicity, we shall thus assume perfect removal of other -contributions. 5 A simple interpolation routine to calculate W zmax is available here: https://github.com/CMBSPEC/GW2SD.git Below we will consider the upper limit on -distortions set by COBE/FIRAS ( < 9 10 −5 95%CL) (;), and the forecasted constraints for PIXIE ( < 3 10 −8 ) (), SuperPIXIE ( < 7.7 10 −9 ) (), Voyage 2050 ( < 1.9 10 −9 ) and 10Voyage 2050 ( < 1.9 10 −10 ) (b), all of which already account for the presence of foregrounds following Abitbol et al.. Scalar contributions Above we discussed separating GW from other, taking the latter to be the standard model expected value. A second discussion is necessary, however, regarding the contribution that scalar perturbations have to a signal. This is important, considering that energetic early-universe phenomena have the potential to generate scalar perturbations as well as tensors, which will enhance the SD production. In the following section we will discuss the scalar contributions for models where it is possible to do so, but some statements apply in general: Chluba et al. (2015a) show that the corresponding window functions for scalar perturbations peak around 10 5 higher than for tensors, but for a narrower range of scales (k 50 − 10, 000 Mpc −1 or f 8 10 −14 − 1.5 10 −11 Hz, as previously discussed). Thus, for tensor perturbations to dominate the spectral distortion signal the scalar spectrum created must be less than 1 part in 10 5 of the tensor spectrum, or must be injected on smaller scales than k ∼ 10 4 Mpc −1. Provided both the wider tensor window, and that some early processes will be almost invisible to scalar probes, the machinery explained above for constraining early tensor energy injection are still of interest and importance, despite the relatively low sensitivity. MINIMALLY PARAMETRIC CONSTRAINTS In this section, we calculate the constraining power of spectroscopic CMB measurements in a minimally parametric fashion. As in Campeti et al., we parametrize the primordial tensor power spectrum using logarithmically spaced tophat functions centered around some ln k i with ln k i+1 − ln k i = 1.2 ∀i. This allow us an easy comparison with Fig. 8 of their paper: Therefore, for each i, we insert Eq. (15a) into Eq., and calculate the maximum value of A i that is compatible with the chosen GW ( 0 ) upper limit. With that information we then use Eq. In Fig. 2 we show the sensitivity curves for COBE/FIRAS, PIXIE, SuperPIXIE, Voyage 2050 and 10Voyage 2050, which all include estimated penalties from foregrounds. For comparison, we also report the sensitivity curves from Campeti et al., which recently compiled the results of many planned experiments (;Smith & Caldwell 2019;Arca ;;;Crowder & Cornish 2005;;;;). Moreover, we show the NANOGrav 12.5 year observation (), interpreted as GW stochastic background according to their 5 frequency power-law model (see, for more discussion on whether the signal can be inflationary). Since the extrapolation of a red spectra would be favourable for a SD detection, we conservatively assume a flat spectrum. While the existing constraint derived from the COBE/FIRAS data is a few order of magnitude higher than other probes, next generation satellites will start to bridge nicely the frequency gap existing between CMB observation and direct GW detection. It is interesting to notice that the upper bound from SDs will cover a very broad range of frequencies (more than 5 decades in f ). As such, any signal that is not sharply peaked in frequency will generate a comparatively higher -distortion, tightening the constraints on specific parametric models, as we will see in the next section. CONSTRAINTS ON SPECIFIC MODELS In this section, we consider concrete models that generate GWs over a wide range of scales. For each of the following models it is enough to insert their corresponding tensor power spectrum into Eq. or to obtain the predicted -distortion, depending on whether the injection is primordial or happens after reheating. Generally speaking, once accounting for the limits on r from Planck (;), we understand that appreciable SDs can only be created by models with substantially enhanced tensor power at small scales. To also avoid future constraints at small scales, models with localized features at f = 10 −15 − 10 −9 Hz are most promising. In the context of PTs, for example, this identifies low-scale dark or hidden sector transitions at energies 10 MeV -10 eV in the post-inflation era as a target. Single-field slow-roll inflation As a benchmark we consider the tensor perturbations generated by single-field slow-roll inflation. This model predicts a very low, almost scale invariant tensor spectrum, and as such we cannot expect SD constraints to be competitive with either CMB measurements or future direct detections at small scales. We however include the model for completeness, and as a point of comparison. The tensor spectrum from this model is given by where the amplitude of tensor and scalar perturbations A T and A S are related by the tensor to scalar ratio by r ≡ A T /A S, and n T = −r/8 (Lyth & Riotto 1999). Current constraints, mostly driven by Planck low-temperature and BICEP2/Keck B-modes data, (;) set the upper limit r 0.002 < 0.06 (95%) at k = 0.002 Mpc −1. Upon noticing |n T | ≤ 0.0075 ≈ 0, one can approximate the result by integrating a flat spectrum yielding (r) ≈ 1.68 10 −13 r which gives the correct result to within ≤ 5% for all values not ruled out by Planck. This shows that for any allowed value of r the SD signal will be out of reach for even the most sensitive SD mission concepts. In principle this contribution is present as a component of tensor spectrum in the other models considered in the following sections. However, since the amount of SD it generates is anyway negligible, we will omit it in the following. Note that the Planck constraint on r will also be considered for other models. Strictly speaking, the aforementioned constraint only apply to a power-law tensor spectrum, a condition not necessarily met by the models we will consider in the following. To provide some context to the SD constraints we will draw, we opt to employ an order-of-magnitude estimate of the Planck constraint, simply requiring that any spectrum of tensor perturbations, P T (k), must satisfy P T (k)/P sf S (k) k=0.002 Mpc −1 < 0.06. In principle, a proper analysis of the Planck and BICEP2/Keck data could be carried out to set constraints on the models that will be discussed here. This, however, goes beyond the scope of the paper. LiteBIRD (), providing low multipole BB information at much higher precision, will allow us to further improve the limits set by Planck on the same range of scales in the near future. Spectator SU axions Many inflationary models require the dynamics of additional spectator fields active during the inflationary period, itself driven by a separate scalar field. Generally speaking, the dynamics of the spectator field generate tensor perturbations in addition to those produced by the vacuum fluctuations of the quasi de Sitter background. In this section, following Campeti et al., we consider an axion-SU spectator field based on the "chromo-natural" inflation model (Adshead & Wyman 2012;). Here, the SU gauge fields acquire an expectation value, the fluctuations around which include a tensor perturbation with a bilinear coupling to the graviton. The dynamics of the spectator SU axion are such that gravitons of a particular helicity are amplified via a transient tachyonic instability, resulting in a (circularly polarized) contribution to the tensor power spectrum. The spectrum for this model is given by (see ) which relates to the spectrum of scalar perturbations In order to constrain this model, we use the best-fit Planck parameters (Planck ) for Eq.. However, r *, k p and are related to the parameters of the gauge theory and are essentially free to vary here. We take as a reasonable set of values, those given in Campeti et al. (their model AX3) (r *, k p, ) = (50, 10 6 Mpc −1, 4.8), which would yield = 2.1 10 −12. Entertaining the question as to which set of parameters would maximize the distortion signal while satisfying both observational and model constraints we find (r *, k p, ) = (265, 2.85 10 4 Mpc −1, 4.02). However, even this best case scenario leaves no appreciable SD signal, yielding = 2.1 10 −11. This result can be understood by considering the parabolic shape of the spectrum in logP-logk space, which due to model constraints cannot peak to sharply (e.g. see Eqs. (A8) and (A11) in ). This means that a spectrum which avoids the Planck constraints cannot simultaneously peak too high in the SD regime. In contrast, the models considered in the following subsections have spectra resembling broken power laws, and can be much more effective in satisfying current constraints while simultaneously generating significant SDs. Ultra-light U audible axions The sensitivity of SD measurements to axion standard model extensions have already been discussed in the literature (). In this subsection however we consider a model proposed in Machado et al. ; Machado et al., in which the axions specifically produce a strong GW signal. In this scenario (generic in the context of string compactifications), one has the presence of one or more U axions with mass m and decay constant f that couple to dark sector photons. At early times during radiation domination, when the Hubble parameter H is greater than m, the axion field is over-damped and is frozen. Once H m, corresponding to the temperature T ≈ mM pl, the axion starts to oscillate around the minimum of its potential, sourcing gauge field production of a particular helicity that goes on to generate GWs. Since these GWs are only produced on sub-horizon scales after the axion starts oscillating, the results of Sect. 3.1 are essential in finding the signal accurately. The audible axion scenario features a qualitative difference with models that secondarily generate gravitation waves via gauge field production during inflation, as the generation occurs during radiation domination, when H < m. The oscillating axion at the minimum of the potential must remain a sub-dominant contribution to the energy budget, otherwise we'd have a phase of intermediate matter domination. It follows that the contribution of the oscillating axion and the subsequently produced dark photons must be sufficiently subleading to the energy density in the radiation fluid. Their relative contributions to the curvature perturbation in total comoving gauge will consequently be suppressed relative to the contribution from fluctuations in the radiation fluid already present before dark photon production (originating from the vacuum fluctuations sourced during inflation). Hence the contribution of scalar perturbations sourced by axion dynamics to the −distortion signal will be subleading to those generated by primordial perturbations from inflation, and can safely be neglected. This model is of particular interest to us as it produces a narrower spectrum of GWs. Thus, to constrain its parameter space it is important to have probes that can cover all phenomenologically relevant frequencies. The GWs produced can be parametrized as a spectrum of the form Here which have both been redshifted to their present-day values. The first two free parameters (i.e., f and m) essentially dictate the height and frequency of the peak in the power spectrum respectively. The second two parameters are limited to ∼ 10 − 100 and ∼ O, and do not significantly change the shape of the spectrum for the range of allowed values. These parameters are therefore degenerate with the first two. We choose fiducial values of = 60 and = 1, but the main results given here hold more generally. The direct dependence of f peak on m means that different types of experiment will probe different mass scales. This is shown Fig. 3, where vertical dotted lines distinguish where different detection methods are dominant. From here it can be seen that SD are sensitive to the ultralight limit of the U audible axion model, a result which again holds for any valid combination of and. Note that Planck extends the limits from COBE/FIRAS at low masses to smaller values of f. Future SDs measurements could significantly improve the limits from Planck to higher masses, covering a wider range of the parameter space of phenomenological interest. We note in particular how SDs can constrain masses in a range not accessible to other measurements (10 −22 −10 −13 eV). Such ultralight axions may be ubiquitous in particular string compactifications (), and moreover, could be a viable dark matter candidate were they to form a condensate at late times (;Marsh 2016), further illustrating the utility of SDs for particle phenomenology. Phase transitions beyond the Standard Model The post-inflationary epoch may have seen a variety of first order phase transitions (PTs) in theories that go beyond the standard model of particle physics. First order PTs are characterized by the fact that latent energy is released, and phases of true vacuum nucleate within false vacuum domains, resulting in bubble collisions (BC) that generate a stochastic GW background. Moreover, magneto-hydrodynamic (MHD) turbulence and sound waves (SW) in the bulk plasma during and after the phase transition also source sub-horizon GWs at commensurate frequencies. If these processes take place during the -era or shortly before, they can potentially result in measurable SDs. Here we once again use the results of Sect. 3.1 to calculate the associated SDs. Referring to the review of Caprini & Figueroa, we see that the spectra resulting from the three different mechanisms for GW production from PTs are given by, with peak frequencies Here, the three principal model parameters are, and w, which fix the amount of latent heat released by the transition as a fraction of the total energy density, inverse time duration of the PT, and velocity of bubble walls respectively. Denoted with * are quantities at the time of the PT, making another key parameter z PT. The first two parameters follow 0 ≤ ≤ 1 and /H * > 1. The velocity of sound waves has been set to unity, since bubble walls usually propagate close to the speed of light. Parameters labelled i ∈ give the weighted contribution from each mechanism. For this work we have used BC = 1, MHD = v and the last of which is valid for w 1. The expected SD limits on PTs given these considerations are shown in Fig. 4. Even for low-energy PTs ( = 0.1) a PIXIE-like mission would explore some of the parameter space not already excluded by Planck; however, it would only see rather long PT. In the more energetic cases ( ≥ 0.5), SD missions could realistically detect PT lasting small fractions of the age of the Universe, and occurring relatively late in cosmic history. Evidently, SDs provide a unique and complimentary window into low scale phase transitions (corresponding to energy scales in the range 10 Mev -10 eV) that are not possible to probe with any other observation. An important caveat to our discussion of this scenario is the potential for the generation of sub-horizon scalar perturbations during and after phase transitions. Sub-dominant contributions arising from the scalar field dynamics have been calculated in Cutting et al., however retaining the scalar contributions from sound waves and MHD turbulence generated after the transition will require further study, and remains an important open question for the present analysis. Our limits can therefore be considered conservative. GUT cosmic string networks Another tell tale sign of physics beyond the Standard Model is the existence of topological defects. Excluding textures, the standard model does not allow for any defects. However, larger gauge symmetries (ubiquitous in models that go beyond the Standard Model) could admit symmetry breaking patterns that generate topological defects in the early Universe (see Kibble 1980Kibble, 1982 which could have persisted into cosmologically observable epochs. Although the simplest models of monopoles and domain walls are tightly constrained (see Sects. 13.5.3 and 14.3.3 in Vilenkin & Shellard 1994), cosmic strings networks remain a theoretical possibility and can impart potentially observable GW signals (see Sect. 10.4 of Vilenkin & Shellard 1994). As an example, we consider a model proposed by Buchmuller et al. which attempts leptogenesis within an SO grand unified theory via a U B−L phase transition, where a local U baryon minus lepton number symmetry is spontaneously broken., showing that late power injection leads to a decrease of less than an order of magnitude for 10 5 < z PT < 10 6. The limits from Planck are also shown for comparison. The temperature at the time of the PT can be found with T PT /MeV ≈ 2 10 −10 z PT. The result of the B − L transition will be a meta-stable CS network generated at the time of the transition, which over the course of the collapse generates a mostly flat spectrum of GWs due to the decay of string loops. An approximate form of their spectrum is given in terms of the model parameters and G as 6 f * = 3 10 14 Hz e −/4 G Buchmuller et al. give a value of ≈ 50 for this particular model, and we use a value of r h 2 = 2.5 10 −5. In reality string network collapse would be a function of time, but to match the formalism outlined in Sect. 3.1 we conservatively assume the entire spectrum emerges at the final moment of collapse given by Buchmuller et al. The spectrum grows ∝ f 3/2 up to f *, and is flat for higher frequencies. Furthermore, f * only depends weakly on G but varies significantly with. This means that once is large enough that the spectrum is flat across the entire window of visibility for a given experiment, the probe will only be sensitive to G. With SD missions probing lower frequencies than astrophysical probes they will be complementary in limiting the lower bounds of the parameter. The potential of SD missions for constraining this model is shown in Fig. 5. Given that the GW spectra produced by CS network collapse has a plateau at smaller scales, for any given sensitivity depicted in Fig. 2, we see that any one of the probes depicted will be equally good at detecting the GW background produced. It is also worth noting that the type of spectrum considered here will hold more generally for a wide range of CS models (see ). Although the generation of scalar perturbations of CS networks in the scaling regime is well understood, the situation is much less clear for the scalar perturbations generated from the decay of meta-stable networks. Moreover, it is unclear whether the dominant decay channel will be via gravitational wave production or scalar perturbations, and the answer will certainly be very model dependent. This remains another open question as far as this study is concerned, and the absence of any such detailed calculations is itself perhaps due to the fact that it may have been unclear in the past what observational consequences, if any, sub-horizon generation of scalar perturbations generated by CS network collapse would have. We hope the results of this paper will provide the necessary motivation for such calculations. Highly energetic events in the early Universe, either during inflation or subsequently during radiation domination, can inject power into the GW spectrum. This can include GWs from sources within the standard CDM cosmology, or from models that invoke physics beyond it. Detecting the GW spectrum is therefore key to further scrutinizing our current paradigm, as well as pushing our knowledge of the early Universe to new and exciting areas. Future experiments will probe these stochastic backgrounds, each sensitive to a range of frequencies/wavelengths dictated by the nature of the experiment. As we have highlighted here, a wide range of GW frequencies ( f = 10 −15 -10 −9 Hz) can only be probed by SD observations. This large span of wavelengths compensates for the relatively low efficiency of generating SDs from GWs, thus making them a potentially powerful probe of physics beyond the Standard Models of both particle physics and cosmology. This work aims to introduce SDs as a complimentary probe through which one can detect and constrain stochastic GW backgrounds. The fundamental element to link these two messengers is the k-space window function, which maps a given GW spectrum into a SD signal imprinted before last scattering . In order to study the injection of power on sub-horizon scales, the window function for primordial tensor perturbations has been generalised , leading to minor changes in some models ( Fig. 3) but large changes in others (Fig. 5). This is essentially related to the fact that GWs have less cosmic history to dissipate their energy to the photon-baryon plasma. A simple python tool is provided at GW2SD 7 and allows one to easily estimate SD limits on various models, given the tensor power spectrum, P T (k, z), that comes into existence at a single redshift z. This is certainly a good approximation for 1'st order phase transitions, and holds to a good approximation for scenarios that dynamically generate GWs over a short duration. Refinements to account for the exact time-dependence of the process are left to future work. To illustrate the utility of SDs for GW cosmology, a series of phenomenological models were discussed, and their resulting SD signals studied: As expected, the tensor perturbations generated by single-field slow-roll inflation are too weak to be measured with SDs (;a). Spectator axion-SU fields too, even in more favourable cases that we considered, will realistically be out of reach in the foreseeable future. The Audible axion model (Sect. 5.3) on the other hand, can have a large region of its parameter space constrained by SDs, particularly for a wide range of masses in the ultra-light regime (Fig. 3). Similarly, the GWs from low scale (10 eV -10 MeV) dark sector phase transitions in the early Universe will be visible with future SD missions if the relative energy content of the participating field is sufficiently large, and the duration sufficiently long (see Sect. 5.4 and Fig. 4). The typically flat GW spectra produced by CS networks can be seen by many instruments, but SDs will be complementary to other probes in being sensitive to string collapse especially in the -era. It is noteworthy that some of the aforementioned models were already constrained with COBE/FIRAS long before first limits from Planck existed. Future CMB spectrometers like SuperPIXIE () could establish a new frontier in this respect. 7 https://github.com/CMBSPEC/GW2SD.git As we have discussed, both in general and for specific models, any SD constraints should include both the scalar and tensor perturbations arising from energetic events (e.g. see ;Amin & Grin 2014, for SDs from scalar perturbations of CS and PTs, respectively). This potential for combining sources is another advantage SD experiments have over GW-based experiments, since the latter are only sensitive to the direct tensor perturbations. This advantage is not easily utilised for the models discussed in this paper, however, since the necessary scalar spectra are generally absent from the literature. Where the inclusion is possible, it is again important to highlight that SDs from tensor perturbations cover a wider range of physical scales than SDs from scalar sources, thus extending the reach of SDs to earlier epochs. In addition, some scenarios do not produce any significant scalar perturbations , making it crucial to account for SDs caused by tensor perturbations. Overall, SDs uniquely probe the presence of small-scale perturbations in regimes that are not directly accessible, thus highlighting the important role that future CMB spectrometers could play in GW cosmology, and, by extension, beyond the Standard Model phenomenology.
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<reponame>woowa-techcamp-2021/store-1
import styled from '@lib/styled-components';
import { IProductListItem } from '@types';
import Link from '@lib/router/Link';
interface IBoardProductsProps {
product: IProductListItem;
}
export default function BoardProduct({ product }: IBoardProductsProps) {
return (
<BoardProductWrapper>
<img className="board__product--img" src={product.imageUrl} alt={product.title} />
<Link to={`/products/${product.id}`}>{product.title}</Link>
{product.price && <p className="board__product--price">{product.price.toLocaleString() + '원'}</p>}
</BoardProductWrapper>
);
}
const BoardProductWrapper = styled.div`
display: grid;
grid-template-columns: 1fr 4fr 1fr 1fr;
padding: 1rem;
align-items: center;
a {
font-size: 1.1rem;
font-weight: bold;
line-height: 1.5em;
&:hover {
text-decoration: underline;
text-underline-position: under;
}
}
.board__product--img {
width: 100%;
max-width: 80px;
}
.board__product--price {
grid-column-start: 4;
}
@media (max-width: ${({ theme }) => theme.media.mobile}) {
grid-template-columns: 1fr 2fr 1fr;
a {
font-size: 1rem;
margin-left: 0.5rem;
}
.board__product--price {
grid-column-start: 3;
font-size: 0.7rem;
}
}
`;
|
async def pause_all(self, seconds: int) -> Dict[str, Any]:
return await self._request(
"post", "watering/pauseall", json={"duration": seconds}
)
|
Simon Birmingham says private trainers costing students and taxpayers three times as much as public educators
Private vocational trainers are charging students – and the taxpayers who give them loans – almost three times as much as Tafes and other public educators.
In Tasmania they are charging 10 times as much, with the average student borrowing $32,981, compared with Tafe fees of just $3470.
The education minister, Simon Birmingham, says the new figures his department released on Monday highlight the “staggering” gap between what providers have been charging for courses and what a Tafe would charge.
“The 2015 data is littered with even more examples of rorting and shonky behaviour from some providers who continue to take advantage of students and taxpayers and tarnish the reputation of the vocational education and training sector,” he says.
Coalition overhauls vocational training loans in private college crackdown Read more
Federal government loans to vocational students have blown out from $325m in 2012 to $2.9bn in 2015. The new figures show that, at the same time, enrolments grew from 57,400 in 2012 to 320,400 in 2015.
More than half of vocational students reported they were unemployed or not seeking a job when they signed up for their course. And nearly four in five said they were studying either to get a job or for job-related reasons such as improving their skills.
However, about 13% of students – almost one in seven – said they were studying for personal interest or self development.
The federal government plans to overhaul the system to restrict loans to courses that meet skills shortages and are most likely to end up with students getting a job.
Birmingham said the old system meant too many students were being signed up for courses simply to boost enrolment numbers or to provide “lifestyle choices” that didn’t lead to work.
“While I understand some people may want to broaden their experiences, ultimately we need to ensure precious taxpayer money is used to support students doing courses with strong employment outcomes, which also increases the prospects of people being able to pay back their government loan,” he said.
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<reponame>AdamKorcz/cncf-fuzzing
// Copyright 2022 ADA Logics Ltd
//
// Licensed under the Apache License, Version 2.0 (the "License");
// you may not use this file except in compliance with the License.
// You may obtain a copy of the License at
//
// http://www.apache.org/licenses/LICENSE-2.0
//
// Unless required by applicable law or agreed to in writing, software
// distributed under the License is distributed on an "AS IS" BASIS,
// WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
// See the License for the specific language governing permissions and
// limitations under the License.
//
package prometheus
import (
fuzz "github.com/AdaLogics/go-fuzz-headers"
log "github.com/sirupsen/logrus"
"github.com/argoproj/argo-rollouts/pkg/apis/rollouts/v1alpha1"
)
func FuzzPrometheusProvider(data []byte) int {
f := fuzz.NewConsumer(data)
metric := v1alpha1.Metric{}
err := f.GenerateStruct(&metric)
if err != nil {
return 0
}
e := log.Entry{}
mock := mockAPI{
value: newScalar(10),
}
p := NewPrometheusProvider(mock, e)
_ = p.Run(newAnalysisRun(), metric)
return 1
}
|
<filename>logger.go<gh_stars>100-1000
package corebgp
import (
"fmt"
)
// Logger is a log.Print-compatible function
type Logger func(...interface{})
var (
logger Logger = nil
)
// SetLogger enables logging with the provided Logger.
func SetLogger(l Logger) {
logger = l
}
func log(v ...interface{}) {
if logger != nil {
logger(v...)
}
}
func logf(format string, v ...interface{}) {
log(fmt.Sprintf(format, v...))
}
|
On the Move (Donna Fargo album)
Background and content
On the Move was recorded in January 1976 at the Columbia Recording Studio and the Quadrafonic Sound Studios in Nashville, Tennessee, United States. The session was Fargo's first recordings for Warner Bros. Records. Fargo's previous label Dot Records was financially unstable and instead, Warner Bros. offered her a seven figure sum to record for the label. On the Move was originally issued as an LP record with five songs contained on each side of the album.
Release
On the Move spawned two singles in 1976. The lead single from the album and the opening track entitled "Mr. Doodles" was released in 1976, peaking at #20 on the Billboard Magazine Hot Country Singles chart and #40 on the Canadian RPM Country Singles chart. The second and final single spawned was "I've Loved You All of the Way" in July 1976. The song reached #15 on the Billboard country singles chart and did not chart the Canadian country chart. On the Move was released in mid 1976 and peaked at #31 on the Billboard Magazine Top Country Albums chart, Fargo's lowest-peaking album on the chart up to that point.
The title of the album can literally refer to Fargo being "on the move" according to Greg Adams of Allmusic, as he related the album title to her transition from Dot Records to Warner Bros. Records. Adams noted the song "I've Loved You All of the Way"'s vocal resemblance to "Dolly Parton meets Joan Rivers". Adams retrospectively gave the album two out of five stars stating, "On the Move is a fair album, but the caliber of songwriting is not up to Fargo's usual standards."
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Innovative Application of Bar Coding Technology to Breast Milk Administration Hospitalized infants often receive expressed breast milk, either from their mother or from banked milk. Breast milk provides optimal nutrition for infants but because it is a body fluid it carries the risk of disease transmission. Therefore, administering the correct breast milk to hospitalized infants is essential. Bar coding technology, used in hospitals to prevent errors related to medication administration, can be proactively applied to prevent breast milk administration errors. Bar coding systems offer advantages over manual verification processes, including decreasing errors due to human factors and providing for automated entry of feedings in the electronic health record. However, potential barriers to successful implementation must be addressed. These barriers include equipment and training costs, increased time to perform the additional steps with bar coding, and work-arounds.
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<reponame>RemiMattheyDoret/SimBit<filename>src/FitnessMap_workInProgress/FitnessMap.h
class TraitSpecificFitnessMap
{
private:
std::vector<std::vector<double>> fitnessEffects;
std::vector<double>* fitnessEffectsInHabitat;
public:
bool isSelection;
bool isMuliplicitySelection;
bool isAllSameEffect;
};
class FitnessMap
{
private:
std::vector<std::vector<double>> T1_FitnessEffects;
std::vector<std::vector<double>> T2_FitnessEffects;
std::vector<std::vector<double>> T56_FitnessEffects;
std::vector<double>* T1_FitnessEffects_inHabitat;
std::vector<double>* T2_FitnessEffects_inHabitat;
std::vector<double>* T56_FitnessEffects_inHabitat;
bool T1_isSelection;
bool T2_isSelection;
bool T56_isSelection;
bool T1_isAllSameFitEffect;
bool T2_isAllSameFitEffect;
bool T56_isAllSameFitEffect;
bool T1_isMuliplicitySelection;
bool T56_isMuliplicitySelection;
bool T1_isEpistasis;
std::vector<std::vector<std::vector<T1_locusDescription>>> T1_Epistasis_LociIndices;
std::vector<std::vector<std::vector<double>>> T1_Epistasis_FitnessEffects; //get fitness value with this->FitnessEffects_ForASingleHabitat[habitat][groupOfLoci][fitnessValueIndex], where the fitnessValueIndex is function of the genotype
public:
template<typename INT>
void setHabitat(const INT habitat) const;
template<typename INT>
uint32_t get(const INT i) const;
};
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Modeling of a Nonlinear Vibration-Based Energy Harvesting System as a Duffing Oscillator The harvesting of ambient energy has become more important over the last years. This paper will investigate an analytical effort to predict the Duffing parameters for a magnetoelastic cantilever structure. The modeling is compared to a nonlinear harvester with point dipoles. The system consists of a harmonic excited cantilever structure with a magnetic tip mass. The beam is firmly clamped to the host structure. A second oppositely poled permanent magnet is located near the free end of the beam. The system is a bistable nonlinear oscillator with two equilibrium positions. Several studies show the better performance of the setup. The approach is not limited for energy harvesting techniques. The setup is suitable for broadband oscillations and also to tune the resonant frequency closer to the excitation frequency.
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Photo by flickr user <a href="http://www.flickr.com/photos/edlabordems/3616570651/">edlabordems</a> used under a <a href="http://www.creativecommons.org">Creative Commons</a> license.
Barack Obama, the Fed, Hitler, Marxism, the government seizing control of health care, ACORN. Somehow all of this came together at a town hall meeting held in Tavares, Florida, on Monday night by Rep. Alan Grayson (D-Fl.), when dozens of Teabaggers, those rightwing activists associated with the so-called Tea Party movement, showed up to slam Grayson and vent their anger at a political world—that is, their version of it.
Two weeks ago, Grayson argued on the House floor that Republicans’ health care plan amounted to “don’t get sick,” and if you do, “die quickly.” Grayson quickly became a hero for Democrats, and a target for GOPers. He later explained that he was being facetious, but the dozens of protesters outside this event were not the least bit amused. And despite the Beltway blather, it wasn’t really Grayson’s comments that had the protesters fired up. They had been mad long before Grayson said what he said.
Chuck Colley, who said he’s new to the Tea Party movement, told me that the President, who he called “Ali Baba,” is “ruining this country” by creating problems “so he can invoke more government.” Obama “wants to be the Marxist leader of this country,” the “Hitler,” Colley said.
The rest of the Teabaggers (every protester I spoke to said he was a member of or otherwise affiliated with the “Tea Party Patriots”) mostly had gripes that had little to do with Grayson’s comments or the actual state of political debate in Washington. Instead, they railed against the usual bogeymen: a government takeover of health care (not happening), Barack Obama (plotting socialist overthrow), and the Federal Reserve (a target they share with Grayson, who has cosponsored a bill to audit the Fed). None of the protesters I spoke with was particularly well informed. Jones didn’t appear to know that Grayson wanted to audit the Fed, even as he was telling me that the economic meltdown was the Fed’s fault. Hoyt, who brought a cardboard cutout of Grayson to the rally, couldn’t say why the cutout had a “Congressman from ACORN” button on its suit pocket.
Jones, Hoyt, and Tillison each voiced support for Patricia Sullivan, a local Tea Party leader who is running against Grayson. Soon enough, Sullivan was there, too, talking up reporters. “It sounds like someone is off their medicine,” she said, referring to Grayson. “[He’s] not thinking clearly.” Sullivan’s congressional run may not have the backing of the Republican establishment, but she clearly has some organizing skills: on her campaign site, Sullivan claims to have organized two 1,000-person tea parties. But there couldn’t have been more than 100 protesters, despite a pre-protest “tailgate” that was organized for the time leading up to the Grayson event.
There were counter-protesters. Bob Jenner was sporting a fedora and holding up a sign that said Grayson: n., backbone. While most Tea Partiers were careful about what they said to reporters, they didn’t always keep their muttering to themselves. “He’s a teacher,” one said of Jenner (who is). “That explains his socialist tendencies.” Another speculated that something about Jenner (his sign? his hat?) would “be good for target practice.” Jenner, who was being interviewed at the time, didn’t catch the thinly-veiled threat.
The town hall itself was fairly uneventful. The vast majority of the Teabaggers didn’t make it in, and those that did were quickly disarmed by Grayson’s stunningly softspoken manner (or perhaps intimidated by his 6’4” frame and rumors of lycanthropy). Besides, everyone already knew what everybody else thought. They’d settled that outside, with chants and counterchants. “Grayson tells the truth!” the Dems hollered.”He lies!” the Tea Partiers would shout back. So while it may have been Alan Grayson’s town hall, Joe Wilson was definitely there in spirit.
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Defining perioperative anaemia in pregnant women challenging the status quo Perioperative anaemia is a significant risk factor for morbidity and mortality. Anaemia during pregnancy is associated with adverse maternal and neonatal outcomes, and postpartum haemorrhage remains a leading cause of maternal mortality worldwide. Caesarean section is an operation incurring moderate risk of bleeding, and rates are rising globally. Recent international consensus guidelines recommend targeting a preoperative haemoglobin > 130 g.l−1 for all patients having surgery with moderatetohigh risk of bleeding, regardless of sex. It is unclear how this recommendation translates to pregnant women, where anaemia is defined at a much lower haemoglobin level of < 110 g.l−1. Longstanding definitions of anaemia during pregnancy are likely to be the result of flawed sampling of a socalled normal but anaemic female population, given the high prevalence of iron deficiency and anaemia in healthy menstruating women. Contemporary data suggest that haemoglobin values in ironreplete pregnant women are higher than previously thought. The definition of anaemia has significant clinical implications, particularly for perioperative management of women undergoing caesarean section. In addition, we should differentiate between lower reference values and optimal haemoglobin targets. The haemoglobin level associated with optimal obstetric and neonatal outcomes requires further investigation in pregnant women.
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On the Way Home there was a moment we were coming down from the turbulent waters of the Maligne it had been raining for what seemed hours on end there was a thick mist hanging in the air, a billowing high above the larches and the pines so that the mountain peaks seemed all but hidden when suddenly without warning the face of one mountain far off to our left began to shine it was as if some mystery had just revealed the merest glimpse of what it was I thought of Peter bartering with Jesus on the Mount of Transfiguration to stay, stay, or Moses alone there on the Mountain as the wind whispered in all but words here I am immerse yourself in me now, now, for even this must pass and you will descend, returning to a world which will or will not care but know too that this moment may well return and it will be as if we came together then for good.
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<filename>src/app/reducers/formElements/form-buider-selector.ts
import {IFormBuilder, IPropertiesObj} from '../../shared/interfaces';
export const selectListStyles = (state: IFormBuilder): IPropertiesObj[] => state.elements ;
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