text stringlengths 8 5.77M |
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It’s almost everyone’s favorite time of year again: Halloween! Even adults love free candy and dressing up and going to parties with their friends. But as much as we love Halloween, sometimes it can kind of freak out our dogs.
It’s easy to understand if you see things from their perspective. Three-foot tall bumblebees and a dozen mop-headed little Harry Potters running around—it isn’t normal. It can seem threatening to many dogs.
Here are some tips compiled by a few of us here at the pet supply store in Henderson, NV to help you prepare your dog for trick-or-treaters this Halloween.
Acclimate them to the noises
If your dog has a problem with the doorbell or people knocking on the door, they’re likely going to have a difficult time this Halloween. You can help your dog get used to the doorbell, and to the additional knocking, by going outside and ringing your own doorbell and knocking on your own door several times a day. While doing this, help your dog to learn not to bark by calming them down, and then rewarding them when they remain calm.
Keep your dog indoors
Outside dogs often have more difficulty with strangers when they’re in the yard than when they’re indoors. So a good idea this Halloween is simply to bring your dog inside for the night. It helps them feel safe to be by your side, and it discourages the type of territorial behavior that is more pronounced when they’re outside in the yard.
Stay calm yourself, and when you notice your dog is uneasy, pet them, give them a treat or take them to your room
Dogs are really intuitive animals, and if you’re worried about your dog, your dog can pick up on that. This is why it is important to remember to stay calm yourself. If you notice that your dog’s tail is between their legs, or they’re tensing up, or trembling, take them back into your room, where they can be alone, and try to help them get some sleep.
Make sure your dog doesn’t get into the candy
When dogs are uncomfortable, they can sometimes act out, just like any other animal, including humans. This means that, while your dog may not normally eat human food or get into anything it’s not supposed to, if it’s freaked out from the trick-or-treaters, it might do something naughty and out of character like getting into the candy. The sugar, in general, is not good for your dog, and of course we all know how bad chocolate is for pups!
Make sure you have a room set up, just in case, where your dog can be safe
Just have a backup plan in case your dog does get upset. Having a backup plan will help you keep calm yourself, which will help keep your dog calmer. Just have a comfortable spot where your dog can hunker down and nap. Make sure to have some dog supplies on hand—visit your local pet supply store in Henderson, NV, if necessary—such as their favorite toy and a few snacks.
If you follow these simple tips, you and your dog should have a really fun Halloween this year.
This Halloween, come down to The Soggy Dog for all your dog supplies. We’re the best pet supply store in Henderson, NV. We’ve got your pup’s favorite snacks and toys, and we’re focused on offering only natural snacks. When your dog has their favorite things, you know how much of a good boy or a good girl they can be. Then you can just sit back, relax, hand out candy and help all the trick-or-treaters have a good, spooky night. |
Summary. While the established electrochemical and microdialysis-based techniques for measuring drugs and neurotransmitters in the brain have unimpeachably contributed to our understanding of brain function, they are not without limitations. For example, when the same dose of cocaine is infused over 5 s versus 90 s the behavioral, metabolic, and even genetic outcomes vary dramatically, suggesting that the 2 min resolution of the most highly resolved of prior in-brain cocaine measurements are poorly matched to timescale of the drug's psychobiology. More generally, no drugs and only a small number of neurotransmitters have been measured to date in the brain with the most behaviorally relevant seconds time resolution. In response, our vision is to adapt electrochemical aptamer-based (E-AB) sensors, an in-vivo measurement platform that does not rely on the chemical or enzymatic reactivity of its targets (thus ensuring generality), to the problem of simultaneously monitoring drugs of abuse and the neurotransmitters they modulate in situ in the brains of freely moving, normally behaving rodents. To this end, we have already demonstrated feasibility by performing the high frequency, multi-hour measurement of more than a half dozen molecules in the blood and brains of live rats. Leveraging these preliminary results we propose here the adaptation of E-AB sensors to the problem of studying of brain chemistry. If successful, the proposed work will greatly expand the number of neurochemically relevant molecules that can be measured in real time and with second resolution in the living brain, thus creating a new window into brain chemistry that provides unique capabilities for closed-loop study and intervention. |
Dipeptidyl Peptidase-4, Wound Healing, Scarring, and Fibrosis.
Scarring and fibrosis are an enormous public health concern, resulting in excessive morbidity and mortality in addition to countless lost health care dollars. Recent advances in cell and developmental biology promise a better understanding of scarring and fibrosis and may translate to new clinical therapies. |
/*
GeoGebra - Dynamic Mathematics for Everyone
http://www.geogebra.org
This file is part of GeoGebra.
This program is free software; you can redistribute it and/or modify it
under the terms of the GNU General Public License as published by
the Free Software Foundation.
*/
package org.geogebra.common.kernel.advanced;
import org.geogebra.common.kernel.CircularDefinitionException;
import org.geogebra.common.kernel.Kernel;
import org.geogebra.common.kernel.arithmetic.Command;
import org.geogebra.common.kernel.commands.CommandProcessor;
import org.geogebra.common.kernel.geos.GeoElement;
import org.geogebra.common.kernel.geos.GeoPoint;
import org.geogebra.common.kernel.prover.AlgoAreConcyclic;
import org.geogebra.common.main.MyError;
/**
* AreConcyclic[<Point>, <Point>, <Point> ]
*/
public class CmdAreConcyclic extends CommandProcessor {
/**
* Creates new command processor
*
* @param kernel
* kernel
*/
public CmdAreConcyclic(Kernel kernel) {
super(kernel);
}
@Override
public GeoElement[] process(Command c)
throws MyError, CircularDefinitionException {
int n = c.getArgumentNumber();
GeoElement[] arg;
arg = resArgs(c);
if (n == 4) {
if (!(arg[0] instanceof GeoPoint)) {
throw argErr(c, arg[0]);
}
if (!(arg[1] instanceof GeoPoint)) {
throw argErr(c, arg[1]);
}
if (!(arg[2] instanceof GeoPoint)) {
throw argErr(c, arg[2]);
}
if (!(arg[3] instanceof GeoPoint)) {
throw argErr(c, arg[3]);
}
AlgoAreConcyclic algo = new AlgoAreConcyclic(cons, c.getLabel(),
(GeoPoint) arg[0], (GeoPoint) arg[1], (GeoPoint) arg[2],
(GeoPoint) arg[3]);
GeoElement[] ret = { algo.getResult() };
return ret;
}
throw argNumErr(c);
}
}
|
Batting
WALTHAM, Mass. – The Brandeis University softball team played second-ranked Emory University even through the first four-and-a-half innings, but the Eagles scored twice in the late innings to emerge with 3-0 University Athletic Association victory.
Both teams had their chances in the early frames, as there were no 1-2-3 inning recorded in the entire contest. Brandeis sophomore CF Amanda Genovese (North Haven, Conn./North Haven) led off the game with a bunt single and stole second and third, but Emory pitcher Sydney Carpenter struck out the side to avoid allowing the early run.
Emory's Lauren Goredetsky tried to manufacture a run of her own in the bottom of the first, when she singled up the middle, moved to second on a sacrifice bunt and stole third. Brandeis senior pitcher Casey Ducinski (Duxbury, Mass./Duxbury) was up to the task, however, getting a foul pop and a strikeout of her own to retired the side.
The Judges mounted a serious threat in the top of the third. Ducinski led off the inning with a single to third base, followed by another bunt hit by Genovese. The two moved to second and third on a wild pitch, and Carpenter issued a walk to rookie shortstop Madison Gagnon (Westlake Village, Calif./Westlake) to load the bases. The Eagle hurler wriggled her way out of the jam, however. Carpenter got a tapper back to the circle for a force at home on the first out. For the second, Emory caught Genovese trying to take too large of a lead off third base and picked her off, and a strikeout kept the Judges off the board.
Brandeis returned the favor in the bottom of the third, when Emory loaded the bases with one out. Ducinski got a line-out and a ground out to sophomore Anya Kamber (Sammamish, Wash./Skyline) at third base. After a relatively uneventful fourth and top of the fifth, Emory finally broke through against Ducinski when right fielder Ally Kersthold led off the frame with her first home run of the season.
Brandeis had a chance to get the run back in the top of the sixth when rookie 2B Danielle Novotny (Milford, N.J./Delaware Valley) and sophomore catcher Cori Coleman (Burr Ridge, Ill./Hinsdale South) each drew a walk, but EU reliever Amanda Kardys got a strikeout and a ground out to maintain the one-run lead. The Eagles got two insurance runs in the sixth as the Judges committed three costly errors. In the Brandeis seventh, Ducinski reached on a one-out single and got to third with two away, but Kardys nailed down the save with a grounder to short.
Ducinski had a fine all-around performance for the Judges in the losing effort. She went 2-3 and reached on an error at the plate, while allowing just five hits in 5.2 innings in the circle. Only one of her three runs allowed was earned as she struck out five and walked two. Genovese also had two hits for the Judges, while two more stolen bases gives her 17 for the season and nine for the tournament. Genovese is four shy of the UAA single-season stolen base record with three games to play.
Gorodetsky was the only player with multiple hits for Emory, while Kersthold's home run produced the game's only RBI. Carpenter improved to 4-0 with five innings of four-hit, nine-K pitching, while Kardys earned her second save of the season with two innings of one-hit ball.
Brandeis returns to action tomorrow with contests against No. 24 Washington University and the University of Rochester at 10 a.m. and 12:30 p.m., respectively. |
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<Folder Include="Service References\" />
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<Import Project="$(MSBuildToolsPath)\Microsoft.CSharp.targets" />
<!-- To modify your build process, add your task inside one of the targets below and uncomment it.
Other similar extension points exist, see Microsoft.Common.targets.
<Target Name="BeforeBuild">
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</Project> |
Q:
Malloc breaks when it oughtn't
I've looked all over google and can't seem to comprehend why malloc is failing in my code. I have included the parts of the code I think are useful to understand the problem.
The strange part is that I used malloc 5 lines above in the exact same way, and it succeeds every time for the first one, but consistently fails for the second one. As I've gone through gdb, the pointer for parent->left_tree is 0x0 before it is malloc-ed, and it works fine, and then when it comes to parent->right_tree, it fails every time with the given cryptic error message. I've tried experimenting with different values inside the malloc, such as malloc(64) and malloc(10000), and the results are identical.
Here is the function of the code where malloc fails:
int
prefix_input( expr_tree_T parent )
{
char *token = get_next_token();
int int_value;
double dub_value;
int type = node_type(token);
if (type == -1)
{
fprintf(stderr, "ERROR: '%s' is invalid input.\n", token);
exit(2);
}
parent->type = type;
if (type == OPERATOR )
{
parent->value.operator = token[0];
parent->left_subtree = malloc(sizeof(expr_tree_T));
mem_check(parent->left_subtree, "left subtree");
prefix_input( parent->left_subtree );
parent->right_subtree = malloc(sizeof(expr_tree_T)); //<-- ***Right here***
mem_check(parent->right_subtree, "right subtree");
prefix_input( parent->right_subtree );
}
else if (type == INTEGER)
{
sscanf( token, "%d", &int_value );
parent->value.int_value = int_value;
parent->left_subtree = NULL;
parent->right_subtree = NULL;
}
else if (type == DOUBLE)
{
sscanf( token, "%lf", &dub_value );
parent->value.double_value = dub_value;
parent->left_subtree = NULL;
parent->right_subtree = NULL;
}
return 0;
}
Here is the code for the struct which is having the memory allocated to:
typedef struct expr_tree_node
{
struct expr_tree_node *left_subtree;
struct expr_tree_node *right_subtree;
int type;
union
{
char operator;
int int_value;
double double_value;
} value;
} * expr_tree_T;
This is all my included header files:
#include <stdio.h>
#include <stdlib.h>
#include <string.h>
#include <unistd.h>
This is how the code is compiled:
gcc -Wall -std=c99 -D_POSIX_SOURCE A12P2.c -o a12p2 -g
This is a sample from debugging with GDB. I can observe that the pointer for parent->right_subtree is at 0, which as I've researched is the safest thing to use malloc on in general.
prefix_input (parent=0x804c008) at A12P2.c:171
171 parent->right_subtree = malloc(sizeof(expr_tree_T));
(gdb) print parent->left_subtree
$7 = (struct expr_tree_node *) 0x804c160
(gdb) print parent->right_subtree
$8 = (struct expr_tree_node *) 0x0
(gdb) s
a12p2: malloc.c:2369: sysmalloc: Assertion `(old_top == (((mbinptr) (((char *) &((av)-
>bins[((1) - 1) * 2])) - __builtin_offsetof (struct malloc_chunk, fd)))) && old_size
== 0) || ((unsigned long) (old_size) >= (unsigned long)((((__builtin_offsetof (struct
malloc_chunk, fd_nextsize))+((2 * (sizeof(size_t))) - 1)) & ~((2 * (sizeof(size_t))) -
1))) && ((old_top)->size & 0x1) && ((unsigned long)old_end & pagemask) == 0)' failed.
Program received signal SIGABRT, Aborted.
0xb7fdd424 in __kernel_vsyscall ()
A:
This type of error indicates that your application has corrupted data structures used by malloc(). This usually happens because you have written outside an allocated block of memory, or have written to memory that has been freed.
In this case, it appears that you're not allocating enough memory for your structures:
parent->left_subtree = malloc(sizeof(expr_tree_T));
Given the prototype of this function, it looks as though expr_tree_T is a typedef for a pointer to a structure, not the structure itself. If this is indeed the case, then sizeof(expr_tree_T) ends up being the size of that pointer, not of the structure, so you're allocating much less memory than is actually needed!
I'd strongly recommend that you change the definition of this type to make it a name for the structure (so the function will now accept a expr_tree_T * as an argument). If you find the stars obnoxious, typedef the pointer to something like expr_tree_ref and use that as appropriate. In your header file, this might look something like:
typedef struct expr_tree {
....
} expr_tree_T, *expr_tree_ref;
Failing that, you will need to specifically reference the structure in your sizeof() expression:
malloc(sizeof(struct what_an_expr_tree_T_points_to))
which is (even once you use the real name, whatever it is) a lot messier than sizeof(expr_tree_T).
|
Q:
Angular UI router 0.2.18 param on root url
I have an issue where I want to have a parameter on the route url e.g
$stateProvider.state('/someRoute', {
url: '/:path',
.....
});
$stateProvider.state('/contact', {
url: '/contact',
.....
});
But if I do that then other pages get misinterpreted as being part of this. for example /contact url thinks that "contact" is the param and not the page.
Is there a way around this or do I need to have a sub-page e.g /something/:path?
A:
The issue is that currently due to the order of the states, your first state will capture all urls as it's expecting some parameter.
/contact satisfies the /:path criteria.
Either move the /:path as the last state. or create a /something/:path
|
---
author:
- Daniel Kressner
- Robert Luce
- Francesco Statti
bibliography:
- 'references.bib'
title: Incremental computation of block triangular matrix exponentials with application to option pricing
---
#### Key words {#key-words .unnumbered}
Matrix exponential, block triangular matrix, polynomial diffusion models, option pricing
|
/*-------------------------------------------------------------------------
*
* Copyright (c) 2009, PostgreSQL Global Development Group
*
* IDENTIFICATION
* $PostgreSQL: pgjdbc/org/postgresql/copy/PGCopyInputStream.java,v 1.1 2009/07/01 05:00:39 jurka Exp $
*
*-------------------------------------------------------------------------
*/
package org.postgresql.copy;
import java.io.IOException;
import java.io.InputStream;
import java.sql.SQLException;
import org.postgresql.PGConnection;
import org.postgresql.util.GT;
import org.postgresql.util.PSQLException;
import org.postgresql.util.PSQLState;
/**
* InputStream for reading from a PostgreSQL COPY TO STDOUT operation
*/
public class PGCopyInputStream extends InputStream implements CopyOut {
private CopyOut op;
private byte[] buf;
private int at, len;
/**
* Uses given connection for specified COPY TO STDOUT operation
* @param connection database connection to use for copying (protocol version 3 required)
* @param sql COPY TO STDOUT statement
* @throws SQLException if initializing the operation fails
*/
public PGCopyInputStream(PGConnection connection, String sql) throws SQLException {
this(connection.getCopyAPI().copyOut(sql));
}
/**
* Use given CopyOut operation for reading
* @param op COPY TO STDOUT operation
* @throws SQLException if initializing the operation fails
*/
public PGCopyInputStream(CopyOut op) {
this.op = op;
}
private boolean gotBuf() throws IOException {
if(at >= len) {
try {
buf = op.readFromCopy();
} catch(SQLException sqle) {
throw new IOException(GT.tr("Copying from database failed: {0}", sqle));
}
if(buf == null) {
at = -1;
return false;
} else {
at = 0;
len = buf.length;
return true;
}
}
return buf != null;
}
private void checkClosed() throws IOException {
if (op == null) {
throw new IOException(GT.tr("This copy stream is closed."));
}
}
public int available() throws IOException {
checkClosed();
return ( buf != null ? len - at : 0 );
}
public int read() throws IOException {
checkClosed();
return gotBuf() ? buf[at++] : -1;
}
public int read(byte[] buf) throws IOException {
return read(buf, 0, buf.length);
}
public int read(byte[] buf, int off, int siz) throws IOException {
checkClosed();
int got = 0;
while( got < siz && gotBuf() ) {
buf[off+got++] = this.buf[at++];
}
return got;
}
public byte[] readFromCopy() throws SQLException {
byte[] result = buf;
try {
if(gotBuf()) {
if(at>0 || len < buf.length) {
byte[] ba = new byte[len-at];
for(int i=at; i<len; i++)
ba[i-at] = buf[i];
result = ba;
}
at = len; // either partly or fully returned, buffer is exhausted
}
} catch(IOException ioe) {
throw new PSQLException(GT.tr("Read from copy failed."), PSQLState.CONNECTION_FAILURE);
}
return result;
}
public void close() throws IOException {
// Don't complain about a double close.
if (op == null)
return;
try {
op.cancelCopy();
} catch(SQLException se) {
IOException ioe = new IOException("Failed to close copy reader.");
ioe.initCause(se);
throw ioe;
}
op = null;
}
public void cancelCopy() throws SQLException {
op.cancelCopy();
}
public int getFormat() {
return op.getFormat();
}
public int getFieldFormat(int field) {
return op.getFieldFormat(field);
}
public int getFieldCount() {
return op.getFieldCount();
}
public boolean isActive() {
return op.isActive();
}
public long getHandledRowCount() {
return op.getHandledRowCount();
}
}
|
Prolonged balloon tamponade in the initial management of inferior vena cava injury following complicated filter retrieval, without the need for surgery.
Advanced techniques have been described to remove embedded inferior vena cava (IVC) filters including the loop snare and modified loop snare (Hangman) techniques. Retrieval of embedded filters have been associated with higher rates of complications including IVC injury and stenosis. We report two challenging embedded retrievals complicated by IVC injury and haemorrhage. Haemostasis was successfully achieved with prolonged balloon tamponade, suggesting that injury to the IVC during filter retrieval may not need urgent surgery. However, both patients received short-term complications related to caval thrombosis and patients in this cohort should be closely observed after retrieval. These cases support rigorous attention to filter indication and follow-up. |
FairMormon has a service where questions can be submitted and they are answered by volunteers. If you have a question, you can submit it at http://www.fairmormon.org/contact. We will occasionally publish answers here for questions that are commonly asked, or are on topics that are receiving a lot of attention. The question and answer below have been edited to maintain confidentiality.
Question:
Why would God allow someone who has a hidden history of sexual misconduct to serve in callings such as a Bishop, Stake President, MTC President, etc.? Wouldn’t the Lord warn those making the call?
Answer from FairMormon volunteer Greg Smith:
Thanks for writing FairMormon. I speak only for myself, not FairMormon or the Church.
You ask an important question, and in a sense it is a version of probably the most difficult question any believer in God confronts. Some have said that it is the only decent objection against a belief in God. The question turns on the “Problem of Evil”–that is, if God is good, why does he allow or tolerate, or permit, evil?
As LDS, we have a fairly robust answer to this–we are in a telestial world, which God sent us to with our permission (and even our shouts of joy) to learn and develop in ways we were unable or unwilling to do so in his presence. This necessitates that free moral agent choices be relatively unconstrained–there isn’t much of a test or much of a show of what we’re really like if God swoops in to prevent or punish any abuse of moral agency.
This principle extends, I think, even to Church leaders. We remember, as you note, the case of Judas–Jesus chose him to be an apostle, and yet Judas would ultimately betray him and cause his death. Could God or Jesus have forseen this? Certainly. Yet, Judas was still permitted to make his own choices, and go his own way. Many of the early leaders of the Church also fell into these sorts of difficulties. John C. Bennett in Nauvoo was able to exploit and abuse many people before he was finally discovered.
The Lord warned the prophet Joseph Smith that this principle was in operation in our day. As D&C 10:39 puts it: “But as you cannot always judge the righteous, or as you cannot always tell the wicked from the righteous, therefore I say unto you, hold your peace until I shall see fit to make all things known unto the world concerning the matter.”
The Lord typically does eventually reveal (or allow to be discovered) the actions of evil people in positions of leadership, or anywhere else, for that matter. But, they aren’t always prevented from evil acts, and punishment and consequences do not usually come immediately. (In some senses, we ought to be grateful for this, since you and I have likewise made mistakes or even committed serious sins–we are granted a period of time in which we can recognize and repent if we choose to do so. An immediate punishment, discovery, or consequence would reduce the chance for genuine, sincere repentence–when consequences come, people often sorrow, but as with the fallen Nephite nation, all too often the sorrow or regret of being caught and exposed in sin is “sorrowing…not unto repentance, because of the goodness of God; but it was rather the sorrowing of the damned, because the Lord would not always suffer them to take happiness in sin.” (Mormon 2:13)
So, those are the sort of ideas that I think need to factor in to any sort of answer or perspective we gain on this type of issue. As I say, it is a difficult one–ultimately, only our trust in God’s justice and mercy can reassure us, along with the knowledge that Jesus suffered for just this type (and all types) of betrayal in our behalf. He is, thus, able to be what Elder Maxwell called “a fully comprehending Christ.” We want and need mercy, but I think these cases show how we couldn’t worship a God who simply overlooked or waved aside all such crimes in others. We want and need justice too. A God who gives a pass to childmolesters and abusers is not one we’d want.
None of this, of course, excuses abuse or bad behavior, or means we shouldn’t expose it. As Joseph Smith told the saints, “Therefore, that we should waste and wear out our lives in bringing to light all the hidden things of darkness, wherein we know them…These should then be attended to with great earnestness….Therefore, dearly beloved brethren, let us cheerfully do all things that lie in our power; and then may we stand still, with the utmost assurance, to see the salvation of God, and for his arm to be revealed.” (D&C 123:13,14,17)
Even in Church discipline matters, we don’t just rely on “the spirit”. You cannot simply say, as a bishop, “The spirit has told me you should be excommunicated.” That way lies things like witch trials–accusations against which one cannot defend, and where the innocent are all too easily swept up into condemnation by either the overzealous, or the wicked. One must have witnesses, and evidence, and the accused are permitted to respond to and question witnesses and evidence.
And, we should not overlook the possibility in some cases that a call may be in error, but the Lord permits it to stand because it will reveal necessary truths about the person called.
I hope these thoughts at least provide you the raw material to develop your own answer to this question.
Please write back if we can help further.
Best,
Greg Smith
FairMormon volunteer
Raymond, Alberta, Canada |
Q:
Value-added tax calculator app
The app calculates the tax which is included in a (given) amount. Because I'm new with both libraries (React.js and Foundation) I would appreciate hints and improvement suggestions.
Live demo on CodePen
var SelectInput = React.createClass({
changeHandler: function(e) {
this.props.setTaxRate(e.target.value);
},
render: function() {
var options = [];
for (let i = this.props.min; i <= this.props.max; i++) {
options.push(<option value={ i } >{ i }</option>);
}
return (
<div>
<select id="tax-rate" ref="taxRate"
onChange={ this.changeHandler }
value={ this.props.preSelected }
title={ this.props.title }>
{ options }
</select>
</div>
);
}
});
var TaxCalculator = React.createClass({
DEFAULT_TAX_RATE: 20,
getInitialState: function() {
return {
totalAmount: 0,
nettoAmount: 0,
includedTax: 0,
taxRate: this.DEFAULT_TAX_RATE
}
},
setTaxRate: function(val) {
this.setState( {
taxRate: parseFloat(val)
} );
},
setTotalAmount: function() {
var toCheck = parseFloat(this.refs.totalAmount.value);
if (typeof toCheck === 'number' && toCheck === toCheck) {
this.refs.totalAmount.classList.remove('invalid-value');
this.refs.calculate.removeAttribute('disabled');
this.setState( {
totalAmount: toCheck.toFixed(2)
} );
} else {
this.refs.totalAmount.classList.add('invalid-value');
this.refs.calculate.setAttribute('disabled');
this.forceUpdate();
}
},
calculate: function() {
this.state.includedTax =
(( this.state.totalAmount / (100 + this.state.taxRate) )
* this.state.taxRate).toFixed(2);
this.state.nettoAmount = (this.state.totalAmount - this.state.includedTax).toFixed(2);
this.forceUpdate();
this.refs.totalAmount.setAttribute('disabled', 'disabled');
},
reset: function() {
this.setState( {
totalAmount: 0,
nettoAmount: 0,
includedTax: 0,
taxRate: this.DEFAULT_TAX_RATE
} );
this.refs.totalAmount.value = 0;
this.refs.totalAmount.removeAttribute('disabled');
this.refs.totalAmount.classList.remove('invalid-value');
},
render: function() {
return (
<div className="calculator-form">
<div className="row">
<div className="callout secondary">
<h3>Value-added tax calculator</h3>
<p>Enter the total amount and the tax rate for to get the amount of the contained tax.</p>
</div>
</div>
<div className="row">
<div className="labeled-input medium-12 large-6 columns">
<label for="total-amount">Total amount: </label>
<input type="text" id="total-amount" required pattern="[0-9]+"
ref="totalAmount" onChange={ this.setTotalAmount }
title="Enter here the total amount."
placeholder="Please enter the total amount as a number here ..." />
</div>
<div className="labeled-input medium-12 large-6 columns">
<label for="Tax-rate">Tax rate: </label>
<SelectInput min="1" max="99"
preSelected={ this.state.taxRate }
setTaxRate={ this.setTaxRate }
title="Enter here the tax-rate." />
</div>
</div>
<div className="row buttons">
<div className="button-group expanded">
<a className="button" onClick={ this.calculate }
disabled="disabled" ref="calculate"
title="Calculate the netto amount and included tax based upon the entered
total amount.">Calculate</a>
<a className="warning button" onClick={ this.reset }>Reset</a>
</div>
</div>
<div className="row">
<div className="labeled-input medium-12 large-6 columns">
<label for="included-tax">Included tax: </label>
<input type="text" id="included-tax" className="read-only"
ref="includedTax"
value={ this.state.includedTax } />
</div>
<div className="labeled-input medium-12 large-6 columns">
<label for="netto-amount">Netto amount: </label>
<input type="text" id="netto-amount" className="read-only"
ref="nettoAmount" value={ this.state.nettoAmount } />
</div>
</div>
</div>
);
}
});
ReactDOM.render(
<TaxCalculator />,
document.querySelector('#app')
);
$radius: 8px;
#app {
background-color: lighten(grey, 35%);
padding-top: 20px;
border-top: 1px solid black;
border-bottom: 1px solid black;
}
body {
background-color: lighten(grey, 25%);
}
.invalid-value {
border: 1px solid crimson;
background-color: lighten(pink, 7%);
}
.container {
margin-top: 50px;
}
label, .button {
font-weight: 800;
}
.buttons {
display: flex;
justify-content: center;
}
.button-group {
width: calc(100% - 30px);
margin-top: 20px;
margin-bottom: 25px;
}
.read-only {
pointer-events: none;
}
.callout {
margin: 0 15px 30px 15px;
}
.labeled-input input, .callout, .button, .labeled-input select {
border-radius: $radius;
}
a.button:first-of-type {
padding-right: 0;
}
a.button:nth-of-type(2) {
padding-left: 0;
}
.callout p {
font-family: georgia;
}
<div class="container">
<div id="app"></app>
</div>
A:
Well, the first thing I would do, to refactor this component, is creating a bunch of presentational components like:
const Row = ({taxRate, setTotalAmount, setTaxRate}) => (
<div className="row">
<div className="labeled-input medium-12 large-6 columns">
<label for="total-amount">Total amount: </label>
<input
type="text"
required pattern="[0-9]+"
ref="totalAmount" onChange={ setTotalAmount }
title="Enter here the total amount."
placeholder="Please enter the total amount as a number here ..." />
</div>
<div className="labeled-input medium-12 large-6 columns">
<label for="Tax-rate">Tax rate: </label>
<SelectInput
min="1" max="99"
preSelected={ taxRate }
setTaxRate={ setTaxRate }
title="Enter here the tax-rate." />
</div>
</div>
)
So, splitting it up will make them more reusable, and make your code look simpler.
This syntax is supported since React 0.14..
The next thing is, don't modify your refs like this:
this.refs.totalAmount.value = 0;
this.refs.totalAmount.removeAttribute('disabled');
this.refs.totalAmount.classList.remove('invalid-value');
this is an Anti-pattern in React, your are degrading React to jQuery. Remember the shit flows always in one direction, so use setState or better Redux to control your data flow, and props in your representational components..
So, no refs modification!!!, react on every data change, by using setState or redux-actions. Split your application in presentational components and container components.
|
Moving into an apartment can be thrilling, exhilarating, and slightly frightening particularly if you’re a first time renter. To celebrate the move, apartment warming celebrations thrown by family and friends are becoming more and more common. The following are several gift ideas that are great for people who rent apartments!
Gifts for Emergencies
Everyone should be prepared for emergencies. When coming up with gift ideas, a fireproof box along with a basket of emergency supplies is a good gift for practical people. The fireproof box will protect important paperwork and sentimental items in case of emergencies like fires, floods, and severe weather. And the basket of emergency supplies will come in handy in case of a power outage.
A wireless security alarm is also a pragmatic gift and, most importantly, offers some peace of mind. Some alarms activate when doors or windows are opened, others will turn lights off and on when the apartment is vacant. Prices vary from about $25 and up.
Other gift ideas for first time apartment tenants include gifts of convenience.
Who wouldn’t like to relax on the couch while the floors are cleaned by robot vacuums? These vacuums, like iRobot’s Roomba, clean at the push of a button and some can be scheduled to automatically run during certain hours of the day. There are various types to select from depending on what you’d like it to do and what kind of floor it’ll clean. The price depends on these factors and the model that you choose.
Whether they’d admit it or not, a lot of people love singing in the shower. That means sometimes getting lost in song and losing track of time. Mull over the idea of gifting a shower radio with a clock display. With this gift, your friend can listen to their favorite songs, sing along, and be on time for work.
So long as you put thought into it, a good present isn’t determined by the amount of money you spend. When considering first time renters, think of presents that will be useful and appreciated, and you’ll be sure to gift good presents at the next apartment warming party you attend. |
SYNTH ANATOMY uses affiliation & partner programs (big red buttons) to finance a part of the activity. If you use these, you support the website. Thanks!
Bastl Instruments Softpop is not a classic semi-modular analog Synthesizer. It works, reacts and sounds different from classic Synthesizers. Softpop takes you on an unpredictable journey full of experimentations, strange sounds and timbres.
I had the opportunity to borrow Softpop for a short time to make a sound demo. The results are interesting and not very familiar. Softpop can be considered as an organic Synth that creates a wide range of sounds from waterdrops, bizarre modulated to industrial inspired sounds. For experimental/noise musicians an excellent synth.
Overview
SoftPop is a playfully organic, semi-modular light and sound synthesizer with a wide variety of sounds: from random dripping water pops to heavy subtractive basslines. Its fully analog core consisting of a heavily feedbacked system of dual triangle-core oscillators, state variable filter and sample and hold is played through an intuitive interface of 6 faders that provide countless combinations which can be explored by anyone.
It can also process external audio thru the filter while using the envelope follower to intuitively synchronize to the incoming signal
Features
fully analog core and signal path
6 faders for controlling two VCOs and VCF and their cross modulations
two wide range triangle-core VCOs 0 & 1
quantizer for VCO 0 (auto-tuner)
VCO 1 has variable waveshape via the modulation setting
∞ resonant state variable VCF (bandpass, lowpass, highpass)
external input with gain and envelope follower for intuitive sync of VCO 1
track & hold circuit for stepped modulations
looping pattern generator with two patterns P1 and P2
RGB led for psychedelic experience
25-point patchbay
secret hack chamber at the back for adventurers
aluminum body enclosure
built-in speaker
additional wooden handle backplate
Bastl Instruments Softpop Synthesizer Sound Demo
More information here: Bastl Instruments
Available here: Bastl Instruments Softpop
Hardware Synthesizer News |
In Nigeria, Malala Calls For Release Of Kidnapped Schoolgirls
Malala Yousafzai, the well-known Pakistani activist, met with Nigerian President Goodluck Jonathan on Monday to discuss the plight of more than 200 kidnapped girls.
AP
Originally published on July 14, 2014 2:17 pm
Boko Haram, the extremist group that kidnapped hundreds of Nigerian schoolgirls last April, has released a new video mocking international calls for the girls' release.
The video was seen as a snub of Malala Yousafzai, the Pakistani activist who gained prominence after being shot in 2012 by the Pakistani Taliban for campaigning for girls' education. She met with Nigerian President Goodluck Jonathan on Monday to discuss the plight of the missing girls.
In the video, obtained by Agence France-Presse, militant leader Abubaker Shelam stands in front of tanks and masked, armed men and chants, "Bring back our army," ridiculing the social media slogan "bring back our girls."
Malala, who turned 17 on Saturday — her birthday is recognized annually by the United Nations as Malala Day — arrived in Nigeria over the weekend. She drew a direct parallel between her situation and that of the abducted girls in terms of violent resistance to the education of women.
"When I heard about the Nigerian girls, that they are being abducted, I felt that my sisters were in prison," Malala said. "This is my feeling, that if we remain silent, then this will spread, this will happen more and more and more."
As we reported last week, more than 60 women and girls who had been abducted by Nigerian extremist group Boko Haram escaped to freedom, after their captors left for a raid. More than 200 schoolgirls abducted from their school in the town of Chibok in April remain missing.
Malala met with five of the girls who escaped. They told her that they had not been debriefed by government investigators, according to the BBC.
That may increase pressure on Nigerian officials to step up their efforts. Jonathan promised Malala he would finally meet with some of the families of the missing girls.
"The great challenge in rescuing the Chibok girls is the need to ensure that they are rescued alive," Jonathan said in a statement.
"Western diplomats said that despite the huge international publicity that the social media campaign has generated, the efforts to find the hostages were little further on than they were back in May, when Britain, America and France began to help," the British Telegraphreported. "With neither a prisoner swap or a rescue considered likely, they said there was little real prospect of any 'breakthrough' in the case in the foreseeable future." |
In the last 24 hours, a computer simulation by a team of Belgian engineers that tracks the “spread droplets” and “slipstream” of the exhalations, coughs, and sneezes of people who are running, walking, or cycling has gone viral. Perhaps you have seen this gif on Twitter, Facebook, or NextDoor. Or, as some people on our staff have seen, perhaps write-ups of it have been texted to you by concerned friends or family:
Though this was not the specific goal of the simulation, it is currently being used on neighborhood groups and social media as scientific evidence that people who are jogging and biking are putting others at risk. If you are getting “droplets” or “globules” on you, the thinking goes, you are at risk of contracting coronavirus.
“People should read and not misread my tweets and texts,” Bert Blocken of Eindhoven University of Technology, the lead researcher on the simulation, wrote in an email to Motherboard. “I have never and nowhere discouraged people from walking, running, or cycling. Rather the opposite. Maybe people should read more, and react less.”
Blocken has yet to publish a peer-reviewed paper about the simulation. In fact, he hasn't even published a non-peer-reviewed study. Instead, he spoke to a reporter in Belgium about it, who wrote a news article, which has now been aggregated and shared widely by many publications. Given what Blocken has put into the world, taken at face value, some people are understandably concluding that it is impossible to run or cycle safely in many cities; he recommends a distance of 65 feet between bikers and other people, something that is impossible to do in cities. The issue with Blocken’s suggestion that we “read more, and react less” is that there is almost nothing to read, and there is no study to critique.
Blocken’s team took the extraordinary step of speaking to the media about his research before publishing anything about it. There is no written study to read or interpret. We do not know the specifics about how the study was done or how the simulation was run because the research team has not shared that information.
On Twitter, Blocken said the “crisis is urgent, so exceptionally we turned order upside down: (1) media, (2) today I submitted the proposal for funding (3) peer review article later. Public cannot wait months for peer review. I have a short text, I will post it on Linked In within the next hour.”
A day later, that LinkedIn post has not been published. What the team has published is something that it’s calling a “white paper,” but which is actually a Google-translated version of the Belgian newspaper article that was not written by Blocken or his team, but which quotes him. Ansys, the company that did the simulation in concert with Blocken, has also published a short but vague press release. In the meantime, this simulation has gone viral.
Studies like this are "not really useful. Not to epidemiologists anyway. The amount of transmission from this route even if it is possible will be dwarfed by that from others."
A Medium post written by Jurgen Thoelen, who describes himself as an “entrepreneur, building clouds in all forms and shapes and life-long athlete” has been shared thousands of times. On Facebook and Twitter, the article is being shared in neighborhood groups and is being used to spur a battle between pedestrians and runners and cyclists. A typical comment is something like this, shared in an Iowa City "Quarantine Survival" Facebook page: “Omg people keep doing this. Runners and bikers with zero regard for fellow pedestrians 🤬🤬” The simulation has also been written up by the Daily Mail, while gifs, stills, and memes of the simulation, shared with little or no context, have spread on their own.
This is all to say that we are unsure of the specifics of this study, what it actually shows, what its limitations might be, and how it was done. What it's suggesting could be accurate and useful, but we have no way of knowing that at the moment. And yet, this research is already being used to ask people to change their behavior and held up as definitive evidence that running and cycling are irresponsible during the pandemic.
Blocken said in an email that this was not his intention.
“Choice made in agreement with all the researchers involved and both university media agencies. The crisis is worldwide and the situation is urgent,” Blocken wrote. “We did not want to keep results behind closed doors until we have found the time to write down the full story. If I would have done the opposite, we would receive criticism about that. Never possible to do right for everybody. Given all the fuss I notice now, I will do an extra other late night effort and post the full story on Linked In tonight.”
“By the way this is aerodynamics work, not virology. Good luck with speeding up procedures in engineering journals," Blocken added. "COVID-19 will not wait months or until our paper is published."
Blocken is right: We face an urgent situation, and it’s important to get rigorous science out as quickly as possible. But hundreds of other scientists have managed to publish peer reviewed research about coronavirus in the last few weeks, on an expedited time scale. Thousands of others have published studies that are not peer reviewed, but that are at least studies in the way we usually think of them: Their methods and findings are explained in a rigorous way that can be critiqued. Even though this is a dire situation, scientific publishing safeguards exist for a reason, and we've already seen during this pandemic that a rushed process has led to bad, inaccurate science being published (that's not to suggest that Blocken's research is bad or inaccurate science, we simply have no way of knowing based on what's been published.)
Even if the simulations hold water and are accurate, virologists and experts should be the ones making public health recommendations, not random "entrepreneurs" on Medium, which is what has happened because these simulations were not published with the specifics of how they were done or what they mean. This type of research is of course important and should be done, but it should be released in a responsible way, with the caveats, limitations, and unknowns explained clearly. Then the research should be used by virologists and public health officials to make concrete recommendations to people.
I showed Blocken's research to William Hanage, an epidemiologist at Harvard's Center for Communicable Disease Dynamics. He said that the virality of Blocken's research is harmful, and that Blocken's suggestion in the white paper that this research is a "modest contribution" toward the fight against Covid-19 "makes my blood boil."
"Where the droplets are is much less relevant than the amount of transmission that occurs via this route"
Crucially, scientists are still unsure how well the coronavirus spreads in the air, and many have cautiously speculated that the overall risk of transmission appears to be less outdoors. Globules and droplets do likely carry the virus, but that doesn’t mean that anyone who gets a droplet on them from someone’s breath is going to be infected. Transmission depends on a host of factors; scientists believe an important one of these is “viral load,” which is a measure of how much of the virus is present.
"On the epidemiology side—where the droplets are is much less relevant than the amount of transmission that occurs via this route," Hanage said. "Advice on physical distancing is really about *reducing* the risk of transmission rather than eliminating it altogether."
He said studies like this are "not really useful. Not to epidemiologists anyway. The amount of transmission from this route even if it is possible will be dwarfed by that from others." He added "it's concerning" how fast the study has traveled … especially "when you consider I have had to write this email rather than putting the finishing touches to a model of nosocomial transmission [in hospitals]."
In a footnote on the white paper, Blocken admits “currently the subject of intensive debates between scientists world‐wide—is to what extent the residue of micro‐droplets with the virus, after evaporation, still carries an infection risk. Further virology research should shed more light on this issue.” Last week, the Atlantic's Ed Yong spoke to many virologists about this, and there currently is no consensus about how dangerous it is to exercise or be outside, but there is much research suggesting that the mental health benefits of exercising outdoors are important and should be taken seriously.
The issue of viral load and transmission is not addressed or mentioned in the Medium article nor in the Belgian newspaper Blocken spoke to.
When I asked if he was concerned about the fact his work had gone viral, especially in write-ups by non-experts, he said, “I am surprised by this question. You with your expertise should know that one can control the first line of media attention, and then people write stories of the stories, and it is impossible to control," Blocken wrote. "That would have happened equally if the full paper had already been published. This is not my first big media coverage, so I have been there, done that. There is free press."
Hanage said it's probably OK to exercise outside as long as you "apply common sense." |
Behold! I have sent you my speech, all streaming with sweat as I am! How should I be otherwise, when sending my speech to one who by his skill in oratory is able to shew that the wisdom of Plato and the ability of Demosthenes were belauded in vain? I feel like a gnat compared with an elephant. How I shiver and shake, as I reckon up the day when you will inspect my performance I am almost out of my wits! |
[A retrospective analysis of 5 cases of major burns treated by goat acellular dermal matrix combined with hyaluronic acid].
To evaluate the clinical efficacy of the goat acellular dermal matrix combined with hyaluronic acid (h-GADM) in the treatment of major burns. A retrospective analysis of 5 patients with major burns undergoing combines microskin and h-GADM grafting. All patients were male, aged 33 to 50 years, and mean burn area were 83% ± 11%, which III degree wounds 60% to 90%. After extensive burns patients admitted to hospital in accordance with conventional treatment processes included fluid resuscitation, airway management, wound management, infection control and other treatment. The patients received the surgery after the shock of spending and hemodynamically stable. Summarized the feasibility and operative techniques of the new method, and elaborated on details by a typical case as an example. All the 5 patients were survival, go through the shock period smoothly, not haven any serious complications as lung infection, wound sepsis, septicemia and kidney failure occurred. A total of nine mircoskin graft operations were undergoing and covered 17 limbs. The average time of the h-GADM desquamtion was (17.7 ± 2.7) days after operation, the hospitalization time was (115 ± 27) days. After (72 ± 6) days, the residual wound was less than 5% total body surface area. The h-GAMD can be a good alternative to cadaver skin in the treatment of major burns. |
FOR PUBLICATION
UNITED STATES COURT OF APPEALS
FOR THE NINTH CIRCUIT
PIT RIVER TRIBE; NATIVE No. 13-16961
COALITION FOR MEDICINE LAKE
HIGHLANDS DEFENSE; MOUNT D.C. No.
SHASTA BIOREGIONAL ECOLOGY 2:04-cv-00956-
CENTER; SAVE MEDICINE LAKE JAM-JFM
COALITION; MEDICINE LAKE
CITIZENS FOR QUALITY
ENVIRONMENT, OPINION
Plaintiffs-Appellants,
v.
BUREAU OF LAND MANAGEMENT;
U.S. DEPARTMENT OF THE INTERIOR;
UNITED STATES FOREST SERVICE;
UNITED STATES DEPARTMENT OF
AGRICULTURE; CALPINE
CORPORATION,
Defendants-Appellees.
Appeal from the United States District Court
for the Eastern District of California
John A. Mendez, District Judge, Presiding
Argued and Submitted
March 12, 2015—San Francisco, California
Filed July 20, 2015
2 PIT RIVER TRIBE V. BLM
Before: William A. Fletcher and Morgan Christen, Circuit
Judges, and Roslyn O. Silver,* Senior District Judge.
Opinion by Judge Christen
SUMMARY**
Environmental Law
The panel reversed the district court’s order granting
judgment on the pleadings in an action brought by
environmental organizations challenging the Bureau of Land
Management’s continuation of 26 geothermal leases in
northeastern California’s Medicine Lake Highlands.
The panel held that the district court incorrectly treated
the environmental organizations’ claims as arising under only
§ 1005(a) of the Geothermal Steam Act. BLM’s 1998
decision to continue the 26 unproven leases in the Glass
Mountain Unit under § 1005(a) was issued simultaneously
with its decision to reverse and vacate its earlier decision to
extend those leases on a lease-by-lease basis under § 1005(g).
The panel held, thus, that the environmental organizations’
challenge to BLM’s decisions issued on May 18, 1998
implicated both § 1005(a) and § 1005(g).
*
The Honorable Roslyn O. Silver, Senior District Judge for the United
States District Court for the District of Arizona, sitting by designation.
**
This summary constitutes no part of the opinion of the court. It has
been prepared by court staff for the convenience of the reader.
PIT RIVER TRIBE V. BLM 3
Because BLM must conduct environmental, historical,
and cultural review under the National Environmental Policy
Act and the National Historic Preservation Act before
granting lease extensions under § 1005(g), the panel held that
the environmental organizations’ claim fell within
§ 1005(g)’s zone-of-interests, and the organizations had
stated a claim under § 1005(g).
The panel declined the environmental organizations’
invitation to rule on the merits of its Geothermal Steam Act
claims, and remanded for further proceedings.
COUNSEL
Jason S. George (argued), Evan H. Stein (argued), Certified
Law Students, Palo Alto, California; Deborah Ann Sivas,
Matthew J. Sanders, and Alicia E. Thesing, Mills Legal
Clinic of Stanford Law School, Stanford, California, for
Plaintiffs-Appellants.
David Taylor Shelledy (argued), Assistant United States
Attorney, and Benjamin B. Wagner, United States Attorney,
Sacramento, California, for Defendants-Appellees Bureau of
Land Management, United States Department of the Interior,
United States Forest Service, and United States Department
of Agriculture.
Rosemary Antonopoulos, Dublin, California; Thomas L.
Sansonetti, Holland & Hart LLP, Cheyenne, Wyoming, for
Defendant-Appellee Calpine Corporation.
4 PIT RIVER TRIBE V. BLM
OPINION
CHRISTEN, Circuit Judge:
The Pit River Tribe and several regional environmental
organizations (collectively Pit River) appeal from the district
court’s order granting judgment on the pleadings on Pit
River’s action challenging the Bureau of Land Management’s
(BLM) continuation of 26 geothermal leases in northeastern
California’s Medicine Lake Highlands. Pit River’s complaint
alleged that BLM’s decision violated the Geothermal Steam
Act, the National Environmental Policy Act (NEPA), the
National Historic Preservation Act (NHPA), and the
government’s fiduciary trust obligation to Indian tribes. The
district court concluded Pit River lacked prudential standing
to bring its Geothermal Steam Act claims because the claims
did not fall within the zone of interests of the Act’s
lease-continuation provision, 30 U.S.C. § 1005(a).1 The
district court rejected Pit River’s other claims on the basis
that BLM had no discretion to consider environmental,
historical, or cultural interests before continuing the leases
under §1005(a).
We conclude that the district court incorrectly treated Pit
River’s claims as arising under only § 1005(a) of the
Geothermal Steam Act. BLM’s 1998 decision to continue the
26 unproven leases in the Glass Mountain unit under
§ 1005(a) was issued simultaneously with its decision to
1
In light of the Supreme Court’s recent case, Lexmark International,
Inc. v. Static Control Components, Inc., the zone-of-interests inquiry may
no longer be considered an element of “prudential standing,” but the
substance of the test remains unchanged for the purposes of this case.
134 S. Ct. 1377, 1387–88 (2014).
PIT RIVER TRIBE V. BLM 5
reverse and vacate its earlier decision to extend those leases
on a lease-by-lease basis under § 1005(g). Thus, Pit River’s
challenge to the decisions issued on May 18, 1998 implicates
both § 1005(a) and § 1005(g). Because BLM must conduct
environmental, historical, and cultural review under NEPA
and NHPA before granting lease extensions under § 1005(g),
Pit River Tribe v. U.S. Forest Serv., 469 F.3d 768, 780–84,
787–88 (9th Cir. 2006) (“Pit River I”), Pit River’s claim falls
within § 1005(g)’s zone of interests and Pit River has stated
a claim under § 1005(g). Accordingly, we reverse the district
court’s decision.
BACKGROUND
I. The Plaintiffs’ Interests
The Medicine Lake Highlands are part of the Pit River
Tribe’s ancestral homeland. Tribal members “consider the
region sacred and continue to use numerous important
spiritual and cultural sites within the highlands.” Pit River I,
469 F.3d at 772. The complaint alleges that exploration of
and development on geothermal leases will interfere with
tribal members’ use of the Medicine Lake Highlands “for a
variety of spiritual and traditional cultural purposes” that
“depend on the physical, environmental, and visual integrity
of these areas, and their quietude.” The complaint alleges
that the non-tribal plaintiffs have environmental, recreational,
aesthetic, and scientific interests in the Medicine Lake
Highlands that are inconsistent with geothermal development.
II. The Geothermal Steam Act
When interest in geothermal power development first
began to grow in the 1960s, the United States Department of
6 PIT RIVER TRIBE V. BLM
the Interior determined that it lacked statutory authority to
dispose of geothermal resources on federal land. Robert B.
Keiter, The Old Faithful Protection Act: Congress, National
Park Ecosystems, and Private Property Rights, 14 Pub. Land
L. Rev. 5, 9 (1993). Congress recognized the necessity of
creating a legal framework governing the development of
geothermal resources on federal land, see Wagner v. Chevron
Oil Co., 321 F. Supp. 2d 1195, 1198 (D. Nev. 2004), and in
1970 it enacted the Geothermal Steam Act for the express
purpose of “promot[ing] the development of geothermal
leases on federal lands.”2 Geo-Energy Partners-1983 Ltd. v.
Salazar, 613 F.3d 946, 949 (9th Cir. 2010) (citing 30 U.S.C.
§ 1001, et seq; Wagner, 321 F. Supp. 2d at 1198).
The Geothermal Steam Act authorizes “the Secretary of
the Interior to ‘issue leases for the development and
utilization of geothermal steam’ on federal land and in
national forests.” Pit River I, 469 F.3d at 772–73 (quoting
30 U.S.C. § 1002). Geothermal leases on federal land have
a primary term of ten years. 30 U.S.C. § 1005(a) (1998). At
the end of that term, the Secretary must grant a continuation
of the lease for a term up to 40 additional years if
“geothermal steam is produced or utilized in commercial
quantities.” Id. Section 1005(d) defines “produced or
utilized in commercial quantities” to include “the completion
of a well capable of producing geothermal steam in
commercial quantities so long as the Secretary determines
2
Congress amended the Geothermal Steam Act in 1998 and 2005.
Except where otherwise noted, we refer to the statute and regulations in
effect when the challenged lease continuations were approved in May
1998. See Pit River I, 469 F.3d at 781 (holding that amendments to lease
continuation and extension provisions of the Geothermal Steam Act
should not be applied retroactively). Both parties acknowledge that this
version of the statute and regulations apply in this case.
PIT RIVER TRIBE V. BLM 7
that diligent efforts are being made toward the utilization of
the geothermal steam.” Where geothermal steam has not
been produced or utilized in commercial quantities by the end
of the initial, ten-year lease term, the Secretary may extend
the lease for successive five-year terms if certain conditions
are met. Id. § 1005(g). Under § 1005(g)’s five-year
extension provision, BLM must conduct a review pursuant to
NEPA and NHPA considering the cultural, historical, and
environmental effects of its leasing decision before making
its lease-extension determination. Pit River I, 469 F.3d at
781, 784–89.
The Geothermal Steam Act also authorizes the Secretary
to approve “cooperative or unit plan[s]” under which multiple
leases are managed as a unit. 30 U.S.C. § 1017 (1998); 43
C.F.R. § 3280.0-2 (1997). The purpose of cooperative or unit
plans is to “conserv[e] natural resources,” 43 C.F.R.
§ 3280.0-2 (1997), and “provide for more efficient
development and production of geothermal resources.”
Geo-Energy Partners-1983, 613 F.3d at 949. The Secretary
has relatively broad discretion to set the terms of a unit plan
and to regulate the leases within the plan. 30 U.S.C. § 1017
(1998). The Secretary must review unit plans every five
years “and, after notice and opportunity for comment,
eliminate from inclusion in such plan any lease or part of a
lease not regarded as reasonably necessary to cooperative or
unit operations under the plan.” Id.
III. The Glass Mountain Leases
The Department of the Interior issued a programmatic
environmental impact statement (EIS) in 1973 addressing
nationwide implementation of the Geothermal Steam Act. Pit
River I, 469 F.3d at 773. With several exceptions not relevant
8 PIT RIVER TRIBE V. BLM
here, the EIS did not address geothermal development in
particular locations. Rather, the EIS suggested that issuing
individual leases may require subsequent, more particularized
EISs. Id. In 1981, BLM and the Forest Service issued an
Environmental Assessment (EA) evaluating “whether to
allow geothermal leasing and casual use exploration on
approximately 266,800 acres of National Forest land in the
Medicine Lake Planning Unit, and an adjacent 26,750 acres.”
Id. After completion of this EA, the Forest Service issued a
Finding of No Significant Impact for potential geothermal
leasing in the Medicine Lake Planning Unit of the Modoc,
Klamath, and Shasta-Trinity National Forests.
In 1982, BLM entered into a “Unit Agreement for the
Development and Operation of the Glass Mountain Area,”
which eventually included the 26 unproven leases at issue in
this appeal. The Unit Agreement included exhaustive rules
governing the management of leases within the unit. Among
many other provisions, the Unit Agreement required the unit
operator to submit a plan of operation establishing deadlines
for progress in exploration and ensuring “proper protection of
the environment and conservation of the natural resources of
the Unit Area.” Article 17.4 of the Unit Agreement provided
that “[d]rilling and/or producing operations performed . . .
upon any tract of Unitized Lands will be accepted and
deemed to be performed upon and for the benefit of each and
every tract of Unitized Land.”
BLM and the Forest Service issued a supplemental EA in
1984, this time addressing “the exploration, development and
production phases of the geothermal program.” Id. at 774.
This document recognized the cultural and historical
importance of the Medicine Lake area to modern Native
American groups. Id. at 774–75. Following completion of
PIT RIVER TRIBE V. BLM 9
the 1984 EA, BLM issued the “Glass Mountain Geothermal
Decision Record,” authorizing leasing on an additional
41,500 acres within the Medicine Lake Highlands.
Between 1982 and 1988, BLM granted the 26 leases that
are the subject of this appeal. In 1989, BLM determined that
a different lease within the Glass Mountain Unit was capable
of producing geothermal steam in commercial quantities (the
“paying-well determination”). In November 1990, one of
Calpine Corporation’s predecessors3 requested five-year
extensions for 23 leases it owned within the Glass Mountain
Unit pursuant to 43 C.F.R. § 3203.1-4(c).4
In the course of processing this lease-extension
application, BLM’s California State Office communicated
with the Nevada State Office, which advised that 40-year
lease continuations should be granted to all of the unproven
Glass Mountain leases pursuant to Article 17.4 of the Unit
Agreement. The California Office disagreed, concluding that
under § 1005 and its implementing regulations, “the 40 year
extension [under § 1005(a)] may only be applied to the lease
with the well capable of production and not to the other
committed leases in the unit.” The California Office reasoned
that the statute and its “implementing regulations refer
specifically to individual leases . . . , not leases within a
3
At various times relevant to this discussion, other entities owned some
or all of the leases at issue here. Calpine was preceded as the Glass
Mountain Unit operator by Union Oil Company and California Energy
General Corporation. To avoid confusion, and because it does not affect
our analysis, we refer to all unit operators and lease owners as “Calpine”
or “Calpine’s predecessor” throughout this opinion.
4
43 C.F.R. § 3203.1-4(c) implements the lease-extension requirements
of 30 U.S.C. § 1005(g)(1).
10 PIT RIVER TRIBE V. BLM
‘cooperative plan, communitization agreement, or a unit plan
of development or operation’ as provided for lease extensions
under 43 CFR 3203.1-4(b).” See 43 C.F.R. §§ 3203.1-3,
3203.1-4 (1997). The California Office requested an opinion
from the Department of Interior Solicitor General to resolve
this difference of interpretation, but it appears that such
opinion was never issued.
In July 1991, under § 1005(a), BLM continued for up to
40 additional years the one lease in the Glass Mountain Unit
on which the paying-well determination had been made.
Under § 1005(g), it also continued for five years the 22 other
leases in the Glass Mountain Unit owned by Calpine’s
predecessor. In September 1991, Calpine requested five-year
extensions for two other leases it held within the Glass
Mountain Unit.5 In October 1991, Calpine’s predecessor
requested that BLM rescind the five-year lease extensions
granted in July of that year and instead grant 40-year lease
continuations to all of the unproven leases within the Glass
Mountain Unit pursuant to Article 17.4 of the lease
agreement. BLM granted extensions for Calpine’s two leases
in March 1992, but declined to grant Calpine’s predecessor’s
request for 40-year lease continuations.
In 1995, BLM found Calpine’s predecessor “in default of
meeting reasonable diligence in the unit,” but approved the
1994/1995 plan of operation on the condition that the unit
operator “will drill at least one well on a federal lease within
and committed to the Glass Mountain Unit” before May 17,
5
No party requested extension of two additional Glass Mountain Leases,
CACA 21929 and 21933 in 1991. Presumably this is because BLM issued
these leases in 1988, so their primary terms were not scheduled to end
until 1998.
PIT RIVER TRIBE V. BLM 11
1996. BLM later rescinded the requirement to drill a well,
but noted that the unit operator should have submitted a
Participating Area designation based on the 1989 paying-well
determination by February 13, 1994. Though that date had
passed, BLM gave the unit operator 60 days to submit a
participating area designation.6
In November 1996, Calpine’s predecessor again requested
that BLM rescind its lease extensions and retroactively grant
40-year continuations of the unproven Glass Mountain leases
pursuant to Article 17.4 of the Unit Agreement. In two
decision letters, BLM reversed course and granted this
request on May 18, 1998. One letter vacated the 24, five-year
lease extensions granted in 1991 and 1992:
On July 18, 1991, and March 20, 1992, based
upon lessee’s requests, this office issued
decisions granting five year extensions under
43 CFR 3203.1-4(c) to 25 geothermal leases.7
This decision applies to the 24 leases which
are currently committed to the Glass
Mountain Unit . . . . However, the Glass
Mountain Unit contains a well capable of
production, and it has been determined
through a careful review and interpretation of
the regulations that the decision to grant 24 of
the 25 extensions was in error.
6
The record does not indicate whether a participating area designation
was ever submitted.
7
The 25th lease extension applied to lease CACA 11707, which is not
a part of the Glass Mountain Unit and not part of this appeal.
12 PIT RIVER TRIBE V. BLM
The other letter granted 40-year continuations to the 268
unproven Glass Mountain leases:
This decision affects 26 of the 27 geothermal
leases currently committed to the Glass
Mountain Unit and Unit Agreement . . . . One
lease committed to the Unit, CACA 12372,
has been determined to be capable of
production, as the result of a paying well
determination, effective February 13, 1989,
and was granted an additional term under 43
[C.F.R. §] 3203.1-3.9
Based upon the paying well determination and
the subsequent granting of an additional term
to lease CACA 12372 under 43 [C.F.R. §]
3203.1-3, all leases committed to the Glass
Mountain Unit at that time should also have
been granted additional terms as a result of
Article 17.4 of the Glass Mountain Unit
Agreement, which states:
“Drilling and/or producing
operations performed hereunder upon
any tract of Unitized Lands will be
accepted and deemed to be performed
upon and for the benefit of each and
every tract of Unitized Land.”
8
This number includes the two unproven leases that were not extended
in 1991 or 1992.
9
43 C.F.R. § 3203.1-3 implements the lease-continuation requirements
of 30 U.S.C. § 1005(a) and (d).
PIT RIVER TRIBE V. BLM 13
Therefore, based on the above, it is the Bureau
of Land Management’s determination that the
26 leases which are committed to the Glass
Mountain Unit be granted an additional term
[up to 40 years], effective February 13, 1989.
(Emphasis in original.). BLM did not explain its legal
rationale for this changed statutory interpretation in either of
the letters issued May 18, 1998. An internal BLM memo
recommending the change reflected the agency’s uncertainty
regarding whether the Geothermal Steam Act and its
implementing regulations required lease continuation and
extension determinations to be made on a lease-by-lease
basis, and noted that there was disagreement between the
California and Nevada offices on this point, but it does not
explain the rationale for adopting the view advanced by the
Nevada office.
IV. Procedural History
A. Pit River I
In 2002, some of the plaintiffs here, including the Pit
River Tribe, filed suit challenging a separate decision made
by BLM in 1998 granting five-year extensions under
§ 1005(g) to two leases in a different unit not at issue here.
Pit River I, 479 F.3d at 777–78. The plaintiffs alleged that
granting these extensions without conducting environmental
review violated NEPA, NHPA, the Geothermal Steam Act,
the National Forest Management Act, and the federal
government’s trust obligations to the Pit River Tribe. Pit
River Tribe v. BLM, 306 F. Supp. 2d 929, 934 (E.D. Cal.
2004). The district court entered summary judgment in favor
of BLM on all claims. Pit River I, 479 F.3d at 778.
14 PIT RIVER TRIBE V. BLM
On appeal, a panel of our court first considered whether
Pit River had Article III standing to bring its claims. Id. at
778–80. BLM argued that Pit River suffered no injury in fact
and that its claims regarding the 1998 lease extensions were
not redressable because the 1998 lease extensions were
supplanted by new extensions in 2002. Id. at 779. We
rejected these arguments, holding that Pit River adequately
demonstrated injury in fact and redressability.10 Id. at
779–80. The panel then considered whether, under the 1998
version of the Geothermal Steam Act, BLM was required to
conduct review under NEPA and NHPA before granting lease
extensions under § 1005(g). Id. at 780–88. Pit River I
observed that the 1998 version of § 1005(g) provided that
geothermal leases “may be extended for successive 5-year
periods,” and concluded that the use of “may” rather than
“shall” gave BLM discretion whether to grant lease
extensions. Id. at 780 (quoting 30 U.S.C. § 1005(g)(1)
(1998)). Pit River I held that, because the decision to grant
the extensions under § 1005(g) was discretionary, and
because earlier programmatic and general leasing EISs did
not adequately consider the effects of geothermal
development on specific leases, “[t]he agencies violated their
duties under NEPA and NHPA and their fiduciary duty to the
Pit River Tribe by failing to complete an environmental
impact statement before extending Calpine’s leases in 1998.”
Id. at 788.
On remand, the parties disputed whether the leasing
process would need to begin anew, thereby necessitating a
new competitive bidding process. Pit River Tribe v. U.S.
Forest Serv., 615 F.3d 1069, 1074 (9th Cir. 2010). The
district court concluded that the lease extensions should not
10
The court did not address prudential standing. See id. at 778–80.
PIT RIVER TRIBE V. BLM 15
be vacated, but remanded the case to the agencies to conduct
proper NEPA and NHPA review, and to permit tribal
consultation. Id. Pit River appealed, but we upheld the
district court’s order.11 Id. at 1085.
B. Pit River II
In 2004, while Pit River I was pending, the plaintiffs here
filed two separate complaints challenging BLM’s May 18,
1998 decisions to vacate its earlier-granted lease extensions
for the 26 unproven Glass Mountain leases and to grant lease
continuations instead. Pit River Tribe v. BLM, Case No. 04-
0956 (E.D. Cal., filed May 17, 2004) and Save Medicine Lake
Coal. v. BLM, No. 04-0969 (E.D. Cal., filed May 18, 2004).
Adjudication of these cases was delayed pending the
resolution of Pit River I and while the parties engaged in
settlement negotiations. In 2012, the district court
consolidated Pit River Tribe and Save Medicine Lake, and the
plaintiffs agreed to file an amended complaint. Pit River
stipulated that it would “only assert causes of action related
to the May 18, 1998 lease extensions and to Federal
Defendants’ alleged failure to provide public records in
response to Plaintiffs’ Freedom of Information Act request.”
Pit River’s amended complaint alleged that BLM’s 1998
decision to continue the leases violated the Geothermal Steam
Act, NEPA, NHPA, and the agency’s fiduciary trust
obligation to Indian tribes. Pit River’s Geothermal Steam Act
claims, which are set out in Paragraph 107 of the amended
complaint, specifically alleged:
11
We reversed in part only to correct two minor errors in the district
court’s order. Id. at 1085.
16 PIT RIVER TRIBE V. BLM
Federal Defendants BLM and Department of
the Interior violated the Geothermal Steam
Act, 30 U.S.C. § 1001 et seq., and its
implementing regulations in that they:
a. Unlawfully failed to terminate or eliminate
the Leases from the Glass Mountain Unit
Agreement when the Unit Operator failed to
comply with the reasonable diligence
requirements of the approved Plan of
Operation in 1995, and this violation is
ongoing and continues to this day;
b. Unlawfully failed to contract the Glass
Mountain Unit Agreement to include only
Lease CA12372 when the Unit Operator
failed to submit a schedule for establishing the
Participating Area for Well No. 31-17, as
required by the Unit Agreement, by the fifth
anniversary of BLM’s determination that such
well was capable of commercial production,
and this violation is ongoing and continues to
this day;
c. Unlawfully failed to terminate the 26
Leases identified in paragraph 1 hereof for
failure to comply with the “due diligence” and
“bona fide efforts” requirements of the GSA,
and this violation is ongoing and continues to
this day;
d. Unlawfully and retroactively continued the
26 Leases identified in paragraph 1 hereof for
an additional period of 40 years in May 1998
PIT RIVER TRIBE V. BLM 17
in the absence of any commercial production,
as defined by the GSA, on those Leases
during the primary lease term; and
e. Unlawfully failed to ensure that activities
and operations authorized by the 1998 Lease
Continuation Decision for the Leases
identified in paragraph 1 would protect the
quality of natural, cultural, and scenic
resources; accommodate other land uses;
protect people and wildlife from unacceptable
noise levels; and prevent undue degradation of
the land.
The amended complaint also alleged that BIA violated the
Freedom of Information Act (FOIA). Defendant Calpine
moved for summary judgment on Pit River’s FOIA claims
and for judgment on the pleadings under Federal Rule of
Civil Procedure 12(c) on all other claims.
The district court granted summary judgment on Pit
River’s FOIA claims,12 and entered judgment on the
pleadings on the remaining claims. The court concluded that
Pit River waived all of the claims alleged in Paragraph 107 of
the complaint except for the claim in subparagraph (d) that
BLM unlawfully continued the 26 unproven leases in May
1998. The court then concluded Pit River lacked prudential
standing to bring its Paragraph 107(d) claim because Pit
River did not fall within the “zone of interests” of the
Geothermal Steam Act’s lease-continuation provision,
§ 1005(a). The court dismissed Pit River’s NEPA, NHPA,
and fiduciary duty claims on the basis that BLM lacked
12
Pit River does not appeal the dismissal of the FOIA claims.
18 PIT RIVER TRIBE V. BLM
discretion to consider environmental, cultural, or historic
factors, or to consult with Indian tribes in considering
whether to grant lease-continuations under § 1005(a). A
pivotal conclusion in the district court’s ruling was its
decision that Pit River’s challenge to BLM’s 1998 decision
rested on only the lease-continuation provision, § 1005(a).
STANDARD OF REVIEW
This court reviews a motion for judgment on the
pleadings under Rule 12(c) de novo. Goldstein v. City of
Long Beach, 715 F.3d 750, 753 (9th Cir. 2013). “Analysis
under Rule 12(c) is ‘substantially identical’ to analysis under
Rule 12(b)(6) because, under both rules, a court must
determine whether the facts alleged in the complaint, taken as
true, entitle the plaintiff to a legal remedy.” Chavez v. United
States, 683 F.3d 1102, 1108 (9th Cir. 2012) (citations and
internal quotation marks omitted).
DISCUSSION
I. Pit River’s Geothermal Steam Act Claims
Because the Geothermal Steam Act does not expressly
provide for a private right of action, Pit River relied on the
Administrative Procedure Act (APA) to bring its challenge to
BLM’s 1998 decisions to vacate its lease extension decisions
and continue the 26 unproven Glass Mountain leases as a
unit. Under § 10(a) of the APA “[a] person suffering legal
wrong because of agency action, or adversely affected or
aggrieved by agency action within the meaning of a relevant
statute, is entitled to judicial review thereof.” 5 U.S.C. § 702.
BLM does not dispute that Pit River has Article III standing
PIT RIVER TRIBE V. BLM 19
to bring its claims.13 In addition to Article III standing, in
order to bring a cause of action under § 10(a), the interests a
plaintiff asserts “must be ‘arguably within the zone of
interests to be protected or regulated by the statute.’” Match-
E-Be-Nash-She-Wish Band of Pottawatomi Indians v.
Patchak, 132 S. Ct. 2199, 2210 (2012) (quoting Ass’n of Data
Processing Serv. Orgs., Inc. v. Camp, 397 U.S. 150, 153
(1970)). The district court reasoned that because “[t]he
statute and regulations applicable here . . . do not permit,
much less require, consideration of environmental concerns
or competing land uses when BLM acts on continuation of an
existing lease,” Pit River’s interests do not fall within the
statutory lease-continuation provision’s “zone of interests.”
A. The “zone of interests” test
The Supreme Court first articulated the zone-of-interests
test in 1970 in Data Processing. 397 U.S. at 153. The Court
stated that standing “concerns, apart from the ‘case’ or
‘controversy’ test, the question whether the interest sought to
be protected by the complainant is arguably within the zone
of interests to be protected or regulated by the statute or
constitutional guarantee in question.” Id. In 1987, the
Supreme Court explained in Clarke v. Securities Industry
Association, that:
13
Pit River I establishes that the requirements of Article III standing are
met here: Pit River suffered an injury in fact that is fairly traceable to
BLM’s conduct and that would likely be redressed by a favorable
decision. See 469 F.3d at 778–80 (holding that Pit River had standing to
challenge BLM’s extension of geothermal leases in Medicine Lake
Highlands).
20 PIT RIVER TRIBE V. BLM
The ‘zone of interest’ test is a guide for
deciding whether, in view of Congress’
evident intent to make agency action
presumptively reviewable, a particular
plaintiff should be heard to complain of a
particular agency decision. In cases where the
plaintiff is not itself the subject of the
contested regulatory action, the test denies a
right of review if the plaintiff’s interests are
so marginally related to or inconsistent with
the purposes implicit in the statute that it
cannot reasonably be assumed that Congress
intended to permit the suit. The test is not
meant to be especially demanding; in
particular, there need be no indication of
congressional purpose to benefit the would-be
plaintiff.
479 U.S. 388, 399–400 (1987) (footnotes omitted). The
zone-of-interests test should be applied consistent with
Congress’s intent “to make agency action presumptively
reviewable” under the APA. Match-E-Be-Nash-She-Wish,
132 S. Ct. at 2210 (quoting Clarke, 479 U.S. at 399).
The Supreme Court has often characterized the zone-of-
interests test as a “prudential standing” requirement. See,
e.g., Fed. Election Comm’n v. Atkins, 524 U.S. 11, 20 (1998);
Bennett v. Spear, 520 U.S. 154, 163 (1997). But last year, in
Lexmark International, Inc. v. Static Control Components,
Inc., the court rejected the “prudential standing” label and
made clear that whether a plaintiff’s claims are within a
statute’s zone of interests is not a jurisdictional question.
134 S. Ct. 1377, 1387–88 (2014); see also Chaudhry v. City
of L.A., 751 F.3d 1096, 1109 (9th Cir. 2014) (“[U]nlike
PIT RIVER TRIBE V. BLM 21
standing, ‘the absence of a valid . . . cause of action does not
implicate subject-matter jurisdiction.’” (quoting Lexmark,
134 S. Ct. at 1387 n.4)). The Court explained:
Although we admittedly have placed [the
zone-of-interests] test under the “prudential”
rubric in the past, it does not belong there . . . .
Whether a plaintiff comes within “the zone of
interests” is an issue that requires us to
determine, using traditional tools of statutory
interpretation, whether a legislatively
conferred cause of action encompasses a
particular plaintiff’s claim. As Judge
Silberman of the D.C. Circuit recently
observed “prudential standing is a misnomer”
as applied to the zone-of-interests analysis,
which asks whether “this particular class of
persons ha[s] a right to sue under this
substantive statute.”
Id. at 1387 (citations omitted) (quoting Ass’n of Battery
Recyclers, Inc. v. EPA, 716 F.3d 667, 675–76 (D.C. Cir.
2013) (Silberman, J., concurring)).
Because Lexmark addressed a claim arising under the
Lanham Act rather than under § 10 of the APA, the Supreme
Court did not directly revisit its APA zone-of-interests
precedent. Id. at 1383. But in discussing the Court’s prior
APA decisions, Lexmark reaffirmed its consistent statement
“that the [zone-of-interests] test ‘forecloses suit only when a
plaintiff’s interests are so marginally related to or inconsistent
with the purposes implicit in the statute that it cannot
reasonably be assumed’ that Congress authorized that
22 PIT RIVER TRIBE V. BLM
plaintiff to sue.” Id. at 1389 (quoting Match-E-Be-Nash-She-
Wish, 132 S. Ct. at 2210).
B. Pit River’s claims fall within the applicable zone of
interests.
The pivotal question here is whether Congress intended
to create a cause of action encompassing Pit River’s claims
when it enacted the Geothermal Steam Act. See id. at 1387.
The parties dispute whether the court may look to the
Geothermal Steam Act’s overall statutory scheme to
determine whether Pit River’s claims fall within the Act’s
zone of interests, but Bennett v. Spear clearly answered this
question. Bennett held, “[w]hether a plaintiff’s interest is
‘arguably . . . protected . . . by the statute’ within the meaning
of the zone-of-interests test is to be determined not by
reference to the overall purpose of the Act in question . . . ,
but by reference to the particular provision of law upon which
the plaintiff relies.” 520 U.S. at 175–76 (first two alterations
in original) (quoting Ass’n of Data Processing Serv. Orgs.,
Inc. v. Camp, 397 U.S. 150, 153 (1970)). We agree with the
district court that, contrary to Pit River’s argument, Pit
River’s ability to challenge the subject leases cannot be
determined by looking to the broad objectives of the
Geothermal Steam Act. But we do not agree that Pit River’s
claims can be fairly described as arising only from § 1005(a).
In 2012, when Pit River’s two cases were consolidated
into one, Pit River stipulated that it would “only assert causes
of action related to the May 18, 1998 lease extensions” in its
amended complaint. At the hearing on BLM’s and Calpine’s
motions for judgment on the pleadings, Pit River explained
that the amended complaint’s allegations regarding inclusion
of the unproven leases within the Glass Mountain Unit were
PIT RIVER TRIBE V. BLM 23
pleaded only as facts, not as distinct legal challenges. The
district court interpreted this explanation as meaning that Pit
River waived all of its Geothermal Steam Act claims except
those in Paragraph 107(d) of the amended complaint, which
alleged BLM “[u]nlawfully and retroactively continued the
26 Leases . . . for an additional period of 40 years in May
1998 in the absence of any commercial production.” The
district court concluded that Pit River’s remaining
Geothermal Steam Act claim relied on only the Act’s lease-
continuation provision, § 1005(a). But neither the stipulation
nor the amended complaint expressly limited Pit River’s
claims to any particular provision of the Geothermal Steam
Act, and Pit River never limited its claims only to § 1005(a).
The transcript from the hearing on the motion for judgment
on the pleadings makes this clear.
First, the district court inquired about the nature of the
claims in Pit River’s amended complaint. Pit River’s counsel
stated that Pit River was not merely challenging BLM’s lease
continuation decision under § 1005(a), but was also
challenging BLM’s decision to reverse course and decide that
the leases could be continued under § 1005(a) as a unit rather
than being subject to lease-by-lease extensions under
§ 1005(g). As counsel explained:
Our view is twofold. One is a legal issue and
one is a factual issue. First of all, on the legal
issue, . . . BLM had taken the position the
leases were not under this mandatory
extension but under a discretionary extension
and then changed [its] mind[].
. . .
24 PIT RIVER TRIBE V. BLM
[A]t the time the decisions were made, there
was a provision, 1005(g), that allowed for
these five-year extensions, and that’s, in fact
what the BLM believed it was originally
extending these leases under. . . .
. . .
So the first question is whether they were
properly under 1005(a) or 1005(g) as it
existed at the time . . . . [W]e believe that
decision whether to renew under § 1005(a) or
1005(g) is a challengeable decision. But even
if we were under Section 1005(a), . . . the
agency has to find that geothermal steam is
produced or utilized in commercial quantities.
(Emphasis added.).
The district court acknowledged this argument, asking
BLM’s counsel: “Why don’t the plaintiffs have a right to
challenge that determination? That’s the legal question she
says exists now. I grant your motion if 1005(a) applies. If
1005(g) applies, that presents different issues and problems
for you.” After BLM responded that it was “precisely the
application of 1005(a) that the plaintiffs challenge here,” the
district court pressed further:
How do they challenge then the decision of
BLM then to . . . , as [Pit River’s counsel]
argues, at one point BLM is proceeding under
1005(g) and then a second opinion comes out
and says: No, no. 1005(a) applies. Why don’t
they have a right to challenge that decision?
PIT RIVER TRIBE V. BLM 25
If they disagree, someone should have a right
to challenge it, shouldn’t they?
BLM’s counsel’s answer was not especially responsive:
Not necessarily. It is not necessarily the case
that any party has standing to challenge a
particular administrative action. That is the
Doctrine of Standing. Because they lack
standing, the question: How do they challenge
it just doesn’t arise. They don’t. They cannot
challenge a decision under that provision of
the statute.
The district court concluded that Pit River had actually
abandoned its challenge to BLM’s decision to apply
§ 1005(a) rather than §1005(g). The court said to Pit River’s
counsel:
You’re arguing to me, again, the evidence is
going to show that they didn’t qualify, that the
secretary or the solicitor or whoever makes
the decision, that the leases should be
extended got it completely wrong. Again, as
I understand the government’s response to
that is: Too late. It doesn’t matter. You’ve
abandoned those claims. You should have
challenged those, that decision earlier. Again,
it comes back to me—there’s two decisions
here: Were those conditions actually met?
Second, do we have to grant the lease
extensions? This lawsuit is only about: Were
the lease extensions legal? And so, again, I’m
having a hard time getting past how we started
26 PIT RIVER TRIBE V. BLM
this argument, which is, none of that is
relevant.
But Pit River did not concede that it had abandoned its
challenge to BLM’s May 18, 1998 change of course; instead,
it made clear, as it stated in the district court hearing, that it
thought “the court needs to look at what was done here in
order to determine whether the BLM’s last-minute reversal to
make this a ministerial, rather than a discretionary decision,
was proper under the law.” Additionally, contrary to the
district court’s suggestion, Pit River could not have
challenged the decision earlier because it appears that BLM
first communicated its changed interpretation of § 1005 and
the implementing regulations when it issued the 1998 letter
retroactively continuing the unproven Glass Mountain leases.
Pit River’s challenge plainly included whether BLM
lawfully vacated its earlier § 1005(g) extension decisions and
changed its interpretation of § 1005 to continue the leases for
up to 40 years. Because Pit River’s operative complaint
challenges BLM’s announcement that the leases were subject
to continuation rather than extension, we conclude that Pit
River’s claims include a challenge under § 1005(g). Pit River
I held that BLM must conduct NEPA and NHPA review
before granting discretionary extensions under the 1998
version of §1005(g).14 469 F.3d at 788.
14
Amendments to the Geothermal Steam Act in 2005 eliminated BLM’s
discretion to consider environmental and cultural factors in making lease-
extension decisions under § 1005(g). Pit River I, 469 F.3d at 780. Thus,
if Calpine elected to have its leases subject to the updated regulations, see
43 C.F.R. § 3200.7 (2007), future extensions of these leases may not be
subject to NEPA or NHPA review. Id.
PIT RIVER TRIBE V. BLM 27
II. The merits of Pit River’s Geothermal Steam Act
claims
Pit River argues it is entitled to judgment on the merits of
its Geothermal Steam Act claims, in particular its claim that
BLM improperly continued other leases within the Glass
Mountain Unit rather than addressing the leases within the
Unit one-by-one to determine whether extensions of those
leases should be granted. Pit River asks our court to remand
to the district court with instructions to enter judgment in its
favor. We decline to do so. The district court did not
consider the merits of Pit River’s Geothermal Steam Act
claims, and determining whether BLM violated provisions of
the Geothermal Steam Act will require careful analysis. The
district court should undertake that task in the first instance.
See, e.g., U.S. Auto Parts Network, Inc. v. Parts Geek, LLC,
692 F.3d 1009, 1021 (9th Cir. 2012) (directing district court
to examine in the first instance issues not previously reached
that might require factual development). Moreover, under
Federal Rule of Civil Procedure 12(c), a plaintiff is not
entitled to judgment on the pleadings if the defendant’s
answer raises issues of fact or affirmative defenses. Gen.
Conference Corp. of Seventh-Day Adventists v. Seventh-Day
Adventists Congregational Church, 887 F.2d 228, 230 (9th
Cir. 1989). In this case, the defendants’ answers do both. We
therefore decline Pit River’s invitation to rule on the merits of
its Geothermal Steam Act claims.
III. Pit River’s NEPA, NHPA, and Fiduciary Duty
Claims
The district court concluded that Pit River’s NEPA,
NHPA, and fiduciary duty claims failed because § 1005(a) is
non-discretionary—BLM is not permitted to consider
28 PIT RIVER TRIBE V. BLM
environmental factors in making lease continuation decisions
and any environmental review would be superfluous. We
agree with the district court that § 1005(a) is
non-discretionary, see Pit River I, 469 F.3d at 780 (citing
Dep’t of Transp. v. Pub. Citizen, 541 U.S. 752, 768 (2004)),
but, as discussed, the district court incorrectly circumscribed
Pit River’s claims. If Pit River prevails on its claim that the
leases here were eligible only for extension under § 1005(g),
BLM will be required to comply with NEPA and NHPA,
including by consulting with affected tribes. Id. at 787–88.
Therefore the district court erred by granting judgment on the
pleadings on Pit River’s NEPA, NHPA, and fiduciary duty
claims.
CONCLUSION
We REVERSE the district court’s judgment and
REMAND for further proceedings consistent with this
opinion.
|
Conjunctival Lymphoma in a Patient on Fingolimod for Relapsing-Remitting Multiple Sclerosis.
The authors describe a 39-year-old woman treated with fingolimod for relapsing-remitting multiple sclerosis for 2 years who then developed a bilateral conjunctival mucosa-associated lymphoid tissue lymphoma. Fingolimod treatment for multiple sclerosis has been associated with lymphoma in 3 previously reported cases. This is the first case of ocular adnexal lymphoma presumed to be due to fingolimod. Given that ophthalmologists regularly monitor many patients on fingolimod for fingolimod-associated macular edema and ophthalmic manifestations of multiple sclerosis, the authors hope to alert physicians of the possibility of ocular adnexal lymphoma in these patients. |
Download three mile walk
Leslie Sansone Walk at Home - Home | Facebook
Track and map every walk with MapMyWalk. payment will be charged to your Google Play account.Walking is one of the most effective forms of exercise, and in this workout program Leslie Sansone shows how to drop pounds, burn.
Top Audio Mixes and CDs for Walkers. can start with just an easy one mile walk.Find great deals for Leslie Sansone - Walk Away the Pounds Express: 3 Mile Advanced Walk (DVD, 2003).Information and links on everything from how to start and maintain a fitness walking program to.Central Park 3 mile. Distance. 3.07. miles. run back to 72nd street and then walk home to cool down ( 3 miles of running plus.82 miles. Download Data Learn.
Can You Solve The 3-Mile Walk Riddle?
Tram tours are. are expected to abide by vehicle rules of the roadway including speed limits and yielding to pedestrians in cross-walk areas.Accumulating those three extra miles a day could be as simple as making.Is fast walking 3 miles a day - everyday - enough to keep you healthy for the.
5 Mile Stride / 3 Mile Fun Walk - New Ross - New Ross, Co
Now download videos in all formats from Youtube using GenYoutube video downloader.We went downtown today (I live in DC) and we walked about 3 miles, at a good pace.Walking at Home American Heart Association 3 Mile Walk. iWalk Strong 3 Mile Walk (Walk at Home) - Duration: 42:38.
Videofitness Workout Reviews: 3 Mile Slim & Sleek Walk
COOPER INSTITUTE AGE AND GENDER NORMS 3-Mile Walking Test
Kendra Kimberly 3 mile walk - Xfinity Help and Support Forums
3 mile walk at 9 weeks, too much?? | Knee & Hip
Hadied on how long does it take to walk 3 miles on a treadmill: Depending on wt and fitness level as well as age calories.By: Erick Payne. Posted:. A central Illinois teenager is starting a 300 mile journey for a good.
The Bright Angel Trail - National Park Service
Start walking at home. 3 mile fast-paced walk. (DVD video
A Thousand-Mile Walk to the Gulf - Yosemite Online
Treat yourself to a safe and easy workout with this 1-2-3 Mile Walk fat burning video and belt. |
Q:
printing results in a formated form
I want to format the result so it would be adjusted
Here is what I wrote so far:
void affichage(int note[][50],char nom[][50],float moy[], float moy_e[], char module[][50],int nb_etudiant, int nb_module){
int i,j;
printf("\n\t\taffichage\n\n");
printf("\t");
strcpy(module[nb_module],"Moy G");
strcpy(nom[nb_etudiant],"Moy C");
for (i=0;i<nb_module;i++){
printf("%5s ",module[i]);
}
printf(" %5s",module[nb_module]);
printf("\n");
for(i=0;i<nb_etudiant;i++){
printf("%-5s ",nom[i]);
for (j=0;j<nb_module;j++){
printf("%-7d ", note[i][j]);
}
printf(" %-7.1f\n",moy_e[i]);
}
printf("\n\n");
printf("%5s ",nom[nb_etudiant]);
for (i=0;i<nb_module;i++){
printf("%-7.1f ",moy[i]);
}
}
A:
As a suggestion, printf returns the length of the string formatted. Since you want to display the student's data, if we suppose you have a table with 2 columns:
X chars Y chars
-------|------ -------|---------
| | |
----------------------------------------
nom | prénom | note
----------------------------------------
Jane | Mari | 15
----------------------------------------
Robert | Daniel | 16
-----------------------------------------
X : number of white spaces - 2
Y : number of white space - 2
it can be any value, but make sure it will be greater than most of the lengths of the property displayed in that column
For Each student, for the first cell (nom) you should first print his name, then you get the length of the printed name PN (printf's returned value), and print ( X - PN) whitespace, then you add the pipe character |.
You do the same for the next property which is prenom, and at last you print \n for a new line.
#include <string.h>
#include <stdio.h>
typedef struct
{
char firstName[25];
char lastName[25];
float grade1;
float grade2;
}Student;
Student createStudent(char* firstName, char* lastName, float grade1, float grade2) {
Student student;
strcpy(student.firstName, firstName);
strcpy(student.lastName, lastName);
student.grade1 = grade1;
student.grade2 = grade2;
return student;
}
/* each column has a width equal to 20 characters 2 for borders and 18 of whitespaces or characters */
void printBorder() {
int i = 0;
int len = 0;
for(i =0 ; i<80; ++i) printf("-"); // top border
printf("\n"); // breakline
printf("|"); // left border of the left cell
len = printf("First Name"); // len is equal to 10
for(i=0; i<18 - len; ++i) printf(" "); // printing whitespace
printf("|"); // print the right border of the cell
len = printf("Last Name"); // len is equal to 9
for(i=0; i<18 - len; ++i) printf(" "); // printing whitespace
printf("|");
len = printf("Grade 1"); // len is equal to 7
for(i=0; i<18 - len; ++i) printf(" ");
printf("|");
printf("Grade 2\n");
for(i =0 ; i<80; ++i) printf("-"); // bottom border of header
printf("\n"); // breakline
}
void printBody(Student* students, int nbrOfStudents) {
int j = 0; // to iterate over students
int len = 0;
int i =0; // for drawing
for(j = 0; j< nbrOfStudents; ++j) {
printf("|"); // left border of the left cell
len = printf("%s", students[j].firstName);
for(i=0; i<18 - len; ++i) printf(" "); // printing whitespace
printf("|"); // print the right border of the cell
len = printf("%s", students[j].lastName);
for(i=0; i<18 - len; ++i) printf(" "); // printing whitespace
printf("|");
len = printf("%.2f", students[j].grade1);
for(i=0; i<18 - len; ++i) printf(" "); // printing whitespace
printf("|");
len = printf("%.2f\n", students[j].grade2);
}
for(i =0 ; i<80; ++i) printf("-"); // bottom border of header
printf("\n"); // breakline
}
int main() {
Student students[3] = {
createStudent("Jane", "Roberson", 99, 75),
createStudent("Amelia", "Coeur-de-lait", 85, 89),
createStudent("Anna", "Stone", 65, 30)
};
printBorder();
printBody(students, 3);
return 0;
}
|
Experiences of sexual coercion in a representative sample of adults: the Second Australian Study of Health and Relationships.
Background It is important to have current reliable estimates of the prevalence, correlates and consequences of sexual coercion among a representative sample of Australian adults and to identify changes over time in prevalence and consequences. Computer-assisted telephone interviews were completed by a representative sample of 20094 Australian men and women aged 16-69 years. The participation rate among eligible people was 66.2%. Sexual coercion (i.e. being forced or frightened into sexual activity) was reported by 4.2% of men and 22.4% of women. Sexual coercion when aged ≤16 years was reported by 2.0% of men and 11.5% of women. Correlates of sexual coercion were similar for men and women. Those who had been coerced reported greater psychosocial distress, were more likely to smoke, were more anxious about sex and more likely to have acquired a sexually transmissible infection. Few people had talked to others about their experiences of sexual coercion and fewer had talked to a professional. There were no significant differences between the First and Second Australian Study of Health and Relationships in whether men or women had experienced coercion, talked to anyone about this or talked to a counsellor or psychologist. Sexual coercion has detrimental effects on various aspects of people's lives. It usually occurs at the ages at which people become sexually active. There is a need to reduce the incidence of sexual coercion, better identify experiences of sexual coercion, and provide accessible services to minimise the detrimental effects of sexual coercion. |
Beach implements pilot program for parking
January 2, 2013
You may not notice the change at first glance but, if you are at one of four different pay-required parking areas on Fort Myers Beach, you will see an additional feature to the meters there.
When feeding the coin meters on Palm Avenue, Strandview Avenue, Newton Park and along all of Old San Carlos Boulevard, do not panic if you do not have enough change in your pants pockets or vehicle. Credit card usage is now available.
As part of a newly implemented pilot program by the Town of Fort Myers Beach, the new meters at the four locations will allow the use of "plastic" money. Call it a technological advance for convenience sake.
"They are going to be in place through April," said Town Public Works Director Cathie Lewis. "We are moving forward with this primarily because of convenience, but also to provide a computer program that will identify whenever there is a problem with a meter so that we can be proactive and repair it right off the bat."
The coin meters can take quarters, dimes and nickels and credit cards, but no receipts will be given. One will have to check their banking statements or online banking system for that access.
A total of 99 new meters have been provided by Innovative Parking Solutions.
The credit card computer program will offer more than convenience. Lewis said that parking meters that are not functioning properly generally take at least 24 hours to be repaired. Before, coin would be unloaded on a two to three day basis and that was the time a problem was detected.
"Sometimes we can have meters that can be inoperable without us knowing where people are either parking for free or have lost coin in it," said Lewis.
Repairs on such coin meters or pay stations are costly as well.
The reason for selecting Old San Carlos Boulevard relates to the high usage there. Palm Street currently has an aging Pay Station that, while still functional, may break soon due the age of the machine.
"Pay stations are expensive to replace, so we felt that we could pilot it at this location to see how well people receive it.
Strandview and Newton Park do not have change machines at those locations. A simple swipe will change that.
"When people utilize those locations, often they can't because they do not have coin or they have to run and get coin at Publix or other places. We want to see if people find it beneficial," said Lewis.
As it does with the regular parking meters, Beach and Street Enforcement will take care of operations with the new multi-purpose meters. The computer program will be monitored at the central parking office.
"Basically, it records every meter every 60 seconds. It knows exactly what is going on when someone uses their credit card by showing the last four digits of the credit card," said Lewis. "We hope people find it much more convenient for them instead of carrying a lot of coin."
There will be no parking rate change with the newly implemented meters, says Lewis.
"There are no changes in our rates. We are not changing any of that aspect of infrastructure," she said.
The Town has offered free parking at all its metered sites during particular holidays. In the past, one would have to read the fine lines on the meters to find out when they didn't have to add coins. Now, technology has improved that situation.
"These meters will also alert people when it is free parking. Sometimes people were not aware and continued to feed the meters when there was free parking. It was difficult to notify them," said Lewis.
According to Town records, there are two types of parking on he Beach: short term and long term.
One can find short-term parking, or metered parking, on Old San Carlos Boulevard, Estero Boulevard, Center Street and Fifth Street. There, metered spaces have a two-hour time limit and cost $2 per hour. Coin change machines are available on Center Street and next to the Shipwreck Store on Old San Carlos Boulevard. Meters are monitored between 9 a.m. and 6 p.m. seven days a week.
Long-term parking is available on all beach access streets and in the lot under the Matanzas Pass Bridge. The cost is $2 per hour, and there is no time limit.
Two beach accesses, Palm Avenue and Connecticut Street, offer Pay-and-Display machines, which allows the parker to use a credit card rather than change to pay for parking.
Prohibited parking areas include on any sidewalk, in the wrong direction (against the flow of traffic), in a handicapped space without a valid permit, in a fire lane and in areas officially marked as prohibited.
If you are in doubt as to whether you are parked illegally, contact BASE at 463-5888 before you park and leave your car. |
/*!
*
* This program is free software; you can redistribute it and/or modify it under the
* terms of the GNU Lesser General Public License, version 2.1 as published by the Free Software
* Foundation.
*
* You should have received a copy of the GNU Lesser General Public License along with this
* program; if not, you can obtain a copy at http://www.gnu.org/licenses/old-licenses/lgpl-2.1.html
* or from the Free Software Foundation, Inc.,
* 51 Franklin Street, Fifth Floor, Boston, MA 02110-1301 USA.
*
* This program is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY;
* without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.
* See the GNU Lesser General Public License for more details.
*
*
* Copyright (c) 2002-2018 Hitachi Vantara. All rights reserved.
*
*/
package org.pentaho.platform.plugin.services.webservices;
import org.apache.axis2.context.ConfigurationContext;
import org.apache.axis2.context.MessageContext;
import org.apache.axis2.context.OperationContext;
import org.apache.axis2.context.ServiceContext;
import org.apache.axis2.description.AxisOperation;
import org.apache.axis2.description.AxisService;
import org.apache.axis2.engine.AxisConfiguration;
import org.apache.axis2.transport.http.AxisServlet;
import javax.servlet.ServletConfig;
import javax.servlet.ServletException;
import javax.servlet.http.HttpServletRequest;
import javax.servlet.http.HttpServletResponse;
import java.io.IOException;
/**
* This class subclasses AxisServlet to expose protected methods and variables
*
* @author jamesdixon
*
*/
public class AxisServletHooks extends AxisServlet {
private static final long serialVersionUID = 3169157817280586159L;
protected AxisService axisService;
protected AxisOperation axisOperation;
protected OperationContext operationContext;
protected ServiceContext serviceContext;
protected MessageContext messageContext;
/**
* Returns the current Axis MessageContext object.
*
* @return message context
*/
public MessageContext getMessageContext() {
return messageContext;
}
/**
* Sets the Axis configuration context object
*
* @param configContext
*/
public void setContext( ConfigurationContext configContext ) {
this.configContext = configContext;
}
/**
* Sets the Axis configuration object
*
* @param axisConfiguration
*/
public void setConfiguration( AxisConfiguration axisConfiguration ) {
this.axisConfiguration = axisConfiguration;
}
/**
* Sets the Axis service context for this request
*
* @param serviceContext
*/
public void setServiceContext( ServiceContext serviceContext ) {
this.serviceContext = serviceContext;
}
/**
* Sets the servlet config object. This is mainly used for standalone and testing purposes
*
* @param servletConfig
* @throws ServletException
*/
public void setServletConfig( ServletConfig servletConfig ) throws ServletException {
if ( servletConfig != null ) {
init( servletConfig );
}
}
/**
* Creates an Axis message context object for this request. If the AxisOperation is null (this will be the case during
* a POST operation) the operation is determined by examining the contentType
*/
@Override
public MessageContext createMessageContext( HttpServletRequest request, HttpServletResponse response,
boolean invocationType ) throws IOException {
messageContext = super.createMessageContext( request, response, invocationType );
if ( axisOperation == null ) {
// we don't know the operation yet so pull it from the requests's contentType
String contentType = request.getContentType();
// parse it looking for action="operation"
int idx = contentType.indexOf( "action=" ); //$NON-NLS-1$
if ( idx != -1 ) {
char delim = contentType.charAt( idx + 7 );
int idx2 = contentType.indexOf( delim, idx + 8 );
if ( idx2 != -1 ) {
String actionStr = contentType.substring( idx + 8, idx2 );
String operationName = actionStr.substring( 4 );
axisOperation = axisService.getOperationByAction( operationName );
}
}
operationContext = serviceContext.createOperationContext( axisOperation );
}
// setup the objects the message context needs to execute
messageContext.setAxisService( axisService );
messageContext.setOperationContext( operationContext );
messageContext.setAxisOperation( axisOperation );
return messageContext;
}
/**
* Handle and HTTP PUT request
*
* @param httpMethodString
* "PUT"
* @param request
* HTTP request
* @param response
* HTTP response
* @throws ServletException
* @throws IOException
*/
public void handlePut( String httpMethodString, HttpServletRequest request, HttpServletResponse response )
throws ServletException, IOException {
new RestRequestProcessor( httpMethodString, request, response ).processXMLRequest();
}
/**
* Handle and HTTP GET request
*
* @param httpMethodString
* "GET"
* @param request
* HTTP request
* @param response
* HTTP response
* @throws ServletException
* @throws IOException
*/
public void handleGet( String httpMethodString, HttpServletRequest request, HttpServletResponse response )
throws ServletException, IOException {
RestRequestProcessor processor = new RestRequestProcessor( httpMethodString, request, response );
processor.processURLRequest();
}
/**
* Handle and HTTP POST request
*
* @param httpMethodString
* "POST"
* @param request
* HTTP request
* @param response
* HTTP response
* @throws ServletException
* @throws IOException
*/
public void handlePost( String httpMethodString, HttpServletRequest request, HttpServletResponse response )
throws ServletException, IOException {
super.doPost( request, response );
}
/**
* Sets the Axis service object for this request
*
* @param axisService
*/
public void setAxisService( AxisService axisService ) {
this.axisService = axisService;
}
/**
* Sets the Axis opertation for the current request
*
* @param axisOperation
*/
public void setAxisOperation( AxisOperation axisOperation ) {
this.axisOperation = axisOperation;
}
/**
* Sets the Axis operation context for the current request
*
* @param operationContext
*/
public void setOperationContext( OperationContext operationContext ) {
this.operationContext = operationContext;
}
}
|
Q:
Jquery .AJAX doesn't works on click event
I'm going to implement the following:
When user presses button AJAX query is performed to servlet. Depending on the request from server, I change label text.
web.xml
<servlet>
<servlet-name>RemindPassword</servlet-name>
<servlet-class>app.RemindPassword</servlet-class>
</servlet>
<servlet-mapping>
<servlet-name>RemindPassword</servlet-name>
<url-pattern>/RemindPassword</url-pattern>
</servlet-mapping>
html code of button
<form>
<div class="field">
<label for="email">Your e-mail:</label>
<input name="email" type="text" class="t">
</div>
<input id ="btn" type="submit" value="Send" />
</form>
JS
<script type="text/javascript">
$(document).ready(function() {
$('#btn').click(function() {
$.ajax({
type: "GET",
url: "/RemindPassword",
//dataType:text,
//data: $("#registerSubmit").serialize(),
success: function(msg){
$('input[type="submit"]').after("<label for='submit'>" + msg+" " +"</label>");
},
error: function(XMLHttpRequest, textStatus, errorThrown) {
$('input[type="submit"]').after("<label for='submit'>" + fail+" " +"</label>");
}
});
});
});
Probably useful information:
I perform AJAX query from domain/someJSP/RemindPassword.
I put servlet in the root of my web app and intentionally put slash before URL in AJAX call. No success. When I used .get JQUERY function it worked when I call it on render bit didn't work when I put ajax call onclick. .ajax didn't work in both cases.
A:
change ID selector, add prevent default and better handle the form submit instead of button click
$('#form1').click(function(e) {
e.preventDefault()
assuming that form tag will have ID=form1
|
Q:
Cannot call methods on char
This error seems to be coming from the following block of code. what is the possible cause of this error?
Cannot call method on char
INSERT INTO #ActiveTerminals
SELECT DISTINCT a.TerminalId, SerialNumber, a.[LoadTime] [LastSale]
FROM Terminal INNER JOIN
(
SELECT DISTINCT Ticket.TerminalId,max(LoadTime) [LoadTime] FROM
Ticket with (NOLOCK)
JOIN ProductDenomination with (NOLOCK) ON (ProductDenomination.DenominationId = Ticket.DenominationId)
WHERE ProductDenomination.ProductId NOT IN (SELECT * FROM dbo.fn_MVParam(@sExcludedProducts)) AND
datediff(day,LoadTime,@dteActiveSalesEndDate) <= @iLastSoldWithinDays
GROUP BY TerminalId
UNION ALL
SELECT DISTINCT VarTicket.TerminalId, max(TransactionDate) [LoadTime] FROM
VarTicket with (NOLOCK)
WHERE VarTicket.ProductId NOT IN (SELECT * FROM dbo.fn_MVParam(@sExcludedProducts)) AND
VarTicket.TerminalId NOT IN (SELECT TerminalId FROM #ActiveTerminals)
AND datediff(day,TransactionDate,@dteActiveSalesEndDate) <= @iLastSoldWithinDays
GROUP BY TerminalId
)a ON (Terminal.TerminalId = a.TerminalId.TerminalId)
ORDER BY a.TerminalId, SerialNumber
A:
For this line:
)a ON (Terminal.TerminalId = a.TerminalId.TerminalId)
change it to this:
)a ON (Terminal.TerminalId = a.TerminalId)
|
// generated by stringer -type=ValidationLevelM20; DO NOT EDIT
package carbon20
import "fmt"
const _ValidationLevelM20_name = "StrictM20MediumM20NoneM20"
var _ValidationLevelM20_index = [...]uint8{0, 9, 18, 25}
func (i ValidationLevelM20) String() string {
if i < 0 || i >= ValidationLevelM20(len(_ValidationLevelM20_index)-1) {
return fmt.Sprintf("ValidationLevelM20(%d)", i)
}
return _ValidationLevelM20_name[_ValidationLevelM20_index[i]:_ValidationLevelM20_index[i+1]]
}
|
Q:
Can running deer be described as "churning"?
I heard a movie description
With the reindeer's legs churning, they fly directly toward the moon.
Can a galloping/running ungulate be described as "legs churning"? Or did I hear it wrong? I don't think it's journeying either, because a person journeys, not legs. I am putting the audio clip here (uploaded to an audio sharing site Clyp) for reference.
Also what are other verbs that describe the legs of a galloping four-legged animal like shown in this pic?
A:
I found that Merriam-Webster's definition of churn includes in one entry:
intransitive verb
1 : to work a churn (as in making butter)
2 a : to produce, proceed with, or experience violent motion or agitation · her stomach was churning · churning legs
b : to proceed by or as if by means of rotating members (such as wheels or propellers) · boats churning across the harbor
This was the first result in a Google search for legs churning; other results seem to show this phrase in common use particularly to refer to cyclists …
|
New from Cambridge University Press!
Edited By Keith Allan and Kasia M. Jaszczolt
This book "fills the unquestionable need for a comprehensive and up-to-date handbook on the fast-developing field of pragmatics" and "includes contributions from many of the principal figures in a wide variety of fields of pragmatic research as well as some up-and-coming pragmatists."
Book Information
The Oxford Applied Linguistics series is aimed at applied linguists,lecturers, teacher trainers, students on advanced/postgraduate courses, andpractitioners interested in gaining a wider perspective on their work. Itprovides up-to-date coverage of the latest research in applied linguistics,together with discussion of psychological, sociological, and othertheoretical issues of relevance to the study of language in the real world.
The Psychology of Second Language Acquisition offers a systematic andaccessible overview of the main psychological areas and theories in orderto keep abreast of the ongoing paradigm shift. Readers will find succinctand up-to-date descriptions of a wide range of psycholinguistic andneuropsychological topics such as language and the brain; neuroimaging andother research methods in psycholinguistics and brain research;non-nativist approaches to language acquisition; explicit/implicit learningand memory, procedural/declarative knowledge, and the automatization oflanguage skills; learner characteristics, age effects, and the criticalperiod hypothesis; and the psychological basis of language learning ineducational contexts. |
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King County sees decline in childhood obesity
New findings published by the federal Centers for Disease Control and Prevention show that youth obesity dropped in low-income school districts that were part of a King County-focused obesity prevention initiative. By increasing healthy food choices and opportunities for physical activity such as improving the quality of physical education, the initiative boosted healthy habits for middle and high school students. These results have promising implications for statewide and national strategies to improve community health.
The report shows a 17 percent decline in youth obesity in King County (from 9.5 percent to 7.9 percent) after Public Health – Seattle & King County partnered with schools and community organizations to implement a two year Communities Putting Prevention to Work (CPPW) obesity prevention initiative ending in 2012. While youth obesity rates fell significantly in CPPW initiative school districts, (Auburn, Highline, Kent, Northshore, Renton, Seattle and Tukwila) rates remained the same in districts not involved in the initiative and were also unchanged in the rest of the state.
"This successful approach to reducing childhood obesity is a model for our state and our nation," said King County Executive Dow Constantine. "It is an excellent example of how we can make our children and, ultimately, our communities healthier by focusing our combined resources on prevention. Overcoming the social inequity we see in King County starts with today's children, and we're seeing positive results."
Statewide, obesity and overweight rates for 10th graders have remained steady for the past decade. The state's Healthy Youth Survey found that about 23 percent of 10th graders are overweight or obese.
"We must do all we can to improve the health of our next generation," said Governor Jay Inslee. "These results in King County show that public health prevention activities can make a difference and we have a good start. Yet, there's much more to do. Effective programs to support healthy, active kids are crucial to the future health of our state."
Investing in children's health now could lead to lower health care costs. This is at the heart of Governor Inslee's Healthiest Next Generation legislation that supports healthy schools, healthy child care and early learning centers, and promotes breastfeeding-friendly environments.
Other prevention initiatives around the state also show promise. For example, a school district in Skagit County has a new one-mile walk zone around each school, allowing kids to walk to school safely and saving the district money on busing. A school district in Benton County made healthy changes to their school lunch program that still appeal to kids and each school now has a salad bar.
"Children today are not as healthy as their parents were when they were kids. We must change that, and these programs show we can," said Washington State Secretary of Health John Wiesman. "Programs like these could be a turning point in fighting the obesity epidemic. Together, we can seize the moment by investing in strategies that promote healthier weight for children who'll be able to live longer, enter the workforce healthier, and reduce costs for health care and businesses."
"Our local obesity prevention initiative took a comprehensive approach, from nutrition standards for school meals and student-led healthy eating and active living promotional campaigns to farm-to-school programs and high-quality physical education," said Dr. David Fleming, Director and Health Officer for Public Health – Seattle & King County. "These promising results show the potential for public health to stop the obesity epidemic and prevent our children from living shorter lives than we do, a current fear of many experts."
Examples of obesity prevention initiative activities in King County schools:
In Auburn, CPPW led to the Commit to Fit Campaign that galvanized students to eat healthier foods and be more active. "We saw the entire district get involved in various ways with the initiative. We had over 6,000 students track their nutrition and physical activity changes," said Auburn High School teacher Lori Jacobs.
Seattle Public Schools established a model physical education program. "When funding was awarded, 75 percent of the equipment that had been at the school had to be thrown away and I had almost zero teaching supplies. The equipment from this grant was critical to my program," said Chellie Lafayette, Physical Education Specialist at Roxhill Elementary.
Highline Schools promoted nutritious food in their school meals. "We worked directly with our students to develop an innovative marketing campaign in the school cafeterias to promote healthy choices. Now, our 11,000 students that eat lunch in our cafeterias every day have the information they need to make better choices," said Chris Neal, Director of Nutrition Services at Highline Schools.
"Preventing obesity is about more than individual choices. It takes positive changes in the places where people live, learn, work and play to make a difference," said Dr. Jim Krieger, Chief of Chronic Disease at Public Health - Seattle & King County. "We focused this initiative on low-income school districts because their youth obesity rates are higher."
About the report data: Youth obesity data are from the Washington State Healthy Youth Survey conducted in grades 8, 10 and 12. The full MMWR report is available on the CDC website.
We encourage an open exchange of ideas on this story's topic, but we ask you to follow our guidelines for respecting community standards. Personal attacks, inappropriate language, and off-topic comments may be removed, and comment privileges revoked, per our Terms of Use. Please see our FAQ if you have questions or concerns about using Facebook to comment. |
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Sunday, April 14, 2013
You Can Make Maple Syrup (Seriously...It's Easy!)
If you can answer "yes" to these 3 questions, then you too, can make your own pure maple syrup:
Do you have a maple tree in your yard?
Do you love pure maple syrup?
Do you love saving money?
All you need is ONEmaple tree! In fact, if you get going today, you could have syrup in as little as 2 days...seriously! If you don't have a maple tree, maybe a friend or neighbor does, so you could make this a joint venture.
And don't worry about what kind of maple you have or how much sap it takes to get what yield, because I discovered ANY maple tree will work! And while Sugar Maples are preferred by maple syrup producers for the greatest yield, don't let that stop you, because we don't have a Sugar Maple (I think ours is a Soft Maple) and in just 2 weeks we have 1.5 gallons of syrup!
I know my blogs are usually about natural skincare topics (I make and sell SkinKissed Naturals - natural skincare products), but I care about healthy, natural food just as much as I care about natural skincare products! And since the sap is flowing like crazy right now where we live (in
Somerset, WI), if you have maple trees in your yard and this sounds like
something you'd like to try, then let's get to it and make some maple
syrup! Besides, what else is there to do in crazy April weather like this?
Today we'll cover finding the right tree(s) and getting them tapped. Then tomorrow we'll cover the nutritional benefits of maple syrup and how to boil the sap down and store your finished syrup.
What You Need To Get Started...
Our next door neighbors were originally from out east, where maple syrup is a really big deal, and they gave us their equipment before they moved to Florida. They convinced me it was easy and I really could do it...and so can you...I'll tell you how!
Here's what you need to get started:
Any maple tree that's at least 10" in diameter
The right temperatures outside
A drill
A tap (also known as a "spile") which our hardware store carries for $2.99 each
That's it! But don't delay, because the syrup is flowing NOW and you can start today with just the first 5 things listed above! Then you can worry about gathering the rest of the items needed to complete the job. So let's break these steps down.
The Right Tree, The Right Conditions
First you need to find a maple tree that is at least 10-12 inches in diameter. Then you need to make sure the weather/temperature conditions are right.
When the weather is below freezing (32 degrees Farenheit) at night and above freezing during the day, it's time to tap the trees! These are the conditions that cause the sap in the trees to flow. In Wisconsin where we live, this is usually some time in March. We've been at this for a couple weeks already, but the sap is still flowing with this crazy weather we're having (I am so OVER this snow in April thing, but it is good for getting maple syrup!).
The diameter of the tree will determine the number of taps you can use on the tree. According to the Minnesota DNR, here's a general guide:
Diameter of TreeNumber of Taps
less than 10" 0
10" to 14" 1
15" to 19" 2
20" to 24" 3
25" or larger 4
Now you need to install the taps (or the correct word is "spile"). There are different styles of these, but I saw them at our local hardware store for $2.99 each.
Drill a hole only the size of the spile (usually 5/16" or 7/16") at a slight angle upward, no more than
2"-3" deep. Blow the shavings out of the hole, then gently tap the
spile with a hammer into the tree, being careful not to split the wood. Choose a
location about 3 feet off the ground, ideally either above a big root or
below a big branch, on the south side of the tree where it gets the
most sun.
Now all you need to do is hang your bucket! You should start to see sap running right away if the conditions are right. It will look like water and has the same consistency.
You might want to figure out a way to cover the bucket to help keep rain, snow and other debris out (but don't worry if some of that stuff gets in...it's bound to...and you're going to filter it and boil it later anyway).
We got lucky and have one great-grand-daddy of a tree so we installed 3 taps (we didn't have a spile for one so my husband rigged a brass fitting with a refrigerator water tube that drips into the pan on the ground). Our daughter loves checking the buckets every day!
Now Just Go Do It!
You will be surprised at how quickly your buckets fill. And when they do, just transfer the sap into a 5 gallon bucket or other container, keeping it in a cool place until you're ready to boil, and keep filling. Then look for the next post tomorrow or Tuesday to learn how to boil it down and make your syrup!
Now go! Hurry! It will be too late when the weather gets warmer, because the sap will stop flowing, we'll have to remove the spiles (then the tree will naturally heal itself), and we'll have to wait until next spring to make syrup again (now go on..go!...You can do it!).
And just like there is no comparison between pure maple syrup and pancake syrup, there is also no comparison between natural skincare products and commercial skincare products. Check out SkinKissed Naturals - healthy, natural skincare products for every skin type at: skinkissednaturals.com.
Yes, we soon figured out we needed to cover it, especially from rain, so we put either plastic or tinfoil around and over the tap and bucket to keep debris and rain out. However, even when we did that, we still would manage to get some stuff in there, so we ran the sap through a fine strainer before adding it to our larger sap bucket and before cooking it down. |
Wednesday, October 5, 2016
Waste Rangers keep streets clean after race
by Riley Grant, Sustainable Schools Program Manager
As the final racers crossed the finish line, I met with local Jr. Girl Scout troop members to survey the area around the Depot Market Square. Our challenge was to clean up the litter left behind by the earlier crowd. The Jr. Girl Scouts were one of the first groups to participate in RE Sources Sustainable Schools new Waste Rangers program, a service-learning program focused on working with youth organizations to raise awareness about solid waste issues in Whatcom County and engage youth in projects to address these issues. Through the litter clean-up following the marathon, the girl scouts learned about some of the issues litter causes in our community, like marine debris caused from litter washing into storm drains on rainy days, or wildlife accidentally eating the litter and getting sick. The girls also learned that a large majority of litter is created inadvertently by people — whether it's forgetting and walking away from your coffee cup, or accidentally dropping something from your pocket while you're getting your phone out, or the wind blowing waste from recycle bins — everyone accidentally creates litter at some point. Our new waste rangers are learning that solid waste issues such as litter is everyone's responsibility to address, and working collectively we can make an impact.
The 3 girl scouts, their parent chaperones and one 4 year old "girl scout in training" were able to collect 10 pounds of litter from the area around the finish line, even after volunteer crews did the majority of the post-race clean up. When asked what they
learned and what they liked, the newly anointed Waste Rangers said they learned that a lot of garbage ends up as litter and they liked that they were able to make a difference and help their community. Even the scout in training said that her favorite thing was helping the big girls find the litter- another of Waste Rangers in the making!
16 comments:
there you go!!still it's clean in where people do not trash but still knowing human nature it's quite impossible not to leave anything after themselves..and writing experts who write my essay for me in 2012 we leave 2.6 trillion pounds of garbage and i am curious where these went
Through the litter tidy up following the marathon, the young lady scouts found out about a portion of the issues litter causes in our group, similar to marine flotsam and jetsam caused from litter washing into storm depletes on blustery days, or natural life inadvertently eating the litter and becoming ill. Coursework Writing Services
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/*
* Copyright 2015-2019 Alexandr Evstigneev
*
* 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 unit.perl;
import base.PerlLightTestCase;
import org.junit.Test;
public class PerlValuesMojoTest extends PerlLightTestCase {
@Override
protected String getBaseDataPath() {
return "testData/unit/perl/perlValues/mojo";
}
@Override
protected void setUp() throws Exception {
super.setUp();
withMojo();
}
@Test
public void testApp() {
doTest();
}
@Test
public void testNew() {
doTest();
}
@Test
public void testDel() {
doTest();
}
@Test
public void testGroup() {
doTest();
}
@Test
public void testAny() {
doTest();
}
@Test
public void testGet() {
doTest();
}
@Test
public void testOptions() {
doTest();
}
@Test
public void testPatch() {
doTest();
}
@Test
public void testPost() {
doTest();
}
@Test
public void testPut() {
doTest();
}
@Test
public void testWebsocket() {
doTest();
}
@Test
public void testUnder() {
doTest();
}
@Test
public void testHelper() {
doTest();
}
@Test
public void testHook() {
doTest();
}
@Test
public void testPlugin() {
doTest();
}
private void doTest() {
initWithTextSmartWithoutErrors("use Mojolicious::Lite;\n" +
"\n" +
"my $var = "+getTestName(true)+";\n" +
"\n" +
"$v<caret>ar;");
doTestPerlValueWithoutInit();
}
}
|
Q:
how can I get a std::set of keys to a std::map
I was writing an algorithm this morning and I ran into a curious situation. I have two std::maps. I want to perform a set intersection on the sets of the keys of each (to find which keys are common to both maps). At some point in the future, I think it's likely I'll also want to perform set subtraction here as well. Luckily, the STL includes functions for both of those operations. The problem is, I can't seem to get a std::set of the keys out of a std::map. Is there any way to do this? I'm looking for something that would be this simple, like it is in Java:
std::set<Foo> keys = myMap.getKeySet();
My understanding is that I can't use the std::set_intersection() function directly on iterators into the maps because the maps expose std::pair objects instead of just keys. Also, I don't think the map guarantees order. I'm also interested in performing this same operation on a pair of std::multimaps, if that makes any difference.
EDIT: I forgot to mention initially that due to the age of the compiler I'm forced to use (MSVC++ 6), most of the nifty template tricks that are available in boost can not be used.
A:
What you basically want is a copy, as std::map doesn't keep the keys in a std::set. std::copy assumes that the value types are compatible, which isn't the case here. The std::map::value_type is a std::pair. You want to copy only the first part of the pair, which means you need a std::transform. Now, since you will be using an insert_iterator on the set, order doesn't matter. The std::set will sort on insertion, even though the map was already sorted.
[edit] Code might be easier. Top of my head, not compiled.
std::transform(MyMap.begin(), MyMap.end(),
std::inserter(MySet, MySet.end()),
boost::bind(&std::pair<Key,Value>::first, _1));
If you've got SGI's select1st, you don't need the boost::bind.
[edit]
Updated for C++14
std::transform(MyMap.begin(), MyMap.end(),
std::inserter(MySet, MySet.end()),
[](auto pair){ return pair.first; });
A:
Map does guarantee order; that's why it's called a sorted associative container. You can use set_intersection with a custom comparator function, the second variant listed here.
So, something like
bool your_less(const your_map::value_type &v1, const your_map::value_type &v2)
{ return v1.first < v2.first; }
set_intersection(m1.begin(), m1.end(), m2.begin(), m2.end(), your_output_it, your_less);
should do the trick. (It is also possible to use boost::lambda and bind to avoid writing a temporary function.)
The default operator< over pairs compares both components. Since you need equivalence only over the first part of the pair (the map key), you need to define your own comparison operator that provides such relation (which is what the function above does).
A:
In practice,
yourmap::const_iterator mi;
set<key_type> k;
for (mi = yourmap.begin(); mi != yourmap.end(); ++mi)
k.insert(mi->first);
return k;
|
The mission of the American Association of Medical Assistants is to provide the medical assistant profession with education, certification, credential acknowledgement, networking opportunities, scope-of-practice protection and advocacy for quality patient-centered health care |
Ray Barry (ice hockey)
William Raymond Barry (October 4, 1928 – August 28, 2018) was an American-born Canadian professional ice hockey player who played 18 games in the National Hockey League. Born in Revere, Massachusetts and raised in Edmonton, Alberta, he played for the Boston Bruins and the Hershey Bears in the 1951-52 season. He died on August 28, 2018 in Calgary.
References
External links
Category:1928 births
Category:2018 deaths
Category:American men's ice hockey centers
Category:Canadian ice hockey centres
Category:Boston Bruins players
Category:Hershey Bears players
Category:Ice hockey people from Alberta
Category:Ice hockey people from Massachusetts
Category:People from Revere, Massachusetts
Category:Sportspeople from Edmonton |
Q:
How to check from hybrid app if the user has disabled push notifications?
I have implemented push notifications to a Worklight application. One of the requirements is to display a message if the user has disabled the push notifications for the application at the OS level.
Is there a way to detect this change? The Worklight's method isPushEnabled: Checks whether push notification is supported.Returns true if the IBM® Worklight® JavaScript API supports push notifications in the current environment.
Even if I disabled push for the AMS App, this method still returns true.
I also searched a solution at the Cordova level but no luck so far.
Thank you
A:
If the users subscribe and unsubscribe on login/logout you could always use the API WL.Client.Push.isSubscribed(alias) to check if the current user is subscribed. If the user is not subscribed you could pop up an alert asking them to subscribe as well as informing them "If you have disabled Push Notification for this application you can re-enable push by going to Settings-> Notification-> AppName".
Without writing Native code I do not know if it is possible to check if the user has disabled push at the OS level. I have seen some solutions written natively though, for example there is some discussion here for iOS:
Enable/Disable Apple Push Notification from iPhone app?
|
Streets of Your Town (TV series)
Streets of Your Town is an Australian two-part factual television documentary that looks at Australian suburbs. The series began on the ABC on 15 November 2016. Tim Ross is a comedian, broadcaster and architecture enthusiast who acts as a tour guide, exploring how and why Australian suburbs look the way they do. Interviewees include Peter McIntyre, Kevin McCloud and Alain de Botton. The series was repeated in May 2017.
References
External links
Official website
Tim Ross - Man About The House
Category:Australian Broadcasting Corporation shows
Category:Australian factual television series
Category:2016 Australian television series debuts
Category:2010s Australian television series
Category:English-language television programs |
Solutions today for tomorrow's information problems
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Disruption
Though it’s a little bit of a puff piece, this is a pretty cool concept. Final has created a credit card that allows you to create an unlimited number of virtual credit cards to provide to online merchants, e.g., Amazon, Netflix. You can have one virtual card for each online merchant. If your card gets…
Startups in the payday lending space say their use of artificial intelligence is allowing them to make better loans at lower rates with fewer defaults. “The power of artificial intelligence versus business intelligence is BI is purely retrospective, whereas AI looks forward into the future and predicts — what will this person do based on…
What goes into building a digital bank? Brian Yurcan of the American Banker looks at two case studies, EQ Bank and BankMobile, to understand how executives develop new, digital-first bank services. The “endeavor involves developing new products, new processes and entirely rethinking [banking],” he writes. “It is so much more than just creating a good mobile…
Where are the credit scores of yesteryear? Writing in the American Banker, columnist Penny Crosman examines the impact of AI and proprietary credit scoring algorithms on the lending industry and consumers. While AI “offers lenders the ability to . . . score those previously deemed unscorable,” Crosman writes, “such scoring techniques also bring uncertainty.” Edited with…
FCA paves way for blockchain-based money. The U.K.’s Financial Conduct Authority (FCA) granted a Small Electronic Money Institution (EMI) registration to blockchain firm Tramonex, making it the first DLT company to gain the EMI designation. Tramonex can now operate as money transmitter and payment facilitator, as well as “issue, distribute and redeem e-money.” Edited with BlogPad… |
The Neuroscience Revolution Will Be Crowdsourced
The editors of Scientific American MIND regularly encounter perspectives on science and technology that we believe our readers would find thought-provoking, fascinating, debatable and challenging. The MIND Guest blog is a forum for such opinions. The views expressed belong to the author and are not necessarily shared by Scientific American. Follow on Twitter @sciammind.
Ben Thomas is an author, journalist, inventor and independent researcher who studies consciousness and the brain. A lifelong lover of all things mysterious and unexplained, he weaves tales from the frontiers of science into videos, podcasts and unique multimedia events. Lots more of his work is available at http://the-connectome.com. Follow on Twitter @theconnectome.
As Albert Einstein famously said, “No problem can be solved from the same level of consciousness that created it.”
The history of science is littered with so-called “intractable” problems that researchers later cracked wide open using techniques their ancestors could hardly imagine. Biologists in the 1950s looked at the staggeringly complex (and beautiful) three-dimensional shapes into which proteins fold and declared that a reliably predictive mathematical model of these convolutions might be unachievable in our lifetimes. But over the past few years, folks with home computers have joined forces to crack many longstanding protein-folding problems using the online game FoldIt.
Instead of relying on the number-crunching power of a single supercomputer or network, crowdsourced games like FoldIt translate vast and complex data sets into simple online interfaces that anyone can learn to operate. The crowdsourced astronomy game Galaxy Zoo also depends on an army of “citizen scientists” for classification of stars hundreds of light years away; while Google built its image search technology on an image-labeling game. In fact, every time you “verify your humanity” on a web form by typing out nonsensical reCAPTCHA text, you’re actually helping Google transcribe books from the world’s libraries into a digital format.
And now, a worldwide team of neuroscience researchers have begun using this crowdsource approach to crack open one of the greatest problems in any scientific field: The construction of a complete wiring diagram for a mammalian brain.
Complexity and simplification
Neuroscientists often compare the task of mapping the brain’s wiring to that of untangling all the cords piled up beneath your desk. It’s just that a human brain contains upward of 84 billion “cords” – nerve cells known as neurons – every one of them sporting multiple “plugs” – connections known as synapses – adding up to as many as 100 trillion (that’s “trillion” with a “t”) interconnections in a single brain.
MIT's Sebastian Seung (far left) and his research group teamed up with (from left to right) Viren Jain, Winfried Denk, Moritz Helmstaedter, Kevin Briggman and Srini Turaga to map the brain's microstructure with an innovative toolbox of techniques.
Throw in the fact that many of these connections are shifting and changing every day, and you can begin to see why some scientists claim that a complete model of a human connectome – a functional map of every neural connection in a human nervous system – is little more than a sci-fi dream right now.
Still, a brain is a finite physical object. Its complexity is enormous, but not ineffable. It can be subdivided into lobes, areas and layers. And just as each level of the ocean and forest is home to its own unique range of life, each layer of the cortex is home mainly to a limited range of specific neuron types, each of which cooperates and competes with others in specific ways.
“If I just told you, ‘There are a lot of trees in a jungle,’ that’d be true, but it’d be a very crude description, because trees come in many different species,” says Sebastian Seung, a neuroscientist at Massachusetts Institute of Technology. “In the same way, neurons come in many cell types, and one of the important tasks in neuroscience today is to identify and enumerate all these different types of neurons in the brain. Nobody knows how many there are.”
This neuron jungle might sound like yet another daunting problem – but in fact, Seung thinks it may provide a simple yet highly accurate way of modeling brain function down at the cellular level. It’s a bit like saying, “We’ll never be able to model the workings of every individual tree in the whole forest – but we don’t have to. All we’ve got to do is understand the behavior of each species.”
Even this is no small task; but Seung and his team have found an innovative way to tackle it.
Solving the unsolvable
Mapping a human connectome demands some conceptual steps up from traditional brain-scanning techniques like fMRI and EEG. So this year, Seung and his colleagues at MIT, along with Moritz Helmstaedter and Winfried Denk at Germany’s Max-Planck Institute for Medical Research, set to work on the problem from a new angle.
The international team succeeded in mapping the precise shapes and points of contact between every single one of the 950 neurons in a block of mouse retina - a first-time achievement in the history of neuroscience.
The researchers chose a very small chunk of nerve tissue – a tiny slice of retina, to be exact – and looked for an efficient way to tease apart its wiring while preserving its structure. “If we take human colorings or tracings of neurons, and we train the computer to emulate them, the computer still makes mistakes,” Seung explains. “So somehow we have to correct the mistakes of the computer – we have to combine human intelligence and artificial intelligence in order to solve this problem.”
The new approach works like this: First, a human operator works through digital slice after slice of brain matter, using computerized tools to draw a “skeleton” of each neuron he or she notices in each slice – similarly to the way computer animators start by drawing a stick figure of an animated character.
Once humans have drawn in these neuronal skeletons, an automated computer algorithm builds out a 3D model of each neuron’s three-dimensional shape. “If people had to color in the full three-dimensional shape of a neuron, instead of just drawing the skeleton, each neuron would take ten to 100 times longer, and the cost of our study could’ve been has high as $10 million,” Seung says. But using this new technique, the international team was able to complete the project at a much lower budget, in a matter of mere months.
In a recent paper published in the journal Nature, Seung and his colleagues at the Max-Planck Institute unveiled their first major success using this approach: A connectomic map of every neuron in a tiny patch of mouse retina. Along the way, the team discovered several new types of neurons, and generated a neuronal wiring map of unprecedented scale and complexity.
Exciting as this retina-mapping project has been, Seung says, it’s only the beginning of his team’s quest for the ultimate goal: A complete map of a human connectome. And to get there, they’re going to need your help.
Crowdsourcing a revolution
Last year, Seung’s lab rolled out a game called EyeWire. The principle is simple: After a few practice rounds, anyone with a computer and an Internet connection can help researchers map the shapes of actual neurons. In the game, these neurons come with their “skeletons” pre-drawn, and players take on the task of coloring in the neurons’ 3D shapes.
Seung and his research assistants developed the crowdsource game EyeWire to enable anyone with a home computer and an Internet connection to help map the trillions of neural connections in a mammalian brain.
Computers and neuroscience experts then compare the results; and if all goes well, the result is a map of a synapse that’s never been mapped before – a brand-new brain discovery made by people just like you.“That makes it a multiplayer game,” Seung says. “People are rewarded for giving the same answers as others, and that’s how they learn. That’s how they’re incentivized to be accurate – and it also makes the game inherently social.”
Seung’s lab is currently putting together the first journal paper documenting brand-new discoveries made with EyeWire. The researchers aim to use this wealth of data to crack another puzzle: How groups of neurons detect motion. “People want us neuroscientists to explain consciousness,” Seung says; “they want us to cure autism. But in fact, for more than 60 years, neuroscientists have been unable to explain how it is that neurons in the retina can detect motion.”
It’s a sobering fact, but one with a silver lining: Thanks to citizen-scientists working through EyeWire puzzles, Seung thinks he and his team have hit on at least one testable explanation of this longstanding neuroscience mystery. To find out what they’ve discovered, though, we’ll have to wait for the upcoming paper.
EyeWire players have already mapped a large number of neurons – and mapping new ones every day – but it’s still clear that long years of work lie between us and our goal of a complete human connectome. The data gathered so far may seem like drop of water in the ocean, but projects like EyeWire are actually proofs-of-concept for a technique of extraordinary power. “It’s clear that is now possible – not easy, but entirely possible – to start mapping mammalian connectomes at the cellular level,” Seung says. “The technology wasn’t there just a few years ago, but technology is advancing rapidly.”
Images: Sebastian Seung
About the Author: Ben Thomas is an author, journalist, inventor and independent researcher who studies consciousness and the brain. A lifelong lover of all things mysterious and unexplained, he weaves tales from the frontiers of science into videos, podcasts and unique multimedia events. Lots more of his work is available at http://the-connectome.com. Follow on Twitter @theconnectome.
5 Comments
Okay, good stuff — but I don’t believe that the Neuroscience Revolution is going to come from increasing information about brain structure, however detailed it might be. What is delaying the revolution is the weakness of our ability to observe the dynamic activity of populations of brain cells.
Along similar lines as the first commentator, having a schematic diagram of the processor circuitry in the device I’m using to access this article allows an enormous variety of software programs to be executing – having the circuit diagram or even an electrical signal trace provides at best little meaningful information regarding the software that is currently executing.
IMO, the human brain is far more than the neural circuit interconnections and chemical microenvironments that control the flow of its electrical signals. The signals it produces also produce the modification of those chemical environments and electrical circuits – it is self-adapting…
What “Neuroscience Revolution” is envisioned, given the exceedingly limited scope of current neuroscience?
I often think celebrity quotes are incorrect, such as Einstein’s in this case. Although I like Albert, his quote doesn’t stand up, say, to the case of Thomas Edison when he made the first electric light. Indeed, he used the same process relentlessly…but tried the process on over 10,000 substances…finally arriving at Tungsten, which was a winner. So, in Edison’s case, persistence at effort…from a certain,unchanging, conscious view…was in fact the right thing to do. Sorry Albert. Nearly all Celebrity quotes can be tossed the other way…Right?
Also, Counting and Mapping Neurons has actually become a scientific prejudice…believe it or not. When Obama gave a large sum of money to the Brain Initiative as it was called…it was quickly pointed out…that the Initiative was going to totally blow by…or omit…the tremendous importantance of Glial cell/calcium Ion messaging. Synapse is not a neuron cell monopoly, right?
I think what Seung is saying…is echoed in many other neurological circles…there really is no effective brain or consciousness theory at the moment. This will probably play out like the physics search for a TOE…a theory of everything for all Fields. In fact, TOE’s themselves will begin to multiple in multiple fields…as more funding and energy are provided. Eventually, all carpenters will have their own hammers…and see the Big U
in that light. It’s a bit relative, right? |
Q:
Java Generic from Activity to fragment to adapter
I am working in android app, have designed a generic adapter and parameterized adapter will inherit this.
public abstract class CarAdapter<T> extends RecyclerView.Adapter<CarAdapter<T>.BaseCarViewHolder> {
protected DialogMakerCar<T> dialogMaker;
protected Context context;
......
child class
public class CarItemAdapter extends CarDialogAdapter<Item> {
public CarItemAdapter(Context context, DialogMakerCar<Item> dialogMaker) {
super(dialogMaker, context);
}
I am calling this adapter in a fragment and that fragment is also need to be generic so that i can call this fragment and adapter for custom objects from activity.
//Fragment to call adapter but its not letting me to use <T> generic
adapter = new CarItemAdapter(getContext(),dialogMaker);
gridRecycler.setHasFixedSize(true);
gridRecycler.setLayoutManager(adapter.getLayoutManager());
Please let me know if you need more details, Thanks
A:
I'm not an Android dev, so can't really give you a real example.
Lets define the interface as following ( I don't know the real method you need so just made a simple example)
public interface ICarAdapter {
public <T> DialogMakerCar<T> getDialogMaker();
public Context getContext();
}
You can defined what the T extends from to avoid warnings when used in the other classes.
Now you need to use this interface in the classes you defined:
public class CarItemAdapter extends DialogMakerCar<Item> implements ICarAdapter{
private DialogMakerCar<Item> dialogMakerCar;
private Context context;
public CarItemAdapter(Context cntxt, DialogMakerCar<Item> dialogMaker) {
dialogMakerCar = dialogMaker;
context = cntxt;
}
/** This will give you a warning, can be avoided
if you define in the interface that T extendes
an interface that Item implements.*/
@Override
public DialogMakerCar<Item> getDialogMaker() {
return dialogMakerCar;
}
@Override
public Context getContext() {
return context;
}
}
In the fragment class:
public class Fragment {
public <T> ICarAdapter createAdapter(T item) {
//You can manage this as you want,
//with a switch, defining an Enum or passing the Class that you want.
if (item instanceof Item) {
return new CarItemAdapter(getContext(),dialogMaker);
}
return null;
}
An then when you want to use it:
public class Activity {
Fragment fragment;
ICarAdapter adapter;
public Activity() {
fragment = new Fragment();
Item item = new Item();
adapter = fragment.createAdapter(item);
adapter.getContext();
adapter.getDialogMaker();
}
Hope at least it helps you a bit.
Other ways to do this:
https://dzone.com/articles/java-generic-factory
https://stackoverflow.com/a/47464801/6708879
Generic factory with unknown implementation classes
|
Henrique I of Kongo
Henrique I Nerika a Mpudi was ruler of the Kingdom of Kongo from 1567 to 1568. Like his predecessor, Henrique died while on campaign at the frontiers of the kingdom. He was killed while fighting the BaTeke of the Anziku Kingdom.
References
See also
List of rulers of Kongo
Kingdom of Kongo
Anziku Kingdom
Category:Manikongo of Kongo
Category:Rulers of the Kingdom of Kongo
Category:1568 deaths
Category:16th-century African people
Category:Military personnel killed in action
Category:Year of birth unknown |
1. Field of the Invention
The invention relates to a method of producing dry sodium dichloroisocyanurate dihydrate.
2. Description of the Prior Art
Alkali metal dichloroisocyanurates, especially the sodium salts, are widely known as a source of available chlorine in sanitizing and bleaching applications. These salts are known to exist in the anhydrous form and in the mono and dihydrate forms when associated with bound water. One of the major drawbacks of employing alkali metal dichloroisocyanurates is the property known as self propagating decomposition. It is known that when these compounds are exposed to high temperature source such as a spark or cigarette they can begin to burn and will continue until all of the material is consumed. It is known, however, that the presence of bound water of hydration lessens the tendency of alkali metal dichloroisocyanurates to decompose in this manner. The dihydrate form of these salts is the most desirable in this respect.
One reason why the dihydrate salt of sodium dichloroisocyanurate has not found wide commercial acceptance is the difficulty in manufacturing this product and more particularly problems associated with the drying step. The most common methods described for drying these salts are vacuum drying, drying in an air circulated oven, and spray drying. As noted in Wenzke, U.S. Pat. No. 3,289,312, none of these methods have provided any commercially acceptable product. Wenzke describes a process in which wet isocyanurate salt solids are fed to a pug mill to which dry anhydrous salt is added to reduce the free water content, followed by drying in a special chamber containing a cage-type mill through which a heated gas stream is flowing. This process is designed to produce an essentially anhydrous product.
Among other techniques proposed for drying this type of compound are the spray granulating process disclosed in Saeman, U.S. Pat. No. 4,005,087; the flash drying method described in Nelson, U.S. Pat. No. 3,951,972, the two-stage fluidized bed drying process described in Japanese Patent Publication No. 43-29,588, and the method of Goelz, U.S. Pat. No. 3,818,002, in which an aqueous solution or suspension of the salt is sprayed into a fluidized bed of dry salt particles and dried by the fluidizing gas. Goelz goes to great lengths to disparage both spray drying and fluidized bed drying of dichloroisocyanurate salts.
The alkali metal dichloroisocyanurate salts dried by the prior art methods have not proved commercially acceptable due to poor stability, and excessive caking and dusting.
Thus, it would be highly desirable to provide a method of drying sodium dichloroisocyanurate dihydrate and related salts which could produce a stable, free-flowing, non-dusting powder product. |
Dissolved and particulate nutrient export from rural catchments: a case study from Luxembourg.
Nutrient enrichment of freshwaters continues to be one of the most serious problems facing the management of surface waters. Effective remediation/conservation measures require accurate qualitative and quantitative knowledge of nutrient sources, transport mechanisms, transformations and annual dynamics of different nitrogen (N) and phosphorus (P) forms. In this paper, nitrate (NO3-N), soluble reactive phosphorus (SRP) and total phosphorus (TP) concentrations and loads are presented for two adjacent rural basins of 306 km2 and 424 km2, and for five sub-basins differing in size (between 1 km2 and 33 km2), land use (extent of forest cover between 20% and 93%) and household pressure (from 0 to 40 people/km2) with the aim of studying the influence of land use and catchment size on nutrient exports. The studied catchments are all situated on Devonian schistous substrates in the Ardennes region (Belgium-Luxembourg), and therefore have similar hydrological regimes. As the study period could not be the same for all basins, annual export coefficients were corrected with the 25 years normalized discharge of the Sure River: two regression analyses (for dry and humid periods) relating monthly nutrient loads to monthly runoff were used to determine correction factors to be applied to each parameter and each basin. This procedure allows for the comparing annual export coefficients from basins sampled in different years. Results show a marked seasonal response and a large variability of NO3-N export loads between forested (4 kg N ha-1 year-1), agricultural (27-33 kg N ha-1 year-1) and mixed catchments (17-22 kg N ha-1 year-1). For SRP and TP, no significant agricultural impact was found. Land and bank erosion control the total P massflow in the studied catchments (0.4-1.3 kg P ha-1 year-1), which is mostly in a particulate form, detached and transported during storm events. Soluble reactive P fluxes ranged between 10% and 30% of the TP mass, depending on the importance of point sources in the basins studied. No relation was found between the size of the basins and the export of nitrate, SRP or TP. Nutrient export, specially for NO3-N and TP, shows significant inter-annual variations, closely linked to inter-annual discharge variations. Flow and load frequency data analysis confirm this association for all the basins on an annual basis. Seasonal or storm specific fluxes strongly deviate from their annual values. |
/*
* Copyright (c) 2016-2020 VMware, Inc. All Rights Reserved.
* This software is released under MIT license.
* The full license information can be found in LICENSE in the root directory of this project.
*/
var WAIT_TIME = 5000;
var WAIT_LOAD_TIME = 5000;
gemini.suite('progress-bar', child => {
// gemini.suite('progress-bar-examples', (child) => {
// child.setUrl('/progress-bars/progress-bar-examples')
// .before((actions, find) => {
// actions.waitForElementToShow('main.content-area', WAIT_TIME);
// actions.wait(WAIT_LOAD_TIME);
// })
// .setCaptureElements('main.content-area')
// .capture('default');
// });
//
// gemini.suite('progress-bar-colors', (child) => {
// child.setUrl('/progress-bars/progress-bar-colors')
// .before((actions, find) => {
// actions.waitForElementToShow('main.content-area', WAIT_TIME);
// actions.wait(WAIT_LOAD_TIME);
// })
// .setCaptureElements('main.content-area')
// .capture('default');
// });
//
// gemini.suite('progress-bar-animations', (child) => {
// child.setUrl('/progress-bars/progress-bar-animations')
// .before((actions, find) => {
// actions.waitForElementToShow('main.content-area', WAIT_TIME);
// actions.wait(WAIT_LOAD_TIME);
// })
// .setCaptureElements('main.content-area')
// .capture('default');
// });
//
// gemini.suite('progress-bar-cards', (child) => {
// child.setUrl('/progress-bars/progress-bar-cards')
// .before((actions, find) => {
// actions.waitForElementToShow('main.content-area', WAIT_TIME);
// actions.wait(WAIT_LOAD_TIME);
// })
// .setCaptureElements('main.content-area')
// .capture('default');
// });
//
// gemini.suite('progress-bar-sidenav', (child) => {
// child.setUrl('/progress-bars/progress-bar-sidenav')
// .before((actions, find) => {
// actions.waitForElementToShow('main.content-area', WAIT_TIME);
// actions.wait(WAIT_LOAD_TIME);
// })
// .setCaptureElements('main.content-area')
// .capture('default');
// });
//
// gemini.suite('progress-bar-loop', (child) => {
// child.setUrl('/progress-bars/progress-bar-loop')
// .before((actions, find) => {
// actions.waitForElementToShow('main.content-area', WAIT_TIME);
// actions.wait(WAIT_LOAD_TIME);
// })
// .setCaptureElements('main.content-area')
// .capture('default');
// });
//
// gemini.suite('progress-bar-static', (child) => {
// child.setUrl('/progress-bars/progress-bar-static')
// .before((actions, find) => {
// actions.waitForElementToShow('main.content-area', WAIT_TIME);
// actions.wait(WAIT_LOAD_TIME);
// })
// .setCaptureElements('main.content-area')
// .capture('default');
// });
//
// gemini.suite('progress-bar-static-cards', (child) => {
// child.setUrl('/progress-bars/progress-bar-static-cards')
// .before((actions, find) => {
// actions.waitForElementToShow('main.content-area', WAIT_TIME);
// actions.wait(WAIT_LOAD_TIME);
// })
// .setCaptureElements('main.content-area')
// .capture('default');
// });
//
// gemini.suite('progress-bar-inline', (child) => {
// child.setUrl('/progress-bars/progress-bar-inline')
// .before((actions, find) => {
// actions.waitForElementToShow('main.content-area', WAIT_TIME);
// actions.wait(WAIT_LOAD_TIME);
// })
// .setCaptureElements('main.content-area')
// .capture('default');
// });
//
// gemini.suite('progress-bar-inline-cards', (child) => {
// child.setUrl('/progress-bars/progress-bar-inline-cards')
// .before((actions, find) => {
// actions.waitForElementToShow('main.content-area', WAIT_TIME);
// actions.wait(WAIT_LOAD_TIME);
// })
// .setCaptureElements('main.content-area')
// .capture('default');
// });
//
// gemini.suite('old-progress-bar-cards', (child) => {
// child.setUrl('/progress-bars/old-progress-bar-cards')
// .before((actions, find) => {
// actions.waitForElementToShow('main.content-area', WAIT_TIME);
// actions.wait(WAIT_LOAD_TIME);
// })
// .setCaptureElements('main.content-area')
// .capture('default');
// });
gemini.suite('progress-bar-examples', child => {
child
.setUrl('/progress-bars/progress-bar-examples')
.before((actions, find) => {
actions.waitForElementToShow('main.content-area', WAIT_TIME);
actions.wait(WAIT_LOAD_TIME);
})
.setCaptureElements('.clr-example')
.capture('default')
.capture('click the 1st show button', function (actions, find) {
this.showButton = find('.prog-example-toggle-0');
actions.click(this.showButton);
actions.wait(2000);
})
.capture('click the 2nd show button', function (actions, find) {
this.showButton = find('.prog-example-toggle-1');
actions.click(this.showButton);
actions.wait(2000);
});
});
gemini.suite('progress-bar-cards', child => {
child
.setUrl('/progress-bars/progress-bar-cards')
.before((actions, find) => {
actions.waitForElementToShow('main.content-area', WAIT_TIME);
actions.wait(WAIT_LOAD_TIME);
})
.setCaptureElements('.clr-example')
.capture('default');
});
gemini.suite('progress-bar-static', child => {
child
.setUrl('/progress-bars/progress-bar-static')
.before((actions, find) => {
actions.waitForElementToShow('main.content-area', WAIT_TIME);
actions.wait(WAIT_LOAD_TIME);
})
.setCaptureElements('.clr-example')
.capture('default');
});
gemini.suite('progress-bar-inline-cards', child => {
child
.setUrl('/progress-bars/progress-bar-inline-cards')
.before((actions, find) => {
actions.waitForElementToShow('main.content-area', WAIT_TIME);
actions.wait(WAIT_LOAD_TIME);
})
.setCaptureElements('.clr-example')
.capture('default');
});
});
|
Pro-parking space group slams Almeria City bike lanes
ALMOST 1,000 people gave support to an anti-bicycle lane platform in Almeria City during its first week.“We aren’t totally against the lanes but we do oppose the massive destruction of parking spaces,” the newly-created Facebook page stated.Its creator, Antonio, explained that the ideal name – ‘Platform against Almeria bike lanes at the expense of parking spaces’ – is too much of a mouthful andadmitted that he had not expected so much support in such a short space of time. He spoke to dozens of people who, like him, are unhappy about the elimination of parking spaces but feel powerless to do anything about it. His mother is one of them, Antonio said.“She asked if there was any point in complaining, because who would take notice of a housewife? That was when I decided to do something,” he added.The platform has now brought in 2,642 ‘likes’ but despite calls to create a physical association, Antonio has his doubts. “My main idea is to make city hall realise that it’s not just a couple of people who oppose this project,” he said.
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The American Petroleum Institute (API) and the International Association of Oil and Gas Producers (IOGP) met at the inaugural Energy Council Business-to-Business Energy Forum in Brussels this week and released a position paper on Thursday to encourage large-scale U.S. liquid natural gas (LNG) importation to Europe.
“We’re experiencing a pivotal moment in U.S. energy leadership, as the number one producer and exporter of natural gas and oil,” Todd Snitchler, API vice president of market development, said in an announcement of the summit and paper. “It’s also a critical time in terms of collaborating and building our Trans-Atlantic LNG relationship, as we have an ability to not only continue to elevate the quality of life in America but globally as well.”
And the benefits of natural gas production go beyond its economic impact, including helping the environment.
“American natural gas has reduced CO2 emissions in the U.S. to the lowest levels we’ve seen in a generation, as well as provided substantial economic benefits to communities across the U.S., and by enabling greater flows of U.S. LNG to the EU we hope to bring more of this clean, affordable and reliable fuel to people around the world,” Snitchler said.
“If we really want to reach our climate objectives in Europe, we need our policymakers to acknowledge the value and role of gas in both in the short, and longer term,” Francois-Régis Mouton, IOGP director of European Union (EU) Affairs said. “The U.S., the UK and others around the world have shown what an impact shifting from coal to gas makes from a CO2 emission reduction and air quality perspective.”
“By making a smart use of Europe’s own gas resources and the LNG supplied by partners such as the U.S., we can bring about a system combining renewables and gas which provides a secure supply of affordable and clean energy to Europeans,” Mouton said.
According to the press release about the meeting and the position paper:
The joint policy recommendations for the U.S. include for the Federal Energy Regulatory Commission (FERC) and the Department of Energy (DOE) to continue to enhance their established review and permitting processes while maintaining transparent and consistent approval timelines; expanding executive branch agency efforts to promote U.S. LNG in EU countries; and for executive branch agencies to highlight U.S. industry standards and promote streamlined approval processes to ensure the construction of critical energy infrastructure in a timely manner.
Regarding recommendations for the EU, the press release stated:
For the EU, the joint policy recommendations include sending consistent signals expressing confidence in the medium and long-term role of natural gas in the EU energy mix; for the European Commission to work with member states to increase interconnectivity and to encourage public entities and businesses to use LNG and compressed natural gas (CNG) in transportation to reduce CO2 emissions and improve air quality; and for the Commission to avoid unduly restrictive gas quality specifications that could create unnecessary barriers for LNG to enter the EU.
According to the U.S. Energy Information Administration (EIA), in 2018 the United States hit record-high natural gas production for the second year in a row.
The EIA also announced in September 2018 that the U.S. became the world’s largest producer of crude oil, surpassing Russia and Saudi Arabia.
Follow Penny Starr on Twitter. |
If you love American football, but hate the idea of physically enduring all that running around and tackling, there’s always been Madden NFL, the video game football simulator that’s been releasing iterative updates annually since 1988. And if you prefer your video-game football with a heavy helping of multitouch gestures, you’ve been able to play Madden on your iOS device since 2009’s Madden 10. On Tuesday, Electronic Arts released its latest iteration of the game for iOS: Madden 12.
Costing $7 for iPhone and $10 for iPad, Madden 12 sports more than 2500 actual NFL players from all 32 teams. You can compete in standalone exhibition games, play through an entire 16-game season, or relive the 2010/2011 playoffs (which no Eagles fan would ever consider doing). EA claims that Madden 12 sports “sharper gameplay and cleaner graphics” than its previous incarnations on iOS.
Among the new features in Madden 12 is the ability to draw custom hot routes for almost any play—running, passing, or defensive. Unlike its Android counterpart, Madden 12 on iOS also includes leaderboards that show you how you stack up against other Madden devotees. (That feature uses EA’s Origin network, and not Apple’s Game Center.)
As in previous editions of the game, you’ll control things with a virtual joystick on one side of your device, and various action buttons—including the ability to slow things down while you trigger specific moves—on the other.
The iPhone and iPod touch version of Madden 12 requires iOS 3.1 or higher; the iPad version requires at least iOS 3.2.
Note: When you purchase something after clicking links in our articles, we may earn a small commission. Read our affiliate link policy for more details. |
WTI and Brent crude oil: average annual spot prices 1990-2016
This graph displays the spot price for West Texas Intermediate and Brent crudes between 1990 and 2016. In 2016, the average spot price for West Texas Intermediate crude oil came to just under 43.14 U.S. dollars per barrel. Brent is a sweet light crude that often used in the manufacture of gasoline. Consequently, Brent is a crucial contributor to gasoline prices. Gas prices in Europe, particularly Norway, are counted among the highest worldwide.
Crude oil spot prices
The world’s growing thirst for oil is likely to create disequilibrium between crude supply and demand, thus triggering price fluctuations at stock exchanges around the globe. Over the last five years, consumption in the United States has increased from 19.2 million barrels per day to 19,396 million barrels per day in 2015. Driven by global economic growth, West Texas Intermediate crude reached annual average price levels near 100 U.S. dollars per barrel for the first time in 2008, when worldwide oil consumption exceeded production by over three million barrels daily. Although the difference can be accounted for by the production of biofuels and oil from unconventional sources, these figures show why adjustment measurements are required to balance supply and demand in the international crude oil market.
Economic theory has it that prices are a key element to adjust supply and demand, but political frameworks appear to be the crucial factor in this case. The WTI price trend will likely be affected by the quality of pipeline infrastructure between the U.S. Gulf and the nation’s oil-trading hub at Cushing, as well as political trends in other oil producing regions. With U.S. shale gas production on the rise, and with Russia accounting for approximately 12 percent of the world’s oil production volume, oil prices may just continue their rollercoaster ride through the next few years. At an estimated 30.32 U.S. dollars in February 2016, one barrel of WTI crude fell to the lowest level since 2011. In March 2017, the price for a barrel of Brent stood at around 49.33 U.S. dollars, while the price for the OPEC basket grades stood at a little over 50.32 U.S. dollars.
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This graph displays the spot price for West Texas Intermediate and Brent crudes between 1990 and 2016. In 2016, the average spot price for West Texas Intermediate crude oil came to just under 43.14 U.S. dollars per barrel. Brent is a sweet light crude that often used in the manufacture of gasoline. Consequently, Brent is a crucial contributor to gasoline prices. Gas prices in Europe, particularly Norway, are counted among the highest worldwide.
Crude oil spot prices
The world’s growing thirst for oil is likely to create disequilibrium between crude supply and demand, thus triggering price fluctuations at stock exchanges around the globe. Over the last five years, consumption in the United States has increased from 19.2 million barrels per day to 19,396 million barrels per day in 2015. Driven by global economic growth, West Texas Intermediate crude reached annual average price levels near 100 U.S. dollars per barrel for the first time in 2008, when worldwide oil consumption exceeded production by over three million barrels daily. Although the difference can be accounted for by the production of biofuels and oil from unconventional sources, these figures show why adjustment measurements are required to balance supply and demand in the international crude oil market.
Economic theory has it that prices are a key element to adjust supply and demand, but political frameworks appear to be the crucial factor in this case. The WTI price trend will likely be affected by the quality of pipeline infrastructure between the U.S. Gulf and the nation’s oil-trading hub at Cushing, as well as political trends in other oil producing regions. With U.S. shale gas production on the rise, and with Russia accounting for approximately 12 percent of the world’s oil production volume, oil prices may just continue their rollercoaster ride through the next few years. At an estimated 30.32 U.S. dollars in February 2016, one barrel of WTI crude fell to the lowest level since 2011. In March 2017, the price for a barrel of Brent stood at around 49.33 U.S. dollars, while the price for the OPEC basket grades stood at a little over 50.32 U.S. dollars.
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Release date
May 2017
Region
Worldwide
Survey time period
1990 to 2016
Method of interview
Online survey
Supplementary notes
Figures from 2014 to 2016 are based on the mean value derived from the year's monthly values. The values for 1990 through 2014 are taken from previous reports. All prices are "Free On Board" (FOB) prices originating from Cushing, Oklahoma and the North Sea region, respectively.
According to the EIA, FOB denotes a transaction whereby the seller makes the product available with an agreement on a given port at a given price; it is the responsibility of the buyer to arrange for the transportation and insurance.
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This is my favorite silly joke which I always tell to people who are sad or sick or just generally need some entertaining. I posted it as a comment for somebody who I thought needed it, but then I figured all that storytelling shouldn't go to waste, so I'm posting it here too.
It is much better told in person, where I use dramatic voices and entertaining hand gestures and body language, but you'll just have to imagine them because this is the Internet.
Now, first you have to know what a Trid is. You're familiar with the Jolly Green Giant? Well there's that little green guy who hangs out with him, right? That's a Trid. Most people don't know this, but there are lots of Trids, a whole village full of them. They all live near the Jolly Green Giant.
One day, one of the Trids decided to talk to the Jolly Green Giant. Remember, Trids are very small. So he climbed a mountain, in order to position himself near the giant's head. He climbed and he climbed and he climbed up the mountain, and when he got to the top, he yelled at the top of his voice, "Hey Jolly Green Giant! What's new besides ho-ho-ho?!"
Well the giant didn't even say anything, he just pulled his leg back, then he kicked the Trid down the hill! And the Trid rolled, and he rolled, and he rolled, then he landed at the bottom, splat!
The Trid was outraged, as you can imagine, but he still wanted to talk to the giant. He decided that he needed help, so he got one of his Trid friends. Together, they climbed and climbed and climbed up the mountain, and when they got to the top, they shouted in unison, "Hey Jolly Green Giant! What's new besides ho-ho-ho?!"
This time the giant wordlessly kicked both Trids down the hill! And they rolled, and rolled, and rolled, then they landed at the bottom, splat!
Well. The Trids decided they needed even more help. So this time the entire village of Trids climbed the mountain. They climbed and climbed and climbed up the mountain, and when they got to the top, the whole village shouted in unison, "Hey Jolly Green Giant! What's new besides ho-ho-ho?!"
Believe it or not, the giant pulled back his leg and kicked the whole village of Trids down the hill! And they rolled, and rolled, and rolled, then they landed at the bottom, splat!
The Trids decided they needed some religious assistance. So they got a Rabbi from a neighboring village to come and help. All the Trids, plus the Rabbi, climbed and climbed and climbed up the mountain, and when they got to the top, the whole village and the Rabbi all shouted in unison, "Hey Jolly Green Giant! What's new besides ho-ho-ho?!"
The giant pulled back his leg, and he kicked all the Trids down the hill, but he left the Rabbi standing there on the top of the mountain. (And the Trids rolled, and rolled, and rolled, then they landed at the bottom, splat!)
The Rabbi, however, was standing there all alone. In confusion, he asked the giant, "I don't understand. Why did you kick all the Trids down the mountain, but leave me here?"
Yeah, I've heard others. "We bulls wobble, but we don't fall down." I don't know the grass houses one though. This has always been my favorite, just for its outrageous silliness, and the shock value when you finally get to the punchline. |
Jiang Chengji
Jiang Chengji (born 25 November 1975) (; born November 25, 1975 in Shanghai) is an international male Chinese butterfly, breaststroke and freestyle swimmer from Shanghai. He competed at the 1996 Summer Olympics in the 100 m butterfly, finishing fourth, 0.07 seconds behind the bronze medal winner. He also finished in 4th place in the 50m freestyle at the same Olympics, 0.04 seconds behind the third place finisher.
Jiang also participated for China in 2000 Summer Olympics in the 50 m freestyle but failed to pass into the later stages, finishing tied 17th, 0.02 seconds outside the time needed to qualify for the semifinals.
Jiang finished third at the 2004–05 FINA Swimming World Cup in the men's freestyle.
On the national stage Jiang also won a record of five gold medals at the Chinese Ninth National Games.
References
Category:1975 births
Category:Living people
Category:Chinese male swimmers
Category:Olympic swimmers of China
Category:Swimmers from Shanghai
Category:Swimmers at the 1996 Summer Olympics
Category:Swimmers at the 2000 Summer Olympics
Category:Asian Games medalists in swimming
Category:Asian Games gold medalists for China
Category:Asian Games silver medalists for China
Category:Swimmers at the 1994 Asian Games
Category:Swimmers at the 1998 Asian Games
Category:Medalists at the 1994 Asian Games
Category:Medalists at the 1998 Asian Games |
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Stephanie Zerwas
Stephanie Zerwas is a psychologist and therapist for children, tweens, teens and adults. She provides counseling for depression, anxiety, and eating disorders. Stephanie is nationally known for her work as a psychotherapist who studies the role of social media on mental health. Her therapy style is warm, empathic, and thoughtful. |
It is a tragic day in Malaysia when grown men like Hishamuddin have succumbed to a bewildering fear of the light.(En/bm/cn)
8 Jul 2011- The Greek philosopher Plato said that “we can forgive a child who is afraid of the dark; the real tragedy of life is when men are afraid of the light”.
It would appear that in Malaysia, there are men holding offices of high power who are inexplicably petrified by the prospect of a group of Malaysians who intend to exercise their basic human rights to gather peacefully to highlight the need to address what they see as electoral flaws. I wish to reiterate DAP’s position of supporting peaceful demonstrations and condemning violent demonstrations.
The act of placing a restriction order on 91 individuals, by barring them from assembling and disallowing them entry into certain spots in Kuala Lumpur this Saturday, is ridiculous and exposes an irrational fear on the part of Home Minister Hishamuddin Tun Hussein Onn and the police.
We agree that conflict and violent demonstrations should be avoided, but from the beginning the Bersih 2.0 rally has always been intended to be a peaceful gathering. There is absolutely no element of violence, despite the painstaking efforts by the Police and the Government to portray it that way.
In fact, the Bersih 2.0 rally was given royal ratification when the Yang di-Pertuan Agong himself deemed fit to grant an audience to Bersih Chairperson Datuk Ambiga Sreenevasan, and to give royal consent to a stadium gathering in any stadium that the Bersih organisers choose.
The Prime Minister himself had advised Bersih to use a stadium, but today we find that his Cabinet Colleagues, in particular the Home Minister, does not understand this simple language. Not only are they not allowing Bersih to use any stadium in the Klang Valley, they have now issued a restriction order on 91 individuals including all Bersih leaders. This is notwithstanding the arbitrary arrests of 193 people over the last few weeks including the 6 from PSM being charged under the Internal Security Act (ISA) 1960!
What is happening to our country when even our leaders are treated as strangers in our own land?
The list of restricted individuals includes not just Bersih leaders Datuk S Ambiga and Parliamentary Opposition Leader Anwar Ibrahim, Mentri Besar of Kelantan Nik Aziz, DAP leader Lim Kit Siang and Selangor State EXCO member Teresa Kok, PAS President Datuk Seri Abdul Hadi Awang and PAS Deputy President Mat Sabu and other PR leaders. How can so many elected leaders of our country be treated as if they are insidious elements?
Let us not forget that the former Bar Council President Datuk Ambiga Sreenevasan was given the Secretary of State’s Award for International Women of Courage by Hillary Clinton and Michelle Obama. The leaders of the world treat her as a courageous woman, yet in Malaysia she is vilified so severely as a public enemy that UMNO leaders ask for her citizenship to be revoked.
Indeed Plato is correct to say that truly it is a tragic day in Malaysia when grown men like Home Minister Hishamuddin have succumbed to a bewildering fear of the light. Or are the police and Hishamuddin still a child who is afraid of the dark and not yet grown men? |
Coordinates and structure factors of the native, native I23 space group, and bulgecin A complexed Cj0843 crystal structures have been deposited with the Protein Data Bank with accession numbers 6CF8, 6CF9, and 6CFC, respectively.
Introduction {#sec001}
============
The bacterial cell wall of Gram-negative bacteria contains a peptidoglycan (PG) sacculus between the outer and inner membranes. The PG is critical to maintain structural and physical integrity of bacteria. The PG layer is a dynamic structure as it needs to be broken down and remodeled during cell growth \[[@pone.0197136.ref001]\], cell division \[[@pone.0197136.ref002], [@pone.0197136.ref003]\], or during formation of large periplasm-spanning structures like flagella or pili \[[@pone.0197136.ref004], [@pone.0197136.ref005]\]. The PG layer is composed of saccharide and amino acid-type building blocks with the saccharide component being a polymer of *N*-acetylglucosamine (GlcNAc) and *N*-acetylmuramic acid (MurNAc). The PG building block GlcNAc-MurNAc-pentapeptide (part of lipid II) is utilized by transglycosylases to polymerase the PG saccharide chains \[[@pone.0197136.ref006]\]. Transpeptidases can subsequently crosslink the peptide moieties of adjacent PG glycan strands. Certain penicillin binding proteins (PBP) can harbor both the transglycosylase and transpeptidase activity. The breakdown of the PG involves a number of enzymes including carboxypeptidases, endopeptidases, amidases, and lytic transglycosylases (LT). The LT enzymes cleave the PG MurNAc-GlcNAc glycosidic bond similar to lysozyme \[[@pone.0197136.ref007]\] with the noted difference that LTs have an additional (2^nd^) cyclization step; this step requires a boat conformation of MurNAc leading to a 1,6-anhydromuramyl product as the predominant terminal saccharide moiety \[[@pone.0197136.ref008], [@pone.0197136.ref009]\]. The active sites of both lysozyme and LT have a conserved glutamic acid which is proposed to act as a proton donor during catalysis of PG degradation \[[@pone.0197136.ref010]--[@pone.0197136.ref012]\]. *E*. *coli* deficient in LT do not exhibit defects in cell growth \[[@pone.0197136.ref013]\] yet such LT mutants can be hypersensitive to antibiotics that inhibit cell wall synthesis \[[@pone.0197136.ref014]\]. Furthermore, a known inhibitor of LT activity, bulgecin A, is known to synergistically inhibit bacterial growth in the presence of β-lactam antibiotics in several Gram-negative bacteria \[[@pone.0197136.ref015], [@pone.0197136.ref016]\]. Therefore, LTs provide an attractive target for the design of inhibitors that can be used in combination with β--lactams to counteract bacterial infections.
Bacterial LTs can be membrane bound or soluble; they are divided into different families and several subfamilies based on their conserved motifs \[[@pone.0197136.ref010], [@pone.0197136.ref017], [@pone.0197136.ref018]\]. Although the overall sequence identity between different LTs is relatively limited, the catalytic glutamic acid and catalytic domain fold are strongly conserved in different families and organisms. We report here structure-function studies of soluble periplasmic LT of *Campylobacter jejuni*. The LT Cj0843 was identified from a virulent strain of *C*. *jejuni* and localized in the periplasm \[[@pone.0197136.ref019]\]. Also, Cj0843 was found to play a role in β--lactam resistance \[[@pone.0197136.ref019]\], and its expression to increase by the presence of mucins \[[@pone.0197136.ref020]\]. Moreover, Cj0843 mutants were also defective in cecal colonization in chickens \[[@pone.0197136.ref019]\]. These results suggest that inhibition of Cj0843 could potentially be therapeutically beneficial to treat campylobacteriosis, one of the most common human infections. Here, we present the crystal structures of LT Cj0843 in the absence and presence of the inhibitor bulgecin A. Furthermore, we carried out biophysical and biochemical analyses as well as molecular dynamics (MD) simulations with PG fragments to yield insights into PG degradation by doughnut-shaped LTs.
Results {#sec002}
=======
Overall structure of *C*. *jejun*i Cj0843 {#sec003}
-----------------------------------------
Both Cj0843 crystal forms reveal an overall protein structure, at 1.87 and 2.28 Å resolution, that adopts a doughnut shape formed by four domains ([Fig 1](#pone.0197136.g001){ref-type="fig"}). The structures from both crystal forms are very similar with a root-mean-square-deviation (RMSD) for 509 Cα atoms of 0.75 Å. At the N-terminus is a small helical domain (NU-domain) connected *via* a flexible linker to the helical U-domain. This flexible linker (residues 75--83) is partially resolved in the P3~1~21 crystal form and fully resolved in the I23 crystal form; it spans 22Å between ordered anchor points I74 and Y84 in the NU-domain and U-domain, respectively. The U-domain anchor point is part of helix α5; this helix is tethered to helix α7 of the U-domain *via* a disulfide bond between C87 and C102. The other end of the U-domain is connected to a distant L-domain *via* a long ordered UL-loop ([Fig 1](#pone.0197136.g001){ref-type="fig"}). Finally, the L-domain is connected to the C-terminal catalytic C-domain. The L- and C-domains of the protein complete the circular doughnut shape as both interact with the NU-domain. The central pore of the 'doughnut' is elliptical and has an inner diameter ranging from 16 to 37Å.
{#pone.0197136.g001}
*C*. *jejuni* is unusual in that it can glycosylate proteins; native Cj0843 was observed to have at least 5 N-linked glycosylation sites, 4 of which had been mapped by mass spectrometry \[[@pone.0197136.ref021]\]. These glycosylated residues are in the U-domain (N99 and N175), L-domain (N329), and C-domain (N376). All four sites are located on the side face or outer perimeter of the doughnut-shaped Cj0843 and are thus distant from the active site ([S1 Fig](#pone.0197136.s001){ref-type="supplementary-material"}; note that the *E*. *coli* expressed Cj0843 is not glycosylated). The exact functional importance of this glycosylation is not known yet general protein glycosylation in *C*. *jejuni* likely increases bacterial viability \[[@pone.0197136.ref022]\].
A structural similarity search of Cj0843 using DALI \[[@pone.0197136.ref023]\] found the *E*. *coli* soluble lytic transglycosylase SLT70 \[[@pone.0197136.ref008], [@pone.0197136.ref024], [@pone.0197136.ref025]\] to have the highest structurally similarity yielding a Z-score of 22.3, representing the number of standard deviations above the mean for this similarity score, and RMSD of 4.5Å for 371 aligned residues with a sequence identity of 19% (PDB ID 1SLY; [Fig 2](#pone.0197136.g002){ref-type="fig"} and [S2 Fig](#pone.0197136.s002){ref-type="supplementary-material"}). This structural similarity is remarkable with the most substantial sequence similarity present in the catalytic C-domain ([S2 Fig](#pone.0197136.s002){ref-type="supplementary-material"}). Recently, the structure of LtgA from *Neisseria meningitides* was determined and found to be very similar to SLT70 \[[@pone.0197136.ref026]\]. Like Cj0843, SLT70 is predominantly an α-helical protein yet about 100 residues longer (645 compared to 541 amino acids for Cj0843; their predicted signal peptide lengths are 27 and 19 amino acids, resp.). Other structurally similar proteins are several membrane LTs such as MltC (PDB ID 4CFP), MltE (PDB ID 2Y8P), MltF (PDB ID 4OYV) with Z-scores around 12--13 (for about 150 aligned residues mostly comprising part of the catalytic domain). The DALI search also found another soluble lytic transglycosylase, SLTB3 of *Pseudomonas aeruginosa* that was structurally similar to Cj0843 with a Z-score of 6.6 and RMSD of 4.9Å for 147 aligned residues (PDB ID 5ANZ)\[[@pone.0197136.ref027]\]. Interestingly, both *E*. *coli* and *P*. *aeruginosa* soluble LTs adopt a doughnut shape, similar to Cj0843 ([Fig 2](#pone.0197136.g002){ref-type="fig"}). The central holes in both Cj0843 and SLT70 are however much larger than that of SLTB3. The crystal structures of these proteins co-crystallized with muropeptides indicating the binding position of PG saccharide moieties ([Fig 2](#pone.0197136.g002){ref-type="fig"}). The circular structure of both SLT70 from *E*. *coli* and SLTB3 *P*. *aeruginosa* suggest that the PG can thread through the hole near the active site of the LT.
{ref-type="fig"}. *E*. *coli* SLT70 (PDB ID: 1QTE; \[[@pone.0197136.ref024]\]) has a similar coloring scheme except it does not have an NU-domain. The SLT70 structure includes a 1,6-anhydromurotripeptide (black sticks) to highlight the location of the active site; the disulfide bond is shown in green. The *P*. *aeruginosa* SLTB3 (PDB ID: 5A07)\[[@pone.0197136.ref027]\] is depicted with a similar muropeptide ligand shown in black sticks; the N-terminal domain (light blue), catalytic domain (red), PG binding domain (purple), and αβ-domain (pink) are shown.](pone.0197136.g002){#pone.0197136.g002}
Cj0843 shares 29--34% sequence similarity with other members of the Epsilonproteobacteria family ([S2 Fig](#pone.0197136.s002){ref-type="supplementary-material"}) such as the exolytic Slt from *Helicobacter pylori*\[[@pone.0197136.ref028]\]; this organism has a postulated link to peptic ulcers and cancer \[[@pone.0197136.ref029], [@pone.0197136.ref030]\]. Their most substantial similarity is located in the catalytic C-domain ([S2 Fig](#pone.0197136.s002){ref-type="supplementary-material"}). The other domains share less sequence conservation in the epsilonproteobacteria LT family yet are nevertheless more similar to each other than to the gammaproteobacteria *E*. *coli* SLT70 ([S2 Fig](#pone.0197136.s002){ref-type="supplementary-material"}). The sequence alignment highlights several regions of sequence conservation that could point to critical functional roles and will be discussed below.
U-domain {#sec004}
--------
The U-domains of Cj0843 and SLT70 are more structurally divergent compared to the other domains. The U-domain of Cj0843 is smaller than SLT70 as it has only 20 α-helices (including the NU-domain helices) compared to SLT70 which has 22 (Figs [1](#pone.0197136.g001){ref-type="fig"} and [2](#pone.0197136.g002){ref-type="fig"}). Also, the α-helices in Cj0843 are in general shorter and not as regularly arranged compared to the supra-helical arrangement in SLT70. An additional difference is that Cj0843 has a split U-domain with a separate N-terminal NU-domain (comprising α1- α4). Being larger, the U-domain of SLT70 completes the circular shape as an entire rigid U-shaped unit without the NU-domain-linker configuration in Cj0843. The Cj0843 U-domain contains a disulfide bond between C87 and C102; it is noteworthy that SLT70 (and LtgA) also contains a disulfide bond in the U-domain (between C106 and C139) providing also structural stability at a similar position along its circular shape (Figs [1](#pone.0197136.g001){ref-type="fig"} and [2](#pone.0197136.g002){ref-type="fig"}). The importance of the disulfide bond for stability was probed using differential scanning fluorimetry (DSF) using the SYPRO orange dye; removing the disulfide bond with reducing agents decreased the melting temperature of Cj0843 from 51.5 to 46.0, a 5.5°C destabilization (Figure A in [S3 Fig](#pone.0197136.s003){ref-type="supplementary-material"}).
A superposition of the Cj0843 U-domain with that in STL70 reveals that the structural similarity in this domain starts with helix α14 (helix 16 in SLT70) and ends with helix α20. The sequence conservation between these two proteins is very limited in this α14-α20 section, in particular near its N-terminus ([S2 Fig](#pone.0197136.s002){ref-type="supplementary-material"}). A DALI search using just the U-domain revealed a structural similarity to *Shigella flexneri* type III secretion chaperone IpgC (Z-score 8.6, RMSD of 2.6Å) despite sharing only 13% sequence identity. Seven of the helices of the U-domain of Cj0843 (α14-α20) superimpose onto the equivalent helices in the TPR motif-containing IpgC. IpgC forms a functional dimer and binds the IpaB peptide in the major curved groove \[[@pone.0197136.ref031]\]. The Cj0843 U-domain uses equivalent faces of its similar 7 helix section to interact with the rest of the U-domain and with the C-domain.
L-domain {#sec005}
--------
The L-domain in Cj0843 is structurally equivalent to the L-domain in SLT70 situated in the same position flanking the C-domain ([Fig 2](#pone.0197136.g002){ref-type="fig"}). The L-domain in Cj0843 has three long α-helices and is smaller compared to the L-domain in SLT70 L-domain which contains 6 helices (4 large and 2 small). The three α helices in Cj0843 are structurally equivalent to 3 of the 4 large helices of the SLT70 L-domain. Like Cj0843, the other members of the epsilonproteobacteria families have the smaller L-domain configuration ([S2 Fig](#pone.0197136.s002){ref-type="supplementary-material"}).
A DALI search with just the Cj0843 L-domain revealed structural similarity to AscG of *Aeromonas hydrophila*, a chaperone component of the type III secretion system (Z-score of 5.1, RMSD 2.6Å for 44 residues). AscG, made up of one-and-a-half TPR motif units, was crystallized in complex with another chaperone AscE \[[@pone.0197136.ref032]\]. AscG uses its helices for protein-protein interactions similar to the corresponding L-domain in LTs interacting with the other LT domains.
C-domain {#sec006}
--------
The C-domains or the catalytic domains of the Cj0843 and SLT70 proteins are structurally very similar in accord with their higher sequence conservation. Most of the active site residues are conserved ([S2](#pone.0197136.s002){ref-type="supplementary-material"} and [S4](#pone.0197136.s004){ref-type="supplementary-material"} Figs as calculated using ConSurf \[[@pone.0197136.ref033]\]) including the catalytic glutamic acid (E390) which is located at the end of helix α25.
A common active site inhibitor of LTs is the natural product bulgecin A which is known to inhibit *E*. *coli* SLT70 \[[@pone.0197136.ref008]\], *H*. *pylori* Slt \[[@pone.0197136.ref015]\], *E*. *coli* MltE \[[@pone.0197136.ref034]\], and *N*. *meningitidis* LtgA \[[@pone.0197136.ref026]\]. To probe whether bulgecin A can also bind to Cj0843, we determined the structure of bulgecin A bound to Cj0843 to 2.04 Å resolution ([Fig 3](#pone.0197136.g003){ref-type="fig"}). Bulgecin A binds in the active site groove with several chemical groups; one of these groups is *N*-acetyl-glucose moiety, a moiety also found in the PG substrate. The *N*-acetyl group hydrogen bonds with the backbone oxygen of Y463 and backbone nitrogen of M410 ([Fig 3B](#pone.0197136.g003){ref-type="fig"}). The hydroxymethyl moiety of the pyrrolidine ring forms a hydrogen bond with the catalytic E390; the pyrrolidine ring nitrogen, likely protonated and mimicking a transition state, is 3.6Å from the carboxyl group of E390 ([Fig 3B](#pone.0197136.g003){ref-type="fig"}). The amide moiety of the pyrrolidine ring forms additional hydrogen bonding interactions in the active site with S399, S401, and E498. The two sulfate moieties of bulgecin A interact either directly or indirectly with the protein; one of the sulfates is situated near the N-terminal end of the α29 helix (near F469) likely providing a favorable helix dipole moment interaction. Bulgecin A binds to the active site of Cj0843 and induces conformational changes that lead to narrowing of the active site groove ([Fig 3C](#pone.0197136.g003){ref-type="fig"}). The distance between M410 and Y463 backbone atoms that hydrogen bond with the *N*-acetyl group decrease from 8.3Å in both unbound structures to 7.5Å in the bulgecin A complex structure ([Fig 3C](#pone.0197136.g003){ref-type="fig"}). Additional clamping movements involve the loop 399--402 and concomitant movement of the NU-domain including residues 59--63. Also, the side chain of F412 flips towards bulgecin A to make 3.5Å anion-pi interactions \[[@pone.0197136.ref035]\] with one of the sulfate moieties of bulgecin A ([Fig 3C](#pone.0197136.g003){ref-type="fig"}). The interaction between Cj0843 and bulgecin A was probed using DSF showing that binding of bulgecin A increased the thermostability of Cj0843 by 9°C (Figure B in [S3 Fig](#pone.0197136.s003){ref-type="supplementary-material"}). This result indicates a strong stabilizing effect of bulgecin A on the Cj0843 structure in agreement with the observation that the active site clamps down on bulgecin A upon binding ([Fig 3C](#pone.0197136.g003){ref-type="fig"}). We subsequently carried out additional DSF measurements of Cj0843 with varying bulgecin A concentrations (only up to 640 μM due to limited availability of the bulgecin A compound, and DMSO concentration considerations); the measured K~d~ of bulgecin A binding to Cj0843 is 210 μM ± 28 μM (Figure C in [S3 Fig](#pone.0197136.s003){ref-type="supplementary-material"}).
{#pone.0197136.g003}
The bulgecin A interactions are similar to those observed for other bulgecin A LT complexes including SLT70 \[[@pone.0197136.ref008]\], SLT35\[[@pone.0197136.ref036]\], MltE \[[@pone.0197136.ref034]\], and LtgA \[[@pone.0197136.ref026]\]. The interacting residues involved are also relatively conserved in the *H*. *pylori* LT, an epsilonproteobacteria LT family member known to be inhibited by bulgecin A \[[@pone.0197136.ref015]\]([S2 Fig](#pone.0197136.s002){ref-type="supplementary-material"}). In concord with the above results, we find that bulgecin A inhibits Cj0843 activity as measured *via* a turbidity assay using substrate PG from the *C*. *jejuni* LT mutant ([Fig 4](#pone.0197136.g004){ref-type="fig"}). Around 50% inhibition is observed at bulgecin A concentrations ranging from 2.5--250μM; a lower concentration of 0.25μM was ineffective as no significant inhibition is to be expected since the 1μM Cj0843 protein concentration in the assay was in excess ([Fig 4A](#pone.0197136.g004){ref-type="fig"}). Consistent with this finding, bulgecin A was also observed to increase the susceptibility of β-lactam resistant *C*. *jejuni* to Amp ([Fig 4B](#pone.0197136.g004){ref-type="fig"}). The Amp resistant *C*. *jejuni* strain could be rapidly killed in the presence of both Amp and bulgecin A after 6 hr of treatment despite its normal growth in the presence of Amp or bulgecin A alone ([Fig 4B](#pone.0197136.g004){ref-type="fig"}).
{#pone.0197136.g004}
Inter-domain linkers {#sec007}
--------------------
Two inter-domain loops or linkers are present in Cj0843. The NU-loop is not well ordered and has an overall basic charge as it contains two lysines. Also, this NU-loop has two prolines which are a common occurrence in mobile linker regions perhaps limiting some flexibility and keeping it away from the attached domain \[[@pone.0197136.ref037]\]. The second linker, the UL-loop, connects the U-domain to L-domain and is well ordered, solvent accessible, and in a roughly similar position in SLT70 yet with limited sequence conservation (Figs [1](#pone.0197136.g001){ref-type="fig"} and [2](#pone.0197136.g002){ref-type="fig"} and [S2 Fig](#pone.0197136.s002){ref-type="supplementary-material"}). Both linker regions (L70-A85 and E289-Q313) were predicted from the amino acid sequence by the DLP-SVM domain-linker predicting server \[[@pone.0197136.ref038]\].
The NU-domain and its interactions with the C-/L-domains {#sec008}
--------------------------------------------------------
The NU-domain is comprised of 4 antiparallel α-helices and has limited structural homologs in the Protein Data Bank. The nearest structural neighbor is the N-terminal domain in translation initiator factor eIF2b-like protein (DALI Z-score of 4.6; RMSD of 2.1Å for 54 Cα; 9% sequence identity; PDBid 4ZEM). The small NU-domain is held together by a hydrophobic core containing I22, L25, I38, Y39, L42, L47, L55, I59, I66, and l70, as well as hydrogen bonds between the conserved D35 and backbone nitrogens of F60 and R61. The NU-domain contacts the C-domain and part of the L-domain through hydrogen bonds, salt bridges, hydrophobic, and van der Waals interactions. NU-domain residue R40 forms a salt-bridge with C-domain residue D428 ([S5 Fig](#pone.0197136.s005){ref-type="supplementary-material"}) whereas NU-domain residues Y36 and Y37 hydrogen bond with D430. The interface also includes van der Waals interactions involving NU-domain residues L25, E28, S31, L32, A33, Y39, R65, and I66. The complementary surface of this interface is comprised of L-domain residues P315, F316, and Q319 and C-domain residues I398, Y402, L404, and F433 ([S5 Fig](#pone.0197136.s005){ref-type="supplementary-material"}). The buried surface at this interface is 678Å^2^ with 57% of this surface being hydrophobic (calculated using PISA \[[@pone.0197136.ref039]\]). The residues of the NU-domain and the C-/L-domain interface are relatively conserved in the epsilonproteobacteria but not in SLT70 as its U-domain contacts only the L-domain ([Fig 2](#pone.0197136.g002){ref-type="fig"} and [S2](#pone.0197136.s002){ref-type="supplementary-material"} and [S4](#pone.0197136.s004){ref-type="supplementary-material"} Figs). This linker-tethered NU-domain and its interactions with the rest of Cj0843 is one of the most salient differences between the structures of Cj0843 and SLT70, and suggests an important conserved functional requirement to maintain the circular nature of soluble LTs in the epsilonproteobacteria family.
Conserved electrostatic surface features and implications for interactions with PG {#sec009}
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The most prominent feature of the electrostatic potential surface of Cj0843 is its predominantly positively charged inner ring surface ([Fig 5](#pone.0197136.g005){ref-type="fig"}). Remarkably, this inner ring surface feature is conserved in SLT70 (and LtgA; [Fig 5](#pone.0197136.g005){ref-type="fig"}) which shares very little sequence conservation with Cj0843 apart from the C-domain ([S2 Fig](#pone.0197136.s002){ref-type="supplementary-material"}). The outer ring surface of these ring-shaped proteins shows a more random distribution of positive, negative, and neutral residues. This ensemble of positive charges on the inside of the ring of Cj0843 explains why the majority of sulfate and acetate ions, that co-crystallized at 200mM concentration in both crystal forms, were observed along the inner ring of the doughnut-shaped Cj0843 protein ([S6 Fig](#pone.0197136.s006){ref-type="supplementary-material"}). Although predominantly positively charged along the inner ring, both Cj0843 and SLT70 (and LtgA) contain a small negatively charged cavity within the central pit. This localized electrostatic exception is due to the presence of the active site residues E390 and E498 in Cj0843 and the equivalent glutamic acids in SLT70 and LtgA ([Fig 5](#pone.0197136.g005){ref-type="fig"}). Overall, the conservation of the positively charged electrostatic surface in the inner rings of Cj0843 and SLT70 suggests a potential functional role in both proteins. A likely role is to attract the negatively charged carboxyl groups of the peptide PG sections in which a single tetrapeptide contains three carboxylates. To predict potential ligand binding pockets on Cj0843, we used SiteMap (Schrodinger) \[[@pone.0197136.ref040]\]. The active site groove (labeled '1' in [Fig 5](#pone.0197136.g005){ref-type="fig"}) received the second highest score of 0.98 whereas the top site ranked site with a score of 1.08 is a strongly positively charged pocket (labeled '2' in [Fig 5](#pone.0197136.g005){ref-type="fig"}). Most of the residues in this pocket 2 are amongst the most conserved in the epsilonproteobacteria LTs ([S4 Fig](#pone.0197136.s004){ref-type="supplementary-material"}) further pointing to an important role. In SLT70, this pocket 2 interacts with the peptide section of the PG GlcNAc-anhMurNAc-L-Ala-L-Ala fragment \[[@pone.0197136.ref024]\].
![The electrostatic surface potential of Cj0843, SLT70, and LtgA.\
The electrostatic surface calculations were done using APBS \[[@pone.0197136.ref041]\], and two opposite views of the doughnut-shaped proteins are shown. The active site groove is indicated by an arrow and labeled '1'; the positively charged pocket 2 is indicated by a yellow '2'.](pone.0197136.g005){#pone.0197136.g005}
To probe the mechanistic importance of Cj0843's doughnut shape and its charge distribution for recognizing the PG substrate, including in pocket 2, we carried out four sets of MD simulations. These sets of MD simulations have the PG strands modeled into the active site either (i) in a substrate-binding mode with either a deprotonated or (ii) protonated E390, (iii) a product-binding mode, or (iv) a more unbiased PG starting position situated mostly outside the central hole of Cj0843. In the substrate PG, the GlcNAc and 1,6-anhydro-MurNAc units on the reducing end that are to be cleaved off are numbered as +1 and +2; the adjacent saccharide moieties prior to the cleaved bond are numbered -1 through -8. In the product PG strand, the +1 and +2 moieties are not present, and the -1 unit has become a 1,6-anhydro-MurNAc termini. The starting position for the substrate-binding mode was obtained by modeling a 5 disaccharide unit PG strand into the active site with the GlcNAc-2 in the same position as the GlcNAc in the bulgecin A complex structure. The ring of the PG MurNAc-1 with its hydroxyl-C6-methyl moiety was positioned similarly to the hydroxyl-methyl-pyrrolidine from the bulgecin A complex structure. The starting positions of the GlcNac+1 and 1,6-anhydro-MurNAc+2 were guided by the SLT70:1,6-anhydromurotripeptide complex \[[@pone.0197136.ref024]\]. The second set of substrate-bound simulations was carried out with the only difference being protonation of E390. For the third set of simulations, the starting position for the product-binding mode was acquired by modeling a 4 disaccharide unit PG strand in the active site with a similar starting position for the GlcNAc-2 and 1,6-anhydroMurNAc-1 moieties as in the substrate simulations yet without the (cleaved) +1 and +2 saccharide moieties. MD simulations for both the substrate and product PG strands were carried out in quadruplicates each with slightly different initial orientations/conformations of both termini of the PG strand. In the final set of MD simulations, the starting PG positions for all moieties but the terminal tetrapeptide were situated outside the central hole. Overall, the root-mean-square-deviation (RMSD) for main chain atoms over time averaged around 3Å (Figures A-D in [S7 Fig](#pone.0197136.s007){ref-type="supplementary-material"}). The largest root-mean-square-fluctuations (RMSF) occurred in the NU-loop and adjacent helices in the U-domain (Figures E-I in [S7 Fig](#pone.0197136.s007){ref-type="supplementary-material"}).
MD of PG in substrate-binding mode {#sec010}
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The two sets of MD simulations of the PG in the substrate-binding mode ([Fig 6A](#pone.0197136.g006){ref-type="fig"}) were analyzed in detail in both the pocket 2 region ([S8 Fig](#pone.0197136.s008){ref-type="supplementary-material"}) and in the adjacent active site groove ([S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"}). These analyses indicate that a number of hydrogen bonds persist throughout most of the independent 60-100ns MD runs: an internal hydrogen bond between the nitrogen of Ala51 of the terminal PG peptide moiety and the O6 atom of 1,6-anhydroMurNAc+2 (Figure B and G in [S8 Fig](#pone.0197136.s008){ref-type="supplementary-material"}), a hydrogen bond of the GlcNAc+1 with S399 and backbone oxygen of E390 (Figures B, C, G, and H in [S8 Fig](#pone.0197136.s008){ref-type="supplementary-material"}), a hydrogen bond of the O6 atom of MurNAc-1 with the catalytic E390 (Figures C and H in [S8 Fig](#pone.0197136.s008){ref-type="supplementary-material"}), hydrogen bonds of the main chain atoms of Y463 and M410 with the *N*-acetyl group of GlcNAc-2 (Figures B and G in [S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"}), and hydrogen bonds of MurNAc-3 with main chain nitrogens of G468 and F469 (Figures D and I in [S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"}).
{#pone.0197136.g006}
The most significant difference between the deprotonated and protonated E390 MD runs is the distance between the catalytic E390 carboxyl group and the O4 oxygen-containing glycosidic bond that E390 assists to undergo cleavage (between MurNAc-1 and GlcNAc+1; Figure A in [S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"}). All 4 MD runs with the protonated E390 yielded a distance of just over 4Å between this O4 atom and the CD atom of deprotonated E390 carboxyl moiety (Figure H in [S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"}). This short distance is only present in the last of the deprotonated E390 MD runs (up to \~75ns; Figure C in [S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"}). Another difference is that all 4 MD runs with the protonated E390 showed instances where the MurNAc-1 ring adopts a boat conformation, with runs 2 and 3 more long-lived and runs 1 and 4 more fleeting (Figure H in [S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"}). This boat conformation was tracked by measuring the distance between C1 and C6 atoms of MurNAC-1, which is \~3.1 and \~3.7Å for the boat and chair conformations, respectively. In contrast, this boat conformation was observed in only the fourth of the deprotonated E390 MD runs (Figure C in [S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"}; the chair to boat conformational change occurred during the 900ps NPT run before the production run 4). This MurNAc-1 boat conformation results in its O6 hydroxyl being within hydrogen bonding distance to the O4 atom of GlcNAc+1 as shown in a 48.59ns time point snapshot of run 3 of the protonated MD run ([Fig 7](#pone.0197136.g007){ref-type="fig"}). The distance between the O6 MurNAc-1 atom and the CD atom of E390 is also more consistently conducive to hydrogen bonding of the O6 atom with the E390 carboxylate oxygens in the protonated E390 MD runs compared to the non-protonated runs (Figures C and H in [S8 Fig](#pone.0197136.s008){ref-type="supplementary-material"}). This hydrogen bonding network, as observed in the 48.59ns time point snapshot, involving E390, the O4 atom of GlcNAc+1, and the O6 atom of MurNAc-1 is just one observed possibility ([Fig 7](#pone.0197136.g007){ref-type="fig"}); future QM/MM analyses could pinpoint the precise hydrogen bonding pattern that occurs during catalysis. In the boat conformation, the acetamide moiety of MurNAc-1 can form hydrogen bonding interactions with the mostly conserved E498 and S401 residues ([Fig 7](#pone.0197136.g007){ref-type="fig"}). These PG:LT interactions involving E498 and S401 are similar as observed in the bulgecin A:LT complex (Figs [3B](#pone.0197136.g003){ref-type="fig"} and [7B](#pone.0197136.g007){ref-type="fig"}). Furthermore, GlcNAc+1's nitrogen makes a hydrogen bond with the backbone oxygen of E390 ([Fig 7](#pone.0197136.g007){ref-type="fig"}). This hydrogen bond is analogous to what GlcNAc makes in the GlcNAc-MurNAc-D-Ala-D-Ala complex with SLT70 \[[@pone.0197136.ref024]\]. The other PG interactions in the run 3 snapshot, involving GlcNAc-2 and MurNAc-3 ([Fig 7](#pone.0197136.g007){ref-type="fig"}), are similar to those described above.
{ref-type="fig"}. Hydrogen bonds are depicted as dashed black lines. MurNAc-1 ('*M-1'*) is observed to be in a boat conformation. Hydrogen atoms for PG and protein are not depicted except for the hydrogens on the protonated side chain of E390 and on the O6 atom of MurNAc-1. B Schematic diagram of the PG strand interactions in the active site of Cj0843 (left, from 57.82 ns time point) compared to the crystal structure of bulgecin A bound in the active site (right).](pone.0197136.g007){#pone.0197136.g007}
The three carboxylate moieties of the terminal tetrapeptide attached to 1,6-anhydroMurNAc+2 make electrostatic interactions within the positively charged pocket 2 on Cj0843. This pocket harbors 8 Arg or Lys residues; their distances to the carboxylates on the terminal PG tetrapeptide residues D-Glu52, DAP53, and D-Ala54 are plotted versus simulation time (Figures D-F and I-K in [S8 Fig](#pone.0197136.s008){ref-type="supplementary-material"}; [S1 Video](#pone.0197136.s013){ref-type="supplementary-material"}). During all 8 trajectories, a minimum of one salt bridge interaction is observed for the tetrapeptide with an additional second salt bridge being present most of the time. Occasionally, up to five salt bridge interactions are observed such as in run 2 of the deprotonated E390 run at around 60ns (Figures D, E, and F in [S8 Fig](#pone.0197136.s008){ref-type="supplementary-material"}). The Glu52 carboxylate favors the subpocket lined by R388, R392, and K505---making interactions with one or more of these residues throughout most of the trajectories. In addition to these PG interactions, we also monitored the width of the active site cleft as well as the variable distance between the α-helices that anchor the NU-loop allowing the circumference of the circular Cj0843 to vary. Furthermore, we monitored the NU-domain interface *via* the distance between A33 and I398, and measured the distance of the L-domain relative to the active site (Figures E and J in [S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"}). Finally, we also monitored the distances of the individual PG disaccharide units and tetrapeptide sections with respect to the active site (Figures F and K in [S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"}). The disaccharide units that are furthest from the active site show the largest distance variations due to limited interactions with Cj0843 being mostly outside its central hole; their attached tetrapeptide moieties show even larger distance fluctuations likely due to these being more flexible compared to the disaccharide units. These additional analyses also show that the active site width, both in the deprotonated and protonated E390 MD series, can occasionally expand. For example, such widening takes place at time points \~12ns and \~65ns in run 1 (Figure E in [S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"}; deprotonated E390 MD series) with a concomitant loss of 1 or 2 hydrogen bonds involving the GlcNAc-2 *N*-acetyl group (Figure B in [S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"}). In this run, the GlcNAc-2-MurNAc-1 disaccharide slips out of the active site from the 65ns time point onward (Figures B-C in [S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"}). This latter event results in an active site widening, now partially empty, that is even more pronounced around the 86ns time point till the end of the run 1 simulation (Figure E in [S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"}). Note that the MurNAc-3 interactions in the active site remained stable during this event (Figure D in [S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"}). While the NU-domain interaction with the rest of Cj0843 remains intact, the distances between the helices α4 and α5 that span the NU-loop between them are remarkably variable allowing the doughnut-shaped ring of Cj0843 to contract and dilate (Figures E and J in [S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"}). The L-domain contains three of the R/K residues, and its center of mass relative to the active site shows some modest fluctuations (Figures E and J in [S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"}).
MD of PG in product-binding mode {#sec011}
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The 260ns MD simulations of the PG strand in the product-binding mode reveal similarities with the substrate-binding mode simulations ([Fig 6B](#pone.0197136.g006){ref-type="fig"} and [S10 Fig](#pone.0197136.s010){ref-type="supplementary-material"}). These similarities involve an internal hydrogen bond between the nitrogen of Ala41 of the terminal PG peptide moiety and the O6 atom of 1,6-anhydroMurNAc-1 (Figures A-B in [S10 Fig](#pone.0197136.s010){ref-type="supplementary-material"}), the hydrogen bonds of the main chain atoms of Y463 and M410 with the *N*-acetyl moiety of GlcNAc-2 (Figure G in [S10 Fig](#pone.0197136.s010){ref-type="supplementary-material"}), and hydrogen bonds of MurNAc-3 with main chain nitrogens of G468 and F469 (Figure H in [S10 Fig](#pone.0197136.s010){ref-type="supplementary-material"}). Additional relatively persistent hydrogen bond interactions involve the backbone oxygen of D-Glu42 with the backbone nitrogen of V400 (Figure C in [S10 Fig](#pone.0197136.s010){ref-type="supplementary-material"}) as well as the internal salt-bridge interaction of the carboxylate moiety of D-Glu42 and the amine group of DAP43 (occurring about 50% of the time), both belonging to the terminal PG peptide section (Figure B in [S10 Fig](#pone.0197136.s010){ref-type="supplementary-material"}). Interestingly, the terminal tetrapeptide section, now attached to 1,6-anhydroMurNAc-1, makes one or more salt-bridge interactions with the positively charged pocket 2 on Cj0843 virtually the entire length of the simulations (Figures D-F in [S10 Fig](#pone.0197136.s010){ref-type="supplementary-material"} and [S2 Video](#pone.0197136.s014){ref-type="supplementary-material"}). The terminal tetrapeptide residues DAP43 and D-Ala44 can make salt bridge interactions in pocket 2 whereas residue D-Glu42 does not as it cannot reach far enough. These observations indicate that the positive charged pocket 2 can interact with the terminal tetrapeptide carboxyl moieties of the PG when bound in a substrate-binding mode as well as the product-binding mode; this despite the latter having a substantially shorter reach as it lacks the cleaved off disaccharide PG unit. The product simulations also showed instances where the width of the active site can become enlarged, such as around 135ns in run 1 and 95ns in run 2 (Figure I in [S10 Fig](#pone.0197136.s010){ref-type="supplementary-material"}); this leads to a concomitant loss of the hydrogen bond between the GlcNAc-2 and the backbone nitrogen of M410 (Figure G in [S10 Fig](#pone.0197136.s010){ref-type="supplementary-material"}). The two helices that anchor the NU-loop also show considerable variability in their distance from each other during each of the runs (Figure I in [S10 Fig](#pone.0197136.s010){ref-type="supplementary-material"}) as also observed in the substrate MD runs. As in the substrate MD runs, the disaccharide units furthest from the active site show the largest distance variations due to their location being mostly outside the central hole (Figure J in [S10 Fig](#pone.0197136.s010){ref-type="supplementary-material"}).
MD of PG in starting position outside central pore {#sec012}
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To probe whether a PG strand could find its way to the active site groove and positively charged pocket 2 in a more unbiased manner, we positioned a 5 disaccharide unit PG strand such that only its terminal tetrapeptide moiety is within the central pore with the remainder of the PG strand positioned in the solvent region. We ran the simulations four times with starting orientations of the PG strand each differing by \~90° in rotation parallel to the central axis of the doughnut-shaped Cj0843. Of the four independent MD runs of 140ns each, two runs resulted in the PG strand entering the central hole whereas the other two runs did not. The two MD runs that showed the PG successfully entering the inner pore were continued for total simulation times of 560ns and 1μs, respectively. In the longest MD run, the PG strand approached and interacted with the positively charged peptide pocket 2 *via* its terminal tetrapeptide; this is similar to the interactions observed in the substrate and product MD simulations ([Fig 8](#pone.0197136.g008){ref-type="fig"}, [S11 Fig](#pone.0197136.s011){ref-type="supplementary-material"}, and [S3 Video](#pone.0197136.s015){ref-type="supplementary-material"}). This tetrapeptide pocket 2 interaction formed at \~310ns and persisted for the remainder of the simulation; it appears to anchor and thus restrict the movement of the entire PG strand (Figures A-C in [S11 Fig](#pone.0197136.s011){ref-type="supplementary-material"}). While this pocket 2 anchoring brought the PG saccharide strand in closer proximity to the active site, the PG saccharide strand did not enter into the active site groove during the 1μs simulation. Nevertheless, the anchoring of the PG strand caused the -2, -1, +1, and +2 saccharide units to be aligned with these moieties' positions in the substrate-binding mode except for a final upward approach towards the active site groove ([Fig 8D](#pone.0197136.g008){ref-type="fig"}). Though not observed within the 1μs simulation, this final movement required for productive substrate-binding is relatively minor as the GlcNAc-2 *N*-acetyl nitrogen atom was within 7.0Å of the backbone oxygen of Y463 around the 560ns time point ([Fig 8D](#pone.0197136.g008){ref-type="fig"} and Figure E in [S11 Fig](#pone.0197136.s011){ref-type="supplementary-material"}); this distance is generally around 3Å to facilitate the critical hydrogen bond interaction that occurs both in the product and substrate-binding modes (Figs [6](#pone.0197136.g006){ref-type="fig"} and [7](#pone.0197136.g007){ref-type="fig"}, Figures B and G in [S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"}, and Figure G in [S10 Fig](#pone.0197136.s010){ref-type="supplementary-material"}). Prolonged, extended simulations will likely capture the completion of this PG approach into the active site groove but are beyond the scope of this work.
{ref-type="fig"} yet with black italicized labels). The 1,6-anhydroMurNAc moiety is colored darker and labeled bold 'aM+2' for both PG strands in each panel. The labels of the moieties of the terminal disaccharide unit to be cleaved off in both the MD PG strand and the reference PG substrate strand are underlined. Residue E390 is labeled and shown in black sticks, and the Arg/Lys residues are shown with green carbon atoms as in [Fig 6](#pone.0197136.g006){ref-type="fig"}. The view is slabbed showing a side view that is roughly in a similar orientation as [Fig 1B](#pone.0197136.g001){ref-type="fig"}. B The PG strand after the NVT and NPT equilibration step but before the production MD run. C Snapshot at 150ns showing the PG has entered the pore but is bound unproductively distant from the active site E390. D Snapshot at 559.6ns showing that the terminal tetrapeptide section has reached the positively charged pocket 2 and makes similar carboxyl interactions as the equivalent tetrapeptide section in the comparison substrate modeled PG strand (arrows). At this latter time point, the glycan strand has approached the active site the closest within the entire 1μs simulation; the nitrogen of the *N*-acetyl moiety of GlcNAc-2 residue is within 7Å the Y463 main chain oxygen. Also, the anchoring in pocket 2 lined up the correct MurNAc-1 and GlcNAc+1 with respect to their equivalent moieties in the substrate-binding mode (red dashed lines) to facilitate cleavage of the terminal disaccharide PG unit pending the final approach to the active site groove.](pone.0197136.g008){#pone.0197136.g008}
The width of the (empty) active site groove was more expanded and more variable in the 1μs simulation with the PG placed outside compared to the substrate and product-binding mode simulations in which the active site groove was occupied by the PG strand (Figure F in [S11 Fig](#pone.0197136.s011){ref-type="supplementary-material"} and [S12 Fig](#pone.0197136.s012){ref-type="supplementary-material"}). A similar active site groove narrowing was observed upon bulgecin A binding ([Fig 3C](#pone.0197136.g003){ref-type="fig"}). As with the previous simulations, the doughnut-shaped ring of Cj0843 was observed to contract and dilate as allowed by the stretching and compacting of the flexible NU-loop; this lead to fluctuations in distance between the α4 helix of the NU-domain and the α5 helix of the U-domain (Figure I in [S7 Fig](#pone.0197136.s007){ref-type="supplementary-material"} and Figure F in [S11 Fig](#pone.0197136.s011){ref-type="supplementary-material"}).
Discussion {#sec013}
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The crystal structure of the soluble LT Cj0843 from *C*. *jejuni* revealed an unusual doughnut-shaped structure containing four domains: NU-, U-, L-, and C-domains ([Fig 1](#pone.0197136.g001){ref-type="fig"}). Its closest known structural homolog is *E*. *coli* SLT70 \[[@pone.0197136.ref008], [@pone.0197136.ref024], [@pone.0197136.ref025]\], despite Cj0843 being about 100 residues shorter and having only significant sequence similarity in the catalytic C-domain ([Fig 2](#pone.0197136.g002){ref-type="fig"} and [S2 Fig](#pone.0197136.s002){ref-type="supplementary-material"}). Cj0843 nevertheless has a similar sized central hole which is formed by a flexible linker-NU-domain configuration that completes the protein's ring shape ([Fig 1](#pone.0197136.g001){ref-type="fig"}). Sequence analysis of other epsilonproteobacteria family LT members show that this ring-completing NU-domain interface is conserved ([S2](#pone.0197136.s002){ref-type="supplementary-material"} and [S4](#pone.0197136.s004){ref-type="supplementary-material"} Figs), suggesting an important functional role. The interface between the NU-domain and the L-/C-domains is only 678Å^2^, on the smaller end of observed protein-protein interfaces; such an interface corresponds to a projected weak affinity of around 10μM \[[@pone.0197136.ref042]\]. However, the NU-domain is physically tethered to the U-domain *via* a ten residue linker making the local effective concentration of this NU-domain very high; we calculate this local concentration to be \~5mM (1 molecule in a volume of a sphere with a diameter of (10+1) residues x 3.8 Å average Cα-Cα distance). This calculation indicates that despite its anticipated low inherent NU-domain affinity for the rest of Cj0843, its high local concentration will keep the interface intact for the majority of the time thereby maintaining the protein's circular shape. Even during the 1μs MD simulation, the NU-domain interaction with C- and L-domains remained intact (Figure F in [S11 Fig](#pone.0197136.s011){ref-type="supplementary-material"}). One potential mechanistic purpose for the soluble LTs ring-shaped architecture is to facilitate processivity of PG cleavage as previously proposed based on their circular shape \[[@pone.0197136.ref043]\]. An additional purpose could be preventing degradation of critical internal PG sections by allowing only non- or minimally cross-linked end sections of PG strands to fit through the central hole. Such non- or minimally cross-linked sections can arise as a result PBP-directed antibiotics which inhibit the transpeptidase reaction yet leave the transglycosylase reaction intact causing structural defects in the PG layer, a defect that can be corrected by LT activity \[[@pone.0197136.ref044]\].
The non-catalytic domains of Cj0843 have distant structural similarity with protein domains involved in protein:protein interactions with each of the obtained DALI Z-scores scores being substantially above the 2.0 cut-off indicating significant similarities \[[@pone.0197136.ref045]\]. Both the L- and U-domain share structural similarity to bacterial chaperone proteins involved in type III secretion systems, AscG and IpgC, respectively. Whether coincidental or due to either divergent or convergent evolution, it is interesting to note that *C*. *jejuni* is naturally competent for transformation \[[@pone.0197136.ref046]\] which could facilitate a divergent evolutionary mechanism. An additional connection is that LTs function in type III secretion systems in many Gram-negative bacteria \[[@pone.0197136.ref047], [@pone.0197136.ref048]\] and are essential for virulence. There is also structural similarity between the L- and U-domains as both domains contain a TPR-like fold which is a common protein-protein interaction motif \[[@pone.0197136.ref049], [@pone.0197136.ref050]\]; such a motif seems well suited for the cumbersome purpose of generating a complicated doughnut-shaped structure *via* inter-domain interactions. The L-domain also forms a vital part of the positively charged pocket 2 to which it provides three R/K residues; the MD simulations indicate that this pocket has a role in anchoring the terminal tetrapeptide moiety. Finally, also the NU-domain shares structural similarity with a protein speculated to be involved in protein:protein interactions: the N-terminal domain of eIF2B, a domain that is postulated to be important for interacting with other proteins \[[@pone.0197136.ref051]\].
We showed that Cj0843 can bind to and is inhibited by bulgecin A (Figs [3](#pone.0197136.g003){ref-type="fig"} and [4](#pone.0197136.g004){ref-type="fig"} and Figures B-C in [S3 Fig](#pone.0197136.s003){ref-type="supplementary-material"}); the measured K~d~ for bulgecin binding was 210 μM ± 28 μM. Bulgecin A did however not result in complete inhibition of Cj0843 ([Fig 4A](#pone.0197136.g004){ref-type="fig"}). This partial inhibition could perhaps be due to relative modest binding affinity of bulgecin A as well as the likely processive nature of the reaction with the PG strand: once anchored into pocket 2, the PG strand stays in very close proximity to the active site groove thereby perhaps blocking bulgecin A entry while it continues to degrade the PG strand. The narrowing of the active site upon bulgecin A ([Fig 3C](#pone.0197136.g003){ref-type="fig"}) and PG binding ([S12 Fig](#pone.0197136.s012){ref-type="supplementary-material"}) is analogous to that previously observed for PG binding to SltB3 \[[@pone.0197136.ref027]\].
Although the catalytic rates for Cj0843 and SLT70 are not known, the k~cat~ for several other LTs has been determined. These k~cat~ values were measured to be 0.45, 2.52, and 19.9s^-1^ for *P*. *aeruginosa* MltB \[[@pone.0197136.ref052]\], SltB1 \[[@pone.0197136.ref053]\], SltB3 \[[@pone.0197136.ref027]\], respectively. Due to their similar active sites, it is likely that the Cj0843 reaction occurs on a similarly slow timescale. Obviously, our MD simulations with a maximal length of 1μs are not long enough to capture an entire lytic reaction cycle yet nevertheless likely captures key events that occur during the reaction. These events include the stable anchoring interactions of the negatively charged terminal tetrapeptide in pocket 2 in the substrate, product, and random starting position MD runs. The latter simulation showed that the PG aligns itself with the catalytic machinery for cleavage of the terminal disaccharide PG unit, thus promoting exolytic activity ([Fig 8D](#pone.0197136.g008){ref-type="fig"}). Additionally, we observed in both MD simulations and crystal structures, a stabilizing clamping or pinching motion of the active site upon bulgecin A ([Fig 3C](#pone.0197136.g003){ref-type="fig"}) or PG strand binding ([S8](#pone.0197136.s008){ref-type="supplementary-material"}--[S12](#pone.0197136.s012){ref-type="supplementary-material"} Figs). Key pinch points are the backbone atoms of M410 and Y463 that form hydrogen bonds with the most deeply embedded portion of either bulgecin A or PG, the N-acetyl group of the GlcNAc. MD simulations showed that the PG bound active site undergoes breathing motions that allow an occasional widening of the active site and subsequent loss of these N-acetyl interactions and a partial PG release from the active site ([S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"}, run 1). Furthermore, the MD simulations also showed that a protonated E390 leads to more catalytically conducive distances between the E390 carboxyl and O4 atom of the PG bond to be cleaved (Figure H in [S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"}). Finally, the simulations also showed that the active site can promote the chair-to-boat conformational change of the MurNAc-1 moiety (Figures C and H in [S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"}); the boat conformation is needed during one of the steps of catalysis to allow the O6 atom to nucleophilically attack the C1 atom to form the 1,6-anhydro-MurNAc end.
Based on our above results, we propose the following events to occur during the hydrolysis of a PG strand in the active site of Cj0843 ([Fig 9](#pone.0197136.g009){ref-type="fig"}). This enzyme serves as a model for other epsilonproteobacterial LTs ([S2 Fig](#pone.0197136.s002){ref-type="supplementary-material"}), gammaproteobacterial LTs (such as SLT70 and Slts from *Pseudomonas aeruginosa* and *Stenotrophomonas maltophilia*; \[[@pone.0197136.ref018]\]), and betaproteobacterial LTs (such as LtgA; [Fig 5](#pone.0197136.g005){ref-type="fig"}):
{ref-type="fig"}. The 8 R/K residues in pocket 2 are indicated, and several additional R/K labels are drawn for illustrative purposes. In addition to E390 (black sphere), M410 and Y463 are labeled 'M' and 'Y', respectively. A narrowing of the active site groove is depicted in states 6--8 with an accompanying shift of the flanking NU-domain. The boat conformation of MurNAc-1 is drawn in state 6. The tetrapeptide sections of the 5 PG disaccharide units are colored as in Figures F and K in [S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"} and [S3 Video](#pone.0197136.s015){ref-type="supplementary-material"}.](pone.0197136.g009){#pone.0197136.g009}
1. [*Electrostatic steering*]{.ul}: The PG 1,6-anhydro-MurNAc terminus of a non- or minimally-cross-linked section of a PG strand can fit and enter the central hole attracted by the positively charged inner surface (state 2 [Fig 9](#pone.0197136.g009){ref-type="fig"}).
2. [*Terminal tetrapeptide homing to pocket 2*]{.ul}: The negatively charged tetrapeptide moieties of the PG strand will interact transiently with the positively charged patches present along the mostly convex surface of Cj0843 until the terminal tetrapeptide finds the positively charged pocket 2. The concave positively charged pocket, with 8 R/K residues available for multivalent interactions with the three tetrapeptide carboxyl moieties, is likely to form relatively strong substrate interactions due to avidity (state 3 [Fig 9](#pone.0197136.g009){ref-type="fig"}).
3. [*Aligning PG strand and bond to be cleaved*]{.ul}: As this tetrapeptide of the 1,6-anhydroMurNAc becomes initially anchored in pocket 2 (in particular utilizing R388, R392, and K505 with R388 being 12.5Å from E390), it limits the movement of the entire PG strand and allows the PG strand to scan positions near the active site more efficiently (state 4 [Fig 9](#pone.0197136.g009){ref-type="fig"}). The anchoring and accompanying distance considerations likely also provide a molecular ruler that favors the alignment of the -1 and +1 saccharides with the catalytic machinery, such as to promote exolytic activity *via* cleaving off the terminal disaccharide PG unit.
4. [*PG strand enters active site groove*]{.ul}: The PG saccharide strand next enters the active site groove (state 5 [Fig 9](#pone.0197136.g009){ref-type="fig"}) with a subsequent narrowing of this groove due to the multiple PG active site interactions including with M410 and Y463 (state 6 [Fig 9](#pone.0197136.g009){ref-type="fig"}). The -1 and +1 saccharide moieties, and flanking groups, are held in their respective positions in part by the terminal Glu52 residue interacting with the R388, R392, and K505 containing subpocket. The boat conformation of MurNAc-1 is hypothesized to be needed for the cyclization step after the protonated E390-assisted cleavage of the bond between MurNAc-1 and GlcNAc+1 \[[@pone.0197136.ref008]\]. MD simulations indicate that transition to the boat conformation can also occur before cleavage, making the two halves of the reaction more concerted.
5. [*PG strand cleavage and product formation*]{.ul}: E390-assisted PG bond cleavage leads to release of the terminal disaccharide unit (state 7 [Fig 9](#pone.0197136.g009){ref-type="fig"}). After this bond cleavage, the second half of the reaction takes place: MurNAc, in the boat conformation, cyclizes to form the terminal 1,6-anhydroMurNAc-1 to complete the product formation. This step involves a nucleophilic attack of the C1 oxocarbonium intermediate by the O6 atom after proton abstraction by E390 \[[@pone.0197136.ref008], [@pone.0197136.ref018]\]. This step is likely aided by the observed interactions of the conserved E498 with the nitrogen of the acetamide moiety of the MurNAc-1 and the S401 interaction with the oxygen of this acetamide group. Analogous interactions were postulated for SLT70 to occur at this step \[[@pone.0197136.ref008]\] and are also observed in the bulgecin A complex for its equivalent N-acetyl moiety ([Fig 3B](#pone.0197136.g003){ref-type="fig"}). The anhydroMurNAc has a low affinity for the protein \[[@pone.0197136.ref024]\], resulting in the release of the cleaved disaccharide-tetrapeptide from the active site and pocket 2 area.
6. [*New (product) tetrapeptide termini swings over to pocket 2*]{.ul}: The tetrapeptide moiety of the new terminus, 1,6-anhydroMurNAc-1, can swing over to interact with the positively charged pocket 2 *via* its terminal two carboxylates (state 8 [Fig 9](#pone.0197136.g009){ref-type="fig"}).
7. [*Product PG strand dislodgement from active site groove*]{.ul}: While the product PG is now newly anchored to pocket 2, the saccharide strand can be dislodged from the active site groove without the PG strand wandering away from the active site region. This PG dislodgment from the groove can occur when the active site is occasionally widening leading to loss of the Y463/M410 hydrogen bonds while the tetrapeptide sections are concomitantly pulling on the PG strand (state 9 [Fig 9](#pone.0197136.g009){ref-type="fig"}). The terminal tetrapeptide can subsequently enhance its electrostatic interactions in pocket 2 using all three of its carboxylates with a likely vital role for the second PG amino acid carboxylate interacting with the R388, R392, and K505 sub-pocket ([Fig 7](#pone.0197136.g007){ref-type="fig"}). This interaction is similar to the equivalent Ala carboxyl moiety in the SLT70 GlcNAc-MurNAc-D-Ala-Ala complex interacting with the conserved SLT70 R476 \[[@pone.0197136.ref024]\]([S2 Fig](#pone.0197136.s002){ref-type="supplementary-material"}).
8. [*Pocket 2-aided ratcheting of PG strand to facilitate processivity of next exolytic cleavage*]{.ul}: While enhancing the pocket 2 interactions with all of its three terminal carboxyl moieties, the PG strand slides deeper through the central hole such that the next terminal disaccharide unit to be cleaved approaches the active site E390. The PG strand will now enter the active site groove again to start the next lytic transglycosylase reaction cycle (state 10 [Fig 9](#pone.0197136.g009){ref-type="fig"}). This processivity may continue until the PG strand is degraded or a PG section is encountered that is too cross-linked to fit through the central hole of Cj0843.
We note that these postulated mechanistic steps are likely the dominant catalytic path, but we anticipate that exceptions at specific steps can occur as a) the mostly exolytic SLT70 was found to also have some minor endolytic activity, and b) the final cyclization step generating the 1,6-anhydroMurNAc can occasionally be skipped \[[@pone.0197136.ref009]\]. The importance of the tetrapeptide moieties in several of the steps in the above mechanism explains why SLT70 was found not to hydrolyze isolated poly-GlcNAc-MurNAc \[[@pone.0197136.ref054]\]. A postulated key role for the second amino acid (i.e., Glu52) in the tetrapeptide PG degradation is consistent with the observed PG peptide lengths. As the length of the peptide moieties in PG can vary from penta-, tetra-, tri-, and dimeric in *C*. *jejuni* \[[@pone.0197136.ref055]\] and other bacteria, even a PG with a minimal dipeptide length can thus likely be degraded. This degradation would be facilitated by binding the key carboxylate of the second residue with the conserved R388, R392, and K505 residues.
The central hole of the Cj0843, SLT70, and LtgA is much more substantial than that in SLTB3 (Figs [2](#pone.0197136.g002){ref-type="fig"} and [5](#pone.0197136.g005){ref-type="fig"}) with the size of the pore being much larger than a single PG strand. This observation suggests that additional mechanism(s) act to promote processivity, such as to prevent a single PG strand from exiting prematurely after a single cleavage event. Such a mechanism might be the postulated ratchet mechanism in [Fig 9](#pone.0197136.g009){ref-type="fig"} that enhances the mostly exolytic nature of this class of doughnut-shaped LTs and processivity in degrading PG strands. Future studies will include QM/MM dynamics to simulate detailed mechanistic steps including proton abstraction events during the reaction as well as to probe whether the hole of the larger LTs can accommodate two cross-linked PG strands.
Materials and methods {#sec014}
=====================
Protein expression and purification {#sec015}
-----------------------------------
The Cj0843 expression vector (Cj0843-pET28b) was used for expression as previously described \[[@pone.0197136.ref019]\]. The protein was expressed by inoculating LB with overnight transformations of BL21 star cells (ThermoFisher) with Cj0843-pET28b. Once the culture reached an OD600 of 0.5, the protein expression was induced with 0.5mM IPTG. Four hours after induction, the cultures were harvested by centrifugation and resuspended in lysis buffer containing 50mM sodium phosphate pH 8.0, 300 mM sodium chloride, and 20mM imidazole. The cells were lysed using a microfluidizer; 5 mM MgCl~2~ and 5 mM ATP was added to the supernatant to remove bound chaperones. After centrifugation, pre-equilibrated Ni-NTA beads (Qiagen) were added to the supernatant followed by rocking at 4°C. The beads with bound proteins were washed with the lysis buffer and the protein was eluted with 50 mM sodium phosphate pH 8.0, 300 mM sodium chloride, and 300mM imidazole. Glycerol was added to the eluate (final concentration 10%) which was flash frozen in liquid nitrogen and stored at -80°C until further use. The protein was further purified using gel filtration Superdex 200 10/300 column (GE Life Sciences) pre-equilibrated with 1x PBS buffer. The protein eluted as a monomer and was determined to be \>95% pure by SDS-PAGE.
The selenomethionine derivatized Cj0843 was expressed using the van Duyne protocol \[[@pone.0197136.ref056]\] and purified using the same protocol described above except that the buffers also included 2mM β-mercaptoethanol.
Crystallization, data collection, and refinement {#sec016}
------------------------------------------------
The protein buffer was exchanged to 10 mM Hepes pH 7.5 using a 30KDa MWCO concentrator (Millipore). Native and selenomethionine derivatized Cj0843 was crystallized using 0.2 M lithium sulfate, 0.1 M Tris pH 8.0, and 39% PEG 400. The thin hexagonal crystals were frozen in liquid nitrogen without additional cryo-protection. Multi-wavelength anomalous dispersion (MAD) diffraction data were collected at the Selenium K-edge absorption peak (0.9791Å), inflection (0.9793Å), and remote wavelengths (0.9116Å; [Table 1](#pone.0197136.t001){ref-type="table"}). The P3~1~21 space group data were processed using Autoxds (A. Gonzalez and Y. Tsai, SSRL) \[[@pone.0197136.ref057]\] and the crystallographic phases were solved using Autosol \[[@pone.0197136.ref058]\]([Table 1](#pone.0197136.t001){ref-type="table"}). The initial model generated by Autosol was further rebuilt using Coot \[[@pone.0197136.ref059]\] and refined against a higher resolution 1.88Å native dataset of Cj0843 using Phenix \[[@pone.0197136.ref060]\] and Refmac \[[@pone.0197136.ref061]\]. The model contains residues 19--76 and 81--532 with residues 77--80 not modeled due to poor density. Cj0843 was also crystallized in a different space group, I23, for which crystals diffracted to 2.3Å ([Table 1](#pone.0197136.t001){ref-type="table"}). After molecular replacement using Molrep \[[@pone.0197136.ref062]\] with the coordinates from the P3~1~21 structure, the subsequent refinement of this I23 space group structure yielded a model of Cj0843 containing residues 18--533. Crystals of Cj0843 in the P3~1~21 space group were also used for soaking experiments involving bulgecin A (2.4mM for 40 min) which yielded a 2.04Å structure with bulgecin A bound in the active site ([Table 1](#pone.0197136.t001){ref-type="table"}). Topology and parameter files for bulgecin A for refinement in REFMAC were obtained using PRODRG \[[@pone.0197136.ref063]\]. Coordinates and structure factors of the native, native I23 space group, and bulgecin A complexed Cj0843 crystal structures have been deposited with the Protein Data Bank with accession numbers 6CF8, 6CF9, and 6CFC, respectively.
10.1371/journal.pone.0197136.t001
###### Data collection, structure solution, and refinement statistics for Cj0843 data sets.
{#pone.0197136.t001g}
Data collection Native Native I23 Bulgecin A complex Selenomethionine multi-wavelength anomalous diffraction
-------------------------------------------- ---------------- ---------------------- ----------------------------- --------------------------------------------------------- --------------------- -----------------
Wavelength (Å) 0.97946 0.97940 0.97946 0.9791 (peak) 0.9793 (inflection) 0.9116 (remote)
Data range 38.82--1.87 38.09--2.28 50--2.04 38.8--2.45 38.73--2.47 38.64--2.47
Space group P3121 I23 P3~1~21 P3~1~21 P3~1~21 P3~1~21
a = b, Å 74.64 178.67 74.29 73.56 73.44 73.29
c, Å 194.09 178.67 190.46 193.98 193.63 193.21
Completeness (outer shell)(%) 98.3 (80.9) 99.6 (97.5) 99.1 (99.6) 99.4 (94.8) 99.6 (96.3) 99.5 (95.8)
Unique reflections (outer shell) 51659 (2700) 42902 (6096) 39342 (3871) 23057 (2423) 22435 (2385) 22329 (2355)
Total number of observations (outer shell) 983855 (33284) 1731887 (227827) 224186 458457 (47762) 430769 (35614) 437577 (45042)
Average multiplicity (outer shell) 19.0 (12.3) 40.4 (37.4) 5.7 (5.2) 19.9 (19.7) 19.2 (14.9) 19.6 (19.1)
Mean I/sd(I) (outer shell) 16.3 (2.1) 21.5 (2.2) 11.6 (2.0) 16.7 (2.8) 16.4 (1.8) 15.1 (2.0)
R~merge~ 0.092 (0.510) 0.111 (2.533) 0.134 (0.647) 0.168 (1.351) 0.153 (1.619) 0.172 (1.769)
**Phasing**
Resolution 38.8--2.48
Number of Se sites 13
Mean FOM 0.56
**Refinement**
R ~work~ 0.191 0.200 0.177
R ~free~ 0.242 0.232 0.220
Resolution (Å) 38.82--1.87 38.82--2.29 50--2.04
Ligands 7 sulfate ions 1 PEG 2 acetate ions 1 bulgecin A 9 sulfate ions
Number of water molecules 409 224 291
RMSD bong length, (Å) 0.009 0.009 0.010
RMSD bond angles, (°) 1.29 1.29 1.31
Differential scanning fluorimetry {#sec017}
---------------------------------
A concentration of 5μM Cj0843 with 10x SYPRO orange fluorescent dye in 1xPBS buffer was used to determine the melting temperature using a Biorad CFX96 instrument. The temperature was ramped up from 20 to 95°C. Standard deviations for the triplicate experiments were found to be below 0.3°C. For obtaining a quantitative measure of bulgecin A affinity for Cj0843, duplicate DSF measurements were carried out with varying concentrations of bulgecin A (5 μM-- 640 μM). The DSF data was analyzed using GraphPad Prism (Graphpad Software, La Jolla, CA) using the Single Site Binding formula \[[@pone.0197136.ref064]\].
*C*. *jejuni* growth assay {#sec018}
--------------------------
An *in vitro* growth assay was performed in a microtiter plate to determine if bulgecin A can potentiate the efficacy of ampicillin (Amp) against β-lactam resistant *C*. *jejuni*. Briefly, the Amp resistant *C*. *jejuni* strain JL974 \[[@pone.0197136.ref019], [@pone.0197136.ref065]\] was grown to exponential phase and was inoculated in Müller-Hinton (MH) broth (200 μL/well) or MH broth supplemented with Amp (128 μg/mL, sublethal concentration), bulgecin A (100 μg/mL), or Amp (128 μg/mL) plus bulgecin A (100 μg/mL). Duplicate wells were used for each specific growth medium. The cultures were incubated at 42°C under microaerophilic condition (85% N2, 10% CO2, 5% O2) for 30 h. During the incubation, 20 μL of samples were taken at different time points (0, 6, 24 and 30 h), serially diluted, and plated on MH agar for enumeration of *Campylobacter* colonies in each sample. The log~10~-transformed colony-forming units (CFU) for each sample was used to compare the growth of the *C*. *jejuni* strain in different media.
Lytic transglycosylase turbidity activity assay {#sec019}
-----------------------------------------------
The turbidimetric assay to monitor LT activity was carried out similarly as previously described \[[@pone.0197136.ref019]\]. PG substrate was isolated from *C*. *jejuni* 81--176 derivative using chloroform extraction method \[[@pone.0197136.ref019]\] with slight modification. In brief, the overnight grown Cj0843 mutant of *C*. *jejuni* 81--176 from 10 Mueller-Hinton plates were harvested and suspended in 40 ml 0.5x PBS (pH7.4). 3 Ml of chloroform was subsequently added to the suspension, and the mixture was gently rocked at room temperature for 30min. Subsequently, the chloroform-extracted crude PG cell walls were pelleted by centrifugation and washed once with 1x PBS (pH7.4). Finally, the crude PG was resuspended in 40 mL of 1x PBS. When turbidity activity measurements were performed, 1μM Cj0843 enzyme is added to the turbid PG cell wall suspension in PBS buffer at 20°C; the reaction volume is 75μl, and the absorbance at 450 nm was measured using a Molecular Devices FilterMax F5 apparatus. The 4.5hr assay was carried out at room temperature and performed in triplicate.
Molecular dynamics simulations {#sec020}
------------------------------
The Cj0843 protein coordinates and all crystallographic water molecules from the I23 space group were selected as starting coordinates for MD simulations as this structure contains the entire NU-loop/linker. The addition of protons and histidine protonation state assignments were carried out using Maestro/Schrodinger Protein Preparation Wizard (Schrodinger, LCC). The VMD software was utilized to place the protein in a rectangular box of water molecules extending 12.5Å in each direction from the protein surface (typical box of around 112 Å x 103 Å x 103 Å). Sodium and chloride ions were added to neutralize the system as well to set the concentration to 0.15M NaCl \[[@pone.0197136.ref066]\]. NAMD was used for MD simulations with the protein using the CHARMM force field parameters \[[@pone.0197136.ref067]\]. The CHARMM parameters for the PG were obtained from Gumbart et al \[[@pone.0197136.ref068]\] with modifications to include the 1,6-anhydro-MurNac termini. Regarding the PG substrate, tetramer peptide L-Ala-D-iGlu-*meso*-Dap-D-Ala was used as it is the predominant PG peptide unit in *C*. *jejuni* \[[@pone.0197136.ref055]\]. The starting conformations of the GlcNAc-MurNAc-tetrapeptide was guided by PDBid coordinates 3d2y, 5ctv, 4gvi, 2cb3, 1qte, and 3td5 containing these moieties. To obtain a starting conformation for modeling the entire PG strands near Cj0843, 4 disaccharide unit and 5 disaccharide unit (i.e., GlcNAc-MurNAc-tetrapeptide) PG strands were subjected to MD simulations by themselves for at least 8ns under similar conditions as for the protein. Bonds with hydrogen atoms were kept rigid using the SHAKE algorithm, and the time-step was 2fs. The system was first minimized for 3,000 steps and equilibrated for 2ps at 300K and an additional 100ps at 310K using NVT (constant number of particles, volume, and temperature). This step was followed by an equilibration NPT (= constant number of particles, pressure, and temperature) molecular dynamic run for 900ps at 310K and 1.01325 bar. After this, the production MD runs were carried out for time periods of 60ns up to 1μs at 310K. The switching function for treating van der Waals interactions was applied between 10 and 12Å. Electrostatic interactions were treated using the particle mesh Ewald summation (PME) with a grid spacing of 1.0Å. Four sets of MD simulations were carried out with Cj0843 with a PG strand comprised of either 4 or 5 disaccharide units; the terminal MurNAc on the reducing end was modeled as a 1,6-anhydro-MurNAc ([Table 2](#pone.0197136.t002){ref-type="table"}). One set of MD simulations had the 5 disaccharide unit PG strand modeled in a substrate-binding mode with a deprotonated catalytic E390. The second set was identical except that the E390 was protonated (a protonated catalytic glutamic acid residue is postulated to aid in the mechanism of LTs \[[@pone.0197136.ref008], [@pone.0197136.ref018]\]). The third set of MD simulations had the 4 disaccharide PG strand modeled as the product in the active site. The fourth set of MD simulations had a 5 saccharide PG strand modeled in a more unbiased starting position situated mostly outside the central hole; this starting position had only the 1,6-anhydro-MurNAc end partially enter the hole in the mechanistically productive entry direction. Each set of MD simulations was comprised of 4 independent runs. Snapshots of the MD productions runs were saved every 10ps for subsequent analysis using the VMD software.
10.1371/journal.pone.0197136.t002
###### Overview of different molecular dynamics simulations carried out for Cj0843 with PG.
{#pone.0197136.t002g}
PG starting position PG length (\# disaccharide-tetrapeptide units) Length MD runs (ns) \# of independent runs Variations in separate runs regarding starting position/ conformations of PG
---------------------------------------------------- ------------------------------------------------ -------------------------- ------------------------ -----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
PG in substrate- binding mode 5 100 4 G-2, M-1, G+1, AnhM+2 moieties modeled as guided by bulgecin A complex and related LT complex structures; other glycan and tetrapeptide moieties positions varied
PG in substrate- binding mode with protonated E390 5 60 4 Same as above
PG in product-binding mode 4 260 4 G-2 and AnhM-1 modeled as guided by bulgecin A complex; other glycan and tetrapeptide moieties positions varied
PG positioned in random starting position 5 140, 140, 560, and 1,000 4 Extended PG strand positioned mostly outside central pore (only terminal tetrapeptide of AnhM+2 is in center of the hole). Each run had a different PG starting orientation varied by a 90° rotation along the central axis of the pore
Supporting information {#sec021}
======================
###### Glycosylation sites mapped onto the Cj0843 structureCj0843.
Native glycosylation sites N99, N175, N329, 376 are shown in spheres with grey carbon atoms. Catalytic E390 is shown in black spheres. The view is related to [Fig 1B](#pone.0197136.g001){ref-type="fig"} *via* a 90° rotation around the horizontal central axis. Domain colors are same as in [Fig 1](#pone.0197136.g001){ref-type="fig"}.
(TIF)
######
Click here for additional data file.
###### Sequence alignment of Cj0843 with LTs from other epsilonproteobacteria and *E*. *coli* SLT70.
The alignment contains homologous LTs from *Helicobacter pylori*, *Epsilonproteobacteria bacterium*, *Sulfurovum lithotrophicum*, *Nitratiruptor* sp. SB155-2, *Lebetimonas* sp. JH292, and SLT70 from *E*. *coli*. The underlined SLT70 residues are in structurally equivalent positions in Cj0843. Residues are color-coded based on conservation; red residues are identical to the Cj0843, residues in orange are similar. The yellow boxed residues show the additional L-domain helix in SLT70. The C87-C102 disulfide bond is indicated in purple line. Blue boxes highlight residues at the interface between the NU-domain and the rest of Cj0843. Residues interacting either directly or indirectly (water-mediated) with bulgecin A are highlighted with a black oval. The black box shows the conserved catalytic glutamic acid. Positively charged residues with a blue bar above them are situated in the positively charged pocket 2.
(TIF)
######
Click here for additional data file.
###### Melting temperature changes of Cj0843 upon reducing its disulfide bond and binding bulgecin A.
(*A*) DSF measurements of Cj0843 in the absence or presence of 10mM DTT and 10mM β-mercaptoethanol.
(*B*) DSF measurements of Cj0843 in the absence or presence of 1.7mM bulgecin A; a 3% DMSO control is included.
(*C*) DSF measurements of Cj0843 with varying concentrations of bulgecin A. Experiments were carried out in duplicate (1.67% DMSO included in the assays).
(TIF)
######
Click here for additional data file.
###### Conserved residues plotted on the surface of Cj0843.
The degree of sequence conservation in Epsilonproteobacteria is color-coded onto the surface of the protein. The NU-domain, with the NU-loop removed, was moved 15Å away to expose the residues at the interface of C-domain, L-domain, and NU-domain. The figure was generated using ConSurf, and residue conservation ranges from non-conserved (dark blue/cyan) to conserved (dark magenta). The left and right figure are different orientations such that their views expose both sides of the C-/L-domain--NU-domain interface each highlighted by a dotted oval. Also conserved is the active site region labeled '2' encompassing pocket 2 and the active site groove.
(TIF)
######
Click here for additional data file.
###### Close-up stereo view of the NU-domain interface with the C- and L-domains of Cj0843.
Color coding of the individual domains is as in [Fig 1](#pone.0197136.g001){ref-type="fig"}.
(TIF)
######
Click here for additional data file.
###### Crystallographically observed ligands bound to the inner ring/active site region in the three Cj0843 structures.
The following molecules were observed with their locations labeled in parentheses: Bulgecin A (1 with carbon atoms in cyan), a PEG molecule (2) and acetate ions (3 and 8; with carbon atoms in green) from the I23 space group structure, and sulfate ions (3--8) from either the bulgecin A complex or P3~1~21 apo Cj0843 structure. Sites 3 to 7 are located in the positively charged pocket 2. The slabbed view into the active site is along an axis perpendicular to the axis of the doughnut-shaped Cj0843 similar to the view in [Fig 3](#pone.0197136.g003){ref-type="fig"}. The C-domain (red), L-domain (yellow), U-domain (blue), and NU-domain (blue/green) are shown with the surface patch comprised of atoms of E390 shown in black.
(TIF)
######
Click here for additional data file.
###### The RMSD versus simulation time and versus residue of the MD runs of Cj0843 with different starting positions of the PG strands.
(*A*) 5 Disaccharide unit PG strand in the substrate-binding mode with deprotonated E390.
(*B*) Same as A but with protonated E390.
(*C*) 4 Disaccharide unit PG strand in the product-binding mode.
(*D*) 1μs MD simulation of 5 disaccharide PG strand with an unbiased starting position.
(*E*) RMSF per residue of the substrate MD runs with deprotonated E390.
(*F*) Same as E but with protonated E390.
(*G*) RMSF per residue of the product MD runs.
(*H*) RMSF per residue of the 1μs MD simulation of 5 disaccharide PG strand in an unbiased starting position. The runs 1, 2, 3, and 4 of the substrate and product MD simulations in A-C and E-G are colored blue, orange, grey, and yellow, respectively.
(*I*) Tube representation of Cj0843 at the end of the 1μs MD simulation color-coded by average RMSF per residue ranging from 0.5 to 5.0Å corresponding to blue-green-red, respectively. The Cj0843 orientation is similar as in [Fig 1A](#pone.0197136.g001){ref-type="fig"}.
(TIF)
######
Click here for additional data file.
###### Inter- and intra-molecular distances near pocket 2 of the PG strand in the substrate-binding mode MD runs.
The catalytic E390 was either deprotonated (*B*-*F*) or protonated (*G*-*K*).
(*A*) Close-up view of pocket 2 area of the active site of Cj0843 with PG strand in substrate-binding mode. Color coding and orientation are the same as in [Fig 6A](#pone.0197136.g006){ref-type="fig"} except a more zoomed in view is shown. Distances that are monitored are shown as colored dashed lines and correspond to those in subsequent panels *B*, *C*, *G*, and *H*.
(*B*) Distances plotted versus time between the CD atom of PG Glu52 and NZ atom of PG DAP53 (blue), the *N*-acetyl nitrogen atom of GlcNAc+1 and the backbone O atom of E390 (red), the nitrogen atom of PG Ala51 and the O6 atom of AnhMurNAc+2 (magenta).
(*C*) Distances are shown for the O6 atom of GlcNAc+1 and the CD atom of E498 (black), O6 atom of MurNAc-1 and the CD atom of E390 (magenta), and the O3 atom of GlcNAc+1 and the OH atom of S399 (green).
(*D*) Distances of the carboxyl CD of PG Glu52 and the NZ atoms of indicated K residues or CZ atoms of indicated R residues.
(*E*) Same as (*D*) but with PG carboxyl atom CZ of DAP53.
(*F*) Same as (*D*) but with PG carboxyl C atom of Ala54.
(*G*)-(*K*) Same as (*B*)-(*F*) but with protonated E390 residue during the simulations.
(PDF)
######
Click here for additional data file.
###### Inter- and intra-molecular distances near active site groove of the PG strand in the substrate-binding mode MD runs.
The catalytic E390 was either deprotonated (*B*-*F*) or protonated (*G*-*K*).
(*A*) Close-up view of active site groove of Cj0843 with PG strand in substrate-binding mode. Distances that are monitored are shown as colored dashed lines and correspond to those in subsequent panels *B*-*D* and *G*-*I*.
(*B*) Distances plotted versus time between the oxygen of the *N*-acetyl moiety of GlcNAc-2 and the backbone nitrogen of M410 (red) and between the nitrogen of the *N*-acetyl moiety of GlcNAc-2 and the backbone oxygen of Y463 (blue).
(*C*) Distances of the O4 atom of GlcNAc+1, belonging to the bond to be cleaved, and the CD atom of E390 (black), and between the C6 and C1 atoms of MurNAc-1 indicative of a chair or boat conformation (brown). A black arrow indicates instances where a boat conformation starts.
(*D*) Distances between the O3 atom of MurNAc-3 and the backbone nitrogen of F468 (yellow), the oxygen atom of the *N*-acetyl moiety of MurNAc-3 and the backbone nitrogen of F469 (pink), the oxygen atom of the *N*-acetyl moiety of MurNAc-3 and the backbone nitrogen of G468 (magenta), and the CZ atom of F412 and the center of mass of residues 463--467 (grey).
(*E*) Distances between the center of mass of the L-domain and the center of mass of residues 388--392 (brown), the center of mass of residues 398--403 & 409--413 with respect to the center of mass of residues 460--470 & 497--502 representing the width of the active site clef (light blue), center of mass of NU-domain helix α4 and center of mass U-domain helix α5 representing the distance across the flexible NU-loop (green), and the distance of the CA atom of NU-domain A33 and CA atom of C-domain I398 representing the distance across the NU-domain interface.
(*F*) Distances of the 5 PG disaccharide units (G*x*M*y*) and their respective tetrapeptide moieties (Pep*xx*-*yy*) with respect to the center of mass of active site residues 463--467.
(*G*)-(*K*) Same as (*B*)-(*F*) but with protonated E390 during MD runs.
(PDF)
######
Click here for additional data file.
###### Inter- and intra-molecular distances of the PG strand in the product-binding mode MD runs.
(*A*) Close-up view of pocket 2 area of the active site of Cj0843 with PG strand in product-binding mode. Distances that are monitored are shown as colored dashed lines. The view and atom coloring are as in [Fig 6B](#pone.0197136.g006){ref-type="fig"} but a more zoomed in view is shown.
(*B*) Distances plotted versus time between the oxygen atom of PG Glu42 and the OH group of S399 (orange), the nitrogen atom of PG Ala41 and the O6 atom of AnhMurNAc-1 (red), and the CD atom of PG Glu42 and NZ atom of PG DAP43 (blue).
(*C*) Distances between the oxygen atom of PG Glu42 and the backbone nitrogen of V400 group of S399 (black), and the oxygen atom of the *N*-acetyl moiety of AnhMurNAc-1 and the OH group of S401 (magenta).
(*D*)-(*F*) Same as in Figures D-F in [S8 Fig](#pone.0197136.s008){ref-type="supplementary-material"} but now with the PG carboxylates from tetrapeptide residues 42--44, respectively.
(*G*) Same as in Figure B in [S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"}.
(*H*)-(*I*) Same as in Figures D-E in [S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"}.
(*J*) Same as Figure F in [S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"} but now lacking the cleaved off terminal disaccharide PG unit.
(PDF)
######
Click here for additional data file.
###### Inter- and intra-molecular distances of the PG strand during the 1μs MD run with starting position outside hole of Cj0843.
Distances plotted versus time. (*A*)-(*C*) Same as Figures D-F in [S8 Fig](#pone.0197136.s008){ref-type="supplementary-material"}. (*D*) Distances plotted versus time between the CD atom of PG Glu52 and NZ atom of PG DAP53 (blue), and the nitrogen atom of PG Ala51 and the O6 atom of AnhMurNAc+2 (red). (*E*) Distances between the oxygen of the *N*-acetyl moiety of GlcNAc-2 and the backbone nitrogen of M410 (red), the nitrogen of the *N*-acetyl moiety of GlcNAc-2 and the backbone oxygen of Y463 (blue), and distances of the O4 atom of GlcNAc+1, belonging to the bond to be cleaved, and the CD atom of E390 (black). (*F*) Same as in Figure E and [S9 Fig](#pone.0197136.s009){ref-type="supplementary-material"}.
(TIF)
######
Click here for additional data file.
###### Distance distributions of the active site width in the different MD simulations.
The width of the active site is defined as the center of mass of residues 398--403 & 409--413 relative to the center of mass of residues 460--470 & 497--502. Twenty distance bins were plotted for the Cj0843 active site width as observed in the substrate-binding mode simulation (green), product-binding mode simulation (magenta), and the 1μs simulation in which the starting PG position was placed outside the central hole of Cj0843 (black).
(TIF)
######
Click here for additional data file.
###### MD simulation of Cj0843 with PG in substrate-binding mode starting position.
Representative section of the substrate-binding mode MD run simulation with a close-up view of the terminal tetrapeptide-1,6-anhydroMurNAc+2-containing section of the PG strand. The domains are colored as in [Fig 1](#pone.0197136.g001){ref-type="fig"}. The PG atoms are shown in a ball-and-stick model with the tetrapeptide carbon atoms colored yellow, and the saccharide carbon atoms colored cyan. The tetrapeptide amino acid carboxylates are labeled by their residue number (52--54). Selected protein atoms are shown in stick model with the carbon atoms of the 8 R/H residues colored cyan and the catalytic E390 atoms shown in black. Hydrogen bonds of the tetrapeptide carboxyl moieties with the R/K residues or with its amine-group are shown as black dashed lines (cut-off of 3.2Å). The video contains part of run 1 of the deprotonated E390 MD substrate simulation. A smoothing step of 2 was used for generating this video.
(MPEG)
######
Click here for additional data file.
###### MD simulation of Cj0843 with PG in product-binding mode starting position.
Representative section of the product-binding mode MD run 2 simulation with a close-up view of the terminal tetrapeptide-1,6-anhydroMurNAc-1-containing section of the PG strand. The tetrapeptide amino acid carboxylates are labeled by their residue number (42--44). The view and color coding are similar as in [S1 Video](#pone.0197136.s013){ref-type="supplementary-material"}.
(MPEG)
######
Click here for additional data file.
###### MD simulation of Cj0843 with PG in distant starting position.
MD simulation of the entire 1μs trajectory of a 5 disaccharide unit PG with a starting position in which only the terminal tetrapeptide moiety is inside the central hole. The PG strand is shown in solid spheres with the saccharide moieties colored by atom type with grey carbon atoms; the 5 tetrapeptide moieties starting at the terminal 1,6-anhydroMurNAc are colored light red, green, olive, orange, and red, respectively. The domain colors of Cj0843 are similar as in [Fig 1](#pone.0197136.g001){ref-type="fig"}. The catalytic E390 is shown as black spheres situated in the red C-domain. The disulfide bond in the blue U-domain is shown as yellow spheres.
(MPEG)
######
Click here for additional data file.
###### Validation report for crystal structure PDB reference 6CF8 from protein data bank.
(PDF)
######
Click here for additional data file.
###### Validation report for crystal structure PDB reference 6CF9 from protein data bank.
(PDF)
######
Click here for additional data file.
###### Validation report for crystal structure PDB reference 6CFC from protein data bank.
(PDF)
######
Click here for additional data file.
We thank A.M. Thunnissen for providing the bulgecin A inhibitor and Vivien Yee for critical reading of the manuscript. We thank beamline personnel at Stanford Synchrotron Radiation Lightsource (SSRL) beamline 9--2 for help with data collection. This work was supported in part by an allocation of computing time from the Ohio Supercomputer Cluster (OSC) and using the CWRU high-performance computer cluster. There was no additional external funding received for this study.
[^1]: **Competing Interests:**The authors have declared that no competing interests exist.
|
Iowa native to pilot shuttle’s return to space
An Iowa native will be piloting the space shuttle Discovery when it lifts off this afternoon at 2:51, NASA’s key “Return to Flight” mission. Hundreds of schoolkids will watch the launch projected live at the Science Center of Iowa’s “Star Theatre” dome.
Kristian Anderson, the center’s space science educator, says the space agency has made numerous important changes since the February 2003 crash of the shuttle Columbia. Anderson says “People need to remember that spaceflight is risky, it is dangerous and it’s never routine and it probably never will be routine like airline travel. If we try to make it perfectly safe, then we’ll never get off the ground and we’ll never get anywhere. Think back to times when we were settling our country. If things were perfectly safe, those wagon trains never would have gone west.”
Shuttles haven’t flown since the Columbia disaster that killed all seven astronauts. While two-and-a-half years is a long time in the lifetime of a child, Anderson says kids in central Iowa haven’t lost their affection and obsession for the final frontier. He says kids are always interested in space exploration and space travel and events like today’s help to maintain the excitement, adding, most kids are interested in at least one of two things: dinosaurs or space exploration.
This will be the second space mission for Burlington native Jim Kelly, Discovery’s pilot. Anderson says Kelly is the latest space hero from the Hawkeye State. He says there’s a sense of pride in Iowa, sending a native son into space, but he points out another astronaut, Peggy Whitson of Mount Ayr, lived aboard the International Space Station for several months a few years back. Whitson was the first Iowa woman in space.
Besides Kelly and Whitson, three other astronauts from Iowa have flown aboard space shuttles: George Nelson of Charles City, David Hilmers of Clinton and Loren Shriver of Jefferson. Also, back in 1968, Walter Cunningham of Creston flew aboard Apollo 7. |
Q:
Calling function of a JQUERY Plugin ( supersized ) via its API as part of a .click
I'm far from proficient in JS, so please forgive any obvious oversights. I've been trying to use the API of the Supersized background slideshow plugin as part of a regular (element).click(function().
The API is documented here incl. the part seemingly important for my problem:
api.goTo( targetSlide ) Triggers transition to target slide number.
//Goes to slide #5 $(element).click(function(){ api.goTo(5); });
Based on this, I would shoot for the following code in order to have a div with class "button" load slide number 5:
$(document).ready(function(){
$(".button").click(function(){
api.goTo(5);
});
});
This doesn't work - and the fact that the name of the plugin isn't anywhere in the code makes it obvious that the above code is lacking something. I just have no idea what. I also tried placing it in various locations within the plugin's source and themes - but no luck so far.
This is a related post I've found. However, the problem this person had was solved by modifying the plugin's theme in a manner that doesn't listen for the click event but rather is triggered by a function within the plugin. Still, I'm including it here as background info.
Any help would be greatly appreciated.
A:
I stumbled upon the same problem - and then realized that I had downloaded SuperSized version 3.1.3 (the latest from the legacy versions here), and totally overlooked the download link for the current version (3.2.4 as of today). However, the API calls are only supported from 3.2 upward - so maybe you are experiencing the same problem?
After downloading the latest version, the very same code you posted worked just fine on my end.
|
You can still make your voice heard by talking about domestic and family violence with those around you in person and on social, or if you’re not sure what to say, share one of the entries to our competition.
Why we’ve used a music competition to #stopthehurting and #enddomesticviolence
Why do kids and teenagers need to know about domestic and family violence?
Understanding what domestic violence looks like and why it’s unhealthy can help stop the cycle of abuse – help prevent young people enacting this behaviour as adults. Even if they don’t want to replicate the behaviour, subconsciously it can become a norm based on the role modelling they grew up with.
It’s also important to bring the issue out from behind closed doors and recognize there’s nothing shameful about being in this situation, and it’s one that unfortunately a lot of kids find themselves in. Even if someone hasn’t experienced domestic and family violence, having a clearer understanding will help them support and understand others.
This campaign was created by kids for kids in collaborative workshops. They shared their perceptions, insights, preferred communication approaches, what they knew and what they wanted to know about domestic and family violence. They made their voices heard. |
Q:
Keep Ubuntu 12.04 Servers synced
we´re having two exactly same VM Ubuntu 12.04 Servers. One is used for development, the other as live server. When new developments are accepted by the client changes have to be transfered to the live server by ftp (which can cause a lot of mess) or by rsync. Further if there´re linux updates. We´re testing them on the one and redo the steps on the live servers.
this all causes a lot of work and seems not to be bulletproof.
What´s a good way to keep servers synced? How do you keep your servers synced?
Let´s say I want all Linux packages, (without network settings -> static Ips), and dirs like /mnt /home /var/www synced?
Thanks,
t book
A:
My solution would be to use something like Chef/Puppet/Salt. That gives you full package control in the OS, as well as full code revisioning.
When you combine it with something like Git/SVN, you can roll an exact clone of your development machine to production, as well as update whatever is there, and roll back easily.
|
Most melanocytic neoplasms, benign melanocytic nevi as well as melanomas, originate from melanocytes situated within epithelial structures throughout the body, mostly the sun-exposed skin of individuals with light complexion. The majority of nevi and melanomas show oncogenic mutations in signaling components of the MAP kinase pathway, in particular *BRAF* and *NRAS*[@R1],[@R2]. However, a subset of melanocytic neoplasms does not show mutations in *BRAF* and *NRAS*[@R3]. One category, uveal melanoma, arises from melanocytes within the choroidal plexus of the eye and is biologically distinct from cutaneous melanoma by characteristic cytogenetic alterations[@R4] and a very strong propensity to metastasize to the liver[@R5]. The other category are intradermal melanocytic proliferations, which can be congenital or acquired, and present in diverse ways ranging from discrete bluish moles (blue nevi) to large blue-gray patches affecting the conjunctiva and periorbital skin (nevus of Ota), shoulders (nevus of Ito), and the lower back (Mongolian spot)[@R6]. A potential connection between intradermal melanocytic neoplasms and uveal melanoma is suggested by the fact that nevus of Ota is a risk factor for uveal melanoma and by an overlap in some of the histomorphologic features of the two conditions[@R7].
Using a forward genetic screen in mice we previously identified hypermorphic mutations in *GNAQ* or *GNA11*as a cause of diffuse skin hyperpigmentation that was due to an increase of intradermal, but not epidermal, melanocytes[@R8]. *GNAQ* and *GNA11* encode members of the q class of G-protein alpha subunits involved in mediating signals between G-protein coupled receptors (GPCRs) and downstream effectors. To investigate whether similar pathways were involved in humans, we sequenced the entire coding regions of *GNAQ* and *GNA11* in a broad spectrum of benign and malignant melanocytic neoplasms. We found mutations in *GNAQ* in 83% of blue nevi (n=29), 50% of "malignant blue nevi" (n=2), and 46% of uveal melanomas (n=48) ([Table 1](#T1){ref-type="table"}, [Supplementary Information, Figure 1a](#SD1){ref-type="supplementary-material"}). Nevus of Ota is a condition in which a subtle proliferation of intradermal melanocytes results in hyperpigmentation of the conjunctiva and periorbital skin. To increase the detection limit for mutations in a background of normal cells, we used a mutation-specific assay and found a mutation in one of 14 cases (6%) ([Supplementary Information, Figure 1b](#SD1){ref-type="supplementary-material"}). No somatic point mutations were found in *GNA11*.
All mutations in *GNAQ* were somatically acquired as assessed by sequencing DNA from adjacent tissue, and occurred exclusively at codon 209 ([Supplementary Information, Table 1](#SD1){ref-type="supplementary-material"}). The glutamine at codon 209 lies within the *ras*-like domain of *GNAQ* (corresponding to residue 61 of RAS and is essential for GTP hydrolysis [@R9]. In RAS family members, mutations at this site, and at codon 12, cause loss of GTPase activity with constitutive activation[@R9]-[@R11]. There is no equivalent of codon 12 in *GNAQ*. In contrast to the findings in humans, the mutations found in the dark skinned mice occurred at I63, V179, and F335 in the mouse proteins and do not cause constitutive activation[@R8].
To date no mutations of *GNAQ* have been described in human neoplasia, but *GNAQ^Q209L^* has been demonstrated to transform 3T3 cells[@R11]. In addition, mutations of the corresponding codon in G alpha S (*GNAS*) are found in human pituitary and thyroid tumors[@R10], [@R12]. To assess the effect of *GNAQ^Q209L^* on human melanocytes, we established epitope-tagged lentiviral expression constructs to transfect normal and genetically modified human melanocytes, the latter of which have an extended life span, but still require additional factors (cAMP, TPA) for growth (hTERT/CDK4^R24C^/p53^DD^ melanocytes[@R13]). Stable transfection of *GNAQ^Q209L^* into primary human melanocytes was insufficient to induce anchorage independent growth (data not shown). In contrast, transfection of *GNAQ^Q209L^* into hTERT/CDK4^R24C^/p53^DD^ melanocytes resulted in anchorage independent growth with efficiencies comparable or slightly greater than transfection with NRAS^Q61R^ ([Figure 1a](#F1){ref-type="fig"}, [Supplementary Information, Table 2](#SD1){ref-type="supplementary-material"}). Furthermore, GNAQ^Q209L^ but not GNAQ^wt^ induced abnormally enlarged nuclei with markedly irregular contours ([Figure 1b](#F1){ref-type="fig"}, [Supplementary Information, Table 3](#SD1){ref-type="supplementary-material"}). To validate *GNAQ^Q209L^* as an oncogene in vivo, we performed tumorigenicity studies in nude mice ([Figure 1c](#F1){ref-type="fig"}). *GNAQ^Q209L^*, but not GNAQ^wt^ or vector control transfected melanocytes gave rise to heavily pigmented tumors at the injection site. The tumor morphology resembled closely the spectrum of atypical blue nevus that in humans has been termed animal type melanoma or pigmented epithelioid melanocytoma[@R6].
Signaling pathways downstream of GNAQ include activation of protein kinase C family members via the release of diacylglycerol (DAG) by phospholipase Cβ. Consistently, *GNAQ^Q209L^*-transformed melanocytes grew in soft agar in the absence of TPA, a synthetic DAG analog ([Figure 1a](#F1){ref-type="fig"}, [Supplementary Information, Table 2](#SD1){ref-type="supplementary-material"}). PKC activation by way of GNAQ activation can activate the MAP-kinase pathway in other cell types[@R14]. Uveal melanomas display MAP-kinase activation[@R15], but none of the uveal melanomas we examined in our study showed mutations in BRAF or NRAS ([Supplementary Information, Table 4](#SD1){ref-type="supplementary-material"}), consistent with other studies[@R3]. We therefore tested whether *GNAQ^Q209L^* would contribute to MAP-kinase pathway activation in human melanocytes and uveal melanoma cells. As shown in [Figure 2](#F2){ref-type="fig"}, GNAQ^Q209L^ transfection into hTERT/CDK4^R24C^/p53^DD^ melanocytes caused increased levels of phospho-ERK compared to control cells transfected with wildtype *GNAQ* (*GNAQ^WT^*) or an empty vector (Vector). Similar results were obtained with *GNAQ^Q209L^* transfection into primary human melanocytes and 293T cells (see [Supplementary Information, Figure 2](#SD1){ref-type="supplementary-material"}). Conversely, siRNA-mediated knock-down of GNAQ in the uveal melanoma cell line, OMM1.3, which harbors the *GNAQ*-^Q209L^ mutation, resulted in a decrease of phospho-ERK levels ([Figure 3a](#F3){ref-type="fig"}). In addition, GNAQ knock-down in OMM1.3 cells causes a substantial decrease in cell number ([Figure 3b](#F3){ref-type="fig"}), loss of anchorage independent growth ([Figure 3c](#F3){ref-type="fig"}) and a marked increase in sub-G0/G1 population ([Figure 3d](#F3){ref-type="fig"}) as compared to control cells. Similar results were obtained when another uveal melanoma cell line Mel202 was treated with siRNA against *GNAQ^Q209L^* ([Supplementary Information, Figure 3](#SD1){ref-type="supplementary-material"}). Mel202 and OMM1.3 stem from different patients, as confirmed by DNA fingerprinting (data not shown.)
In summary, our data identify *GNAQ* as a novel oncogene in human neoplasia. GNAQ operates downstream of several GPCRs that are important in melanocyte homeostasis and neoplasia. GNAQ is involved in endothelin signaling, which is essential for melanocyte survival early during development[@R16]. Gq signaling may also contribute to the association observed for melanoma invasion and metastasis with Wnt family members[@R17], since Frizzled receptors can couple to Gq[@R18]. Furthermore, Gq signaling is likely to underlie the ability of the metabotropic glutamate receptor gene, *GRM1*, to cause dermal melanocytic neoplasia and ocular melanoma in transgenic mice[@R19].
The location of neoplastic melanocytes induced by somatic *GNAQ* mutation in humans is very similar to the location of melanocytes affected by germline *GNAQ* (and *GNA11*) mutations in mice[@R8]. In both cases, the melanocytic proliferations spare epithelial structures. However, our previous work in mice suggests that these mutations do not interfere with homing of melanocytes to epithelial structures, but instead lead to an increase of the total melanoblast pool[@R8]. In humans, it is not known whether the adult dermis contains any residual sparse populations of melanocytes in which *GNAQ* mutations could occur and induce intradermal melanocytic tumors[@R6], [@R20]. Acquired blue nevi are typically small and well circumscribed, raising the possibility that they arise from an intradermal population of melanocytes that remains to be characterized. By contrast, nevus of Ota involves different structures such as periorbital skin, conjunctiva, neurovascular bundles, ganglia, and uvea, suggesting these *GNAQ* mutations may arise early in a migrating melanoblast. This later neoplasm shows strong similarities to the murine studies and indicates a specific window for Gq signaling in terms of cell type and developmental time that is conserved across species.
Our findings identify *GNAQ* as a genetic link between nevus of Ota and uveal melanoma and help explain why nevi of Ota are a risk factor for uveal melanoma[@R7]. The risk is small, as only about 1 in 400 nevi of Ota progress to uveal melanoma and future studies will have to elucidate the role of *GNAQ* mutations in this risk. In our experiments, *GNAQ* behaves similar to the oncogenes, *BRAF* and *NRAS*, in that its mutation is insufficient for full progression to melanoma. This is illustrated best by blue nevi, which are generally stable lesions that rarely become malignant ("malignant blue nevus")[@R6]. Thus MAPK activation appears to be an early event in neoplasms with *GNAQ* mutations, as it is in neoplasms with *BRAF* and *NRAS* mutations[@R2]. Further studies are necessary to determine whether the difference in tissue involvement between melanocytic neoplasms with *BRAF* mutations and those with *GNAQ* mutations is a functional consequence of the mutations themselves, or indicates differences in the target cell populations in which these mutations occur.
Uveal melanoma is a highly aggressive cancer without any effective treatment options once it metastasizes. Although it only accounts for approximately 5% of all melanomas, it represents the most common intraocular malignancy in the United States and has a five-year disease specific survival rate of approximately 70%[@R21]. Our study identifies signaling components downstream of *GNAQ* as potential targets in this dreadful disease.
Methods Summary {#S1}
===============
Detailed descriptions of reagents and experiments can be found in the full Methods. *GNAQ* and *GNA11* were sequenced in DNA extracted from archival, paraffin-embedded biopsies under the approval of the institutional review boards at UCSF, Stanford and UBC. Primary, hTERT/CDK4^R24C^/p53^DD^, and melan-a melanocytes were stably infected with FG12 lentiviral expression vectors expressing flag-tagged wildtype GNAQ or GNAQ^Q209L^, empty vector or NRAS^Q61R^. Infection efficiencies were estimated by the proportion of cells expressing GFP. To assess anchorage independent growth, melanocytes were plated on soft agar, cultured for 28 days and stained with 0.005% crystal violet. For tumorigenicity experiments, 1 million lentiviral transfected melan-a cells were injected into each nude mouse, housed at UBC according to CCAC guidelines. For immunofluorescence, lentiviral transfected cells were cultured on coverslips for 5 days and incubated with antibodies against pERK (E-4, Santa Cruz Biotechnology), cyclin D1 (M-20, Santa Cruz Biotechnology) and GNAQ (C-19, Santa Cruz biotechnology). OMM1.3 and Mel202 cells were transfected with two different pools of siRNA against GNAQ: pool 1: 5′-CAAUAAGGCUCAUGCACAAUU-3′, 5′-CGACGAGAAUAUCAAUUAUUU-3′, 5′-GCAAGAGUACGUUUAUCAAUU-3′, 5′-UAGUAGCGCUUAGUGAAUAUU-3′; pool 2: 5′-AUGCACAAUUAGUUCGAGAUU-3′, 5′-UAUGAUAGACGACGAGAAUUU-3′, 5′-CAGACAAUGAGAACCGAAUUU-3′, 5′- CGCCACAGACACCGAGAAUUU-3′). For western blot analysis, 5-20 μg of protein was extracted from lentiviral or siRNA transfected cells. Primary antibodies were: pERK, cyclin D1, GNAQ, Cyclophilin B (Abcam), anti-FLAG M2 (Sigma), Anti-ERK ½ pAb (Promega), and β-actin (Sigma). Secondary antibodies were labeled with horseradish peroxidase. Relative cell numbers were quantified by the CyQUANT® Cell Proliferation Assay Kit (Invitrogen). Cell cycle measurements were performed on a FACSCalibur after staining with propidium iodide. Student's t-test and Fisher's Exact test were used for statistical comparison.
Full methods {#S2}
============
DNA {#S3}
---
DNA was obtained from archival paraffin-embedded biopsies under the approval of the institutional review boards at UCSF, Stanford and the University of British Columbia. For each sample, 20 um sections were microdissected, washed in xylene and ethanol and digested with proteinase K. DNA was then extracted with phenol-choloroform-isoamyl-alcohol.
Sequencing {#S4}
----------
Biopsy DNA was amplified using PCR. For *GNAQ* exon 5, the primers used were 5′-cccacaccctactttctatcatttac-3′ and 5′-ttttccctaagtttgtaagtagtgc-3′. PCR products were used as templates for sequencing reactions using Big Dye (ABI). Samples identified with mutations in both sequencing directions were replicated at least twice. Mutations 1-3 were verified with RFLP. Mutations 1 and 2 create an Eco0109I restriction site, while mutation 3 produces an AflII restriction site.
Sensitive assay for Q209 mutations in mixed cell populations {#S5}
------------------------------------------------------------
The peptide nucleic acid, Actctctgacctttggc-CONH~2~, was resuspended in 50% DMF and used at a final concentration of 4 uM against 2 ng template DNA in a 25 ul reaction. The reaction conditions were 0.25 mM dNTPs, 6X BSA, 2 U Hotstar Taq, 1× Hotstar Taq buffer, and 0.5 uM each primer, 5′-ttttccctaagtttgtaagtagtgc-3; and 5′-atccattttcttctctctgacc-3′. PCR consisted of 40 cycles of 95 degrees (1 min), 73 degrees (1 min), 57 degrees (45 sec), and 72 degrees (1 min).
Plasmids {#S6}
--------
A *GNAQ^Q209L^* cDNA plasmid was obtained from UMR cDNA Resource Center. The wild-type counterpart was generated by site-specific mutagenesis. The coding regions of both constructs were epitope-tagged with an N-terminal Flag-tag and cloned into the lentiviral expression vector FG12. All constructs were sequenced for confirmation.
Cell culture {#S7}
------------
hTERT/CDK4^R24C^/p53^DD^ melanocytes were cultured in glutamine containing Ham's F12 supplemented with 7% FBS, 50 ng/ml TPA, 0.1 mM IBMX, 10 μM Na~3~VO~4~, 1 mM dbcAMP. Primary normal melanocytes were cultured in MCDB153 supplemented 20% FBS, 2% chelated FBS, 5 μg/ml L-glutamin, 15 μg/ml cholera toxin, 0.5 ng/ml bFGF, 100 nM ET3 and 1.68 mM SCF. Cell lines OMM1.3, Mel202 and 293T were cultured in RPMI supplemented with 10% fetal bovine serum. Melan-a cells were cultured in glutamine-containing RPMI media supplemented with 10% FCS and 200 nM TPA.
Lentiviral infection {#S8}
--------------------
Viral supernatant were generated using 293T cells transfected with 10 μg plasmid and appropriate lentiviral packaging plasmids. Media was changed 16 hr after transfection and the virus was harvested 40 to 56 hr later. hTERT/CDK4^R24C^/p53^DD^, melan-a and normal melanocytes were infected and infection efficiencies were estimated by the presence of GFP expressing cells.
Transient transfection {#S9}
----------------------
293T cells were seeded in 6-well plates at 1×10^6^ cells per well with RPMI/10% FCS. Transfections were carried out using Lipofectamine 2000 (Invitrogen) and 2 μg plasmid pcDNA™6.2/V5-DEST® Gateway vector (Invitrogen) alone or containing the complete coding region for either *GNAQ^Q209L^* or *GNAQ^WT^*, respectively. Cells were lysed 48 hour post-transfection and assayed for protein content.
Tumorigenicity study {#S10}
--------------------
Melan-a cells were lentiviral transfected with *GNAQ^WT^*, *GNAQ^Q209L^* and empty vector control. Seven days post infection, cells were resuspended in DMEM at 5 million cells per milliliter. Four month old, albino female nude mice (NU/J) were injected with 0.2 ml subcutaneously. Mice were palpated weekly.
Cell proliferation assay {#S11}
------------------------
Relative cell numbers were quantified by the CyQUANT® Cell (Invitrogen) Proliferation Assay Kit according to the manufacturer's protocol using 96-well plates. 7.5×10^3^ cells were transfected and the fluorescent intensity was read after 72 hr.
Immunofluorescence {#S12}
------------------
Human primary and hTERT/CDK4^R24C^/p53^DD^ melanocytes were cultured on cover slips in 6 well plates and infected with lentiviral vectors containing either *GNAQ^Q209L^GNAQ^WT^*, or an empty vector as control. Five days after infection, cells were fixed with 4% formaldehyde in PBS, permeabilized with 0.2 % Triton X100 and incubated with 3% BSA. Antibodies against pERK (E-4, Santa Cruz Biotechnology), cyclin D1 (M-20, Santa Cruz Biotechnology) and GNAQ (C-19, Santa Cruz biotechnology) were detected using secondary antibodies labeled with Alexa Fluor 594 and 532 (Molecular Probes). Images were taken at fixed exposures with an Axio Image M1 microscope (Zeiss, Germany). The fluorescence intensities were quantified using ImageJ software and the mean pixel intensities were used for statistical analysis using Microsoft Excel and Data Desk.
Soft agar assay {#S13}
---------------
10×10^3^ human primary melanocytes, hTERT/CDK4^R24C^/p53^DD^ melanocytes stably expressing *GNAQ^Q209L^*, *GNAQ^WT^*, *NRAS^Q61R^* or vector control and siRNA treated OMM1.3 and Mel202 cells were suspended in full media containing 0.35% agar and plated on a lower layer of 0.5% agar in 6 well plates. After 28 days, cells were stained with 0.005% crystal violet. Colony number and size were quantified using ImageJ software.
Cell cycle analysis {#S14}
-------------------
72 hr post transfection with siRNA against *GNAQ*, OMM1.3 and Mel202 cells were trypsinized, washed with cold PBS and fixed with 70% ethanol. Fixed cells were stained with propidium iodide. Cell cycle measurements were performed on a FACSCalibur (BD Biosciences), with minimum of 20,000 events, and profiles were analyzed using FlowJo and ModFit.
siRNA transfection {#S15}
------------------
OMM1.3 and Mel202 were plated in RPMI/10% FCS in 6 well or 96 well plates at 1.5×10^5^ or 5×10^3^ cells per well, respectively. Two different pools; each comprised of four siRNA duplexes (pool 1: 5′-CAAUAAGGCUCAUGCACAAUU-3′, 5′-CGACGAGAAUAUCAAUUAUUU-3′, 5′-GCAAGAGUACGUUUAUCAAUU-3′, 5′-UAGUAGCGCUUAGUGAAUAUU-3′; pool 2: 5′-AUGCACAAUUAGUUCGAGAUU-3′, 5′-UAUGAUAGACGACGAGAAUUU-3′, 5′-CAGACAAUGAGAACCGAAUUU-3′, 5′-CGCCACAGACACCGAGAAUUU-3′) against *GNAQ* and ON-TARGETplus controls (all Dharmacon) were transfected in lipofectamine RNAiMax (1μl/pmol siRNA) at 100 nM. siRNA complexes were formed in Optimem. Cells were lysed for *analysis* 72-96 hours post-transfection. For soft agar assay, 48 post transfection cells were used.
Western blot analysis {#S16}
---------------------
Cells were washed twice with ice-cold PBS and lysed in 50 mM Tris---HCl pH 7.8, 1% NP-40, 10% glycerol, 150 mM NaCl, 1 % Sodium deoxycholate, 1% sodium dodecyl sulfate, supplemented with protease inhibitor, phosphatase inhibitor and EDTA (Pierce Biotechnologies). The protein content of the lysates was determined by the BCA Protein Assay Reagent (Pierce Biotechnologies). 5-20 μg of protein were separated by SDS---PAGE and transferred to Immobilon-P membrane (Millipore). Primary antibodies were: pERK (E-4, Santa Cruz Biotechnology), cyclin D1 (M-20, Santa Cruz Biotechnology) and GNAQ (C-19, Santa Cruz biotechnology), Cyclophilin B (Abcam), anti-FLAG M2 (Sigma), Anti-ERK ½ pAb (Promega), and β-actin (Sigma). Secondary antibodies were labeled with horseradish peroxidase.
Statistical analysis {#S17}
--------------------
Immunofluorescence data and CyQUANT measurements were analyzed using Student's t-test. Fisher's Exact test was used to compare the proportion of atypical cells.
Supplementary Material {#SM}
======================
We thank Dr. William Harbour, Washington University, Saint Louis, for providing additional DNA samples from uveal melanomas and Drs. Pablo Viciana-Rodriguez and Allan Balmain for providing advice. hTERT/CDK4^R24C^/p53^DD^ melanocytes were a gift from Dr. David Fisher, Dana Farber Cancer Institute[@R13], normal human melanocytes from foreskin were a gift from Dr. Meenhard Herlyn, The Wistar Institute, and OMM1.3 and Mel202 cells were originally from Dr. Bruce Ksander, Schepens Eye Research Institute. The melan-a cells were a gift from Dr. Dorothy Bennett, St George's University, London[@R23].This work was supported by grants from the National Cancer Institute (P01 CA025874 Project 2 to BCB) the Melanoma Research Alliance, the Canadian Institutes of Health Research (MOP-79511 to CVR), and the National Institutes of Health (GSB).
![*GNAQ^Q209L^* transforms melanocytes\
**a**, *GNAQ^Q209L^* induces anchorage independent growth in soft agar of hTERT/CDK4^R24C^/p53^DD^ melanocytes in a TPA-independent manner with comparable efficiency as NRAS^Q61R^. **b,** Cells expressing Flag-tagged GNAQ^Q209L^ showed enlarged nuclei with irregular contours after 5 days. **c,** Melan-a cells[@R23] stably transduced with GNAQ^Q209L^, but not with wild-type GNAQ (n=3) or vector control (n=4), induce highly pigmented tumors of spindled and epithelioid melanocytes after 10 weeks in four out of five animals.](nihms-74666-f0001){#F1}
{#F2}
{#F3}
######
Frequency of *GNAQ* mutations in melanocytic neoplasms The number and type of samples analyzed is shown.
--------------------------------------------------------------------------------------------------------------
Diagnosis \%\ N
Mutant
---------------------------- -------------------------------------------------------------- -------- ---------
**Cutaneous and mucosal**\ Melanoma on skin without chronic sun-induced damage (non-\ 0% 15
**melanomas** CSD)[@R22]
Melanoma on skin with chronic sun-induced damage (CSD)[@R22] 4% 27
Acral melanoma 0% 15
Mucosal melanoma 0% 14
"Malignant blue nevus" 50% 2
Melanoma arising in congenital nevus 0% 3
Spitzoid melanoma 0% 2
**Total** **78**
**Nevi** Blue nevus 83% 29
Nevus of Ota 6% 17
Congenital nevus 0% 7
Deep penetrating nevus 0% 16
Proliferating nodule in giant congenital nevus 0% 7
Spitz nevus 0% 8
**Total** **84**
**Ocular melanomas** Uveal melanoma 46% 48
Uveal melanoma cell line 27% 15
Conjunctival melanoma 0% 11
**Total** **74**
**Grand Total** **236**
--------------------------------------------------------------------------------------------------------------
|
The invention relates generally to seal devices and, more particularly, to mechanisms for facilitating quick mounting of seal devices to host bearings.
In conventional shaft bearings such as pillow blocks and the like, it is common practice to seal bearings between the shaft and its supporting housing with any one of a number of different types of seal devices, such as labyrinth type seals, O-rings, quad-rings, V-rings, or flinger type, or any combination of the seals. An example of this practice is illustrated and described in U.S. patent application, Ser. No. 07/232,673, filed August 16, 1988, of which the present invention is an improvement.
In applying and mounting one or more seal devices in a bearing block, it is customary to utilize a seal carrier device to which the one or more seal devices are applied and to mount the carrier device and the seal devices with the shaft extending therethrough to the block or housing for the bearing. A snap-ring which is also retained within the carrier device is arranged around a groove therein and adapted to be retained within an annular groove formed in an internal cylindrical surface of the bearing block or housing. Such installation of the carrier device requires that the snap-ring be squeezed inwardly to permit slipping of the same into the cylindrical opening and then released to fit into the groove when it assumes its normal unflexed orientation.
In the past, such squeezing of the snap ring is performed by the operator by manually grasping the outer surface of the snap-ring and inserting the ring along with one or more sealing devices or combinations thereof into the internal chamber of the block housing. Such attempts are not always successful during the initial try requiring additional attempts in order to succeed in positively locating the snap-ring within an annular groove and allowing the same to expand to be retained within the groove. In some cases, a special tool is employed which is arranged to encircle the snap ring and with manipulation, to flex the snap ring internally and permit the application of the same into the bearing housing. The use of fingers for this operation generally results in bruised fingertips and expenditure of time as well as producing frustration and anger within the operator.
Another arrangement for squeezing a snap-ring into its flexed condition is disclosed in application Ser. No. 07/232,673, identified above. This arrangement comprises the use of an annular inclined surface which drives the snap-ring inwardly into its flexed condition as the seal carrier member is forced inwardly into a bearing block.
The present invention has been devised to obviate the disadvantages described above and permit quick and easy mounting of a snap-ring for a sealing device that is also economical in use and manufacture. In accomplishing these goals, means have been devised which will maintain a snap-ring in its inwardly flexed condition while mounted on the carrier ring as the same is inserted within the bearing housing to mount the sealing devices therein. The retaining means comprises a rod-like member or pin releasably held within an opening formed in the carrier member and extending axially relative thereto in engagement with the free ends of the snap-ring thereby holding the free ends in a fixed condition when the snap-ring is flexed inwardly. After the carrier member with the sealing devices mounted thereon and the snap-ring retained in its flexed condition are positioned within the bearing housing with the snap-ring opposite the annular groove formed for receiving the snap-ring, the pin is released or withdrawn from the opening in a carrier member. In this manner, the free ends of the snap-ring are released, thereby permitting the snap-ring to assume its normal unflexed condition within the annular groove.
Therefore it is a principal object of the present invention to improve shaft bearings of the type utilizing snap-rings to maintain sealing devices therein.
Another object of the present invention is to provide a method for mounting a snap-ring and sealing system within a bearing block which requires very simple manipulative steps to secure the same within.
These and other objects of the present invention will apparent after reading the following description taken in conjunction with the drawings wherein: |
Q:
Can I override onCreate() function via cordova plugin
By default, after I create a cordova android project, the MainActivity.java looks like this:
import android.os.Bundle;
import org.apache.cordova.*;
public class MainActivity extends CordovaActivity
{
@Override
public void onCreate(Bundle savedInstanceState)
{
super.onCreate(savedInstanceState);
// Set by <content src="index.html" /> in config.xml
loadUrl(launchUrl);
}
}
Now I need to add a line getWindow().addFlags(WindowManager.LayoutParams.FLAG_KEEP_SCREEN_ON);
before the loadUrl(launchUrl) to prevent the app go to sleep mode.
But in some reason we don't want to break the default structure, that is, can I use cordova plugin to override onCreate() function separately other than insert this line of code directly?
Or does anyone have an idea to achieve the goal to keep your app always in front?
A:
Here I found a solution, works fine for me.
public class KeepAwake extends CordovaPlugin {
@Override
public boolean execute(String action, JSONArray args, CallbackContext callbackContext) throws JSONException {
if (action.equals("keepAwake")) {
this.keepAwake(callbackContext);
return true;
}
return false;
}
private void keepAwake(final CallbackContext callbackContext){
cordova.getActivity().runOnUiThread(
new Runnable() {
public void run() {
cordova.getActivity().getWindow().addFlags(WindowManager.LayoutParams.FLAG_KEEP_SCREEN_ON);
callbackContext.sendPluginResult(new PluginResult(PluginResult.Status.OK));
}
});
}
}
|
Q:
Is there any way to make UITextFieldDelegate more dynamic in swift?
I nearly have a UITextFieldDelegate in a UIViewController,and I make
import UIKit
class testViewController: UIViewController,UITextFieldDelegate{
@IBOutlet weak var textName: UITextField!
override func viewDidLoad(){
super.viewDidLoad()
textName.delegate = self
}
func textFieldShouldReturn(textField: UITextField) -> Bool {
return true
}
}
it works very well.
but my question is, when i have two, or three UITextFields, and have different function,what should i do? Is there any way to make UITextFieldDelegate more dynamic in swift? just like java do? I remember that java may do like that:
textName.delegate = UITextFieldDelegate{
func textFieldShouldReturn(textField: UITextField) -> Bool {
return true
}
}
textAddress.delegate = UITextFieldDelegate{
func textFieldShouldReturn(textField: UITextField) -> Bool {
return true
}
}
A:
The delegate methods take a parameter that identifies the text field for which the demarcate methods are being called. You can use this to provide different behaviours for different text fields.
|
If you decide to continue service after your trial, your selected subscription plan will automatically renew thereafter. You will be charged at then-current rates. Fees and taxes apply. To cancel you must call SiriusXM at 1-866-635-2349. See SiriusXM Customer Agreement for complete terms at siriusxm.com. All fees and programming subject to change. ©2018 Sirius XM Radio Inc. All rights reserved. |
A white supremacist website in Idaho is sending out an extremely racist robocall against Florida Democratic gubernatorial candidate Andrew Gillum.
Voters in Florida received the robocall on Tuesday, and HuffPost obtained audio of the recording. Speaking in an exaggerated minstrel dialect, an actor pretends to be Gillum, saying: “Well hello there. I is the Negro Andrew Gillum, and I be asking you to make me governor of this here state of Florida.”
Minstrel music plays in the background, and a monkey screeches occasionally to refer to Gillum, who is the mayor of Tallahassee.
The ad says Gillum’s health care plan will be quite cheap, because he’ll just give chicken feet to people as medicine. It talks about how Jewish people are going to vote for him, because Jews are “the ones that been putting Negroes in charge over the white folk, just like they done after the Civil War.”
HuffPost reader Rusty Gordon noted that the music in the background of the ad appears to be from “Amos ‘n’ Andy,” the controversial ― and popular ― radio and television show that relied on racial stereotypes.
At the end of the robocall, a disclaimer says it was paid for by The Road To Power, a white supremacist website and podcast based in Idaho that sent out a similar call against Gillum in August, when he was running in the Democratic primary. The group has been linked to racist robocalls in Virginia, Oregon, California, Idaho, Iowa and Pennsylvania.
In early September, after the group’s earlier call, Gillum said he wants “to make sure that we don’t racialize, and, frankly, weaponize, race as a part of this process.”
The Anti-Defamation League notes that Scott Rhodes, the man behind Road to Power, is a white supremacist who “achieved local notoriety in late 2017 when police linked him to the distribution of white supremacist propaganda at Sandpoint (Idaho) High School, harassment of a Sandpoint resident, and threatening, anti-Semitic calls that included recordings of Hitler.”
“These disgusting, abhorrent robocalls represent a continuation of the ugliest, most divisive campaign in Florida’s history,” Geoff Burgan, a spokesman for Gillum, said Tuesday. “We would hope that these calls, and the dangerous people who are behind them, are not given any more attention than they already have been.”
Gillum, who would be Florida’s first black governor if elected, has faced racist comments and dog whistles throughout his campaign. The morning after the primaries, former Rep. Ron DeSantis (R-Fla.) ― Gillum’s opponent ― went on TV and warned voters not to “monkey this up by trying to embrace a socialist agenda with huge tax increases and bankrupting the state.”
“Our campaign has absolutely nothing to do with this robocall and joins those in condemning it,” DeSantis spokesman Stephen Lawson said Tuesday. “In fact, we would encourage the Gillum campaign to join us in rooting out and exposing once and for all those who are behind this disgusting call.”
Even Idaho officials ― Gov. C. L. “Butch” Otter (R) and Boise Mayor David Bieter (D) chimed in against The Road To Power on Tuesday, saying this “kind of bigotry will not be tolerated in Idaho.”
This story has been updated with comment from DeSantis’ campaign and Idaho officials, and more information about the music in the robocall.
Correction: This piece originally referred to DeSantis as a congressman. He resigned last month. |
(* Time stamp counter
==================
This module tries to estimate time based on the CPU time stamp counter (TSC). The time
estimates reported by this module are monotonically increasing. It uses [Time.now ()]
as its measure of "real time" to do this.
Historically, the rate of increment of the TSC (sometimes referred to as the TSC
frequency) varied based of CPU overclocking, temperature, load etc. On modern Intel
CPU's the TSC is expected to be stable. On Linux systems, the "constant_tsc" in
/proc/cpuinfo indicates that the machine has a stable TSC rate. While this module
assumes that the TSC is relatively stable, it can adapt to small variations in the TSC
frequency.
Simple Overview
===============
Here is an explanation of how this module works. The module measures the change in
real time and the change in TSC at every calibration call and maintains an EWMA of
these deltas. It then uses the EWMA values to do linear regression where time is the
estimated value and TSC is the predictor. The linear regression done at every
calibration step produces an updated time/tsc slope. Using this time/tsc slope and
the latest value of real time, the module estimates time in terms of tsc.
Ensuring Monotonicity of Time
=============================
The simple picture above is complicated by the presence of noise. There are two
significant sources of noise. The first is the noise caused by variations in the
frequency of TSC. The second, and probably the more significant one, is noise in real
time, i.e. noise in the [Time.now ()] call.
(1) [Time.now ()] calls suffer from the overhead of transition from the user program to
a kernel vdso and
(2) It is affected by NTP updates.
(3) Another significant source of error comes from loss of precision. [Time.now]
reports a 64-bit float of which it has 52 bits of mantissa. The 52 bits of mantissa
for time in seconds from Unix epoch only allows for precision in the order of
micro-seconds. Consequently the measurement of time using [Time.now] can only be
precise in the order of micro-seconds.
Noise in measuring real time and in the rate of time/tsc implies that at each
calibration point the estimated time "jumps" up or down with respect to the estimate
value of time before calibration. In other words, the time estimated using the EWMA
linear regression is not strictly monotonic.
We report a monotonic time in terms of the estimated time, by maintaining a separate
slope called the "monotonic time/TSC slope". At every calibration point, we take the
last estimated time and adjust the monotonic time/TSC slope such that it catches up to
the estimated time in a fixed number of cycles. If the expected change in slope is too
high, we bound the rate of change of the monotonic time/TSC slope. As long as
monotonic time has not caught up with the estimated time we report time in terms of the
adjusted monotonic time slope. Once we have caught up to the estimated time, we start
reporting the estimated time.
We can chose the number of cycles to allow for catchup to be any number we wish. A
number in the order of 1E6-1E9 TSC steps allows for a gradual catchup rate without too
many abrupt changes in the rate of reported time. The bound to rate of change is
expressed in percentage terms of slope and is at max the ratio by which we expect the
underlying TSC frequency to change on the machine. It is defined as
[max_perc_change_from_real_slope] below.
It is worth noting that the approximation of the monotonic slope trying to catch up
with the estimate slope can be achieved in many other ways. A more principled approach
to this would be to use a PID controller that adapts to error and gets the reported
monotonic time to smoothly fit the estimated time. However PID controllers are
computationally more expensive and we use a simpler linear approximation.
*)
[%%import
"config.h"]
open! Core
open Poly
open! Import
let max_percent_change_from_real_slope = 0.20
let () =
assert (0. <= max_percent_change_from_real_slope);
assert (max_percent_change_from_real_slope <= 1.)
;;
let ewma ~alpha ~old ~add = ((1. -. alpha) *. old) +. (alpha *. add)
type t = Int63.t [@@deriving bin_io, compare, sexp]
type tsc = t [@@deriving bin_io, compare, sexp]
include (Int63 : Comparisons.S with type t := t)
let diff t1 t2 = Int63.( - ) t1 t2
let add t s = Int63.( + ) t s
let of_int63 t = t
let to_int63 t = t
let zero = Int63.zero
[%%ifdef
JSC_ARCH_SIXTYFOUR]
(* noalloc on x86_64 only *)
external now : unit -> tsc = "tsc_get" [@@noalloc]
module Calibrator = struct
(* performance hack: prevent writes to this record from boxing floats by making all
fields mutable floats *)
type float_fields =
{ (* the most recent observations and regression results *)
mutable time : float
; mutable sec_per_cycle : float
(* mutable sec_error_intercept : float; *)
(* this time value is monotonically increasing *)
; mutable monotonic_time : float
; mutable monotonic_sec_per_cycle : float (* for linear regression *)
; mutable ewma_time_tsc : float
; mutable ewma_tsc_square : float
; mutable ewma_time : float
; mutable ewma_tsc : float (* for computing time in nanos *)
; mutable nanos_per_cycle : float
; mutable monotonic_nanos_per_cycle : float
}
[@@deriving bin_io, sexp]
type t =
{ (* the most recent observations and regression results *)
mutable tsc : tsc (* this time value is monotonically increasing *)
; mutable monotonic_until_tsc : tsc (* for computing time in nanos *)
; mutable time_nanos : Int63.t
; mutable monotonic_time_nanos : Int63.t
; floats : float_fields
}
[@@deriving bin_io, fields, sexp]
let tsc_to_seconds_since_epoch =
let[@inline] convert t tsc base mul =
base +. (mul *. Int63.to_float (diff tsc t.tsc))
in
fun [@inline] t tsc ->
0.
+.
(* performance hack: stops float boxing *)
if tsc < t.monotonic_until_tsc
then
0.
+. (* performance hack: stops float boxing *)
convert t tsc t.floats.monotonic_time t.floats.monotonic_sec_per_cycle
else
0.
+. (* performance hack: stops float boxing *)
convert t tsc t.floats.time t.floats.sec_per_cycle
;;
let tsc_to_nanos_since_epoch =
let convert t tsc base mul =
(* Scale an int by a float without intermediate allocation and overflow. *)
Int63.( + )
base
(Float.int63_round_nearest_exn (mul *. Int63.to_float (diff tsc t.tsc)))
in
fun t tsc ->
if tsc < t.monotonic_until_tsc
then convert t tsc t.monotonic_time_nanos t.floats.monotonic_nanos_per_cycle
else convert t tsc t.time_nanos t.floats.nanos_per_cycle
;;
(* The rate of response to the variations in TSC frequency can be controlled via alpha.
Alpha should be in (0,1] and controls the decay of the subsequent EWMA calculation.
A low number such as 0.01 suggests that the TSC is largely stable and small
variations should be treated as noise. Setting this number to 0.6 or higher
indicates that each new measurement of the TSC should significantly outweigh past
measurements which has the effect of making time calibration more responsive to
frequency changes. In this module we have chosen a value of alpha that varies with
the duration of time, i.e. longer time samples are given more weight and shorter time
samples are given lesser weight. *)
let alpha_for_interval time_diff = 0. +. Float.max 0. (1. -. exp (-0.5 *. time_diff))
let catchup_cycles = 1E9
let initial_alpha = 1.
(* performance hack: This function is the same as
{[
match Float.iround_up float with
| None -> if_iround_up_fails
| Some i -> Int63.(+) int i
]}
but I couldn't find a way to make the simple version stop allocating, even with
flambda turned on *)
let iround_up_and_add int ~if_iround_up_fails float =
if Float.( > ) float 0.0
then (
let float' = Caml.ceil float in
if Float.( <= ) float' Float.iround_ubound
then Int63.( + ) int (Int63.of_float_unchecked float')
else if_iround_up_fails)
else if Float.( >= ) float Float.iround_lbound
then Int63.( + ) int (Int63.of_float_unchecked float)
else if_iround_up_fails
;;
let[@inline] calibrate_using t ~tsc ~time ~am_initializing =
let estimated_time =
0. +. (* performance hack: stops float boxing *)
tsc_to_seconds_since_epoch t tsc
in
let time_diff_est = time -. estimated_time in
let time_diff = time -. t.floats.time in
let tsc_diff = Int63.to_float (diff tsc t.tsc) in
let alpha =
if am_initializing then initial_alpha else alpha_for_interval time_diff
in
(* update current times *)
t.floats.time <- time;
t.tsc <- tsc;
(* update ewma and regression. *)
t.floats.ewma_time_tsc
<- ewma ~alpha ~old:t.floats.ewma_time_tsc ~add:(tsc_diff *. time_diff);
t.floats.ewma_tsc_square
<- ewma ~alpha ~old:t.floats.ewma_tsc_square ~add:(tsc_diff *. tsc_diff);
t.floats.ewma_tsc <- ewma ~alpha ~old:t.floats.ewma_tsc ~add:tsc_diff;
t.floats.ewma_time <- ewma ~alpha ~old:t.floats.ewma_time ~add:time_diff;
(* linear regression *)
t.floats.sec_per_cycle <- t.floats.ewma_time_tsc /. t.floats.ewma_tsc_square;
(* t.sec_error_intercept <- t.ewma_time -. t.sec_per_cycle *. t.ewma_tsc; *)
(* monotonic predicted time and slope. *)
t.floats.monotonic_time <- estimated_time;
if not am_initializing
then (
let catchup_sec_per_cycle =
(* The slope so that after [catchup_cycles], the monotonic estimated time equals
the estimated time, i.e. solve for [monotonic_sec_per_cycle] in:
{[
t.monotonic_time + monotonic_sec_per_cycle * catchup_cycles
= t.time + t.sec_per_cycle * catchup_cycles
]}
Note that [time_diff_est = t.time - t.monotonic_time]. *)
t.floats.sec_per_cycle +. (time_diff_est /. catchup_cycles)
in
t.floats.monotonic_sec_per_cycle
<- (if Float.is_positive time_diff_est
then
0.
+. (* performance hack: stops float boxing *)
Float.min
catchup_sec_per_cycle
(t.floats.sec_per_cycle *. (1. +. max_percent_change_from_real_slope))
else
0.
+. (* performance hack: stops float boxing *)
Float.max
catchup_sec_per_cycle
(t.floats.sec_per_cycle *. (1. -. max_percent_change_from_real_slope)));
(* Compute the number of cycles in the future at which monotonic estimated time
equals estimated time, i.e. solve for [cycles] in:
{[
t.monotonic_time + t.monotonic_sec_per_cycle * cycles
= t.time + t.sec_per_cycle * cycles
]}
This value might get very small when the two slopes are about the same. In such
cases we just use the estimated slope always. *)
t.monotonic_until_tsc
<- time_diff_est /. (t.floats.monotonic_sec_per_cycle -. t.floats.sec_per_cycle)
|> iround_up_and_add tsc ~if_iround_up_fails:Int63.zero);
(* Precompute values required for [tsc_to_nanos_since_epoch]. *)
t.time_nanos <- Float.int63_round_nearest_exn (t.floats.time *. 1E9);
t.floats.nanos_per_cycle <- t.floats.sec_per_cycle *. 1E9;
t.monotonic_time_nanos
<- Float.int63_round_nearest_exn (t.floats.monotonic_time *. 1E9);
t.floats.monotonic_nanos_per_cycle <- t.floats.monotonic_sec_per_cycle *. 1E9
;;
let now_float () =
1E-9 *. Int.to_float (Time_ns.to_int_ns_since_epoch (Time_ns.now ()))
;;
let initialize t samples =
List.iter samples ~f:(fun (tsc, time) ->
calibrate_using t ~tsc ~time ~am_initializing:true)
;;
let collect_samples ~num_samples ~interval =
assert (Int.( >= ) num_samples 1);
(* We sleep at differing intervals to improve the estimation of [sec_per_cycle]. *)
let rec loop n sleep =
let sample = now (), now_float () in
if Int.( = ) n 1
then [ sample ]
else (
ignore (Unix.nanosleep sleep);
sample :: loop (n - 1) (sleep +. interval))
in
loop num_samples interval
;;
let create_using ~tsc ~time ~samples =
let t =
{ monotonic_until_tsc = Int63.zero
; tsc
; time_nanos = Int63.zero
; monotonic_time_nanos = Int63.zero
; floats =
{ monotonic_time = time
; sec_per_cycle = 0.
; monotonic_sec_per_cycle = 0.
; time
; ewma_time_tsc = 0.
; ewma_tsc_square = 0.
; ewma_time = 0.
; ewma_tsc = 0.
; nanos_per_cycle = 0.
; monotonic_nanos_per_cycle = 0.
}
}
in
initialize t samples;
t
;;
let create () =
let time = now_float () in
let tsc = now () in
let samples = collect_samples ~num_samples:3 ~interval:0.0005 in
create_using ~tsc ~time ~samples
;;
(* Creating a calibrator takes about 3ms. *)
let t = lazy (create ())
let cpu_mhz = Ok (fun t -> 1. /. (t.floats.sec_per_cycle *. 1E6))
(* performance hack: [@cold] so [time] is always unboxed. [now_float] and
[calibrate_using] need to be inlined into the same function for unboxed [time].
Preventing [calibrate] from being inlined makes the compiler's inlining decision
more predictable. *)
let[@cold] calibrate t =
calibrate_using t ~tsc:(now ()) ~time:(now_float ()) ~am_initializing:false
;;
module Private = struct
let create_using = create_using
let calibrate_using = calibrate_using
let initialize = initialize
let nanos_per_cycle t = t.floats.nanos_per_cycle
end
end
[%%else]
(* noalloc on x86_64 only *)
external now : unit -> tsc = "tsc_get"
(* Outside of x86_64, [now] returns the result of clock_gettime(), i.e. the current time
in nanos past epoch. *)
module Calibrator = struct
type t = unit [@@deriving bin_io, sexp]
let tsc_to_seconds_since_epoch _t tsc = Int63.to_float tsc *. 1e-9
let tsc_to_nanos_since_epoch _t tsc = tsc
let create_using ~tsc:_ ~time:_ ~samples:_ = ()
let create () = ()
let initialize _t _samples = ()
let calibrate_using _t ~tsc:_ ~time:_ ~am_initializing:_ = ()
let calibrate _ = ()
let t = lazy (create ())
let cpu_mhz =
Or_error.unimplemented
"Time_stamp_counter.Calibrator.cpu_mhz is not defined for 32-bit platforms"
;;
module Private = struct
let create_using = create_using
let calibrate_using = calibrate_using
let initialize = initialize
let nanos_per_cycle _ = 1.
end
end
[%%endif]
module Span = struct
include (
Int63 :
module type of struct
include Int63
end
with module Private := Int63.Private)
module Private = struct
let of_int63 t = t
let to_int63 t = t
end
[%%ifdef
JSC_ARCH_SIXTYFOUR]
let to_ns t ~(calibrator : Calibrator.t) =
Float.int63_round_nearest_exn (Int63.to_float t *. calibrator.floats.nanos_per_cycle)
;;
(* If the calibrator has not been well calibrated and [ns] is a large value, the
following can overflow. This happens rarely in hydra in a way that difficult to
reproduce. We've improved the exn here so that we have more information to debug
these spurious errors when they come up. *)
let of_ns ns ~(calibrator : Calibrator.t) =
try
Float.int63_round_nearest_exn
(Int63.to_float ns /. calibrator.floats.nanos_per_cycle)
with
| exn -> raise_s [%message "" ~_:(exn : Exn.t) (calibrator : Calibrator.t)]
;;
[%%else]
(* [tsc_get] already returns the current time in ns *)
let to_ns t ~calibrator:_ = t
let of_ns ns ~calibrator:_ = ns
[%%endif]
let to_time_span t ~calibrator = Time.Span.of_ns (Int63.to_float (to_ns t ~calibrator))
end
let calibrator = Calibrator.t
let to_time t ~calibrator =
Calibrator.tsc_to_seconds_since_epoch calibrator t
|> Time.Span.of_sec
|> Time.of_span_since_epoch
;;
let to_nanos_since_epoch t ~calibrator = Calibrator.tsc_to_nanos_since_epoch calibrator t
let to_time_ns t ~calibrator =
Time_ns.of_int63_ns_since_epoch (to_nanos_since_epoch ~calibrator t)
;;
module Private = struct
let ewma = ewma
let of_int63 = of_int63
let max_percent_change_from_real_slope = max_percent_change_from_real_slope
let to_nanos_since_epoch = to_nanos_since_epoch
end
|
Q:
Can't get values from rows/cells in GridView
I'm trying get values from a GridView using the following code:
foreach (GridViewRow row in this.dgvEstudios.Rows)
{
var xy = row.Cells[1].Text;
}
Always get a an empty string ("") as the value returned from .Text, why does this happen? I have set EnableViewState to true
A:
If there are controls in each cell you will need to get the value like this:
Label lblEmailAddress = GridView.Rows[e.CommandArgument].FindControl("lblEmailAddress");
string Email = lblEmailAddress.Text;
in that case it it the control in the cell that has the value not the cell iteslf.
A:
The cell might have controls inside it (e.g. LiteralControl or an HyperLink). This is what you should be looking for.
row.Cells[1].Controls collection, you should look for.
|
Q:
Use inline Request.QueryString to build url
Not sure if I'm asking this right, but I have this:
<a href="mypage.aspx?id=<% Request.QueryString["id"].ToString(); %>&sec=map">
Map
</a>
But it doesn't add the ID to the url query string. Not sure what to do cause I really don't want to have to make a bunch of literals to build this on code side.
The url I get is:
mypage.aspx?id=&sec=map
A:
You need an = after the <% otherwise the value is not written out. You will then need to remove the semi-colon as well:
<a href="mypage.aspx?id=<%= Request.QueryString["id"].ToString() %>&sec=map">
Map
</a>
See this question for more details on the various meanings of <%.
|
MAC Paint Pot Reviews
Firstly I hate how heavy each one of these weigh, not good for traveling at all. The colour varieties are not that great at all. I have three of them, they work well and do have staying power but I find that once it gets dry it's not comfortable to have on and the colour loses it's stay. It's hard to control over the lid as well. I dont think I will buy another one so that's a big negative indicator for me
— 5 years, 7 months ago
Love them! Hands down thats it. And I hate hate hate cream shadows. I use Painterly everyday as a base or sometimes by its self if im down on time. Since I've been using these I haven't had to worry about my shadows not staying on all day.
— 5 years, 9 months ago
These are the holy grail for eye lid/ eye shadow primers! I have this in Painterly and my eyeshadow no matter what kind does not budge or crease...i wish it was a bit more softer of a formula but its still amazing!
— 5 years, 10 months ago
I am African American and I have them in Delft, Painterly and Quite Natural. I use them with an eyeshadow base for extra crease protection. I use them before I use certain eyeshadows that I want to be intensified. I use all of them and I love them!!
— 5 years, 11 months ago
I have been using MAC products for a few years now and it is the best! I have a few of the paint pots. I use painterly more often than not as an eyeshadow base and as a neutral base for underneath my slicker lipsticks and glosses. Sometimes all alone with a neutral liner and a light lip tint as not to let my lips get too dry. The paint pots are an essential in my makeup closet!
— 6 years, 2 months ago
i have medium to dark skin tone. and it is hard to get some colors to show the way i want on my eyes or to stay and not be absorbed by my skin. so this primer is my best friend. apply it with a brush like it is eye shadow and then apply the color over it. i use a color close to my complexion and it has a shimmer so that i could actually not use shadow and still look smashing lol
— 6 years, 2 months ago
I have soft ochre - its a neutral yellowish beige. I sometimes use it by itself. The other times I use it under some eyeshadows to make the colors more vibrant. It does hide my undereye dark circles which is good too. However, it does crease after 8 or so hours with me.
I don't think I will buy again because this one jar is lasting me a pretty long time.
— 6 years, 3 months ago
I bought "Bare Study" paint pot because I'd heard it made an excellent shadow primer, and the rumors were true. I'd tried a Paint, which I found too dry, but the creamy texture of the paint pot is perfect for me. I use this great neutral shimmer all over my eyelids, right up to my browbone, and because it's so subtle you only see shine. I use it on it's own and love it, or any shadow app...read morelied over top always last for at least 12 hours without a crease. I'm just running low (I've had it since October, and I use it every day! That's pretty darn good) and I'm definitely getting it again.— 6 years, 3 months ago |
Contact
Latest News
Welcome to our new website. We hope that the new site will be more useful in terms of the information offered and more current than our old site. For those of you who knew the old site some important changes in terminology will be obvious: interns become "Lay Missionaries" etc.
The Lived Theology School (LTS) at St John the Compassionate Mission has been receiving Lay Missionaries for the past few years. We now, in response to requests, wish to take this experience a step forward and to provide opportunities for those who wish to serve the Church and the poor as Brothers/Sisters of Mercy. |
Patrick Semansky/Associated Press
It's unfair to pin the Baltimore Orioles' demise entirely on Chris Davis. He hasn't pitched since 2012, after all, so he has nothing to do with the 5.02 ERA at the heart of their 15-32 record.
But when a team signs a guy to a seven-year, $161 million contract, it generally hopes said guy isn't one of Major League Baseball's worst players by the third year of that deal.
Davis was bad enough when he managed only a .732 OPS, 26 home runs and minus-0.1 rWAR (the Baseball Reference version of wins above replacement) in 2017. Now he's sunk to a .500 OPS, four homers and minus-1.0 WAR in 2018.
Entering Monday, Davis' WAR was tied for fourth-worst among qualified hitters:
1. Ian Desmond, COL: -1.3
2. Jesse Winker, CIN: -1.2
3. Dexter Fowler, STL: -1.1
T4. Chris Davis, BAL: -1.0
T4. Christian Vazquez, BOS: -1.0
Davis isn't the only big-money player on this list, as Ian Desmond and Dexter Fowler are also drastically underperforming relative to their contracts. Even still, the sum of their guaranteed money ($152.5 million) comes up short of what Davis' deal guarantees him.
Is the 32-year-old's contract weighing on his mind? His manager thinks so.
"Yeah, I'm sure that's part of it," Buck Showalter told reporters after benching Davis in Boston on Sunday. "I know that's part of it. It's something that Chris is trying to fight through."
Had Davis' deal been bad from the moment he signed it in January 2016, that'd be one thing. However, it was perfectly defensible at the time.
Mitchell Layton/Getty Images
Davis was fresh off a season in which he'd led MLB with 47 home runs. That marked the second time in three years that he was the majors' leader in dingers, with the other being his 53-homer eruption in 2013. Many of these blasts were the result of effortless swings.
At the time, home runs were hard to come by. There were only 0.94 home runs hit per game between 2013 and 2015, and it was too soon to know whether a spike in homers during the second half of 2015 would last.
For the Orioles, the chance to retain Davis thus meant a chance to retain something precious. And they ended up getting a better deal than the surface numbers would indicate. His contract includes $42 million in deferred money, which brings his average annual salary down to $17 million.
However, there's no denying that the Orioles made a massive bet on the twilight years of a hitter who already had a fatal flaw.
Davis has been saddled with way-above-average strikeout rates since he first broke into the majors with the Texas Rangers in 2008. While strikeouts aren't a terrible thing in their own right, any player who can't avoid them needs to do other things well.
Davis clearly had power covered. The other was patience, as he drew walks in 11.9 percent of his plate appearances between 2013 and 2017.
In 2018, however, Davis' BB% has fallen below the MLB average at a rate of only 8.2 percent. That's partly because he's swinging more often than he has in recent years, and partly because pitchers are being more aggressive within the strike zone against him:
Entering Monday, Davis was seeing pitches in the zone at the same rate as Miguel Rojas. The Marlins infielder isn't as feckless a hitter as he used to be, but his career home run total (11) doesn't even match Davis' career high for a single month (12 in both June 2013 and September/October 2015).
While this seems outrageous, it also gets at how much Davis has diminished as a power threat.
His fateful 2015 season was also the first year of the Statcast era, and the new system revealed that he hit the ball with an average launch angle of 17.3 degrees and at an average speed of 91.9 mph.
Behold a scatter chart that hints at how rare that combination of slugging goodness was that season:
Data courtesy of BaseballSavant.MLB.com.
But as the Statcast era has progressed, the foundations of Davis' slugging ability have crumbled. In 2018, he's managing only an average launch angle of 11.8 degrees and average exit velocity of 87.3 mph.
In turn, he's gone from a shining beacon to a needle in a haystack:
Data courtesy of BaseballSavant.MLB.com.
Most hitters in MLB have progressed in the opposite direction with their power strokes, so we can rule out Davis being afflicted by a leaguewide trend.
As for other explanations, Oriole Park at Camden Yards hasn't gotten any bigger. Davis himself, meanwhile, hasn't gotten any smaller. He's still a massive 6'3", 230-pounder with enough strength to deal with even the toughest of batting donuts.
The most plausible explanation is that Davis' bat speed just isn't what it once was.
Statcast doesn't have a reliable measurement for such things, so this is admittedly difficult to prove. But his power output sends strong signals that his swing isn't as mighty as it used to be, and it's also apparent that he can't get around on fastballs anymore. In 2015, he had little trouble pulling heaters to the right side. In 2018, he's hit them almost exclusively to the left side of the field.
In all, it's nothing but bad signs all the way down for Davis. The Orioles signed him with the hope that he would continue to be an elite power hitter. Instead, his power is drying up, and his value is going with it.
All they can do now is keep signing the checks and hope against hope that'll turn into money well spent.
Stats courtesy of Baseball Reference, FanGraphs and Baseball Savant. |
Q:
Not able to pull the css class with ng-class directive of AngularJS
I want to create a table with sorting(ascending / descending) feature on click event (clikcking on table headers), using ng-clickof AngularJS.
I have shared the code on Plunker.
The problem is that I am not able to pull the class name meant to display arrow icons.
Following is the HTML code.
<body ng-controller="myController">
<div>
<br /><br />
<table>
<thead>
<tr>
<th ng-click="sortData('name')">Name <div ng-class="getSortClass(name)"></div></th>
<th ng-click="sortData('dateOfBirth')">Date Of Birth <div ng-class="getSortClass(dateOfBirth)"></div></th>
<th ng-click="sortData('gender')">Gender <div ng-class="getSortClass(gender)"></div></th>
<th ng-click="sortData('salary')">Salary <div ng-class="getSortClass(salary)"></div></th>
<th ng-click="sortData('salary')">Salary <div ng-class="getSortClass(salary)"></div></th>
</tr>
</thead>
<tbody>
<tr ng-repeat="employee in employees | orderBy : sortColumn : reverseSort">
<td>{{employee.name | uppercase}}</td>
<td>{{employee.dateOfBirth | date:"dd/MM/yyyy"}}</td>
<td>{{employee.gender | lowercase}}</td>
<td>{{employee.salary | number:3}}</td>
<td>{{employee.salary | currency :"$"}}</td>
</tr>
</tbody>
</table>
</div>
Following is the module & controller code
var app = angular.module("app", []);
app.controller("myController", function($scope) {
var employees = [
{name: "Ali", dateOfBirth: new Date ("November 2, 1983"), gender: "Male", salary: 5555.555},
{ name: "Tauseef", dateOfBirth: new Date("December 21, 1993"), gender: "Female", salary: 6666.021 },
{ name: "Reza", dateOfBirth: new Date("June 31, 2002"), gender: "Female", salary: 12345.5689 },
{ name: "Gul", dateOfBirth: new Date("May 21, 1996"), gender: "Male", salary: 24587.2568 },
{ name: "Mohammad", dateOfBirth: new Date("April 21, 1997"), gender: "Male", salary: 5879.3654 },
{ name: "Ersahd", dateOfBirth: new Date("March 21, 1993"), gender: "Male", salary: 1011.3548 },
{ name: "Afroz", dateOfBirth: new Date("February 9, 1986"), gender: "Male", salary: 3533.126 },
{ name: "Waseem", dateOfBirth: new Date("January 21, 1986"), gender: "Male", salary: 6788.1287 }
];
$scope.employees = employees;
$scope.sortColumn = "name";
$scope.reverseSort = false;
$scope.sortData = function (column) {
$scope.reverseSort = ($scope.sortColumn == column) ? !$scope.reverseSort : false ;
$scope.sortColumn = column;
}
$scope.getSortClass = function(column) {
if($scope.sortColumn == column)
{
return $scope.reverseSort ? 'arrow-down' : 'arrow-up';
}
}
});
Sorting is working fine but the class which is meant for displaying the arrow icon of sort is not being pulled.
A:
try this. you must pass parameter in single quotation.
<th ng-click="sortData('gender')">Gender <div ng-class="getSortClass('gender')"></div></th>
|
Q:
I cant show content of control in canvas control, but image is showed
<Grid x:Name="grdTouchZoom" RenderTransform="1 0 0 1 0 0" IsManipulationEnabled="True" Background="Transparent">
<Grid Background="Transparent"/>
<Canvas>
<Image Name="img" Source="c:/1.jpg" />
<ContentControl x:Name="rt" Content="{Binding CurrentView}" Margin="0,0,0,0">
</ContentControl>
</Canvas>
</Grid>
That's my code to make slide book application. I intend use canvas object to moving my page control by changing Canvas.Left, but when I put my control which contain CurrentView object, it's not showed. I try with image control, it worked. I put my contentcontrol was out side canvas, it worked.
Where's my wrong?
A:
Instead of ContentControl try with Border, Bind the CurrentView with its Child
|
---
title: Elemento <sectionGroup> para <configSections>
ms.date: 05/01/2017
f1_keywords:
- http://schemas.microsoft.com/.NetConfiguration/v2.0#configuration/configSections/sectionGroup
helpviewer_keywords:
- sectionGroup Element
- <sectionGroup> Element
ms.assetid: 6c27f9e2-809c-4bc9-aca9-72f90360e7a3
ms.openlocfilehash: eb221027470fe6e485f8fcc4b939b71e4f219712
ms.sourcegitcommit: b16c00371ea06398859ecd157defc81301c9070f
ms.translationtype: MT
ms.contentlocale: es-ES
ms.lasthandoff: 06/06/2020
ms.locfileid: "77215259"
---
# <a name="sectiongroup-element-for-configsections"></a>Elemento \<sectionGroup> para \<configSections>
Define un espacio de nombres para las secciones de configuración.
[**\<configuration>**](configuration-element.md)\
[**\<configSections>**](configsections-element-for-configuration.md)\
**\<sectionGroup>**
## <a name="syntax"></a>Sintaxis
```xml
<sectionGroup name="section group name">
<!-- Configuration sections -->
</sectionGroup>
```
## <a name="attribute"></a>Atributo
| | Descripción |
| --------- | ----------- |
| **name** | Atributo necesario.<br><br>Especifica el nombre del grupo de sección que se está definiendo. |
## <a name="parent-element"></a>Elemento primario
| | Descripción |
| --- | ----------- |
| [**\<configSections>** Element](configsections-element-for-configuration.md) | Contiene la sección de configuración y las declaraciones de espacio de nombres. |
## <a name="child-elements"></a>Elementos secundarios
| | Descripción |
| --- | ----------- |
| [**\<section>**](section-element.md) | Contiene una declaración de sección de configuración. |
## <a name="remarks"></a>Comentarios
Al declarar un grupo de secciones, se crea una etiqueta de contenedor para las secciones de configuración y se garantiza que no hay conflictos de nomenclatura con las secciones de configuración definidas por otro usuario. Puede anidar **\<sectionGroup>** elementos entre sí.
## <a name="example"></a>Ejemplo
En el ejemplo siguiente se muestra cómo declarar un grupo de secciones y declarar secciones dentro de un grupo de secciones:
```xml
<configuration>
<configSections>
<sectionGroup name="mySectionGroup">
<section name="mySection"
type="System.Configuration.NameValueSectionHandler,System" />
</sectionGroup>
</configSections>
<mySectionGroup>
<mySection>
<add key="key1" value="value1" />
</mySection>
</mySectionGroup>
</configuration>
```
## <a name="configuration-file"></a>Archivo de configuración
Este elemento puede usarse en el archivo de configuración de la aplicación, el archivo de configuración del equipo (*Machine. config*) y los archivos *Web. config* que no están en el nivel de directorio de la aplicación.
## <a name="see-also"></a>Consulte también
- [Esquema del archivo de configuración para el .NET Framework](index.md)
|
The invention concerns a drilling machine, in particular, a manual drill, whereby optionally (i) the rotating motion of a hollow drive spindle may be transmitted to a drilling tool, or (2) an impact effect may be obtained on the end of an axially movable drilling tool in an impact drill holder by means of an impact bolt guided through the drive spindle.
Manual drills of this type are known (Hilti Operating Instructions for Hammer Drill TE 12, 1981). In the known configurations, in which the rotating drive is effected by means of an electric motor, and the impact bolt is driven pneumatically by a piston reciprocated by an electric drive, special hammer drill tools must be provided for the impact drilling mode of operation; they are designed for positive entrainment. Thus, it is known either to provide longitudinal grooves on the shaft of the tool shaft to engage a plurality of balls provided on the drill spindle, or to design the shaft in a hexagonal form or the like, thereby making it possible to prevent rotation by inserting the tool into a corresponding positive guide, while maintaining axial mobility. Even though these known configurations have a switching position in which essentially only the rotating motion is transmitted, it is a disadvantage in the case of the hammer-type tools that they remain mobile in the axial direction. A further disadvantage is that conventional drilling tools, such as those used in pure drilling machines, may be used only with the insertion of an additional drill chuck, which in turn, has a fastening shaft designed to correspond to the shaft of the impact drilling tools and therefore again cannot be secured satisfactorily in rotation and in the axial direction.
There are further manual drills in which the rotating drive for the drill chuck is combined with a ratchet-like intermediate piece (as described in DE-AS 1155 657), which also provides a certain impact motion, which, however, is not comparable to the intensive, actual impact motion obtained with the afore-mentioned hammer drills. Machines of the last mentioned type may be used (especially for household purposes) for purely drilling work and to a certain extent for work similar to impact drilling, but are not suitable for work requiring an intensive impact action, for example, drilling in concrete or rock.
It is the object of the present invention to design a drilling machine, in particular, a manual drill of the above-mentioned type, so that it is suitable both for use with drilling tools having a smooth shaft and as a hammer drill, without the need for the installation and removal of a drill chuck. |
2016 Ipswich Assembly
posted by Dave Copeman | 1486.20sc
The 2016 Ipswich Assembly is our accountability assembly. It's when we, as organised local citizens, can ensure that our leaders work with us around the stories of hardship and injustice that we've heard.
Our faith institutions, unions and community organisations will gather together and call for public committments by our Ipswich decisionmakers to help address access to mental health services and safety issues.
We will be calling for the Ipswich City Council to invest in a community response to renew our city heart, and lend vacant spaces to emerging enterprises and activities that will bring life and excitement back to the city centre. This will make the city a safer and more welcoming space for everyone.
We will demand of health leaders for the West Moreton area that they support a Collective Impact project to improve access to mental health services, and work with community organisations to create a more supportive and healthy Ipswich.
We need to fill Ipswich City Uniting Church to the rafters! Please RSVP below and join us! |
Human or animal tissue is susceptible to many forms of damage. The damage can have many causes, including: non-complicated acute wounding, complicated chronic wounding, trauma, exercise related trauma and pathological damage.
An example of non-complicated acute wounding is a wound caused by surgery. Complicated chronic wounding may include wounds such as diabetic and venous ulcers, pressure sores and burns. Trauma wounds may include lacerations, contusions, incisions and blunt trauma such as bullet injuries. Exercise related trauma may occur to muscles, tendons and ligaments as a result of overuse, misuse and abuse. Pathological damage may cause joint problems, such as osteo-artritis and rheumatoid arthritis.
Repair of damaged tissue involves regeneration of tissue cells which occurs naturally as a result of repair mechanisms in the human or animal body. Often the natural repair of damaged tissue can be a lengthy process or does not occur at all as a result of the debilitating effects of infection or permanent damage to the tissue repair mechanisms.
The time taken to repair damaged tissue can cause many related problems, such as infection or re-infection of the damaged tissue, prolonged pain, temporary or permanent disability, scarring or aesthetic embarrassment for the injured person. For athletes and animals, such as horses, tissue damage prevents participation in training or competitions.
Thus, it is advantageous to provide a device for treating damaged tissue that promotes faster tissue repair.
Dressings for promoting tissue repair have been known for many years. These dressings are coated with substances which are absorbed into the damaged tissue and actively encourage cellular regeneration and prevent infection. However, such dressings only provide a slight improvement in the speed of the healing process. In the case of serious trauma or large areas of wounding, such dressings can become ineffectual and, in some cases, create more damage, for example by preventing oxygen getting to the surface of the wound. In the case of muscle, ligament or tendon damage, such dressings have no therapeutic effect at all, except to act as a support to the damaged area whilst repair occurs naturally.
In recent years, electrical treatment of damaged tissue has become known as an effective method of treatment of damaged tissue. This method involves supplying electrical current to a treatment area (i.e. either directly to the external wound or to the surface of the skin near the damaged tissue). Electrodes are fixed to the treatment area and a current generating device is connected to the electrodes. Originally, these devices supplied current at a fixed amplitude ranging from 1 to 10 milliamps. It was found that supplying current via electrodes to the treatment area significantly improved the time taken to repair damaged tissue. However, supplying current at such levels can result in discomfort for the user of the device. Therefore, more recent developments have included supplying electrical current to the surface of a treatment area with a constant amplitude waveform typically having an amplitude in the range of 10 to 800 microamps. Electrical current in this range is commonly known as “micro-current” and the electrical stimulation it causes cannot generally be detected by a user of the device.
Some existing current generating devices for supplying current to electrodes fixed to a treatment area are described in PCT Publication Nos. 00/02622, 01/03768, 98/23326 and 98/40121 and U.S. Pat. No. 5,395,398. All of the current generating devices described in the aforementioned documents comprise a remote unit with attached electrodes. The electrodes must be fixed to the treatment area, typically with tape. Wires connect the electrodes to the current generating unit which is remote from the treatment area. Treatment with such devices requires specialist knowledge about the operation of the device and electrodes, including knowing where to locate the electrodes and how to connect them to the current generating device. This often necessitates frequent visits to clinics by a user of the device. Furthermore, there is the annoyance of having to carry a separate current generating unit. Generally, the user has to remain immobile whilst treatment is being carried out.
PCT Publication No. 94/22529 describes an elastic housing with electrodes sewn into specific positions which can be worn by a user. When the housing is worn by a user, the electrodes are in the correct anatomic position for optimal treatment of the tissue which is to be treated. A current generating unit is fixed to the housing by insertion into a small pocket on the housing. The current generating unit is connected to the electrodes and supplies current to the electrodes with a waveform chosen from a number of different waveforms by the user using a control pad on the generating unit. The waveforms have constant amplitude and constant frequency.
One problem with the device of PCT Publication No. 94/22529 is that it is difficult to obtain good conductivity between the electrode and the treatment area. Since the electrodes are sewn into the housing, they are not necessarily fixed to the treatment area appropriately even when the housing is correctly worn. The size and shape of the treatment area around which the housing is worn can vary from one user to another and even change shape or size over time. Furthermore, the treatment area itself can change its physical condition as it is repaired. In particular, levels of infection, temperature and pH may vary over time. Thus, a treatment programme chosen for a particular patient when treatment is commenced may need to be varied as treatment progresses. In addition, it has become apparent that supplying alternating current with a simple waveform having constant amplitude and frequency is not necessarily the most effective waveform for encouraging cell regeneration.
Accordingly, it is an aim of the present invention to provide an improved device for treating damaged tissue that increases the rate of cell regeneration.
It is a further aim of the present invention to provide an improved device for treating damaged tissue that integrates separate elements into a single device that can easily be applied to a treatment area by an uninformed user and which has improved conductivity between the electrodes and the treatment area.
It is a still further aim of the present invention to provide an improved device for treating damaged tissue that integrates separate elements into a single device that can easily be applied to a treatment area by an uninformed user and which adapts its programme of treatment according to the physical condition of the treatment area. |
The Whale Wars Season 3 DVD introduces you to the Sea Shepherds, a group of dedicated activists whose mission is to save the whales. With the support of the Ady Gil, a futuristic ship that help the world record for circumnavigation, the crew is geared up to fight. The Whale Wars DVDs give you an inside look into the true campaign and conflicts.
The Whale Wars Season 3 DVD follows Sea Shepherd's 6th Antarctic Whale Defense Campaign, named Operation Waltzing Matilda in honor of Australia's unofficial national anthem, on the three-month journey to the South Ocean Whale Sanctuary to stop illegal whaling. As in previous campaigns, the conflict between Sea Shepherd and the whalers grows more intense with each engagement — and Animal Planet documents the action in the new 12-part series.
Buy the Whale Wars Season 3 DVD and be taken on a three month journey across the South Ocean Whale Sanctuary as the crew of the Sea Shepherd battles would-be killers of the incredible whales of the Antarctic.
"The issues surrounding whaling in the Southern Ocean are important and complex, and Whale Wars returns once again to capture them in all their intensity," says Marjorie Kaplan, president and general manager of Animal Planet. "The majesty of these beautiful creatures and the lengths to which the Sea Shepherds will go in order to prevent whaling has made Whale Wars entertaining yet vital television. The series has become a trademark for the new Animal Planet, and audiences now expect to kick off summer television viewing with its return."
In June 2009, Sea Shepherd announced its 2009-10 Antarctic campaign, called Operation Waltzing Matilda. The campaign would include the record-breaking Earthrace vessel, now renamed Ady Gil in honor of the benefactor who helped acquire the vessel for Sea Shepherd. The Ady Gil was a futuristic styled ship that held the world record for circumnavigation of the globe by a motorized vessel. The eco-friendly vessel usually ran on a low emission fuel "derived mainly from animal fat, soybeans or other forms of bio-diesel" but was forced by operational reasons to switch to a more polluting petroleum diesel. Pete Bethune, the operator, said that an agreement was reached with Sea Shepherd for the boat to adopt a support role.
Sea Shepherd Founder and President Captain Paul Watson said, "Ships are expendable, endangered and protected whales are not. We lost a ship and we have one crewmember taken prisoner, and no injuries were caused nor sustained. I think we did bloody well this year and 528 whales were saved. We won’t stop until whaling ends."
This DVD is excellent, I love it, have a very well information about what the Sea Shepherd's crew did in the 2009-2010 campaing to protect the whales.This is one of my favorites DVD that I have.I only have a word for this DVD: ¨Awesome¨
I have just finished watching Season 3 of "Whale Wars." This dvd contained the Sea Shepherd activists in the very real headlines of 2010: Cap. Paul Watson, Peter Bethune, and Chuck Swift. My heart broke for the loss of that beautiful boat Ady Gil. It is truly an honor to support them. Now I have them on dvds.
I have enjoyed every aspect of this series and the work of Sea Shepherd in saving the lives of whales in the sanctuary. It shows the cruelty of the Japanese and the bravery of the men and women who put their lives in danger to protect these wonderful animals.
I really liked the show but there are a couple of attack scenes that are fake and show the nishu marou coming towards a dingy and the waves are completely different heights and they never show both boats in the same scene. [...] |
What is the average Env., Health, and Safety Engineer II salary for Topeka, KS?
How much does a Env., Health, and Safety Engineer II in Topeka,
KS make? The median annual Env., Health, and Safety Engineer II salary in Topeka,
KS is $63,776, as of November 30, 2016, with a range usually between
$59,181-$67,274 not including bonus and benefit information
and other factors that impact base pay. However, the salary for someone with the title Env., Health, and Safety Engineer II may vary depending on a number of factors including industry,
company size, location, years of experience and level of education. Our team of Certified Compensation Professionals has analyzed survey data collected from thousands of HR departments at companies of all sizes and industries to present this range of annual salaries for people with the job title
Env., Health, and Safety Engineer II in Topeka, KS.
This chart describes the expected percentage of people who perform the job of Env., Health, and Safety Engineer II in the United States that make less than that annual salary. For example the median expected annual pay for a typical Env., Health, and Safety Engineer II in the United States is $63,776 so 50% of the people who perform the job of Env., Health, and Safety Engineer II in the United States are expected to make less than $63,776.
This chart describes the expected percentage of people who perform the job of Env., Health, and Safety Engineer II in Topeka, KS that make less than that salary. For example 50% of the people who perform the job of Env., Health, and Safety Engineer II in Topeka are expected to make less than the median.
Source: HR Reported data as of December 2016
Implements and maintains company policies adhering to local, state and federal environmental, health and safety regulations. Involved in the design and development of facilities, work areas and work procedures and makes environmental, health and safety recommendations accordingly. Responsible for preparing, maintaining, and updating environmental policy and procedure manuals. Ensures compliance with all environmental, health and safety regulations, and keeps abreast of any changes to laws and regulations that impact the organization. Serves as contact with all federal, state, and local regulatory bodies. May require a bachelor's degree in area of specialty and 2-5 years of experience in the field or in a related area. Familiar with standard concepts, practices, and procedures within a particular field. Relies on limited experience and judgment to plan and accomplish goals. Performs a variety of tasks. Works under general supervision. A certain degree of creativity and latitude is required. Typically reports to a supervisor. View full job description |
Loneliness among British men has been described as a “silent epidemic” with an estimated eight million admitting to feeling lonely at least once a week.
But more worryingly, around 10 per cent say they prefer to keep it hidden.
The study, which was conducted as part of Spotlight on Men month, surveyed 1,200 men and was launched by the Jo Cox Commission on Loneliness.
It found that 11 per cent of men say they are lonely on a daily basis with 35 being the average age men say they feel most isolated.
Around 35 per cent said being lonely made them feel depressed, with nine per cent revealing that they had no regular friends.
Those who felt this way said the situations that made them feel lonely included moving away from friends and family (18%), going through a breakup (17%), being unemployed (17%) and the death of a family member (17%).
Idalia Candelas - 'Postmodern Loneliness' Show all 8 1 /8 Idalia Candelas - 'Postmodern Loneliness' Idalia Candelas - 'Postmodern Loneliness' Idalia Candelas - 'Postmodern Loneliness' Idalia Candelas - 'Postmodern Loneliness' Idalia Candelas - 'Postmodern Loneliness' Idalia Candelas - 'Postmodern Loneliness' Idalia Candelas - 'Postmodern Loneliness' Idalia Candelas - 'Postmodern Loneliness' Idalia Candelas - 'Postmodern Loneliness'
Over a quarter of men aged 65-69 said retiring had made them feel lonely.
“Loneliness is a silent epidemic hidden inside every family and community in the UK and can affect any one of us and at any time,” said Labour MP Rachel Reeves, who co-chairs the commission.
”For the next month, we will explore how and why men experience loneliness and, most importantly, shine a light on the practical steps that can be taken to combat it.
With an estimated 1.5 million men in England and Wales predicted to live alone by 2030, the data hopes to start a much conversation about how men can conquer loneliness. |
Q:
Is there a way to create executable file for UWP[C++/xaml] application?
I am trying to find a way to provide .exe (executable) file without side-loading the application or going through microsoft app store publishing process.
Also if its not possible, which type of App platform provide this facility.
A:
It's not possible for UWP applications. You must generate an app package and install it via side-loading (if you don't want to go through the Store).
You could create a WPF application (or many other types of applications, for that matter) to have an executable at the end of the compilation.
|
Brick Alley Pub & Restaurant
While in Newport, we stayed at The Newport Harbor Hotel and Marina. It was nothing special and the service was fine. The cost of rooms were very high for the holiday weekend. The room was fairly small and very basic. We requested a room with a balcony which was nice.
On the Harbor
The main reason for staying there was the location right on the harbor and in the middle of town. We were able to walk to everything and since taxis and Ubers were practically nonexistent, it was well worth it.
Balcony View
After relaxing in the room for a bit, it was time to go back out for dinner. I heard good things about a restaurant near the hotel, so we gave it a shot. Just a couple blocks away on Thames Street was Brick Alley Pub & Restaurant.
Lunch at Brick Alley Pub & Restaurant
We gave the hostess our name and it was about a 20-25 minute wait, Not too bad. Apparently this place can get very busy. We went to the upstairs bar and had a couple of beers while waiting for our name to be called over the speaker system.
Waiting
We looked over the menu while we waited. We were getting hungry. The menu had a huge selection and offered dishes like steaks, fresh seafood, pastas, nachos, wings, pizza, and a decent wine and cocktails selection. Our names were called and we were seated at a table in the very back room.
Back Room
We decided to try some appetizers. Now I heard this place was known for their Portuguese clams dish. It sounded really good. The recipe was also featured in an issue of Bon Appetit. We had to get an order. Bon Appetit also voted their lobster roll as the best in America, but I wanted to save the lobster roll fix for the beach the next day.
The Clams
We also ordered a cup of their Creamy Newport Clam Chowder and the Fried Point Judith Calamari. We asked asked if they could fry the banana peppers too, make them “Rhode Island Style”. She said she would ask the cook and there was no problem at all.
In a fairly short time, all of our appetizers came out. The clam chowder was super rich and creamy. Heavy, but tasty. I can only imagine how much cream was put in it.
Clam Chowder
The fried calamari was good, nothing special. It was crispy and somewhat greasy. They fried the banana peppers and lemon slices as well, so that was pretty good and explained the extra grease. It was at this point that we realized we probably didn’t have to order entrees since this turned out to be more than enough food.
Fried Calamari
Then the dish we were waiting for – the Portuguese Clams.
Gary’s Portuguese Littleneck Clams
They were amazing! The broth was extremely flavorful with the olive oil, garlic, and chorizo. So simple, but done so well. We could not get enough of it. I have never seen him so excited about a dish before. We used the bread to soak up all that deliciousness. Mmmmm! I was getting pretty full at this point. I just wanted to pick up the bowl of clams and drink that broth. We still had our entrees coming so I had to stop myself.
Flavorful Broth
I ordered the Baked Lobster Mac ‘N’ Cheese. That seemed to be another well-known dish.
Lobster Mac and Cheese
It was alright. I was not too crazy about it. I was also pretty stuffed from our appetizers and really only took a few bites, so that may have affected my enjoyment of the dish.
Cheesy
We also ordered the Marinated Sirloin Steak Tips. They were a bit bland and we weren’t expecting so much sauce on them.
Steak Tips
The side of broccoli seemed a tad undercooked. The side of mashed potatoes were really good.
We didn’t do much damage to our entrees since we got a bit too involved with those appetizers.
Overall, we enjoyed our dinner at Brick Alley. We were much more impressed with the appetizers than our particular entrees. Desserts sounded good, but there was no more room. We would each just get an order of those delicious clams next time! So good! |
Kale, mushroom and pork stir fry
When I opened the veg box this week to find a big bag of dark green kale staring me in the face, I knew autumn had arrived. And I was stumped.
As the seasons change, I always feel like I’ve forgotten each one’s vegetables. And I’d totally forgotten what to do with kale (another good reason I’ve started this blog). So I googled kale recipes, and found this beauty from Hugh Fearnley-Whittingstall.
Today was *supposed* to be a vegetarian day so I planned to switch out the beef for Portobello mushrooms, also in our veg box – until I realised there were only three in there… Luckily, we had a single pork chop lurking in the fridge so I threw that in to my adapted version. Not a vegetarian day in the end, but we managed not to waste the lonely chop and it wasn’t a lot of meat for three.
So how was it, without beef, without five-spice, and with mushrooms? Not at all bad, if I do say so myself. Give it a go, and let me know what you think!
Serves 3
What you’ll need
1 tbsp sunflower oil
1 pork chop sliced into strips
1 small red onion
3-4 large flat mushrooms, sliced
200g kale, sliced
1 tbsp cashew nuts
A dash lime juice
3 nests of egg noodles
For the marinade
3 cloves of garlic, finely chopped
3 tsp finely grated ginger
1 small red chilli (optional)
3 tbsp soy sauce
1 tbsp rice wine vinegar
1 tsp allspice
1 tbsp brown sugar
;
How to make it
Mix the marinade ingredients together in a bowl, and add the sliced pork. Leave to marinate for at least 20 minutes.
Heat up your work, and toast the cashew nuts. This will only take a few seconds, so keep the nuts moving. When toasted and crisp, set on one side.
Rinse your kale in a colander over the sink, then tip a freshly-boiled kettle of water over it so that it wilts. It’ll go bright green and tasty-looking.
Set your wok over a high heat once again, and add a spoon of oil. Use a slotted spoon to take the pork from the marinade, and place in the wok. Stir fry for 2-3 minutes, until browned.
Next, chuck in your red onion. Keep it moving, until the onion is softened.
Now cook the noodles according to packet instructions.
Meanwhile, add a spoonful of your marinade, then chuck in the kale. Keep everything moving around the wok, until the kale has wilted some more. This should only take a few minutes. Add more marinade if you need to, but remember that the kale will give up some of its liquid as it wilts, and you don’t want it to become soggy.
Remove your wok from the heat, add a dash of lime juice and sprinkle over the cashews. Stir once more, and check the seasoning.
Split the noodles between three bowls, pile the stir fry over the top and spoon on some juice from the pan. |
Due to redistricting and the new top two Open Primary, there will be more competitive races for congress and the state legislature this November than we have seen in this state in over a decade. L.A. Times reports “Recent developments put the party within reach of gaining the two seats it needs for a two-thirds majority in the Legislature’s upper house.”
Allan Hoffenblum, publisher of the California Target Book, wrote a four-part series for Fox & Hounds Daily, describing where those competitive races will be. We’ll talk Hoffenblum about what these developments mean for the people and the politics of CA.
We’ll ask him what he thinks about the propositions on the ballot too. CalWatchDog has a lot of coverage on the initiatives, with two propositions, Prop 30 and Prop 32 testing the political grip the special interests and public employee unions have on CA’s voters and their support.
Related Links:A Democratic supermajority for California’s Senate?Recent developments put the party within reach of gaining the two seats it needs for a two-thirds majority in the Legislature’s upper house.
October 06, 2012|By Patrick McGreevy, Los Angeles Times
“…Should Prop 30 fail in November, Brown will have a chance to start playing Moneyball. Here are some ideas for the manager of the major league Sacramento Spenders…”
Tune in LIVE at 10:00 a.m. PDT on CRNtalk.com on CRN 1 or on USTREAM TV’s CRNStudioLive!”
If you tune in on CRN, give the player a few minutes to pop up and start streaming. Give yourself enough time so you don’t miss the program.
Sometimes the programing display for CRN 1 is not current, and it may say another program is playing. If it’s Tuesday, you can be sure Gadfly Radio is on from 10 am to 11 am PT! The number to call if you have any questions or comments during the show is 1-800-336-2225
Hi Bob. Thank you for your post. Nobody forced us off the air.
I’m so sorry to read that CRN would play commercials right over the show. That’s disappointing. I’m going to post our show up on our podcast page in less than an hour. All of our shows are up on our podcast page if you missed any of them and would like to peruse.
Sign up for the feed and the newsletter so I can let you know what we do next. Hope you’ve enjoyed the show. It’s been a great pleasure to produce and host.
It depends on my partner. We’ll keep doing what we do, and cutting back as we have, and doing more for ourselves to save money. As long as we can afford to be here, we will do so. It’s a beautiful place worth standing for. Public awareness and opinion are critical as are powerful grassroots coalitions around unwavering principles.
About Martha Montelongo
Dedicated to promoting policies that empower private citizens and business owners and support policies that advance economic and personal freedom and liberty and nourish civil society.Learn More
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The status quo of education in the U.S. is destructive to our Nation, and to ignore this truth is to be numb, unconscious or in denial of reality.
"If an unfriendly foreign power had attempted to impose on America the mediocre educational performance that exists today, we might well have viewed it as an act of war. As it stands, we have allowed this to happen to ourselves. We have even squandered the gains in student achievement made in the wake of the Sputnik challenge. Moreover, we have dismantled essential support systems which helped make those gains possible. We have, in effect, been committing an act of unthinking, unilateral educational disarmament."--A Nation At Risk - April 1983
Drug War Clock for Current Year
Police arrested an estimated 858,408 persons for cannabis violations in 2009. Of those charged with cannabis violations, approximately 89 percent were charged with possession only.
Source: Uniform Crime Reports, Federal Bureau of Investigation Your tax dollars at work--but for whom?
Search Site
The Gadfly
Dedicated to considerations of justice and the pursuit of goodness… "to sting people and whip them into a fury, all in the service of truth." --Plato on Socrates |
Hate crime: Man arrested in Bethnal Green antisemitic incident
Dunbridge Street... where man is arrested on suspicion of antisemitic hate crime. Picture: Google Google
Police have arrested a suspect carrying a knife following an alleged antisemitic hate crime incident in the street at Bethnal Green.
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The 34-year-old was arrested near Dunbridge Street, off Vallance Road, yesterday morning for a suspected "racially aggravated public order offence", police said.
A knife was said to have been recovered from the suspect who was held in custody.
The incident was reported at 10am yesterday when a Jewish man was threatened in Dunbridge Street by a suspect carrying a knife. |
Accuracy of side-chain prediction upon near-native protein backbones generated by Ab initio folding methods.
The ab initio folding problem can be divided into two sequential tasks of approximately equal computational complexity: the generation of native-like backbone folds and the positioning of side chains upon these backbones. The prediction of side-chain conformation in this context is challenging, because at best only the near-native global fold of the protein is known. To test the effect of displacements in the protein backbones on side-chain prediction for folds generated ab initio, sets of near-native backbones (< or = 4 A C alpha RMS error) for four small proteins were generated by two methods. The steric environment surrounding each residue was probed by placing the side chains in the native conformation on each of these decoys, followed by torsion-space optimization to remove steric clashes on a rigid backbone. We observe that on average 40% of the chi1 angles were displaced by 40 degrees or more, effectively setting the limits in accuracy for side-chain modeling under these conditions. Three different algorithms were subsequently used for prediction of side-chain conformation. The average prediction accuracy for the three methods was remarkably similar: 49% to 51% of the chi1 angles were predicted correctly overall (33% to 36% of the chi1+2 angles). Interestingly, when the inter-side-chain interactions were disregarded, the mean accuracy increased. A consensus approach is described, in which side-chain conformations are defined based on the most frequently predicted chi angles for a given method upon each set of near-native backbones. We find that consensus modeling, which de facto includes backbone flexibility, improves side-chain prediction: chi1 accuracy improved to 51-54% (36-42% of chi1+2). Implications of a consensus method for ab initio protein structure prediction are discussed. |
Q:
Math brackets in python?
Now I'm talking about MATH brackets, not python brackets, I know that parentheses () work like in maths, ex:
i = 5*(2+2)
print (i)
#output = 20
But square brackets [] and curly brackets {} don't work... (I know why they don't work)
Thank you,
Using Python 3.2.2
A:
You don't need "math" brackets -- just use nested parentheses. Humans use [] in writing out complex math expressions to make them more readable to other humans, but this isn't necessary. They don't mean anything different than regular parentheses. So, when writing code, just stick to the parentheses.
|
Film: The Big Short
22 February 2016
Director: Adam McKay
IMDb: 7.9
Rotten Tomatoes: 88%
Parkville Station: 7
The Big Short does what no Macroeconomics lecturer could ever do – make me understand what caused the Global Financial Crisis, and what on earth sub-prime mortgage loans really are. And make it all fascinating. Following the story of the men who saw the GFC coming where none of the big banks could, the film doesn’t really give us any protagonists. Everyone in the film is trying to capitalise, and the losers aren’t the big banks – they’re the everyday people. Despite this, it provides some hope, and some sense of vindication against the Wall Streeters who aren’t quite as brilliant as they think they are.
The film is odd, there’s no getting around that. It jumps between different narrative styles, makes Steve Carrell play a serious part, and explains economic theory via Margot Robbie in a bathtub, but it all kind of holds together. And it’s worth the ride regardless. |
This is my last low-detailed map. Someone showed me what people meant by "detail" and I was too far along in this map to start over to make it to this week's /newstuff. So this is low-detailed I know that. Hope you enjoy it though.
Of course as far as detail is concerned, there is no heightened rule that says, "lots of detail makes maps better." The classic episodes and doom 2 are living proofs of that. The focus, really, should be in how effectively and consistently detail is used. And of course ideas and gameplay will always take priority as well. Ahem, anyway, this map is okay. The connectivity and structure of the level, I thought, needed more attention than the palatable idea of greater detail. |
Q:
Spring Protype Scope Behaviour
As far as I read from spring documentation, if I put a prototype scoped bean inside a larger scoped bean, prototype scoped bean acts like as if it is also a view scoped bean. Meaning, it will only be initialized when the container bean is initialized.
In my prototype scoped bean, I have a simple property and a getter setter for that.
@Repository
@Transactional( readonly=true )
@MyPrototypeScope // see definition of this one at [1]
class MyPrototypeScopedBean {
protected String member ;
public String getMember( ) { return this.member ; }
public void setMember( String member ) {
this.member = member ;
System.err.println( "member is set to " + this.member + ", class is : "
+ this.getClass( ).getName( ) ) ;
}
protected void someMethod( ) {
System.err.println( "The member is " + member + ", class is : "
+ this.getClass( ).getName( ) ) ;
}
}
My view scoped bean autowires it and tries to use it.
class MyViewScopedBean {
@Autowired
MyPrototypeScopedBean proto ;
....
public void problematicMethod( ) {
MyPrototypeScopedBean tmpReference = this.proto ; // to be sure we access it only once
tmpReference.setMember( "X" ) ;
System.err.println( "Value of member is " + tmpReference.getMember( ) + ", class is : "
+ this.getClass( ).getName( ) ) ;
this.proto.someMethod( ) ;
}
}
In the above case, I expect to see an output like below:
member is set to X, class is : com.xxx.MyPrototypeScopedBean$$EnhancerBySpringCGLIB$$xxxxxx
Value of member is X, class is : com.xxx.MyPrototypeScopedBean
The member is X, class is : com.xxx.MyPrototypeScopedBean
But instead, what I see is similar to below:
member is set to X, class is : com.xxx.MyPrototypeScopedBean$$EnhancerBySpringCGLIB$$xxxxxx
Value of member is null, class is : com.xxx.MyPrototypeScopedBean
The member is null, class is : com.xxx.MyPrototypeScopedBean
As if, spring somehow gives me a fresh instance for each reference of the "proto", be it a member access or a method call.
My code is obviously more complicated than this, but this is what the design is supposed to do. So, my question is, am I expecting something wrong? Is there any configuration issues that could cause this problem? Or this is just a symptom of a bug in some place else?
thank you.
Update 1:
Following the suggestion of skaffman, I have added the class names, at the end of println statements. Code and outputs are updated to reflect the changes.
Also added the scope definitions on the bean.
[1]
@Target( { ElementType.TYPE, ElementType.METHOD } )
@Retention( RetentionPolicy.RUNTIME )
@Documented
@Scope( BeanDefinition.SCOPE_PROTOTYPE )
public @interface MyPrototypeScope {
ScopedProxyMode proxyMode( ) default ScopedProxyMode.TARGET_CLASS ;
}
A:
Your hunch is correct: Every time you access this.proto, you get a new prototype. To implement this, Spring wires a proxy into the field. Every time that you access a method, Spring creates a new instance, calls the method, ... and eventually, you realize you have a problem.
So assigning the result of this.proto to a local variable doesn't help. Spring doesn't wrap accesses to the field, so it doesn't matter how you access it.
That means for beans with scope prototype, you have to be very, very careful. The best way to use them is to just call a single method and then get rid of them. My solution was to add a test case to the code which scans the whole spring configuration, fails for any beans in the scope BeanDefinition.SCOPE_PROTOTYPE and use my own factories instead.
If you need stateful prototyped beans, then there are two options:
Create a singleton factory and use that to create instances when you need one.
Use Spring to autowire a bean instance after you created it.
The first step works well in Java config:
@Autowired
private BarFactory barFactory;
@Bean
public Foo foo() {
Foo result = new Foo();
result.setBar(barFactory.create());
return result;
}
The second one uses Spring's BeanFactory:
@Autowired
private ApplicationContext appContext;
....
public void problematicMethod( ) {
MyPrototypeBean tmp = new MyPrototypeBean();
appContex.getappContext.getAutowireCapableBeanFactory().autowireBean( tmp );
...
}
I think you can't rely on @PostConstruct in this case; instead you have to call those methods yourself.
Related:
Spring autowire and prototype scope
|
Estonian language lessons will take place on 'language trains' between Tallinn and Narva to mark Estonian Language Learning Week later this month, ERR News reports.
The lessons will take place on September 24-26 on the Tallinn-Narva-Tallinn passenger service, and the sessions will be run by the Estonian Language House at the Integration Foundation.
According to the 2011 census, 95.7% of the population in Narva are native Russian speakers.
Director of the Estonian Language House, Margarita Källo, said that trains are an excellent alternative to the classroom.
"At the start of the language trains there is free Estonian language training in a special section of the carriage where everyone is welcome."
The Estonian language train is being funded by the Ministry of Education and Research, the Integration Foundation, and the national rail operator, Elron.
Estonian Ministry of Education and Research has declared 2019 the Year of the Estonian Language. |
/*
* Copyright 2010-2020 Amazon.com, Inc. or its affiliates. All Rights Reserved.
*
* Licensed under the Apache License, Version 2.0 (the "License").
* You may not use this file except in compliance with the License.
* A copy of the License is located at
*
* http://aws.amazon.com/apache2.0
*
* or in the "license" file accompanying this file. This file 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.amazonaws.services.iot.model.transform;
import com.amazonaws.services.iot.model.*;
import com.amazonaws.transform.SimpleTypeJsonUnmarshallers.*;
import com.amazonaws.transform.*;
import com.amazonaws.util.json.AwsJsonReader;
/**
* JSON unmarshaller for response DescribeEndpointResult
*/
public class DescribeEndpointResultJsonUnmarshaller implements
Unmarshaller<DescribeEndpointResult, JsonUnmarshallerContext> {
public DescribeEndpointResult unmarshall(JsonUnmarshallerContext context) throws Exception {
DescribeEndpointResult describeEndpointResult = new DescribeEndpointResult();
AwsJsonReader reader = context.getReader();
reader.beginObject();
while (reader.hasNext()) {
String name = reader.nextName();
if (name.equals("endpointAddress")) {
describeEndpointResult.setEndpointAddress(StringJsonUnmarshaller.getInstance()
.unmarshall(context));
} else {
reader.skipValue();
}
}
reader.endObject();
return describeEndpointResult;
}
private static DescribeEndpointResultJsonUnmarshaller instance;
public static DescribeEndpointResultJsonUnmarshaller getInstance() {
if (instance == null)
instance = new DescribeEndpointResultJsonUnmarshaller();
return instance;
}
}
|
The Sydney Morning Herald confirms what a lot of us thought upon hearing about those bombings. Local Thai also think they were almost certainly linked to Muslim separatists of Malay heritage in the South. They would like self rule. Sound familiar? It should, we are also looking at similar things in the southern Philipines, in Mindanao. In fact this is a recurring theme in ever more European cities.
Bangkok: A wave of bombings targeting Thailand's tourist areas last week is likely to be linked to southern Malay separatist militants fighting south-east Asia's longest running war, according to sources with knowledge of the conflict.
If proven – and no group has yet claimed responsibility – the attacks mark an alarming escalation of the conflict by militants who have for years concentrated their violence to four southern border provinces.
Beheadings, bombings, drive-by shootings, assassinations, extrajudicial killings and vicious assaults have left more than 6300 people dead and at least 11,500 injured in violence that is rarely reported outside of Thailand.
The conflict pits armed and organised ethnic Malays – almost all of whom are Muslims – against the predominantly Buddhist Thai state.<<<<<<<<<<<<<Read the rest here.
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In order to prevent a return to truck driving I invite you to hit the RED BUTTON above if you think what I'm doing is worth supporting. The button takes you to my Patreon page where you can hit their RED BUTTON on the top right of that page and choose your amount. I appreciate it! |
Lanier was riding east on Heim Road about 9:20 p.m. Saturday when an oncoming car tried to turn left onto Sylvan Drive, said Mount Dora police Lt. David Taylor. The car hit the side of the bike and knocked Lanier onto the sidewalk.
The bike had no lights, but the area was well lit with streetlights, Taylor said.
The driver of the car was Steve Vaughn, 61, of 1324 Sylvan Drive, Mount Dora, Taylor said. An investigation is under way, Taylor said. |
275 F.3d 478 (6th Cir. 2001)
RONALD FIELDS, PETITIONER-APPELLEE,v.MARGARET BAGLEY, WARDEN, RESPONDENT-APPELLANT.
No. 00-4032
UNITED STATES COURT OF APPEALS FOR THE SIXTH CIRCUIT
Argued: December 10, 2001Decided and Filed: December 19, 2001
Appeal from the United States District Court for the Northern District of Ohio at Cleveland. No. 98-02826--Kathleen McDonald O'Malley, District Judge.[Copyrighted Material Omitted]
Carlos Warner (argued), Donald Green (briefed), Cuyahoga County Public Defender Office, Cleveland, OH, for Appellee.
M. Scott Criss (argued and briefed), Office OF The Attorney General, Corrections Litigation Section, Columbus, Ohio, for Appellant.
Before: Jones and Cole, Circuit Judges; Sargus, District Judge.*
OPINION
Per Curiam.
1
The district court granted petitioner-appellee, Ronald Fields, a writ of habeas corpus because his due process rights and rights to counsel were violated due to his lawyer's ineffective assistance. Fields's lawyer neither notified Fields of a state-court appeal of his successful motion to suppress evidence nor represented Fields during that appeal. Margaret Bagley, the warden, appealed the district court's grant of the writ of habeas corpus to this Court. Because the district court's decision is well-reasoned and because Bagley did not raise issues beyond those considered by the district court, we see no reason to embellish upon the district court's opinion, which we attach as an appendix. We AFFIRM the district court's opinion and ADOPT it as our own.
APPENDIX
2
UNITED STATES DISTRICT COURT NORTHERN DISTRICT OF OHIO EASTERN DIVISION
3
RONALD FIELDS, Plaintiff,
4
v.
5
MARGARET BAGLEY, Warden Lorain Correctional Institution, et al., Defendants.
Case No. 1:98cv02826
JUDGE O'MALLEY
MEMORANDUM & ORDER
6
Ronald Fields filed this habeas corpus petition, pursuant to 28 U.S.C. § 2254, challenging his incarceration after pleading "no contest" to two counts of aggravated trafficking, Ohio Rev. Code § 2925.03, and one count of possession of criminal tools, Ohio Rev. Code § 2923.24. Fields alleges that he is being held unconstitutionally because he was denied the effective assistance of counsel, in fact, any assistance of counsel, in the state's appeal of the trial court's ruling suppressing the evidence upon which the charges against him were based. This case was designated to an administrative track and, pursuant to local rule 72.2 (b) and 16.2 (a), the Court referred it to Magistrate Judge David S. Perelman for a report and recommendation. On November 19, 1999, the Magistrate Judge recommended that the Court grant Fields's petition. Respondents filed a timely objection to the Magistrate Judge's Report and Recommendation. For the reasons stated below, Fields's Petition for Habeas Corpus is GRANTED.
I. BACKGROUND
7
On December 14, 1994, police officers discovered cocaine during a search of Ronald Fields's bag following his arrival at the Cleveland Hopkins International Airport. Fields was arrested, taken into custody and charged with two counts of aggravated trafficking, and one count of possession of criminal tools. Fields retained counsel, attorney Donald Tittle, who filed a Motion to Suppress. On March 10, 1995, the trial court held a suppression hearing. On April 19, 1995, the trial court suppressed the cocaine because it found that it was the fruit of an unreasonable search and seizure. Fields was released from custody at that time on a $100,000 bond and was permitted to return to his home in Seattle, Washington.
8
On April 26, 1995, the state filed an appeal from the trial court's decision to suppress the cocaine. The state served Fields's attorney, Donald Tittle, but made no effort to serve Fields himself. Tittle, apparently, no longer believed he represented Fields. Tittle states in his affidavit that, at that time, he informed both the prosecutor and the court of appeals that he had not been retained to represent Tittle for the state's appeal and that he believed that Tittle was indigent. Tittle did not, however, file a motion to withdraw from representation before the appeals court reached a decision on the suppression issue and neither Tittle nor Fields filed a brief on the merits.
9
On February 1, 1996, the Eighth District Court of Appeals for the State of Ohio reversed the trial court's order suppressing the evidence. See State v. Fields, Cuyahoga App. No. 68906, unreported (Feb. 1, 1996). The trial judge, later, signed an affidavit stating that the prosecutor had not provided the appellate court with a full record. The transcript submitted to the appellate court did not contain the trial judge's statement that he granted the motion to suppress because he did not find the police officers' testimony credible.
10
The opinion first appeared with Tittle's name on it as counsel of record. Tittle filed a motion asking to have his name removed from the opinion. On February 6, 1996, the Cuyahoga County Public Defender filed a motion for reconsideration of the appellate court opinion, because Fields was not represented by counsel on appeal. On February 29, 1996, the appellate court denied the motion for reconsideration and granted Tittle's motion to remove his name as counsel of record on appeal.
11
The Cuyahoga County Public Defender's office then filed an appeal to the Ohio Supreme Court claiming that Fields was denied the assistance of counsel on appeal. On July 2, 1997, the Supreme Court denied leave to appeal. Fields also filed an application to reopen in the appellate court, pursuant to Ohio Rule of Appellate Procedure 26(B). On September 5, 1997, the appellate court denied the application on the basis that "Rule 26(B). . . only permits a defendant to apply for reopening of an 'appeal from the judgment of conviction and sentence', based on a claim of ineffective assistance of appellate counsel. The appellate judgment applicant is attempting to reopen is not an appeal from a conviction and sentence, but an appeal by the state pursuant to Crim R. 12(J) and App. R. 4(B)(4)." See Resp. Ex. W. Fields then appealed the appellate court's decision not to reopen the case to the Supreme Court. The Supreme Court dismissed the appeal as not involving any substantial constitutional question.
12
After the case was remanded to the trial court, Fields entered a plea of nolo contendere to the three counts against him. On April 27, 1998, Fields filed a notice of appeal to the Eighth District Court of Appeals. On July 6, 1998, Fields moved to dismiss his direct appeal in order to pursue remedies in Federal Court.
II. LAW & ANALYSIS
13
Fields asserts that he was denied any assistance of counsel on the state's interlocutory appeal of the trial court's suppression order. Respondent contends the Court should not grant Fields's petition because (1) petitioner has not exhausted his state remedies as to the issue raised in that petition, (2) the issue lacks merit, either because Fields cannot show that he lacked effective assistance of counsel on appeal, or under the doctrine of invited error. The Court will address each of respondent's arguments in turn.
A. Exhaustion
14
Fields asserts that he has exhausted the only claim presented to this Court. He asked the appellate court to reconsider its decision and to reopen the case. The appellate court refused. He has also presented the issue twice to the Ohio Supreme Court, who, both times, refused to hear it. Despite these efforts, Respondent asserts that petitioner failed to exhaust his claims because he did not pursue a direct appeal from his sentence and conviction after pleading nolo contendere. Respondent asserts further that, because the time has run on Fields's ability to directly appeal his sentence and conviction, Fields is barred from attempting to exhaust those claims now because they would be procedurally defaulted.1
15
The Court agrees with the Magistrate Judge that Fields has exhausted his claims. Fields has taken his claim to the highest court in Ohio, and that court had the ability to review the claim on its merits. This is all that is necessary to exhaust his claim. See Tuggle v. Seabord, 806 F.2d 87, 91 (6th Cir. 1986) ("Once an issue of asserted constitutional violation has been presented to the State's highest court, the doctrine of exhaustion of remedies does not require future repetitive presentations to such court by additional attempts through a variety of successive motions"); Coleman v. Maxwell, 351 F.2d 285, 286 (6th Cir.1965)("It is clear to this court that once an issue of asserted federal constitutional violation has been presented to the highest state court in the state concerned, that the doctrine of exhaustion of remedies does not require futile repetitive presentation to such court by repeated attempts through a variety of motions"). "[O]nce [a] federal claim has been fairly presented to the state courts, the exhaustion requirement is satisfied." Castille v. Peoples, 489 U.S. 346, 350 (1989) quoting Picard v. Connor, 404 U.S. 270, 275 (1971); Anderson v. Harless, 459 U.S. 4, 6 (1982); Koontz v. Glossa, 731 F.2d 365, 369 (6th Cir.1984).
16
Because Fields has presented this constitutional issue twice to both the Ohio Appellate Court and the Ohio Supreme Court, and there is no reason to believe those courts would or could change their views of the issue, the issue is exhausted and not subject to procedural default.2 Cf. Coleman v. Thompson, 501 U.S. 722, 749 (1991) ("In all cases in which a state prisoner has defaulted his federal claims in state court pursuant to an independent and adequate state procedural rule, federal habeas review of the claims is barred unless the prisoner can demonstrate cause for the default and actual prejudice as a result of the alleged violation of federal law, or demonstrate that failure to consider the claims will result in a fundamental miscarriage of justice").3
B. Merits
1. Assistance of Counsel
17
The respondent asserts two arguments on the merits of Fields's habeas petition. First, respondent asserts that Fields cannot prevail on an ineffective assistance of counsel claim under Strickland v. Washington, 466 U.S. 668 (1984). This Court agrees with the Magistrate Judge that the absence of counsel on Fields's appeal of the trial court's suppression finding satisfies Strickland.
18
A defendant is entitled to the effective assistance of counsel in his first appeal as a matter of right. See Smith v. Robbins, 145 L. Ed. 2d 756, 775 (2000); Evitts v. Lucey, 469 U.S. 387, 396 (1985). As the Supreme Court has stated "a criminal appellant must face an adversary proceeding that - like a trial - is governed by intricate rules that to a layperson would be hopelessly forbidding. An unrepresented appellant - like an unrepresented defendant at trial - is unable to protect the vital interests at stake." Id. The state's interlocutory appeal of a trial court's order suppressing evidence is an appeal requiring the effective assistance of counsel just as a direct appeal from a conviction would. See U.S. Ex. Rel. Thomas v. O'Leary, 856 F.2d 1011 (7th Cir. 1988).4
19
Under Strickland, counsel's conduct will only be deemed constitutionally deficient if both of the following are true: (1) counsel's conduct fell below basic standards of assistance, and (2) but for counsel's professional failures, the result of the trial would likely have been different - i.e., the defendant was prejudiced thereby. In Strickland, therefore, the Supreme Court held that a petitioner must demonstrate cause and prejudice to prevail on an ineffective assistance of counsel claim. To demonstrate cause, the petitioner must show "that counsel's representation fell below an objective standard of reasonableness." Strickland, 466 U.S. at 687-88. "The objective standard of reasonableness is 'highly deferential' and includes a 'strong presumption that counsel's conduct falls within the wide range of reasonable professional assistance.'" Skaggs v. Parker, 27 F.Supp.2d 952, 967 (1998) quoting Strickland, 466 U.S. at 688, 689. Under this standard, "[t]he assistance required of counsel is not that of the most astute counsel, but rather that of 'reasonably effective assistance.'" Id.
20
Fields's counsel did not provide any assistance at all, let alone effective assistance. Respondent, itself, points out that Fields's counsel breached his duty to inform his client and the court of the fact that he no longer represented Fields and to inform his client that an appeal had been taken. See Boyd v. Cowan, 494 F.2d 338 (6th Cir. 1974) ("Denial of constitutional right to appeal [may result from] failure of retained counsel to perfect an appeal when the facts in the case impose a duty upon him to do so"). Fields's counsel, moreover, violated several Ethical Considerations under the Ohio Code of Professional Responsibility in leaving his client with no representation on appeal of the suppression issue. See EC 2-30 ("Trial counsel for a convicted defendant should continue to represent his client by advising whether to take an appeal and, by representing him through the appeal unless new counsel is substituted or withdrawal is permitted by the appropriate court."); EC 2-31 ("a lawyer should protect the welfare of his client by giving due notice of his withdrawal, suggesting employment of other counsel, delivering to the client all papers and property to which the client is entitled, cooperating with counsel subsequently employed, and otherwise endeavoring to minimize the possibility of harm"). See also Summers v. Thompson, 444 F.Supp. 312, 314 (M.D. Tenn. 1977) (finding ineffective assistance of counsel when counsel failed to notify his client that he was withdrawing from further representation). The Court, therefore, finds that Fields passes the first prong of Strickland.
21
The Court also finds that Fields was prejudiced by the lack of assistance. In this respect, the Court must ascertain whether counsel's conduct "so undermined the proper functioning of the adversarial process that the trial cannot be relied on as having produced a just result." Skaggs v. Parker, 27 F.Supp.2d 952, 967 (1998) quoting Strickland, 466 U.S. at 686.Fields was not able to present any argument to advocate for affirmation of the suppression order, which, by itself, is enough to show prejudice. See U.S. Ex Rel. Thomas v. O'Leary, 856 F.2d 1011 (7th Cir. 1988) (holding that lack of counsel during state's appeal of trial court's decision to suppress evidence is ineffective assistance of counsel per se). See also United States v. Cronic, 466 U.S. 648 (1984) ("The presumption that counsel's assistance is essential requires us to conclude that a trial is unfair if the accused is denied counsel at a critical stage of his trial"); Green v. Arn, 809 F.2d 1257, 1263 (6th Cir. 1987) vacated on other grounds, 108 S.Ct. 52 (1987), reinstated 839 F.2d 300 (6th Cir.1988) ("Where the Sixth Amendment claim is the denial, rather than the ineffective assistance, of counsel, the criminal defendant need only show that counsel was absent during a critical stage of the proceedings in order to establish the constitutional violation. Absence from the proceedings is deficient performance as a matter of law, and prejudice is presumed").
22
More specifically, however, Fields was unable to point out that the appellate court did not have the full record of the suppression proceedings before it. The trial court's statement that it was suppressing the drugs because it did not find the testimony of the police officers to be credible was not included in the transcript. See Aff. of Judge Richard McMonagle ("I stated in open court that I was granting the motion because I did not find the police officers testimony credible. The statement that I did not find the officers' testimony credible was not contained in the transcripts of the proceedings although it should have been in them"). The appellate court, therefore, was unaware of this basis for the trial court's decision. If the trial court's credibility determination had been included in the transcript, the appellate court would have been required to give that determination great deference.5 The appellate court's analysis of the reasonableness of the search and seizure, therefore, would have changed substantially. This clearly satisfies the prejudice prong of Strickland.6 The Court, thus, finds that Fields lacked the effective assistance of counsel on the appeal of the suppression hearing.
2. Invited Error
23
Second, respondent argues that Fields cannot raise an error that he provoked under the doctrine of invited error. The doctrine of "invited error" is a branch of the doctrine of waiver in which courts prevent a party from inducing an erroneous ruling and later seeking to profit from the legal consequences of having the ruling set aside. Harvis v. Roadway Express, Inc., 923 F.2d 59, 61 (6th Cir.1991). When a petitioner invites an error in the trial court, he is precluded from seeking habeas corpus relief for that error. See Leverett v. Spears, 877 F.2d 921, 924 (11th 1989); Draugh v. Jabe, 803 F.Supp. 70, 75 (E.D.Mich.1992).
24
Respondent proffers no evidence that Fields invited any error, however, but merely insinuates that the Cuyahoga County Public Defenders office and Fields's retained counsel, Tittle, colluded to leave Fields without counsel on appeal so that he would have a reason to appeal the reversal of the suppression to the Supreme Court. This argument borders on the absurd; why would Tittle create an issue for appeal, when the remedy for that error would be to provide Fields with counsel on appeal, something that Tittle simply could have done in the first instance. This argument also ignores that the Ohio Court of Appeals, apparently, would had to have taken part in the collusion when it agreed to grant Tittle's motion to remove his name from the appeal. That Tittle later reinvolved himself in Fields's case by filing a motion to re-open proceedings, and that Tittle worked with the Cuyahoga County Public Defenders office to provide evidence that he did not believe that he represented Fields on appeal is not evidence of collusion, or evidence that Fields invited this error to create an issue for appeal; it is simply evidence that Tittle came to realize that his abandonment of Fields was both improper and prejudicial. The Court finds this argument to have no merit.
III. CONCLUSION
25
Accordingly, the Court adopts the report and recommendation of Magistrate Judge David S. Perelman. Fields's Petition for Habeas Corpus is GRANTED; Fields must be provided the opportunity to defend the appeal of the trial court's suppression ruling in the state court of appeals. If Fields is not provided such opportunity within ninety (90) days of this Order, his conviction must be vacated.
26
IT IS SO ORDERED.
Notes:
*
The Honorable Edmund A. Sargus, Jr., United States District Judge for the Southern District of Ohio, sitting by designation.
1
"[I]f the petitioner failed to exhaust state remedies and the court to which the petitioner would be required to present his claims in order to meet the exhaustion requirement would now find the claims procedurally barred[, then] there is a procedural default for purposes of federal habeas regardless of the decision of the last state court to which the petitioner actually presented his claims." See Coleman v. Thompson, 501 U.S. 722 (1991).
2
In Ohio, the law-of-the-case doctrine "provides that the decision of a reviewing court in a case remains the law of that case on the legal questions involved for all subsequent proceedings in the case at both the trial and reviewing levels." Nolan v. Nolan, 11 Ohio St. 3d 1, 4, 2-13 (1984). Although there is some possibility that the Court of Appeals and the Ohio Supreme Court could have addressed Fields's constitutional issue on a direct appeal from his conviction and sentence, notwithstanding this law of the case doctrine, see State v. Patterson, 1996 WL 210773 (Ohio App. 1996), that possibility is slim. While it is true that the law of the case doctrine is only "considered to be a rule of practice rather than a binding rule of substantive law and will not be applied so as to achieve unjust results," Nolan, 11 Ohio St.3d at 3-4, exceptions to the law of the case doctrine are only applied under the rarest of circumstances, and may not be invoked as a way in which an unsuccessful litigant can have his case redetermined. See Gen. Acc. Ins. Co. v. Ins. Co. of N. Am., 90 Ohio App.3d 490 (1993); Weaver v. Motorists Mut. Ins. Co., 68 Ohio App.3d 547 (1990). Thus, the possibility that these Courts might address the issue under some rare exception to the law of the case doctrine does not mean that Fields has not sufficiently exhausted the issue.
3
If the issue had been presented to the state Supreme Court only once, and that Court had refused to consider it based on a procedural rule (such as the inapplicability of Rule 26(B) to interim appeals by the state), this Court's view of the exhaustion question might well be different. That is not the case here, however.
4
Indeed, respondent does not assert that the state's appeal of the suppression decision was not a critical stage of the proceeding during which Fields would have no right to counsel.
5
When considering a motion to suppress, the trial court is the primary judge of the credibility of witnesses and the weight of the evidence. State v. Fanning, 1 Ohio St.3d 19, 20 (1982). If the trial court's findings are supported by competent and credible evidence, then the appellate court must accept them. See State v. Williams, 86 Ohio App. 3d 37, 41 (1993). A reviewing court can evaluate evidence in terms of sufficiency, but it cannot second guess the trial court's determination of credibility. Id. Once the trial court determines the facts, however, the appellate court determines "without deference, whether the court has applied the appropriate legal standard." See State v. Anderson, 100 Ohio App.3d 688, 691 (1995). See also State v. Klump, 2000 WL 744981 (Ohio App. June 12, 2000).
6
The Ohio Court of Appeals was aware of Fields's lack of counsel at the appellate stage; it allowed Tittle to withdraw his name from the appeal without giving Fields the chance to present argument to the appellate court through substitute counsel, despite multiple requests to do so.
|
Catherine of Vendôme
Catherine de Vendôme (1354 – 1 April 1412) was a ruling countess of Vendôme and of Castres from 1372 until 1403.
Life
She was the daughter of John VI of Vendôme and Jeanne of Ponthieu. She married John I, Count of La Marche, in 1364.
In 1372 inherited Vendôme on the death of her niece Jeanne and administered it jointly with her husband, then (after his death) with her second son Louis until 1403.
Issue
James II, Count of La Marche and Castres (1370–1438)
Isabelle (born 1373), a nun at Poissy
Louis, Count of Vendôme (1376–1446)
John, Lord of Carency (1378–1457), married c. 1416 Catherine, daughter of Philip of Artois, Count of Eu, without issue, married in 1420 at Le Mans, his mistress Jeanne de Vendômois, with whom he had issue
Anne (c. 1380 – September 1408, Paris), married in 1401 John of Berry, Count of Montpensier (d. 1401), married in Paris in 1402 Louis VII, Duke of Bavaria
Marie (1386 – aft. 11 September 1463), Lady of Brehencourt, married Jean de Baynes, Lord of Croix
Charlotte (1388 – 15 January 1422), married in 1411 at Nicosia King Janus of Cyprus
Ancestry
References
Sources
Category:1354 births
Category:1412 deaths
Category:Counts of Vendôme
Category:French suo jure nobility
Category:Counts of Castres
Category:14th-century women rulers
Category:15th-century women rulers
Category:14th-century French people
Category:14th-century French women
Category:15th-century French people
Category:15th-century French women |
Contact fastrak44
Ambulances have been called to Clarkson station after a train crashed into another stationary train while rail commuters were boarding their Perth-bound ride on Tuesday morning.Public Transport Authority spokesman David Hayes said precautionary ambulances were called after some passengers expressed they had neck pain after the accident.Mr Hayes said it is believed an empty train had travelled up behind the stationary Perth-bound train and hit it as commuters boarded.He said the incident was at low speed and the two trains had been taken out of service.Advertisement"It was a bit of a bump and a jar. It's not 100 miles an hour and bodies everywhere," he said.
Posted: 03 Sep 2013 10:41
Contact fastrak44
Ambulances have been called to Clarkson station after a train crashed into another stationary train while rail commuters were boarding their Perth-bound ride on Tuesday morning.Public Transport Authority spokesman David Hayes said precautionary ambulances were called after some passengers expressed they had neck pain after the accident.Mr Hayes said it is believed an empty train had travelled up behind the stationary Perth-bound train and hit it as commuters boarded.He said the incident was at low speed and the two trains had been taken out of service.Advertisement"It was a bit of a bump and a jar. It's not 100 miles an hour and bodies everywhere," he said.
Contact steamboy65
As a reasonably regular user of Clarkson station, I've been expecting an incident of this nature for some time. When trains leave Nowergup depot in quick succession in the early morning, it appears to be common practice for an empty train to pull in close behind one that is in the platform loading.
I would question why this is necessary. Obviously the signalling will allow it, but the closest together any departures are timed is 3 minutes. This leaves ample time for one train to clear the platform before the next arrives. It's all very well to blame rail surface contamination but the whole issue could be avoided if there was a bit more separation maintained between trains.
I've also noticed similar practices at Whitfords in the past. It would be interesting to know if this is the way the automatic route setting is designed or whether it requires some manual input in the control room to allow entry into an occupied platform.
It was certainly interesting to see what appeared to be a 7 car train when I got off the bus this morning!
Contact Northmetro
according to the channel seven news there were millipedes on the line causing on of the trains to slidesteamboy65
Had same issue couple months ago whilst on footplate of the HVTR Restaurant Train....
Crawling along at 10km hr and we slowly came to a stop with slow wheel spin. On inspection of the situation we noticed thousands of the little things all over the rails! Bit of a wipe with sole of a size 11 steel cap boot to clear the rails up to 5 metres in front of the locomotive we were under way again..... |
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Power Cables
Structure of the New Standard
AJH Cable Solutions aims to provide excellent customer care without compromising quality or price at the highest standards possible. To ensure this, all products are manufactured in accordance with BS EN 62305, BS EN 50164 and BS 7430.
BS 65551 has now been replaced with a combination of new standards based on the recently introduced CENELEC (European) standards.
Structure of the New Standard:
BS EN 62305 is a series of publications in four parts, all of which have to be taken into consideration when designing lightning protection.
BS EN 6230 (Part 1) General Principles. This is an introduction to other parts of the standard and covers the general principles involved in the design. The sources and types of damage that need to be evaluated are clarified together with the types of loss/ risk that are possible due to lightning. It defines the relationship between damage and loss that are the basis for the risk assessment calculations in part 2 and also introduces the concepts Lightning Protection Zones (LPZs) and separation distances used when preparing a lightning protection scheme. The definitions of lightning current parameters are also provided and these are used in selection and implementation protection measures as detailed in parts 3 and 4.
BS EN 62305-2 (Part 2) Risk Management. This is significantly more detailed than in previous standards and details the process for determining the risk of lightning damage to structures and their contents. The results of the risk assessment determine the level of Lightning Protection System (LPS), both internal and external, required.
BS EN 62305-3 (Part 3) Physical Damage to Structures and Ufe Hazard. This part of the new standard relates most closely with BS 6651 and deals with the protection measures to be used in and around a structure. It gives guidance on the design of both internal and external Lightning Protection Systems. An external LPS consists of an Air Termination System, a Down Conductor System and an Earth Termination System the parts of which require to be connected by components complying with the BS EN 50164 series.The AJH Cable Solutions range of products are tested by independent testing facilities and comply with the BS EN 50164 series of standard for the manufacture of lightning protection components. BS EN62305-4 (Part 4) Electrical and Electronic Systems within Structures. This standard covers the protection of electrical and electronic systems within structures. Using the concept of Lightning Protection Zones (LPZs) it covers the design, installation, maintenance and testing of an LEMP – Lightning Magnetic Impulse Protection system within a structure.
Lightning Protection Components:
Previous standards for Lightning Protection recommended the use of specific materials for lightning protection components. Now with the release of BS EN 50164 series of standards the focus is on performance and testing. This standard consists of the following parts. |
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