text stringlengths 8 5.77M |
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# Kalaallisut translations for mouse-touchpad-plug package.
# Copyright (C) 2018 THE mouse-touchpad-plug'S COPYRIGHT HOLDER
# This file is distributed under the same license as the mouse-touchpad-plug package.
# Automatically generated, 2018.
#
msgid ""
msgstr ""
"Project-Id-Version: mouse-touchpad-plug\n"
"Report-Msgid-Bugs-To: \n"
"POT-Creation-Date: 2019-06-26 22:45+0200\n"
"PO-Revision-Date: 2018-03-05 23:53+0000\n"
"Last-Translator: Automatically generated\n"
"Language-Team: none\n"
"Language: kl\n"
"MIME-Version: 1.0\n"
"Content-Type: text/plain; charset=ASCII\n"
"Content-Transfer-Encoding: 8bit\n"
#: src/Plug.vala:43
msgid "Mouse & Touchpad"
msgstr ""
#: src/Plug.vala:44
msgid "Configure mouse and touchpad"
msgstr ""
#: src/Plug.vala:63
msgid "General"
msgstr ""
#: src/Plug.vala:64 src/Plug.vala:117 src/Plug.vala:118 src/Plug.vala:119
#: src/Plug.vala:120
msgid "Mouse"
msgstr ""
#: src/Plug.vala:65 src/Plug.vala:121 src/Plug.vala:122 src/Plug.vala:123
#: src/Plug.vala:124 src/Plug.vala:125 src/Plug.vala:126 src/Plug.vala:127
#: src/Plug.vala:128
msgid "Touchpad"
msgstr ""
#: src/Plug.vala:110
msgid "Primary button"
msgstr ""
#: src/Plug.vala:111
msgid "Reveal pointer"
msgstr ""
#: src/Plug.vala:112
msgid "Long-press secondary click"
msgstr ""
#: src/Plug.vala:113
msgid "Long-press length"
msgstr ""
#: src/Plug.vala:114
msgid "Middle click paste"
msgstr ""
#: src/Plug.vala:115
msgid "Control pointer using keypad"
msgstr ""
#: src/Plug.vala:116
msgid "Keypad pointer speed"
msgstr ""
#: src/Plug.vala:118 src/Plug.vala:122
msgid "Pointer speed"
msgstr ""
#: src/Plug.vala:119
msgid "Pointer acceleration"
msgstr ""
#: src/Plug.vala:120 src/Plug.vala:126
msgid "Natural scrolling"
msgstr ""
#: src/Plug.vala:123
msgid "Tap to click"
msgstr ""
#: src/Plug.vala:124
msgid "Physical clicking"
msgstr ""
#: src/Plug.vala:125
msgid "Scrolling"
msgstr ""
#: src/Plug.vala:127
msgid "Ignore while typing"
msgstr ""
#: src/Plug.vala:128
msgid "Ignore when mouse is connected"
msgstr ""
#: src/Views/General.vala:30
msgid "Primary button:"
msgstr ""
#: src/Views/General.vala:34
msgid "Left"
msgstr ""
#: src/Views/General.vala:37
msgid "Right"
msgstr ""
#: src/Views/General.vala:73
msgid "Pressing the control key will highlight the position of the pointer"
msgstr ""
#: src/Views/General.vala:79
msgid "Long-press secondary click:"
msgstr ""
#: src/Views/General.vala:84
msgid "Long-pressing and releasing the primary button will secondary click."
msgstr ""
#: src/Views/General.vala:90
msgid "Length:"
msgstr ""
#: src/Views/General.vala:106
msgid "Speed:"
msgstr ""
#: src/Views/General.vala:112
msgid "This disables both levels of keys on the numeric keypad."
msgstr ""
#: src/Views/General.vala:131
msgid "Reveal pointer:"
msgstr ""
#: src/Views/General.vala:135
msgid "Control pointer using keypad:"
msgstr ""
#: src/Views/General.vala:146
msgid ""
"Middle or three-finger clicking on an input will paste any selected text"
msgstr ""
#: src/Views/General.vala:152
msgid "Middle click paste:"
msgstr ""
#: src/Views/Mouse.vala:30 src/Views/Touchpad.vala:48
msgid "Hardware default"
msgstr ""
#: src/Views/Mouse.vala:31
msgid "None"
msgstr ""
#: src/Views/Mouse.vala:32
msgid "Adaptive"
msgstr ""
#: src/Views/Mouse.vala:40 src/Views/Touchpad.vala:86
msgid "Pointer speed:"
msgstr ""
#: src/Views/Mouse.vala:42
msgid "Pointer acceleration:"
msgstr ""
#: src/Views/Mouse.vala:46 src/Views/Touchpad.vala:95
msgid "Natural scrolling:"
msgstr ""
#: src/Views/Touchpad.vala:49
msgid "Multitouch"
msgstr ""
#: src/Views/Touchpad.vala:50
msgid "Touchpad areas"
msgstr ""
#: src/Views/Touchpad.vala:64
msgid "Two-finger"
msgstr ""
#: src/Views/Touchpad.vala:65
msgid "Edge"
msgstr ""
#: src/Views/Touchpad.vala:66
msgid "Disabled"
msgstr ""
#: src/Views/Touchpad.vala:88
msgid "Tap to click:"
msgstr ""
#: src/Views/Touchpad.vala:90
msgid "Physical clicking:"
msgstr ""
#: src/Views/Touchpad.vala:93
msgid "Scrolling:"
msgstr ""
#: src/Views/Touchpad.vala:97
msgid "Ignore while typing:"
msgstr ""
#: src/Views/Touchpad.vala:99
msgid "Ignore when mouse is connected:"
msgstr ""
|
Ener-Con is proud to welcome our 2014 Guest of Honour Michael Chain to the convention this August!
Michael is best known to Transformers fans as the Generation 1 voices of Powerglide, Hoist, Red Alert, Raoul & Skids! As well Michael is an accomplished musician & writer, having worked on cartoon series like She-Ra, Rambo, Police Academy and more.
Michael will be at Ener-Con all weekend long, meeting fans and signing autographs, as well as taking part in a Q&A and Script reading alongside Ener-Con attendees.
Fraser Paintcustoms will be bringing his amazing skills to Ener-Con! Fraser will be set up all weekend offering to battle damage Transformers for attendees, as well as showing off and selling his other great work.
As well Fraser will be hosting a panel on how to battle damage a Transformer, and customizing in general! Here is your chance to learn some tips and tricks from one of the best customizers in Manitoba!
As well a children's activity area will be set up all weekend long featuring scheduled activities for kids to take part in. From papercraft Transformers building courtesy of Kiriharu, to coloring, to a Build Your Own Kreon panel(for a slight cost being passed long to charity by Ener-Con) there will be a ton of things for kids to see and do at Manitoba's First Transformers Fan Convention!
You can find Kiriharu at www.kiriharu.com and print off your own papercrafts for free!
Ener-Con is pleased to welcome IDW Comic Artist James Raiz as a special guest!
James will be making his first convention appearance since 2002!
Known currently for his work on IDW's recent ongoing 'Dark Cybertron' series, James has been working on Transformers for over a decade going all the way back to Dreamwave's Armada series in 2002. His credits include many different subgenres from the Transformers franchise including Generation 1, Beast Wars, 2007 Transformers the Movie, Armada, Energon & Cybertron plus more! As well his work has appeared on Hasbro package art at toy stores near you.
In addition to Transformers James has also worked on high profile title for Marvel & DC like Wonder Woman, The Incredible Hulk & Birds of Prey. As well he works as a visual artist for film, TV and Video Games with credits including Splinter Cell: Blacklist, Abraham Lincoln Vampire Hunter & Stargate: The Ark of Truth just to name a few.
James will be at Ener-Con all weekend long meeting fans, signing autographs, showcasing his art, selling prints and taking part in Q&A's and Panels.
Ener-Con will feature dozens of different vendors, from local collectors trying to sell off a few items to expand their own collections to larger sellers like Evolution Collectibles!(Seen here as they were set up at Calgary Expo!) |
High cholesterol costs Australia $4 billion
News / 2018.11.28
Share this
High cholesterol placed an estimated $4 billion burden on the Australian economy in 2017-18, with more than one in three adult Australians, or 7.1 million people, estimated to be living with high cholesterol, according to a new Heart Foundation report.
Most of this cost is due to heart disease and ischaemic stroke, for which high cholesterol is a key risk factor. In fact, in Australia more than half of the $7.3 billion cost of heart disease, and twelve per cent of the $1.3 billion cost of ischaemic stroke, can be attributed to high cholesterol.
High cholesterol also places a burden on individuals. In 2017-18 it was estimated that Australians spent close to $100 million out-of-pocket on lipid lowering medications.
Heart Foundation Group CEO, Adjunct Professor John Kelly AM, said: “Despite these figures, the lack of symptoms associated with high cholesterol mean that most Australians with the condition are not receiving the recommended treatment.
“This puts them at a greater risk of heart attack and stroke, and of developing life-threatening diseases such as heart disease and type 2 diabetes. Thousands of heart attacks and strokes could be averted if people aged 45-74 visited their GP for a heart health check and those with high cholesterol were properly treated and managed.”
The Heart Foundation recommends establishing a national target for heart health checks, with the aim of having 90 per cent or more of the eligible population assessed for cardiovascular risk within five years. |
Q:
Email Collector / Implementation
I am implementing a simple RoR webpage that collect emails from visitors and store them as objects.
I'm using it as a mini-project to try RoR and BDD. I can think of 3 features for Cucumber:
1. User submits a valid email address
2. User submits an existing email address
3. User submits an invalid email
My question is, for scenarios 2 and 3, is it better to handle this via the controller? or as methods in a class? Perhaps something that throws errors if an instance is instantiated in sceanrio 2 or 3?
Implementation is below, love to hear some code reviews in addition to answers to questions above. Thanks!
MODEL:
class Contact < ActiveRecord::Base
attr_accessor :email
end
VIEW:
<h1>Welcome To My Experiment</h1>
<p>Find me in app/views/welcome/index.html.erb</p>
<%= flash[:notice] %>
<% form_for @contact, :url => {:action => "index"} do |f| %>
<%= f.label :email %><br />
<%= f.text_field :email %>
<%= submit_tag 'Submit' %>
<% end %>
CONTROLLER:
class WelcomeController < ApplicationController
def index
@contact = Contact.new
unless params[:contact].nil?
@contact = Contact.create!(params[:contact])
flash[:notice] = "Thank you for your interest, please check your mailbox for confirmation"
end
end
end
A:
To perform the last two steps, I recommend you use rails validations. For example, try updating your model to look something like this:
class Contact < ActiveRecord::Base
attr_accessor :email
validates_uniqueness_of :email
validates_format_of :email, :with => /\A(\S+)@(\S+)\Z/i
end
|
Q:
mod_rewrite rule
What rule translates urls like so?
host.com/plastic_toys/pink_barbie/
host.com/index.php?q=plastic+toys+pink+barbie
The number of components in the category and product name vary.
Edit:
I guess this rule does part of the job:
RewriteRule ^([^/]*)/([^/]*)$ /index.php?q=$1+$2 [L]
The problem with the above rule is that it does not take care of converting underscores to +, so it translates like this:
host.com/plastic_toys/pink_barbie/
host.com/index.php?q=plastic_toys+pink_barbie
I guess I have to delegate that conversion to PHP. Now is there a way to test if the rule actually does the conversion the way I imagine it would?
A:
Is there a reason (existing code, etc) that you need to do this totally as a rewrite?
Normally, I do
RewriteCond %{REQUEST_FILENAME} !-f
RewriteCond %{REQUEST_FILENAME} !-d
RewriteRule ^(.*)$ index.php?q=$1 [L,QSA]
and then parse $_GET["q"] or even just parse $_SERVER["REQUEST_URI"] directly. preg_match() is your friend here.
It takes way less time to use one of these two methods than it does trying to come up with a weird rewrite.
A:
First - I would suggest using the following rules:
RewriteCond %{REQUEST_FILENAME} !-f
RewriteCond %{REQUEST_FILENAME} !-d
RewriteRule ^([a-zA-Z_]+)/([a-zA-Z_]+)/?$ /index.php?q1=$1&q2=$2 [L,QSA]
The RewriteCond each check that a valid file or directory does not exist (for instance if you want to have a static /help.html and it exists, or /FAQ/index.php and it exists then the RewriteRule will not fire.
I've split out the parameters into 2 items - so you can treat them as separate parameters (if you want to treat it as 1 parameter just change it to /index.php?q=$1-$2 or some other separator that you want - I would say do not use + since you want to parse off that character anyway).
|
Jamaican anti-gay lawyer, Shirley Richards, wrote a letter to the editor condemning the cancellation of a performance by homophobic reggae artiste, Queen Ifrica. Ifrica was scheduled to perform at Rastafest in Toronto on August 24. This event was partially funded by the Toronto Public Library and Service Canada, both of which are taxpayer-supported entities.
Citing several incidents where anti-gay persons have had their freedom of speech curtailed, she concludes that this will lead to the end to freedom of thought in Jamaica(!). She wrote in “The LGBT Agenda and Free Speech” in the Jamaica Gleaner: What has happened to Queen Ifrika is just another example of the danger that the lesbian, gay, bisexual and transgender agenda poses to free speech. This is what Crystal Dixon discovered. In 2008, she dared to write in a local newspaper that choosing homosexual behaviour is not the same as being black or handicapped. These were some of her words: “As a black woman, I take great umbrage at the notion that those choosing the homosexual lifestyle are ‘civil rights victims.’ Here’s why. I cannot wake up tomorrow and not be a black woman.” For these words she lost her job as associate vice-president, University of Toledo. … [Richards also cites the removal of “ex-gay” gospel singer Donnie McClurkin from the program of an Aug. 24 Martin Luther King Jr. memorial concert on Aug. 24 and a reported demotion of an employee of the Trafford Housing Trust in England for various Facebook posts opposed to marriage equality.] We warn of a growing cultural totalitarianism – at this point, it is insisting on no criticism in speech with punishment for those who dare to disobey. Soon it will be mandatory endorsement in speech. Will it also move to mandatory endorsement in thought?
Her views have been expressed by the over 13 groups opposing the challenge to the Jamaican anti-sodomy law which is currently before the court.
Please see my response to her letter below.
Dear Ms. Richards,
CVM TV reported that on August 22, 2013, there was a mob attack on the home of 5 suspected gay men in Manchester.
This is the 6th public and reported homophobic incident in a month and is therefore not an anomaly. Like all acts of crime, this incident is merely representative of a general trend since TV cameras cannot possibly capture every assault.
The attack on Aug. 22 follows:
1) The murder of 17 year-old cross-dresser, Dwayne Jones at a public street-party on July 22 and the dumping of his body in nearby bushes while party-goers went on dancing. The country’s Minister of Justice condemned the barbaric act;
2) The mob attack of a suspected police officer in downtown Kingston on August 1 who had to be rescued by other officers firing shots in the air and teargas into the crowd;
3) A mob attack on the home of 2 gay persons in St. Catherine also on August 1. They too had to be rescued by police;
4) A homophobic performance at a publicly funded national independence celebration on August 6 for which the Minister of Culture had to publicly apologize; and
5) A mob attack on a cross-dresser in St. Catherine on August 10. The police again had to rescue the individual.
[Huffington Post reports on the 6th homophobic attack in Jamaica in a month on Aug. 22. “A new video that shows a mob of people barricading five gay men inside of their home in a Jamaican village is currently making the rounds on the Internet. … The men were reportedly trapped in their home by the crowd until police arrived and escorted them to safety.”]
This spate of attacks demonstrates that the Jamaican government MUST do more to promote and protect the human rights of LGBT Jamaicans. Apologizing after the fact is not enough.
These brutal assaults also demonstrate that the hate Jamaicans feel towards LGBT citizens is real. Therefore, Ifrica’s anti-gay music cannot be encouraged in this toxic environment. It is reasonable that her freedom of speech be limited in order to save lives. Allowing her to continue her vitriolic performance at taxpayers’ expense would be tantamount to shouting “Fire!” in a crowded theatre with all the exits barricaded! Someone will get hurt.
Preventing Ifrica from singing about her hate for gays is a small price to pay in order to save lives.
Related articles |
Q:
When ACID is not important?
I read a topic on Cassandra DB. It wrote that it's good for app that do not require ACID property.
Is there any application or situation that ACID is not important?
A:
There are many (most?) scenarios where ACID isn't needed. For example, if you have a database of products where one table is id -> description and another is id -> todays_price, and yet another is id -> sales_this_week, then there's no need to have all tables locked when updating something. Even if (for some reason) there are some common bits of data across the three tables, depending on usage, having them out of sync for a few seconds may not be a problem. Perhaps the monthly sales are only needed at the end of the month when aggregating a report. Not being ACID compliant means not necessarily satisfying all four properties of ACID... in most business cases, as long as things are eventually consistent with each other, it may be good enough.
It's worth mentioning that commits affecting the same cassandra partition ARE atomic. If something does need to be atomically consistent, then your data model should strive to put that bit of information in the same partition (and as such, in the same table). When we talk about eventual consistency in the context of cassandra, we mean things affecting different partitions (which could be different rows in the same table), not the same partition.
The canonical example of "transaction" is a debit from one account, and a credit from another.... this is "important" because "banks". In reality, this is not how banks operate. What such a system does need is a definitive list of transactions (read transfers). If you were to model this for cassandra, you could have a table of transfers consisting of (from_account, to_account, amount, time, etc.). These records would be atomically consistent. Your "accounts" tables would be updated from this list of transfers. How soon this gets reflected depends on the business. For example, in the UK, transfers from Lloyds bank to Lloyds bank are almost instant. Whereas some inter-bank transfers can take a couple of days. In the case of the latter, your account's balance usually shows the un-deducted amount of pending transfers, while a separate "available balance" considers the pending transfers.
Different things operate at different latencies, and in some cases ACID, and the resultant immediate consistency across all updated records may be important. For a lot of others though, specially when dealing with distributed systems with lots of data, ACID at the database level may not be required.
Even where "visible consistency" is required, it can often be handled with coordination mechanisms at the application level, CRDTs, etc. To the end user, the system is atomic - either something succeeds, or it doesn't, and the user gets a confirmation. Internally, the system may be updating multiple database, dealing with external services, etc., and only confirming when everything's peachy. So, ACID for different rows in a table, or across tables in a single database, or even across multiple databases may not be sufficient for externally visible consistency. Cassandra has tunable consistency where by you can use data modelling, and deal with the tradeoffs to make a "good enough" system that meets business requirements. If you need ACID transactionality across tables, though - Cassandra wouldn't be fit for that use case. However, you may be able to model your business requirements within cassandra's constraints, and use it to get the other scalability benefits it provides.
|
My Garry's Mod Gallery
I've not really got much to say this week as, between Bionic Commando and Order of War this has been a pretty boring week for me, truth be told. I've spent most of my time playing through Clive Barker's Undying again and realising it wasn't as good as I remembered and playing Garry's Mod 10.
Garry's Mod 10, or GMod, for those not in the know began life as a small mod for Half-Life 2 that allowed you to fiddle about with the game physics. Over time it evolved and grew, with new tools getting added in along the way until it ended up as it is now - a commercial product that's the video game equivalent of a Lego set.
Garry's Mod 10 is, to me, the ultimate sandbox game. You can do anything. You can create anything. You can manipulate ragdolls however you want - which isn't always a good thing. You can weld items together, add rockets, wheels, ropes, pulleys and balloons. You can literally make anything from sculptures to rocket-powered mecha robots.
Click to enlarge any picture
Then, as if that weren't enough, you can create your own models to import into the game and your own gamemodes and rule systems using the LUA language. There's tonnes of add-ons out there for it which let you do everything from role-play as shopkeepers to simulate desert island scenarios.
For me, the main draw of Garry's Mod has always been the posing and, even before it was a commercial product I was active on the official forums creating simple comics and screenshots from within the game.
My posing isn't all that great admittedly, but I enjoy fooling around with the game and putting small little situations together. Unlike most of the bit-tech crew I'm not a great photographer, so this is the closest I can get. Lacking anything else to talk about, I thought I'd share some of my weekend creations with you all and, if you're into Garry's Mod yourself then I'd love to share models and poses with you in the forums. |
Q:
How to enable extension on WebView2
I've installed a Chrome extension on Microsoft Edge (Chromium) to play HLS video. I've tried on Microsoft Edge (Chromium) and it works fine. The HLS URL is http://localhost/hls/taiguo/playlist.m3u8 and on Microsoft Edge browser and it displays the URL as follows: extension://ekcifneimckhkjdfklkkpdlnckcjhmke/index.html#http://localhost/hls/taiguo/playlist.m3u8.
When I use WebView2 to embed the browser in a Windows application following [Getting Started with WebView2 (developer preview)] (https://docs.microsoft.com/en-us/microsoft-edge/hosting/webview2/gettingstarted) sample code:
` CreateCoreWebView2EnvironmentWithDetails(nullptr, nullptr, nullptr,
Callback(
[hWnd](HRESULT result, ICoreWebView2Environment* env) -> HRESULT {
RETURN_IF_FAILED(result);
// Create a CoreWebView2Host and get the associated CoreWebView2 whose parent is the main window hWnd
env->CreateCoreWebView2Host(hWnd, Callback<ICoreWebView2CreateCoreWebView2HostCompletedHandler>(
[hWnd](HRESULT result, ICoreWebView2Host* host) -> HRESULT {
if (host != nullptr) {
webviewHost = host;
webviewHost->get_CoreWebView2(&webviewWindow);
}
// Add a few settings for the webview
// this is a redundant demo step as they are the default settings values
ICoreWebView2Settings* Settings;
webviewWindow->get_Settings(&Settings);
Settings->put_IsScriptEnabled(TRUE);
Settings->put_AreDefaultScriptDialogsEnabled(TRUE);
Settings->put_IsWebMessageEnabled(TRUE);
// Resize WebView to fit the bounds of the parent window
RECT bounds;
GetClientRect(hWnd, &bounds);
webviewHost->put_Bounds(bounds);
// Schedule an async task to navigate to Bing
webviewWindow->Navigate(L"http://localhost/hls/taiguo/playlist.m3u8");`
If I run the above code, the app will just download the playlist.m3u8 file without playing the video. If I change the URL parameter of webviewWindow->Navigate(...) to:
webviewWindow->Navigate(L"extension://ekcifneimckhkjdfklkkpdlnckcjhmke/index.html#http://localhost/hls/taiguo/playlist.m3u8");
Then I get an error message as shown below:
App screen capture
I hope someone can tell me how to run extension using WebView2 API.
A:
I work on the WebView2 project. Let me start by saying WebView2 currently does not support Extensions. It's a fairly complicated feature and there are quite a few design choices we'd have to make, so before these are ironed out, we deliberately turn extensions off. We're definitely open to supporting it in the future, and there is an issue on our feedback repo tracking the feature request - https://github.com/MicrosoftEdge/WebViewFeedback/issues/81. It'd be lovely to have you chime in and talk about your use case, so we have more context on what you're looking for. For example, developers enabling arbitrary extensions for their app (e.g. I want to have an ad-blocker watching over my web content), which I think is what you're asking, is very different from giving end users a way to install extensions in webview.
That said, from a technical standpoint, even if WebView2 supports extensions today, user-installed extension from the browser would not show up in WebView2. The browser stores its extensions in its user data folder (see C:\Users\username\AppData\Local\Microsoft\Edge SxS\User Data\Default\Extensions for Canary), which also contains stuff like cookies, caches, etc. WebView2 apps have their own user data folder, and cannot use the browser user data because of the security implications.
|
“I Am Willing to Give up This Desire” (Share)
Editor’s Note:Encouraged by our readers’ great interaction with the social and marital problems that we share with them on a weekly basis, we would like to continue our Counseling Q & A series.
This week, you are invited to read through this problem of a young man who really wants to overcome his sex addiction. You can share your advice and thoughts on how he can find ways out of this destructive habit.
Use the comment box to share your advice. Next week, we will post an answer from one of our professional counselor responding to this problem. Keep an eye on our updates!
Because of being sexually abused at a very early age, and then being involved in masturbation, I’m unable to stop it now.
Though in the last three months I have not practiced it, but I still feel a strong craving. I don’t know how to overcome this. Sometimes while sleeping, it happens automatically, and at that time I’m really unable to control this practice.
I used to read the articles published in Onislam.net for overcoming masturbation, and I know every way to overcome it, but the real problem is how to practice these ways and methods when my heart is not willing to practice them.
Now my real problem and question is how can I stop this craving? I pray five times a day, I also fast during Ramadan, but when having these thoughts, I think to myself that I am a hypocrite when offering prayers.
Now, I can’t concentrate on my prayers, and also I don’t get out of the bed even to offer prayers. Please suggest to me some ways to stop thinking about sex-related activities, and to actually stop from the heart.
Editor's Choice
Solidarity among the Muslim community members is one of the strategies that Islam uses to combat hunger. It is not acceptable in Islam that people live under the poverty line while others are spending... |
<!DOCTYPE html>
<html>
<head>
<meta charset="utf-8">
<meta name="viewport" content="width=device-width, initial-scale=1">
<title>EPUB.js Storage Example</title>
<script src="../node_modules/jszip/dist/jszip.min.js"></script>
<script src="../node_modules/localforage/dist/localforage.min.js"></script>
<script src="../dist/epub.js"></script>
<link rel="stylesheet" type="text/css" href="examples.css">
<style type="text/css">
#offline {
position: fixed;
top: -40px;
left: 0;
background-color: yellow;
width: 100%;
text-align: center;
padding: 10px 0;
transition: top .5s;
z-index: 99;
}
</style>
</head>
<body>
<div id="offline">You are offline. Loading from Storage.</div>
<div id="viewer" class="spreads"></div>
<div id="prev" class="arrow">‹</div>
<div id="next" class="arrow">›</div>
<script>
var book = ePub("https://s3.amazonaws.com/moby-dick/", {
store: "epubjs-test"
});
var rendition = book.renderTo("viewer", {
width: "100%",
height: 600
});
var displayed = rendition.display();
displayed.then(function(renderer){
// Add all resources to the store
// Add `true` to force re-saving resources
book.storage.add(book.resources, true).then(() => {
console.log("stored");
})
});
var next = document.getElementById("next");
next.addEventListener("click", function(){
rendition.next();
}, false);
var prev = document.getElementById("prev");
prev.addEventListener("click", function(){
rendition.prev();
}, false);
var keyListener = function(e){
// Left Key
if ((e.keyCode || e.which) == 37) {
rendition.prev();
}
// Right Key
if ((e.keyCode || e.which) == 39) {
rendition.next();
}
};
rendition.on("keyup", keyListener);
document.addEventListener("keyup", keyListener, false);
var msg = document.getElementById('offline');
book.storage.on("online", function () {
console.log("online");
msg.style.top = "-40px";
});
book.storage.on("offline", function () {
console.log("offline");
msg.style.top = "0px";
});
</script>
</body>
</html>
|
Q:
BlackBerry - How to improve this search feature over a VerticalFieldManager that holds custom managers
I have a screen with a VerticalFieldManager
for holding a list of custom managers.
The screen also contains a EditField that
behaves as a search field, so when the user
enters some text, my app loops over an array
of custom managers and compares the entered text with the text from
every manager in the array.
If the text from a manager matches
the entered string, I append that custom manager to the
VerticalFieldManager.
These are the relevant parts of my code :
EditField _editField;
TempBeanPlaces [] _placesList;
VerticalFieldManager _vfmCellPlaces;
....
This is the constructor of TemBeanPlaces :
public TempBeanPlaces(String pPlaceName,
CellPlaceManager pCellPlaceManager) {
placeName = pPlaceName;
cellPlaceManager = pCellPlaceManager;
}
...
And this codes handles the search :
_editField.setChangeListener(new FieldChangeListener() {
public void fieldChanged(Field field, int context) {
String text = _editField.getText().toLowerCase();
_vfmCellPlaces.deleteAll();
for (int i = 0; i < _placesList.length; i++) {
TempBeanPlaces tempBeanPlaces = _placesList[i];
if(tempBeanPlaces.getPlaceName().toLowerCase().indexOf(text) != -1) {
_vfmCellPlaces.add(tempBeanPlaces.getCellPlaceManager());
}
}
updateLayout();
}
});
This works ok when the array _placesList is not too large (length of 50, for example),
otherwise the app becomes too slow.
How could I optimize my code for large amounts of custom managers?. For example, in case the
array contains 600 elements.
I really need to improve this feature. I just have read about the ListField in BlackBerry,
but since I have this code done, maybe I don't need to rewrite everything with ListFields.
Thanks in advance!
A:
Answered a similar question on BB forums here:
How-to-improve-this-search-feature-over-a-VerticalFieldManager
There are three workable options that I would consider:
use addAll() to add all the Managers at once thus significantly
reducing the layout time
using 'paging' so you only add the first 15, and add later
selections if the user wishes you too
Use ListField
The first 2 options would enable you to retain the current Manager code.
Try these options, in the order given, and let us know which works for you.
Update
Given that options 1 has not worked for you, and you are not allowed to do option 2, then perhaps I can suggest option 1.5. Add only the first 25 or so, but add some scroll control that detects when you are getting near the end of your VFM and when you are within 1 screen, it adds some more. This will cause a scrolling glitch at that point but the list will look continuous without the huge hit at the start.
I don't think anyone is going to scroll through 600 entries. If your search displays the number found, that will give your users an indication, and they will probably try a different search if the number is too large. And because you have not added every single item, you have speeded up the process significantly.
A variation on this is to not add al the entries until the user moves focus off the EditField onto the list.
The other thing you could look at doing it having this 'search' process done in a Thread, asynchronously, and cancel it if the user updates the edit Field with some new input.
Alternatively if option 1 has NOT worked for you, can I suggest you try just adding 10 at most, and see if the glitch is still present. If so, then I suspect there is an issue in the processing of your Fields, such as some paint loop or layout loop. Compare this with the time taken to add 10 LabelFields. Perhaps we can optimise the processing in your custom Managers that will overcome this.
Further edit
I had a random thought that perhaps restricting the height of a VFM might restrict the painting done. Not true, I've tested and the only Fields painted are those that are visible. So the performance hit is with the layout not the paint.
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Iron-catalyzed C(sp(2))-H and C(sp(3))-H arylation by triazole assistance.
Modular 1,2,3-triazoles enabled iron-catalyzed CH arylations with broad scope. The novel triazole-based bidentate auxiliary is easily accessible in a highly modular fashion and allowed for user-friendly iron-catalyzed C(sp(2) )H functionalizations of arenes and alkenes with excellent chemo- and diastereoselectivities. The versatile iron catalyst also proved applicable for challenging C(sp(3) )H functionalizations, and proceeds by an organometallic mode of action. The triazole-assisted CH activation strategy occurred under remarkably mild reaction conditions, and the auxiliary was easily removed in a traceless fashion. Intriguingly, the triazole group proved superior to previously used auxiliaries. |
In what is being touted as a first in the country, all police personnel in Andhra Pradesh, including constables and inspectors, will now get a weekly-off.
In an official statement, the government said, "Police constables, head constables, assistant sub-inspectors, sub-inspectors and inspectors will get to avail a weekly day off under the new system."
The YSRCP government said that this would come into effect from Wednesday and would benefit around 67,804 police personnel.
While the Telugu Desam Party (TDP) government had also considered implementing the decision, it had not materialised. This was a crucial issue and also one of the assurances given by Chief Minister Y S Jagan Mohan Reddy when he was on the campaign trail.
According to media reports, the state government took the decision by acting on the recommendations made by a committee headed by Additional Director General of Police (Law and Order) Ravi Shankar Ayyanar.
The committee had looked into two main aspects; work pressure and strength availability of each wing under the state police, to list out if it was possible to ensure that personnel get a weekly off without disturbing law and order in the state. It proposed 19 models, out of which one has been selected.
A separate IT platform has been prepared to monitor the weekly offs and ensure that it is done in a transparent way, the state government said.
Andhra DGP Gautham Sawang also interacted with the heads of various police wings and associations from all the districts and assured them that he would personally monitor and review the weekly off system once a month.
He also said that apart from allowing them time for their personal work, it would also help in improving their physical and mental health.
Read: Andhra inspector turns MP: Photo of him and former boss saluting each other is viral |
<!DOCTYPE html PUBLIC "-//W3C//DTD XHTML 1.0 Strict//EN" "http://www.w3.org/TR/xhtml1/DTD/xhtml1-strict.dtd">
<!--
* WYMeditor : what you see is What You Mean web-based editor
* Copyright (c) 2005 - 2009 Jean-Francois Hovinne, http://www.wymeditor.org/
* Dual licensed under the MIT (MIT-license.txt)
* and GPL (GPL-license.txt) licenses.
*
* For further information visit:
* http://www.wymeditor.org/
*
* File Name:
* wymiframe.html
* Iframe used by designMode.
* See the documentation for more info.
*
* File Authors:
* Jean-Francois Hovinne (jf.hovinne a-t wymeditor dotorg)
-->
<html>
<head>
<title>WYMeditor iframe</title>
<link rel="stylesheet" type="text/css" media="screen" href="wymiframe.css" />
</head>
<body></body>
</html>
|
FDA clearance validates Eeva System, which enables in-vitro fertilization (IVF) clinicians to offer the proprietary Eeva™ Test and further demonstrates commitment by Merck Serono and Auxogyn to bring innovative technologies to the IVF community
MISSISSAUGA, ON, June 11, 2014/CNW/ - Merck Serono, the biopharmaceutical division of Merck KGaA, Darmstadt, Germany, today announced that the proprietary Early Embryo Viability Assessment (Eeva™) System of Merck Serono's strategic partner Auxogyn received clearance from the U.S. Food and Drug Administration (FDA) through its de novo classification process, a regulatory pathway for select novel, low-to-moderate risk medical devices that are first-of-a-kind. Merck Serono is the exclusive commercial partner of Auxogyn, Inc., for the Eeva™ System in Europe and Canada.
The Eeva™ Test, used adjunctively to traditional morphology, is the first and only prognostic, non-invasive embryo test to receive clearance from the FDA. The Eeva™ Test utilizes proprietary software that automatically analyzes embryo development against scientifically derived cell-division timing parameters captured through continual video imaging. This objective information provided to reproductive endocrinologists and embryologists helps to optimize treatment plans for their patients.
"The FDA clearance of the Eeva™ System reinforces the value of the applicability of the Eeva™ Test in the IVF lab and may improve IVF outcomes. It marks another significant and exciting milestone in our continued collaboration with Auxogyn to further support the clinical development and commercialization of their Eeva™ Test," said Meeta Gulyani, Head of Strategy and Global Franchises at Merck Serono. "We, therefore, welcome this further validation for the potential of the Eeva™ Test to objectively identify the embryos with the highest implantation potential, which may ultimately improve patient outcomes."
The Eeva™ System received the CE Mark in 2012 and has been commercially available in the European Union ever since, and more recently in Canada since 2013. The potential of the Eeva™ System led to an expansion of the original partnership agreement to include a licensing agreement between Merck KGaA, Darmstadt, Germany and Auxogyn, announced in April 2014 for the exclusive rights to commercialize the Eeva™ Test in Europe and Canada. Auxogyn plans to commercialize the Eeva™ Test in the United States later this year.
"We're excited to receive the de novo FDA clearance for the Eeva™ System and believe this marks a significant milestone in the field of IVF," said Lissa Goldenstein, president and CEO of Auxogyn. "We have followed a rigorous, years-long clinical validation process and regulatory pathway to bring the Eeva™ Test to market. Our clearance provides a new level of confidence to IVF clinicians who, for the first time, have quantitative information that can be used in addition to traditional morphology to aid in deciding which embryo or embryos to transfer."
According to the European Society of Human Reproduction and Embryology (ESHRE), approximately five million additional babies have been born worldwide since 1978 as a result of assisted reproduction technologies (ART), like IVF.1 This trend may increase due to advancements in ART and IVF technologies such as the Eeva™ Test.
About AuxogynAuxogyn is revolutionizing the field of reproductive medicine by translating scientific discoveries in early embryo development into clinical tools. The company's flagship product, the Eeva™ Test, delivers consistent, objective and quantitative information regarding embryo viability that IVF clinicians and infertility patients can use to make important treatment decisions. Auxogyn is privately held and funded by Kleiner Perkins Caufield & Byers, MS Ventures, SR One and TPG Biotech.
About Merck SeronoMerck Serono is the biopharmaceutical division of Merck KGaA, Darmstadt, Germany. With headquarters in Darmstadt, Germany, Merck Serono offers leading brands in 150 countries to help patients with cancer, multiple sclerosis, infertility, endocrine and metabolic disorders as well as cardiovascular diseases. In the United States and Canada, EMD Serono operates as a separately incorporated subsidiary of Merck Serono division of Merck KGaA, Darmstadt, Germany.
Merck KGaA, Darmstadt, Germany, is a leading company for innovative and top-quality high-tech products in the pharmaceutical and chemical sectors. With its four divisions Merck Serono, Consumer Health, Performance Materials and Merck Millipore, Merck KGaA, Darmstadt, Germany, generated total revenues of € 11.1 billion in 2013. Around 38,000 Merck KGaA, Darmstadt, Germany, employees work in 66 countries to improve the quality of life for patients, to further the success of customers and to help meet global challenges. Merck KGaA, Darmstadt, Germany, is the world's oldest pharmaceutical and chemical company – since 1668, the company has stood for innovation, business success and responsible entrepreneurship. Holding an approximately 70 percent interest, the founding family remains the majority owner of the company to this day. Merck, Darmstadt, Germany is holding the global rights to the Merck name and brand. The only exceptions are Canada and the United States, where the company is known as EMD.
About EMD Serono, CanadaEMD Serono is a Division of EMD Inc., Canada, a subsidiary of Merck KGaA, Darmstadt, Germany. In Canada, EMD Serono provides innovative drug therapies that address unmet medical needs in the areas of neurodegenerative diseases, fertility and endocrinology. EMD Serono, Canada employs approximately 150 people across Canada and is headquartered in Mississauga, Ontario. For more information, please visit to www.emdserono.ca. |
Q:
java class to read csv files
Here is my class to read a csv file and I was wondering if there is any improvements that I should do. I feel there are some performance improvements or in exception handling because I just took IO exceptions.
package com.mypackage.utils;
import com.opencsv.CSVParserBuilder;
import com.opencsv.CSVReader;
import com.opencsv.CSVReaderBuilder;
import com.opencsv.enums.CSVReaderNullFieldIndicator;
import java.io.File;
import java.io.IOException;
import java.nio.file.Paths;
import java.util.*;
public class FileReader {
private String path;
private CSVReader reader;
private List<String> linesList;
private Set<List<String>> splitLinesSet;
public FileReader(String path) {
this.path = path;
}
public boolean readFile() {
this.splitLinesSet = new HashSet<>();
try {
File file = Paths.get(path).toFile();
reader = new CSVReaderBuilder(new java.io.FileReader(file))
.withCSVParser(new CSVParserBuilder()
.withSeparator('|')
.withFieldAsNull(CSVReaderNullFieldIndicator.NEITHER).build())
.build();
read();
reader.close();
} catch (IOException e) {
System.err.println("Error in reading CSV: " + e.getMessage());
return false;
}
return true;
}
public Set<List<String>> getSplitLinesSet() {
return splitLinesSet;
}
private void read() throws IOException {
String[] lines;
while ((lines = reader.readNext()) != null) {
linesList = new ArrayList<>();
Collections.addAll(linesList, lines);
splitLinesSet.add(linesList);
}
}
}
A:
I tend to advocate not passing things around which need to be closed, thus my advice is:
inline the read method
remove the reader field, and
... declare the same as a local variable
perferably, declare that local reader variable in a try-with-resources block and throw out the explicit close()-call
Note that these changes are just about robustness and maintainability and will not affect performance or error handling.
Edit, after the comment asking for code edit. (Note: sorry, I am a newbie in the code review community, I hope this does not break any principle here.)
public class FileReader {
private String path;
private List<String> linesList;
private Set<List<String>> splitLinesSet;
public FileReader(String path) {
this.path = path;
}
public boolean readFile() {
this.splitLinesSet = new HashSet<>();
File file = Paths.get(path).toFile();
try (
CSVReader reader = new CSVReaderBuilder(new java.io.FileReader(file))
.withCSVParser(new CSVParserBuilder()
.withSeparator('|')
.withFieldAsNull(CSVReaderNullFieldIndicator.NEITHER).build())
.build();
) {
String[] lines;
while ((lines = reader.readNext()) != null) {
linesList = new ArrayList<>();
Collections.addAll(linesList, lines);
splitLinesSet.add(linesList);
}
} catch (IOException e) {
System.err.println("Error in reading CSV: " + e.getMessage());
return false;
}
return true;
}
public Set<List<String>> getSplitLinesSet() {
return splitLinesSet;
}
}
Note: this was just syntactic shuffling of lines in a text editor - I have not put this through an IDE or a compiler, but I think it shows the principles.
|
Services & Procedures
At South Shore Long Island Periodontics & Implantology, we offer an incredible range of services so that we can meet all of your needs related to your periodontal health.
Each of our doctors is Board Certified and a Diplomate of the American Board of Periodontology and has the experience and expertise needed to provide exceptional care. We see patients who have been referred by their primary dental care providers and also those who have self-referred to our office.
A periodontist is a dentist who has specialized in the prevention, diagnosis, and treatment of periodontal disease. Each of our doctors has also specialized in cosmetic periodontal procedures to help you improve the appearance of your smile, so that you can always put your best face forward.
Treating Periodontal Disease at All Ages and Stages
Periodontal disease can strike at any age. No matter how old you are or how advanced your disease is, we will help stop this chronic infection in its tracks. We also have a number of treatments to repair the damage that the disease causes to both the soft gum tissue and the firm dental bone that helps to hold your teeth in place.
From deep cleaning treatments to antibiotics to surgical procedures, we’ve got you covered.
Dental Implants to Restore Lost Teeth
Periodontal disease is the number one cause of missing teeth in American adults. Just because you’ve lost teeth, however, doesn’t mean they have to stay missing. Our dentists are specialists in IMPLANTOLOGY – the art and science of replacing missing teeth with dental implants.
Perhaps you’ve been told in the past that you can’t get dental implants. If so, please see us for a second opinion. We can likely recommend a range of options that will help prepare your bone for a dental implant, from grafting to sinus lifts.
Advanced Technology for Superior Care
Dental technology is constantly evolving, and we are dedicated to staying on top of the latest developments. Before we invest in a new technology, however, we ask ourselves whether it will significantly improve our patients’ comfort, efficiency of treatment, and final outcomes.
One particular technology that we are proud of is the I-CAT® Cone Beam CT Scanner. This technology allows us to create a 3-D model of your head so that we can plan treatment and place implants with incredible precision and predictability. We also perform microbiological testing to identify the exact strain of bacteria causing problems as well as its susceptibilities so that target treatment with minimal side effects. We encourage you to visit our Technology page so that you can see the high-tech solutions we’ve implemented in our practice. |
Q:
WebAPI only binds first parameter
Dead simple question, possibly not so simple answer. Posting JSON.
public void Post(Model1 model1, Model2 model2)
{}
model1 is populated but not model2 (null).
public void Post(Model2 model2, Model1 model1)
{}
Now, model2 is populated but not model1 (null).
Why?
Edit
The reason for two parameters? Model2 used to be referenced from Model1, but that didn't work. That's when I split them up.
Edit
Right. Thanks marcind for the answer to the question above. Now for the reason the original setup didn't work. I'm not the forms universe anymore. I post Json. If you have child objects in your model then post child objects in your json.
Given
class ProductEditModel {
public string Name {get; set;}
}
class UserEditModel {
public string User {get; set;}
public ProductEditModel Product {get; set;}
}
the following
{"user": "philip", "product.name": "barbie"}
is not going to work. You'd even get an error if you in js try and setup the sematic equivalent
{user: "philip", product.name: "barbie"}
Neither of the following work either, I don't know why they would:
{"user": "philip", "productname": "barbie"}
{"user": "philip", "product_name": "barbie"}
What does work and which should be obvious holding my profession is
{"user": "philip", "product": {"name": "barbie"}}
Please kick me.
Beware! The following will not work given corresponding edit to the model above.
{"user": "philip", "ProductEditModel": {"name": "barbie"}}
A:
Not sure which version you are using, but the general rule we have settled on is that when binding complex types Web API considers the entire body of the request to represent a single entity and thus a single action parameter. In your case if you want to bind multiple Models you could introduce a custom binding object or alternatively you could bind to a Model[] or some other collection type.
|
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The victory of the October Revolution was a victory over revisionism
Nick G.
The Great October Socialist Revolution, the centenary of which we celebrate this year, was the greatest practical vindication of genuine Marxism.
Its success was guaranteed by the leadership of the great V.I. Lenin and his unremitting struggles against every kind of bourgeois reformism and unprincipled opportunism. In particular, it was his opposition to the watering down of Marxism, to the stripping away of its revolutionary essence, that educated the class-conscious workers of Russia, raising their ideological level to the point where, in the incredibly complex and ever-changing situation after the abdication of Tsar Nicholas II in March 1917, they kept their eyes on the prize of a workers’ and peasants’ state rather than the bourgeois state of Kerensky, the Cadets and the Octobrists (parties of the capitalists and landlords).
Marx and Engels fought utopian and idealistic versions of socialism
Marx and Engels fought to establish their theories from the laws of dialectical and historical materialism. They analysed the history of class society from its inception through to the revolutionary upheavals of mid-nineteenth century Europe and wrote the Communist Manifesto in opposition to various types of utopian and idealist “socialism”. They also wrote at length to refute the influential, but unscientific, views of Duhring and Proudhon.
The ideological struggles led by Marx and Engels resulted, as Lenin noted, in the defeat of “pre-Marxist socialism”. From that point on, bourgeois efforts to turn the workers from revolution and proletarian dictatorship could no longer stand “on its own independent ground, but on the general ground of Marxism, as revisionism” (Lenin On Marxism and Revisionism).
European revisionism
Scientific socialism extends recognition of the class struggle (which is in plain view of the blindest of Freddies) to the necessity for the overthrow of the capitalist ruling class by means of revolution. It requires that the workers smash the old machinery of state and create their own institutions to keep the restorationists of the old order in check.
Opportunists seeking to build parliamentary careers on the backs of the oppressed were then forced to “stand on the ground of Marxism” in order to fight it. Only as “Marxists” could they have the access to the advanced workers, could they have the credibility with the revolutionary vanguard of workers, that would enable them to divert the workers from the path of the revolutionary movement.
The German Eduard Bernstein was the first significant “Marxist” to “interpret” Marxism to support opposition to it. He argued that the Marxism of the Manifesto was too impetuous, too youthful, and that in their later years, Marx and Engels matured to a point where achieving peaceful reforms through parliament was preferable to upheavals and revolution. Of course, it would be wonderful to peacefully legislate the ruling class out of existence, but it has never once happened in history. What Marx and Engels knew to be true still stands.
Other significant “Marxists” (some of whom were indeed Marxist at one time or another) included the Russian Plekhanov and another German, Karl Kautsky.
In 1895, Engels discovered that his introduction to a new edition of The Class Struggles in France, written by Marx in 1850, had been edited by Bernstein and Kautsky in a manner which left the impression that he had become a proponent of a peaceful road to socialism. On April 1, 1895, four months before his death, Engels wrote to Kautsky:
“I was amazed to see today in the Vorwärts an excerpt from my ‘Introduction’ that had been printed without my knowledge and tricked out in such a way as to present me as a peace-loving proponent of legality quand même (at all costs). Which is all the more reason why I should like it to appear in its entirety in the Neue Zeit in order that this disgraceful impression may be erased. I shall leave Liebknecht in no doubt as to what I think about it and the same applies to those who, irrespective of who they may be, gave him this opportunity of perverting my views and, what’s more, without so much as a word to me about it.”
The “peace-loving proponents of legality”, who sought to distort Marxism in their own image, later formed the core of those who placed defence of their respective fatherlands ahead of proletarian internationalism following the outbreak of the predatory imperialist war for the division of the world (1914-18).
Lenin denounced Plekhanov, Kautsky, and other leaders of the Second International as social-patriots (socialists in words, but bourgeois patriots in deeds), social-pacifists (socialist in words but pacifists rejecting revolutionary struggle against one’s own bourgeoisie in deeds), social-chauvinists (socialists in words, but reactionary chauvinists in deeds), social-nationalists (socialists in words but narrow bourgeois nationalists in deeds) and social-imperialists (socialists in words but supporters of imperialism in deeds).
These hyphenated “socialists” were the revisionists of a particular time and place, the time when competing capitalist ruing classes were using their “own” workers to kill other workers for the sake of a redivision of the colonies and financial spheres of interest of the world.
The fight for Red October
The February Revolution in Russia that led to the abdication of Nicholas II in March was the result of proletarian action but a gift to the capitalists and landlords. The provisional government first of all refused to accept the overthrow of the Tsar, urging Nicholas to abdicate in favour of his young son who would ensure the Romanov dynasty via a Regency under his brother Michael. They wanted to keep as much of the old state intact as was needed for a more vigorous prosecution of the war effort.
From exile, Lenin exerted every effort to prevent revisionist elements from giving legitimacy to the new bourgeois rulers. Intense struggles between the Mensheviks and the Bolsheviks were played out in the Petrograd Soviet and other centres of workers’ revolutionary organisation. The subsequent victory of the October Revolution was a victory over revisionist influence in the working class.
Building socialism means fighting revisionism
After the death of Lenin in 1924, the key leadership of the Soviet Union was taken up by Joseph Stalin who, together with the Soviet people, was relentlessly demonised and maligned by the international bourgeoisie and imperialists. In the 1930s, at a time when the rest of the capitalist world was in deep economic depression wreaking enormous hardships, hunger, homelessness and poverty on the majority of the world’s people, the Soviet Union was in the throes of rapidly industrialising its economy and collectivisation of agriculture, able to provide full employment, housing, high standard free education and health, real equality for women, free child care, security for the people and promote vibrant and powerful art and culture of the working people.
The key to the successful construction of socialism by Stalin and the collective leadership around him was confidence in the strength of the working class and its ally, the peasants. Stalin, and the majority of the Communist Party of the Soviet Union maintained confidence in the working class to achieve their goals at a time when so many around him argued that building socialism in such a backward and impoverished country as Russia was impossible without simultaneous socialist uprisings in the more advanced European countries. They argued that support from the latter was an essential precondition for building socialism in Russia.
The people of the Soviet Union could not have achieved such momentous social and industrial progress without enormous confidence, support and enthusiasm for socialism and the Communist Party of the Soviet Union. Indeed, revisionism feeds primarily on the lack of courage, the lack of confidence in the ability of the people to surmount incredible difficulty, evident in backward, wavering sections of the working class and the petty-bourgeois elements that are drawn to it.
The strength of the economic and political foundations of the Soviet Union enabled it to withstand the horrific loss of life and destruction of cities and infrastructure that were inflicted by the Hitlerites, with the urgings and support from other imperialist powers, in World War 2. Indeed, the turning tide of World War 2 was the succession of defeats inflicted on the Nazis by the Soviet Red Army.
Yet war took its toll. Up to 20 million Soviet people had died, and there was huge economic destruction. The greatly increased economic and military power of the USA was now mobilised against a weakened Soviet Union. The 1948 Berlin Airlift hammered this power imbalance home. Not all Soviet leaders maintained Stalin’s confidence in the future.
Revisionism an ever-present danger
Following Stalin’s death in 1953, Khrushchev - in the face of strong opposition by leaders such as Molotov and Kaganovich - together with his revisionist followers in the Party, used the leadership of the Communist Party of the Soviet Union to rewrite essential teachings of Marxism, introducing economic and political policies that refuted the continuing class struggle under socialism on the one hand, and on the other, created and favoured a new privileged social and political elite, and sought cooperation with, rather than defeat of, imperialism.
Erroneous theories such as the “state of the whole people”, the “party of the whole people” and the “disappearance” of the dictatorship of the proletariat facilitated the anti-socialist activities of managers now given responsibility for pursuing profit at all costs including the reduction of wage costs by putting workers on the scrap heap. It enabled party and government leaders to make decisions about the allocation of socially- and increasingly, privately-appropriated surplus value that took away the leading role of the working class and vested it in a new bourgeoisie. As the power and influence of this group grew it quite deliberately sought the restoration of capitalism in the USSR. State-owned means of production were transferred, either overtly or covertly, to private hands and those that remained state-owned functioned as components of state monopoly capitalism.
With such a high level of centralisation and monopoly in the formation of private and state-monopoly capital under Khrushchev, the drive for capital accumulation inevitably took on an imperialist perspective, in the first place through the unequal economic and political relations embedded in COMECON (the Council for Mutual Economic Assistance) and the East European “people’s democracies”. The imperialism of the Soviet Union under Khrushchev and his heirs, carried out by a party and nation still cloaked in the garb of Marxism-Leninism, was correctly characterised through a revival of Lenin’s term “social-imperialism”. The post-Stalin Soviet Union, unfortunately and regrettably, was indeed socialist in words, but imperialist in deeds.
The logical conclusion of Khrushchev’s revisionism was the formal dismantling of the great Soviet Union by Gorbachev in 1991, and its degeneration into a land of corrupt and gangsterish rulers and an increasingly impoverished populace.
The rejection of revisionism by the people of former Soviet Union is expressed in the continuing public support for Lenin and Stalin and longings for the socialist country before dismantling of socialism starting with the Khrushchev era. In contrast, there’s been no sign of support for Khrushchev and his successors.
Nor has revisionism disappeared. The Chinese Communist Party invented the “Theory of the Three Represents” to facilitate its transformation from a party of the proletariat to a party of new capitalist elements. According to the Chinese Communist Party its priority is to build “harmony” between classes. Mao Zedong had taught that contradiction resides in all things, that class contradictions and class struggle would exist throughout the entire socialist era, and that ideological struggle against bourgeois and petty-bourgeois ideology would be required “for a fairly long period of time”.
History proves that in all Communist Parties existing in class societies, capitalist or socialist, revisionism is an ever-present danger, and class struggle doesn’t cease. In the circumstances of a party such as our own, a small party in a developed country, perseverance in building a revolutionary movement will always be under an immense pressure of bourgeois influence, ideas of class reconciliation, lack of scientific confidence based on dialectical materialism, and hence of revisionism. Nevertheless, we must persevere with the organisational, political and ideological principles drawn from scientific socialism, from Marxism-Leninism.
Is the cup half empty, or is the cup half full? Are we inspired by October 1917, or gutted by December 1991? Times are tough and the Australian people are yet to build leadership or mass organisations capable of overthrowing capitalism. Yet, under the most difficult circumstances imaginable, the Soviet people managed to do just that. There can only be one answer: the cup is neither half full nor half empty: it is overflowing with lessons to integrate into Australian reality.
Lenin’s victory over revisionism, and the creation of the first workers’ state in history, continue to inspire us. |
Sacred Heart Church (Bellevue, Kentucky)
Sacred Heart Church (also known as Herz Jesu Kirche), of Divine Mercy Parish, which is part of the Roman Catholic Diocese of Covington, is a historic church at 341 Taylor Avenue in Bellevue, Kentucky. It is part of the Roman Catholic Diocese of Covington.
It was built in 1892 and added to the National Register of Historic Places in 1974.
The official website for this church is: dmsbcatholic.com
See also
National Register of Historic Places listings in Campbell County, Kentucky
References
Category:Roman Catholic churches in Kentucky
Category:Churches on the National Register of Historic Places in Kentucky
Category:Gothic Revival church buildings in Kentucky
Category:Roman Catholic churches completed in 1892
Category:19th-century Roman Catholic church buildings in the United States
Category:Churches in Campbell County, Kentucky
Category:National Register of Historic Places in Campbell County, Kentucky |
Hiiraan Online
Wednesday, June 1, 2016
MOGADISHU (HOL) - A suicide car bomb blast and gunfire rocked a hotel in the Somali capital as fighters from the Al-Qaeda linked Al Shabab group pressed a deadly assault on the Ambassador hotel in the heart of the city.
At least three people were confirmed dead in the ongoing raid, which comes just days before the start of the Muslim holy month of Ramadan during which militants often step up attacks on Somali government and African Union forces.
Witnesses told HOL that the brazen raid began after a huge blast hit at the gates of the hotel with volley of gunshots ripped through the area as security forces battled with the attackers.
There was no immediate claim of responsibility for the attack.
HOL will keep you posted for any further updates as they come. |
Well, you can now add Southwest Airlines to the list of companies who are doling out bonuses to workers and increasing philanthropic donations thanks to the new tax bill. Gary Kelly, the chairman and CEO of Southwest, said his company would not waste another minute capitalizing on the most extensive tax reform in 30 years to give their 55,000+ employees a $1,000 bonus, which will be doled out on January 8. Here’s the statement from Mr. Kelly:
JUST IN: Southwest Airlines to give all full-time and part-time employees a $1,000 cash bonus on Monday & company will also make $5M in charitable donations and invest in its Boeing fleet due to tax reform passage. https://t.co/YKho1O67Ek
I’m proud to report we are rewarding our Employees with a $1,000 bonus with the anticipated savings from the tax reform legislation, we are contributing an additional $5 million in charitable donations, and we are making investments in our fleet and our business. pic.twitter.com/h4GVqRrXzX
"We applaud Congress and the President for taking this action to pass legislation, which will result in meaningful corporate income tax reform for the transportation sector in general, and for Southwest Airlines, in particular," said Southwest's Chairman and Chief Executive Officer Gary Kelly.
"We are excited about the savings and additional capital, which we intend to put to work in several forms—to reward our hard-working Employees, to reinvest in our business, to reward our Shareholders, and to keep our costs and fares low for our Customers."
Kelly continued, "I am also proud to report that we have donated an incremental $5 million to charitable causes as a result of tax reform. Throughout 2018, we will work with our charitable partnerships to put this money to work in the communities we serve and where our Employees work and live."
Southwest aren’t the only ones who are making good use of the climate this tax bill has created. Wells Fargo, AT&T, Boeing, and Comcast are doing the same with their employees. That means NBC and MSNBC reporters will be receiving bonuses as well. American Airlines also announced yesterday that bonuses for their workers are coming (via Dallas Morning News):
American Airlines plans to give a one-time $,1000 bonus to its employees — except officers — in a bid to share some of the anticipated benefits from the recent federal tax code overhaul that slashed the corporate tax rate from 35 percent to 21 percent.
American joins another big regional employer, AT&T, that is also giving its employees a one-time $1,000 bonus in response to the tax reform. And Boeing Co. pledged $300 million for employee training and improving workplace infrastructure.
The bonus for American employees will be paid in the first quarter of 2018, according to a note to employees co-signed by CEO Doug Parker and president Robert Isom. The bonus is estimated to cost the Fort Worth-based carrier about $130 million.
The economy is growing near four percent. Consumer confidence is at a 17-year high. Unemployment is at a near two-decade low. Over 220,000 new jobs were created in November; the economy is booming. While President Trump, who signed the GOP’s tax bill into law on December 22, has not received credit for the economy, a new CNBC survey said that might be changing as well. |
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Johnsonburg girls tennis downs Clearfield, 9-0
JOHNSONBURG – Johnsonburg girls tennis won its first match of the season with a 9-0 sweep of Clearfield Wednesday afternoon at Johnsonburg Area High School. “I feel good for them, they work hard,” Johnsonburg coach Gregg Dauber said. “They were there, they were there the last several matches. They’re close, they finally broke through. I’m happy for them. It’s not from a lack of effort, they work really hard.”At No. 1 singles, Taylor Scida won 6-1, 6-2 over Lauren Whitmer of Clearfield. Riley Fannin of Johnsonburg was victorious at No. 2 singles with a 6-0, 6-2 victory over Yesh Patel. Paige Martonik was a 6-1, 6-2 winner in No. 3 singles action over Liz Lanager of Clearfield. Josie Del Rio won 6-2, 6-1 over Rachel Johnson of Clearfield in the No. 4 singles match. Cheyenne Johnson was the winner in No. 5 singles with a 6-1, 6-0 victory over Rayana Kavelack. In No. 1 doubles, the Johnsonburg team of Scida/Fannin won 8-0 over Whitmer/Patel. The team of Del Rio/Martonik won 8-2 in No. 2 doubles action over Lanager/Johnson. Cheyenne Johnson and Andrea Taylor won in No. 3 doubles over Abby Welker by Emily Ramsey by a score of 8-1. Paige Secco and Ann Carnahan secured an 8-2 victory in No. 4 doubles over Rachel Johnson and Kavelack. Dauber said the tennis players are improving as the season has gone on, especially with the busy schedule the Ramettes have had in the last few days. “We haven’t been able to practice because we’ve had a match the last seven days without counting weekends, Dauber said. “We haven’t been able to work on anything so we’re working on the fly and they’re doing real well. Everybody’s improving, that’s all you can ask for.” Johnsonburg is scheduled to play at DuBois for a 3:30 p.m. match today. “ECC was tough, they’re a good team,” Dauber said. “We got to go to DuBois if it doesn’t rain. Hopefully, we can give them a run. All the girls are playing better and I’m happy for them, they deserve it. They worked hard.” |
Q:
Creating Lucene Index On SQL Server Database
I am creating a custom web application in C# .NET and I have a completely custom built database schema. I need a search engine application which is comprehensive enough to search the entire database I am using. We have decided to use Lucene .NET and probably Solr on top. I would like some help though as I'm a beginner.
Firstly, how do I go about creating a Lucene .NET index using C# on a SQL Server 05 or 08 database?? If anyone can help me by explaining the steps involved, where to reference Lucene .NET files from etc. any help would be much appreciated.
Secondly, we are proposing using Solr on top to add additional functionality, but how do I go about doing this? What way does it run and what is required etc?? If using Solr on a Microsoft SQL Server box, must I use SolrNet over Solr?
Thanks in advance for all help received!
A:
use Lucene .NET and probably Solr on top
Solr doesn't run on top of Lucene.NET. It's a stand-alone Java Search server built on top of Java (original) Lucene.
The simplest way to import data from a relational database into Solr is using the DataImportHandler.
SolrNet is a client, a .net library that communicates with Solr via HTTP. I briefly explained how the interactions work in this blog post.
|
Trump Nominates Kavanaugh, Anti-Gunners Furious
While leading Second Amendment organizations are hailing President Donald Trump’s nomination of Judge Brett Kavanaugh to succeed retiring Justice Anthony Kennedy on the U.S. Supreme Court, perhaps the best gauge of the importance of this nomination is the reaction of the gun prohibition lobby.
“Judge Brett Kavanaugh’s extreme outlier approach to the Second Amendment would elevate gun rights above public safety and put in jeopardy the full range of gun safety laws — including assault weapons and large-capacity magazine prohibitions, minimum age requirements, safe storage requirements, and other common-sense gun safety laws.”
Judge Kavanaugh wrote a dissent in a case that banned possession of most semi-auto rifles in the District of Columbia. In his dissent, he observed, “It follows from Heller’s protection of semi-automatic handguns that semi-automatic rifles are also constitutionally protected and that D.C.’s ban on them is unconstitutional. (By contrast, fully automatic weapons, also known as machine guns, have traditionally been banned and may continue to be banned after Heller.)
“D.C.’s registration requirement,” Kavanaugh added, “which is significantly more stringent than any other federal or state gun law in the United States, is likewise unconstitutional…”
The angst from anti-gunners is countered by enthusiasm from Second Amendment groups. Chris Cox, executive director of the National Rifle Association’s Institute for Legislative Action, released a statement in which he hoped the Senate swiftly confirms Kavanaugh.
“President Trump has made another outstanding choice in nominating Brett Kavanaugh for the U.S. Supreme Court,” Cox stated. “He has an impressive record that demonstrates his strong support for the Second Amendment.
“Judge Kavanaugh has demonstrated his clear belief that the Constitution should be applied as the Framers intended,” Cox added. “To that end, he has supported the fundamental, individual right to self-defense embraced by Justice (Antonin) Scalia in the historic Heller decision. ”
Alan Gottlieb, founder and executive vice president of the Second Amendment Foundation quickly hailed the nomination.
“We’re encouraged by this nomination,” Gottlieb said in a statement, “because by adding Judge Kavanaugh, we might see the high court become more willing to accept and rule on important Second Amendment issues, such as right-to-carry.
“While the Supreme Court has twice affirmed in the last ten years that the Second Amendment protects a fundamental, individual right to keep a firearm for home defense,” he continued, “but the court has yet to even begin defining the right to bear arms outside of the home or business, in public.
“We know that the Court will face enormous challenges on other rights issues,” Gottlieb observed, “but the right to keep and bear arms is a cornerstone of the Bill of Rights that has set this nation apart as a beacon of freedom and liberty. It is time for the court to examine the constitutionality of various state laws that restrict the right to carry, for example, and make arbitrary decisions about who can exercise that right.”
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About Dave Workman
Dave Workman is an award-winning career journalist with an expertise in firearms and the outdoors. He is the author of several books dealing with firearms politics. He has a degree in editorial journalism from the University of Washington and is a lifelong Washington resident. |
A few Sundays ago, I read Rainer Maria Rilke’s Letters to a Young Poet.
And I have now re-read it.
So many passages are worth pondering. I shall share a few.
“Leave to your opinions their own quiet undisturbed development, which, like all progress, must come from deep within and cannot be pressed or hurried by anything. Everything is gestation and then bringing forth. to let each impression and each germ of a feeling come to completion wholly in itself, in the dark, in the inexpressible, the unconscious, beyond the reach of one’s own intelligence, and await with deep humility and patience the birth-hour of a new clarity: that alone is living the artist’s life: in understanding as in creating.
“There is here no measuring with time, no year matters, and ten years are nothing. Being an artist means, not reckoning and counting, but ripening like the tree which does not force its sap and stands confident in the storms of spring without the fear that after them may come no summer. It does come. But it comes only to the patient, who are there as through eternity lay before them, so unconcernedly still and wide. I learn it daily, learn it with pain to which I am grateful: patience is everything!”
Speaking about sensual pleasure: “In one creative thought a thousand forgotten nights of love revive, filling it with sublimity and exaltation. And those who come together in the night and are entwined in rocking delight do an earnest work and gather sweetnesses, gather depth and strength for the song of some coming poet, who will arise to speak of ecstasies beyond telling. And they call up the future; and though they err and embrace blindly, the future comes all the same, a new human being rises up, and on the ground of that chance which here seems consummated, awakes the law by which a resistant vigorous seed forces its way through to the egg-cell that moves open toward it. Do not be bewildered by the surfaces; in the depths all becomes law.”
On solitude and suffering: “We are set down in life as in the element to which we best correspond, and over and above this we have through thousands of years of accommodation become so like this life, that when we hold still we are, through a happy mimicry, scarcely to be distinguished from all that surrounds us.. We have no reason to mistrust our world, for it is not against us. Has it terrors, they are our terrors; has it abysses, those abysses belong to us; are dangers at hand, we must try to love them. And if only we arrange our life according to that principle which counsels us that we must always hold to the difficult, then that which now still seems to us the most alien will become what we most trust and find most faithful. How should we be able to forget those ancient myths that are at the beginning of all peoples, the myths about dragons that at the last moment turn in to princesses; perhaps all the dragons of our lives are princesses who are only waiting to see us once beautiful and brave. Perhaps everything terrible is in its deepest being something helpless that wants help from us.”
A benediction: “Do you remember how [your] life yearned out of its childhood for the “great”? I see that it is now going on beyond the great to long for greater. For this reason it will not cease to be difficult, but for this reason too it will not cease to grow.
“And if there is one thing more that I must say to you, it is this: Do not believe that he who seeks to comfort you lives untroubled among the simple and quiet words that sometimes do you good. His life has much difficulty and sadness and remains far behind yours. Were it otherwise he would never have been able to find those words.”
May we all go beyond for the greater, and never cease to grow, and embrace the difficulty.
Like this:
Heavenly Father, in your Word you have given us a vision of that holy City to which the nations of the world bring their glory: Behold and visit, we pray, the cities of the earth. Renew the ties of mutual regard which form our civic life. Send us honest and able leaders. Enable us to eliminate poverty, prejudice, and oppression, that peace may prevail with righteousness, and justice with order, and that men and women from different cultures and with differing talents may find with one another the fulfillment of their humanity; through Jesus Christ our Lord. Amen.
Like this:
After his vet visit this morning (a clean bill of health, and a report of activity that I will share on Saturday), I texted the foster to say “make it so.”
And so it is.
Nelson Clinger (his new name, in my mind) is an acrobat, funny, inquisitive, clingy, spirited little guy. Less than eleven pounds. Full of life. And my companion for what I hope will be many years to come.
He has taken to sleeping under the piano bench when I’m teaching my lessons on Zoom. |
The Battle for Aleppo and the Remaking of the Medieval Middle East
About the Book
A history of the 1119 Battle of the Field of Blood, which decisively halted the momentum gained during the First Crusade and decided the fate of the Crusader states
In 1119, the people of the Near East came together in an epic clash of horses, swords, sand, and blood that would decide the fate of the city of the Aleppo--and the eastern Crusader states. Fought between tribal Turkish warriors on steppe ponies, Arab foot soldiers, Armenian bowmen, and European knights, the battlefield was the amphitheater into which the people of the Near East poured their full gladiatorial might. Carrying a piece of the true cross before them, the Frankish army advanced, anticipating a victory that would secure their dominance over the entire region. But the famed Frankish cavalry charge failed them, and the well-arranged battlefield dissolved into a melee. Surrounded by enemy forces, the crusaders suffered a colossal defeat. With their advance in Northern Syria stalled, the momentum of the crusader conquest began to evaporate, and would never be recovered.
About the Author
Nicholas Morton is a senior lecturer at Nottingham Trent University. The author or editor of three books, Morton lives in Nottinghamshire, UK.
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"This narrative of the first half of Augustine's life conjures the intellectual and social milieu of the late Roman Empire with a Proustian relish for detail." --New York Times
In Augustine, celebrated historian Robin Lane Fox follows Augustine of Hippo on his journey to the writing of his Confessions. Unbaptized, Augustine indulged in a life of lust before finally confessing and converting. Lane Fox recounts Augustine's sexual sins, his time in an outlawed heretical sect, and his gradual return to spirituality. Magisterial and beautifully written, Augustine is the authoritative portrait of this colossal figure at his most thoughtful, vulnerable, and profound.
Kingdoms of Faith
By Brian A. Catlos
A magisterial, myth-dispelling history of Islamic Spain spanning the millennium between the founding of Islam in the seventh century and the final expulsion of Spain's Muslims in the seventeenth
In Kingdoms of Faith, award-winning historian Brian A. Catlos rewrites the history of Islamic Spain from the ground up, evoking the cultural splendor of al-Andalus, while offering an authoritative new interpretation of the forces that shaped it.
Prior accounts have portrayed Islamic Spain as a paradise of enlightened tolerance or the site where civilizations clashed. Catlos taps a wide array of primary sources to paint a more complex portrait, showing how Muslims, Christians, and Jews together built a sophisticated civilization that transformed the Western world, even as they waged relentless war against each other and their coreligionists. Religion was often the language of conflict, but seldom its cause--a lesson we would do well to learn in our own time.
Reviews
"A riveting account of a battle that changed the course of the Crusades. Nicholas Morton captures the intensity, importance, and aftermath of the confrontation to produce a sparkling history of one of the key turning-points of the Middle Ages."-Peter Frankopan, author of The Silk Roads: A New History of the World
"Nicholas Morton tells the gripping story of the medieval struggle for Aleppo, vividly bringing to life the Muslims and Christians who shaped their times. More than just a chronicle of a battle, this book sheds revealing light on the First Crusade and its aftermath, disposing of myths, and laying bare the high stakes that drove men on all sides of the conflict."-Thomas Madden, author of Istanbul: City of Majesty at the Crossroads of the World
"In The Field of Blood Nicholas Morton reverses the usual perspective and asks, 'Why didn't the Crusader States succeed?' Unlikely as it sounds now, there seemed a real possibility in the first half of the twelfth century that the French knights would soon rule the whole of Syria and perhaps Egypt too. Morton's analysis of these events is meticulous, his knowledge of the politics and military practices of the medieval world formidable, and his ability to understand these events from multiple perspectives-Turkish, French, Arab, Armenian, among others-wholly remarkable."-Jay Rubenstein, author of Armies of Heaven: The First Crusade and the Quest for Apocalypse |
Charles Hoskinson, Mitbegründer von Ethereum und Gründer von Cardano, erklärte über Twitter, dass Kritiker die gigantische Anzahl der institutionellen Investoren übersehen würden, die darauf warten, ihr Geld in Kryptowährungen fließen zu lassen.
Laut Hoskinson ist die Wall Street bereit, Billionen an US-Dollar nach der „nächsten Welle der Regulierung“ zu investieren.
What's often missed by the cryptocurrency is going to die broken record media is that after the next wave of regulation, wall street is showing up to the party with all their locked up capital. That's tens of trillions of dollars entering the space eventually. Future is bright — Charles Hoskinson (@IOHK_Charles) June 21, 2018
Die Aussage ist aus unserer Sicht deshalb so bemerkenswert, weil Charles Hoskinson normalerweise nicht dafür bekannt ist bullische Statements zum Kryptowährungsmarkt und dessen Preisentwicklung zu veröffentlichen.
Hoskinson, der Gründer von IOHK und Cardano ist eigentlich dafür bekannt die Entwicklung der Technologie und die Vorteile, die hierfür für die Menschheit entstehen, in den Vordergrund zu stellen. Insofern ist das Statement aus unserer Sicht durchaus außergewöhnlich und umso höher zu bewerten.
Die Wall Street wartet
Wie wir über die vergangenen Wochen berichteten, warten zahlreiche „Big Player“ der Wall Street darauf in den Kryptowährungsmarkt einzusteigen und damit große Mengen an institutionelle Geld in den Markt zu pumpen.
Das von Goldman Sachs unterstützte Startup Circle kündigte vor kurzem an, mit Unterstützung von Bitmain einen Stablecoin zu launchen, um die Volatilität auf dem Kryptowährungsmarkt zu minimieren und den Wall-Street-Investoren den Weg zu ebnen. Goldman Sachs selbst kündigte darüber hinaus an, einen Bitcoin-Trading Desk einzuführen, über den institutionelle Investoren mit großen Geldmengen direkt in den Bitcoinhandel einsteigen können.
Die größte Börse der USA, die Nasdaq führte vor wenigen Wochen aus, dass Bitcoin und Ethereum bald an der Nasdaq gehandelt werden könnten, wenn die entsprechend notwendigen Regulierungen eingeführt und der Markt „reif“ dafür ist.
Coinbase entwickelt mit Coinbase Custody in Zusammenarbeit mit der SEC einen Service, um Kryptowährungen nach höchsten Sicherheitsstandards lagern zu können. Weiterhin wurde mit Coinbase Prime eine Umgebung geschaffen, die speziell auf die Bedürfnisse institutioneller Investoren zugeschnitten ist.
Mit dem Hardware Wallet Hersteller Ledger, sowie Nomura und Global Advisors haben sich drei namhafte Unternehmen zusammengeschlossen, um eine Börse zu entwickeln, mit dem Namen Komainu, die nur für Großanleger wie institutionelle Investoren zugelassen ist.
In London ist Ende Mai eine neue Kryptowährungsbörse LMAX Digital an den Start gegangen, die nur institutionellen Investoren zugänglich ist. Auf dieser Plattform sollen etablierte Kryptowährungen wie Bitcoin, Ethereum, Litecoin, Ripple und Bitcoin Cash handelbar sein.
Die von den Winklevoss Zwillingen betriebene Kryptowährungsbörse Gemini ist eine Partnerschaft mit Caspian eingegangen, um institutionelle Händler mit mehreren Börsen über eine einzige Schnittstelle zu verbinden. Darüber hinaus arbeitet Gemini mit der Nasdaq zusammen, um eine sicherere Handelsplattformen zu schaffen und die technischen Anforderungen institutioneller Händler zu erfüllen.
Alles in allem schreitet die Entwicklung der Kryptowährungen weiter voran, trotz des derzeitigen Bärenmarktes und Abwärtstrends.
Wie Charles Hoskinson feststellt, wartet die Wall Street förmlich darauf „Zehntausende Billionen“ an US-Dollar nach der „nächsten Welle der Regulierung“ in den Kryptomarkt zu pumpen. Gegenwärtig repräsentieren Kryptowährungen lediglich einen kleinen Bruchteil des weltweiten Vermögens mit rund 250 Milliarden US-Dollar, während andere Anlagegüter Billionen von Dollar innehaben.
Disclaimer: — Der Handel mit Kryptowährungen birgt ein großes finanzielles Risiko und kann bis zum Totalverlust des eingesetzten Kapitals führen. Coin-hero.de stellt keine Anlageberatung und Empfehlung im Sinne des Wertpapierhandelsgesetzes (WpHG) dar. Die Webseiteninhalte dienen ausschliesslich der Information und Unterhaltung der Leser. Die hier getroffenen Aussagen stellen lediglich unsere eigene Meinung und keine Kaufempfehlung dar. Bitte unternehmen Sie auch eigene Recherchen, bevor Sie in Kryptowährungen investieren. Wir übernehmen keinerlei Haftung für jegliche Art von Schäden. Bitte lesen Sie auch unseren Haftungsausschluss im Impressum. — |
Ginger Snaps
These were the reason I ordered. These can't be found in stores in this area anymore and my brother and I miss them. These were our birthday surprise but now he is going to hold me responsible for keeping them on hand. I guess I can live with that.
These cookies are the classic ginger snaps that you devoured as a kid! The warm spice and crunch of our ginger snaps makes them an irresistible morsel to constantly keep on hand. They’re flavored with a hit of hot real ginger and sweetness from molasses.
Because ginger snaps are crunchy and have a spiciness to them, they’re great when paired with coffee or tea. Another option is to serve them with gelato or ice cream, where the contrasting textures and tastes complement one another. If you want to go the simpler route and nibble on them throughout the day, that’s great, too (shh…that’s what we do).
Ginger snaps originated during the Middle Ages when ginger found its way from Southeast Asia to Europe. They then eventually found their way to America when Europe colonized the Americas. When they were first created, ginger snaps were made with molasses because it was cheaper than granulated sugar, and the tradition was carried on because the flavor of the molasses was so tasty. This cookie has been around for hundreds of years, so you can feel good about munching on a treat with great heritage!
In addition to being a great snack with your tea, the ginger in ginger snaps possesses many health benefits. For thousands of years, ginger has been used for its anti-inflammatory and pain relief qualities.
Health Tips
1. A Brigham Young University study found that ginger worked better than dimenhydrinate (the active ingredient in over-the-counter motion-sickness medication) at preventing and treating motion sickness.
2. Ginger has anti-inflammatory properties and can be used to reduce the symptoms of rheumatoid arthritis, osteoarthritis, and various other muscular disorders according to the Journal of Medicinal Food.
3. The University of Michigan Comprehensive Cancer Center found that ginger can destroy ovarian cancer cells. In addition, they also looked into how ginger could hinder the progression of colorectal cancer cells.
These are a hit on my job ..my co-workers are having me order these for them..
darlene, New York, NY
January 30, 2015
Nice taste. like the crunch of the cookie
Richard, Palm Coast, FL
January 3, 2015
The ginger snaps were as gingery as I hoped they would be. Thank you for another great snack!
Sara, Riverview, FL
December 12, 2014
Good cookies to give during the holidays!
Brenda, Little Elm, TX
December 8, 2014
This are the best, tastiest Ginger Snaps ever! I ordered them to use in the crust for a pumpkin cheesecake, but I'm not sure they'll last that long. My husband and I cannot keep our hands out of the bag! |
UPDATED, Monday AM: Early morning estimates show Disney/Marvel’s Black Panther now making $112 million for the weekend, a 45% dip from its Week 1, which is an amazing second-weekend hold for a four-quad event film of this size. Disney will report its official figure later this morning.
All records still stand: Second-best second domestic weekend ever (after Star Wars: The Force Awakens’ $149.2M); record second-weekend haul for a Marvel movie (beating The Avengers’ $103M); and second-fastest to $400M in 10 days, along with Jurassic World behind Force Awakens (eight days). But also, Black Panther has the smallest second-weekend decline ever for an MCU title, beating the sophomore-session holds of Thor (-47%), Iron Man (-48%) and Avengers (-50%) and Doctor Strange (-50%).
The running domestic box office for Black Panther is just under $404M, and the Ryan Coogler-directed Marvel title has pushed the entire 2018 domestic box office to an awesome $1.9 billion for the period of January 1-25. According to ComScore, that’s 12.5% ahead of the same period last year, and 10% ahead of 2016, which wound up being a banner year at the U.S./Canada box office with $11.4 billion. Black Panther‘s second Sunday minted $35.4M, -26% from Saturday.
New Line/Warner Bros.’ Game Night has grown $2M in its weekend projections since Friday night, now coming in at $17M after a $4.4M Sunday, down 37% in second.
Paramount’s Annihilation is spot-on with its Sunday AM outlook with $11M for the weekend in fourth after a $3M Sunday, down 27%.
UPDATED, Sunday AM: Disney has confirmed this morning what industry estimates saw last night: Black Panther will hit $400M at the domestic box office by end of today, making the Ryan Coogler-directed Marvel movie the second-fastest to that point, along with Jurassic World, in 10 days. Black Panther gets to $400M in four days less than The Avengers (14 days) and ranks behind the Star Wars: Force Awakens record of eight days.
Disney
The Disney release posted $47.6M on Saturday, +66% which puts its second weekend at $108M, -46%. Can’t mention enough how this Marvel movie goes higher and higher, so if we’ve grown this much since Friday, we’re bound to grow even more by the end of today. At this pace, Black Panther would own the second-best second weekend at the B.O. behind Force Awakens ($149.2M), and well ahead of Avengers‘s sophomore sesh of $103M. Imax auditoriums delivered an outstanding $9M in weekend 2 at 404 sites, taking the large format exhibitor’s domestic cume to $36M. T’Challa’s Imax run continues to outstrip all other MCU titles, including Avengers:Age of Ultron, which made $28.9M after 10 days.
Screen Engine/ComScore’s PostTrak shows that the movie continues to wow with a 92% overall positive score, males under 25 leading the way (29%), followed by guys over 25 (27%) and females over 25 (26%), with a moviegoer make-up of 37% Caucasian, 33% African American, 18% Hispanic and 7% Asian.
New Line
New Line/Warner Bros.’ Game Night grew 25% on Saturday over Friday with $7M, taking its opening to $16.6M in second place, and as we mentioned, that’s OK, not fantastic, and a bit of a rebound from the studio’s R-rated laugh recession last year with The House, Fist Fight, and Alcon’s Father Figures. New Line kept this comedy as economically sound as possible, with a production cost under $40M, which is their range for the genre. At this box office level with Game Night, New Line is in the same boat of other R-rated original IP comedy openers such as Mike & Dave Need Wedding Dates ($16.6M opening, $46M final domestic), Office Christmas Party ($16.9M, $54.8M), and How to Be Single ($17.8M, $46.8M), so figure it comes in within $40M-$50M at the domestic B.O. when all is said and done. R-rated comedies remain the quagmire for many studios (outside of Universal’s Girls Trip geared toward African American audiences), as studios and comedy creators continue to scratch their heads and figure out how to pull in younger crowds who’ll fuel breakout successes.
Another hurdle here with Game Night is in its packaging: The larger cast of Kyle Chandler, Jesse Plemons, and Billy Magnussen aren’t known for their comedy chops, not to mention Jason Bateman typically plays the straight man to someone crazier in his comedies, i.e. Charlie Day in Horrible Bosses and Melissa McCarthy in Identify Thief; even Tony Hale and Will Arnett on Arrested Development. Though McAdams has starred in comedies in the past, such as Mean Girls and Wedding Crashers, she has largely built her track record on more serious fare over the last decade, such as Spotlight, HBO’s True Detective, Doctor Strange, Southpaw and Terrence Malick’s To The Wonder. Really, how can an average potential moviegoer know that this is a comedy?
Knowing that they had a different, clever comedy, Warner Bros. sought to capture that irreverent attitude in its marketing and trailers. This is one of the reasons why they didn’t go with the silly standard stars-on-the-poster concept (though that will be implemented overseas); the studio was looking to break form and keep within the pic’s unique sense of humor. The challenge here lied in selling to the young ‘uns (under 25) on what ‘game night’ is (those of us raised on Parker Brothers and Milton Bradley board games in the ’80s know exactly what it is); and so Warners executed an extensive grass-roots program that tapped into local influencers, game & trivia night takeovers, and an aggressive college program that touched down on nearly 200 campuses across the US & Canada. With test scores solid, Warners screened Game Night extensively with AMC, Regal, Alamo Drafthouse, The CW Plus, and Soho House, as well as with eight influencers whose fan bases reached north of 36M. In purchased media over six weeks, Warner Bros. went after older men during the AFC/NFC Championship Games, the Winter Olympics, and NCAA Basketball, as well as broader demo fare such as Ellen’s Game of Games Finale and The Bachelor’s Winter Games.
Screen Engine/ComScore’s PostTrak shows a 78% overall positive and 3 1/2 stars (out of 5) overall audience response to CinemaScore’s B+ for Game Night. PostTrak polls continually throughout the weekend, not just Friday night. Those females under 25 (repping only 14% of moviegoers) enjoyed the Bateman-McAdams feature the most at 85% positive. Females over 25 (36%) and males over 25 (35%) respectively gave the comedy 76% and 78% overall positive scores. Game Night played best in the big cities, especially in the West and Southwest.
Sony’s Peter Rabbit is +103% in its third Saturday, with $5.7M sending its weekend to $12.5M in third place, -29%. Versus Universal/Illumination’s Hop, which, like Peter Rabbit with James Corden, was built around the comedic sensibility of another British comedian, Russell Brand, saw the feature adaptation of Beatrix Potter’s classic in weekend 3 pacing behind that 2011 title by 13%, with $71.2M at the domestic B.O. Hop ended its stateside run at $108M, so figure Peter Rabbit lands in the low $90Ms.
Paramount/Skydance’s Annihilation in 4th place drew $4.1M on Saturday, +8%, rising its three-day to $11M. PostTrak showed 71% overall positive and three-stars, with males out-numbering females to the female-led sci-fi action pic, 56% to 44%. Annihilation played best in the big cities, particularly in the West, and all ten of its best theaters are in New York, Los Angeles, and San Francisco.
Every Day landed a 64% in the top two boxes, with a lowly 39% recommend in regards to audience reaction. Kids rated it much higher, with 65% in the top two boxes and a 52% recommend. The single largest demo attending were 18-24 at 26%. Those who showed were 68/32 female and 61% under 25. Pic’s opening was $3.1M. If it can leg out to $10M, that would be good for this $5M production (before $8M digital P&A).
Studio reported figures for the weekend of Feb. 23-25:
1..) Black Panther (DIS), 4,020 theaters (0) / $28.9M Fri /$47.6M Sat/ $31.56M Sun/3-day: $108M (-47%)/Total: $400M/Wk 2
2..) Game Night (NL/WB), 3,488 theaters / $5.6m Fri (includes $1M previews)/$7M Sat/ $4M Sun/3-day: $16.6M /Wk 1
3..) Peter Rabbit (SONY), 3,707 theaters (-18) / $2.8M Fri /$5.8M Sat/ $3.9M Sun/3-day: $12.5M (-29%) /Total: $71.2M/Wk 3
4..) Annihilation (PAR), 2,012 theaters / $3.8M Fri (includes $900k previews)/$4.1M Sat/ $3.1M Sun/3-day: $11M /Wk 1
5..) Fifty Shades Freed (UNI), 3,265 theaters (-503) / $2.3M Fri/$3M Sat/ $1.5M Sun/3-day: $6.9M(-60%)/Total: $89.5M/Wk 3
6..) Jumanji: Welcome to the Jungle (SONY), 2,519 theaters (-281) / $1.3M Fri /$2.65M Sat/$1.65M Sun/ Sun/3-day: $5.6M (-29%)/Total:$387.2M/ Wk 10
7..) The 15:17 to Paris (WB), 2,752 theaters (-290) / $1M Fri/$1.6M Sat/$970K Sun/3-day: $3.6M(-53%)/Total: $32.2M/ Wk 3
8..) The Greatest Showman (FOX), 1,601 theaters (-335) / $905K Fri /$1.55m Sat/ $945K Sun/ 3-day: $3.4M (-32%)/Total: $160.7M/Wk 10
9..) Every Day (OR), 1,667 theaters / $1M Fri (includes $115k previews)/$1.3M Sat/ $715K Sun/3-day: $3.1M /Wk 1
10..) Early Man (LG), 2,494 theaters / $355K Fri/$792K Sat/$553K Sun/3-day: $1.7M (-47%)/Total: $6.7M/Wk 2
Notables:
Three Billboards Outside Ebbing, Missouri (FSL), 691 theaters (-89) / $287K Fri /$585K Sat/ $348K Sun/ 3-day: $1.22M (-19%)/Total: $50.1M/Wk 16
The Post (FOX), 795 theaters (-255) / $315K Fri /$545K Sat/ $340K Sun/ 3-day: $1.2M (-40%)/Total: $78.8M/Wk 10
The Shape of Water (FSL), 721 theaters (-236) / $298K Fri /$495K Sat/ $307K Sun/ 3-day: $1.1M (-33%)/Total: $55.3M/Wk 13
Samson (PURE), 1,140 theaters (-109) / $258K Fri /$407K Sat/$285K Sun/3-day: $950K (-51%)/Total: $3.7M/Wk 2
Writethru after 3rd Update, Saturday AM: We knew earlier in the week that Black Panther would crack the century mark at the B.O. in its second weekend, and that’s exactly what it’s doing with a current industry 3-day estimate of $104.1M (-48%) after a $28.8M Friday. Don’t underestimate this Disney/Marvel release, it will only get bigger.
Disney
The broken records continually change, and at this time Black Panther looks to rank as the third-best second weekend ever behind The Avengers’ $103M; the best-ever for a Marvel movie and the best sophomore session for any title in the pre-summer period beating Disney’s Beauty and the Beast last year ($90.4M). The pic cracked past $300M Friday, and by Sunday will see a 10-day run of $396.05M.
On the upside, Black Panther‘s awesome second frame continues to prove that event titles, when they’re groundbreaking and speak up to audiences rather than down, can perform even better in the off-season than they do in the summer. They can single-handedly defy the handicaps of winter weather and school calendars (ComScore reports that 15% K-12 are off, and only 2% colleges).
Part of Marvel’s secret sauce here is that they don’t see the titles that they pump out as merely ‘superhero’ or comic-book movies, but rather smart, genre-bending cinema. These hits can’t be built on the backs of fans alone.
At a Deadline screening for Logan back in December — a film that proved again last March following Deadpool that R-rated comic book movies can actually rally at the box office — the pic’s director James Mangold made an excellent point: “I don’t think there is anything as the superhero genre, and if there is, it’s a pretty sucky genre,” said the director. “There’s fantasy films and heroic films like Ben Hur, The Dark Knight, the story of Jesus Christ and Gladiator; all are stories about heroes.” Stick to a superhero formula, and you’ll yield a stagnant movie, and that’s exactly what Black Panther specifically does not do. It’s more than a spy movie, more than a comic-book movie, and audiences are showing how much they love the freshness of this heroic movie with their wallets.
Black Panther‘s rays continue to shine brightly on social media as people leave the auditorium: The pic’s social media universe across Facebook, Instagram, Twitter and YouTube has jumped from 901M last weekend to 981M within five days per RelishMix. Last Thursday, daily YouTube views for the Ryan Coogler-directed movie were at 390K and they’ve now spiked to 575K daily views per day for each top video. After the record-breaking Twitter surge from 137k to 559k hashtags for #BlackPanther and @BlackPanthermovie last Friday, you’d expect to see a rapid taper during the week. But that’s not the case: While Saturday saw a total of 543K, that eased to 480K on Monday, and a daily 352K. “Remember activity over 100k is exceptional,” says RelishMix.
On the downside, the marketplace isn’t a boats-all-rise situation with wide entries getting slowed at the box office. Sorry, distribution heads: Just because your movie is opening within the tracking range, doesn’t mean it’s deemed a success.
Warner Bros.
New Line/Warner Bros.’ Game Night is earning $15.1M in 2nd place (lower than what we saw last night) after $1M Thursday night, a $5.6M Friday, and a B+ CinemaScore which is toward the middle of its tracking range of $13M-$21M. That’s OK for this $37M-budgeted pic (before P&A), not fantastic, and an improvement both B.O. and audience grade-wise from Warner Bros.’ string of R-rated clunkers last year including Fist Fight ($12.2M opening, B), The House ($8.7M, B-) and Alcon’s Father Figures ($3.3M, B-).
We hear Game Night tested well, and as such Warner Bros. held several advance screenings, and ultimately received the blessing of Rotten Tomatoes critics (82% certified fresh) which is quite a feat when you have a comedy, because they can be vicious. “The convo surrounding Game Night is fairly positive, mostly coming from those fans who have attended advanced screenings,” says RelishMix. “Those who have seen it early have described it as hilarious. Also, many have praised the fact that it features strong leads including Rachel McAdams and Jason Bateman. The plot has also been well praised as original in a time when many films aren’t seen that way by many moviegoers.” Women, who turned up at 56%, enjoyed Game Night giving it a A-; it’s the over 25 crowd at 86% who are giving this a B+.
New Line
On the minus side, we hear that some insiders are grumbling about Game Night‘s release date in the wake of Black Panther. And then there’s the marketing campaign, with trailers that rivals have criticized as being more of a serious sell than funny. Then there’s those absurdist one sheets which are advertising game pieces with burglar masks instead of stars Jason Bateman and Rachel McAdams. What’s that all about? Some will try to blame the sluggish environment for R-rated fare, however, it smells like New Line had something to work with here from the decent audience reaction and critical reviews. Says Rolling Stone‘s Peter Travers, “Farce is a beast to get right in movies. The fact that Game Night hits the mark more often than it hits a wall is cause for cheering.” Laughter is contagious, so let’s see if Saturday night pegs Game Night toward a better end-game.
Paramount
Paramount/Skydance’s sci-fi-environmental auteur title Annihilation from director Alex Garland is coming in at the low end of its tracking range with $10.7M for the weekend in 4th place with $3.85M for today. Paramount continues to pay for the sins of the previous executive administration of the late Brad Grey and Vice Chairman Rob Moore. Grey had a predilection for auteur type films that could potentially be awards bait read Arrival, Whiskey Tango Foxtrot, mother!, Suburbicon and Downsizing, but the previous regime overspent on them greatly and that’s why most of them have capsized at the box office. $68M for absurdist comedy Downsizing? $30M for the gonzo thriller mother!? Far too much for haughty, fringe, experimental fare.
One of the trickier aspects about Rotten Tomatoes is that its metric leans favorably toward auteurs and critics enjoyed Annihilation at 87% certified fresh. When that’s the case, these scores don’t translate into great ticket sales. Reviewers enjoyed the fact that Garland stuck to his Ex Machina styling, and didn’t sell out to Hollywood with a Jurassic Park-type picture. However, the audience’s smacking it with a C CinemaScore means Annihilation was too slow for them. Those between 18-24 gave Annihilation its bests grade of a B, but they only repped 11% of the audience. Last weekend Paramount opted to trailer their best wares on Black Panther, and that was Mission: Impossible – Fallout. More males than females turned out for this women action movie, 60% to 40%. Both gave it a C.
Paramount Pictures
But wait, wasn’t Arrival slow? How did that movie get away with that pace? We understand that its story of a mother’s anguish, coupled with its spiritual sensibility, is what spurred moviegoers to spend $100.5M on that pic, and of course there was the pic’s eight Oscar nominations including best picture (it won one for sound editing).
Paramount earnestly tried to sell this film on its greater attributes of being a largely female driven action film. Some will believe the pic faltered because of the whitewashing controversy it faced, i.e., Natalie Portman’s character was originally of Asian descent and Jennifer Jason Leigh’s character being Native American in Jeff VanderMeer’s Southern Reach trilogy (details that weren’t revealed until the series’ second novel). While such controversial noise doesn’t typically impact the average moviegoers’ purchasing decision, studio marketing executives believe that when building a pic’s promotional momentum, it’s better to be controversy-free. Arguably, the whitewashing syndrome with Ghost in the Shell was significantly louder and was more severe considering it’s a popular 30-year-old manga property and starred Marvel superstar Scarlett Johansson. In regards to Annihilation, did moviegoers even know it was based on a book? VanderMeer himself didn’t raise any objections about the studio and filmmaker’s artistic license with the characters. Portman, Leigh and Garland weren’t even aware of the characters’ ethnic backgrounds as the first novel never delve into them. The pic’s drooping at the B.O. lies more in the fact that it’s a slow-paced, funky piece of specialty sci-fi cinema. The current administration is trying to get beyond these high-priced arthouse movies, and if there was no question about the pic’s risk, Paramount would have never sold foreign to Netflix (sans China).
Orion
Orion’s $5M-teenage production Every Day based on the David Levithan YA novel is coming in with $3M. This label is dedicated to narrowly targeted audiences, with low digital-driven P&A spends (I hear this was around $8M). Should the film get to $10M at the domestic B.O. for them, it’s considered a high point as it triggers their MGM TV deals, which are some of the richest in the world. It’s an OK result for what the pic is. Those who showed up gave it a B+. It wasn’t the teenagers who gave this movie its best grades (under 18 at 54% of the crowd gave it a B+), but the middle-age folk 35-49 who repped 9% of Friday night moviegoers and graded Every Day an A-.
Industry estimates for weekend of Feb. 23-25: — chart updating
1..) Black Panther (DIS), 4,020 theaters (0) / $28.8M Fri (-62%) /3-day: $104.1M (-48%)/Total: $396M/Wk 2
2..) Game Night (NL/WB), 3,488 theaters / $5.6m Fri (includes $1M previews)/3-day: $15.1M /Wk 1
3..) Peter Rabbit (SONY), 3,707 theaters (-18) / $2.8M Fri (-30%) /3-day: $12.1M (-31%) /Total: $70.8M/Wk 3
4..) Annihilation (PAR), 2,012 theaters / $3.85m Fri (includes $900k previews)/3-day: $10.7M /Wk 1
5..) Fifty Shades Freed (UNI), 3,265 theaters (-503) / $2.3M Fri (-59%)/3-day: $6.9M(-60%)/Total: $89.5M/Wk 3
6..) Jumanji: Welcome to the Jungle (SONY), 2,519 theaters (-281) / $1.3M Fri (-28%)/3-day: $5.6M (-29%)/Total:$387.2M/ Wk 10
7..) The 15:17 to Paris (WB), 2,752 theaters (-290) / $995K Fri (-52%)/3-day: $3.54M(-53%)/Total: $32.1M/ Wk 3
8..) The Greatest Showman (FOX), 1,601 theaters (-335) / $910K Fri (-31%) / 3-day: $3.4M (-32%)/Total: $160.7M/Wk 10
9..) Every Day (OR), 1,667 theaters / $1M Fri (includes $115k previews)/3-day: $3M /Wk 1
10..) Early Man (LG), 2,494 theaters / $353K Fri (-58%)/3-day: $1.4M (-55%)/Total: $6.5M/Wk 2
Notables:
Samson (PURE), 1,140 theaters (-109) / $258K Fri (-55%)/3-day: $915K (-52%)/Total: $3.67M/Wk 2
2nd Update, Friday 1:03PM: Right now industry estimates have Black Panther at $92M, which reps a 54% decline and falls between the second weekend declines of The Avengers (-50% with $103M) and Avengers: Age of Ultron (-59%, $77.7M). By the end of the weekend on this pace, Black Panther will see a domestic running tally of $384M.
However, this is a movie that has continually defied expectations so we may see business grow by tonight. Remember, a bulk of the 18-24 crowd comes out for those 10PM or later shows, and Marvel movies get to this enormous size on repeat customers. Black Panther‘s second Friday is at $25M, -67% because opening day was padded by Thursday night previews. Still, this is historic business for the second month of the year in which snow and ice exist in parts of the nation, despite a “heat” wave in the NorthEast.
New Line’s Game Night is playing to a $6M opening day, and a weekend that’s between $16.5M-$18M. We’ll have a better idea tonight if word of mouth syncs with the critical heat on this R-rated movie.
Paramount’s Annihilation is set to collect an estimated $3.5M today and $10M for the weekend, now at the lower end of its tracking.
Orion’s microbudget Every Day after earning $115K from Thursday previews is looking at $1.1M today and $3.2M over three days.
1st Update, Friday 7:16AM: In the face of Disney/Marvel’s Black Panther earning $14.2M alone yesterday for a running total that will cross $300M today, New Line/Warner Bros.’ Game Night and Paramount’s Alex Garland sci-fi environmental pic Annihilation respectively pulled in $1M and $900K.
Annihilation was booked at 1,850 venues yesterday and will raise its theater count to 2,012 today. Game Night will play in 3,488. Game Night is projected between $13M-$21M while Annihilation was pegged between $10M-$12M. The upside for them in a Black Panther-dominated market? Both titles have awesome Rotten Tomatoes Scores with Annihilation at 90% certified fresh and Game Night at 83% certified fresh and that’s hopeful in regards to changing the minds of those moviegoers are pledge allegiance to RT.
Disney
These are good starts considering that T’Challa is expected to take in more than $104M in weekend two (it’s actually better for Game Night considering how audiences have been like mules when it comes to R-rated comedies in the last year). However, last night has given rival studios to Disney hope that all boats will rise in a Black Panther world. Through yesterday, he’s made close to $292M and he’ll be the fastest Mavel title to $300M in 8 days, beating The Avengers’ 9 days. Black Panther will tie with Jurassic World and Star Wars: The Last Jedi in regards to the number of days to $300M, which all rank second behind Star Wars: The Force Awakens which cleared the three century mark in a record 5 days.
Paramount
In regards to comps to Annihilation, there are films like Life which made $800K on its first Thursday before posting a $4.4M Friday and $12.5M opening. There’s also Arrival, which at a $1.45M Thursday yielded a $9.4M Friday and $24.1M three-day. Annihilation cost a net of $40M before P&A. This is the second feature directorial by Oscar nominee Garland whose 2015 release Ex Machina which was a notable sleeper on the arthouse circuit with $25.4M, becoming A24’s third highest release behind Oscar best picture winner Moonlight ($27.9M) and current five-time nominee Lady Bird ($46.6M).
Game Night bulldozes comps for such R-rated summer laugh duds as Rough Night ($700K Thursday, $3.3M Friday, $8M weekend) and The House ($800K Thursday, $3.3M and $8.7M). The Hitman’s Bodyguard, which fared the best of them all, was an action comedy, which Game Night has elements of. That pic Ryan Reynolds-Samuel L. Jackson buddy comedy posted $1.65M on its Thursday night before an $8M Friday and $21.3M opening.
Also opening today is Orion’s teenage drama Every Day in under 2,000 locations. Pic is specifically targeted at the LGBT community and females 13-24. Tracking has the microbudget movie opening between $2M-$4M. |
Once again Kanye West has tricked Progressives into showing their true colors. After months of Tweets and other declarations of support for Trump, it all culminated yesterday in a lunchtime meeting between Kanye and Trump himself.
Of course, the Progressive plantation bosses went into overdrive attacking Kanye for daring to think for himself. And their obsessive attacks on everything about Kanye from his education, to his reading skills, to his mental health prove that Progressive outrage and anger is all fake. Progressives are only outraged when their stranglehold on a traditionally Democratic voting demographic is threatened.
A huge fear the Democrats have is losing the faith of black voters. A small percentage of black voters moving to the Republican party could spell doom for the Democrats for decades to come. And this is exactly the reason they are falling over themselves in an attempt to demonize West and portray him as a fool and mentally unstable.
This is exactly the same scenario behind the Progressive’s faux outrage over the treatment of illegal immigrants. They don’t really care how immigrants are treated, but new immigrants often vote for Democrats, so immigrants are a huge voting demographic for the Democrats and one that they can increase very easily by simply easing immigration policies.
This is why they show outrage over immigration policies, because once again it threatens their hold on a voting demographic if immigration enforcement is tightened.
It’s the same with the Democrats recent outrage over Justice Brett Kavanaugh. They claimed to care about sexual abuse, but in reality they simply care that the court will have a conservative on the bench instead of an activist liberal judge. If they cared about women’s abuse accusations, they would look in the mirror and see many high profile Democrats who have been accused of abuse, and accused with real evidence and police reports. But Democrats ignore these accusations and instead feign outrage over Brett Kavanaugh.
Progressives are only outraged when their power is threatened. It’s an old tactic and one they have overplayed since Trump took office. They take a policy issue and divide it into two sides, one side being moral, and other being immoral. Of course, they take the moral side and then feign outrage over anyone who dares take the side they deemed as immoral. But looking a little deeper into each issue shows a common root cause for their outrage, and that’s a threat to their power.
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A natural history study of adolescents and young adults with sickle cell disease as they transfer to adult care: a need for case management services.
Life expectancy for adolescents with SCD now extends well into adulthood. As a result, adolescents transfer to adult care. Little empirical evidence exists to show how transfer occurs and how well the current practices now work. The aim of this study was to obtain a database on the experience of adolescents/young adults with SCD that transfer to adult care. We assessed their treatment compliance, independence, and whether they receive uninterrupted care. Data were obtained through patient and provider interviews and patient record reviews. Results indicate patients leave pediatric care without adequate transfer preparation and readiness to transfer is not the major consideration in the decision to transfer, follow-up often ceases once the patients leave pediatric care, and patients who maintain follow-up appointments are more efficient in managing their illness (self-efficacy). The model for a structured transitioning process is provided with recommendations for nurse case managers to maintain follow-up. |
Introduction {#Sec1}
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China produces antibiotics about 210,000 tons of each year, of which 48 percent are used in agriculture and animal husbandry^[@CR1]^. China is the largest producer user of antibiotics in the world based on the market sales data^[@CR2]--[@CR5]^. Besides, China leads the world in the consumption of antibiotics in the livestock-breeding industry^[@CR6]^. In the process of aquaculture, veterinary antibiotics are usually used as feed additives to improve animal growth rate and feed conversion rate^[@CR7],[@CR8]^, it accounts for more than 70% of the aquatic product dosage^[@CR9]^. The antibiotics which used in aquaculture cannot be completely absorbed by animals, and 70% to 80% of them enter the water body or sink into the sediment^[@CR10]^, and it still have antibacterial, gene mutation activity and so on, resulting in environmental pollution and ecological damage. The heavy uses of veterinary antibiotics generated high levels of antibiotic residues in China. So far, it has been reported that antibiotic residues in the surrounding environment of animal breeding farms are detected^[@CR11],[@CR12]^. Large amounts of antibiotic residues in sewage environments^[@CR13]^, estuaries and coastal waters^[@CR14],[@CR15]^. In the Pearl River waters of China, residual concentrations of quinolones antibiotics such as ofloxacin and norfloxacin have reached the level of mg/L^[@CR16]^. In addition to the aquaculture environment, fluoroquinolone antibiotic residues have been found in other natural environments such as reservoirs, lakes and rivers in China, with concentrations ranging from 1--100 ng/L^[@CR17],[@CR18]^. There are different levels of antibiotic residues in water, sediments, aquatic plants and animals of Baiyang Lake in China, the concentration level can reach up to mg/L^[@CR19]^. Moreover, the concentration of oxytetracycline, tetracycline, norfloxacin and ofloxacin were detected in the sediments of the Zhujiang River were 100, 72.6, 1120 and 1560 ng/g, respectively^[@CR16]^.
The accumulation of antibiotic residues in water and sediments in freshwater aquaculture areas in China, which can inhibit the decomposition ability of soil and cause harm to aquatic organisms. As well as can induce the production of resistant bacteria and can alter microbial activity and community composition in groundwater^[@CR20]^. The residual antibiotics in water environment may be absorbed by the absorption and enrichment of the aquatic animals and plants^[@CR21]--[@CR23]^. Meanwhile, it will lead to serious environmental problems including ecological risk and human health damage^[@CR24]^.
Fluoroquinolones are a well-known class of orally deliverable, bactericidal, broad spectrum antimicrobial agents that are currently used to treat serious bacterial infections^[@CR25]^, which are especially active against Gram-negative bacteria and they are used both in human and animals^[@CR26]^. Some fluoroquinolones available for clinical use or in development have one or two chiral centers in their chemical structure. These compounds are available either as racemates (ofloxacin, gemifloxacin, clinafloxacin), enantiomers (levofloxacin, moxifloxacin) or diastereoisomers (sparfloxacin)^[@CR27],[@CR28]^.
Flumequine (9-fluoro-6, 7-dihydro-5-methyl-l-oxo-1H, 5H-benzo\[ij\]quinolizine-2-carboxylic acid^[@CR29]^) is one of the most commonly used second-generation quinolones antibiotics, which has one chiral carbon and consists of a pair of enantiomers (Fig. [1](#Fig1){ref-type="fig"}). Its absolute configuration was confirmed with *S*-(−)-Flumequine and *R*-(+)-Flumequine^[@CR30]^. The main mechanism of flumequine is to inhibit the DNA gyrase for the necessary of the cell replication, thereby blocking the replication of bacterial DNA to achieve the purpose of the sterilization^[@CR31]^. Flumequine has a good effect on diseases caused by infection with Aeromonas salmonicida, Escherichia coli, which are especially active against Gram-negative bacteria and is widely used in the treatment of systemic infectious diseases in livestock and aquatic animals^[@CR32],[@CR33]^. Studies have shown that high doses of flumequine can cause distortion of rat embryonic development^[@CR34]^. There is no report that low doses of flumequine are harmful to animals and humans, but if people intake antibiotic residue food for long time, the potential risk can not be underestimated. Therefore, the residue of flumequine has aroused widespread concern at home and abroad^[@CR35]^. 7-hydroxyflumequine is the main metabolite of flumequine, which has two chiral carbon and consist four enantiomers (Fig. [2](#Fig2){ref-type="fig"}). A survey has shown that 60--70% of the most frequently prescribed drugs and the drug candidates under development are single enantiomers^[@CR36]^. For any enantiomeric drug, an enantiomeric impurity can produce different pharmacological, toxicological, metabolic, and pharmacokinetic effects within the chiral environment of a biological system^[@CR37]--[@CR39]^. Studies have shown that there is a significant difference in the antibacterial activity of the flumequine enantiomers^[@CR40]^. Therefore, it is necessary to analyze and detect antibiotics, and further, concerned with it's enantioselective behaviors in the environment.Figure 1Chemical structure of flumequine (C\*=chiral center).Figure 2Chemical structure of 7-hydroxyflumequine (C\*=chiral center).
In the present study, we report on the development of using the Lux 5 µm Cellulose-2 column to separate flumequine enantiomers and develop a method based on solid-phase extraction followed by high performance liquid chromatography-electrospray time of flight mass spectrometry for the determination of flumequine antibiotic. Meanwhile, we use the Lux 5 µm Cellulose-4 chiral column to separate 7-hydroxyflumequine which is the main metabolite of flumequine. There is no report on the chiral analytical methods of flumequine and its metabolites enantiomers in water and sediment. To the best of our knowledge, the current report is the first time to simultaneous present the enantioselective analysis of flumequine and its metabolite in water and sediment samples using chiral HPLC-Q-TOF/MS. This method which will be potentially beneficial for research in this area will be sensitive, selective, not so much time-consuming and easily applicable to analyze water and sediment samples.
Experimental {#Sec2}
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Chemical reagents and apparatus {#Sec3}
-------------------------------
Racemic flumequine standard (purity at 99.9%) and S-(−) and R-(+)-flumequine enantiomers (purity \>90.0%) were obtained from CNW Technologies. Racemic 7-hydroxyflumequine were prepared by Peking University Health Science Center. Acetonitrile, methanol and n-hexane (HPLC grade) were purchased from Sigma Aldrich (USA). The HPLC water was prepared through a Milli-Q system (Millipore, MA, USA). All other chemicals and reagents were of analytical grade supplied by Guoyao Chemical Co. (Shanghai, China). 0.22 µm Filter Unit was from Bonna-Agela Technologies Co.,Ltd, (Beijing, China). Cleanert PEP Solid phase extraction cartridges (500 mg/6 mL) were purchased from Bonna-Agela Technologies. High-speed refrigerated centrifuge (CR22G) was purchased from Hitachi Led. (Tokyo, Japan). A 5600 Accurate-mass tandem quadrupole-time-of-flight (Q-TOF) mass spectrometer (SCIEX, Co., Ltd.) was used to quantify flumequine enantiomers. JASCO 2000 HPLC (Jasco Co., Tokyo, Japan) equip with circular dichroism detector (CD-2095).
Preparation of working standards {#Sec4}
--------------------------------
Standard solutions of racemic flumequine, racemic 7-hydroxyflumequine, S-(−) and R-(+)-flumequine enantiomers were prepared in pure ACN, obtaining a final concentration of 200.0 µg/L. All solutions were protected against light and stored in the dark at 4 °C.
Validation of method {#Sec5}
--------------------
The linear range, limit of detection (LOD), limit of quantification (LOQ), specificity, accuracy and precision were determined to validate the performance of the method.
The linearity of the method was evaluated based on the peak areas of the matrix-matched standard solutions in triplicate at eight concentration levels, ranging from 1.0 to 200.0 µg/L. The LOD was the concentration that produced a signal-to-noise (S/N) ratio of 3, whereas the LOQ was based on a S/N ratio of 10^[@CR41]^.
The recovery assay was determined by spiking the flumequine and 7-hydroxyflumequine enantiomers analytes into sediment samples at 10, 50, 100 µg/L and 5, 10, 20 µg/L for water samples. Six spiked samples on each level were extracted as described above and the recovery of each one was calculated. The concentration of target enantiomers were then determined using the external standard calibration to obtain the recovery and accuracy. The relative standard deviations (RSDs) of the measured values were calculated to evaluate the precision of the method. The repeatability was calculated using the data obtained from the recovery. The precision was calculated using the same data obtained for the recovery and repeatability.
When using LC-MS/MS to measure complex samples, the matrix usually has an enhancing or inhibiting effect on the ionization of the analyte, which is the matrix effect. The matrix effect affects the sensitivity and repeatability of the instrument, which is an important factor influencing the reliability and accuracy of the instrument.
Therefore, the matrix effects (MEs) can be evaluate by using the formula (the slope of the curve obtained from the matrix matched standard solution/the slope of the curve made of the non-matrix standard solution − 1) × 100%, with a matrix-induced effect when the value is negative and matrix enhancement occurring when the value is positive.
Samples collection {#Sec6}
------------------
Sediment samples were obtained from the pool in Tianjin. Using the bottom sampler to collect sediment samples at the bottom of the pool. All samples were refrigerated storage at 4 °C and return to the laboratory. These samples did not contain the target analytes. After the natural drying process, the sediment samples were homogenized into powder and were passed through mesh sieve and stored in the refrigerator at −20 °C until analysis.
Sample preparation {#Sec7}
------------------
### Sediment {#Sec8}
Dry sediment samples (2.00 ± 0.01 g) were weighed into 50 mL centrifuge tube, and then 10 mL ACN and EDTA-Mcllvaine buffer solution (40:60, v/v) were added to the tube. Subsequently, the mixtures were homogenized for 1--2 min and were extracted by an ultrasonic oscillator for 10 min. The mixtures were further centrifuged at 8000 rpm for 5 min and the above steps are repeated three times then the extraction solution was transferred into 150 mL round-bottom flask for drying using a rotary evaporator (45 °C). After that, diluted with water to 30 mL, pour into 50 mL centrifuge tube until serve.
Cleanup with Cleanert PEP (Polar Enhanced Polymer) cartridge. For this analysis, 30 mL extraction solution was slowly passed through Cleanert PEP cartridges, the flow rate is about no more than 2 mL/min, which was previously activated by sequential flushing with 6 mL MeOH and 6 mL purified water. After the sample was loaded, the SPE cartridge was washed with 6 mL 0.2%Acid Aqueous Solution, The retained analytes were eluted with 6 mL MeOH. The organic solvent was dried by pure nitrogen, then the resultant residue was re-dissolved in 1 mL MeOH and filtered through a 0.22 µm filter for HPLC-Q-TOF/MS analysis and quantitation.
### Water {#Sec9}
50 mL water samples were cleaned-up with Cleanert PEP cartridge, the process was as described above. Flumequine and 7-hydroxyflumequine have the same process of extraction and cleanup.
Q-TOF-MS analysis {#Sec10}
-----------------
### Flumequine analysis {#Sec11}
Chromatographic separations were carried out on Lux 5 µm Cellulose-2 (250 mm × 4.6 mm i.d. × 5 µm, Phenomenex, USA) column. The mobile phase consisted of 0.2% acetic acid in water as solvent A and acetonitrile as solvent B. The gradient elution program was as follows: 0--20 min, A:B(45:55,V/V); 20--24 min, A:B(5:95, V/V); 24--25 min, A:B(45:55, V/V); The total run time was 30 min at a flow of 1 mL/min. The separation is isocratic, using a wash step with a high acetonitrile concentration to clean the column. The column temperature was maintained at 30 °C. The injected volume of the test sample was set at 1 µL. Q-TOF detection equipped with an electrospray ionization source (ESI) was performed in positive ion mode, nebulizer pressure, 55 psi; collision energy, 10 V; capillary voltage, 5.5 kV; ion temperature, 600 °C; the mass range of m/z 100--700.
### hydroxyflumequine analysis {#Sec12}
The spatial configuration of flumequine and 7-hydroxyflumequine is different, so different chiral stationary phase are needed to separated them. We choose normal-phase chromatography elution mode and the Lux 5 µm Cellulose-4 (250 mm × 4.6 mm i.d. × 5 µm, Phenomenex, USA) column to separate 7-hydroxyflumequine. The mobile phase consisted of 0.3% TFA in ethyl alcohol as solvent A and n-hexane as solvent B. The total run time was 20 min at a flow of 1 mL/min. The column temperature was maintained at 30 °C. The injected volume of the test sample was set at 1 µL. Q-TOF detection equipped with an electrospray ionization source (ESI) was performed in positive ion mode, nebulizer pressure, 55 psi; collision energy, 10 V; capillary voltage, 5.5 kV; ion temperature, 600 °C; The mass range of m/z 100--700.
Results and Discussion {#Sec13}
======================
Separation condition optimization and elution order {#Sec14}
---------------------------------------------------
In the preliminary experiments, the enantioseparation of flumequine on two cellulose-based columns (Lux 5 µm Cellulose-2 and Lux 5 µm Cellulose-3, 250 mm × 4.6 mm i.d. × 5 µm particle size) was tested. Cellulose-2 and Cellulose-3 both are derivatives of polysaccharides chiral column. Cellulose-3 column has one cellulose benzoate-based chiral selector. However, it is an effective way to increase the hydrogen bonding between solute and stationary phases to introduce into amino in chiral stationary phases for Cellulose-2 column. Hence, better chromatographic separation of flumequine enantiomers can be achieved when Lux 5 µm Cellulose-2 is used. So, optimization of chromatographic conditions below was subsequently conducted using a Lux 5 µm Cellulose-2 column. The chromatographic separation behavior was to some extent affected by changing the amount or type of organic and acidic modifiers in the mobile phase. When using acetonitrile as the organic mobile phase B with the mobile phase ratios of A:B varied from 10:90 to 50:50, the resolutions (Rs) for flumequine enantiomers were range from 0.63 to 2.01. In the ratio of 50:50, an acceptable Rs value (2.01) result indicated that the flumequine enantiomers were completely separated with the mobile phase was acetonitrile and 0.2% acid aqueous (50:50).
By coupling the chiral LC to the optical rotation detection and UV detection sequentially using the same stationary and mobile phases, both (−)enantiomer forms were eluted out earlier than the (+) forms for chiral flumequine (Fig. [3](#Fig3){ref-type="fig"}).Figure 3The CD and UV chromatogram of flumequine on Lux Cellulose-2.
The enantioseparation of 7-hydroxyflumequine on the Lux 5 µm Cellulose-4 column. The mobile phase ratio of A:B was varied from 40:60 to 10:90. It was found that each condition did not have a significant effect on the enantioselective separation efficiency. However, the better chromatographic separation of 7-hydroxyflumequine enantiomers can be achieved when TFA in the mobile phase. Therefore, the ethyl alcohol solution containing amount of TFA (0.3%) was chosen for the solvent A. In addition, the optimization of mobile phase ratio were tested, by comparison, the best chromatographic enantioseparation for the four enantiomers of the 7-hydroxyflumequine in the ratio of 70:30 (Fig. [4](#Fig4){ref-type="fig"}).Figure 4The separation of 7-hydroxyflumequine was performed on Lux Cellulose-4.
Mass spectrometric analysis of flumequine {#Sec15}
-----------------------------------------
The MS/MS analysis of protonated flumequine was carried out by HPLC/QTOF-MS. Mobile phase A is 0.2% acetic acid solution and mobile phase B is ACN. The flow rate was set at 1 mL/min and the column temperature was set at 30 °C. Elution of the two enantiomers was observed within 13.9 min (the first effluent fraction, *S*-(−)-Flumequine) and 16.4 min (the second effluent fraction, *R*-(+)-Flumequine) (Fig. [5](#Fig5){ref-type="fig"}). The margin of error between the measured and calculated masses ranged from −0.2 to 0mDa, indicating good accuracy. The protonated molecular ions (\[M + H\]^+^) and the fragment ions of \[M + H\]^+^ were all measured (Fig. [6](#Fig6){ref-type="fig"}). The most possible elemental compositions and the product ions were listed in Table [1](#Tab1){ref-type="table"}.Figure 5The separation was performed on Lux Cellulose-2.Figure 6MS/MS spectra of flumequine (Abscissa: counts vs mass-to-charge m/z; Ordinate: Intensity).Table 1Elemental composition, measured and calculated masses, and mass errors of protonated flumequine and its fragment ions.Elemental compositon (\[M + H\]^+^)Measured\
M~W~ (Da)Theoretical\
M~W~ (Da)Error\
(mDa)Error\
(ppm)Collision energy\
/eVC~14~H~12~NO~3~F262.0873262.0874−0.1−0.492C~10~H~5~NOF174.0333174.0349−1.6−9.518C~11~H~5~NO~2~F202.0293202.0298−0.5−2.661C~14~H~11~NO~2~F244.0761244.0768−0.7−2.955
Sample preparation optimization {#Sec16}
-------------------------------
Sample preparation is the crucial step in environmental analysis. It is highly influenced by the physical and chemical properties of analytes studied. The main goal is to concentrate analytes in sample, to remove interferences from matrix and to prepare analyte in suitable form for subsequent chromatographic analysis^[@CR42]^.
Acetonitrile/ethyl acetate (1: 1, V/V) and acetonitrile/PBS buffer solution (1: 1, V/V) as extracting agent to examine the efficiency. When the acetonitrile/PBS buffer solution was used as the extracting agent, the extraction recoveries for the flumequine enantiomers range from 13.4\~17.7%, and for the 7-hydroxyflumequine range from 11.2\~13.5%. However the extraction efficiency of acetonitrile/ethyl acetate for the two drugs were not good.
When using ACN/EDTA-Mcllvaine solution as extraction solvent, the extraction efficiency is satisfied. And then, optimize the ratio of ACN and EDTA-Mcllvaine solution, select the ratio of ACN and EDTA-Mcllvaine solution were 10:0, 9:1, 8:2, 7:3, 6:4, 5:5. It was found that when the ratio was 6:4 the recoveries for the two drugs were the highest. (Table [2](#Tab2){ref-type="table"})Table 2The average recoveries and RSD% of flumequine and 7-hydroxyflumequine at different extraction solvent ratios. (n = 3) .Extraction SolventFlumequine7-hydroxyflumequineRecovery(%)RSD(%)CV%Recovery(%)RSD(%)CV%ACN/EDTA-Mcllvaine\
(10:0, V/V)39.701.734.3740.201.603.98ACN/EDTA-Mcllvaine\
(9:1, V/V)37.775.2313.8542.856.7015.64ACN/EDTA-Mcllvaine\
(8:2, V/V)47.276.3513.4435.653.219.00ACN/EDTA-Mcllvaine\
(7:3, V/V)60.042.253.7567.74.216.22ACN/EDTA-Mcllvaine\
(6:4, V/V)77.931.852.3776.693.274.26ACN/EDTA-Mcllvaine\
(5:5, V/V)61.300.400.6564.71.171.81
Solid phase extraction cartridges optimization {#Sec17}
----------------------------------------------
In order to select appropriate capacity of the SPE cartridges, after rotary evaporator drying and diluted with water, then using the above optimized preparation method to process the samples. The cartridges recoveries experiments were carried out using three solid phase extraction cartridges, Sep-Pak C18 (500 mg, 6 mL), Poly-sery HLB (60 mg, 3 mL), Cleanert PEP (150 mg, 6 mL), respectively. Through the further enrichment of the C18 cartridges filtrate, it was found that there was a large amount of the antibiotic residue in the filtrate, which leads to loss some analytes and low recovery rates, therefore C18 cartridges was unable to absorb flumequine and 7-hydroxyflumequine in the extraction solvent. The recoveries of flumequine enantiomers through an HLB cartridges range from 17.8\~22.2%, and of the 7-hydroxyflumequine range from 13.4\~14.3%. Here, PEP cartridge was chosen as the absorbent for the flumequine enantiomers and 7-hydroxyflumequine infusion samples because of its satisfied recovery range from 77\~81.8%, 70.1\~78.69%, respectively.
Classical C18 sorbent is the most commonly used SPE column which chemistries was bonded silica. Silica based sorbents are not suitable for the extraction of quinolone antibiotics because of it was effective only for non-polar compounds. Cleanert PEP (Polar Enhanced Polymer) are functionalized polystyrene/divinylbenzene extraction cartridges which show the most robust recovery ratio and reproducibility for both polar and non-polar compounds, and they are allowing working in wide range of pH (from pH 1 to 14). However, comparing to the HLB cartridges, PEP cartridges were much more efficient, yielding high recoveries for flumequine enantiomers and 7-hydroxyflumequine. Therefore, this kind of cartridges can also be used for the extraction of other fluoroquinolones antibiotics.
Method validation {#Sec18}
-----------------
### Recoveries and precision {#Sec19}
The recoveries of method were evaluated by spiking the blank samples at three different concentration levels of the flumequine and 7-hydroxyflumequine (10, 50, 100 µg/L for sediment samples and 5, 10, 20 µg/L for water samples). Intra - day precision were obtained by measuring 6 replicates of different matrices at 3 spiked levels within one day. Inter - day precision were obtained for 5 consecutive days. The results of the average recovery, standard deviation and relative standard deviation of the studied flumequine and 7-hydroxyflumequine are summarized in Table [3](#Tab3){ref-type="table"}. The method presented satisfactory mean recoveries values from 71.7 ± 12.5% to 84.6 ± 5.6% for both flumequine enantiomers in different matrix. The intra - day precision were range from 5.1\~12.2%, and the inter - day precision were range from 4.5\~16.4%. The results of precision for 7-hydroxyflumequine were also appropriate, the mean recoveries values from 69.9 ± 13.1% to 83.9 ± 3.5% in different matrix. The intra - day precision and inter - day precision were range from 3.5\~13.1%, 3.0\~7.6%, respectively.Table 3Spiked average recoveries and relative standard deviations(RSDs) of flumequine and 7-hydroxyflumequine. (n = 6).SampleSpiked (µg/L)Flumequine7-hydroxyflumequineIntra - dayInter - dayIntra - dayInter - dayRecovery (%)RSDRecovery (%)RSDRecovery (%)RSDRecovery (%)RSDWater579.712.282.65.376.34.773.16.21084.66.773.14.573.35.177.54.92083.85.184.65.683.93.577.75.8Sediment1073.66.371.712.569.913.170.33.05074.312.273.25.176.26.273.47.610077.511.976.016.471.87.472.37.4
### Matrix effect {#Sec20}
This manuscript evaluated the matrix effects of each enantiomer of flumequine and racemic 7-hydroxyflumequine in sediment samples (Table [4](#Tab4){ref-type="table"}). It was shown that there were matrix-induced effect for the enantiomers of flumequine and 7-hydroxyflumequine. The difference in matrix effects of two enantiomers of flumequine are not significant. When all of these problems are considered together, we adopted the method of preparing matrix matched standard solution which can eliminate the effect of the matrix and can meet the requirement of residual detection completely.Table 4Evaluation of matrix effects of flumequine and 7-hydroxyflumequine in sediment.Calibration curve without matrixR^2^Calibration curve with matrixR^2^Matrix effect(%)*S*-(−)-flumequineY = 318748x − 2816410.9944Y = 152208x − 2113230.9915−52.2*R*-( + )-flumequineY = 344863x − 3183340.9919Y = 187164x − 1775600.9927−45.77-hydroxyflumequineY = 55563x − 505190.9936Y = 39069x − 397060.9822−29.7
### Linearity, LOD and LOQ {#Sec21}
We obtained a very good linearity within the concentration range of 1.0 to 200.0 µg/L(1.0, 2.0, 5.0, 10, 20, 50, 100, 200) for each enantiomer of flumequine and 7-hydroxyflumequine prepared in the matrix-matched solvent in water and sediment samples were satisfactory. The calibration curves and correlation coefficients for flumequine enantiomers and 7-hydroxyflumequine in different matrix were showed in Table [5](#Tab5){ref-type="table"}.Table 5The linear regression equations, regression coefficients (R^2^) and limits of detection (LODs) for enantiomers of flumequine and 7-hydroxyflumequine in different samples by HPLC-Q-TOF/MS determination.EnantiomersSamplesRegression equationR^2^LOD (µg/kg or µg/L)*S*-(−)-FlumequineWaterY = 23910x − 1181.70.99542.5SedimentY = 152208x − 2113230.99155.0*R*-(+)-FlumequineWaterY = 52291x − 487090.99272.5SedimentY = 187164x − 1775600.99275.07-hydroxyflumequineWaterY = 91664x− 1185650.99883.2SedimentY = 39069x − 397060.98227.0
In water samples, the values obtained for the LOD were 2.5 µg/L for S-(−)-Flumequine and R-(+)-Flumequine, respectively, and for LOQ they were 8.0 µg/L for two enantiomers. In sediment samples, the LOD and LOQ were 5.0 µg/kg and 15.0 µg/kg for both the enantiomers. The LOD for 7-hydroxyflumequine was estimated as 3.2 µg/L in water samples, and as 7.0 µg/kg in sediment samples. The LOQ were 10 µg/L and 20 µg/kg in water and sediment samples respectively.
Application {#Sec22}
-----------
### Application to the real sediment samples {#Sec23}
A total of three different sediment samples were obtained from different pools of Xiqing District of Tianjin. The samples were extracted and cleaned-up according to Sections 2.4 and 2.5 followed by simultaneous and enantioselective determination of flumequine. The HPLC-Q-TOF/MS chromatograms obtained from the sediment samples at different times after application of flumequine enantiomers are shown in Fig. [7](#Fig7){ref-type="fig"}. The resolution between (+)enantiomer and (−)enantiomer was greater than 2.0 under all separation conditions tested, demonstrating sufficient robustness. The results suggest that the chiral method for the separation and determination of flumequine enantiomers, which are characterized by high sensitivity and specificity, rapidity, and possibility of performing the simultaneous analysis of water and sediment samples, become more and more important.Figure 7The HPLC-Q-TOF/MS chromatograms of flumequine obtained from real sediment samples.
Conclusions {#Sec24}
===========
In the present work, chiral separation methods were developed for the determination of flumequine and 7-hydroxyflumequine enantiomers, which were validated for the simultaneous and quantitative determination of the enantiomers of flumequine and its main metabolite 7-hydroxyflumequine enantiomers in water and sediment. The method showed good performance regarding the linearity and instrumental repeat ability.
Meanwhile, effects of the sample preparation and solid phase extraction cartridges were optimized, the recoveries were found to be good with Cleanert PEP. The effect extraction solvent of the sample was studied and found that the ACN and EDTA-Mcllvaine solution was more suitable for extraction of all the test compounds. Experimental results showed that the determination method has high sensitivity and low detection. Moreover, the method developed can be applied to Simultaneous analysis of flumequine antibiotic and its metabolite in water and sediment matrices.
Yuchang Qin and Xu Gu contributed equally to this work.
**Publisher\'s note:** Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This work was supported by the National Natural Science Foundation of China (Contract No. 21407176) and the Special Basic Research Fund for Central Public Research Institutes.
Y.Q. and X.G designed research; Y.G. and X.Y. analyzed data; M.X. and Z.Z. performed experiment; J.L., X.G. and T.Y. edit the manuscript; M.X. wrote the paper. All authors reviewed the manuscript.
Competing Interests {#FPar1}
===================
The authors declare no competing interests.
|
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|
Baby Boomers (ages 48-66 in 2012), Gen Xers (ages 36-47) and Gen Yers (ages 22–35 this year) were asked their attitudes about supporting either their adult children or their aging parents or grandparents. The online study of more than 2,000 ages 21-65 shows that all generations want to be able to provide financially for their children and grandkids. Makes sense, right?
Not so fast: There are differences in how the various groups studied want to spend their money.
It comes down to this: Boomers, as they approach retirement, are most concerned about being able to fund and enjoy their later years. They don’t want to end up taking “handouts” from their kids or being dependent on them in other ways. And, they also don’t want to bankroll them forever. This mind-set is reflected in the MetLife study.
Stripped of dense statistics, here are the results I found most fascinating:
Almost all of those studied from all three generations believe they should help pay college tuition for their kids as well as when there’s a financial emergency not created by the child. It is the younger group, however, who feel parents should be even more generous to their children and grandchildren.
Fewer Boomers than Gen X or Y’s say that parents with health or financial woes should live with them-hmmm, could it be that independence thing, again? But all generations agree relatively proportionately (Gen Xers trail slightly): Parents or in-laws who need financial support from adult children should get it.
What do these findings mean? That Boomers, a.k.a. the “Me” generation, are more selfish than the next generations? That they’re just scared they haven’t saved adequately? Or, do they think they’ve sacrificed enough already? Might it be that when X and Y get older, they’ll see the situation differently?
I’m also wondering why parents who financially support their kids as they grow up (that’s double digit years or beyond) are so reluctant to take money (or housing) from their grown children-their replacement as earners? Mom, Dad, and Grandpa somehow regard it as unnatural.
I’m banking that part of it may be a reluctance to acknowledge the role reversals that they’ve seen with their own parents. Your thoughts? |
Choijin Lama Temple
The Choijin Lama Temple (; Official name given by Manchu Qing Emperor Guangxu (1871 – 1908): , ; Gosimbin Jadenblh juktenen, , English; Compassion Perfection Temple, Chinese:興仁寺) is a Buddhist monastery in Ulaanbaatar, the capital of Mongolia.
The complex consists of six temples originally occupied by the brother of the ruler the Eighth Bogd Jetsun Dampa Khan, Choijin Lama Luvsankhaidav, who was the state oracle and 'Precious Wisdom and Clear Devotion' Khutugtu at the time. The complex was begun in 1904 and completed in 1908, in honor of the State Oracle Lama Lubsanhaidub /Losang Kedrup/, brother of the eighth Bogd Khan. The Choijin Lama Museum was originally a Buddhist temple complex, consisting of one main and five branch temples. It was active until 1937, when it was closed during the height of Communist repression against Buddhism and other religious traditions. In 1938 the complex was re-established as museum due to skillful efforts of wise people. This was how it was saved throughout communism.
The main temple features an 18th-century gilt statue of Buddha Sakyamuni with a statue of Choijin Lama Luvsankhaidav on the Buddha's right and the embalmed corpse of Baldan Choephel on his left. In addition, the temple boasts a copious collection of religious instruments, thangka paintings, silk embroideries, wood carvings, statues, and a biggest collection of cham dance masks).
The annex to the temple contains another temple, named 'Zankhang' and a central square in which Choijin Lama Luvsankhaidav performed Oracle trance rituals.
The Zuu Temple, dedicated to the Buddha Shakyamuni features papier-mache sculptures of Buddha in the past, present, and future. The 16 arhat disciples of Buddha appear on the temple walls with four Maharajas protectors shown sitting in caves on either side of the door.
The Yidam Temple was used as a place of prayer by Choijin Lama Luvsankhaidav, and therefore closed to the public. In its center is a gilt bronze sculpture of one of the 84 Indian yogis, or Mahasiddha. Also depicted are the tantric gods Kalacakra, Mahamaya, Vajradhara and others with their shakti or consorts in postures of meditation that symbolize power and strength.
The fourth temple, the temple of amugulang or peace, is dedicated to the first Mongolian reincarnation of Boghda Jevzundamba, Undur Gegeen Zanabazar, (1635-1724).
Museum
The museum, it preserves a rich heritage of Buddhist artifacts. Located in central Ulaanbaatar directly south of Sukhbaatar square, the museum is open year-round (with reduced hours during the winter months). Explanations of the almost overwhelming collection are not as detailed as they could be, but each temple has room attendants who can provide additional material. The museum itself and its objects also show the re-emergence of Buddhism in Mongolia after Communist repression, with a particularly interesting display on Buddhist cham dancing and its modern revival.
References
External links
Choijin Lama Temple Museum website
Category:Buddhism in Ulaanbaatar
Category:Buddhist monasteries in Mongolia
Category:Buildings and structures in Ulaanbaatar
Category:Tibetan Buddhism in Mongolia |
We’re being invaded & we’re doing nothing about it
I gotta vent. We / our country is sitting back & not doing a damn thing about illegals/ invaders invading our country! They are coming here in the thousands daily. They are killing our people, our police,our border guards, our fellow citizens. What are we doing? Talk talk talk. They are stealing our resources, our jobs, our taxes, our benefits, starting businesses, and we’re ok with it. We’re letting them! We’re helping them! Giving them jobs,places to live, money, food, healthcare,educations, putting them in schools with our children, accomidating them, making two signs! One english one spanish. Even phine messages are bilingual. Our politicians are ok with it. Our news media is for it. Our chambers of commerce are for it. Our countrymen are betraying us for MONEY! We’re sick! Sick in the head & the heart. What country in their right mind would put up with such a thing? We should be preventing them at the border. We should be rounding them up & be tracking them down & shooting them for invading our country but we’ve made it illegal to defend our country! WHY?
What i meant about doing something is shooting them crossing the border. The ones that are here we need more enforcement. Prosecute people & business hiring them with hefty hefty fines even taking their business from them & locking them up. Sell their business to someone else. Authorize police to check those who look like they are from Central America & mexico. Also foreigners who look like they are from foreign countries & who obviously cannot speak English. And whatever other ways police know how to identify illegals. Take the glives off of them. Like Sheriff Joe Arpaio was doing. Etc...
THAT would stop this invasion. The threat of violence done in return to the violence they are doing to us, plundering, invading, killing, spreading sickness, destroying our schools, our standard of living, OUR HOPES.
Call your members of Congress.... daily if necessary and demand they shut down all immigration and deport everyone here illegally.... Tell them if they won;t they can join the illegals when America finally wakes up and deports them.
LIGHTER SIDE
ALERT ALERT
House Speaker Nancy Pelosi must be taking night classes at the Alexandria Ocasio-Cortez School of Government.
Pelosi, the 79-year-old third-highest ranking official in the U.S. government, was speaking to the Center for American Progress today when she mistakenly said there are “two co-equal branches” of government, before correcting herself to say there are three.
Watch:
“First of all, let me just say, we take an oath of office to protect and defend the Constitution of the United States,” Pelosi said.
“Democrats take that oath seriously, and we are committed to honoring our oath of office. I’m not sure that our Republican colleagues share that commitment, and I’m not sure that the president of the United States does, too,” she claimed.
“So, in light of the fact that the beauty of the Constitution is a system of checks and balances— two co-equal branches— three co-equal branches of government,” she corrected with a laugh.
“A check and balance on each other,” she continued. “Con— Constitution spells out the pri— pa, uh, the duties of Congress and one of them is oversight of the president of the United States, another one of them is to impeach the president of the United States,” Pelosi said.
In November, Alexandria Ocasio-Cortez rallied supporters on Facebook to pitch in and help Democrats take back “all three chambers of Congress.”
“…the Progressive movement works and it wins in all districts…If we work our butts off to make sure that we take back all three chambers of Congress– three chambers of government…,” she said during the virtual appearance.
She clarified that she meant the “presidency, the Senate and the House.”
According to the Constitution, the three branches of government are the legislative, executive and judicial.
Below: Nancy Pelosi is continuing to promote the false narrative that President Trump is involved in a cover-up and therefore may be guilty of an impeachable offense. Millie Weaver joins Alex to break down the propaganda being used to overturn the democratic election of 2016 |
Is risk assessment the new clinical model in public mental health?
Australian public mental health services have seen a rapid adoption of risk assessment into clinical practice over the past decade. It is timely to review the role of risk assessment in clinical practice, evidence for its validity and to explore its role in clinical decision-making. There is little evidence to support the current form of risk assessment used in public mental health. The continued focus in risk may lead public psychiatrists into a bind where their specialist role is defined by a capacity that they do not fully possess. Further work is required to find ways of demonstrating our attention to the possibility of adverse outcomes whilst maintaining our skills and capacity to manage mental illness with complexity and balance within the limitations of rational decision-making. |
A Shared Telos? Two Paths of Becoming God: Technology and Cooperation
Ethan Schimmoeller, MD candidate, MA candidate in bioethics, Student, University of Cincinnati College of Medicine, The Ohio State University
The recently published book, Euthanasia and Assisted Suicide: Lessons from Belgium, concludes that, since legalization in 2002, “death by euthanasia in Belgium is…regarded as a normal death and a benefit not to be restricted.” Whereas the normal secular death increasingly comes under the domain of decision via ‘physician-assistance’, can robust, traditional religion reveal an alternative that reaches beyond lifeless moralism? More fundamentally, do secular medicine and Christianity possibly share teleology? This paper will reflect upon dying, transcendence, and breathing Life into dead matter.
Medicine has embraced a technological paradigm of asserting mastery over nature, as evidenced by the clear turn in recent years toward euthanasia and assisted suicide. In the language of George Grant, making and knowing have fused into willing, resulting in techne-logos as much more than neutral instrument for relieving the human estate. Technology, rather, captures our assumption of mastery over nature, and consequently forms the very paradigm for knowledge, resulting in artificial necessity. Past ‘givens’ of human life, namely, death, thus present themselves as obligatory objects to be mastered by the will to power. Nature, especially the body, is seen as formless and void until the will can transform it. In the language of medical ethics today, physicians present value-free facts to autonomous patients who must impose subjective value upon them. With post-Darwinian biology proclaiming man to merely result from chance and dead matter, assisted-dying provides the final vehicle for an appropriate, reciprocal conclusion.
If only in the collective mind, the will has triumphed in asserting itself to construct reality. Humanism quickly evolves into trans-humanism by uniting the will to power with cybernetics to take an evolutionary leap: the post-human god emancipated from natural necessity and givens, with the will to define the terms of its own existence. Technology, as paradigm for our era, is the new religion, promising to transform us into immanent gods.
These ends of mastery hearken to ‘becoming partakers of the Divine nature.’ By cooperation, rather than mastery, Christ promises to transform each believer into God by participation, making us ‘sons in the Son.’ The living God, who comes to us hidden as bread and wine, shows that true God-ness requires ‘humbling oneself, becoming obedient to death, even death on a cross.’ Thus, euthanasia and the immanent post-human god are exposed as hollow and lifeless by the true God-man, who unites immanence and transcendence.
If we are to take this authentic Divinization seriously, Christians must not embrace a technological stance towards the world. Rather, we ought to energetically become ‘obedient unto death’ and care for the dying. This posture will open the door to demonstrating a better way to die in the prospect of euthanasia becoming the normative death in this country. |
/*
* Copyright (c) 2009, 2010 Petri Lehtinen <petri@digip.org>
*
* Jansson is free software; you can redistribute it and/or modify
* it under the terms of the MIT license. See LICENSE for details.
*/
#define _GNU_SOURCE
#include <ctype.h>
#include <errno.h>
#include <limits.h>
#include <stdio.h>
#include <stdlib.h>
#include <string.h>
#include <stdarg.h>
#include <assert.h>
#include <jansson.h>
#include "jansson_private.h"
#include "strbuffer.h"
#include "utf.h"
#define TOKEN_INVALID -1
#define TOKEN_EOF 0
#define TOKEN_STRING 256
#define TOKEN_INTEGER 257
#define TOKEN_REAL 258
#define TOKEN_TRUE 259
#define TOKEN_FALSE 260
#define TOKEN_NULL 261
/* read one byte from stream, return EOF on end of file */
typedef int (*get_func)(void *data);
/* return non-zero if end of file has been reached */
typedef int (*eof_func)(void *data);
typedef struct {
get_func get;
eof_func eof;
void *data;
int stream_pos;
char buffer[5];
int buffer_pos;
} stream_t;
typedef struct {
stream_t stream;
strbuffer_t saved_text;
int token;
int line, column;
union {
char *string;
int integer;
double real;
} value;
} lex_t;
/*** error reporting ***/
static void error_init(json_error_t *error)
{
if(error)
{
error->text[0] = '\0';
error->line = -1;
}
}
static void error_set(json_error_t *error, const lex_t *lex,
const char *msg, ...)
{
va_list ap;
char text[JSON_ERROR_TEXT_LENGTH];
if(!error || error->text[0] != '\0') {
/* error already set */
return;
}
va_start(ap, msg);
vsnprintf(text, JSON_ERROR_TEXT_LENGTH, msg, ap);
va_end(ap);
if(lex)
{
const char *saved_text = strbuffer_value(&lex->saved_text);
error->line = lex->line;
if(saved_text && saved_text[0])
{
if(lex->saved_text.length <= 20) {
snprintf(error->text, JSON_ERROR_TEXT_LENGTH,
"%s near '%s'", text, saved_text);
}
else
snprintf(error->text, JSON_ERROR_TEXT_LENGTH, "%s", text);
}
else
{
snprintf(error->text, JSON_ERROR_TEXT_LENGTH,
"%s near end of file", text);
}
}
else
{
error->line = -1;
snprintf(error->text, JSON_ERROR_TEXT_LENGTH, "%s", text);
}
}
/*** lexical analyzer ***/
static void
stream_init(stream_t *stream, get_func get, eof_func eof, void *data)
{
stream->get = get;
stream->eof = eof;
stream->data = data;
stream->stream_pos = 0;
stream->buffer[0] = '\0';
stream->buffer_pos = 0;
}
static char stream_get(stream_t *stream, json_error_t *error)
{
char c;
if(!stream->buffer[stream->buffer_pos])
{
stream->buffer[0] = stream->get(stream->data);
stream->buffer_pos = 0;
c = stream->buffer[0];
if((unsigned char)c >= 0x80 && c != (char)EOF)
{
/* multi-byte UTF-8 sequence */
int i, count;
count = utf8_check_first(c);
if(!count)
goto out;
assert(count >= 2);
for(i = 1; i < count; i++)
stream->buffer[i] = stream->get(stream->data);
if(!utf8_check_full(stream->buffer, count, NULL))
goto out;
stream->stream_pos += count;
stream->buffer[count] = '\0';
}
else {
stream->buffer[1] = '\0';
stream->stream_pos++;
}
}
return stream->buffer[stream->buffer_pos++];
out:
error_set(error, NULL, "unable to decode byte 0x%x at position %d",
(unsigned char)c, stream->stream_pos);
stream->buffer[0] = EOF;
stream->buffer[1] = '\0';
stream->buffer_pos = 1;
return EOF;
}
static void stream_unget(stream_t *stream, char c)
{
assert(stream->buffer_pos > 0);
stream->buffer_pos--;
assert(stream->buffer[stream->buffer_pos] == c);
}
static int lex_get(lex_t *lex, json_error_t *error)
{
return stream_get(&lex->stream, error);
}
static int lex_eof(lex_t *lex)
{
return lex->stream.eof(lex->stream.data);
}
static void lex_save(lex_t *lex, char c)
{
strbuffer_append_byte(&lex->saved_text, c);
}
static int lex_get_save(lex_t *lex, json_error_t *error)
{
char c = stream_get(&lex->stream, error);
lex_save(lex, c);
return c;
}
static void lex_unget_unsave(lex_t *lex, char c)
{
char d;
stream_unget(&lex->stream, c);
d = strbuffer_pop(&lex->saved_text);
assert(c == d);
}
static void lex_save_cached(lex_t *lex)
{
while(lex->stream.buffer[lex->stream.buffer_pos] != '\0')
{
lex_save(lex, lex->stream.buffer[lex->stream.buffer_pos]);
lex->stream.buffer_pos++;
}
}
/* assumes that str points to 'u' plus at least 4 valid hex digits */
static int32_t decode_unicode_escape(const char *str)
{
int i;
int32_t value = 0;
assert(str[0] == 'u');
for(i = 1; i <= 4; i++) {
char c = str[i];
value <<= 4;
if(isdigit(c))
value += c - '0';
else if(islower(c))
value += c - 'a' + 10;
else if(isupper(c))
value += c - 'A' + 10;
else
assert(0);
}
return value;
}
static void lex_scan_string(lex_t *lex, json_error_t *error)
{
char c;
const char *p;
char *t;
int i;
lex->value.string = NULL;
lex->token = TOKEN_INVALID;
c = lex_get_save(lex, error);
while(c != '"') {
if(c == (char)EOF) {
lex_unget_unsave(lex, c);
if(lex_eof(lex))
error_set(error, lex, "premature end of input");
goto out;
}
else if((unsigned char)c <= 0x1F) {
/* control character */
lex_unget_unsave(lex, c);
if(c == '\n')
error_set(error, lex, "unexpected newline", c);
else
error_set(error, lex, "control character 0x%x", c);
goto out;
}
else if(c == '\\') {
c = lex_get_save(lex, error);
if(c == 'u') {
c = lex_get_save(lex, error);
for(i = 0; i < 4; i++) {
if(!isxdigit(c)) {
lex_unget_unsave(lex, c);
error_set(error, lex, "invalid escape");
goto out;
}
c = lex_get_save(lex, error);
}
}
else if(c == '"' || c == '\\' || c == '/' || c == 'b' ||
c == 'f' || c == 'n' || c == 'r' || c == 't')
c = lex_get_save(lex, error);
else {
lex_unget_unsave(lex, c);
error_set(error, lex, "invalid escape");
goto out;
}
}
else
c = lex_get_save(lex, error);
}
/* the actual value is at most of the same length as the source
string, because:
- shortcut escapes (e.g. "\t") (length 2) are converted to 1 byte
- a single \uXXXX escape (length 6) is converted to at most 3 bytes
- two \uXXXX escapes (length 12) forming an UTF-16 surrogate pair
are converted to 4 bytes
*/
lex->value.string = malloc(lex->saved_text.length + 1);
if(!lex->value.string) {
/* this is not very nice, since TOKEN_INVALID is returned */
goto out;
}
/* the target */
t = lex->value.string;
/* + 1 to skip the " */
p = strbuffer_value(&lex->saved_text) + 1;
while(*p != '"') {
if(*p == '\\') {
p++;
if(*p == 'u') {
char buffer[4];
int length;
int32_t value;
value = decode_unicode_escape(p);
p += 5;
if(0xD800 <= value && value <= 0xDBFF) {
/* surrogate pair */
if(*p == '\\' && *(p + 1) == 'u') {
int32_t value2 = decode_unicode_escape(++p);
p += 5;
if(0xDC00 <= value2 && value2 <= 0xDFFF) {
/* valid second surrogate */
value =
((value - 0xD800) << 10) +
(value2 - 0xDC00) +
0x10000;
}
else {
/* invalid second surrogate */
error_set(error, lex,
"invalid Unicode '\\u%04X\\u%04X'",
value, value2);
goto out;
}
}
else {
/* no second surrogate */
error_set(error, lex, "invalid Unicode '\\u%04X'",
value);
goto out;
}
}
else if(0xDC00 <= value && value <= 0xDFFF) {
error_set(error, lex, "invalid Unicode '\\u%04X'", value);
goto out;
}
else if(value == 0)
{
error_set(error, lex, "\\u0000 is not allowed");
goto out;
}
if(utf8_encode(value, buffer, &length))
assert(0);
memcpy(t, buffer, length);
t += length;
}
else {
switch(*p) {
case '"': case '\\': case '/':
*t = *p; break;
case 'b': *t = '\b'; break;
case 'f': *t = '\f'; break;
case 'n': *t = '\n'; break;
case 'r': *t = '\r'; break;
case 't': *t = '\t'; break;
default: assert(0);
}
t++;
p++;
}
}
else
*(t++) = *(p++);
}
*t = '\0';
lex->token = TOKEN_STRING;
return;
out:
free(lex->value.string);
}
static int lex_scan_number(lex_t *lex, char c, json_error_t *error)
{
const char *saved_text;
char *end;
double value;
lex->token = TOKEN_INVALID;
if(c == '-')
c = lex_get_save(lex, error);
if(c == '0') {
c = lex_get_save(lex, error);
if(isdigit(c)) {
lex_unget_unsave(lex, c);
goto out;
}
}
else if(isdigit(c)) {
c = lex_get_save(lex, error);
while(isdigit(c))
c = lex_get_save(lex, error);
}
else {
lex_unget_unsave(lex, c);
goto out;
}
if(c != '.' && c != 'E' && c != 'e') {
long value;
lex_unget_unsave(lex, c);
saved_text = strbuffer_value(&lex->saved_text);
value = strtol(saved_text, &end, 10);
assert(end == saved_text + lex->saved_text.length);
if((value == LONG_MAX && errno == ERANGE) || value > INT_MAX) {
error_set(error, lex, "too big integer");
goto out;
}
else if((value == LONG_MIN && errno == ERANGE) || value < INT_MIN) {
error_set(error, lex, "too big negative integer");
goto out;
}
lex->token = TOKEN_INTEGER;
lex->value.integer = (int)value;
return 0;
}
if(c == '.') {
c = lex_get(lex, error);
if(!isdigit(c))
goto out;
lex_save(lex, c);
c = lex_get_save(lex, error);
while(isdigit(c))
c = lex_get_save(lex, error);
}
if(c == 'E' || c == 'e') {
c = lex_get_save(lex, error);
if(c == '+' || c == '-')
c = lex_get_save(lex, error);
if(!isdigit(c)) {
lex_unget_unsave(lex, c);
goto out;
}
c = lex_get_save(lex, error);
while(isdigit(c))
c = lex_get_save(lex, error);
}
lex_unget_unsave(lex, c);
saved_text = strbuffer_value(&lex->saved_text);
value = strtod(saved_text, &end);
assert(end == saved_text + lex->saved_text.length);
if(errno == ERANGE && value != 0) {
error_set(error, lex, "real number overflow");
goto out;
}
lex->token = TOKEN_REAL;
lex->value.real = value;
return 0;
out:
return -1;
}
static int lex_scan(lex_t *lex, json_error_t *error)
{
char c;
strbuffer_clear(&lex->saved_text);
if(lex->token == TOKEN_STRING) {
free(lex->value.string);
lex->value.string = NULL;
}
c = lex_get(lex, error);
while(c == ' ' || c == '\t' || c == '\n' || c == '\r')
{
if(c == '\n')
lex->line++;
c = lex_get(lex, error);
}
if(c == (char)EOF) {
if(lex_eof(lex))
lex->token = TOKEN_EOF;
else
lex->token = TOKEN_INVALID;
goto out;
}
lex_save(lex, c);
if(c == '{' || c == '}' || c == '[' || c == ']' || c == ':' || c == ',')
lex->token = c;
else if(c == '"')
lex_scan_string(lex, error);
else if(isdigit(c) || c == '-') {
if(lex_scan_number(lex, c, error))
goto out;
}
else if(isupper(c) || islower(c)) {
/* eat up the whole identifier for clearer error messages */
const char *saved_text;
c = lex_get_save(lex, error);
while(isupper(c) || islower(c))
c = lex_get_save(lex, error);
lex_unget_unsave(lex, c);
saved_text = strbuffer_value(&lex->saved_text);
if(strcmp(saved_text, "true") == 0)
lex->token = TOKEN_TRUE;
else if(strcmp(saved_text, "false") == 0)
lex->token = TOKEN_FALSE;
else if(strcmp(saved_text, "null") == 0)
lex->token = TOKEN_NULL;
else
lex->token = TOKEN_INVALID;
}
else {
/* save the rest of the input UTF-8 sequence to get an error
message of valid UTF-8 */
lex_save_cached(lex);
lex->token = TOKEN_INVALID;
}
out:
return lex->token;
}
static char *lex_steal_string(lex_t *lex)
{
char *result = NULL;
if(lex->token == TOKEN_STRING)
{
result = lex->value.string;
lex->value.string = NULL;
}
return result;
}
static int lex_init(lex_t *lex, get_func get, eof_func eof, void *data)
{
stream_init(&lex->stream, get, eof, data);
if(strbuffer_init(&lex->saved_text))
return -1;
lex->token = TOKEN_INVALID;
lex->line = 1;
return 0;
}
static void lex_close(lex_t *lex)
{
if(lex->token == TOKEN_STRING)
free(lex->value.string);
strbuffer_close(&lex->saved_text);
}
/*** parser ***/
static json_t *parse_value(lex_t *lex, json_error_t *error);
static json_t *parse_object(lex_t *lex, json_error_t *error)
{
json_t *object = json_object();
if(!object)
return NULL;
lex_scan(lex, error);
if(lex->token == '}')
return object;
while(1) {
char *key;
json_t *value;
if(lex->token != TOKEN_STRING) {
error_set(error, lex, "string or '}' expected");
goto error;
}
key = lex_steal_string(lex);
if(!key)
return NULL;
lex_scan(lex, error);
if(lex->token != ':') {
free(key);
error_set(error, lex, "':' expected");
goto error;
}
lex_scan(lex, error);
value = parse_value(lex, error);
if(!value) {
free(key);
goto error;
}
if(json_object_set_nocheck(object, key, value)) {
free(key);
json_decref(value);
goto error;
}
json_decref(value);
free(key);
lex_scan(lex, error);
if(lex->token != ',')
break;
lex_scan(lex, error);
}
if(lex->token != '}') {
error_set(error, lex, "'}' expected");
goto error;
}
return object;
error:
json_decref(object);
return NULL;
}
static json_t *parse_array(lex_t *lex, json_error_t *error)
{
json_t *array = json_array();
if(!array)
return NULL;
lex_scan(lex, error);
if(lex->token == ']')
return array;
while(lex->token) {
json_t *elem = parse_value(lex, error);
if(!elem)
goto error;
if(json_array_append(array, elem)) {
json_decref(elem);
goto error;
}
json_decref(elem);
lex_scan(lex, error);
if(lex->token != ',')
break;
lex_scan(lex, error);
}
if(lex->token != ']') {
error_set(error, lex, "']' expected");
goto error;
}
return array;
error:
json_decref(array);
return NULL;
}
static json_t *parse_value(lex_t *lex, json_error_t *error)
{
json_t *json;
switch(lex->token) {
case TOKEN_STRING: {
json = json_string_nocheck(lex->value.string);
break;
}
case TOKEN_INTEGER: {
json = json_integer(lex->value.integer);
break;
}
case TOKEN_REAL: {
json = json_real(lex->value.real);
break;
}
case TOKEN_TRUE:
json = json_true();
break;
case TOKEN_FALSE:
json = json_false();
break;
case TOKEN_NULL:
json = json_null();
break;
case '{':
json = parse_object(lex, error);
break;
case '[':
json = parse_array(lex, error);
break;
case TOKEN_INVALID:
error_set(error, lex, "invalid token");
return NULL;
default:
error_set(error, lex, "unexpected token");
return NULL;
}
if(!json)
return NULL;
return json;
}
static json_t *parse_json(lex_t *lex, json_error_t *error)
{
error_init(error);
lex_scan(lex, error);
if(lex->token != '[' && lex->token != '{') {
error_set(error, lex, "'[' or '{' expected");
return NULL;
}
return parse_value(lex, error);
}
typedef struct
{
const char *data;
int pos;
} string_data_t;
static int string_get(void *data)
{
char c;
string_data_t *stream = (string_data_t *)data;
c = stream->data[stream->pos];
if(c == '\0')
return EOF;
else
{
stream->pos++;
return c;
}
}
static int string_eof(void *data)
{
string_data_t *stream = (string_data_t *)data;
return (stream->data[stream->pos] == '\0');
}
json_t *json_loads(const char *string, json_error_t *error)
{
lex_t lex;
json_t *result;
string_data_t stream_data = {
.data = string,
.pos = 0
};
if(lex_init(&lex, string_get, string_eof, (void *)&stream_data))
return NULL;
result = parse_json(&lex, error);
if(!result)
goto out;
lex_scan(&lex, error);
if(lex.token != TOKEN_EOF) {
error_set(error, &lex, "end of file expected");
json_decref(result);
result = NULL;
}
out:
lex_close(&lex);
return result;
}
json_t *json_loadf(FILE *input, json_error_t *error)
{
lex_t lex;
json_t *result;
if(lex_init(&lex, (get_func)fgetc, (eof_func)feof, input))
return NULL;
result = parse_json(&lex, error);
if(!result)
goto out;
lex_scan(&lex, error);
if(lex.token != TOKEN_EOF) {
error_set(error, &lex, "end of file expected");
json_decref(result);
result = NULL;
}
out:
lex_close(&lex);
return result;
}
json_t *json_load_file(const char *path, json_error_t *error)
{
json_t *result;
FILE *fp;
error_init(error);
fp = fopen(path, "r");
if(!fp)
{
error_set(error, NULL, "unable to open %s: %s",
path, strerror(errno));
return NULL;
}
result = json_loadf(fp, error);
fclose(fp);
return result;
}
|
Q:
Sort an array which contains number and strings
I am trying to sort an array which contains strings, numbers, and numbers as strings (ex. '1','2'). I want to sort this array so that the sorted array contains numbers first and then strings that contain a number and then finally strings.
var arr = [9,5,'2','ab','3',-1 ] // to be sorted
arr.sort()
// arr = [-1, 5, 9, "2", "3","ab"] // expected result
//arr = [-1, "2", 5, 9, "ab"] // actual result
I have also tried
var number =[];
var char =[];
arr.forEach(a=>{
if(typeof a == 'number') number.push(a);
else char.push(a);
})
arr = (number.sort((a,b)=> a>b)).concat(char.sort((a,b)=> a>b))
// arr = [-1, 5, 9, "2", "3","ab"] // expected result
// arr = [-1, 5, 9, "2", "ab", "3"]// actual result
A:
The shortest is probably:
arr.sort((a, b) => ((typeof b === "number") - (typeof a === "number")) || (a > b ? 1 : -1));
A:
You can sort the numbers first and then the non-numbers by using .filter() to separate both data-types.
See working example below (read code comments for explanation):
const arr = [9,5,'2','ab','3',-1];
const nums = arr.filter(n => typeof n == "number").sort(); // If the data type of a given element is a number store it in this array (and then sort)
const non_nums = arr.filter(x => typeof x != "number").sort(); // Store everything that is not a number in an array (and then sort)
const res = [...nums, ...non_nums]; // combine the two arrays
console.log(res); // [-1, 5, 9, "2", "3", "ab"]
A:
It seems you have done most of the work in your second attempt.
All I have done here is used Array.concat to join the sorted results of number and char together.
var arr = [9, 5, '2', 'ab', '3', -1] // to be sorted
var number = [];
var char = [];
arr.forEach(a => {
if (typeof a == 'number') number.push(a);
else char.push(a);
})
var sorted = number.sort().concat(char.sort());
console.log(sorted)
|
What happened to these 30 carbine cases?
A situation that perhaps our M1 carbine gurus will diagnose easily - but which I find a bit puzzling.
Today I fired 30 test rounds of 30C - reloads all using new (unfired, anyway) LC brass, 14.8g of H110, and 3 brands of SR primers - Tula, Wolf, and CCI. All worked just fine. I wanted to see how the brass - untrimmed, but under 1.290 after resizing and expansion - and the various primers worked. I also wanted to see if a larger charge (I used 14.5g of H110 or a bit less in my first 30C reloads) brought the point of impact up a bit @ 50 and 100yds (it did).
Then for comparison, practice, and fun, I fired about 30 S&B factory rounds (before switching over to my Mosin Nagant to continue my epic struggle to determine whether I do in fact have to move the front sight about .001" to the right to center the hits @ 100yds - and to happily fire a Garand that the shooter next to me graciously offered to share).
Of those, about a third showed a distinctive dent in the case mouth when I recovered them. I hope the photos here show what I'm talking about.
Each and every LC case was fine (that is, no real distortions or dents to the case mouths). A few questions:
1) what would cause this dent in the case mouths?
2) why some, and not others?
3) why was the LC brass unaffected?
I know (well, I think I know) that the S&B factory might be a little under-powered compared to my reloads. But I can't come up with how that fact might cause 1/3 of the cases to be dented on extraction/ejection.
One more question - can I salvage these cases by bending the case mouths back out to (approx.) round, or do they go in the scrap can?
Footnote: the nearby Garand shooter, happily, didn't want his brass, so now I have a start on my stock of 30-06 cases to feed my recently arrived CMP 1955 HRA Service Grade M1, now undergoing stock cleaning. And there were also scads of .223 cases I happily scooped up to add to my can of that caliber, which I plan to clean and sell.
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FROGO207
June 22, 2012, 06:40 AM
What you are seeing is the brass hitting somewhere on the rifle when ejected. It might be more power or might be less causing the brass to bounce off the top or bottom of the ejection port. Probably low power allowing the front of the case to bounce off side of the receiver near the back of the barrel. It is no big deal other than the need to bend out the case mouths when reusing the brass. FWIW I have saved brass that has been crushed lots worse so no worries IMHO. Using the proper propellant charge for the weight bullet to get a good speed of ejection impulse to smoothly eject the brass will make the problem a non issue. Just takes a bit of experimentation to achieve usually. As always if things get worse over time on any recoil operated firearm check the recoil buffer for wear and replace if necessary.
USSR
June 22, 2012, 07:27 AM
I agree with FROGO207's assessment. Get yourself some sort of round tapered tool to tap into the case neck and remove the "ding". You will likely need it for your Garand anyways. I use a knife sharpener.
Don
cfullgraf
June 22, 2012, 09:31 AM
I frequently use a pair of needle nose pliers to round out cases. I just leave the jaws closed and put the nose of the pliers in the case mouth to iron it out.
Also, you can spread the jaws a little while in the case to help push the dent out.
The round outside of the jaws work well at getting the case mouth expanded out back to near round.
I have both a miniature and standard pair of pliers and use the one appropriate for the task.
Then, the resize die will finish the job and get the mouth round again.
blarby
June 22, 2012, 09:36 AM
A resize pin will fix this without any intervention.
rcmodel
June 22, 2012, 11:30 AM
+1
The cases do a double back flip out of the rifle on ejection and hit the receiver or bolt handle.
Look for tiny little brass tracks on the bolt handle or receiver and you will see where.
That ain't nothing to worry about.
They will be straight after you resize them.
And for sure after you expand them.
rc
16in50calNavalRifle
June 22, 2012, 12:14 PM
Thanks all for your help. I did suspect it was the charge and the ejection process - trying to think if I have seen any/much of this before when I shot factory ammo (incl. S&B). Since most of the factory cases and all of the "new" LC brass was fine, I'm not going to worry about it.
Already decided to try and load my 30C right at the original 15g level - carbine has a front sight that seems high and shoots low, even lower with less than max. loads, the larger charge seemed to resolve that yesterday (I am reluctant to get into grinding down the front sight blade). I have had a handful of stovepipes with some earlier reloads, and the full/standard load should probably take care of both that and these dents.
Good to hear about fixing the dents. I tried that on a few 45ACP and 9mm cases in my initial loading runs, but did not have great success. Need to find the right tool for the job.
USSR
June 22, 2012, 01:46 PM
16in50calNavalRifle,
Get a simple knife sharpening steel like shown below. Note how it tapers at the point which allows you to insert it a dinged neck, and then give it a slight whack on the handle with the palm of your hand and, voila, instant round neck!!!
Don - thanks. Just looked and sure enough I have one of those in the kitchen. Will give it a try when I do my next 30C run (still waiting for Lee to return my expander die body, which was putting those scratches on the cases). After that, I'll look into how to use the thing to, uh ..... sharpen knives! I have a fairly nifty knife sharpener thinggy I use for sharpening, but really should inform myself on how to use that steel.
realbuffdriver
June 24, 2012, 11:14 AM
My experience with S&B carbine ammo is that it's a bit hotter than the loads that I have worked up. I've also experienced case mouth "dings" with 45ACP ammo that was loaded hotter. That's almost surely the issue.
I bought 1000 rounds of S&B when it was $8.50 per box. Wish I had bought a lot more. It's accurate and the cases reload very nicely.
Best of luck with your carbine reloading!
hang fire
June 25, 2012, 01:29 AM
S&B does load a bit hot sometimes, may just be burning rate of powder they use. I noticed it with my 6.5x55 Swede when shooting 2900+ fps, 131 grain S&B in it. Though accurate, I opted to not shoot the remaining 17 rounds.
16in50calNavalRifle
June 25, 2012, 02:28 AM
Thanks for the input guys. The data I've seen for S&B does not indicate greater velocity than USGI - but I don't have a chrono yet so I don't know what my USGI "duplicate" loads are doing (actually @ 14.8g of H110 there's still some room for .2g more, which is what I will try next).
S&B ammo has always performed well for me - but as a reloader now, I AM a bit wary of their tight primer pockets (at least in 9mm). I segregate the S&B cases (darn thoughtful of them to splash that red laquer on the primers, makes it easy to pick them out of the pile) for now and hope to use them some day after reaming out the pockets a bit .... but that "some day" will probably be a ways off, as I'm unlikely to go to that trouble until I've worked through my nice stock of other 9mm brass.
Hacker15E
June 25, 2012, 08:03 AM
Why are you 'wary' of tight primer pockets?
Just because of the pain of swiping a reamer through them?
moxie
June 25, 2012, 09:05 AM
16in50,
As recommended by others above, please just resize and expand before you use pliers or other means to bend the brass. Those dents are minor and should disappear in the sizing and expanding process.
TonyT
June 25, 2012, 09:10 AM
I agree with MOXIE. Just resize and expand the cses, do not attempt to bend the brass with pliers or other contrivances.
Carl N. Brown
June 25, 2012, 09:55 AM
I don't reload .30 carbine much, may be 200 or 300 rounds since 2001, but when I do I use the case mouth flaring tool from my .32 revolver reloading kit, because a percentage of casings will show a dent on the mouth. I always assumed they had impacted the concrete at the range. In fact, since they went to an asphalt surface I have noticed fewer dents when I sort the brass by manufacturer after decapping, saving the brass for when it will pay to reload.
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Q:
how to fix the end of procedure trigger error
is there a way to fix this error or there is something i am missing in my code,im learning postgresql and i have been working on table inheritance and triggers i have two tables the temporary_object table and the persons table the persons table inherits all the properties the the temporary object has,then i have created a trigger function on the persons table which checks the records with the same id before updating the tables my problem comes when i try to run the insert query,im getting these errors
ERROR: end of trigger procedure achieved without RETURN
CONTEXT: function PL / pgSQL muli_function ()
ERROR: end of trigger procedure achieved without RETURN
SQL-state: 2F005
Context: The PL / pgSQL muli_function ()
this is by insert query
INSERT INTO persons (id, time_create, time_dead, First_name, Last_name) values (1, '2011-10-07 15:25:00 EDT', '2011-10-07 3:25 PM EDT', 'sathiya', 'james');
and this my trigger function and trigger itself
CREATE FUNCTION muli_function() RETURNS trigger AS '
BEGIN
IF tg_op = ''UPDATE'' THEN
UPDATE persons
SET time_dead = NEW.time_create
Where
id = NEW.id
AND time_dead IS NULL
;
RETURN new;
END IF;
END
' LANGUAGE plpgsql;
CREATE TRIGGER sofgr BEFORE INSERT OR DELETE OR UPDATE
ON persons FOR each ROW
EXECUTE PROCEDURE muli_function();
and these are my two tables query
CREATE TABLE temporary_object
(
id integer NOT NULL,
time_create timestamp without time zone NOT NULL,
time_dead timestamp without time zone,
PRIMARY KEY (id, time_create)
);
CREATE TABLE persons
(
First_Name text,
Last_Name text
)
INHERITS (temporary_object);
A:
Try this:
CREATE FUNCTION muli_function() RETURNS trigger AS '
BEGIN
IF tg_op = ''UPDATE'' THEN
UPDATE persons
SET time_dead = NEW.time_create
Where
id = NEW.id
AND time_dead IS NULL
;
END IF;
RETURN new;
END
' LANGUAGE plpgsql;
UPD Better something like this:
CREATE FUNCTION muli_function() RETURNS trigger AS '
BEGIN
IF tg_op = ''UPDATE'' THEN
IF NEW.time_dead IS NULL THEN
NEW.time_dead = NEW.time_create
END IF;
END IF;
RETURN new;
END
' LANGUAGE plpgsql;
|
The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogenase complexes share their E2 and E3 components for their function and both generate reactive oxygen species.
Herein are reported unique properties of the novel human thiamin diphosphate (ThDP)-dependent enzyme 2-oxoadipate dehydrogenase (hE1a), known as dehydrogenase E1 and transketolase domain-containing protein 1 that is encoded by the DHTKD1 gene. It is involved in the oxidative decarboxylation of 2-oxoadipate (OA) to glutaryl-CoA on the final degradative pathway of L-lysine and is critical for mitochondrial metabolism. Functionally active recombinant hE1a has been produced according to both kinetic and spectroscopic criteria in our toolbox leading to the following conclusions: (i) The hE1a has recruited the dihydrolipoyl succinyltransferase (hE2o) and the dihydrolipoyl dehydrogenase (hE3) components of the tricarboxylic acid cycle 2-oxoglutarate dehydrogenase complex (OGDHc) for its activity. (ii) 2-Oxoglutarate (OG) and 2-oxoadipate (OA) could be oxidized by hE1a, however, hE1a displays an approximately 49-fold preference in catalytic efficiency for OA over OG, indicating that hE1a is specific to the 2-oxoadipate dehydrogenase complex. (iii) The hE1a forms the ThDP-enamine radical from OA according to electron paramagnetic resonance detection in the oxidative half reaction, and could produce superoxide and H2O2 from decarboxylation of OA in the forward physiological direction, as also seen with the 2-oxoglutarate dehydrogenase hE1o component. (iv) Once assembled to complex with the same hE2o and hE3 components, the hE1o and hE1a display strikingly different regulation: both succinyl-CoA and glutaryl-CoA significantly reduced the hE1o activity, but not the activity of hE1a. |
Anyone else get a recall for Camshaft Position Sensor (CMP)? I have a 00' F250 and have had it for about a year and looking at the symtoms for a bad CMP, my truck sure does fit the description. Anyone know how long this service takes, what's all involved?
Symptoms
ĽA failed camshaft position sensor will show up in a number of ways. The worst-case scenario is that there is no spark in the combustion chamber. Other symptoms can include excessively long cranking time when starting cold, rough running on an intermittent basis, poor idle, stumbling or hesitation, a drop in mileage and stalling upon acceleration. These symptoms may also be caused by a failure in the wiring of the sensor.
In some of the affected vehicles, the Camshaft Position (CMP) Sensor may fail due to circuit
degradation. If the CMP Sensor should fail, the engine may stall. In the event of an engine stall, a
crash could result without warning. A new CMP Sensor with improved reliability is now available.
SERVICE ACTION
Dealers are to inspect the CMP Sensor to verify which design level sensor is installed in the affected
vehicles, and replace all prior level sensors. This service must be performed on affected vehicles at no
charge to the vehicle owner.
OWNER NOTIFICATION MAILING SCHEDULE
Parts to repair this condition are currently not available in sufficient quantities to service all of the
affected vehicles. Therefore, to ensure that an ample supply of parts is available, owners of affected
vehicles will be notified in separate phase mailings over several months. Phase mailing will begin the
week of December 17, 2007; prioritized by age of vehicle. Dealers should repair any affected vehicles
that arrive at their dealerships, whether or not the customer has received a letter.
.
OWNER REFUNDS
Ford Motor Company is offering a refund for owner-paid repairs covered by this recall if the
repair was performed prior to the date indicated in the reimbursement plan, which is posted with
this bulletin.
Dealers are also authorized to refund owner-paid emergency repairs that were performed away
Anyone else get a recall for Camshaft Position Sensor (CMP)? I have a 00' F250 and have had it for about a year and looking at the symtoms for a bad CMP, my truck sure does fit the description. Anyone know how long this service takes, what's all involved?
Symptoms
ĽA failed camshaft position sensor will show up in a number of ways. The worst-case scenario is that there is no spark in the combustion chamber. Other symptoms can include excessively long cranking time when starting cold, rough running on an intermittent basis, poor idle, stumbling or hesitation, a drop in mileage and stalling upon acceleration. These symptoms may also be caused by a failure in the wiring of the sensor.
In some of the affected vehicles, the Camshaft Position (CMP) Sensor may fail due to circuit
degradation. If the CMP Sensor should fail, the engine may stall. In the event of an engine stall, a
crash could result without warning. A new CMP Sensor with improved reliability is now available.
SERVICE ACTION
Dealers are to inspect the CMP Sensor to verify which design level sensor is installed in the affected
vehicles, and replace all prior level sensors. This service must be performed on affected vehicles at no
charge to the vehicle owner.
OWNER NOTIFICATION MAILING SCHEDULE
Parts to repair this condition are currently not available in sufficient quantities to service all of the
affected vehicles. Therefore, to ensure that an ample supply of parts is available, owners of affected
vehicles will be notified in separate phase mailings over several months. Phase mailing will begin the
week of December 17, 2007; prioritized by age of vehicle. Dealers should repair any affected vehicles
that arrive at their dealerships, whether or not the customer has received a letter.
.
OWNER REFUNDS
Ford Motor Company is offering a refund for owner-paid repairs covered by this recall if the
repair was performed prior to the date indicated in the reimbursement plan, which is posted with
this bulletin.
Dealers are also authorized to refund owner-paid emergency repairs that were performed away
Most of my trucks symptoms are excessively long cranking time when starting cold, rough running on an intermittent basis, poor idle, stumbling or hesitation, a drop in mileage. Of course the drop in mileage is probably due to the rims and tires.
John 14:66.Jesus told him, I am the way, the truth, the life. No one comes to the Father exept through Me
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I ended up putting the original black one back in trucks runs better. They also reflash the computer when they put in the new gray CPS atleast that is what I was told so I never took it in and had them do the recall because I don't want them reflecting anything
yeah I bought my truck with that recall notice in the consol, but i got the notice the other day also. I havnt decided if its worth messin with...... course my truck only has 80k on it..... what will the reflash consist of? better or worse afterward?
Jim
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Motivate – Educate – Inspire
When #scicomm criticism took a wrong turn
Let’s talk about the real reasons for #scicomm being increasingly popular.
A couple of days ago Science – a highly-regarded scientific magazine has published a letter which has shaken science communicators’ world. A faulty understanding of the reasons why science communicators publish their posts/pictures /videos caused the most outrage (click on the picture to read the full story).
I have to say I am a newbie in the science communication field, nevertheless I’ve been enjoying it from day one. The real aims for opening this blog and turning my Instagram account into motivational and popular science resource were not to solve the gender inequality issues. I started motivelina.com to spread the knowledge and to shrink the barrier between a scientist and general public. I simply felt that if I meant to stay in a lab behind closed doors for most of my life, I may as well just never become a researcher. Stephen Hawking, Neil deGrasse Tyson, Richard Dawkins, Michio Kaku, Sam Harris and many others started sharing their knowledge way before Instagram was popular and they did an amazing job, becoming role models for people like myself.
We live in 21st century which means that all professions become more public and the only way to not be alienated and misunderstood by the society is to open up. Doctors, lawyers, journalists, politicians, housewives – all of them are sharing their knowledge online. And it’s brilliant! It was never as easy to learn how a day of a teacher/vet/surfer looks like. Why do we have to witness undermining the public roles of the female scientists?
We all want to live in a wiser and less hateful (or less envious) societies. We come out of our comfort zones and publish posts hoping that BigPharma/ GMO/ vaccinations/ microwaves/ the shape of the Earth are not going to be the issues in future. We share in order to get people’s trust, engagement and inspire younger generations to follow our career paths!
The letter reads as an envious attack on a particular Instagram account. The author of this quite badly written piece of work tries to show-off hate towards her campus friend (@Science.Sam). How? By demonstrating that she should spend more time fighting ‘policy changes at governmental institutions’ rather than taking pictures on Instagram. Wright mentions the gender inequality issues by saying:
I have come to understand #scicomm on Instagram as a digital demonstration of the efforts that many female scientists exert daily to correct for gender disparities.
Can we for once not include gender pay gaps and inequalities into every single outreach activity done by women? Firstly, equal amount of men and women in the lab would not help science. It would be more desirable to employ people based on their interest in science rather than their gender. Secondly, if Wright wanted to help women in the science field (and she seems like she is willing to), she should stop criticising successful women and start teaching the unsuccessful ones how to smash their interviews or have balls to ask for a pay rise.
Let’s not cry because there are more men in science. We are not bothered that there are more women than men in nursing.
When I’ve read this:
Female scientists spend demonstrably more time teaching, mentoring, and participating in community outreach than their male colleagues, just as there are far more female #scicommers on Instagram than male.
I thought of all the male scientists, who I mentioned in the first paragraph. They spent enormous amount of time writing books, creating podcasts or lecturing. The words ‘demonstrably more time’ did not convince me at all.
Wright also says:
When I next interview for a job, I won’t have an Instagram page to show that my love of science doesn’t make me boring and unfriendly. Publicly documenting the cute outfit I wear and the sweet smile I brandish in the lab isn’t going to help me build a fulfilling career in a field.
Personally, I don’t think any extra-curriculum hobby like owing an instagram account or baking will get you a job in science. Nevertheless, I’m sure that nowadays good networking skills can get you a job quite easily.
If we want to help out women in our filed – hey, let’s not criticise them! This shows why women struggle in professional life – because per every amazing, self-driven, top-quality female worker, there will be five of her work colleagues (also women), so envious and ruthless, that they will try to destroy her career. It is the painful truth which I experienced myself. Instead of empowering each other, we judge – very often publicly. In my opinion, this is far more important issue than gender inequality. Because if we sort things out in our own garden, it will be easier to come forward to tackle bigger problems.
How is #scicomm community doing?
The response is absolutely enormous. Scientist outreach movements like #scientistswhoselfie increase their popularity gaining new supporters every hour. It might be that the criticism of the scientists activity on Instagram has taken a wrong turn and instead of putting people off from outreach projects, will make it more popular.
Please feel free to use the comment section below to attach links to your own outreach projects, accounts, blogs and I will be more than happy to follow you and promote them on this blog!
Thanks for this. I had originally missed the Science article, but just checked it out.
It’s a surprisingly bitter and petty-sounding article for a journal like Science to have published. It honestly sounds more like a criticism of pretty, feminine women daring to be pretty and feminine in public! A very disappointing article.
I think that any way of making scientists (whether female or male) seem more normal, human or accessible can only be a good thing. And as a lot of the general public receive the majority of news or information through social media, what better way to communicate our science too!
I have very similar reasons to you for starting this project. I didn’t think for a second that it would improve gender equality (although it is ANOTHER 3 women talking about science). I just wanted to help with the public understanding of science and to be honest it’s quite a lot of fun too!
Hi Lay It Out!
Thanks for reaching out to me, I’m very excited to connect with other people (women!!), who also enjoy sharing science. I will definitely follow your journey!
I totally agree with your remarks on that article. I’m utterly surprised by the fact that Science has published something so controversial. We have other magazines for these kind of comments but let’s leave the scientific ones objective and thoughtful.
Well spotted the social media role in our society. Of course it is all done with a great cause! Scientists can be pretty, funny and have good public speaking skills – why would they stick to the traditional means of communication? We are living in amazing times, let’s see what future brings 🙂
I have to agree with your arguments regarding „equality” between men and women (or in any other instance). It’s not fair to hire the same amount of men and women. Why wouldn’t you want to hire the best? And it’s really annoying to see how social media plays an important role in getting a job. |
Massive Green Roof Helps Postal Service Deliver Big Energy Savings
WASHINGTON, DC — Green roofs, green buildings and an energy management system have put the U.S. Postal Service (USPS) on the fast track to achieve its energy reduction goal.
The USPS said Thursday it is more than two-thirds of the way to reducing energy use by 30 percent by 2015.
An impressive component of the agency’s multi-pronged energy strategy is its green roof topping its Morgan mail processing facility in Midtown Manhattan. Covering nearly 2.5 acres, the year-old green roof is the largest of its kind in New York City.
The roof is meeting or exceeding the agency’s initial estimates for performance. For example, it is on track to reduce polluted stormwater runoff by 75 percent in the summer and 40 percent in the winter. The facility is enjoying a 40 percent per month reduction in energy use, with average monthly energy expenses about 15 percent lower than previous levels, also due to the replacement of 1,600 windows and other energy-saving measures.
“A year ago, the Postal Service projected the green roof would help the Morgan facility save $30,000 in annual energy expenses,” Tom Samra, vice president of facilities, said in a statement. “We’re pleased to have surpassed that goal, saving more than $1 million since the implementation of the green roof and other energy-saving measures at Morgan.”
On top of savings it is delivering, the green roof will also pay dividends over the long run since it will last 50 years, twice as long as its predecessor.
USPS also credits its newly implemented Enterprise Energy Management System (EEMS) with helping it manage and measure energy data, saving some $400 million since 2007. Combined with other green building practices, such as its LEED certifications, the USPS has cut energy intensity 21 percent since 2003. |
Brown Passport Covers
Choose a brown passport cover made of leather to protect your passport.
There is a variety of tones to choose from, ranging from light to dark.
We also have a selection of black passport covers as well as colors such as red, blue and pink. |
'Go Spaceship Go' printed from http://nrich.maths.org/
A spaceship driven by an infinite source of power accelerates with constant power through deep space. We watch it fly away from Earth and record its speed and progress.
Show that after a certain time of travelling it will take longer than one day for the velocity of the spaceship to increase by $1 \mathrm{\ m\ s^{-1}}$.
Find this time of travelling (in years) if the spaceship starts travelling from rest and has a power to weight ratio of $500 \mathrm{\ W\ kg^{-1}}$. How fast would the spaceship be travelling at this time?
NOTES AND BACKGROUND
Of course, this problem uses entirely classical, Newtonian physics. A proper analysis would need to take into account special relativity, and it is worth considering how important this might be given the answer. It is also worth noting that the spaceship is actually quite powerful, given that a typical sportscar has a power to weight ratio of around $200 \mathrm{\ W\ kg^{-1}}$ . |
Article content continued
This has to do with something called intellectual property rights (IPRs). Usually when talk turns to IPRs people think about patents. But there’s also something called data protection.
The data that’s being protected is information about the effectiveness and safety of drugs that comes out of the clinical trials that brand-name drug companies do when they want approval to market a new drug.
Generic drugs essential to pharmacare
The data is the private property of the brand-name companies and can’t be used by anyone else, including generic companies, for a period of time.
It would be very costly for generic companies to do the original testing all over again, and it would also be unethical because the results of the trials are already known. So generic companies use the data once it’s no longer protected.
Data protection is not a sexy topic, but it’s important in determining how quickly some low-cost generics can reach the market. The presence of generics keeps public drug plans affordable and will be essential for any pharmacare plan.
Right now, seven out of every 10 prescriptions are filled with generic drugs, but paying for generics only uses up 21 cents out of every dollar that is spent on prescription drugs in Canada. A generic prescription is about one-third the price of a brand-name one.
Patents already mean that brand-name drugs are on the Canadian market for more than 12 years without any competition. When patents run out, generic drugs can be sold, but sometimes patents expire before the data protection period is up. Until the data protection period ends, there can’t be any generics. What’s more, unlike patents, data protection can’t be challenged in the courts. |
A: The 14th roster spot must be a player under either a standard contract or a 10-day contract. Two-way contracts do not count into such math, even if the players are moved onto the NBA roster while still on their two-way deals. The Heat are required to add a 14th player by Feb. 21, although the NBA allows a degree of wiggle room based on a team's schedule. Since the Heat play Feb. 21 in Philadelphia, I would expect the addition to come earlier, to allow for acclimation. I would anticipate, in the wake of the moves to reduce the clutter in the primary rotation, that a player added most likely would be a developmental prospect, which would allow for a forward-thinking approach. Of course, if a primary player is injured, then I could possibly see the Heat keeping the flexibility for a veteran. |
Sexual imagery is often used in magazine and TV ads, presumably to help entice buyers to purchase a new product. But new research suggests that women tend to find ads with sexual imagery off-putting, unless the advertised item is priced high enough.
The findings, published in Psychological Science, a journal of the Association for Psychological Science, reveal that women’s otherwise negative attitudes about sexual imagery can be softened when the images are paired with a product that connotes high worth.
“Women generally show spontaneous negative attitudes toward sexual images,” write psychological scientist Kathleen Vohs, a researcher at the Carlson School of Management at the University of Minnesota, and colleagues. “Sexual economics theory offers a reason why: The use of sexual imagery is inimical to women’s vested interest in sex being portrayed as infrequent, special, and rare.”
Vohs and colleagues predicted that women’s negative attitudes toward sexual imagery might soften if sex is depicted in a way that is consistent with the values of sex being seen as highly valued and of great worth. Sexual imagery may be less off-putting to women, for example, if it is paired with high-priced consumer goods, which can convey exclusivity and high value.
To test this prediction, Vohs and colleagues Jaideep Sengupta and Darren Dahl had male and female participants come to the lab and view advertisements for women’s watches. In some of the advertisements, the watch was presented with a sexually explicit image, whereas in others the watch was pictured with a majestic mountain range. Importantly, some of the ads priced the watch at $10 and others at $1,250.
To measure the participants’ gut reactions toward the ads, the researchers had them memorize a 10-digit code before viewing the ads, a cognitive distraction designed to prevent them from thinking too deeply about the ads. Then, after reciting the code, participants were asked about their attitudes and emotional reactions toward the ads.
Overall, women who saw the sexual imagery with the cheap watch rated the ad more negatively in comparison to women who saw the sexual imagery with the pricey watch. These negative ratings seem to be driven by women’s negative emotions — feeling upset, disgusted, unpleasantly surprised, or angry — in response to the ad that paired sexual imagery with the cheap watch.
Men, on the other hand, reported similar reactions to the sex-based ads, regardless of the advertised price of the watch.
The researchers note that price only made a difference for women in regards to the ads that included sexual imagery. Female participants showed no differences in ratings for the cheap and expensive watches when they were paired with the mountain range.
A second study replicated these results and ruled out the possibility that men’s ratings didn’t differ because they deemed the women’s watches to be irrelevant: Men gave similar ratings to sexually explicit ads that included men’s watches, regardless of how the watches were priced.
While the findings are in line with the predictions generated by sexual economics theory, Vohs and colleagues were surprised nonetheless:
“We were able to get these effects even when participants weren’t actually in a purchasing scenario,” she says. “Just a quick exposure to an ad was enough for theories of sexual economics to kick in,” Vohs explains. “This suggests that the process happens at a deep, intuitive level.” |
Background {#Sec1}
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Genomic tools allow investigators to devise therapies targeting specific molecular abnormalities in tumors. One such alteration is the loss of neurofibromin 1 (NF1), an important tumor suppressor that regulates the activity of *RAS* GTPases \[[@CR1], [@CR2]\]. Heterozygous mutation or deletion of *NF1* causes neurofibromatosis type 1 (NF), one of the most frequently inherited genetic disorders \[[@CR3]\]. NF patients often develop plexiform neurofibromas (PNs), benign nerve tumors for which the only therapy is surgery. However, resection is often impossible due to the tumor's intimate association with peripheral and cranial nerves \[[@CR4]\]. PNs can transform to malignant peripheral nerve sheath tumors (MPNSTs), which are chemo- and radiation-resistant sarcomas with a dismal 20% 5-year survival \[[@CR5]\]. In addition, patients with NF are susceptible to a broad spectrum of other tumors including low-grade/pilocytic astrocytomas, pheochromocytomas, optic nerve gliomas, and juvenile myelomonocytic leukemias \[[@CR6]\]. Many aggressive non-NF associated (sporadic) tumors have recently been shown to harbor *NF1* mutations, including glioblastoma (GBM), neuroblastoma, melanoma, thyroid, ovarian, breast, and lung cancers \[[@CR7]\]. Therefore, somatic and inherited loss of *NF1* function is emerging as a driver of tumors from different organ sites.
Several groups including our own have been working to develop therapeutic approaches to target tumors with loss of NF1. Previously, our lab developed a high throughput approach using yeast and mammalian screening platforms to identify tool compounds and drug targets for cancer cells in which NF1 loss drives tumor formation. Our pipeline identified small molecules that selectively kill or stop the growth of MPNST cells carrying a mutation in *NF1* or yeast lacking the *NF1* homolog *IRA2* \[[@CR8]\]. We also developed an assay in yeast to identify the targets of our lead tool compounds and found that one of these compounds (UC-1) shares a mechanism (phosphorylation of RNA Pol II CTD Ser2/5) with experimental drugs in clinical trials \[[@CR8]\]. UC-1 impacts CTD phosphorylation, which is regulated by the CTD kinase Ctk1, the yeast homolog of human Cdk9. We showed that deletion of *CTK1* was synthetic lethal with loss of the yeast *NF1* homolog *IRA2*. Furthermore, we have found that inhibitors of this process (dinaciclib, SNS-032) can inhibit other types of RAS-dysregulated tumor cells \[[@CR9]\].
However, relying on genetic data alone to identify tumors that may be susceptible to therapies targeting NF1 loss may leave a proportion of potentially actionable tumors unrecognized. NF1 tumor suppressor activity can be lost via mutation of the genomic locus, proteasome-mediated degradation, inhibition by miRNA, *de novo* insertion of an Alu element, and C → U editing of the *NF1* mRNA \[[@CR10]--[@CR14]\]. This complexity presents challenges when trying to identify tumors that will benefit from molecules that exert synthetic lethality with dysregulation of *NF1/RAS* pathways.
The Cancer Genome Atlas (TCGA) has released a large volume of data on several cancer tissues measured on a variety of genomic platforms. In the present study, we leverage TCGA GBM RNAseq expression data with matched mutation calls to construct a classifier capable of identifying an NF1 inactivation signature. This strategy sidesteps the problem of functional characterization of mutations by evaluating a regulator's downstream gene expression activity. We applied this signature to predict NF1 inactivation in a cohort of biobanked GBMs. In general, this approach can be translatable to any gene producing measurable downstream transcriptome-wide effects.
Methods {#Sec2}
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The Cancer Genome Atlas Data used for building the classifier {#Sec3}
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We downloaded RNAseq and mutation data from TCGA Pan Cancer project from the UCSC Xena data portal \[[@CR15]\] and subset each dataset to only the GBMs \[[@CR16]\]. The data consists of 607 GBMs; of which 291 have mutation calls, 172 have RNAseq measurements, and 149 have both RNAseq and mutation calls. Of these 149 samples, 15 have inactivating *NF1* mutations (10.1%) and were used as gold standard positives in building the classifier (Additional file [1](#MOESM1){ref-type="media"}: Table S1). Additionally, to reduce dimensionality while avoiding unexpressed and invariant genes, we subset to the top 8,000 most variably expressed genes by median absolute deviation. We z-scored all gene expression measurements. This resulted in the final input matrix with dimension 149 samples by 8,000 genes. For use in platform independent predictions, we used Training Distribution Matching (TDM) to transform the TCGA RNAseq data to match a microarray expression distribution \[[@CR17]\].
Since we are also aware of the *NF1* mutation status for each of the samples, we form a supervised learning task -- predicting when a sample has loss of *NF1* activity. Our "X" matrix is formed by the RNAseq measurements for all 149 samples measured by 8,000 genes, which are the features in the model. Our "y" vector consist of {0, 1} elements where a 1 corresponds to a sample with an inactivating *NF1* mutation and a 0 is an *NF1* wildtype sample. The machine learning task is to find the feature weights, or gene coefficients, that best minimize our objective function. Along with these feature weights corresponding to the genes' importance in the learning task, we also output a probability estimate for each sample that they have loss of *NF1* activity.
Hyperparameter optimization of the logistic regression classifier {#Sec4}
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Using the GBM RNAseq data, we trained logistic regression classifiers with an elastic net penalty using stochastic gradient descent to detect tumors with NF1 inactivation. We chose a penalized regression model because it is simple to train and has easily interpretable outputs including importance scores for each gene (feature weights) associated with the downstream consequences of *NF1* loss of function and a probability for each sample that *NF1* is lost. An elastic net logistic regression model has also been successfully implemented in similar studies \[[@CR18]--[@CR20]\].
We identified high-performing alpha and L1 mixing parameters using 5-fold cross validation ensuring balanced membership of *NF1* mutations in each fold. Briefly, alpha controls how weight penalty and the L1 mixing parameter tunes the amount of test set regularization by controlling the sparsity of the features. An L1 mixing parameter value of zero corresponds to the L2 penalty and a value of one corresponds to the L1 penalty, with L1 bringing a sparser solution. We used python 3.5.1 and Sci-kit Learn for machine learning implementations \[[@CR21]\].
Ensemble classifier construction and application to the validation set {#Sec5}
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After selecting optimal hyperparameters, we constructed 500 classifiers that would compose our ensemble model. Specifically, across 100 different random initializations, we subset the full TCGA GBM data into five folds and trained a single classifier for each training fold.
We borrowed terminology from the epidemiology field to describe data partitioning. We trained our models on a "training" partition and assessed model performance on a "test" partition, which refers to the held out cross-validation fold. The independent "validation set" refers to the GBM dataset generated in a different lab (see Fig. [1a](#Fig1){ref-type="fig"}).Fig. 1Logistic regression classifier with elastic net penalty training and testing errors over 100 iterations for Training Distribution Matching (TDM) transformation of The Cancer Genome Atlas Glioblastoma RNAseq data. **a** Schematic describing the terms used for training, testing, and validating our model. We applied 5-fold cross validation to the full dataset which consists of training and testing splits in each fold. The model is then applied as an ensemble classifier on a set of in-house samples (validation set) (**b**) Receiver operating characteristic (ROC) curves for all 500 classifiers that make up the ensemble model applied to both training and testing set. Also shown is the aggregate performance of the ensemble classifier. **c** The cumulative density of area under the ROC curve (AUROC) for training and testing partitions
Because of the small number of gold standard positive training examples, we were concerned about the stability of our model solutions. Therefore, we constructed an ensemble classifier from the 500 models. Specifically, we assigned each classifier a weight using the specific randomization's "test set" cross-validation AUROC. Lastly, for the final *NF1* inactivation prediction, we used the mean of the weighted predictions across all iterations as the *NF1* inactivation prediction. We applied this ensemble classifier to the validation set in which NF1 protein levels were directly measured.
Effect sizes and power analysis {#Sec6}
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We calculated the decision function of each ensemble classifier applied to all samples in the training and testing 5-fold cross validation folds to calculate Cohen's D effect size between predicted *NF1* wildtype and *NF1* inactive samples \[[@CR22]\]. The Cohen's D metric quantifies the difference between *NF1* wildtype and *NF1* inactive samples according to the mean classifier score and directly demonstrates how different the ensemble model predicts the two groups to be.
Moreover, we were also concerned that our relatively small validation set would not provide us with enough power to observe a detectable effect in the ensemble model's final prediction. We performed a one-tailed Welch's two-sample *t*-test comparing the NF1 protein concentration of our validation samples that were predicted to be either *NF1* wildtype or *NF1* deficient. Using the given sample size, Cohen's D effect size, and a significance threshold of α = 0.05, we calculated the power of the prediction scores on the validation set. The power analysis was two-sample, one-tailed and incorporated unequal sample sizes in each group.
Validation sample acquisition {#Sec7}
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Thirteen flash-frozen, de-identified GBM samples were obtained from the Maine Medical Center Biobank. Samples were received on dry ice and stored at −80 °C until isolation of DNA/RNA/protein. To isolate DNA, tumor fragments of approximately 20 mg in mass were harvested on an aluminum block pre-chilled on dry ice. Samples were then immediately transferred to a mortar and pestle containing a small volume of liquid nitrogen. The fragments were pulverized in the mortar and pestle, and the liquid nitrogen was allowed to evaporate. Next, samples were immediately processed with a DNA/RNA/Protein Purification Plus kit (Norgen Biotek) following the standard operating protocol for animal tissue. DNA concentration and quality were assessed using an ND-1000 (Nanodrop), a Qubit Fluorometer (Thermo Scientific), and a Fragment Analyzer (Advanced Analytical Technologies). To isolate RNA, −80 C tumor fragments were placed in 5--10 volumes of RNAlater-ICE Frozen Tissue Transition Solution (Ambion) and placed at −20 °C until RNA extraction with a mirVana miRNA isolation kit, without phenol, following the standard operating protocol (Thermo Scientific). Samples were homogenized using a manual homogenizer in the presence of mirVana lysis buffer. RNA concentration and quality were determined using a Qubit Fluorometer (Thermo Scientific) and a Fragment Analyzer (Advanced Analytical Technologies). To isolate protein, small tumor fragments were pulverized and lysed in approximately three volumes of ice-cold radioimmunoprecipitation assay (RIPA) buffer (150 mM sodium chloride, 1% v/v nonidet P40, 0.5% w/v sodium deoxycholate, 0.05% w/v sodium dodecyl sulfate, 50 mM Tris pH 8.0) containing 1 mM sodium orthovanadate, 1 mM sodium fluoride, 1 mM phenylmethylsulfonyl fluoride, and 1X protease inhibitor cocktail (0.1 μg/mL leupeptin, 100 μM benzamidine HCl, 1 μM aprotinin, 0.1 μg/mL soybean trypsin inhibitor, 0.1 μg/mL pepstatin, 0.1 μg/mL antipain). Samples were passed through a 25 5/8 g needle and subsequently sonicated on ice to promote efficient lysis and DNA shearing. After a 30 min incubation on ice, lysates were cleared by centrifuging at 16100 × g for 20 min. HEK293T, U87-MG, and U87-MG cells treated for two hours with one micromolar bortezomib (Selleckchem) and ten micromolar MG132 (Selleckchem) were also prepared in RIPA buffer. Protein samples were stored at −80 °C until analysis.
Cell culture {#Sec8}
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U87-MG and HEK293T cells were purchased from ATCC. Cell lines were regularly passaged and were cultured in Dulbecco's Modified Eagle Medium (Corning) with 10% v/v fetal bovine serum (Gibco) at 37 °C in 5% CO~2~.
Recent data regarding the U87MG cell line published by Allen et al. suggest that the U87MG cell line distributed by ATCC is not from the same tumor as the cell line that was originally isolated in Uppsala. Transcriptome analysis comparing ATCC U87MG cell line to known tumor transcriptomes indicate that the ATCC U87MG cell line is a central nervous system tumor and is likely a glioblastoma cell line \[[@CR23]\].
In the present study, we employ this cell line as a control representing an NF1-deficient tumor cell line. Previous studies have shown that the U87MG cell line has elevated proteasome-mediated degradation of NF1 and that this cell line required the loss of NF1 protein to promote tumorigenesis in xenograft tumor models \[[@CR10]\]. Given that the ATCC U87MG cell line is a well-characterized and broadly-used model of NF1 deficient tumor cells \[[@CR10], [@CR24]--[@CR26]\], we propose that the use of the ATCC U87MG cell line is an appropriate control for Fig. [2](#Fig2){ref-type="fig"}.Fig. 2Performance of our classifier on a validation set. **a** Two distinct western blots for each of our twelve samples. The controls are U87-MG, an *NF1* WT glioblastoma cell line that exhibits proteasomal degradation of the NF1 protein. U87 + PI are U87-MG cells are treated with the proteasome inhibitors (PI) MG-132 and bortezomib to block proteasome-mediated degradation of NF1. We used the NF1/tubulin ratio normalized to U87 + PI as our NF1 protein level estimate. **b** Prediction scores for each of the 500 classifiers weighted by cross validation test set AUROC where a negative number indicates *NF1* wildtype and a positive number is indicates NF1 inactivation. Darker shades of blue indicate higher observed NF1 protein concentrations. **c** We quantify protein against U87 + PI and provide the mean of the weighted predictions. **d** Based on weighted predictions, we show the abundance of NF1 protein compared to U87 + PI
RNA microarray {#Sec9}
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After RNA isolation and QC, samples were labeled for the GeneChip Human Transcriptome Array 2.0 (HTA 2.0, Affymetrix). Labeling was performed with Affymetrix Proprietary DNA Label (biotin-linked) using a WT Plus Kit (Affymetrix) provided with the HTA 2.0, following the standard operating protocol for HTA 2.0, including PolyA controls. Hybridization, washing, and staining were performed with the WT Plus Kit, following the standard operating protocol for HTA 2.0. Washing and staining were performed using a GeneChip Fluidics 450. Scanning was performed with a GeneChip Scanner 3000. These data were deposited in the Gene Expression Omnibus under accession GSE85033.
Validation sample processing {#Sec10}
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We applied a quality control pipeline \[[@CR27]\] to all CEL files generated by the HTA 2.0. All validation samples passed processing quality control, which included an inspection of spatial artifacts, MA plots, probe distributions, and sample comparison boxplots. We summarized transcript intensities using robust multi-array analysis (RMA) \[[@CR28]\]. We determined batch normalization was unnecessary after a guided principal components analysis (gPCA) using sample processing date and array plate ID as potential batch effect confounders \[[@CR29]\]. Lastly, we collapsed HTA2.0 transcripts into gene level measurements using the 'collapseRows()' function with the "maxmean" method from the R package WGCNA \[[@CR30]\]. We used the pd.hta.2.0 platform design file (version 3.12.1) and the Bioconductor package "hta20sttranscriptcluster.db" (version 8.3.1) to map manufacturer transcript IDs to genes. We performed all preprocessing steps using R version 3.2.3.
Western blotting {#Sec11}
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Prior to sodium dodecyl sulfate polyacrylamide gel electrophoresis, protein sample concentration was determined using a Pierce BCA Protein Assay Kit (Thermo Scientific). Protein samples were prepared with 1X Laemmli sample buffer (50 mM Tris pH 6.8, 0.02% w/v bromophenol blue, 2% w/v SDS, 10% v/v glycerol, 1% v/v beta-mercaptoethanol, 12.5 mM EDTA) and 50 μg of tumor protein. Volumes were normalized with RIPA buffer including the protease/phosphatase inhibitors described above. SDS-PAGE was performed using a 4-15% Mini-PROTEAN TGX gel (Bio-Rad) for 1 h at 120 V. The samples were then transferred to a nitrocellulose membrane for 2 h and 45 min at 400 mA in cold transfer buffer (384 mM glycine, 50 mM Tris, 20% methanol, 0.005% w/v sodium dodecyl sulfate. Following this, the blots were then blocked in 5% w/v BSA or 5% w/v nonfat dry milk in Tris-buffered saline (137 mM NaCl, 2.7 mM KCl, 19 mM Tris, 0.05% v/v Tween 20, pH 7.4) for 25 min. Immunoblotting was performed with the following antibodies and conditions (vendor, species, diluent, dilution, incubation time, incubation temperature): anti-NF1 D7R7D \#14624 (Cell Signaling, rabbit, 2% BSA, 1:1000, overnight, 4 °C), anti-tubulin B-1-2-5 (Santa Cruz, mouse, 2% milk, 1:10000, 1 h, RT), anti-EGFR D38B1 \#4267 (Cell Signaling, rabbit, 2% milk, 1:1000--1:2000, 1 h, RT), p-ERK ½ (p44/42 MAPK) \#9101 (Cell Signaling, rabbit, 2% BSA, 1:2000, overnight, 4 °C), SUZ12 D39F6 \#3737 (Cell Signaling, rabbit, 2% milk, 1:1000, overnight, 4 °C). Anti-NF1 D7R7D was a kind gift from Cell Signaling Technologies, Inc.
The binding of the primary antibodies was detected by incubation with secondary antibodies goat anti-rabbit HRP 1:20000 or goat anti-mouse HRP 1:10000 (Jackson Immunoresearch Laboratories Inc.) at room temperature in 2% milk in TBST and detection of HRP activity using Pierce ECL Western Blotting substrate (Thermo Scientific), or in the case of *NF1*, SuperSignal West Femto Maximum Sensitivity Substrate (Thermo Scientific). The chemiluminescent signal was captured with MED-B medical x-ray film (Med X Ray Company Inc.). Between primary antibodies, the membrane was stripped twice for 10 min at room temperature using a mild stripping buffer containing 1.5% w/v glycine, 0.1% w/v SDS, 1% v/v Tween 20 at pH 2.2 (Abcam). One sample was eliminated due to low yield, and apparent degradation as determined by western blotting (all proteins examined were undetectable with the exception of tubulin, not shown). Densitometry was performed using Li-COR Image Studio Lite 5.0. Briefly, intensity measurements for *NF1* and tubulin were taken using equally-sized regions for all bands. The background was subtracted using the local median intensity from the left and right borders (size = 2) of each measurement region. *NF1* values were divided by tubulin intensity to adjust for protein loading. All measurement ratios were then normalized by dividing values by the "U87 + PI" measurement for each blot, respectively.
Reproducibility of computational analyses {#Sec12}
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We provide software with a permissive open source license to reproduce all computational analyses \[[@CR31]\]. Ensuring a stable compute environment, we performed all analyses in a Docker image \[[@CR32]\]. This image and source code can be used to freely confirm, modify, and build upon this work.
Results {#Sec13}
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Classifier performance {#Sec14}
----------------------
Using 5-fold cross validation across a parameter sweep, we identified optimal hyperparameters at alpha = 0.15 and L1 mixing = 0.1 (Additional file [2](#MOESM2){ref-type="media"}: Figure S1). To assess model performance, we performed 100 random initializations of five-fold cross-validation. These models had mean test area under the receiver operating characteristic curve (AUROC) of 0.77 (95% Quantiles: 0.53 -- 0.95) and a mean train AUROC of 0.997 (95% Quantile: 0.98 -- 1.00) (Additional file [3](#MOESM3){ref-type="media"}: Figure S2). We repeated this procedure after TDM transformation (Additional file [4](#MOESM4){ref-type="media"}: Figure S3) and achieved comparable results with alpha = 0.15 and l1 mixing = 0.1 (mean test AUROC = 0.77, 95% Quantiles: 0.51 -- 0.96; mean train AUROC = 0.998, 95% Quantiles: 0.99 -- 1.00) (Fig. [1b](#Fig1){ref-type="fig"}). Because the validation set was measured by microarray, we used the classifier trained on TDM transformed data to construct our ensemble classifier. We also determined the Cohen's D effect size estimate for all training and testing partitions across all 5-fold cross validation iterations of the TDM transformed model (Additional file [5](#MOESM5){ref-type="media"}: Figure S4). The classifier consistently and robustly separated *NF1* wildtype and *NF1* inactivated GBM samples with high effect sizes (Training: mean Cohen's D = 3.07, 95% CI = 2.24 -- 4.16; Testing: mean Cohen's D = 1.27, 95% CI = 0.19 -- 2.67).
Identification and characterization of NF1 deficient glioblastoma tumor samples {#Sec15}
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We characterized NF1 protein concentrations as well as other molecules involved in RAS signaling in the 12 GBM samples (Fig. [2a](#Fig2){ref-type="fig"}). Two samples (CB2, 3HQ) had no apparent NF1 protein. Eight other samples had similar or less NF1 signal than the U87-MG NF1-low control (H5M, LNA, YXL, VVN, R7K, TRM, UNY, W31). Two samples (PBH, RIW) had equal or greater NF1 than the positive control, U87-MG + proteasome inhibitors (preventing NF1 degradation). We also observed variable EGFR content in these samples, with non-existent to low levels (3HQ, YXL, R7K), or medium to large EGFR signal (CB2, H5M, PBH, LNA, YXL, VVN, RIW, TRM, UNY, W31). All GBM samples had high concentrations of phospho-ERK1/2 signal relative to cell line controls. Samples with increased phospho-ERK1/2 may have greater Ras pathway activation. This can be attributed to multiple factors, including increased EGFR expression and/or NF1 inactivation.
Our ensemble classifier predicted four samples to have NF1 inactivation (CB2, UNY, R7K, and 3HQ) and eight samples to be *NF1* wildtype (W31, TRM, PBH, VVN, LNA, RIW, H5M, and YXL) (Fig. [2b](#Fig2){ref-type="fig"}). Because two samples, (CB2 and H5M) were measured on both western blots (Fig. [2c](#Fig2){ref-type="fig"}), we used the mean of their NF1 protein level across both experiments.
We performed a one-tailed Welch's *t*-test to determine if NF1 protein concentrations were significantly higher in *NF1* wildtype versus *NF1* deficient samples based on our classifier predictions (Fig. [2d](#Fig2){ref-type="fig"}). We did not observe a significant difference across groups (*t* = −1.38, *p* = 0.098, effect size = 0.699). Additionally, while the effect size was fairly large, a power analysis indicated that 22 samples per group would be required to achieve a power = 0.8 at that effect size. With a lack of glioblastoma samples with quantified NF1 protein available, the trend of less protein present in samples scored as *NF1* inactivated by the classifier nevertheless remains promising.
One of the samples predicted to be NF1 inactive contains detectable NF1 protein (R7K), suggesting that this sample may have NF1 inactivation not detectable by assaying protein, have a different alteration that phenocopies NF1 loss, or is incorrectly predicted by the classifier. Conversely, there are three samples predicted to be NF1 wildtype that have low or undetectable protein (YXL, VVN, W31), which either indicates unknown elements that confound the detection of some NF1 dysregulated tumors or a classification error.
Highly contributing genes {#Sec16}
-------------------------
We observed several genes that consistently contributed to the ensemble classifier performance (Fig. [3](#Fig3){ref-type="fig"}). Since we applied several classifiers to the validation set as an ensemble, we took the sum of all classifier's gene weights across all 500 iterations to define these consistently contributing genes. While the data indicate that these genes have an impact on classifier performance, the data do not indicate whether changes in the expression of these genes are a direct consequence in changes in NF1 signaling. Expression of genes such as *TXNIP, ARRDC4, ISPD, C10orf107*, and *DUSP18* appear to be predictive of intact NF1 signaling. Among the list of genes that appear to be expressed in tumors with loss of NF1 function are *QPRT, ATF5, HUS1B, PEG10, HMGA2, RSL1D1, and NRG1*. A full list of positive and negative weight genes that were two standard deviations beyond the gene weight distribution is provided in Additional file [6](#MOESM6){ref-type="media"}: Table S2.Fig. 3Genes that contribute to the classifier performance. Genes are shown ranked by their weighted contribution to the ensemble classifier. Weights are scaled to unit norm. The top ten positive and top ten negative contributing high weight genes are given on the right
We also performed over-representation analysis of the most influential genes in the classifier to identify gene ontology (GO) sets and pathways that may be predictive of NF1 status \[[@CR33]--[@CR36]\]. For high-weight genes predictive of intact NF1 signaling, we observed GO sets involved in plasma membrane-localized proteins (GO:0005886, GO:0071944, GO:0016324) and homeostasis (GO:0048871, GO:0001659, GO:0048873, GO:0031224), among others. Annotated pathways associated with genes from this dataset include hematopoietic stem cell differentiation, thyroid cancer, voltage-gated potassium channels, and RHO GTPase functional pathways.
For high-weight genes predictive of NF1 loss of function, we observed GO sets related to cellular adhesion (GO:0007155, GO:0098742), negative regulation of signaling (GO:0009968, GO:0023507, GO:0010648), and nervous system development (GO:0051962, GO0007416, GO: 0050808), among others. These genes were also enriched for elements of the phototransduction cascade and thyroxine production pathways.
Discussion {#Sec17}
==========
A machine learning classifier, based on gene expression data, can capture signal associated with the inactivation of a tumor suppressor. Our classifier is able to detect subtle downstream changes in gene expression as a result of the tumor responding to NF1 loss of function. This finding supports using mRNA as a summary measurement capable of capturing system-wide responses to molecular events beyond transcription factor alterations. Machine learning has been applied to gene expression in a variety of studies with various goals \[[@CR37]--[@CR41]\]. In a similar study, Guinney et al. trained a classifier to model RAS activity in colorectal cancer and demonstrated its clinical utility by predicting response to MEK inhibitors and anti-EGFR based treatments \[[@CR18]\]. With a wealth of signal embedded in gene expression and a rapidly growing library of datasets, the performance of machine learning models is likely to rapidly improve. An increase in performance leads to more reliable clinical applications that would potentially predict the effectiveness of pathway-specific targeted therapies.
While our classifier was able to predict NF1 inactivation status to an extent, its performance is far from being clinically actionable. A major difficulty in developing a reliable classifier in this case is contamination in gold standard positives and negatives. While we aim to detect NF1 inactivation events, our gold standard positives can only include samples with known *NF1* mutation status. Conversely, we expect that negative samples (about 90% of the data) are also contaminated with NF1 inactivated samples due to protein loss and other mechanisms. We cannot determine scenarios where NF1 is inactivated beyond mutation at scale in the TCGA data. Another challenge with the construction of classifiers from such data is overfitting. Even after hyperparameter optimization we observed substantial overfitting (Fig. [2](#Fig2){ref-type="fig"}), which has also been observed in competitions (see, for example, supplementary figure S2 of Noren et al. 2016 \[[@CR42]\] in which the best performing algorithms also overfit). Finally with a small number of positive examples the model performance is unstable, which demonstrates high variability in gold standard samples used to train the model \[[@CR43]\]. We employed ensemble classification to mitigate this issue as averaging over heterogeneous models would result in a relatively stable classifier (see Fig. [2b](#Fig2){ref-type="fig"}). In summary, our results are promising but these challenges are substantial and significant work remains to reach a robust classifier with clinical utility.
The performance of the classifier appears to be impacted by many cancer related genes. For example, genes such as *TXNIP* and *ARRDC4*, which are both indicative of lactic acidosis, correlate with better clinical outcomes, and contribute to predicting tumors with intact NF1 signaling \[[@CR44]\]. We also observed transcripts that are more highly expressed in brain tissue than either other normal tissue (*ISPD, C10orf107*), or more highly expressed in normal brain tissue than glioma (*EPHA5*) \[[@CR45]--[@CR47]\]. *DUSP18* contributes to the prediction of *NF1* wildtype status and is a negative regulator of ERK phosphorylation, possibly by regulating *SHP2* phosphorylation \[[@CR48]\]. It is unclear whether the expression of these genes is a direct result of *NF1* expression, the result of signaling downstream of *NF1*, or a consequence of other phenomena (such as expression of *SPRED1*, an NF1 binding partner that is essential for *NF1* signaling). Future studies could elucidate the potential connections between *NF1* and the genes identified as important for the performance of this classifier.
Over-representation analysis of these data highlighted changes in potassium channel expression. It was previously demonstrated that *NF1* wild-type Schwann cells have altered K+ channel activity as compared to *NF1* ^*−/−*^ Schwann cells suggesting that this may be one factor by which *NF1* mutant and wild-type cells can be distinguished \[[@CR49]\].
Regarding prediction of NF1 inactivated tumors, we observed several genes that have been linked to cancer such as *QPRT*, which is highly expressed in malignant pheochromocytomas as compared to benign; *RSL1D1* (CSIG), which stabilizes *c-myc* in hepatocellular carcinoma; *PPEF*, which is highly expressed in astrocytic gliomas as compared to normal brain tissue \[[@CR50]--[@CR52]\]; and *PEG10*, a poor prognostic marker and regulator of proliferation, migration, and invasion in several tumor types \[[@CR53]--[@CR55]\]. We also observed *ATF5,* a gene for which expression in malignant glioma is correlated with poor survival \[[@CR56]\]. Knockdown of *ATF5* in GBM cells causes cell death in vitro and in vivo \[[@CR57]\]. Analysis of genes that contribute to the prediction of *NF1* inactivation yielded several GO terms related to neural development. It is well established that loss of *NF1* can result in abnormal neural development and/or tumorigenesis \[[@CR14], [@CR58], [@CR59]\]. We also observed genes associated with the mesodermal commitment pathway, components of which are linked to the epithelial to mesenchymal transition in human cancer cells \[[@CR60]--[@CR62]\]. Analysis of this pathway may be informative in identifying tumors with *NF1* loss because mesenchymal GBMs are enriched for tumors with *NF1* loss \[[@CR63]\].
Our ensemble classifier was able to robustly detect the samples with the highest and lowest NF1 protein concentrations, but it struggled with samples of intermediate NF1 concentrations. This could be a result of an enrichment of mechanisms causing NF1 inactivation beyond protein abundance, an overrepresentation of mesenchymal tumors in NF1 inactivated samples contaminating dataset splits \[[@CR63]\], poor classifier generalizability, or incomplete data transformation between RNAseq and microarray data. Because training and testing performance were similar between transformed and non-transformed data (see Fig. [1](#Fig1){ref-type="fig"} and Additional file [4](#MOESM4){ref-type="media"}: Figure S3) we don't anticipate performance to be impacted much by platform differences or classifier generalizability. Nevertheless, we demonstrated the ability of system-wide gene expression measurements to capture downstream consequences of a complex biological mechanism that would otherwise require several different types of data acquisition to capture.
Conclusions {#Sec18}
===========
A machine learning classifier for transcriptomic data was able to detect signal associated with the inactivation of *NF1*, a tumor suppressor gene. The gene is an important regulator of the oncogene *RAS* and is inactivated frequently in GBM and in other tumors. The measurement of NF1 inactivity cannot be comprehensively captured by any single genomic characterization such as targeted sequencing or fluorescence in situ hybridization. This difficulty arises from diverse and complex biological mechanisms that inactivate the tumor suppressor in a variety of ways. However, we demonstrated that measuring system-wide RNA can capture subtle downstream changes that occur in response to NF1 inactivation. Improving classification performance is required before transitioning such a model into clinical use, but our method could be used to characterize cell lines or patient-derived xenograft (PDX) models with inactive NF1. Eventually, with more data and improved classification, we expect machine-learning models constructed on system-wide transcriptomics will translate into clinically relevant predictions that will guide targeted therapy.
Additional files {#Sec19}
================
Additional file 1: Table S1.NF1 mutations in the TCGA GBM dataset (UCSS Xena, hg19). (XLSX 12 kb) Additional file 2: Figure S1.Non-transformed RNAseq results of The Cancer Genome Atlas Glioblastoma parameter sweep for stochastic gradient descent logistic classifiers with elastic net penalty. (A) Training and testing area under the receiver operating characteristic curve (AUROC) is given for each parameter tested. All accuracies are presented following 5-fold cross validation after 50 random initializations. (B) The l1 mixing parameter with the optimal alpha and (C) the classifier performance across all random starts for the best hyperparameters. (PNG 711 kb) Additional file 3: Figure S2.Logistic regression classifier with elastic net penalty training and testing errors over 100 iterations for non-transformed The Cancer Genome Atlas Glioblastoma RNAseq data. (A) Receiver operating characteristic (ROC) curve and shows the average training and testing performance of 5-fold cross validation over 100 random initializations as well as each individual classifier in the ensemble model. (B) The cumulative density of area under the ROC curve (AUROC) for all training and testing partitions. (PNG 240 kb) Additional file 4: Figure S3.Training Distribution Matching (TDM) transformation of RNAseq results of The Cancer Genome Atlas Glioblastoma parameter sweep for stochastic gradient descent logistic classifier with elastic net penalty. (A) Training and testing area under the receiver operating characteristic curve (AUROC) is given for each parameter tested. All accuracies are presented following 5-fold cross validation after 100 random initializations. (B) The l1 mixing parameter with the optimal alpha and (C) the classifier performance across all random starts for the best hyperparameters. (PNG 724 kb) Additional file 5: Figure S4.Cohen's D effect size estimates across five fold cross validation parameters for all 100 iterations of the TDM transformed ensemble classifier. The effect size for the test set is consistently lower than the training set (left). Additionally, the training and testing decision functions for gold standard NF1 deficient vs. NF1 wildtype samples shows a difference in mean estimates (right). The decision function represents the raw score of all samples as applied to the respective classifiers through each of the 100 iterations of five fold cross validation on the TCGA training set. (PNG 580 kb) Additional file 6: Table S2.Ranked genes contributing greater than two standard deviations to ensemble classifier. (XLSX 27 kb)
ATCC
: American type culture collection
AUROC
: Area under the receiver operating characteristic curve
BCA
: Bicinchoninic acid
BSA
: Bovine serum albumin
CTD
: C-terminal domain
ECL
: Enhanced chemiluminescence
GBM
: Glioblastoma
GO
: Gene ontology
gPCA
: Guided principal components analysis
HRP
: Horseradish peroxidase
HTA 2.0
: Human Transcriptome Array 2.0
MPNST
: Malignant peripheral nerve sheath tumor
NF
: Neurofibromatosis type I
NF1
: Neurofibromin
PDX
: Patient derived xenograft
PI
: Proteasome inhibitors
PN
: Plexiform neurofibroma
QC
: Quality control
RIPA
: Radioimmunoprecipitation assay
RMA
: Robust multi-array analysis
ROC
: Receiver operating characteristic
SDS-PAGE
: Sodium dodecyl sulfate-polyacrylamide gel electrophoresis
TCGA
: The Cancer Genome Atlas
TDM
: Training distribution matching
UCSC
: University of California Santa Cruz
This work was supported by the MMC BioBank, a core facility of the Maine Medical Center Research Institute, and the Dartmouth Genomics Shared Resource, a core facility of the Norris Cotton Cancer Center.
Funding {#FPar1}
=======
This work was funded by the Genomics and Computational Biology PhD Program at The University of Pennsylvania to GPW, The Gordon and Betty Moore Foundation GBMF4552 to CSG, NINDS R01 NS095411 to YS and CSG, Children's Tumor Foundation Young Investigator Award 2014-01-12 to RJA, a Nancy P. Shea Trust grant to YS, a Prouty Pilot Grant from the Friends of the Norris Cotton Cancer Center to YS, a Synergy grant to YS, CSG and CF funded by NIH NCATS UL1 TR001086 to The Dartmouth Center for Clinical and Translational Science, NCI Cancer Center Support Grant P30 CA023108 to the Dartmouth-Hitchcock Norris Cotton Cancer Center. RJA is an Albert J. Ryan Fellow. The funders had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
Availability of data and materials {#FPar2}
==================================
All source code is available under a permissive open source license in the nf1_inactivation GitHub repository, <https://github.com/greenelab/nf1_inactivation>. We also provide a docker image to replicate the computational environment at <https://hub.docker.com/r/gregway/nf1_inactivation/>. Additionally, all validation data is available under Gene Expression Omnibus accession number GSE85033.
Authors' contributions {#FPar3}
======================
GPW built, analyzed, and interpreted the classifier, generated the figures, created all source code, and wrote the manuscript. RJA performed all experiments, interpreted the classifier, and wrote the manuscript. SJB interpreted the results and was a major contributor to the manuscript. CEF was a major contributor to the study design and was a major contributor to the manuscript. YS designed the study, interpreted the results, and wrote the manuscript. CSG designed the study, interpreted the results, and wrote the manuscript. All authors read and approved the final manuscript.
Competing interests {#FPar4}
===================
The authors declare that they have no competing interests.
Consent for publication {#FPar5}
=======================
Not Applicable
Ethics approval and consent to participate {#FPar6}
==========================================
The Dartmouth-Hitchcock Medical Center Committee for the Protection of Human Subjects declared IRB review and approval is not required since the study does not meet the regulatory definition of human subjects.
|
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Fluid Distribution Header (FDH)
Fluid distribution headers are used as versatile manifolds in a variety of gas and liquid applications, providing a flow path with multiple outlets, similar to a large branch fitting. With an inlet on one end, a drain on the other end, and multiple outlets on either side, the Fluid Distribution Header uses Swagelok components for enhanced reliability. The unique body design with solidly mounted components eliminates twisting. Easily connect multiple Fluid Distribution Headers inline to create longer lengths.
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The complete catalog contents must be reviewed to ensure that the system designer and user make a safe product selection. When selecting products, the total system design must be considered to ensure safe, trouble-free performance. Function, material compatibility, adequate ratings, proper installation, operation, and maintenance are the responsibilities of the system designer and user.
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Do not mix or interchange product components with those of other manufacturers." |
culate the common denominator of h and 91/75.
525
Let d = 48 - 46. Let g be (-10)/(4 - 4 - d). Suppose -g*l + 40 = -30. Calculate the least common multiple of 38 and l.
266
Let z = -51401 - -2518437/49. Let o = -71/59418 - -22555822/1455741. Let f = z + o. Find the common denominator of f and 43/27.
54
Suppose 47*x - 70 = 46*x. What is the least common multiple of 60 and x?
420
What is the least common multiple of ((-322)/35 - -8)*((-2)/(-2) - 451) and 540?
540
Calculate the common denominator of 39/280 and (-730)/(-219) + (-3470)/1176.
1960
Let y = 10591 + -10559. What is the least common multiple of y and 196?
1568
Calculate the common denominator of -3*53992/(-82365) - (1 - -1) and 61/2907.
14535
Find the common denominator of 1/((-120)/(-50))*(64/122)/(-4) and -59/297.
18117
Let p(y) = 91*y**2 + 79*y - 209. Calculate the least common multiple of 462 and p(3).
5082
What is the smallest common multiple of 212 and (-863 + 15)*(5 - 7)?
1696
Let f = -205 + 211. Suppose 0 = -7*a - f + 62. What is the lowest common multiple of a and 64?
64
Let m = 1/1804 + -145237/27060. Let v be 1/(-3)*(2 - -22). Find the common denominator of (-554)/(-36) + v + 15/18 and m.
90
Let o = 285727/829980 + -322/783. Find the common denominator of 37/20 and o.
1060
Let l be 3 + 2 - 4/4. Suppose 5*g = -2*v - 0*v + 20, g - l = -5*v. Calculate the least common multiple of g and 179.
716
Let l be 2 - (-4 - -5 - 47). Let u = -45 + l. Suppose 4*w - 5 + 13 = 4*r, -5*r = -u*w - 16. What is the lowest common multiple of r and 3?
15
Let o = 115356169/912 + -126487. Find the common denominator of o and -31/16.
912
Let v = -21 + 23. Suppose -v*z = -19 + 7. Suppose z*s - s = 10. What is the lowest common multiple of s and 8?
8
Suppose -3*i = 0, -72*i + 77*i - 24 = -h. What is the smallest common multiple of 36 and h?
72
Let d = 1018183/37332 - 983/36. Calculate the common denominator of d and -26/85.
5185
Let w be ((-327)/(-84) + -4)/(18/50608). Let v = 12821/42 + w. Calculate the common denominator of v and 25/18.
126
Let m = 2983/36 + -736/9. Let a = -16/911 + 37799/25508. What is the common denominator of a and m?
84
Suppose -4*s + 89 = 33. Calculate the lowest common multiple of s and 13 - (253/(-77) - (-2)/7).
112
Suppose 0 = -4*j + 60, j + 7300 = 3*p + 7243. Let t(b) = 2*b**2 - 3*b + 2. Calculate the lowest common multiple of p and t(4).
264
Suppose -4*t + 2*b = -6*t - 78, -3*t - 116 = 4*b. Find the common denominator of 1 + 1 - 510/(-24) and (-6)/7*175/t.
4
Let s be (-6)/(-10) + (429730/(-3300))/(-49). Let x = s - -54/11. Find the common denominator of x and 82/39.
78
Find the common denominator of ((-2)/(-56)*-31)/(3 - (-494)/(-8)) and -9/10.
3290
Let b(h) = -h**3 + 9*h**2 - 11*h + 12. Let n be ((-14)/1)/(-9 - -7). What is the least common multiple of b(n) and 45?
495
Suppose -11*l - 2*n = -9*l - 494, 753 = 3*l - n. Calculate the least common multiple of (7 - l/40) + 333/4 and 7.
84
Suppose -5*i + 4*b = -145, 10*i + b + 145 = 15*i. Let m = i - 23. What is the smallest common multiple of m and 24?
24
Let f = -258631/33 - -7836. What is the common denominator of f and -49/264?
264
What is the smallest common multiple of 1818 and (6/10 - 1) + (-616)/110 + 1521?
9090
Calculate the common denominator of -5 + -4 + 8118/960 and -131/240.
480
Let q be -5*(-4)/10 + 141368. Let f = -1001889192/7087 + q. Let t = 276349/155914 - f. What is the common denominator of t and 149/24?
264
Let y = -383951/56 + 6856. Calculate the common denominator of 77/78 and y.
2184
Find the common denominator of (-582)/8*1/(-42) and (27 + 11682/(-432))*(-324)/(-40).
560
Suppose 240*a = 3*v + 237*a - 12069, 3*v - 12093 = -5*a. What is the lowest common multiple of 3294 and v?
36234
Let y be -4 - (-4 - -5 - 48). Suppose -5*b = 2*u - y, 3 + 16 = 2*u - 3*b. Calculate the smallest common multiple of 21 and 2 + ((-14)/7)/((-1)/u).
210
Suppose 5*b + 2*w = w + 4453, b - 5*w = 901. Calculate the least common multiple of 486 and b.
5346
Let k = -29159 - -19446. What is the lowest common multiple of 6/(-36) + (k/6)/(-11) and 4?
588
Let y(x) = -6*x - 41. Let q be y(-8). Find the common denominator of (261/(-15) + 0)/(-5 + q) and 29/73.
730
Let r(m) = -48*m + 222. Let a(k) = -16*k + 74. Let h(x) = 20*a(x) - 6*r(x). Calculate the least common multiple of 14 and h(4).
140
Calculate the common denominator of -26 and -11 + 18783/621 + 2/23.
3
Let y = 1895/4 + -469. Let s = -37/269 - 21049/5380. What is the common denominator of s and y?
20
Let m = 51 + -51. Suppose m = a - 40 + 2. Suppose 4*i - j - a = -0*j, 0 = 3*i - 3*j - 33. What is the least common multiple of 18 and i?
18
Find the common denominator of 50/18480*13 + (-4)/44 and 73/9.
5544
Let m = -25 + -3. Find the common denominator of m*(-3)/18*6/(-40) and 482/40 - (-4)/16.
10
Suppose x + 3*o = 496, -234*x + 236*x = -5*o + 988. What is the lowest common multiple of x and 4?
484
Let i = -5438 - -5468. Let c = -99 + 58. Let d = c - -57. Calculate the least common multiple of d and i.
240
Suppose -13*l + 15*l - 34*l = -2432. Calculate the smallest common multiple of l and 247.
988
Suppose h + 14 = 2*h - 5*l, 2*l + 7 = -h. Suppose 35738*n = b + 35744*n - 83, -27 = b + n. Find the common denominator of (h - 24)*1/(-2) and b.
2
Let q(i) = i**3 + 127*i**2 - 2*i - 114. What is the smallest common multiple of 1204 and q(-127)?
6020
Suppose 8*p - 3*p = 105. Calculate the lowest common multiple of 5200/(-350) + 18 + 2/(-14) and p.
21
Suppose -5*j + 41 = 4*z, j = 34*z - 31*z - 45. Suppose 5*b - 30 = 2*u, 4*b + 15 - 42 = u. Calculate the least common multiple of b and z.
56
Let i(j) = 20*j + 147. Let o be i(18). Let f = o - 364. What is the smallest common multiple of f and 13?
143
Let i = 75989 + -3343327/44. Let g = -1/22 + i. What is the common denominator of 39/20 and g?
20
Let y be ((-2)/(-4))/(5/20). Suppose -3*i + 4*a = -62, 2*a = -3*i + y + 48. Let g(b) = 22*b - 304. What is the lowest common multiple of i and g(15)?
234
Suppose -13*n - 736 = -1048. Calculate the smallest common multiple of n and 1024.
3072
Suppose r + 3*w + 545 = -r, -2*r - 570 = -2*w. Find the common denominator of 13/2 and -4*1/14 - 3335/r.
8
Suppose -25 = -0*l - 5*l. Suppose -1 + 49 = -4*s. Calculate the lowest common multiple of s/27 + (-31)/(-9) and l.
15
Suppose -4*y - d + 41 = 2*d, 2*d - 6 = 0. Suppose y = 4*o + 20. Calculate the smallest common multiple of (4 - -14)/3 + o and 57.
57
Let o be (-15)/12 - (1 + (-58)/8). Suppose -2*q - 6 = 0, -o*u = -0*u + q - 22. What is the smallest common multiple of 6 and u?
30
Let c be -15*(6 - 44/10). Let j = c + 68. What is the least common multiple of 100 and j?
1100
What is the common denominator of ((-249)/25564)/(2/(-14) + 3830/10640) and -71/9?
7623
Suppose -10 = -y - y. Suppose 4*t = 4*o - 4, 5*o + y*t - 25 = -0*o. What is the smallest common multiple of o and 1*18/(3 - 2)?
18
Calculate the common denominator of -65/198 and (6/(-6 + -36))/(-9*6/21).
198
What is the common denominator of (-8)/660 - (-154934)/33330 and (-194)/(-20) - (-2)/(-5)?
110
Suppose -3*h + 3*z + 276 = 0, 3*h + 5*z - 151 - 117 = 0. What is the least common multiple of (4 - 1)/((-3)/7)*-7 and h?
637
Let q be 3 + (-4)/12*3. Suppose -5*l + 628 = -q*o, 4*l - 288 = 5*o + 228. Calculate the lowest common multiple of 14 and l.
868
Let o = -114 - -352. Find the common denominator of 2/200*o + -4 and (5 - 7) + 2/(-96)*-3.
400
Suppose -3*k + 63 = 15. Suppose -k = 169*b - 173*b. Let a = -15 + 25. Calculate the lowest common multiple of a and b.
20
What is the common denominator of 1/32 and (-21235)/9864 + 2/((-1)/(1/(-3)))?
288
Suppose 1 = 3*c + 4. Calculate the lowest common multiple of 27 and c + 5 - -3 - 2.
135
Let c = 61 - 106. Let d = 46 + c. Calculate the smallest common multiple of ((-118)/(-10))/d + (-32)/40 and 2.
22
Suppose l + 18 = -4*b + b, 4*b + 46 = -5*l. Calculate the lowest common multiple of ((-2)/4)/(((-35)/l)/(-35)) and 40.
120
Let m = -3366/31 - -304397/2790. Find the common denominator of m and -34/801.
8010
Let g be (-1373)/(-6) + 40/240. Let j = g - 220. Calculate the lowest common multiple of 51 and j.
153
Let g = 1650219/601 - 11911837470/4362659. Let p = 908/61 - g. Calculate the common denominator of p and 3.
119
Let z(p) = 3*p**2 - 224*p - 1278. What is the l |
import pytest
def test_justification_stores_hash(protocol_instantiated):
protocol_instantiated.execute('M-0-A SJ-1-A M-1-B')
validator_0 = protocol_instantiated.global_validator_set.get_validator_by_name(0)
validator_1 = protocol_instantiated.global_validator_set.get_validator_by_name(1)
justification = validator_1.justification()
assert justification[validator_0] == protocol_instantiated.messages['A'].hash
assert justification[validator_1] == protocol_instantiated.messages['B'].hash
def test_justification_includes_justified_messages(protocol_instantiated):
protocol_instantiated.execute('M-0-A M-0-B S-1-B M-1-C')
validator_0 = protocol_instantiated.global_validator_set.get_validator_by_name(0)
validator_1 = protocol_instantiated.global_validator_set.get_validator_by_name(1)
justification = validator_1.justification()
assert protocol_instantiated.messages["A"].hash not in justification.values()
assert protocol_instantiated.messages["B"].hash not in justification.values()
assert justification[validator_1] == protocol_instantiated.messages['C'].hash
protocol_instantiated.execute('SJ-1-B')
justification = validator_1.justification()
assert justification[validator_0] == protocol_instantiated.messages['B'].hash
assert justification[validator_1] == protocol_instantiated.messages['C'].hash
def test_add_justified_message(protocol_instantiated):
protocol_instantiated.execute('M-0-A M-0-B SJ-1-A')
validator_0 = protocol_instantiated.global_validator_set.get_validator_by_name(0)
validator_1 = protocol_instantiated.global_validator_set.get_validator_by_name(1)
assert protocol_instantiated.messages['A'] in validator_0.view.justified_messages.values()
assert protocol_instantiated.messages['A'] in validator_1.view.justified_messages.values()
assert protocol_instantiated.messages['B'] in validator_0.view.justified_messages.values()
assert protocol_instantiated.messages['B'] not in validator_1.view.justified_messages.values()
@pytest.mark.parametrize(
'test_string, justified_messages, unjustified_messages',
[
('M-0-A M-0-B S-1-B', [['A', 'B'], []], [[], ['B']]),
('M-0-A M-0-B S-1-B SJ-1-A', [['A', 'B'], ['A', 'B']], [[], []]),
('M-0-A M-0-B M-0-C S-1-C S-1-B', [['A', 'B', 'C'], []], [[], ['B', 'C']]),
]
)
def test_only_add_justified_messages(test_string, justified_messages, unjustified_messages, protocol_instantiated):
protocol_instantiated.execute(test_string)
for v in protocol_instantiated.global_validator_set:
if v.name >= 2:
continue
for message in justified_messages[v.name]:
assert protocol_instantiated.messages[message] in v.view.justified_messages.values()
assert protocol_instantiated.messages[message] not in v.view.pending_messages.values()
for message in unjustified_messages[v.name]:
assert protocol_instantiated.messages[message] not in v.view.justified_messages.values()
assert protocol_instantiated.messages[message] in v.view.pending_messages.values()
@pytest.mark.parametrize(
'test_string, justified_messages, unjustified_messages, resolving_string',
[
(
'M-0-A M-0-B S-1-B',
[['A', 'B'], []],
[[], ['B']],
'SJ-1-A'
),
(
'M-0-A SJ-1-A M-0-B M-0-C M-0-D M-0-E S-1-E',
[['A', 'B', 'C', 'D', 'E'], ['A'], []],
[[], [], ['E']],
'S-1-B S-1-C S-1-D'
),
(
'M-0-A SJ-1-A M-0-B M-0-C M-0-D M-0-E S-1-E',
[['A', 'B', 'C', 'D', 'E'], ['A'], []],
[[], [], ['E']],
'S-1-D S-1-B S-1-C'
),
]
)
def test_resolve_message_when_justification_arrives(
test_string,
justified_messages,
unjustified_messages,
resolving_string,
protocol_instantiated
):
protocol_instantiated.execute(test_string)
for validator in protocol_instantiated.global_validator_set:
if validator.name >= 2:
continue
idx = validator.name
view = validator.view
for message in justified_messages[idx]:
assert protocol_instantiated.messages[message] in view.justified_messages.values()
assert protocol_instantiated.messages[message] not in view.pending_messages.values()
for message in unjustified_messages[idx]:
assert protocol_instantiated.messages[message] not in view.justified_messages.values()
assert protocol_instantiated.messages[message] in view.pending_messages.values()
protocol_instantiated.execute(resolving_string)
for validator in protocol_instantiated.global_validator_set:
if validator.name >= 2:
continue
idx = validator.name
view = validator.view
for message in justified_messages[idx]:
assert protocol_instantiated.messages[message] in view.justified_messages.values()
assert protocol_instantiated.messages[message] not in view.pending_messages.values()
for message in unjustified_messages[idx]:
assert protocol_instantiated.messages[message] in view.justified_messages.values()
assert protocol_instantiated.messages[message] not in view.pending_messages.values()
def test_multiple_messages_arriving_resolve(protocol_instantiated):
test_string = "M-0-A SJ-1-A M-0-B M-0-C M-0-D M-0-E M-0-F S-1-F"
protocol_instantiated.execute(test_string)
val_1 = protocol_instantiated.global_validator_set.get_validator_by_name(1)
assert protocol_instantiated.messages['F'] in val_1.view.pending_messages.values()
val_1.receive_messages(protocol_instantiated.global_view.justified_messages.values())
assert protocol_instantiated.messages['F'] in val_1.view.justified_messages.values()
|
Sleep Medicine in Practice - SLEE5030
Year - 2018
This capstone unt provides the opportunity to bring together and apply qall previous learning from the course and ppply it in a very practical way that will inform the basis of future professional practice.
There are two components to this capstone unit - a presentation and scoring of sleep studies. Each component must be successfully completed.
Presentation: students will prepareand deliver online a topic chosen in collaboration with the course coordinator. The 10 minute presentation is to be well structures, well referenced and engaging.
Sleep scoring: students will be taight to use sleep scoring software to analyse multiple short sleep studies and then analyse two 8 hour sleep studies. Detailed reports on these studies are required for copmpletion. (The software to analyse the sleep studies will be provided)
Courses that offer this unit
Non-award/non-degree study If you wish to undertake one or more units of study (subjects) for your own interest but not towards a degree, you may enrol in single units as a non-award student. Cross-institutional study If you are from another Australian tertiary institution you may be permitted to undertake cross-institutional study in one or more units of study at the University of Sydney.
To help you understand common terms that we use at the University, we offer an online glossary. |
Nitrogen removal from landfill leachate using a compact constructed wetland and the effect of chemical pretreatment.
Onsite treatment of leachate was implemented at the Tveta Landfill, adjacent to the city of Södertälje, Sweden. The system consists of leachate collection in a pond, precipitation of metals with chemicals, a constructed wetland, and forest irrigation. This article describes the constructed wetland and its effectiveness at removing ammonia in the system. Pulsed-discharge hydrology and wetland ecology formed the basis for the development of a compact constructed wetland (CCW). The system presented here has most design similarities with vertical sub-surface flow wetlands, though this system is run in batch mode. Chemically purified leachate and untreated leachate were applied to separate sections of the CCW using a filling and emptying schedule. A leachate treatment cycle of about 14 days duration was used, involving a 7 day submerged phase followed by a 7 day drained period. The removal efficiency varied between 40 and 75% on a mass basis. A maximum mass removal rate of up to 5.1 g m(-2) d(-1) was achieved in wetlands receiving leachate after chemical pretreatment. In wetlands receiving non-treated leachate a net release of up to 18 g m(-2) N occurred in the form of nitrate. This indicated a considerable nitrification but limited denitrification in those systems. It was unclear whether the chemical treatment enhanced the nitrogen removal efficiency because of lower toxicity and/or content of fewer competing cations, or other mechanisms. Mechanisms responsible for the NH4-N removal in the CCW system have to be further investigated. |
Q:
Get category name from category id laravel
I am very new to laravel and have two table one post table and one category table. I have only one category related to one post, so i add category id in post table.So now i want to display all post with category name.
post table:
id,name,category_id,status
category Table:
id,name
i want to dispaly like
POST NAME
CATEGORY NAME
I have two model category and post, so how can i write the eloquent relationship or give me a simple way to get the array of post with category name
A:
In your Post model:
public function category() {
return $this->belongsTo(Category::class);
}
Now it will be available to you from the Post model directly
$post = Post::find($id);
$category_name = $post->category->name;
Edit for question in comment:
There are a number of ways you can get posts by category name, for easy of use I would do this:
In category model:
public function posts() {
return $this->hasMany(Post::class);
}
Now you have it available through the category model:
$category = Category::where('name', $name)->first();
$posts_collection = $category->posts()->get();
A:
On your Post model you can write the category relationship like this:
public function category() {
return $this->belongsTo(Category::class); // don't forget to add your full namespace
}
You can then do something like this...
$posts = Post::with('category')->get();
which will get all your posts with the category it belongs to.
You can then iterate over the $posts variable, for example, using blade...
@foreach ($posts as $post)
<tr>
<td>{{ $post->name }}</td>
<td>{{ $post->category->name }}</td>
</tr>
@endforeach
Read up further here: https://laravel.com/docs/5.4/eloquent-relationships#defining-relationships
|
package org.json;
import java.io.IOException;
import java.util.HashMap;
import java.util.Map;
import junit.framework.TestCase;
import org.junit.After;
import org.junit.Before;
public class JSONObjectTest extends TestCase {
public static JSONObject testJson(boolean ordered) {
JSONObject json = new JSONObject(ordered);
Map<String, Object> map = new HashMap<>();
map.put("abc", 1);
map.put("def", "Hello World");
map.put("ghj", new String[]{"Hello", "World"});
json.putAll(new JSONObject(map));
json.put("eins", 1);
json.put("zwei", 2);
json.put("drei", 3);
json.put("vier", 4);
json.put("fuenf", 5);
return json;
}
JSONObject testObject;
@Before
public void setUp() throws Exception {
this.testObject = testJson(true);
}
@After
public void tearDown() throws Exception {
}
public void test() throws IOException {
Object a = this.testObject.get("ghj");
assertTrue(a instanceof JSONArray);
String t0 = this.testObject.toString();
JSONObject j0 = new JSONObject(t0);
String t1 = j0.toString();
assertEquals(t0, t1);
}
}
|
857 P.2d 92 (1993)
Robert Scott FITZGERALD, Appellee,
v.
Cynthia L. SHARUM (formerly Fitzgerald), Appellant.
No. 79286.
Court of Appeals of Oklahoma, Division No. 1.
June 29, 1993.
As Corrected July 14, 1993.
John C. Howard, Scarlett A. Howard, El Reno, for appellant.
Mark Henricksen, Lanita Henricksen, El Reno, for appellee.
Released for Publication by Order of the Court of Appeals of Oklahoma, Division No. 1.
MEMORANDUM OPINION
GARRETT, Judge:
Cynthia L. Sharum (Cynthia) and Robert Scott Fitzgerald were divorced in September, 1984. Cynthia was granted custody of the two minor children born of the marriage. Robert was ordered to pay child support. In September, 1991, Cynthia moved to modify the judgment by increasing the amount of child support.
The trial court determined that there had been material, permanent and substantial change since the entry of the decree requiring modification of the amount of child support, and increased the amount of child support paid by Robert from $350.00 to $552.06 per month. Pursuant to the modified child support, responsibility for medical insurance for the children was changed from Robert to Cynthia. Robert was ordered to pay 51% of the insurance premium, and 51% of the medical costs not covered by insurance. Cynthia filed a motion for new trial contending the trial court erred because it did not consider all the monthly income of Robert for child support guideline (Guideline) purposes. The Guidelines are found at 43 O.S. 1991 § 118. She appeals.
Robert owns a trucking company. The amount considered by the Court as income for Robert was $3,678.00 per month, which *93 includes a net monthly average payroll of $3,500.00; $117.00 of medical insurance benefits paid by Robert's corporation on his behalf; interest income of $58.00 a month; and, $3.00 a month of income from miscellaneous monies paid to Robert by his corporation.
Specifically, Cynthia contends the trial court failed to consider the evidence showing that Robert had received additional compensation from his corporation. Cynthia contends the corporation paid Robert's federal withholding (income) tax, state withholding (income) tax, and social security tax which were not considered as a part of Robert's gross income. Cynthia also asserted the corporation retained cash at the end of the year that was not distributed to Robert, but should have been considered as income for him for that year. Finally, Cynthia contends the corporation made payments on a pickup truck used by Robert, paid insurance payments on the pickup, and paid Robert's personal telephone bill and other miscellaneous items which were not considered as income for Robert.
The transcript of the proceeding reveals that Cynthia called herself and Robert as witnesses. Robert's testimony revealed he was the sole shareholder, officer and employee of his trucking company; his 1991 personal income tax return showed he received $822.00 in interest in that year and $4000.00 in dividend income. He further testified the corporation paid the insurance payment for him and his children's health benefits and the corporation had purchased a pickup truck, and paid insurance on that pickup, which was his sole method of transportation for the previous three months, and he had received loans from the corporation but had repaid only a portion thereof. He testified the pickup was used for corporation business, that he had wrecked his personal passenger car approximately three months earlier, and intended to purchase a new personal automobile soon. He also testified the corporation paid other miscellaneous items, e.g. meals, checks written for cash, the tag for the pickup, certain clothing for himself, and an answering machine for his home, but that the corporation telephone number was the same as his personal telephone number.
Cynthia contends that failure to include the federal income tax, state income tax, and social security tax lowered Robert's monthly average income. Using figures from Robert's evidence, his income was reduced by $618.00 per month for failing to consider these items. That amount would be $833.00 per month, by using Cynthia's evidence. This evidence includes a review of the corporation's ledger sheets. Cynthia contends the trial court erred as it failed to follow 43 O.S. 1991 § 118(3) which requires a Court to carefully consider income and expenses from the operation of a business, and that expense reimbursements are to be considered if they are significant and reduce personal living expenses. Cynthia also contends the corporation was paying $200.41 per month in medical insurance, and it was error to require her to carry the insurance and show only $117.00 as income attributable to health insurance for Robert.
Robert contends the Guidelines allow the trial court discretion in computing child support. He contends the loans he received from the corporation were repaid by him, and therefore were not income, and if the trial court erred in not considering certain taxes, any error was offset by considering loans from the corporation as income.
The Court viewed the witnesses and evidence, and determined that payments made by the corporation for the vehicle driven by Robert, and the attendant insurance payments, were not to be considered as personal income, but were to be considered corporate expenses. The trial court made the same determination for the costs of the telephone and retained earnings held by the corporation. Modification of child support obligations is a matter addressed to the sound discretion of the trial court, whose rulings thereon will not be disturbed absent a showing of abuse of weight of the evidence. Wade v. Wade, 570 P.2d 337 (Okl. 1977); Huchteman v. Huchteman, 557 P.2d 427 (Okl. 1976).
In the case below, the evidence before the trial court was disputed. 43 O.S. 1991 § 118(3) requires the trial court to "carefully *94 review income and expenses from self-employment or operation of a business to determine an appropriate level of gross income available to the parent to satisfy a child support obligation." The trial court reviewed this evidence and made a determination that these items were corporate assets as opposed to personal assets. We cannot say it was against the clear weight of the evidence and abuse of discretion to do so.
However, it was error for the trial court to fail to consider any federal income tax, state income tax, or social security tax paid by the corporation for Robert's benefit. A portion of the social security tax is normally paid by an employer. This portion may not be considered as income for Robert. However, any other portion not normally paid by an employer must be included as income. A self employed person may not "disallow" this portion of their income merely by virtue of the business paying his or her taxes. It was contrary to law to disregard this evidence, and the matter must be remanded on this issue.
Robert argues the trial court had the discretion to deviate from the level of child support suggested by the Guidelines pursuant to 43 O.S. 1991 § 118. This is correct. However, § 118 authorizes the trial court to do so only where the amount of child support is unjust, inequitable, unreasonable or inappropriate under the circumstances. If the Court deviates from the guidelines, it must make specific findings of fact supporting that action. Here, this was not done.
Cynthia's request for attorney fees on appeal is denied. The trial court may consider a request for attorney fees below.
AFFIRMED IN PART; REVERSED IN PART, AND REMANDED.
ADAMS, P.J., not participating.
JONES, J., concurs.
|
india
Updated: Jul 08, 2019 17:30 IST
India on Monday lodged a strong protest with the UN rights office over its report on the situation in Jammu and Kashmir and asserted that it is merely a continuation of the earlier “false and motivated” narrative and ignores the core issue of cross-border terrorism emanating from Pakistan.
Last year, the Office of the UN High Commissioner for Human Rights (OHCHR) released its first-ever report on Kashmir and in an update of that report it claimed on Monday that “neither India nor Pakistan have taken any concrete steps to address the numerous concerns raised”.
Hitting out at the report, Ministry of External Affairs Spokesperson Raveesh Kumar said: “The update of the report of the OHCHR is merely a continuation of the earlier false and motivated narrative on the situation in the Indian state of Jammu and Kashmir.”
The assertions in the report are in violation of India’s sovereignty and territorial integrity and ignore the core issue of cross-border terrorism, he said. “A situation created by years of cross-border terrorist attacks emanating from Pakistan has been ‘analysed’ without any reference to its causality. The update seems to be a contrived effort to create an artificial parity between the world’s largest and the most vibrant democracy and a country that openly practices state-sponsored terrorism,” Kumar said.
“We have registered our strong protest regarding the update with the Office of the High Commissioner for Human Rights,” he said.
(This story has been published from a wire agency feed without modifications to the text. Only the headline has been changed.) |
# -*- coding: utf-8 -*-
from twisted.internet.defer import inlineCallbacks
from globaleaks.db.appdata import load_appdata
from globaleaks.handlers import admin
from globaleaks.rest import requests
from globaleaks.tests import helpers
# special guest:
stuff = u"³²¼½¬¼³²"
class TestNotificationInstance(helpers.TestHandlerWithPopulatedDB):
_handler = admin.notification.NotificationInstance
@inlineCallbacks
def test_get(self):
handler = self.request(role='admin')
response = yield handler.get()
self.assertEqual(response['smtp_server'], 'mail.globaleaks.org')
@inlineCallbacks
def test_put(self):
handler = self.request(role='admin')
notif_desc = yield handler.get()
notif_desc['smtp_server'] = stuff
notif_desc['smtp_password'] = 'widdlyscuds'
handler = self.request(notif_desc, role='admin')
response = yield handler.put()
self.assertEqual(response['smtp_server'], stuff)
|
114 F.3d 307
324 U.S.App.D.C. 453
UNITED STATES of America, Appellee,v.Darvis Orlando DINGLE, Appellant.
No. 95-3168.
United States Court of Appeals,District of Columbia Circuit.
Argued February 18, 1997.Decided June 13, 1997.
Neil H. Jaffee, Assistant Federal Public Defender, argued the cause for appellant, with whom A.J. Kramer, Federal Public Defender, was on the briefs.
Jeanne M. Hauch, Assistant U.S. Attorney, argued the cause for appellee, with whom Eric H. Holder, Jr., U.S. Attorney, John R. Fisher and Roy W. McLeese, III, Assistant U.S. Attorneys, were on the brief.
Before: WALD, GINSBURG and ROGERS, Circuit Judges.
[324 U.S.App.D.C. 455] Opinion for the Court filed by Circuit Judge ROGERS.
ROGERS, Circuit Judge:
1
Appellant Darvis Orlando Dingle appeals his conviction by a jury of possession of cocaine base with intent to distribute, 21 U.S.C. § 841(a), on the principal ground that the evidence was insufficient to establish that he either possessed any drugs, or aided and abetted his codefendant in possessing drugs. He also challenges the district court's failure sua sponte to instruct on the lesser included offense of possession and its drug-quantity attribution at sentencing. We hold that the evidence was sufficient to convict Dingle as an aider and abettor, and that his challenges to the instructions and his sentence are meritless; accordingly, we affirm.
I.
2
Dingle was arrested after the police executed a search warrant for an apartment at 1435 Sheridan Street in Northwest Washington. Dingle, who did not own or live in the apartment, was found there along with his co-defendant, Gregory Boykin, and a small quantity of drugs. During the search, the police observed Boykin throwing a larger quantity of drugs out the window of the apartment. At the first trial, the jury convicted Boykin, but was unable to reach a verdict as to Dingle and the district court declared a mistrial. On retrial, a second jury convicted Dingle, and the district court sentenced him to 100 months' imprisonment.
3
The government's evidence at the second trial established that a team of officers led by Detective Milton Norris went to the door of the apartment, where Norris knocked and announced, "Police, search warrant." At that point, Norris heard footsteps inside that sounded as though a person were running toward the rear of the apartment. Norris tried to open the door, but it was locked. At that point, he instructed another officer to force the door open with a sledgehammer. The officer struck the door once, and a voice inside the apartment said, "Wait a minute, wait a minute," or words to that effect. According to Norris, the voice was fading away, as though the speaker were moving away from the door. At about the same time, officers outside the building observed a man, later identified as Boykin, tossing something out of the apartment window.
4
The officers forced the door open with the sledgehammer. When they entered the apartment, which was well-kept and lightly furnished, Dingle was standing near the doorway next to a small bar, and Boykin was coming out of the back bedroom. Scattered on the floor of the living room, in the hallway between the living room and the bedroom, and on a window ledge in the bedroom, were several ziplock bags containing small amounts of cocaine base. The police also found a plastic wrapping containing 3.5 grams of cocaine base on the bed in the bedroom, and a number of empty ziplock bags in a dresser drawer in the bedroom. Outside the bedroom window, the police found a plastic wrapping containing 43.04 grams of cocaine base and smaller quantities of cocaine base in ziplock bags. In addition, a razor blade and plate, both coated with cocaine residue, were on the bar next to Dingle. The police also recovered a pager and $645 on Dingle's person.
5
The government's narcotics expert testified that crack cocaine is typically packaged in small ziplock bags for street-level distribution. He explained that drug dealers typically break cocaine down into individual dosage units using a razor blade or other cutting implement, and that experienced drug dealers typically do not need a scale to separate cocaine into individual doses. Prior to being packaged in individual doses, crack cocaine is often stored in "bulk" form in a larger plastic bag or container. The expert further explained that drug dealers will pay others to use their residences to perform this packaging process. Finally, he explained that it is common for drug buyers and sellers to contact one another using a pager. In the expert's opinion, the evidence found in the apartment was consistent with a drug distribution operation, based on the quantity of drugs found and the manner of packaging.
6
Dingle testified that he went to the apartment to visit some friends, Donald Stewart and Brenda Kellogg, and their one-and-a-half-year-old daughter, who lived in the apartment. He described Stewart and Kellogg as "real good friends," whom he had [324 U.S.App.D.C. 456] known for five years and visited two to three times a week. When he arrived, both the front door of the apartment building and the door to the apartment were unlocked. The apartment lights were on, and the radio was playing, so Dingle went inside. He decided to "play a game on Mr. Stewart" by locking the door to "teach[ ] him a lesson." After a time, Boykin knocked on the door, and Dingle, who recognized Boykin as a friend of Kellogg, let him inside the apartment. Boykin went back toward the bedroom, and Dingle sat down on a bar stool in the living room. Dingle then heard the police knock at the door, and said, "Who is it?" The officers identified themselves, and he said, "Wait a minute," and unlatched the door. Once the door was unlatched, the officers knocked it open.
7
Dingle also claimed that he was planning to pay the $645 to his wife, to whom he owed about $700 in child support. He testified that he had borrowed $300 from his father, and earned the rest doing "side jobs" cleaning carpets. He claimed that he had the pager so that his family and his employers could contact him.
8
In rebuttal, Officer Gerard Burke testified that the police did not find a baby's crib, toys, furniture, or clothes, or any women's clothes in the apartment. While the police did find a bill with Donald Stewart's name in the apartment, they were unable to locate Stewart himself; Burke had unsuccessfully attempted to contact Stewart both at the time of Dingle's arrest and during the trial. He also testified that the door to the apartment building had been left open by undercover officers so that the police could execute the search warrant.
II.
9
In assessing the sufficiency of the evidence, the court views the evidence in the light most favorable to the government, drawing all reasonable inferences in its favor. See, e.g., United States v. Walker, 99 F.3d 439, 441 (D.C.Cir.1996). Our inquiry is limited to the question of whether "any rational trier of fact could have found the essential elements of the crime beyond a reasonable doubt." Jackson v. Virginia, 443 U.S. 307, 319, 99 S.Ct. 2781, 2789, 61 L.Ed.2d 560 (1979). Where a defendant presents evidence in his defense, the jury is entitled to consider all of the evidence, and on appeal the court does likewise, looking to the entire record, and not simply to the evidence in the government's case-in-chief. United States v. Foster, 783 F.2d 1082, 1085 (D.C.Cir.1986) (en banc).
10
Dingle contends that there was insufficient evidence to convict him of possession with intent to distribute cocaine base because the government showed merely that he was present with Boykin in a small apartment where drugs were found. The government responds that there was sufficient evidence to convict Dingle of either constructively possessing the drugs in the apartment jointly with Boykin, or aiding and abetting Boykin in possessing the drugs. Of course, the "[m]ere presence of the accused on the premises, or simply his proximity to the drug," United States v. Staten, 581 F.2d 878, 884 (D.C.Cir.1978), is alone insufficient to establish either constructive possession or aiding and abetting. United States v. Thorne, 997 F.2d 1504, 1510 (D.C.Cir.), cert. denied, 510 U.S. 999, 114 S.Ct. 568, 126 L.Ed.2d 467 (1993); United States v. Poston, 902 F.2d 90, 95 (D.C.Cir.1990). To establish constructive possession, the government had to show not only that Dingle knew of the drugs, but that he was in a position to exercise dominion and control over them. United States v. Lucas, 67 F.3d 956, 959 (D.C.Cir.1995). "There must be some action, some word, or some conduct that links the individual to the narcotics and indicates that he had some stake in them, some power over them." United States v. Pardo, 636 F.2d 535, 549 (D.C.Cir.1980). To establish aiding and abetting, the government had to prove both that Boykin was guilty as a principal and that Dingle had "sufficient knowledge and participation to indicate that [he] knowingly and willfully participated in the offense in a manner that indicated that he intended to make it succeed." United States v. Raper, 676 F.2d 841, 849 (D.C.Cir.1982).
11
The evidence is clearly sufficient to establish that Dingle knew of the drugs since [324 U.S.App.D.C. 457] several ziplock bags containing cocaine base were in plain view on the living room floor near where he was standing. The only question is whether there was sufficient evidence that Dingle took any action that would indicate either an ability to exercise dominion and control over the drugs, or an effort to assist Boykin in possessing the drugs. The court has considered a defendant's ownership of or residence in premises where drugs are found in plain view to be sufficient evidence of dominion and control to establish constructive possession. See, e.g., Walker, 99 F.3d at 441; United States v. Jenkins, 928 F.2d 1175, 1179-80 (D.C.Cir.1991). Evidence suggesting that a defendant has regular access to the premises, such as possession of a key, may also be sufficient to establish constructive possession. See United States v. Lindsey, 47 F.3d 440, 445 (D.C.Cir.), vacated on other grounds sub nom. Robinson v. United States, --- U.S. ----, 116 S.Ct. 665, 133 L.Ed.2d 516 (1995). Here there was no evidence that Dingle owned or resided in the apartment, or that he had regular access to it. Nor is Dingle's case like United States v. Dunn, 846 F.2d 761 (D.C.Cir.1988), on which the government relies, where the defendant was observed pitching things into a nearby room where drugs and a gun were found. Id. at 764. The police did not observe any actions by Dingle that suggest such physical control over the drugs.
12
The government focuses on the fact that Dingle, by his own admission, shouted "wait a minute, wait a minute," when the police started to break down the door. The government characterizes this as an attempt by Dingle to stall the police to give Boykin the opportunity to dispose of the drugs. Cf. United States v. Washington, 12 F.3d 1128, 1136-37 (D.C.Cir.), cert. denied, 513 U.S. 828, 115 S.Ct. 98, 130 L.Ed.2d 47 (1994). As Dingle contends, standing alone this evidence would be insufficient to establish his guilt beyond a reasonable doubt because any occupant of an apartment might respond in a similar manner to an attempt by the police to break down the door. However, Dingle's testimony provided further evidence that he was actively assisting Boykin in the possession of drugs. Dingle acknowledged that upon entering the apartment, he locked the door behind him, thus indicating some measure of control over the apartment and its contents. He later opened the door to admit Boykin, and then relocked it. Because the expert's testimony made clear that the apartment bore all the hallmarks of a drug packaging and distribution center, the jury could reasonably have concluded that Dingle was actively trying to assist Boykin. Dingle's possession of a large quantity of cash and a pager, which the expert described as a tool of the drug distribution trade, were also suggestive of his involvement.1 Washington, 12 F.3d at 1137; Thorne, 997 F.2d at 1512. Taking all of these circumstances into account, the jury could reasonably conclude that Dingle's statement, "wait a minute, wait a minute," at the same time that Boykin was attempting to dispose of the drugs, was an attempt to stall the police.
13
Dingle's reliance on United States v. Zeigler, 994 F.2d 845 (D.C.Cir.1993), is misplaced. There the police searched an apartment that had previously been divided into two units, and found in one of the units cocaine, a gun, $740 in cash, and a razor blade in a locked briefcase inside a locked laundry room. Id. at 846. Zeigler resided in the other unit, and the government presented no evidence that she ever entered the laundry room or had the combination to the locks on the door or the briefcase. Id. at 848. The court rejected the government's constructive possession theory, holding the evidence insufficient to establish either knowledge of the drugs, or dominion or control over them. Id. As noted, Dingle's knowledge of the drugs, which were in plain view throughout the apartment, is clear, and based on Dingle's description of his activities, the jury could conclude that he knew of Boykin's drug possession and sought to assist him.
14
[324 U.S.App.D.C. 458] The evidence against Dingle is comparable to the evidence in Washington. Washington was riding in the front passenger seat of a car as it attempted to elude police. 12 F.3d at 1131. A co-defendant who was sitting in the back seat jumped out of the car, and then ran alongside it for about a block before throwing a bag of drugs into the car through the driver's side window. Id. Washington acknowledged in his testimony that he had pulled the bag through the window. Id. at 1137. The court held that his admission, combined with Washington's possession of $586 and a pager purchased by the driver of the car, was sufficient to establish aiding and abetting. Id. Here, as in Washington, the defendant's testimony as to his actions, in conjunction with his presence on the scene and his possession of cash and a pager, is sufficient to establish aiding and abetting.
15
Furthermore, the jury was entitled to take into account the government's rebuttal evidence in assessing Dingle's claim of innocent presence. See Foster, 783 F.2d at 1085. Dingle testified that he went to the apartment to visit his friends, Stewart and Kellogg, and their one-and-a-half-year-old daughter. He claimed that Stewart and Kellogg were good friends whom he visited several times a week. Yet when the police searched the apartment, they found no evidence suggesting that either a baby or an adult woman resided in the apartment. Indeed, the only evidence to suggest that either Stewart or Kellogg had ever resided in the apartment was a single bill in Stewart's name. Officer Burke also testified that he repeatedly attempted to contact Stewart at a telephone number Dingle had provided under oath in front of the jury during the second trial, but was unable to reach him or determine a corresponding address. Based on the expert testimony, the jury could reasonably have concluded that the apartment was being used for drug packaging operations, and that Officer Burke's rebuttal testimony eviscerated Dingle's explanation that he was merely in the apartment for a friendly social visit.
16
In Zeigler, the court held that any negative inferences that a jury may draw from the demeanor of a defendant who testifies should not ordinarily be considered in a sufficiency analysis. 994 F.2d at 849-50; see also Thorne, 997 F.2d at 1511. The court reasoned that "[t]here is no principled way of deciding when the government's proof, less than enough to sustain the conviction, is nevertheless enough to allow adding negative inferences from the defendant's testimony to fill the gaps." Zeigler, 994 F.2d at 850. Contrary to Dingle's contention, this rule poses no obstacle to appellate consideration of the government's rebuttal evidence. The Zeigler rule does not apply where "the defendant's testimony, on its face, [is] utterly inconsistent, incoherent, contradictory, or implausible." Id. at 849. While Dingle's testimony was not internally inconsistent, the government's rebuttal evidence made it extremely implausible. A jury viewing the government's evidence could reasonably find that Dingle's account was false, regardless of his demeanor, and that he was in the apartment for illicit purposes.
17
With or without considering the implausibility of Dingle's explanation for his presence in the apartment, the jury could reasonably conclude that he aided and abetted Boykin in the possession of drugs with the intent to distribute them. Thus, because we hold that the evidence was sufficient to support Dingle's conviction on that basis, the court need not consider whether the jury could also have reasonably found that Dingle had constructive possession of the drugs. Griffin v. United States, 502 U.S. 46, 56-57, 112 S.Ct. 466, 472-73, 116 L.Ed.2d 371 (1991); Walker, 99 F.3d at 442.
III.
18
Dingle's remaining contentions do not require extensive discussion. His contention that the district court erred by failing sua sponte to give an instruction on the lesser included offense of simple possession is meritless. Because Dingle neither asked for such an instruction nor objected to the district court's failure to give one, our review is for plain error, and we find none. FED. R.CRIM. P. 30, 52; United States v. Campbell, 684 F.2d 141, 148 (D.C.Cir.1982); see also United States v. Olano, 507 U.S. 725, 732-37, 113 S.Ct. 1770, 1776-80, 123 L.Ed.2d 508 (1993). It has long been the rule in this [324 U.S.App.D.C. 459] circuit that "[i]n general, the trial judge should withhold charging on [a] lesser included offense unless one of the parties requests it, since that charge is not inevitably required in our trials, but is an issue best resolved, in our adversary system, by permitting counsel to decide on tactics." Walker v. United States, 418 F.2d 1116, 1119 (D.C.Cir.1969). In deciding whether to request such an instruction, defense counsel must make a strategic choice: giving the instruction may decrease the chance that the jury will convict for the greater offense, but it also may decrease the chance of an outright acquittal. Here, defense counsel adverted to precisely such a choice during a colloquy with the district court about the verdict form; defense counsel maintained that the government could not show, as the indictment charged, that Dingle possessed with intent to distribute 50 grams, and that a special verdict form on drug quantity was therefore appropriate. Although the district court rejected the special verdict form request, defense counsel did not seek an instruction on simple possession, possibly because Dingle had testified that he did not use cocaine and that he had simply come to the apartment to visit his friends. Defense counsel then chose to argue to the jury that the government's evidence was insufficient and Dingle was simply in the wrong place at the wrong time. In view of that strategic decision, Dingle has not demonstrated that it was plain error for the district court not to give a lesser included offense instruction.
19
Finally, Dingle's contention that the district court erred in attributing to him, for purposes of sentencing, the entire quantity of drugs that Boykin threw out the window, in addition to the much smaller quantities found on the living room floor, is meritless. The evidence was sufficient to establish that Dingle aided and abetted Boykin; he is therefore responsible for the same quantity of drugs that Boykin possessed. 18 U.S.C. § 2; U.S. SENTENCING GUIDELINES MANUAL §§ 1B1.3, 2X2.1 (1995); see also United States v. Nieto, 60 F.3d 1464, 1469 n. 4 (10th Cir.1995), cert. denied, --- U.S. ----, 116 S.Ct. 793, 133 L.Ed.2d 742 (1996); United States v. Pierson, 53 F.3d 62, 64-65 (4th Cir.1995). Because the district court's finding that Boykin and Dingle jointly possessed all of the cocaine in the apartment, except for the rock found on the bed in the bedroom, is not clearly erroneous, see United States v. Lam Kwong-Wah, 966 F.2d 682, 688-89 (D.C.Cir.), cert. denied, 506 U.S. 901, 113 S.Ct. 287, 121 L.Ed.2d 213 (1992), the district court properly sentenced both defendants in the guidelines range appropriate for possession of 35 to 50 grams of cocaine base.
20
Accordingly, we affirm the judgment of conviction.
1
While many people possess pagers or cash for legitimate reasons, see United States v. Brown, 16 F.3d 423, 431 (D.C.Cir.), cert. denied, 513 U.S. 900, 115 S.Ct. 257, 130 L.Ed.2d 178 (1994), in this circuit possession of such items is probative evidence of both possession and intent to distribute. United States v. Crowder, 87 F.3d 1405, 1412 (D.C.Cir.1996) (en banc), vacated on other grounds, --- U.S. ----, 117 S.Ct. 760, 136 L.Ed.2d 708 (1997)
|
[Role of adrenergic-neural regulation in failing heart due to aortic regurgitation in rabbits].
The purpose of this study was to determine the characteristics of the role of adrenergic-neural regulation in the pathophysiology of heart failure, produced by aortic regurgitation (AR), especially in relation to the compensatory process. AR was produced by perforation of the aortic valves in 25 rabbits. Another 6 normal rabbits served as controls. Myocardial beta-adrenoceptors and catecholamines were measured in 17 rabbits with AR after various periods: 1 day (n = 5), 1 week (n = 6), and 4 weeks after production of AR (n = 6). Serial blood samples were taken without anesthesia through a catheter placed in the jugular vein for determination of the serum catecholamine level in 8 rabbits with AR. Left ventricular free wall weight increased 1 week and 4 weeks after AR. Wall thickness didn't increase until 4 weeks had passed. Maximal binding sites of myocardial beta-adrenoceptors were reduced from 67.8 +/- 16.7 fmol/mg. protein in the controls to 37.6 +/- 9.21 day after AR (p less than 0.01). Down regulation persisted for 1 week (37.3 +/- 5.5). This change was reversed in the 4-week group (55.5 +/- 13.9). Myocardial norepinephrine content was preserved at 1 day, but depleted at 1 week after AR. In the 4-week group it was restored. Serum norepinephrine level increased 1 day after AR. However, it returned toward the normal range thereafter.(ABSTRACT TRUNCATED AT 250 WORDS) |
Characterization of 5-hydroxytryptamine (5-HT) receptor subtypes influencing colonic motility in conscious dogs.
We examined the effects of exogenous 5-hydroxytryptamine (5-HT) and selective 5-HT receptor agonists and antagonists on proximal, middle and distal colonic motility in conscious fasted dogs with extraluminal force transducers implanted chronically. 5-HT (0.003-0.1 mg/kg i.v.) dose-dependently enhanced motility along the entire length of the colon. The 5-HT (0.03 mg/kg i.v.)-induced response was inhibited by 0.1-1.0 mg/kg i.v. methysergide, a 5-HT1/2 antagonist, at all recording sites and by 0.1-1.0 mg/kg i.v. ketanserin, a 5-HT2A antagonist, at the middle and distal sites only. At 1 mg/kg i.v., YM060, a 5-HT3 antagonist, reduced the amplitude of the initial transient high-amplitude contractions induced by 5-HT, but did not affect the tonic contraction induced by 5-HT. At doses up to 3 mg/kg i.v., 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino) ethyl ester (SDZ205-557), a 5-HT4 antagonist, and hexamethonium (up to 10 mg/kg i.v.) did not affect 5-HT-induced responses at any recording site. Renzapride, a 5-HT4 agonist, also stimulated motility along the entire length of the colon at 0.3 mg/kg i.v.. The renzapride-induced response was inhibited by 1 mg/kg i.v. SDZ205-557 or 3 mg/kg i.v. hexamethonium. m-Chlorophenylbiguanide (m-CPBG), a 5-HT3 agonist, (1 mg/kg i.v.) produced a transient high-amplitude contraction at all recording sites and this contraction was eliminated by pretreatment with 0.03 mg/kg i.v. YM060. The contraction produced by m-CPBG declined rapidly, so the increase in the motility index by m-CPBG was not significant at any recording site. Of the antagonists tested, 0.1-1 mg/kg i.v. methysergide produced a delayed and prolonged contractile response at the middle and distal sites. The onset of the response was delayed about 20 min after application and the response was maintained over the subsequent 60-min observation period. The methysergide (1 mg/kg i.v.)-induced response was inhibited by 3 mg/kg i.v. hexamethonium. The other antagonists, ketanserin, YM060 and SDZ205-557, had no contractile effect at any recording site. These results indicate that exogenous 5-HT stimulates motility along the entire length of the fasted canine colon and that 5-HT-induced responses in the proximal colon are mediated mainly by 5-HT1, whereas those in the middle and distal colon are mediated by both 5-HT1 and 5-HT2 receptors. Renzapride and methysergide also stimulate colonic motility via additional mechanisms. The activation of 5-HT4 receptors and the blockade of endogenous 5-HT inhibitory regulation via 5-HT1 receptors may be involved in the action of renzapride and methysergide respectively. |
Introduction
============
Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder due to a variable combination of increased platelet destruction and impaired platelet production, as a consequence of defects in central and/or peripheral immune tolerance which allow the escape of autoreactive lymphocytes.^[@b1-1041124]--[@b3-1041124]^ B cells have a well-established role in the pathogenesis of the disease, as the source of antibodies directed against platelet-surface glycoproteins.^[@b4-1041124]--[@b6-1041124]^
Rituximab, a monoclonal antibody directed against CD20, a membrane glycoprotein expressed on the surface of B cells, was introduced for the treatment of B-cell lymphomas towards the end of the 1980s.^[@b7-1041124]^
Binding to an antigen that is only expressed on mature B cells, rituximab leads to a fast and deep, but reversible B-cell depletion.^[@b8-1041124]^ The transience of the B-cell depletion and the low toxicity profile represented the rationale for its use in the treatment of autoimmune conditions, especially those in which B-cell activity was considered the main pathogenic mechanism, such as ITP. Many studies have been carried out in this field: in monotherapy, with different dose schedules and in combination with other drugs, proving its efficacy, although some differences exist across certain studies.
Rituximab has also been explored in a number of other autoimmune auto-antibody-mediated diseases such as systemic lupus erythematosus,^[@b9-1041124]^ rheumatoid arthritis,^[@b10-1041124]^ autoimmune hemolytic anemia,^[@b11-1041124]^ type II mixed cryoglobulinemia,^[@b12-1041124]^ myasthenia gravis,^[@b13-1041124]^ multiple sclerosis,^[@b14-1041124]^ thrombotic thrombocytopenic purpura,^[@b15-1041124]^ Sjogren syndrome,^[@b16-1041124]^ pemphigus^[@b17-1041124]^ and others. Despite these extensive investigations, autoimmune conditions for which rituximab is licensed by the Food and Drug Administration and the European Medicines Agency are rheumatoid arthritis and ANCA-associated vasculitis.
In this review, we discuss the development and current role of rituximab in the management of ITP.
Pathophysiology of immune thrombocytopenia
==========================================
The milestone role of autoantibodies in the pathogenesis of ITP was first reported in 1951 by Harrington *et al*., who showed that the infusion of plasma from ITP patients into normal controls caused thrombocytopenia, thus imputing the cause of the disease to a plasma-derived factor.^[@b4-1041124]^ This "factor" was subsequently identified as an IgG anti-platelet antibody, directed against platelet glycoprotein (GP) IIb/IIIa and/or the GPIb-IX-V complex.^[@b5-1041124]^ Very rarely, antibodies against GPIa-IIa or GPIV can be found (5%).^[@b18-1041124]^
Antibody-opsonized platelets are then recognized through the Fcγ-receptors by macrophages in the spleen, liver and bone marrow, phagocytized and prematurely destroyed.^[@b19-1041124]^ Other mechanisms through which antibodies can mediate platelet destruction are complement deposition with intravascular lysis and induction of platelet apoptosis.^[@b20-1041124]--[@b23-1041124]^ Plasma from patients with ITP also inhibits megakaryocyte growth and function in the bone marrow.^[@b6-1041124],[@b24-1041124]^
The Ashwell-Morell receptors in hepatocytes have been invoked as a further pathogenic mechanism, because they physiologically remove desialylated, "old" platelets from the circulation. Anti-GPIb/IX autoantibodies are thought to enhance the desialylation of GPIb, increasing hepatic clearance of platelets.^[@b25-1041124],[@b26-1041124]^
Many abnormalities have been shown in T cells of patients with ITP: an altered Th1/Th2 balance, with an increased number of Th1 T-helper cells^[@b27-1041124],[@b28-1041124]^ and a decrease in the number and function of regulatory T cells.^[@b29-1041124],[@b30-1041124]^ The abnormal activation of cytotoxic CD8^+^ T cells may also have a role in the pathogenesis of ITP, contributing to both platelet destruction and impaired platelet production.^[@b31-1041124]^
Circulating thrombopoietin levels in ITP are not increased proportionally to the level of thrombocytopenia, and are usually normal or only slightly increased.^[@b32-1041124]^
Early history of rituximab
==========================
In the late 1980s, the idea of using monoclonal antibodies that recognize tumor-associated antigens for the treatment of hematologic malignancies became reality, and rituximab became a well-tolerated and highly effective option initially used for patients with multi-refractory lymphoproliferative diseases.^[@b7-1041124]^ CD20, a transmembrane glycoprotein expressed on the surface of normal and malignant B cells, appeared ideal for targeted therapy, because it does not shed from the cell surface and is not internalized upon antibody binding.^[@b33-1041124]^ CD20 is expressed from early pre-B to mature B lymphocytes, but is not expressed on hematopoietic stem cells, plasma cells or other cells of the body.^[@b34-1041124]^ Rituximab is a type 1 IgG1-κ human-mouse chimeric mono clonal antibody directed against CD20, which acts through three mechanisms: complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity and induction of direct apoptosis of the target cell.^[@b35-1041124]^
The first report of a case in which rituximab was used for the treatment of an autoimmune disease was published in 1998, when a patient with a cold agglutinin disease and a small IgM paraprotein was successfully treated with four weekly infusions of rituximab.^[@b36-1041124]^ A few years later, in 2001, the first report of the successful use of rituximab for the treatment of ITP associated with a low-grade non-Hodgkin lymphoma was published.^[@b37-1041124]^ Since then, rituximab has been widely used for the treatment of autoimmune manifestations associated with lymphoproliferative disorders, and, because it is a therapy borrowed from lymphomas, the dose schedule of 375 mg/m^2^ weekly for 4 weeks also became the "standard dose" of rituximab in autoimmune diseases.
Since CD20 is also expressed in normal B cells, there was a strong rationale for using rituximab to deplete pathological antibodies in autoimmune diseases. One of the first cases, published in 2000, was that of a young man with refractory myasthenia gravis who, after four standard doses of rituximab, experienced a complete clinical response with disappearance of anti-acetylcholine receptor antibodies, and he did not relapse.^[@b13-1041124]^ This case was an impressive proof of principle that transient B-cell depletion secondary to rituximab treatment may positively modulate the immune system, inhibit the production of autoantibodies, and cause long-term clinical improvement.
Rituximab in immune thrombocytopenia
====================================
In 2001, Stasi *et al*. reported the results of the first prospective study in which 25 patients with chronic ITP were treated with four weekly infusions of rituximab at a dose of 375 mg/m^2^. The overall response rate (ORR) was 52%, with 28% sustained responses. No clinical or laboratory parameters were found to predict treatment response, but they noticed that women and younger patients had a better chance of response, and that, in some patients who relapsed, retreatment was effective.^[@b38-1041124]^
Subsequent studies showed that the overall initial response to rituximab used as second- or further-line of therapy ranges between 52% and 73%, with the complete response (CR) rate ranging between 20% and 54%^[@b39-1041124]--[@b48-1041124],[@b56-1041124],[@b58-1041124],[@b68-1041124]^ ([Table 1](#t1-1041124){ref-type="table"}). In a systematic review including 313 adult patients with chronic ITP, a response rate of 62.5% and a CR rate of 46.3% were found, with a median duration of response of 10.5 months.^[@b42-1041124]^
######
Most relevant studies with rituximab administered at a standard dose of 375 mg/m^2^ weekly for 4 weeks in patients with immune thrombocytopenia.
Three different patterns of response can be distinguished: a first group of patients respond rapidly, within the first month; in the second group, the platelet count starts increasing after 3-4 weeks, and a CR is achieved within 8 weeks after treatment; in the third group of patients, the platelet count increases very slowly, only reaching normal values 3 months after therapy.^[@b46-1041124]^
Only two randomized, placebo-controlled studies have been performed. One very small pilot randomized trial compared rituximab with placebo as second-line therapy. No difference in terms of treatment failure (65.6% *vs*. 80.8%)^[@b47-1041124]^ was found between the two groups. Overall platelet count response (i.e. platelet count ≥30×10^9^/L) was achieved by 62.5% of the patients in the rituximab group and 73.1% in the placebo group at 6 months.
In the much larger RITP trial,^[@b48-1041124]^ the rate of treatment failure was not significantly different between patients given rituximab or placebo (58% *vs*. 69%), and the ORR was 81% in the rituximab group compared to 73% in the placebo group. Improvements in platelet counts were seen up to week 72 in the rituximab arm.
Rituximab doses
---------------
"Standard dose" rituximab results in a marked reduction of malignant and non-malignant B cells in peripheral blood and bone marrow.^[@b49-1041124]^ Since the total mass of B cells is much smaller in patients with ITP than in patients with lymphoma, it was not clear whether a lower dose of rituximab or a different schedule could be equally effective. Potential advantages of the lower dose include avoidance of severe side effects, steroid-sparing effects, the greater possibility of administering repeated courses, and decreased cost. Zaja *et al*. investigated the efficacy of rituximab given at a dose of 100 mg ("low dose") weekly for 4 weeks in 48 ITP patients.^[@b50-1041124]^ In an indirect, non-randomized comparison, both the initial response (ORR 60.5% and CR 39.5%) and the duration of response (12- and 24-month cumulative relapse-free survival rates of 61% and 45%, respectively) were moderately lower in this group than in patients treated with "standard dose". The time to response was also longer than that observed with the "standard dose". This may be due to the fact that the depth of B-cell depletion reached in peripheral blood might not correlate with the depletion in other organs, and the 100 mg dose is probably not enough.
A recent UK study retrospectively compared 113 patients who received "standard dose" rituximab to 169 who received the "low dose". They found that the low dose was not significantly different from the standard dose with regards to ORR (at 2 months, 56% *vs*. 59%; at 6 months, 62% *vs*. 64%), time to maximum platelet count (77 *vs*. 74 days), time to next treatment (4.6 *vs*. 4.3 months) and duration of response.^[@b51-1041124]^
Some groups explored a fixed dose of rituximab, 1000 mg given twice on days 1 and 15, which is the dose schedule licensed for rheumatoid arthritis. Khellaf *et al*., in a prospective registry including 248 patients, compared the "standard dose" to the "rheumatoid arthritis-like" regimen. They did not find any difference in terms of initial or long-term response between the two groups.^[@b41-1041124]^ In a multi-center, single-arm study (R-ITP1000 study), Tran *et al*. found that the "rheumatoid arthritis-like" fixed dose led to an ORR of 44% at week 8 in patients with relapsed/refractory ITP.^[@b52-1041124]^
A multicenter, randomized, phase II Dutch trial compared three rituximab dosing schemes in 156 patients with relapsed or refractory ITP: "standard dose" rituximab, two weekly 375 mg/m^2^ doses and two weekly 750 mg/m^2^ doses. Response rates were similar within the three arms (63%, 59% and 61%, respectively), with a relapse-free survival of 72% at 1 year and 58% at 2 years.^[@b53-1041124]^
The results of the most relevant studies with different dosing schedules of rituximab are summarized in [Table 2](#t2-1041124){ref-type="table"}.
######
Most relevant studies with different dose schedules of rituximab.
Factors predictive of response
------------------------------
Over the years, multiple factors have been investigated with the aim of predicting response to treatment. Several studies highlighted the correlation of age and gender with outcome. In the very first study, Stasi had already pointed out that women and young patients had better responses.^[@b38-1041124]^ This finding was subsequently extended by Bussel *et al*.,^[@b54-1041124]^ who showed that women of child-bearing age whose duration of ITP was less than 24 months had a long-term response comparable with that obtained after splenectomy (60% long-term treatment-free responses). Another study with the same treatment schedule pointed out that adolescent females with an ITP duration of less than 12 months had the longest duration of response.^[@b55-1041124]^ Similar results were also reported with rituximab alone: young (\<40 years) women had a significantly higher probability of achieving a response (73%), a complete response (56%), and as well as a better long-term response (47% after 72 months) compared with the other groups.^[@b56-1041124]^ It must be noted, however, that in several other studies the predictive role of age and gender could not be confirmed.^[@b40-1041124],[@b41-1041124],[@b43-1041124],[@b46-1041124],[@b57-1041124]^ A disease duration of less than 12 months has also been frequently related to better outcomes,^[@b41-1041124],[@b43-1041124],[@b54-1041124],[@b58-1041124]^ as well as the achievement of complete remission,^[@b39-1041124],[@b40-1041124],[@b46-1041124],[@b54-1041124],[@b56-1041124]^ while the influence of a previous splenectomy is not completely clear.^[@b40-1041124],[@b46-1041124]^
The role of antiplatelet autoantibodies (APA) as factors predictive of response is controversial. Differently from other autoimmune diseases, APA in ITP are neither very specific nor sensitive, and for this reason APA are not currently recommended as a diagnostic test for ITP.^[@b59-1041124],[@b60-1041124]^ A reduction of APA levels has been associated with an increase in platelet count,^[@b61-1041124]^ and the presence of platelet-bound antibodies has been associated with a better response to rituximab.^[@b62-1041124]^ The persistence of autoantibodies in non-responders may suggest that rituximab had not removed the long-lived, antibody-producing plasma cells. There is also a small cohort of patients who respond despite undetectable antibodies: in those cases, either laboratory assays are not able to identify the antibody, or the response comes from the elimination of B-cell-mediated activation of T cells.^[@b61-1041124]^
A more recent study did not show any correlation between the presence of APA and the response to rituximab, but found that rituximab resulted in a significant reduction of anti-GPIIb/IIIa but not anti-GPIb/IX levels.^[@b63-1041124]^ In an unconfirmed study, patients with anti-GPIb/IX were shown to have a lesser response to intravenous immunoglobulins and steroids.^[@b64-1041124],[@b65-1041124]^ In patients treated with rituximab, the presence of antibodies against GPIIb/IIIa led to a higher response rate than that in patients without anti-GPIIb/IIIa, while the presence of anti-GPIb/IX did not significantly influence the outcome.^[@b66-1041124]^ This is potentially due to the different modes of action of the autoantibodies: anti-GPIIb/IIIa antibodies induce platelet destruction by Fc-dependent phagocytosis, while the action of anti-GPIb/IX may be FcR-independent^[@b67-1041124]^ and instead increase the hepatic clearance of desialylated platelets.
In summary, the role of APA in response to rituximab remains unclear and may depend on the laboratory doing the testing, the phase of the disease, and which tests are performed.
Long-term outcome of rituximab treatment of immune thrombocytopenia
-------------------------------------------------------------------
Only a small proportion of patients maintain a long-term remission after rituximab: in a prospective French study in 248 adult patients, Khellaf *et al*. found that after a median follow-up of 24 months, 39% of patients were still responding.^[@b41-1041124]^ In other studies a long-term response, at approximately 2 years after initial treatment, was observed in about 40% of patients.^[@b39-1041124],[@b56-1041124],[@b68-1041124]^ However, the only study with a 3-5 year follow up showed that the response was maintained after 5 years in only 21% of adults and 26% of children treated with rituximab.^[@b40-1041124]^
Given that a long-term response greater than 20-30% would be desirable, several strategies have been implemented in order to augment response rates and sustained remissions.
Anticipated use of rituximab in patients with immune thrombocytopenia
---------------------------------------------------------------------
Although not supported by randomized, controlled trials, some studies pointed out that better outcomes can be achieved if rituximab is administered in an early stage of the disease.^[@b46-1041124],[@b58-1041124]^ Following this observation, two studies^[@b69-1041124],[@b70-1041124]^ compared the combination of "standard dose" rituximab and dexamethasone (40 mg/day for 4 days) to dexamethasone alone as first-line therapy in adult patients with ITP. In both studies the combination led to higher sustained response rates (63%^[@b69-1041124]^ *vs*. 36% and 58%^[@b70-1041124]^ *vs*. 37%), compared to those achived with dexamethasone alone.
Combination treatment to improve long-term outcome with rituximab
-----------------------------------------------------------------
Since rituximab affects almost exclusively B cells, without directly affecting the activity of other cells of the immune system (in particular T cells and plasma cells), the combination with other drugs with different modes of action looked appealing. The addition of 28 mg/m^2^ dexamethasone (as an anti-plasma cell treatment), given for three 4-day cycles at 2-week intervals, to "standard-dose" rituximab was explored in a cohort of 67 patients (41 adults and 26 children) with ITP, of whom only five were treatment-naïve. This combination led to a 75% initial response rate and an almost 50% estimated long-term cure rate at 5 years.^[@b54-1041124]^ However, the good long-term responses were seen almost exclusively in women of child-bearing age within 1 year of diagnosis.
The combination of high-dose dexamethasone, low-dose rituximab and cyclosporine (TT4) administered over 1 month was tested in 20 ITP patients (including 7 with newly diagnosed ITP and 5 with secondary ITP), with the aim of targeting, in addition to B cells, also plasma cells and T cells. The response rate at 6 months was 60% and among responders, the relapse-free survival rate was 92% at 12 months and 76% at 24 months. The treatment was well tolerated.^[@b71-1041124]^
Two Chinese studies explored the combination of low-dose rituximab with recombinant human thrombopoietin. The first study enrolled 14 patients with refractory ITP, who had an ORR of 93%.^[@b72-1041124]^ The second was a randomized, open-label study in which the combination was compared with rituximab 100 mg weekly for 4 weeks in patients with relapsed or refractory ITP. The group treated with the combination had a substantially shorter time to response (7 *vs*. 28 days).^[@b73-1041124]^ The long-term response rate (79.2% *vs*. 71.1%) was not significantly different between the two groups.
Gómez-Almaguer *et al*. recently published the results of a single-center, pilot study conducted to assess the safety and efficacy of the combination of eltrombopag, low-dose rituximab and dexamethasone in 13 newly diagnosed ITP patients. The ORR was 100%, with 92% CR rate and a relapse-free survival rate of almost 80% at 12 months.^[@b74-1041124]^
The results of the most relevant studies of the use of rituximab in combination with dexamethasone and other drugs in ITP are summarized in [Table 3a](#t3a-1041124){ref-type="table"} and [3b](#t3b-1041124){ref-type="table"}, respectively.
######
Studies with rituximab plus dexamethasone.
######
Studies with rituximab in combination with drugs other than dexamethasone.
Efficacy of rituximab retreatment
---------------------------------
Limited data are available concerning retreatment with rituximab. In a retrospective study, Hasan *et al*. explored the response to retreatment with standard-dose rituximab in patients with chronic ITP: 80% of the retreated patients responded again to standard-dose rituximab.^[@b75-1041124]^
Zaja *et al*. showed that even low-dose rituximab can be effective in patients who previously responded to the standard dose of the drug, although only three patients received a second course of rituximab.^[@b50-1041124]^ Khellaf *et al*. reported that most of 11 patients retreated with rituximab responded again.^[@b41-1041124]^ In other studies, very small numbers of patients were retreated with rituximab, in most of cases with good responses.^[@b38-1041124],[@b56-1041124],[@b68-1041124],[@b76-1041124]--[@b78-1041124]^
Rai *et al*., in 17 patients with autoimmune cytopenias (including 11 cases of ITP) who previously responded, but then relapsed after a standard course of rituximab, explored the use of rituximab maintenance: a single 375 mg/m^2^ infusion every 4 months for a total of 2 years: 88% of patients achieved a CR, with a mean duration of response of 48 months.^[@b79-1041124]^
B-cell recovery after rituximab
-------------------------------
The depletion of circulating B cells after rituximab administration is rapid (within 1 week) and deep, with B-cell counts remaining low in the peripheral blood for at least 6-12 months.^[@b8-1041124]^ The repopulating pool is dominated by immature B cells, while memory B cells recover after 2 years.^[@b80-1041124]^ A similar depth of peripheral B-cell depletion has also been observed with low-dose rituximab.^[@b50-1041124]^ In the vast majority of patients who achieve a complete remission, the recovery of B cells is not associated with disease relapse,^[@b46-1041124]^ while in non-responders or in patients who relapse, B cells tend to reappear sooner in the peripheral blood and increase to higher levels.^[@b40-1041124],[@b46-1041124]^ Rituximab also induces nearly complete depletion of splenic B cells, and in patients who do not respond the recovery of B cells in the spleen is faster.^[@b81-1041124]^
Effects of rituximab on T cells
-------------------------------
In rituximab responders, all the immune-system abnormalities seen in patients with active disease tend to revert towards normal: in the peripheral blood, there is restoration of the Th1/Th2 and Tc1/Tc2 ratios, a decreased expression of Fas ligand and Bcl-2 mRNA, an increased expression of Bax mRNA and an increased number of regulatory T cells^[@b82-1041124],[@b83-1041124]^. The numbers of interleukin-10-producing B cells (regulatory B cells) and interleukin-6-producing B cells are also normalized after treatment.^[@b84-1041124]^
In contrast, these abnormalities are still detectable in the spleens of non-responders: reduced regulatory T cells, an increased Th1/T-regulatory cell ratio,^[@b81-1041124]^ and persistence of the Tc1 polarization with CD8^+^ cytotoxic T cells displaying the phenotype of effector memory T cells with a restricted T-cell receptor repertoire.^[@b85-1041124]^ These findings suggest that the action of rituximab is not limited to B cells and humoral immunity, but that rituximab also affects cellular immunity. In a mouse model of T-cell-mediated ITP, B-cell depletion resulted in a significantly decreased proliferation of splenic CD8^+^ T cells *in vitro*, which correlated with an in vivo normalization of platelet counts.^[@b86-1041124]^
However, T-cell remodulation in responders seems not to be a specific effect of rituximab since similar changes have also been observed in patients who respond to dexamethasone or thrombopoietin receptor agonists.^[@b87-1041124]--[@b89-1041124]^ It is possible that other biological factors concur to this effect. In particular, it has been proposed that the platelet count increase itself, either directly or via release of transforming growth factor-β, may cause a positive immune-modulating effect.^[@b90-1041124]^
Why a proportion of patients do not respond to rituximab is unknown. This could be caused by either the persistence of long-lived, antibody-secreting plasma cells in the spleen^[@b81-1041124],[@b91-1041124]^ and/or in the bone marrow or by the abnormal activation of T cells, whose activity is not switched off by B-cell depletion. Finally, if the patient does not actually have ITP this would likely explain non-response as well.
Adverse events
--------------
Rituximab is generally a well-tolerated therapy, and adverse events are usually mild and easily manageable. The major concerns derive from the possible induction of hypogammaglobulinemia, and the increased risk of certain infections.
Infusion reactions after the first administration of rituximab are experienced by a variable proportion of patients, ranging from nearly 60% in the first trials^[@b46-1041124]^ to 15% in the more recent reports,^[@b41-1041124]^ and are related to immediate cytokine release. They are usually easily manageable, and serious adverse reactions are exceptional, especially if prednisone is included in premedication.
Serum sickness is a much rarer adverse reaction, characterized by fever, rash, polyarthralgia or arthritis, proteinuria, hematuria, elevated inflammatory markers and decreased complement, which usually arises 10-14 days after treatment.^[@b92-1041124]^ It is the result of immune activation against the chimeric mouse-human drug, with the formation and deposition of immune complexes, and consequent activation of the complement cascade.^[@b93-1041124]^ This type III delayed hypersensitivity reaction to rituximab has been reported more commonly in autoimmune disorders than in hematologic malignancies, but overall it remains a very rare occurrence in adults, with less than 50 cases having been reported.^[@b92-1041124]^
### Hypogammaglobulinemia
Since rituximab does not affect pre-existing long-lived plasma cells, there are not significant changes in the IgG or IgM levels in patients treated with one "standard dose" course.^[@b38-1041124],[@b46-1041124]--[@b48-1041124]^ However, patients treated with multiple courses are more likely to develop hypogammaglobulinemia, which usually recovers spontaneously in a few months.^[@b94-1041124]^ Since dexamethasone also affects plasma cells, 10-20% of patients treated with the combination may experience a marked hypogammaglobulinemia, which usually recovers within 1 year.^[@b50-1041124],[@b54-1041124],[@b70-1041124]^
Some reports suggest that a pre-existing hypogammaglobulinemia can be aggravated by rituximab, which can in some cases trigger or accelerate the development of a real common variable immunodeficiency (CVID).^[@b95-1041124],[@b96-1041124]^ It is worthwhile remembering that ITP may be the initial manifestation of CVID and can precede its diagnosis by years.^[@b97-1041124]^ It is therefore important, in ITP patients treated with rituximab, to monitor immunoglobulin levels before and after therapy. In addition to monitoring and possibly even temporarily giving intravenous immunoglobulin replacement, prior assessment of genetic markers and vaccine responses^[@b98-1041124],[@b99-1041124]^ may be useful.
The efficacy and safety of standard-dose rituximab in patients with CVID-associated ITP or autoimmune hemolytic anemia was assessed in a multicenter, retrospective, French study. The ORR was 85%, with a 74% CR rate and a sustained response rate of 60% at a median follow up of 39 months; severe infections occurred in 24% of patients, four of whom were not on immunoglobulin replacement therapy. The authors concluded that rituximab is highly effective and relatively safe in the management of CVID-associated immune cytopenias, and that immunoglobulin replacement is strongly recommended in this cohort of patients.^[@b100-1041124]^
### Infections
An increased risk of infections after rituximab therapy is generally uncommon and more frequently observed in severely immunocompromised patients.^[@b101-1041124]^ Chugh *et al*., in a meta-analysis including five trials and 463 ITP patients treated with rituximab, did not find an increased risk of infection.^[@b102-1041124]^ Khellaf *et al*. concluded that the risk of infections was acceptable (cumulative incidence of 2.3 infections per 100 patient-years at a median follow up of 24 months), with the most severe infections occurring in adults older than 70 years of age, who suffered from severe comorbidities.^[@b41-1041124]^
Rituximab therapy reduces the genesis of new long-lived plasma cells, thus impairing the immune response to vaccines. Vaccines against encapsulated bacteria (*Streptococcus pneumoniae*, meningococci and *Haemophilus influenzae*) should be administered before rituximab, considering that patients, especially non-responding ones, may require a subsequent splenectomy.^[@b103-1041124]^
Reactivation of hepatitis B virus (HBV) is a well-recognized complication of immunosuppressive therapy. Patients who are HBcAb positive (likely occult carriers) should receive antiviral prophylaxis with lamivudine, while patients with HBsAg or HBV-DNA positivity (active carriers and inactive carriers) should be referred to a hepatologist and treated with entecavir or tenofovir.^[@b104-1041124]^
A rare but life-threatening infection that has been linked to rituximab is progressive multifocal leukoencephalopathy (PML), caused by the activation of Jakob-Creutzfeld virus and its spread to the central nervous system.^[@b105-1041124]^ This complication, although rare, has been almost only reported in patients with lymphoproliferative disorders, and only a very few cases have been observed in patients with autoimmune diseases, especially in systemic lupus erythematosus.^[@b106-1041124],[@b107-1041124]^ Furthermore, patients who develop PML are usually profoundly immunocompromised from combination chemotherapy, and rituximab is often just one of the many drugs received.^[@b108-1041124],[@b109-1041124]^ There is only one well-studied case of PML in ITP and the course was unusual with the PML occurring more than 3 years after exposure to rituximab.
The occurrence of late-onset (\>4 weeks after treatment) neutropenia has been described in patients treated with rituximab for both malignant^[@b110-1041124]^ and non-malignant conditions,^[@b111-1041124],[@b112-1041124]^ including a few ITP patients.^[@b40-1041124]^ Most cases appear to be self-limiting and resolve without issue,^[@b113-1041124]^ and according to some authors retreatment with rituximab is safe.^[@b86-1041124]^
### Malignancies
Immunosuppression secondary to rituximab could increase the risk of second primary malignancies. In large follow-up studies, rituximab has not been shown to increase the risk of cancer in patients with rheumatoid arthritis,^[@b114-1041124]^ among non-Hodgkin lymphoma patients^[@b115-1041124]^ and in patients with ANCA-associated vasculitis.^[@b116-1041124]^
No malignancies were reported in ITP by Arnold *et al*. in a meta-analysis including more than 300 patients,^[@b42-1041124]^ or in other studies,^[@b40-1041124],[@b41-1041124],[@b58-1041124]^ including combination studies with dexamethasone.^[@b54-1041124],[@b69-1041124],[@b70-1041124]^ In other reports nearly 3-4% of patients developed a second primary malignancy after having received rituximab for ITP, but the low percentage and the heterogeneity of the neoplasia led the authors to conclude that a causative relationship with rituximab could not be assessed.^[@b39-1041124],[@b44-1041124],[@b56-1041124]^
Use of rituximab in children
============================
Following the development of rituximab for adults with ITP, studies soon migrated to pediatric patients ([Table 4](#t4-1041124){ref-type="table"}).
######
Rituximab in children.
The first large series was reported in 2005 and included 24 chronic ITP patients who were refractory to or relapsed after previous treatments. The ORR to "standard-dose" rituximab was 78%, with a 63% CR rate and an overall sustained response rate of 37%.^[@b117-1041124]^
The first prospective phase I/II study of rituximab in children and adolescents with chronic ITP included 36 patients with severe refractory ITP or Evans syndrome treated with "standard-dose" rituximab. After a follow up of 1 year, 31% of them maintained a platelet count \>50×10^9^/L.^[@b118-1041124],[@b119-1041124]^
A systematic review including 14 studies with a total of 323 pediatric ITP patients reported a pooled response rate of 68%, and a pooled CR rate of 39%, with a median duration of response of 12.8 months.^[@b120-1041124]^
"Low-dose" rituximab has also been tested in children with ITP: Taube *et al*. explored the efficacy of a single dose of rituximab (375 mg/m^2^) in 22 patients with chronic ITP; the ORR was 59%, with a 27% CR rate, and 36% of patients maintained a long-term remission (median duration of remission 13.5 months; range 2-16 months).^[@b121-1041124]^
Oved *et al*. explored the addition of three 4-day cycles of dexamethasone (28 mg/m^2^) to "standard-dose" rituximab in 33 children with persistent/chronic ITP. The ORR was close to 50%, and 62% of the responders maintained the remission for a median of 35.5 months.^[@b122-1041124]^
Factors predictive of response were also sought in children. Bennett *et al*.^[@b118-1041124]^ found a weak association between response and Evans syndrome, female sex and black race. Parodi and colleagues performed a retrospective study including 49 children (77% with chronic ITP) treated with "standard-dose" rituximab (ORR 69%, 60% relapse-free survival at 36 months), and found a significantly higher probability of relapse-free survival in males aged \>14 years and females aged \>12 years (88.9% *vs*. 56.7%), in patients who achieved a CR (70.2% *vs*. 25%) and in patients who achieved the response within 20 days of treatment (73.7% *vs*. 22%).^[@b123-1041124]^
Among 80 pediatric patients with chronic ITP treated with rituximab (ORR 64%), Grace *et al*. found a higher response rate in patients who had previously responded to steroids (87.5% *vs*. 47.9%) and in those with secondary ITP (89.5% *vs*. 55.7%).^[@b124-1041124]^
In a study by Oved *et al*.,^[@b122-1041124]^ female adolescents with ITP lasting less than 24 months had a higher sustained remission rate (47%) than that of either the entire group (27%) or the male patients (7%).
The drug is usually well tolerated also in children, with a toxicity profile superimposable to that of adult patients in terms of immediate and long-term toxicity.^[@b117-1041124],[@b118-1041124],[@b125-1041124],[@b40-1041124],[@b123-1041124]^ Significant hypogammaglobulinemia was observed in 15% of patients treated with the combination of rituximab and dexamethasone,^[@b122-1041124]^ although this adverse event was transient.
The reported rate of serum sickness was higher in pediatric patients than in adults, particularly in the first series, occurring in up to 10% of the former.^[@b117-1041124],[@b118-1041124]^ Clinical manifestations ranged from severe to mild. Laboratory confirmation can be sought by checking levels of C3 and C4; of note, certain pediatric patients may have a congenitally low C4 level (which may predispose to ITP) and C4 levels should, therefore, be checked prior to rituximab treatment.
Discussion
==========
Twenty years after the first use of rituximab in ITP, published studies show an ORR of nearly 60% and a CR rate of 50%. Long-term remissions occur in 20-30% of patients, with slightly different outcomes possibly related to different selection of populations of patients.
In the interpretation of the results it is worth noting that heterogeneous criteria for response were adopted across different studies (according to older or updated criteria); moreover, older studies included mostly chronic, plurirefractory patients, while in the more recent studies patients with newly diagnosed/persistent ITP were also included. Finally, the ability to compare studies is often only partial because of different follow-up periods.
The data from placebo-controlled studies seem discouraging, but some considerations should be made: in the experimental treatment and placebo arms, patients were allowed to continue corticosteroid therapy, which could have biased the results: in the placebo arms the ORR were 67% (39% CR)^[@b48-1041124]^ and 73% (46% CR).^[@b47-1041124]^ Probably a more meaningful observation is that the median time to relapse in patients who achieved an overall response was 36 weeks in the rituximab group and 7 weeks in the placebo group.^[@b48-1041124]^
The main criticism that only 20% to 30% of patients achieve long-term remission for more than 3-5 years deserves further consideration. The main "error" was probably the mistaken belief that rituximab could represent the medical substitute of splenectomy: a single treatment administered once in a lifetime that could definitively cure many or even most patients with ITP. In some groups of patients, it is worth considering that even a sustained response of 12-18 months can have a significant, positive effect on a patient's quality of life: during this period of time, they do not have to take any ITP medication and can avoid frequent hospital checks.
Furthermore, several clinical studies found that in young women a course of rituximab administered before the chronic phase (ITP duration \<12 months) can lead to response rates and at least mid-term remission rates comparable to those obtained with splenectomy. This finding suggests that at least in some selected patients the treatment outcome may be much better.
Retreatment with rituximab is effective in most cases, especially in patients who maintained the preceding remission for more than 12 months.
Biomarkers predictive of response, including the controversial role of anti-platelet antibody testing, are still lacking and further studies are needed for their establishment and subsequent application in clinical practice.
The efficacy and safety of combinations of treatment with rituximab and other agents, such as thromboietin-receptor agonists, immunosuppressive agents, agents targeting plasma cells or yet others, need to be better evaluated and proven in comparison studies with rituximab monotherapy.
As far as concerns different rituximab doses, comparisons between the "standard dose" and "rheumatoid arthritis dose" did not reveal different results in terms of efficacy and toxicity. Low-dose rituximab could be equally effective, although prospective studies comparing the standard dose and low doses are lacking.
Rituximab is a well-tolerated drug; serious side effects are extremely rare and life-threatening infectious complications are usually only seen in patients with other concomitant causes of immunodeficiency.
Conclusions
===========
In conclusion, based on what has been published in the last 20 years, it is still difficult to give clear indications on when, to whom and how rituximab should be administered. In 2019, the choice of rituximab over other treatment options has to be weighed considering the individual patient's features and expectations, the disease's characteristics, the availability of the drug and the single center's experience.
The authors of this review think that rituximab still represents a valuable therapeutic option for patients with ITP and, based on current knowledge, believe that it should be considered especially (although not exclusively) at an early stage of the disease, as second- or third-line therapy, in young patients (particularly young women) and in patients treated with curative purposes.
Supplementary Material
======================
###### Lucchini et al. Graphical Abstract
###### Disclosures and Contributions
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: [www.haematologica.org/content/104/6/1124](http://www.haematologica.org/content/104/6/1124)
|
Meyers&Poehler Reunite for REALLY
Seth Meyers and Amy Poehler reunited on “Late Night” Wednesday to play a fan-favorite game from their old “SNL” days. The former “Weekend Update” gang dropped a new topical version of “REALLY!?!” to slam sexist Sports Illustrator comments on whether or not women’s sports are worth watching.
http://goo.gl/jCNRVh |
Chemical modification of PS-ASO therapeutics reduces cellular protein-binding and improves the therapeutic index.
The molecular mechanisms of toxicity of chemically modified phosphorothioate antisense oligonucleotides (PS-ASOs) are not fully understood. Here, we report that toxic gapmer PS-ASOs containing modifications such as constrained ethyl (cEt), locked nucleic acid (LNA) and 2'-O-methoxyethyl (2'-MOE) bind many cellular proteins with high avidity, altering their function, localization and stability. We show that RNase H1-dependent delocalization of paraspeckle proteins to nucleoli is an early event in PS-ASO toxicity, followed by nucleolar stress, p53 activation and apoptotic cell death. Introduction of a single 2'-O-methyl (2'-OMe) modification at gap position 2 reduced protein-binding, substantially decreasing hepatotoxicity and improving the therapeutic index with minimal impairment of antisense activity. We validated the ability of this modification to generally mitigate PS-ASO toxicity with more than 300 sequences. Our findings will guide the design of PS-ASOs with optimal therapeutic profiles. |
<?php
final class DrydockRepositoryOperationListController
extends DrydockRepositoryOperationController {
public function shouldAllowPublic() {
return true;
}
public function handleRequest(AphrontRequest $request) {
return id(new DrydockRepositoryOperationSearchEngine())
->setController($this)
->buildResponse();
}
}
|
As of the end of June, Google are now offering the free "Google Apps for Nonprofits" cloud computing suite to qualified charities in Northern Ireland.
As Google Resellers primarily supplying not-for-profit organisations, we at Avec have been lobbying Google for years to extend this offering to Northern Ireland, and we are delighted that they have at long last done so.
Google Apps for Nonprofits provides all the same benefits and features as the "for Work" or business package which costs £35/year per user.
Google have recently announced that they will give preference to more secure websites as well as sites that offer mobile-compatible versions in their search rankings.
Priority in the rankings will go to sites that use encryption via an SSL certificate, making them less vulnerable to hacking.
A thumbnail guide to building your organisation’s mobile presence...
In IT as in fashion, the latest trends dominate discourse. Hardly a week passes now that I’m not asked by at least one client, ‘Should I have a mobile app?’
Of course, if the question really is, ‘Should I have a mobile communications and engagement strategy?’, the answer is an unqualified yes.
These days, you can be sure that half or more of your constituency or client base will want to access information from you using a mobile device, whether a smartphone or a tablet.
THIRD SECTORAs a not-for-profit company, Avec is an ideal solution provider to other not-for-profit organisations and social economy businesses, and we are a leading supplier of consultancy and support services to the voluntary and community sector in Northern Ireland.
CLIENT FOCUSAvec is committed to working with our clients to help them achieve their own strategic goals. You get on with your real work, and leave the rest to us.
EXCELLENT VALUEAvec strives at all times to provide the best possible value to its clients by delivering top quality services at reasonable cost. We have a long experience of providing enterprise-level solutions to not-for-profit organisations and small businesses with limited budgets. |
Q:
Vb.Net LINQ query nested list
I have list of cPoint objects. Every cPoint has list of cPosition objects. I have to make query that returns only cPoints whose cPositions meet the criteria and and every single cPoint must contain only those cPositions that meet the criteria. Is it possible with LINQ?
'classes
Public Class cPoint
Private _PointName As String
Public Positions As colPositions
'...
End Class
Public Class cPosition
Private _X As Double
Private _Y As Double
Private _Z As Double
Private _IntervalStart As Long
'...
End Class
Public Class cPoints
Inherits System.ComponentModel.BindingList(Of cPoint)
End Class
Public Class cPositions
Inherits System.ComponentModel.BindingList(Of cPosition)
End Class
The closest thing I did is this query but it does not return filtered cPoints. Every item in query has two objects: 1. filtered Point (with unfiltered child Positions) and 2. filtered Positions that belong to that Point.
Dim PtList As cPoints
'...
'my query
Dim query = (From pt In PtList
From pos In pt.Positions
Where (pos.IntervalStart < 222)
Select New With {Key .PT = pt,
Key .PTPOS = (From position In pt.Positions Where (position.IntervalStart < 222)).ToList}).Distinct
A:
So you want the points whose positions ALL have interval more than 222? Just use the All Linq method as the follow example:
Module Module1
'classes
Public Class cPoint
Private _PointName As String
Public Positions As cPositions
''' <summary>
''' Needed because we want to construct cPoints object using cPosition list within Linq
''' </summary>
''' <param name="posList"></param>
''' <remarks></remarks>
Public Sub New(posList As IEnumerable(Of cPosition))
Positions = New cPositions
For Each cp As cPosition In posList
Me.Positions.Add(cp)
Next
End Sub
'default
Public Sub New()
End Sub
End Class
Public Class cPosition
Private _X As Double
Private _Y As Double
Private _Z As Double
Private _IntervalStart As Long
Public Sub New(x As Double, y As Double, z As Double, iss As long)
_X = x
_Y = y
_Z = z
_IntervalStart = iss
End Sub
''' <summary>
''' Added a property to access from outside class
''' </summary>
''' <value></value>
''' <returns></returns>
''' <remarks></remarks>
Public Property IntervalStart As Long
Get
Return _IntervalStart
End Get
Set(value As Long)
_IntervalStart = value
End Set
End Property
End Class
Public Class cPoints
Inherits System.ComponentModel.BindingList(Of cPoint)
End Class
Public Class cPositions
Inherits System.ComponentModel.BindingList(Of cPosition)
End Class
Sub Main()
Dim ptlist As cPoints = New cPoints
Dim point1 = New cPoint
point1.Positions = New cPositions
point1.Positions.Add(New cPosition(1, 2, 3, 4))
point1.Positions.Add(New cPosition(1, 2, 3, 1000))
point1.Positions.Add(New cPosition(1, 2, 3, 2000))
point1.Positions.Add(New cPosition(1, 2, 3, 1))
Dim point2 = New cPoint
point2.Positions = New cPositions
point2.Positions.Add(New cPosition(1, 2, 3, 1))
point2.Positions.Add(New cPosition(1, 2, 3, 2))
point2.Positions.Add(New cPosition(1, 2, 3, 444))
point2.Positions.Add(New cPosition(1, 2, 3, 555))
ptlist.Add(point1)
ptlist.Add(point2)
'selects all the points in ptlist that have all their positions with interval start more than 222.
Dim result = From pt In ptlist
Where pt.Positions.All(Function(l As cPosition)
'put whatever condition here.
Return l.IntervalStart > 222
End Function)
Select pt
'select all the points. each point, will have all the positions that are less than 222.
Dim result2 = From pt In ptlist
Select New cPoint(pt.Positions.Where(Function(l As cPosition)
Return l.IntervalStart < 222
End Function))
For Each a In result2
Console.WriteLine(a.Positions.Count)
Next
End Sub
End Module
|
Damon Runyon Researchers
Meet Our Scientists
Monica E. McCallum, PhD
Dr. McCallum studies a compound, called alanosine, which exhibits anti-cancer activity against cells from sarcomas, mesothelioma, and pancreatic cancer. This compound is produced by a soil-dwelling bacterium. She seeks to elucidate how bacteria produce alanosine. Understanding the genes and enzymes that assemble this molecule will guide the discovery of additional novel chemotherapeutic agents that may be produced by bacteria. |
---
abstract: 'We calculate initial conditions for the hydrodynamical evolution in ultrarelativistic heavy-ion collisions at the LHC and RHIC in an improved next-to-leading order perturbative QCD + saturation framework. Using viscous relativistic hydrodynamics, we show that we obtain a good simultaneous description of the centrality dependence of charged particle multiplicities, transverse momentum spectra and elliptic flow at the LHC and at RHIC. In particular, we discuss how the temperature dependence of the shear viscosity is constrained by these data.'
address:
- 'Department of Physics P.O.Box 35, FI-40014 University of Jyväskylä, Finland'
- 'Helsinki Institute of Physics, P.O.Box 64, FI-00014 University of Helsinki, Finland'
- 'Department of Physics, P.O.Box 64, FI-00014 University of Helsinki, Finland'
- 'Frankfurt Institute for Advanced Studies, Ruth-Moufang-Str. 1, D-60438 Frankfurt am Main, Germany'
author:
- 'R. Paatelainen'
- 'K. J. Eskola'
- 'H. Holopainen'
- 'H. Niemi'
- 'K. Tuominen'
title: 'Next-to-leading order improved perturbative QCD + saturation + hydrodynamics model for $A$+$A$ collisions'
---
heavy-ion collisions, initial state, minijets, perturbative QCD
Introduction
============
In this talk we report the results from the recent studies [@Paatelainen:2013at; @Paatelainen:2012at], where we have extended the EKRT model [@EKRT] to next-to-leading order (NLO) in perturbative QCD (pQCD), and shown the viability of the model in describing the initial energy density of the produced quark-gluon plasma (QGP) in $A$+$A$ collisions at the LHC and RHIC. Our updated framework combines a rigorous NLO pQCD computation of the minijet transverse energy $(E_T)$ production with the saturation of gluons and hydrodynamics. Latest knowledge of NLO nuclear parton distributions (nPDFs) [@EPS09; @EPS09s] is utilized. Identifying the key parameters and charting the uncertainties of the model, we obtain a good simultaneous agreement with the charged particle multiplicities and hadron transverse momentum ($p_T$) spectra measured in Au+Au collisions at RHIC and Pb+Pb at the LHC.
The write-up is organized as follows: In Sec. 2 we present the updated NLO pQCD + saturation framework for the calculation of the minijet $E_T$. In Sec. 3, we discuss the saturation-wise transversally averaged initial conditions in the 5% most central collisions [@Paatelainen:2012at]. Finally, in Sec. 4, we discuss the extension to local saturation, which allows us to calculate the initial density profiles at all centralities [@Paatelainen:2013at], and through viscous hydrodynamics, study the temperature dependence of shear viscosity.
Minijet $E_T$ production
=========================
The minijet $E_T$ produced into a rapidity region $\Delta y$ in $A$ + $A$ collisions at an impact parameter $\mathbf{b}$ and above a $p_T$ scale $p_0$, can be computed as $$\frac{{\rm d} E_T}{{\rm d}^2 \mathbf{s}} = T_A(\mathbf{s} + \frac{\mathbf{b}}{2})T_A(\mathbf{s} - \frac{\mathbf{b}}{2})\sigma\langle E_T \rangle_{p_0,\Delta y,\beta},$$ where $\mathbf{s} = (x,y)$ is the transverse location, and $T_A(\mathbf{s})$ the nuclear thickness function with the Wood-Saxon nuclear density profile. The first $E_T$-moment of the minijet $E_T$ distribution $\sigma\langle E_T \rangle_{p_0,\Delta y,\beta}$ in NLO is computed as [@EKL; @ET; @Paatelainen:2012at] $$\sigma\langle E_T \rangle_{p_0,\Delta y,\beta} = \sum_{n=2}^{3}\frac{1}{n!}\int [{\rm DPS}]_n \frac{{\rm d}\sigma^{2\rightarrow n}}{[{\rm DPS}]_n}\tilde{S}_{n},$$ where the integrations take place in $4-2\epsilon$ spacetime dimensions, and the $2\rightarrow n$ differential partonic cross sections are denoted as ${\rm d}\sigma^{2\rightarrow n}/[{\rm DPS}]_n$. The infrared (IR) and collinear (CL) divergencies present in the partonic NLO cross sections can be regulated by computing the ultraviolet (UV) renormalized squared $2\rightarrow 2$ and $2\rightarrow 3$ scattering matrix elements of order $\alpha_s^3$, in $4-2\epsilon$ dimensions and in the $\overline{\text{MS}}$ scheme [@Ellis] (see also [@RistoPhD]). In getting from the IR/CL regulated and UV renormalized squared matrix elements to the physical quantities we apply the procedure by S. Ellis, Kunszt and Soper [@Kunszt]. The nPDFs [@EPS09; @EPS09s] together with the CTEQ6M parton distributions [@CTEQ6M:2002] are used in the computation of $\sigma\langle E_T \rangle_{p_0,\Delta y,\beta}$. The measurement functions $$\tilde{S}_n = \Theta(\sum_{i=1}^{n}p_{T,i} \geq 2p_0)E_{T,n}\Theta(E_{T,n}\geq\beta p_0),$$ where $E_{T,n} = \sum_{i=1}^{n}\Theta(y_i \in \Delta y)p_{T,i}$ and $\Theta$ is the step function, define the total minijet $E_T$ produced in $\Delta y$, and the hard scattering in terms of the minijet transverse momentum $p_{T,i}$ and the cut-off scale $p_0$. The hardness-parameter $\beta$ defines the minimum $E_T$ required in the interval $\Delta y$. As discussed in [@Paatelainen:2012at], any $\beta \in [0,1]$ is acceptable for the rigorous, IR and CL safe, NLO computation.
The saturation criterion for the minijet $E_T$ production in $A$+$A$ collision at non-zero impact parameters is formulated as [@Paatelainen:2013at] (see also the discussion in [@Paatelainen:2012at; @EKT1]) $$\label{eq: saturation}
\frac{{\rm d}E_T}{{\rm d}^2\mathbf{s}}(p_0,\sqrt{s_{{\rm NN}}},\Delta y,\mathbf{s},\mathbf{b},\beta) = \frac{K_{\rm sat}}{\pi}p_0^3\Delta y,$$ with an unknown proportionality constant $K_{\rm sat} \sim 1$. For given $K_{\rm sat}, \beta$ and cms-energy $\sqrt{s_{NN}}$, we solve the above equation for $p_0 = p_{\rm sat}(\sqrt{s_{NN}},A,\mathbf{s},\mathbf{b};K_{\rm sat},\beta)$ and obtain the total ${\rm d}E_T(p_{\rm sat})/{\rm d}^2\mathbf{s}$ produced in a rapidity region $\Delta y$.
pQCD + average saturation + ideal hydrodynamics
===============================================
Let us first discuss the NLO pQCD + averaged (non-local) saturation and ideal hydrodynamics framework introduced in [@Paatelainen:2012at]. The average saturation criterion for central $(\mathbf{b}=0)$ $A$+$A$ collisions is obtained by integrating over the transverse plane ${\rm d}^2\mathbf{s}$ in Eq. : $$\label{eq:avesaturation}
E_T(p_0,\sqrt{s_{NN}},\Delta y,\beta) = K_{\rm sat}R_A^2p_0^3\Delta y,$$ where $R_A$ is the nuclear radius. Once the average saturation momentum scale $p_0 = p_{\rm sat}(\sqrt{s_{NN}},A;K_{\rm sat},\beta)$ fulfilling the average saturation criterion above is found, the saturated minijet $E_T(p_{\rm sat})$ is converted into the initial QCD matter energy density as $$\epsilon(\tau_0) = \frac{{\rm d}E_T}{{\rm d}^2\mathbf{s}}\frac{1}{\tau_0\Delta y},$$ by assuming that the system thermalizes at formation, $\tau_0=1/p_{\rm sat}$. Furthemore, since the transversally-averaged saturation considered here does not fix the transverse profile for the produced initial energy density, we use either a binary collision (BC) or wounded nucleon (WN) transverse profile. The correlated parameters of the NLO pQCD calculation, $\beta$ and $K_{\rm sat}$, can be fixed based on the measured charged-particle multiplicity at one given cms-energy. When $\beta$ and $K_{\rm sat}$ are fixed, the initial conditions for any other cms-energy can be calculated.
5.5cm 5.5cm
In the left panel of Fig. \[fig:results1\] we show the average NLO minijet $E_T$ computed in the mid-rapidity acceptance $\Delta y=1$ with several different $(K_{\rm sat},\beta)$ pairs for the 5 % most central Au+Au collisions at the RHIC energy $\sqrt{s_{NN}} = 200$ GeV and Pb+Pb collisions at the LHC energy $\sqrt{s_{NN}} = 2.76$ TeV, as a function of the $p_0$ scale. For the implementation of the centrality selection here see [@Paatelainen:2012at]. The red bands show the range of values for $E_T$ and $p_0$ that reproduce the measured charged particle multiplicities [@Aamodt:2010pb; @CMSMUL:2011] (LHC) and [@PHENIXMUL:2005; @STARSPECT:2009; @BRAHMSMUL:2002] (RHIC) after an ideal-hydrodynamic evolution. Figure \[fig:results1\] shows directly that there are several different correlated parameter pairs $(K_{\rm sat},\beta)$ that reproduce the measured LHC and RHIC charged-particle multiplicites simultaneously.
Using then one possible parameter combination, $\beta = 0.75$ and $K_{\rm sat}=1$, we show in Fig. \[fig:results1\] (right) the computed charged-particle multiplicity ${\rm d}N_{\rm ch}/{\rm d}\eta$ and in Fig. \[fig:results2\] the $p_T$ spectra of $\pi^+, K^+,p$ and $\bar p$ in 5% most central Au+Au collisions at RHIC and Pb+Pb collisions at the LHC. Also, the comparison with the data measured at RHIC [@STARSPECT:2009; @PHENIXSPECT:2004; @BRAHMSSPECT:2004] and at the LHC [@ALICESPECT:2012] is shown.
5.9cm 5.9cm
pQCD + local saturation + viscous hydrodynamics
===============================================
Next, we discuss the results obtained in our recent study [@Paatelainen:2013at], where the initial energy density profile for any centrality and impact parameter was computed by using the new pQCD + local saturation + viscous hydrodynamics framework.
Once the solution $p_0 = p_{\rm sat}(\mathbf{s})$ of the transversally local saturation criterion, Eq. , is known for given $K_{\rm sat}$ and $\beta$, the local energy density is obtained as $$\epsilon(\mathbf{s},\tau_s) = \frac{{\rm d}E_T}{{\rm d}^2\mathbf{s}\tau_s\Delta y} = \frac{K_{\rm sat}}{\pi}p_{\rm sat}^4,$$ where the local formation time is $\tau_s = 1/p_{\rm sat}$. Note that the formation time $\tau_s$ is different at different points in the transverse plane. However, for the hydrodynamical evolution, we need the initial state at a fixed $\tau_0$. For this reason we need to evolve the energy density at all points to the same fixed $\tau_0$. Our strategy is as follows: First, we choose a minimum scale $p^{\rm min}_{\rm sat}=1$ GeV, corresponding a maximum time $\tau_{s }=1/p^{\rm min}_{\rm sat}$, for which we assume that we can still trust the pQCD calculation. Second, we evolve the energy densities from $\tau_s$ to $\tau_{0}$ using either Bjorken free streaming (FS) or the Bjorken hydrodynamic scaling solution (BJ). We take these two limits to represent the uncertainty in the evolution: In the free streaming case the transverse energy is preserved, while the other limit corresponds the case where a maximum amount of the transverse energy is reduced by the longitudinal pressure. The region below the minimum scale $p^{\rm min}_{\rm sat}$ is considered as a boundary. To obtain the energy density in this region we use an interpolation, which smoothly connects the FS/BJ-evolved pQCD energy density to the binary profile $\epsilon \propto T_AT_A$ at the dilute edge. For more details see Ref. [@Paatelainen:2013at].
For the hydrodynamical evolution, we take the 2+1 D setup introduced in [@Niemi:2011ix]. We use the lattice QCD and hadron resonance gas based equation of state s95p-PCE-v1 [@Huovinen:2009yb] with a chemical freeze out temperature $T_{\rm chem} = 175$ MeV. The freeze-out temperature is here always $T_{\rm dec} =100$ MeV. The parametrizations of the temperature dependent shear viscosity $\eta/s(T)$, for which we show the following results, are shown in Fig. \[fig:results3\]. The shear-stress and transverse flow are initially set to zero.
5.9cm
In Fig. \[fig: results4\]a and \[fig: results4\]b we show the computed centrality dependence of the charged hadron multiplicity in Pb+Pb collisions at $\sqrt{s_{NN}}=2.76$ TeV and in Au+Au collisions at $\sqrt{s_{NN}}=200$ GeV compared with the ALICE (LHC) [@Aamodt:2010pb], PHENIX [@PHENIXMUL:2005] and STAR [@STARSPECT:2009] (RHIC) data. In practice, the calculation in Figs. \[fig: results4\]a and \[fig: results4\]b are performed for each fixed $\{\beta, {\rm BJ}/{\rm FS}, \eta/s(T)\}$, and the remaining parameter $K_{\rm sat}$ is always tuned such that the multiplicity in the 0-5% most central collisions at the LHC is reproduced. Next, the obtained centrality dependence of the computed $p_T$-spectra of charged hadrons are shown in Figs. \[fig: results4\]c for the LHC and in Fig. \[fig: results4\]d for RHIC. The data are from [@Abelev:2012hxa] and [@Adams:2003kv; @Adler:2003au], correspondingly. Finally, in Figs. \[fig: results4\]e and \[fig: results4\]f we show the elliptic flow coefficients $v_2(p_T)$ at the LHC and RHIC, respectively. The data are from [@Aamodt:2010pa] (LHC) and [@Bai] (RHIC).
All the selected parameter combinations give a good description of the $p_T$ spectra simultaneously at the LHC and RHIC. The elliptic flow coefficients depend strongly on the $\eta/s(T)$ parametrization: an ideal fluid description would not give the correct $v_2(p_T)$, while with both $\eta/s(T)$ parametrizations considered here we get a good agreement with the data. Before engaging in a more complete global analysis for $\eta/s(T)$, the initial event-by-event density fluctuations need to be considered in this framework. This is work in progress.
5.9cm 5.9cm 5.9cm 5.9cm 5.9cm 5.9cm
Acknowledgments {#acknowledgments .unnumbered}
===============
This work was financially supported by the Jenny and Antti Wihuri Foundation (RP) and the Academy projects of Finland 133005 (KJE) and 267842 (KT). We thank CSC-IT Center Science for supercomputing time.
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|
About
Rupert Alexander Lloyd Grint (born 24 August 1988) is an English actor best known for playing Ron Weasley in the Harry Potter films. In December 2007, Grint was ranked #16 in the list of Forbes Top twenty earners under 25 with an annual earning of US$4 million.
Rupert Alexander Lloyd Grint (born 24 August 1988) is an English actor best known for playing Ron Weasley in the Harry Potter films. In December 2007, Grint was ranked #16 in the list of Forbes Top twenty earners under 25 with an annual earning of US$4 million. See Less |
Inadvertent thoracic duct catheterization during transjugular central venous cannulation. A case report.
An aberrant placement of a central venous catheter into the upper part of the thoracic duct with loop formation in the left innominate vein was observed on catheterizing via the left internal jugular vein. The misplacement, which did not have any deleterious effects, was caused by the atypical insertion site of the thoracic duct at the dorsocaudal wall of the left innominate vein and, possibly, by its incompetent closing valve. The stiffness of the nylon catheter used may also have been a contributory factor. The possible causes of this complication of central venous catheterization are discussed. The preferential use of the right internal jugular vein is stressed. |
My eyebrow hairs can grow fairly long and grooming them daily isn't actually a desirable option. For months I had to use this greasy, greasy, Vaseline to tame my brows (they take on a dirty powdery look if I don't).
Yesterday, I grabbed this little tube of gold in "Naturel" while Lancome was giving out gifts. It's nothing extraordinary, but it's light weight and allows your brows to breathe, you might need some touch ups but nothing too much.
I got the clear shade of this product. It keeps my brows in place with a flexible hold, and doesnt smudge my brow pencil which is a BIG plus. I dont use it every day, but when i go out with friends or to any special occasion I make sure to put this on, because I can make my brows look immpecable very quickly and easily. I definitely reccomend this :)
I have blonde hair and sparse thin eyebrows that are even blonder. This blonde brow color/mascara-like brush is terrific - makes my brows look natural and on the taupe-side vrs reddish as so many blonde eye brow colors tend to do. I am also very pleased at how easily I can apply it and have it quickly look both professional and natural.
Great for shaping and filling in your brows quickly. Just brush it on and your brows look great. Wipe off any excess before you use it so it doesn't get clumpy.Keeps my brows in place as well. Good product.
This is the best brow color/polish I've found to date and I'm loving the effects. I have blonde brows and this colors them perfectly, it also looks completely natural unlike a lot of other products I've tried over the years. It adds a bit of texture as well which creates a natural look and feel. Love it!!
I use this in Taupe and it's a good color match for my light brows. It colors the hairs and makes my brows look thicker. It's quick and easy to use. I've repurchased it many times. I wish it weren't so expensive but I've tried many other brands and like this one the best.
I have purchased this product numerous times. Is this the perfect brow product? No. It is definitely one of the easiest to get me out the door in less than 5 minutes.
Taupe is perfect for me--I'm fair with blond highlights and blue undertones--and it does okay with filling in.
I think for the must have brow set, it's definitely Anastasia's wax based brow powder with the setting gel. However, that product breaks, is more time consuming, and is too often sold in sets with crap that I don't need. The price is much higher, and as the product frequently breaks, it makes it much more expensive. Also, doesn't travel well.
This product does the job well enough, is fast, fills the brow okay, stays in place all day long (unlike smashbox) offers a natural look, travels extremely well, and if you pick it up on eBay, is a great deal.
Worth trying. If you get it in a department store and hate it, return it. If you get it on eBay, you're not out all that much money. |
Design and evaluation of a crystalline hybrid of molecular conductors and molecular rotors.
Combining recent concepts from the fields of molecular conductivity and molecular machinery we set out to design a crystalline molecular conductor that also possesses a molecular rotor. We report on the structures, electronic and physical properties, and dynamics of two solids with a common 1,4-bis(carboxyethynyl)bicyclo[2.2.2]octane (BABCO) functional rotor. One, [nBu(4)N(+)](2)[BABCO][BABCO(-)](2), is a colorless insulator where the dicarboxylic acid cocrystallizes with two of its monoanionic conjugated bases. The other is self-assembled by electrocrystallization in the form of black, shiny needles, with highly conducting molecular slabs of (EDT-TTF-CONH(2))(2)(+) (EDT-TTF = ethylenedithiotetrathiafulvalene) and anionic [BABCO(-)] rotors. Using variable-temperature (5-300 K) proton spin-lattice relaxation, (1)H T(1)(-1), we were able to assign two types of Brownian rotators in [nBu(4)N(+)](2)[BABCO][BABCO(-)](2). We showed that neutral BABCO groups have a rotational frequency of 120 GHz at 300 K with a rotational barrier of 2.03 kcal mol(-1). Rotors on the BABCO(-) sites experience stochastic 32 GHz jumps at the same temperature over a rotational barrier of 2.72 kcal mol(-1). In contrast, the BABCO(-) rotors within the highly conducting crystals of (EDT-TTF-CONH(2))(2)(+)[BABCO(-)] are essentially "braked" at room temperature. Notably, these crystals possess a conductivity of 5 S cm(-1) at 1 bar, which increases rapidly with pressure up to 50 S cm(-1) at 11.5 kbar. Two regimes with different activation energies E(a) for the resistivity (180 K above 50 and 400 K below) are observed at ambient pressure; a metallic state is stabilized at ca. 8 kbar, and an insulating ground state remains below 50 K at all pressures. We discuss two likely channels by which the motion of the rotors might become slowed down in the highly conducting solid. One is defined as a low-velocity viscous regime inherent to a noncovalent, physical coupling induced by the cooperativity between five C(sp3)-H···O hydrogen bonds engaging any rotor and five BABCO units in its environment. The rotational barrier calculated with the effect of this set of hydrogen bonds amounts to 7.3 kcal mol(-1). Another is quantum dissipation, a phenomenon addressing the difference of dynamics of the rotors in the two solids with different electrical properties, by which the large number of degrees of freedom of the low dimensional electron gas may serve as a bath for the dissipation of the energy of the rotor motion, the two systems being coupled by the Coulomb interaction between the charges of the rotors (local moments and induced dipoles) and the charges of the carriers. |
Rauwolscine hydrochloride is a potent and specific alpha2 adrenergic receptor antagonist with a Ki of 12 nM. IC50 & Target: Ki: 12 nM (alpha2 adrenergic receptor)[1]In Vitro: [3H]Rauwolscine binding to alpha2 adrenergic receptor is reversible, stcreospccific, and saturable. [3H]Rauwolscine specifically labels both the high and low affinity states of the alpha2 adrenergic receptor in brain membranes[1]. [3H]Rauwolscine also behaves as a 5-HT1A receptor agonist and this conclusion is compatible with earlier functional studies, indicating that rauwolscine (as well as yohimbine) has agonistic properties at the level of 5-HT autoreceptors[2]. When using [3H]5-HT as a radioligand, rauwolscine is determined to have relatively high affinity for the human receptor (Ki human=14.3 nM, Ki rat=35.8 nM)[3]. Saturation studies shows that the affinity of [3H]Rauwolscine is similar in mouse, rat, rabbit, dog (2.33-3.03 nM) except man where it is significantly higher (0.98 nM) [4]. |
D1. 22 rounds on rings for pullups.
D2. About 16 minutes, still slow reps with a pause at the top and bottom of each rep.
D3. 8:33. I did the pullups at 10,6,6,5 and 5. Pushups started with 27, then petered out with much smaller sets. Squats were straight through, though the pace slowed considerably around #40.
On Tuesday I will be getting blood drawn for a physical. I am interested to see how the diet and exercise have affected blood sugar and cholesterol. Those have been trending badly the last few years.
D1. 25 rounds, pullups on rings. I am going to try to eke out 27 next time.
D2. Around 15-16 minutes. I enjoy going very slowly for each rep on these days. I am keeping the rest period to two minutes from now on. Takes a while, but a nice change of pace.
D3. 7:17. I surprised myself here. Over a minute off from last week. Did 12, 8, 6 and 6 for pullups. Push ups started with 24, I planned on doing 16 after that but had to make smaller sets. Squats felt better this week.
Weight is now 175 +/- a pound. Just turned 42. I don't have the nerve yet to post photos like Cheapo does.
Wow, that week showed really good improvement for times! I am thinking about scaling down rest periods for every week I stay on the same level, maybe 30 seconds a week, or maybe just take it down to a flat 2 minutes.
Will you continue with 2 minutes for when you move up a level? I guess D2 is more about strength, and not about time, so can't hurt? How hard was the transition?
Thank you, art50. If and when I level up my D2 rest period will probably go to three minutes. Shortening the rest periods will come over time and incrementally. I wouldn't care if I didn't think somehow that doing so will help cut down the D3 time. I suspect it might.
The way I've been doing the D2 breaks on the last two levels is to do strict 3 minute breaks until I get the total exercise time down to 5 minutes. Then I'll go down to strict 2 minute breaks. If I get it down to 5 minutes again, I'll shorten the breaks further. This provides another nice intermediate goal for the D2 workout in between the long struggle to level up.
D1. 22 rounds. I know I could have done at least a little better. I did keep my form pretty strict on all reps.
D2. About fifteen. Very strict form, slow and controlled. I didn't need to break the push-up position on any of those. Usually I feel like taking a break during push-ups on the fourth and fifth rounds.
D3. 5:17. I surprised myself and did the pull ups 20, 6 and 6. I also got through the push-ups quicker by shortening breaks. I think if I knew how close I was I might have found it in me to bust them out quicker. I really want those 17 seconds!
D1, 27 rounds. I was determined to increase my D1 number, inspired by the likes of Rosencrantz. I used a Kettlebell timer app on my iPad. I set the work periods at 45 seconds with 0 second rest periods for 27 cycles. I set another timer for 20 minutes, just to make sure. Having the big iPad relentlessly chugging along with the countdown kept me more focused. I found if I sped throug the reps, I could get about 14 seconds to catch my breath. If I took my time, I didn't get as gassed but had to immediately begin the next round. Next week I will set the work periods at 42 seconds, which should give me 28 rounds after 20 minutes. As long as I stay on L6, I will whittle it to 40 second work periods.
I got very short of breath during pull-ups. Knowing I came so close last week gave me the extra shove to get through the rest. I kept the push up breaks very short, 3-4 deep breaths. Now that level 6 is in the bag, I'm taking a week at level 3 then going to level 7. We had our first dusting of snow in my area. Can't wait to get skiing again. |
Q:
Determine tile identity of tile set displayed on Google Maps/OpenStreetMap
I'm not sure if this is best way of approaching this, so I will explain where I'm coming from first.
I want to load data onto my webpage containing a map based off a lat/long point. The only way I know how to do this is to constantly be getting the a lat/lng point in the displayed map. Obviously this isn't very efficient since I either need to keep track of this point, or constantly be polling it. Each time I had the updated this point, I'd have to do some sort of processing to determine it's map location, which would add even more inefficiency. When I had that, I could then proceed to load my data.
My idea was that if I could pull down an id of map tiles of a particular region at a set zoom level, then I wouldn't need to do the crazy/complicated lat/lng processing. But, my stumbling block is that I don't know of any way this is possible.
A:
So you want the Quadtile?
Google Map APi (v3) Quadtree visualized
http://koti.mbnet.fi/ojalesa/quadtree/quadtree_intro.htm
Credit to Esa
|
Q:
accessing python dictionary
I am writing code that will search twitter for key words and store them in a python dictionary:
base_url = 'http://search.twitter.com/search.json?rpp=100&q=4sq.com/'
query = '7bOHRP'
url_string = base_url + query
logging.info("url string = " + url_string)
json_text = fetch(url_string)
json_response = simplejson.loads(json_text.content)
result = json_response['results']
print "Contents"
print result
The resulting dictionary is :
Contents[{
u 'iso_language_code': u 'en',
u 'text': u "I'm at Cafe en Seine (40 Dawson Street, Dublin) w/ 2 others. http://4sq.com/7bOHRP",
u 'created_at': u 'Wed, 06 Oct 2010 23:37:02 +0000',
u 'profile_image_url': u 'http://a1.twimg.com/profile_images/573130785/twitterProfilePhoto_normal.jpg',
u 'source': u '<a href="http://foursquare.com" rel="nofollow">foursquare</a>',
u 'place': {
u 'type': u 'neighborhood',
u 'id': u '898cf727ca504e96',
u 'full_name': u 'Mansion House B, Dublin'
},
u 'from_user': u 'pkerssemakers',
u 'from_user_id': 60241195,
u 'to_user_id': None,
u 'geo': None,
u 'id': 26597357992,
u 'metadata': {
u 'result_type': u 'recent'
}
}]
Status: 200 OK
Content - Type: text / html;charset = utf - 8
Cache - Control: no - cache
Expires: Fri, 01 Jan 1990 00: 00: 00 GMT
Content - Length: 0
How can I access the 'from_user' and what is the 'u' before the key and value?
A:
result[0][u'from_user']
The u prefix means that it's a unicode instead of a str.
|
Sources said there were fears Abedi may have taken advantage of the conflict to make the simple journey across the Med to Syria without alerting the British authorities.
One revealed: “His potential ties to Syria now very much forms one line of inquiry.”
Cops are also probing whether Abedi, who is believed to have been known to MI5, acted alone or as part of a larger extremist network to carry out the worst terror attack Britain has seen since the 7/7 London bombings.
And Met Police Assistant Commissioner Mark Rowley admitted there were “gaps in our knowledge” about Abedi and the PM said it was possible a “wider group of individuals” could have been involved in the “cowardly” attack.
Eight-year-old schoolgirl Saffie Roussos was named as one of the victims along with student Georgina Callander, 26-year-old John Atkinson and brave aunt Kelly Brewster, 32, who shielded her niece from the deadly blast.
Mums Alison Howe, 44, and Lisa Lees, 43, were also killed while waiting for their kids to leave the show and teenager Olivia Campbell who sparked an emotional TV appeal have also been listed among the dead.
The latest victims confirmed dead are Angelika and Marcin Klis, a Polish couple whose daughter launched a desperate appeal to find them yesterday.
Cops swooped on two addresses in Manchester after the deadly nail bomb blast
US security sources, citing British intelligence officials, said Abedi was born in 1994 to parents who had fled to the UK to escape the Gaddafi regime.
His dad is understood to have left the UK in 2011 to try and overthrow the Libyan leader.
The Mail Online reports when Gaddafi was killed the family put a massive flag on the roof of their house.
Neighbour Debbie Smith, 53, said: “I think they were glad he was dead.”
Home Secretary Amber Rudd has said Abedi was known "up to a point" to the intelligence services.
When asked in an interview with the BBC this morning if the attacker was a "lone wolf" or not Rudd said: "It seems likely, possible, that he wasn’t doing this on his own."They are believed to have emigrated to London before moving to south Manchester.
Abedi’s family have told of their horror at finding out he was behind the massacre.
They described the fanatic as a “brilliant” footballer who loved Manchester United and Spanish giants Real Madrid.
One male relative, who asked not to be named, told The Sun how he had seen Abedi just ten days ago looking “happy, relaxed and smiling” as he secretly plotted the attack.
Thousands paid their respects to the victims at a vigil in Albert Square outside Manchester Town Hall
Dr Sam Grogan, the university's Pro-Vice Chancellor Student Experience, said: "All at the University of Salford are shocked and saddened by the events of last night. Our thoughts are with all those involved, their families and their friends.
"We have provided, and continue to provide, support to all students and staff who have been affected."
Abedi and his brother reportedly worshipped at Didsbury mosque, south Manchester, where their father was a "well-known figure".
Mosque trustee Fawaz Haffar said Abedi's dad used to perform the azan, the call for prayer before 1,000 of the faithful and his brother worked as a volunteer.
When asked whether he had ever seen the terrorist praying at the mosque, he said: "He probably did, I have never seen him, I don't know him.
"I came earlier to ask any of the employees whether they knew him, people said they don't know him. There are many mosques, he may be attending another mosque. I honestly do not know."
Salman reportedly stopped going to the mosque in 2015 as he objected to anti Isis comments, according to Mohammed Saeed, the imam of Didsbury Mosque.
He said: “Salman used to come to the mosque occasionally, he wasn’t particularly friendly towards me because he didn’t like my anti-IS sermons.
“He didn’t like what I was saying and showed me the face of hate. He came to the mosque less and less after that.”
ARE YOU THE LUCKY WINNER?
FANATICS FLOOD BACK TO BRITAIN
ISIS jihadi brides are ordered back to Britain as thugs face oblivion in Syria and Iraq
Following an emergency Cobra meeting, Mrs May said the independent body which sets the threat level has increased it from “severe” to “critical”.
She said: "This means that their assessment is not only that an attack remains highly likely but that a further attack may be imminent.
The defiant PM described the massacre as “callous and cowardly” and declared “terrorists will never win”.
“His victims were innocent children, young people and their families - our thoughts and prayers are with them all.
"I want to re-iterate what I said about the professionalism of the emergency services and the bravery of the people in Manchester.
"Through their actions, they proved that cowardice will always be defeated by bravery, that evil can be overcome by good and that our values, the liberal, pluralistic values of Britain, will always prevail over the hateful ideology of the terrorists.
ISIS said in a statement published by its Amaq News Agency (a news outlet linked to ISIS in Syria) : “With Allah's grace and support, a soldier of the Khilafah managed to place explosive devices in the midst of the gatherings of the crusaders in the British City of Manchester.
"This was in revenge of Allah’s religion, in an endeavour to terrorise the mushrikin, and in response to their transgressions against the lands of the Muslims.
Fans flee from seats in the Manchester Arena as panic spreads after explosion
“We just grabbed each other and got away. One lass was laying in her mother’s arms. I’m not sure if she has collapsed in shock or was injured.”
Abby Mullen said she was also leaving the venue at the time of the blast and refuted earlier claims it had been caused by a speaker or balloon, which had circulated on social media after the explosion.
She wrote on Facebook: "As we where leaving a bomb or explosion went off centimetres in front of me.
"Peoples skin/blood&faeces where everywhere including in my hair & on my bag. I'm still finding bits of god knows what in my hair. I am fine & back in my hotel I hope everyone involved and in front of me is okay."
Chris Parker, 33, was walking through the station towards the box office when the explosion went off.
He said he saw at least six people seriously injured on the floor and told The Sun: “I was walking through and one huge bang went off.
“There was nuts and bolts flying everywhere, and also human flesh. It was just one bang and a white flash. I treated a woman called Pauline. I’ve got blood on my hands. It was like a war zone inside where the box office is.
“There looked to be at least six people potentially fatally wounded. I saw one woman’s leg off. It is mayhem.” |
A Sad Day at the National Zoo
It was a somber Sunday for the National Zoo in Washington, D.C. After hearing sounds of distress from its mother, Mei Xiang, zookeepers discovered the giant-panda cub born last weekend had died.
The zoo workers who took care of Mei Xiang and her cub are puzzled by the cub’s death. They are also very upset. "Every loss is hard," said National Zoo director Dennis Kelly. "This one is especially devastating."
A Sad Discovery
CHIP SOMODEVILLA—GETTY IMAGES
National Zoo officials are devastated from the loss of the panda cub.
Zookeepers were alerted when Mei Xiang made an unusual honking noise on Sunday morning. Upon arriving at the panda’s den, keepers found the 6-day-old cub dead. National Zoo officials say the cub had abnormalities in its liver, but they could not immediately determine a cause of death. The cub had shown no signs of suffering or infection. Officials expect to know more after a medical examination in the next two weeks. The tiny cub had not yet been named. Zoo officials had planned to follow Chinese custom and give the cub a name after 100 days.
Fragile Cubs
Panda cubs are extremely delicate infants. They are born entirely blind and covered with only a thin coat of fur. Most are not longer than five inches at birth. Developments are slow in a cub’s early days. A baby panda cannot see for more than a month after being born and cannot walk for the first 75-80 days of its life. It depends entirely on its mother for guidance and comfort.
The relationship between a panda cub and its mother is very important but can also be dangerous. Grown female pandas are about 1,000 times heavier than their cubs. While attempting to nurse, mothers can accidentally crush their fragile young. Though this tragic accident is common, the cub found at the National Zoo showed no signs of trauma. Its heart and lungs were intact, confirming that Mei Xiang did not crush the cub.
Officials say Mei Xiang is not acting like her usual self but is slowly beginning to eat again. She is reported to be holding a plastic toy at night as comfort for the loss of her cub. Zookeepers will continue to watch and monitor Mei Xiang until she returns to her normal behavior. The National Zoo hopes to learn from this tragedy and gain a better understanding of cub health in giant pandas. |
Afghan youth throw stones toward US soldiers standing at the gate of Bagram airbase during a protest against Koran desecration at Bagram, about 60 kilometres (40 miles) north of Kabul, on February 21, 2012. Afghan protestors firing slingshots and petrol bombs besieged one of the largest US-run military bases in Afghanistan, furious over reports that NATO had set fire to copies of the Koran. Guards at Bagram airbase responded by firing rubber bullets from a watchtower, an AFP photographer said as the crowd shouted 'Allahu akbar, Allahu akbar' (God is greater). (Getty Images)
BAGRAM, Afghanistan (Reuters) - About 2,000 Afghans protested outside the main U.S. military base in Afghanistan on Tuesday over a report that foreign soldiers improperly disposed of copies of the Koran.
U.S. helicopters fired flares to try to break up as many as 2,000 demonstrators who massed outside several gates to the base, chanting anti-foreigner slogans and throwing stones.
Roshna Khalid, the provincial governor's spokeswoman, said copies of the Muslim holy book had been burnt inside Bagram airbase, an hour's drive north of the capital Kabul, citing accounts from local laborers.
"The laborers normally take the garbage outside and they found the remains of Korans," Khalid said.
More...
Thousands of Afghans go apeshit over a report that NATO soldiers may have improperly disposed of Korans. At the same time, nobody cares about hundreds of Korans burned in a Shiite mosque torched by Sunnis in Iraq Call it a Muslim paradox. |
INTRODUCTION
============
The idea of generating a logo from aligned sets of sequences was introduced in 1990 by Schneider and Stephens ([@gks469-B1]). The intention of a sequence logo is to concentrate into a single plot the general consensus, the order of predominance of residues at every position, the relative frequencies of every residue at every position, the amount of information present at every position and significant locations. This logo is then able to present all of the relevant information to the viewer in a fast and concise manner.
Several webservers exist to generate sequence logos from MSA's ([@gks469-B2; @gks469-B3; @gks469-B4; @gks469-B5]). All these servers suffer from different limitations in the handling sequence redundancy and low number of observations. Moreover, to the best of our knowledge, all public sequence logo servers, with the exception of the *Icelogo* ([@gks469-B4]) and *two-sample* logo ([@gks469-B5]) methods, focus on displaying the position-specific enrichment of amino acids, discarding the equally valuable information related to amino acid depletion. *Seq2logo* aims at resolving these issues allowing the user to include sequence weighting to correct for data redundancy, pseudo counts to correct for low number of observations ([@gks469-B6; @gks469-B7; @gks469-B8]) and five different logotype representations each capturing different aspects related to amino acid enrichment and depletion. In addition to the usual Shannon logo ([@gks469-B9]), *Seq2Logo* includes the option to create Kullback--Leibler (KL) ([@gks469-B10]) logos where the depleted (under-represented) amino acids are represented on the negative *y*-axis. Besides the conventional KL logo, *Seq2Logo* can also display a weighted KL logo, where the relative height of each amino acid is proportional to the log-odds ratio and a probability weighted KL logo, where the relative height of each amino acid is proportional to the product of the probability and log-odds ratio. Finally, inspired by the work of Fujii *et al*. ([@gks469-B11]), *Seq2Logo* also includes an option to visualize PSSM (position-specific scoring matrix) logos, where the height of a bar is given by the sum of the absolute value of the PSSM weight matrix values and the height of a given amino acids is proportional to the absolute value of the weight matrix score. In particular, the weighted KL logo provides a visual and highly intuitive representation of both amino acid enrichment and depletion in for instance receptor binding motifs. Besides allowing input in the format of peptides and MSAs, the *Seq2Logo* server accepts inputs such as Blast sequence profiles, providing easy access for non-expert end-users to characterize and identify functionally conserved/variable amino acids in any given protein of interest.
MATERIALS AND METHODS
=====================
*Seq2Logo* implements two strategies to improve the accuracy of the estimated sequence logo. The first strategy is sequence weighting which corrects for data redundancy. The second strategy is pseudo counts which correct for a low number of observations. Sequence weighting is implemented as described in ([@gks469-B6],[@gks469-B8]) and pseudo counts as described in ([@gks469-B7]). For details, see [Supplementary Data](http://nar.oxfordjournals.org/cgi/content/full/gks469/DC1).
In a sequence logo, the height of the bar is equal to the information content at each amino acid position. The information content is calculated using the relation , where *p~a~* and *q*~a~ are the observed probability (calculated from the data) and background probability, respectively, of the amino acid a. If an equiprobable background amino acid distribution is applied, a conventional Shannon sequence logo is displayed. If a background amino acid distribution reflecting the prevalence of the different amino acids is applied, a Kullback--Leibler sequence logo is displayed. The choice of the Kullback--Leibler logotype in *Seq2Logo* not only provides correction for the uneven distribution of amino acids, but also expresses the depleted amino acids (where *p*~a~ \< *q*~a~) on the negative side of the *y*-axis. This enables the user to quickly identify enriched and depleted (under-represented) amino acids. To enhance the identification and information of the depleted amino acids, *Seq2Logo* includes another logotype called weighted Kullback--Leibler. This logo type presents each individual amino acid proportional to its relative log-odds score \[log~2~(*p*~a~/*q*~a~)\]. Another logotype is included called probability weighted Kullback--Leibler, where the relative height of each individual amino acid is proportional to *p*~a~ · log~2~(*p*~a~/*q*~a~). Finally, *Seq2Logo* includes an option to display PSSM-logos ([@gks469-B11]), where the height of a bar is equal to the sum of the absolute value of the PSSM weight matrix values and the height of each amino acid is proportional to the absolute value of the weight matrix score (with negative values displayed on the negative *y*-axis).
THE WEB SERVER
==============
The *Seq2Logo* server has a simple interface that allows non-expert users to generate and customize accurate logos from any amino acid sequence data of interest.
Input
-----
The interface is split in two parts for easy overview. The first and the most important part is submission ([Figure 1](#gks469-F1){ref-type="fig"}, left panel). Here, the user can upload or paste in the input data in addition to specifying the logotype (Shannon, Kullback--Leibler, Weighted Kullback--Leibler, probability weighted Kullback--Leibler or PSSM-logo) and conditions for handling the input data (sequence weighting and pseudo counts). *Seq2Logo* can read sequence data in the following formats: Fasta, ClustalW, Raw peptide sequences and Weight/Blast matrix (for details on each format refer to [Supplementary Data](http://nar.oxfordjournals.org/cgi/content/full/gks469/DC1)). The detection of the format happens automatically through the identification of key elements from each format. In the submission part, the user further specifies which output files should be created. In the graphical layout ([Figure 1](#gks469-F1){ref-type="fig"}, right panel), the user can customize the graphical layout of the logo plot. Page size sets the resolution of the image and stacks per line and lines per page determine how the logo should look. Assigning each amino acid symbol to a color defines the amino acid colors. There are six colors to choose from: Red, green, blue, yellow, purple or orange. All amino acids left out will be black. Several predefined color-schemes are available. The user can also rotate the position numbers on the *x*-axis and hide various features of the graph. Figure 1.The submission (left) and graphical layout (right) part of the web interface. In the submission part the user specifies the input file, the format of output files, the logotype and the conditions for the handling of the input data. In the Graphical Layout part, the user customizes the graphical layout of the logo plot; page size, stacks per line, lines per page, colours, bars, rotation of position numbers and title.
Output
------
An example of the output from *Seq2Logo* generated using the input specifications from [Figure 1](#gks469-F1){ref-type="fig"} is shown in [Figure 2](#gks469-F2){ref-type="fig"}. The figure shows on the positive *y*-axis, the amino acids enriched at each peptide position and on the negative *y*-axis the corresponding depleted amino acids. In this case, the logo is calculated from a set of 13 artificial peptide sequences proposed to bind the HLA-A\*02:01 class I major histocompatibility complex (MHC) molecule. This molecule has a binding motif with strong interactions at P2 and P9 both positions with prevalence for hydrophobic amino acids ([@gks469-B12]). Figure 2.Output from *Seq2Logo*. The upper panel shows the sequence logo calculated from a set of 13 artificial peptide sequences using the specification defined in [Figure 1](#gks469-F1){ref-type="fig"} (sequence weighting using clustering, pseudo count with a weight of 200 and logotype as Kullback--Leibler). Enriched amino acids are shown on the positive *y*-axis and depleted amino acids on the negative *y*-axis. The lower panel gives the position-specific (log-odds) scoring matrix (PSSM) calculated by *Seq2Logo*. Each line corresponds to a position and gives the consensus amino acid and the log-odds scores for the 20 amino acids.
One of the distinct powers of *Seq2Logo* is its ability to deal with data redundancy and low number of observations. To the best of our knowledge, no other public sequence logo servers share this ability. In [Figure 3](#gks469-F3){ref-type="fig"}, the cruciality of these features for the generation of accurate sequence logos describing a binding motif is illustrated. The figure displays Shannon sequence logos generated by *Seq2Logo*, using different option to improve the accuracy, as well as sequence logos generated by *Weblogo* ([@gks469-B2]) and *EnoLOGOS* ([@gks469-B3]). When comparing the logos calculated from the small sample data set with the logo obtained from the larger data set, it is apparent that the inclusion of sequence weighting and pseudo counts have a significant positive impact on the overall accuracy of the binding motif description. Figure 3.Sequence logos generated from small sequence samples. All logos except the right logo in the lower row were calculated from a set of 13 artificial peptide sequences proposed to bind HLA-A\*02:01 (see [Figure 1](#gks469-F1){ref-type="fig"}). The upper row shows logos calculated by *Seq2Logo* using: (i) without sequence weighting and pseudo count correction, (ii) sequence weighting by clustering and no pseudo count correction and (iii) sequence weighting by clustering and pseudo count correction with a weight on prior of 200. The lower row shows logos calculated using: (i) *Weblogo* with 'small sample correction', (ii) *EnoLOGOS* and (iii) *Seq2Logo* from a set of 229 HLA-A\*02:01 9mer ligands downloaded from the SYFPEITHI database ([@gks469-B12]) with sequence weighting by clustering and pseudo count correction with a weight on prior of 200.
The other distinct feature of *Seq2Logo* compared to most other public sequence logo server is the display of depleted amino acids on the negative *y*-axis in Kullback--Leibler logos. Most sequence logo servers display the relative height of the different amino acids in a manner proportional to their frequency, thus displaying only the position-specific enrichment of amino acids, discarding the equally valuable information related to amino acid depletion. To improve on this issue, *Seq2Logo* includes a series of distinct logotypes (see [Figure 4](#gks469-F4){ref-type="fig"}). In addition to the usual Shannon logo, *Seq2Logo* includes the option to create Kullback--Leibler (KL) logos where depleted amino acids are represented on the negative *y*-axis. Besides the conventional KL logo, *Seq2Logo* can also display a weighted KL logo, where the relative height of each amino acid is proportional to the log-odds ratio and a probability weighted KL logo, where the relative height of each amino acid is proportional to the product of the probability and log-odds ratio. In particular, the weighted KL logo provides a visual and highly intuitive representation of both amino acid enrichment and depletion in for instance receptor binding motifs. Besides these information-based logotypes, *Seq2Logo* offers the possibility of displaying PSSM-logos calculated either from a log-odds weight matrix derived by *Seq2Logo* from a multiple sequence alignment or from a user-defined PSSM. In the PSSM-logo, the height of the bar and amino acid at each position is proportional to the absolute value of the PSSM weight matrix values. This logotype is particularly powerful when illustrating depletion of a small set of amino acids form otherwise variable positions in a sequence motif. One such example is N-linked glycosylation sites that are known to have the motif N-X-S/T where X can be any amino acid but P. Visualizing this motif as an information-based sequence logo will not capture the depletion of P at the position between N and S/T as all amino acids except P are found at this position, hence making the overall information content very small. On the other hand, visualizing the motif as a PSSM-logo, the strong depletion of P at the position between N and S/T becomes apparent (see [Figure 5](#gks469-F5){ref-type="fig"}). Figure 4.The different logotype representations covered by *Seq2Logo*. Sequence logos generated from at set of 13 artificial peptide sequences proposed to bind HLA-A\*02:01 (see [Figure 1](#gks469-F1){ref-type="fig"}). All logos were calculated using clustering and pseudo counts with a weight on prior at 200. Upper row, left panel: Shannon, right panel: Kullback--Leibler. Lower row left panel: weighted Kullback--Leibler, right panel: probability weighted Kullback--Leibler. Figure 5.PSSM-logo for the N-linked glycosylation motif. The motif was calculated from a set of 2128 unique experimentally verify N-glycosylation sites downloaded from the UniprotKB protein database. Only peptide fragments of length 11 (5 before and 5 after the N) were included in the analysis.
A powerful way to characterize sequence conservation/variation within a protein family is by use of sequence profiles. Such sequence profiles can be obtained using Psi-Blast ([@gks469-B7]). *Seq2Logo* accepts input of such sequence profile in the Blast profile format allowing easy access for non-expert end-users to characterize and identify functionally conserved/variable amino acids in any given protein of interest. Blast sequence profile can be generated either in-house using a command like 'blastpgp −d db −e 0.00001 −j 4 −Q blastprofile −i fasta −o out', where d*b* is the sequence database used to search by Blast, −*e* defines the *e*-value cut-off for significant hits, −*j* defines the number of Psi-blast iterations, −*i* is the input file in FASTA format, −*Q* is the output file for the blast profile (the file to be used by *Seq2Logo* to visualized the sequence profile) and −o is the file for the blast output. Alternatively, the *Blast2logo* webserver ([www.cbs.dtu.dk/biotools/Blast2logo](www.cbs.dtu.dk/biotools/Blast2logo) (14 May 2012, date last accessed)) can be used to obtain the sequence profile. [Figure 6](#gks469-F6){ref-type="fig"} demonstrates the use of *Seq2Logo* to display a sequence profile for Rhamnogalacturonan acetylesterase (PDBid 1K7C, chain A). The active site of 1K7C.A is defined by the residues S9, G42, N74, D192 and H195 ([@gks469-B13]). All these residues are highly conserved in the sequence logo (in fact they are among the 10 residues with the highest information content, data not shown). Another striking observation from the logo is the lack of sequence information in the area between positions 75 and 105, suggesting that this part of the protein is highly variable (most likely an insertion) within the protein family. Both these observations illustrate the power of sequence profiles combined with *Seq2Logo* as a simple tool to identify functionally important residues and insertions in protein sequences. Figure 6.*Seq2Logo* visualization of a Blast sequence profile for 1K7C chain A. The Blast profile was obtained using Blast2logo ([www.cbs.dtu.dk/biotools/Blast2logo](www.cbs.dtu.dk/biotools/Blast2logo) (14 May 2012, date last accessed)) searching against the nr70 sequence database with default options. The active site of 1K7C:A is defined by the residues S9, G42, N74, D192 and H195 ([@gks469-B13]). All these residues show up as highly conserved in the sequence logo.
INTEGRATING *SEQ2LOGO* WITH OTHER PREDICTION SERVERS
====================================================
To improve the usability and make *Seq2Logo* able to cooperate with other programs and servers, a form-handler was implemented on the server that makes it possible to send input data directly to *Seq2Logo*. This simple form-handler allows a quick and easy transfer of data to *Seq2Logo* and defines a platform for using *Seq2Logo* as a visualization tool for other programs. The form data sent to *Seq2Logo* is inserted directly into the input field. An instruction of how to implement this transfer can be found at: <http://www.cbs.dtu.dk/biotools/Seq2Logo-1.0/bin/easytransferbutton.html> (14 May 2012, date last accessed).
DISCUSSION AND CONCLUSION
=========================
Sequence logos provide a powerful way to visualize amino acid preferences in a receptor binding motif, as well as sequence conservation/variation and the location of functionally essential residues in multiple sequence alignments. Accurate estimation of a sequence motif is often compromised by data redundancy and low number of observations. Inappropriate handling of these issues can lead to inaccurate estimation of the sequence motif and subsequent poor sequence logo representation. Moreover, the majority of sequence logo webservers have a poor visualization of the information related to amino acid depletion since they focus on displaying the position-specific enrichment of amino acids.
Here, we have proposed a novel sequence logo generator, *Seq2Logo* that aims at addressing these shortcomings and allow non-expert end-users, via an easy to use web-interface, to generate accurate sequence logos from protein sequence data. We have demonstrated that *Seq2Logo* can deal with sequence redundancy and low number of observations in a manner superior to that of other public available sequence logo generators like *Weblogo* and *ENOlogos*. Besides the conventional Shannon sequence logo, *Seq2Logo* also incorporates distinct logotypes where depleted amino acids are displayed on the negative *y*-axis. These logotypes offer a unique possibility for *Seq2Logo* to display for instance receptor-binding motifs in a format that highlights both favored and disfavored amino acids at the different positions in the motif.
A sequence profile is a powerful way to capture position-specific information about sequence conservation/variation within a protein family. *Seq2Logo* accepts sequence profiles in the Blast format as input and can in a very simple and intuitive manner be used in combination with Blast as a tool to visualize sequence profiles and identify functionally conserved/variable amino acids in any given protein of interest.
Finally, to allow other servers dealing with multiple sequence alignments and binding motifs to directly cooperate with *Seq2Logo* and benefit from its improved features, the server includes a form-handler that enables communication with *Seq2Logo* via a simple html form. This feature has allowed for a simple and effective improvement to two of our own webservers *NNAlign* ([@gks469-B14]) and Blast2logo ([www.cbs.dtu.dk/biotools/Blast2logo](www.cbs.dtu.dk/biotools/Blast2logo) (14 May 2012, date last accessed)), and we believe this to be an additional feature that will become very useful for other webserver developers within the field of for instance receptor-binding motif characterization.
In its current form, *Seq2Logo* can only handle amino acid input data. The reason for this limitation is that most of its unique features like pseudo count estimates from Blosum substitution matrices and sequence weighting of are specific for amino acid data. The ability to also handle nucleic acids will be a part of a future update for the method.
In conclusion, we believe *Seq2Logo* to be an important and novel tool for non-expert users to construct accurate sequence logos describing receptor binding motifs and sequence variations in multiple sequence alignments.
SUPPLEMENTARY DATA
==================
[Supplementary Data](http://nar.oxfordjournals.org/cgi/content/full/gks469/DC1) are available at NAR Online: Supplementary Methods and Supplementary References \[6--8,15,16\].
FUNDING
=======
Funding for open access charge: National Institutes of Health (NIH) \[contract nos HHSN272200900045C and HHSNN26600400006C\].
*Conflict of interest statement*. None declared.
|
Q:
Accessing Private variables in a child class?
So i was browsing some code and i came across:
public class Person
{
private string message;
public override string ToString()
{
return message;
}
public static Person CreateEmployee()
{
return new Employee();
}
class Employee : Person
{
public Employee()
{
this.message = "I inherit private members!";
}
}
}
Can someone please explain how the private variable "message" is being used/accessed even though its private??
A:
Private members are accessible to all code within the class, including nested classes.
If you move the Employee class outside the Person class, it will fail until you make the field protected.
A:
The simple fact is, this works because compilers allow it to - the designers thought it was a good thing. Once code is compiled, private/public variables are stored in memory in exactly the same way. (The CLR is simply aware of different metadata attributes for them.)
The justification is: nested classes and their members are still considered to lie conceptually/hierarchically within the parent class. Hence, private members of the parent class are always accessible by these semantics. Besides, it just makes life easy for programmers in many cases without breaking the object-oriented encapsulation rule!
In fact, if you want to think about this in terms of code, any code that falls within the open and close braces of a given class can access its private members, regardless of whether it immediately lies within a nested class/struct/etc.
|
Because most wine is blended from multiple tanks and barrels, these barrels may have been treated separately, and with different fining agents. Technically those agents may remain in the wine, but only in extremely low levels, parts per million. The Vegan wine scene is very small, and because of the nature of winemaking, those “Vegan” wines typically come from extremely small lots, where this can be certified from start to finish.
Most of the Kirkland Signature wines will not meet that criteria and very few branded wines on the shelf anywhere in the world will.
For instance: The Kirkland Signature Napa Chardonnay 2011 and 2012 used
Gelatin, Casein and Milk as fining agents." |
Q:
Windows Phone set font-size for Thai in css
I have to show Thai and Roman text in a WebView (with NavigateToString). In CSS I've defined the font-sizes for Roman as 1.0em and for Thai as 1.8em. But Thai is displayed very small, smaller than Roman. If I set the font-size for Thai to 8em, then the result is about I want to have.
OK, I can set the font-size to 8.0. But if this wrong behavior an bug in the OS, and Microsoft correct it in the next version, then my customers will have Thai script in 800% that fills up the screen.
Is this a bug in the OS? Or am I missing something obvious?
Edit: this is the generated html
<html>
<head>
<title>ClickThai</title>
<meta http-equiv="Content-Type" content="text/html; charset=UTF-8">
<style type="text/css">
<!--
.Text { font-size: 1.0em}
.News { font-size: 1.0em; font-weight: bold; color: #333333}
.ThaiText { font-size: 2.0em; line-height: 2.2em;}
.TTiT { font-size: 1.0em; line-height: 1.3em;}
.Tones { font-size:80%; position:relative; bottom: 0.1em; letter-spacing: -0.15em; color: #FF0000;}
.Tonex { font-size:80%; position:relative; bottom: 0.1em; letter-spacing: -0.15em; color: #00FF00;}
.NoWrap { white-space:nowrap;}
-->
</style>
</head>
<body bgcolor="#FFFFFF" text="#000000">
<table width="100%" border="0" cellspacing="0" cellpadding="2">
<tr>
<td bgcolor="#00FF00">
<p class="ThaiText">ไก่</p>
</td>
</tr>
</table>
<p class="News">Transcription</p>
Description
</body>
</html>
It works on Internet Explorer and other browsers. Not in WebView on Windows Phone.
A:
Because my app is an universal app I have added my code to the Windows 8.1 area.
There the size specifications are correctly rendered.
Conclusion: The code is error-free, but there is a bug in Windows Phone 8.1 when rendering the css font sizes within html tables.
|
Q:
How many ways can we paint the sides of a pyramid if two adjacent sides can't have the same color?
Given $4$ different colours, we want to paint the four sides of a pyramid in such a way as to sides that share an edge do not have the same colour. We're allowed to use the same colour more than once otherwise.
I drew a pyramid viewed from the top, to help me visualize.
The solution to this problem is $4\cdot3\cdot2\cdot2+4\cdot3\cdot1\cdot3$. However, I can't quite understand why. I was hoping anyone would provide an intuitive explanation.
A:
First label the sides by their (inter)cardinal directions. We have NE, NW, SE and SW.
NW and SE either have the same color, or different colors. This splits us off into two cases:
Different color. Pick the color for NE first. There are 4 to choose from. Then pick the color for NW, there are 3 to choose from. Now, since we said SE would be different from NW, and it has to be different from NE, there are 2 colors to choose from. Finally, there are 2 colors to choose from for SW. In total, $4\cdot 3\cdot 2\cdot 2$ possibilities.
Same color. Pick the color for NE first. There are 4 to choose from. Now pick the color for NW. There are 3, since it can't be the same as NE. Then there is only 1 available choice for SE since we said it would be the same as NW, and finally, since NW and SE have the same color, there are 3 available for SW. In total $4\cdot 3\cdot 1\cdot 3$ possibilities.
Add them together, and you have the answer.
|
{
"images" : [
{
"idiom" : "universal",
"scale" : "1x"
},
{
"idiom" : "universal",
"filename" : "gift_gai_@2x.png",
"scale" : "2x"
},
{
"idiom" : "universal",
"filename" : "gift_gai_@3x.png",
"scale" : "3x"
}
],
"info" : {
"version" : 1,
"author" : "xcode"
}
} |
5, -3, 0.1, -24?
-3
Which is the closest to -1/3? (a) -3/7 (b) 1/3 (c) -1/2 (d) -2 (e) -1620
a
Which is the closest to -1/3? (a) -76 (b) -0.09 (c) 2/7 (d) 5 (e) -2.8
b
What is the closest to -0.23449 in 0.039, 1/4, -4?
0.039
Which is the nearest to -0.2? (a) -2/35 (b) 3 (c) -2.3 (d) 5
a
What is the nearest to -1523 in 3, -3/7, 0.4, -4?
-4
What is the nearest to 2/9 in 1/80, -12, -0.3, 0.8?
1/80
What is the nearest to -0.1 in -2, -203, -6.1?
-2
Which is the closest to 0? (a) -0.5 (b) -11 (c) -2/5 (d) 0.476 (e) -10
c
What is the nearest to -0.3 in 126, -10, 0, -0.3, -2?
-0.3
What is the closest to 3 in 11, 0, -1/3, -14?
0
What is the closest to 0.06 in 3997/3, 1, 5?
1
Which is the nearest to -0.2? (a) 122 (b) -0.3 (c) 1.6 (d) 7/3
b
What is the nearest to -1 in 619, -705, 3, 5?
3
Which is the nearest to -8? (a) -4 (b) -43.7 (c) -0.2
a
Which is the nearest to 0.8246? (a) -0.4 (b) -1 (c) 0.3
c
What is the nearest to 298 in -2/13, -0.3, -5, -2?
-2/13
Which is the nearest to 4? (a) 2/105 (b) 0.5 (c) -2/3 (d) 0.4 (e) 110
b
What is the closest to 10 in 1.24, 8, 1, 4?
8
What is the nearest to -2/5 in -0.2, 21, 1.04, 3?
-0.2
What is the nearest to -26 in -0.5, 0.37, 0.01, 3?
-0.5
What is the nearest to -0.2 in 0.7029, -3/5, -13?
-3/5
Which is the nearest to 0.2? (a) 2/17 (b) -0.5 (c) 5 (d) 5.9
a
What is the nearest to -1.1 in -0.3, 0.2, -0.95?
-0.95
What is the closest to 2 in 3/22, -646, 5?
3/22
Which is the nearest to 1/5? (a) 3 (b) 16.98 (c) 0.02 (d) 0 (e) 4
c
What is the nearest to -3 in -1, 2/5, -5/16, -0.06?
-1
Which is the nearest to -3/4? (a) 4/3 (b) 2 (c) -2/487 (d) 53
c
Which is the closest to 245? (a) 1/5 (b) -6 (c) -3/7 (d) -1
a
What is the closest to 2 in 2/5, 13, 2/13, 2/7?
2/5
What is the nearest to 3 in 0.2, -32611, 0.3?
0.3
What is the closest to -3/5 in 4, -0.5, -3269, -1/4?
-0.5
What is the nearest to -3 in 3.7, -54, 0.5?
0.5
What is the closest to -52 in -0.4, -5, 13, 0.1?
-5
Which is the closest to 20.2? (a) 2 (b) -2/7 (c) 1 (d) -6.3
a
Which is the closest to 0.1? (a) -4 (b) 2/13 (c) -1 (d) -1.1 (e) -24/7
b
What is the closest to 0 in -0.044, 4, 175, 2/21, -0.4?
-0.044
What is the nearest to -0.6 in -2, 2173, 0.2?
0.2
Which is the nearest to -29/3? (a) -10/3 (b) -3 (c) 2/5 (d) 1/3
a
What is the closest to 1 in 3/5, -2, 3447?
3/5
What is the closest to -17 in 23, -4/11, 1, -0.5?
-0.5
Which is the closest to 1/2091? (a) -1/8 (b) -2 (c) -5 (d) -3/4
a
What is the nearest to 654.2 in 11/6, -4, -3?
11/6
What is the closest to -0.7 in -2/7, -0.0761, -0.2?
-2/7
What is the nearest to -41 in -0.3, -5, 0.5, 1.4?
-5
Which is the closest to -21? (a) -1/5 (b) 1/17 (c) -1 (d) -1/3 (e) -0.01
c
Which is the closest to -3? (a) -1.25 (b) -1/4 (c) -3 (d) -0.036 (e) 33
c
Which is the closest to 1/2? (a) 9 (b) -0.037 (c) 0.2 (d) -2
c
What is the nearest to 1 in -2/185, -5, 2/3, 49/5?
2/3
What is the closest to -0.017 in 5, 5/227, 4, -2?
5/227
What is the nearest to 0.1 in -42, 3, -2/265?
-2/265
What is the nearest to 3/2 in -3388, 3, 1/2?
1/2
What is the nearest to -270 in -1.5, 3, 2/9?
-1.5
Which is the closest to -3? (a) -1/3 (b) 18.8 (c) -15
a
What is the nearest to -1 in -9, -212/29, -3?
-3
Which is the nearest to -0.01? (a) 2 (b) -5 (c) 0.01 (d) 5 (e) 169
c
Which is the nearest to -3? (a) -2/3 (b) -0.2 (c) 4 (d) 72/5 (e) 2/7
a
Which is the nearest to 13? (a) 0.8 (b) 2 (c) 2/11 (d) 3/5 (e) -8
b
What is the nearest to 1 in 264, 9, -1/2, -0.3, -10?
-0.3
Which is the nearest to 0.1? (a) -5.1 (b) 4/5 (c) -0.1 (d) -0.3
c
What is the closest to -0.1 in -1, -4, 0.2, -194, -0.03?
-0.03
What is the closest to 0.3 in -1/3, -2/3, 765, 0.4?
0.4
Which is the nearest to 1/4? (a) -66 (b) 1.4 (c) -3 (d) -4
b
What is the closest to -2.6 in -0.5, 0.14, -2/11, 1/6, -1/6?
-0.5
What is the closest to 10 in -79, 2/3, 4, 1, 5?
5
What is the nearest to -0.09 in -2, -5, 18.5, 0.5?
0.5
Which is the closest to -1? (a) -0.4 (b) 20447/3 (c) -0.2
a
Which is the nearest to -12/7? (a) -3 (b) 1/4 (c) 3
a
What is the closest to 1 in -2/13, -3, 629?
-2/13
Which is the nearest to 4? (a) 2/7 (b) -7152 (c) 41
a
Which is the closest to -381? (a) -5 (b) -12 (c) -4 (d) -0.5
b
Which is the nearest to 2? (a) -15 (b) 2 (c) 1 (d) 8/29 (e) -2
b
Which is the nearest to 0.06? (a) -21 (b) -203 (c) 0.2 (d) -1/3 (e) -2/11
c
Which is the closest to -1705? (a) -1/8 (b) -9 (c) -2
b
Which is the nearest to -1? (a) -0.1 (b) -0.4 (c) 94 (d) -4/181
b
What is the nearest to -0.02 in -0.08, 2/11, -1, 20?
-0.08
What is the closest to 2/5 in 9, -56.4, 0.1, 4/3, 1/4?
1/4
What is the closest to 119 in 4, -0.4, 3/10, -30?
4
What is the nearest to 26/27 in -19/3, -1, 0.3, 0, -4?
0.3
Which is the closest to 1.4? (a) 2/7 (b) -3/2 (c) -294 (d) -2/5 (e) -2/7
a
What is the closest to -10 in 3/13, -0.5, -4, -2?
-4
Which is the closest to -2? (a) 4/5 (b) -2/3 (c) -36 (d) 0.3 (e) 26
b
Which is the closest to 1.23? (a) -6.9 (b) 2/5 (c) 4 (d) -5
b
What is the nearest to -1/15 in 689, -0.1, 0.19, 0.1, -5?
-0.1
Which is the nearest to 2? (a) -3 (b) -27 (c) -0.5 (d) -4/13
d
What is the nearest to -3716 in -4, -1, 3?
-4
Which is the nearest to 15? (a) 4 (b) -2/7 (c) 1/3 (d) 5613
a
What is the closest to 2 in -1/3, 1225, -4/5, -1/4, -2/5?
-1/4
Which is the closest to 114? (a) -2/9 (b) 0.4 (c) -0.5 (d) 10
d
What is the nearest to 7 in -0.53, -2/5, -0.09?
-0.09
Which is the nearest to -1? (a) 0.2 (b) -2.54 (c) -6 (d) 7/2
a
Which is the closest to 1? (a) 2/9 (b) -0.3 (c) -1 (d) 2/45 (e) -5/32
a
What is the nearest to 3/8 in -2/7, 2, 3/7, 45/4?
3/7
What is the nearest to 3/4 in -1, -4, 6/5, 0.8?
0.8
What is the closest to 1 in -88/5, -2/15, -3/4, 1.1, -5?
1.1
Which is the closest to -3/13? (a) -2.63 (b) 4 (c) -4 (d) 0.3
d
What is the nearest to 1 in -0.4, 3, 5, -35, -2/3?
-0.4
Which is the closest to -1? (a) 5 (b) 1/4 (c) 183 (d) -14.9
b
What is the nearest to 1.3 in 13, 40, -0.2, -2, -3/2?
-0.2
What is the closest to 0 in -3, 0.5, 2, -92?
0.5
Which is the nearest to 48? (a) -4 (b) 54.2 (c) 3 (d) 1
b
Which is the nearest to 0.56? (a) 0.3 (b) -0.8 (c) -4/7
a
Which is the nearest to 0.331? (a) 1 (b) -3 (c) 1/2 (d) 3
c
Which is the nearest to 5? (a) 39 (b) -1309 (c) -3
c
What is the closest to -0.2 in -2, -8, -1, 61?
-1
What is the closest to -0.1 in -2/3, 1.1635, 1/6?
1/6
Which is the nearest to 6/5? (a) 3/4 (b) -0.6 (c) -6/31
a
What is the nearest to -1.1 in 0.2, 395, 103?
0.2
What is the nearest to 2/9 in -1, 2/383, -3?
2/383
What is the closest to 1/8 in -3/7, -1/3, 5, 1/11?
1/11
Which is the closest to 0? (a) -4.7 (b) 80.58 (c) 2/9
c
Which is the nearest to -0.1? (a) -5 (b) -1013 (c) 17 (d) -1 (e) 1/7
e
What is the nearest to 0.15 in -3, 26, 4/5?
4/5
What is the nearest to 1/33 in -23, -4, -0.4, 3?
-0.4
Which is the closest to 0.1? (a) 70 (b) 7 (c) -0.1 (d) -8
c
What is the closest to -40 in 8/5, 5/37, 2/11?
5/37
Which is the nearest to 0.2? (a) 0.51 (b) -4/7 (c) 0.3 (d) 0.4 (e) 46
c
Which is the nearest to 4971? (a) -1/4 (b) 3/7 (c) 0.1 (d) 3/41
b
Which is the nearest to 5? (a) 0.7 (b) 3/4 (c) -10/23 (d) -4 (e) 5
e
Which is the closest to 1? (a) -0.9 (b) -2/53 (c) 0.5 (d) 3/5 (e) -5/14
d
Which is the closest to 0? (a) -1 (b) 7/5 (c) -2/115 (d) 5 (e) 2/69
c
Which is the closest to -4/7? (a) 3/2 (b) -37 (c) -0.07 (d) 3
c
What is the nearest to 1 in -2/7, 1, 0.0478, 34.4?
1
Which is the closest to -3? (a) -0.24 (b) -2/5 (c) -1102
b
What is the nearest to 13 in 289, 8, 2/7?
8
What is the closest to 2/13 in -2, 0.39, 4, -0.1, 0.061?
0.061
Which is the nearest to 1.5? (a) -29 (b) 2/51 (c) -5 (d) -1/3
b
What is the closest to 1 in -2, 716, 1, 2?
1
What is the nearest to 3 in 25, 5, -2/7?
5
What is the closest to -5 in -1/3, 3, 4, 149.4?
-1/3
Which is the closest to 4? (a) -0.068 (b) 0.3 (c) -70
b
Which is the nearest to -0.0104? (a) -0.5 (b) -1 (c) -353
a
Which is the closest to 179? (a) 0.1 (b) 3/13 (c) -4 (d) -1 (e) -3
b
What is the nearest to -2/11 in 2/3, -7/617, -4?
-7/617
Which is the closest to -64? (a) -3 (b) 1/2 (c) 2 (d) 24
a
What is the nearest to 10 in 300, 3/40, 4/ |
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"name": "Field - Discovering Statistics",
"path": "Field - Discovering Statistics",
"description": "Deze map bevat datasets van Field, A. P. (2017). <i>Discovering Statistics Using IBM SPSS Statistics<\/i> (5th ed.). London: Sage. Deze datasets zijn gemaakt door Andy Field, aan wie dus het copyright toebehoort. Andy Field heeft vriendelijk toegezegd dat we deze datasets in de JASP datalibrary mogen gebruiken. Deze datasets zijn ook beschikbaar op de website die bij Andy Field's boek hoort: https://edge.sagepub.com/field5e. Zonder Andy Field's expliciete toestemming mogen deze datasets niet voor commerciele doeleinden worden gebruikt, de data mag niet worden aangepast, en de data mag niet worden gepresenteerd zonder dat de bron is genoemd (i.e., the terms of a CC BY-NC-ND license <br><br> ",
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"name": "Albumverkoop",
"path": "../../../Data Library/4. Regression/Album Sales.jasp",
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"name": "Alcohol Attitudes",
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"description": "Attitudes naar water, wijn, en bier na het bekijken van positieve, neutrale, of negatieve beelden van het drinken - iedere participant komt terug in iedere cel van het 3x3 design. <br><br> <i>Fictieve data van Andy Field.<\/i>",
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"name": "Bierbril",
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"description": "Mediaan aantrekkelijkheidsbeoordelingen van 50 aantrekkelijke of onaantrekkelijke gezichten na het drinken van verschillende hoeveelheden alcohol. <br><br> <i>Fictieve data van Andy Field.<\/i>",
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"name": "Bush Tucker Food",
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"description": "Het aantal seconden voordat een beroemdheid overgeeft na het eten van vies eten - iedere beroemdheid heeft vier verschillende soorten vies eten gegeten. <br><br> <i>Fictieve data van Andy Field.<\/i>",
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"name": "Dansende Katten",
"path": "../../../Data Library/5. Frequencies/Dancing Cats.jasp",
"description": "Het aantal katten dat heeft geleerd te dansen, getraind door een van de twee types van conditioneren. <br><br> <i>Fictieve data van Andy Field.<\/i>",
"kind": "file",
"associated_datafile": "../../../Data Library/5. Frequencies/Dancing Cats.csv"
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{
"name": "Dansende Katten en Honden",
"path": "../../../Data Library/5. Frequencies/Dancing Cats and Dogs.jasp",
"description": "Het aantal katten en honden dat heeft geleerd te dansen, getraind door een van de twee types van conditioneren. <br><br> <i>Fictieve data van Andy Field.<\/i>",
"kind": "file",
"associated_datafile": "../../../Data Library/5. Frequencies/Dancing Cats and Dogs.csv"
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{
"name": "Examenangst",
"path": "../../../Data Library/4. Regression/Exam Anxiety.jasp",
"description": "Vragenlijst van studenten voor een examen (variabelen zijn angst, voorbereiding, en cijfer). <br><br> <i>Fictieve data van Andy Field.<\/i>",
"kind": "file",
"associated_datafile": "../../../Data Library/4. Regression/Exam Anxiety.csv"
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{
"name": "Angst voor Statistiek",
"path": "../../../Data Library/1. Descriptives/Fear of Statistics.jasp",
"description": "Responses van 2571 studenten op een SPSS Angst Vragenlijst. <br><br> <i>Fictieve data van Andy Field.<\/i>",
"kind": "file",
"associated_datafile": "../../../Data Library/1. Descriptives/Fear of Statistics.csv"
},
{
"name": "Onzichtbaarheidsmantel",
"path": "../../../Data Library/2. T-Tests/Invisibility Cloak.jasp",
"description": "Het aantal snode plannen uitgevoerd door twee groepen mensen, mensen met en zonder een onzichtbaarheidsmantel. <br><br> <i>Fictieve data van Andy Field.<\/i>",
"kind": "file",
"associated_datafile": "../../../Data Library/2. T-Tests/Invisibility Cloak.csv"
},
{
"name": "Uiterlijk of Persoonlijkheid",
"path": "../../../Data Library/3. ANOVA/Looks or Personality.jasp",
"description": "Voorkeurscores van tien mannen en tien vrouwen voor negen speed-date partners die varieerden in aantrekkelijkheid (hoog, gemiddeld, laag) en charisma (hoog, ietwat, geen). <br><br> <i>Fictieve data van Andy Field.<\/i>",
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"name": "De Grootste Leugenaar",
"path": "../../../Data Library/4. Regression/The Biggest Liar.jasp",
"description": "Creativiteit testscores en een rangorde in een liegwedstrijd. <br><br> <i>Fictieve data van Andy Field.<\/i>",
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"associated_datafile": "../../../Data Library/4. Regression/The Biggest Liar.csv"
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{
"name": "Viagra",
"path": "../../../Data Library/3. ANOVA/Viagra.jasp",
"description": "Mannen hun libido (en dat van hun partners) nadat zij verschillende doseringen Viagra hebben gehad. <br><br> <i>Fictieve data van Andy Field.<\/i>",
"kind": "file",
"associated_datafile": "../../../Data Library/3. ANOVA/Viagra.csv"
}
]
},
{
"name": "Moore, McCabe, & Craig - Introduction to the Practice of Statistics",
"path": "Moore, McCabe, & Craig - Introduction to the Practice of Statistics",
"description": "Deze map bevat datasets van Moore, D. S., McCabe, G. P., & Craig, B. A. (2012). <i>Introduction to the Practice of Statistics<\/i> (7th ed.). New York: W. H. Freeman and Company. Moore, McCabe, and Craig generously agreed that we can include the data sets in the JASP data library. These data sets are also publicly available on the website that accompanies their book: whfreeman.com/ips7e. Without the authors' explicit consent, these data sets may not be distributed for commercial purposes, these data sets may not be edited, and these data sets may not be presented without acknowledging their source (i.e., the terms of a CC BY-NC-ND license <br><br> ",
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"name": "Universiteitsucces",
"path": "../../../Data Library/4. Regression/College Success.jasp",
"description": "Middelbare schoolcijfers, SAT scores, en Grade Point Average van 224 universiteitsstudenten. <br><br> <i>Data van Moore, McCabe, & Craig.<\/i>",
"kind": "file",
"associated_datafile": "../../../Data Library/4. Regression/College Success.csv"
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{
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"path": "../../../Data Library/2. T-Tests/Directed Reading Activities.jasp",
"description": "Leesprestaties van twee groepen leerlingen - een controle groep en een groep die Directed Reading Activities heeft uitgevoerd. <br><br> <i>Data van Moore, McCabe, & Craig.<\/i>",
"kind": "file",
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{
"name": "Facebook Vrienden",
"path": "../../../Data Library/3. ANOVA/Facebook Friends.jasp",
"description": "Voorkeurswaarderingen voor Facebookprofielen - vijf groepen beoordelen dezelfde profielen, alleen het aantal vrienden op dat profiel is gemanipuleerd. <br><br> <i>Data van Moore, McCabe, & Craig.<\/i>",
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"path": "../../../Data Library/4. Regression/Fidgeting and Fat Gain.jasp",
"description": "Vetopslag van participanten en hun onbewuste fysieke activiteiten. <br><br> <i>Data van Moore, McCabe, & Craig.<\/i>",
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"name": "Gezondheidsgewoontes",
"path": "../../../Data Library/5. Frequencies/Health Habits.jasp",
"description": "fysieke activiteiten en fruitconsumptie van 1184 studenten. <br><br> <i>Data van Moore, McCabe, & Craig.<\/i>",
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"path": "../../../Data Library/3. ANOVA/Heart Rate.jasp",
"description": "Hartslag van mannelijke en vrouwelijke hardlopers en vaak stilzittende participanten na 6 minuten oefeningen. <br><br> <i>Data van Moore, McCabe, & Craig.<\/i>",
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"associated_datafile": "../../../Data Library/3. ANOVA/Heart Rate.csv"
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{
"name": "Maan en Agressie",
"path": "../../../Data Library/2. T-Tests/Moon and Aggression.jasp",
"description": "Het aantal disruptieve gedragingen door dementiepatienten tijdens twee verschillende fases van de maancyclus. <br><br> <i>Data van Moore, McCabe, & Craig.<\/i>",
"kind": "file",
"associated_datafile": "../../../Data Library/2. T-Tests/Moon and Aggression.csv"
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"name": "Fysieke Activiteit en BMI",
"path": "../../../Data Library/4. Regression/Physical Activity and BMI.jasp",
"description": "Participanten hun Body Mass Index en het gemiddeld aantal stappen per dag. <br><br> <i>Data van Moore, McCabe, & Craig.<\/i>",
"kind": "file",
"associated_datafile": "../../../Data Library/4. Regression/Physical Activity and BMI.csv"
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{
"name": "Reactie op Oogkleur",
"path": "../../../Data Library/3. ANOVA/Response to Eye Color.jasp",
"description": "Attitudes na advertenties over een merk zoals ervaren door vier verschillende groepen - elke groep kreeg dezelfde advertentie te zien, alleen de oogkleur van het model was gemanipuleerd. <br><br> <i>Data van Moore, McCabe, & Craig.<\/i>",
"kind": "file",
"associated_datafile": "../../../Data Library/3. ANOVA/Response to Eye Color.csv"
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{
"name": "Gewichtstoename",
"path": "../../../Data Library/2. T-Tests/Weight Gain.jasp",
"description": "Gewicht van 16 participanten voor en na een achtweekse periode van extreme kalorie inname. <br><br> <i>Data van Moore, McCabe, & Craig.<\/i>",
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"associated_datafile": "../../../Data Library/2. T-Tests/Weight Gain.csv"
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"name": "Slaap",
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"description": "Het extra aantal uren dat tien patienten sliepen na inname van twee 'soporific drugs' (dat wil zeggen, slaaptabletten). <br><br> Het voorbeeldsbestand in JASP laat zien hoe beschrijvende statistieken worden gebruikt. <br><br> <i>Dataset bijgesloten in R.<\/i>",
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"associated_datafile": "Sleep.csv"
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{
"name": "2. T-Toetsen",
"path": "2. T-Tests",
"description": "",
"kind": "folder",
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"name": "Directed Reading Activities",
"path": "Directed Reading Activities.jasp",
"description": "Leesprestaties van twee groepen leerlingen - een controlegroep en een groep die Directed Reading Activities heeft uitgevoerd. <br><br> Het voorbeeldbestand in JASP laat zien hoe een onafhankelijke steekproeven t-toets kan worden toegepast. <br><br> <i>Data van Moore, McCabe, & Craig.<\/i>",
"kind": "file",
"associated_datafile": "Directed Reading Activities.csv"
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{
"name": "Oogbewegingen",
"path": "Eye Movements.jasp",
"description": "Het aantal correct herinnerde woorden in twee groepen participanten - tijdens de retentie interval kreeg een groep de instructie om te focussen op een stip centraal getoond in de taak. <br><br> Het voorbeeldbestand in JASP laat zien hoe een 'Bayesiaanse t-toets onafhankelijke steekproeven' kan worden toegepast.<br><br> <i>Subset van de data gerapporteerd in Matzke et al. (2015).<\/i>",
"kind": "file",
"associated_datafile": "Eye Movements.csv"
},
{
"name": "Onzichtbaarheidsmantel",
"path": "Invisibility Cloak.jasp",
"description": "Het aantal snode plannen uitgevoerd door twee groepen mensen, mensen met en zonder een onzichtbaarheidsmantel. <br><br> Het voorbeeldbestand in JASP laat zien hoe een onafhankelijke steekproeven t-toets kan worden toegepast. <br><br> <i>Fictieve data van Andy Field.<\/i>",
"kind": "file",
"associated_datafile": "Invisibility Cloak.csv"
},
{
"name": "Keukenrollen",
"path": "Kitchen Rolls.jasp",
"description": "Openness to Experience scores voor twee groepen studenten - terwijl de persoonlijkheidsvragenlijst werd ingevuld, roteerden beide groepen een keukenpapierrol met hun handen (een groep met de klok mee, de andere groep tegen de klok in). <br><br> Het voorbeeldbestand in JASP laat zien hoe een Bayesiaanse en frequentistische onafhankelijke steekproeven t-toets kan worden toegepast. <br><br> <i>Data gerapporteerd in Wagenmakers et al. (2015).<\/i>",
"kind": "file",
"associated_datafile": "Kitchen Rolls.csv"
},
{
"name": "Maan en Agressie",
"path": "Moon and Aggression.jasp",
"description": "Het aantal disruptieve gedragingen door dementiepatienten tijdens twee verschillende fases van de maancyclus. <br><br> Het voorbeeldbestand in JASP laat zien hoe een gepaarde t-toets kan worden toegepast. <br><br> <i>Data van Moore, McCabe, & Craig.<\/i>",
"kind": "file",
"associated_datafile": "Moon and Aggression.csv"
},
{
"name": "Stereogrammen",
"path": "Stereograms.jasp",
"description": "De tijd die twee groepen participanten nodig hadden om de voorwerpen verborgen in een stereogram te vinden - de ene groep werd vooraf ingelicht over de scene, de andere groep niet. <br><br> Het voorbeeldbestand in JASP laat zien hoe een 'Bayesiaanse t-toets onafhankelijke steekproeven' kan worden toegepast.<br><br> <i>Data gerapporteerd in Frisby & Clatworthy (1975).<\/i>",
"kind": "file",
"associated_datafile": "Stereograms.csv"
},
{
"name": "Gewichtstoename",
"path": "Weight Gain.jasp",
"description": "Gewicht van 16 participanten voor en na een achtweekse periode van extreme kalorie inname. <br><br> Het voorbeeldbestand in JASP laat zien hoe een one sample t-toets kan worden toegepast. <br><br> <i>Data van Moore, McCabe, & Craig.<\/i>",
"kind": "file",
"associated_datafile": "Weight Gain.csv"
}
],
"debug": false
},
{
"name": "3. ANOVA",
"path": "3. ANOVA",
"description": "",
"kind": "folder",
"children": [
{
"name": "Alcohol Gedrag",
"path": "Alcohol Attitudes.jasp",
"description": "Attitudes naar water, wijn, en bier na het bekijken van positieve, neutrale, of negatieve beelden van het drinken - iedere participant komt terug in iedere cel van het 3x3 design. <br><br> Het voorbeeldbestand in JASP laat zien hoe een herhaalde metingen ANOVA kan worden toegepast. <br><br> <i>Fictieve data van Andy Field.<\/i>",
"kind": "file",
"associated_datafile": "Alcohol Attitudes.csv"
},
{
"name": "Bierbril",
"path": "Beer Goggles.jasp",
"description": "Mediaan aantrekkelijkheidsbeoordelingen van 50 aantrekkelijke of onaantrekkelijke gezichten na het drinken van verschillende hoeveelheden alcohol. <br><br> Het voorbeeldbestand in JASP laat zien hoe een ANOVA kan worden toegepast. <br><br> <i>Fictieve data van Andy Field.<\/i>",
"kind": "file",
"associated_datafile": "Beer Goggles.csv"
},
{
"name": "Beestjes",
"path": "Bugs.jasp",
"description": "In hoeverre mensen geleedpotigen willen vermoorden, op basis van hoe zij verschillen in hoe eng ze zijn (laag, hoog) en hoe vies ze eruit zien (laag, hoog) - elke participant beoordeeld iedere geleedpotige op beide maten. <br><br> Het voorbeeldbestand in JASP laat zien hoe een mixed design ANOVA kan worden toegepast. <br><br> <i>Subset van de data gerapporteerd in Ryan, Wilde, & Crist (2013).<\/i>",
"kind": "file",
"associated_datafile": "Bugs.csv"
},
{
"name": "Bush Tucker Food",
"path": "Bush Tucker Food.jasp",
"description": "Het aantal seconden voordat een beroemdheid overgeeft na het eten van vies eten - iedere beroemdheid heeft vier verschillende soorten vies eten gegeten. <br><br> Het voorbeeldbestand in JASP laat zien hoe een herhaalde metingen ANOVA kan worden toegepast. <br><br> <i>Fictieve data van Andy Field.<\/i>",
"kind": "file",
"associated_datafile": "Bush Tucker Food.csv"
},
{
"name": "Erotische Foto's en Liefde",
"path": "Erotic Pictures and Love.jasp",
"description": "Mannen en vrouwen hun gevoelens voor hun partners na het zien van erotische of artistische foto's. <br><br> Het voorbeeldbestand in JASP laat zien hoe een factorial 2 x 2 ANOVA kan worden toegepast. <br><br> <i>Subset van de data gerapporteerd in Balzarini et al. (2016).<\/i>",
"kind": "file",
"associated_datafile": "Erotic Pictures and Love.csv"
},
{
"name": "Facebook Vrienden",
"path": "Facebook Friends.jasp",
"description": "Voorkeurswaarderingen voor Facebookprofielen - vijf groepen beoordelen dezelfde profielen, alleen het aantal vrienden op dat profiel is gemanipuleerd. <br><br> Het voorbeeldbestand in JASP laat zien hoe een eenzijdige ANOVA kan worden toegepast. <br><br> <i>Data van Moore, McCabe, & Craig.<\/i>",
"kind": "file",
"associated_datafile": "Facebook Friends.csv"
},
{
"name": "Hartslag",
"path": "Heart Rate.jasp",
"description": "Hartslag van mannelijke en vrouwelijke hardlopers en vaak stilzittende participanten na 6 minuten oefeningen. <br><br> Het voorbeeldbestand in JASP laat zien hoe een 2 x 2 tussen-subjects ANOVA kan worden toegepast. <br><br> <i>Data van Moore, McCabe, & Craig.<\/i>",
"kind": "file",
"associated_datafile": "Heart Rate.csv"
},
{
"name": "Uiterlijk of Persoonlijkheid",
"path": "Looks or Personality.jasp",
"description": "Voorkeurscores van tien mannen en tien vrouwen voor negen speed-date partners die varieerden in aantrekkelijkheid (hoog, gemiddeld, laag) en charisma (hoog, ietwat, geen). <br><br> Het voorbeeldbestand in JASP laat zien hoe een mixed design ANOVA kan worden toegepast. <br><br> <i>Fictieve data van Andy Field.<\/i>",
"kind": "file",
"associated_datafile": "Looks or Personality.csv"
},
{
"name": "Pijngrenzen",
"path": "Pain Thresholds.jasp",
"description": "Pijngrenzen voor mensen met verschillende haarkleuren. <br><br> Het voorbeeldbestand in JASP laat zien hoe een eenzijdige ANOVA kan worden toegepast. <br><br> <i>Data van McClave & Dietrich (1991).<\/i>",
"kind": "file",
"associated_datafile": "Pain Thresholds.csv"
},
{
"name": "Reactie op Oogkleur",
"path": "Response to Eye Color.jasp",
"description": "Attitudes na advertenties over een merk zoals ervaren door vier verschillende groepen - elke groep kreeg dezelfde advertentie te zien, alleen de oogkleur van het model was gemanipuleerd. <br><br> Het voorbeeldbestand in JASP laat zien hoe een eenzijdige ANOVA kan worden toegepast. <br><br> <i>Data van Moore, McCabe, & Craig.<\/i>",
"kind": "file",
"associated_datafile": "Response to Eye Color.csv"
},
{
"name": "Zangers",
"path": "Singers.jasp",
"description": "\"Lengte in inches van de zangers in de New York Choral Society in 1979. De data zijn gegroepeerd op basis van stemdeel. Het stembereik voor ieder stemdeel neemt toe in hoogte op de volgende volgorde: Bass 2, Bass 1, Tenor 2, Tenor 1, Alto 2, Alto 1, Soprano 2, Soprano 1.\" <br><br> Het voorbeeldbestand in JASP laat zien hoe een Bayesiaanse tussen-subjects ANOVA kan worden toegepast. <br><br> <i>Data set in R.<\/i>",
"kind": "file",
"associated_datafile": "Singers.csv"
},
{
"name": "Tandgroei",
"path": "Tooth Growth.jasp",
"description": "\"De response is de lengte van odontoblasts (cellen verantwoordelijk voor tandgroei) in 60 cavia's. Elk dier kreeg een van de drie doseringen van vitamine C (0.5, 1, en 2 mg/dag), toegediend op een van de volgende twee manieren: in sinaasappelsap of in ascorbinezuur (een vorm van vitamine C en gecodeerd als VC).\" <br><br> Het voorbeeldbestand in JASP laat zien hoe een 2 x 2 ANOVA kan worden toegepast. <br><br> <i>Data set in R.<\/i>",
"kind": "file",
"associated_datafile": "Tooth Growth.csv"
},
{
"name": "Viagra",
"path": "Viagra.jasp",
"description": "Mannen hun libido (en dat van hun partners) nadat zij verschillende doseringen Viagra hebben gehad. <br><br> Het voorbeeldbestand in JASP laat zien hoe een ANCOVA kan worden toegepast. <br><br> <i>Fictieve data van Andy Field.<\/i>",
"kind": "file",
"associated_datafile": "Viagra.csv"
}
],
"debug": false
},
{
"name": "4. Regressie",
"path": "4. Regression",
"description": "",
"kind": "folder",
"children": [
{
"name": "Adam Sandler",
"path": "Adam Sandler.jasp",
"description": "Rotten Tomatoes beoordelingen en box office succes van films waarin Adam Sandler de hoofdrol speelt. <br><br> Het voorbeeldbestand in JASP laat zien hoe een Bayesiaanse Pearson's correlatie kan worden toegepast. <br><br> <i>Data verzameld op Rotten Tomatoes in 2015 door E.J. Wagenmakers.<\/i>",
"kind": "file",
"associated_datafile": "Adam Sandler.csv"
},
{
"name": "Albumverkoop",
"path": "Album Sales.jasp",
"description": "Factoren die albumverkoop zouden kunnen beinvloeden. <br><br> Het voorbeeldbestand in JASP laat zien hoe een lineaire regressie kan worden toegepast. <br><br> <i>Fictieve data van Andy Field.<\/i>",
"kind": "file",
"associated_datafile": "Album Sales.csv"
},
{
"name": "Veiling",
"path": "Auction.jasp",
"description": "De verkoopprijs en leeftijd van antieke klokken, en het aantal bieders in iedere veiling. <br><br> Het voorbeeldbestand in JASP laat zien hoe een lineaire regressie kan worden toegepast. <br><br> <i>Data van Mendenhall & Sincich (1993).<\/i>",
"kind": "file",
"associated_datafile": "Auction.csv"
},
{
"name": "Big Five Persoonlijkheidskenmerken",
"path": "Big Five Personality Traits.jasp",
"description": "Scores op de Big Five persoonlijkheidskenmerken vragenlijst van 500 participanten. <br><br> Het voorbeeldbestand in JASP laat zien hoe een Pearson's correlatie kan worden toegepast. <br><br> <i>Data gerapporteerd in Dolan et al. (2009).<\/i>",
"kind": "file",
"associated_datafile": "Big Five Personality Traits.csv"
},
{
"name": "Universiteitsucces",
"path": "College Success.jasp",
"description": "Middelbare school cijfers, SAT scores, en Grade Point Average van 224 universiteitstudenten. <br><br> Het voorbeeldbestand in JASP laat zien hoe een lineaire regressie kan worden toegepast. <br><br> <i>Data van Moore, McCabe, & Craig.<\/i>",
"kind": "file",
"associated_datafile": "College Success.csv"
},
{
"name": "Examenangst",
"path": "Exam Anxiety.jasp",
"description": "Vragenlijst van studenten voor een examen (variabelen zijn angst, voorbereiding, en cijfer). <br><br> Het voorbeeldbestand in JASP laat zien hoe een Pearson correlatiecoefficient kan worden toegepast. <br><br> <i>Fictieve data van Andy Field.<\/i>",
"kind": "file",
"associated_datafile": "Exam Anxiety.csv"
},
{
"name": "Vetopslag en Friemelen",
"path": "Fidgeting and Fat Gain.jasp",
"description": "Vetopslag van participanten en hun niet-bewuste fysieke activiteiten. <br><br> Het voorbeeldbestand in JASP laat zien hoe een lineaire regressie kan worden toegepast. <br><br> <i>Data van Moore, McCabe, & Craig.<\/i>",
"kind": "file",
"associated_datafile": "Fidgeting and Fat Gain.csv"
},
{
"name": "Glasgow Norms",
"path": "Glasgow Norms.jasp",
"description": "Een set van normatieve beoordelingen voor 5,553 Engelse woorden op negen psycholinguistische dimensies. <br><br> Het voorbeeldbestand in JASP laat zien hoe een Bayesiaanse correlatie kan worden toegepast. <br><br> <i>Data van Scott et al. (2017).<\/i>",
"kind": "file",
"associated_datafile": "Glasgow Norms.csv"
},
{
"name": "Fysieke Activiteit en BMI",
"path": "Physical Activity and BMI.jasp",
"description": "Participanten hun Body Mass Index en het gemiddeld aantal stappen per dag. <br><br> Het voorbeeldbestand in JASP laat zien hoe een lineaire regressie kan worden toegepast. <br><br> <i>Data van Moore, McCabe, & Craig.<\/i>",
"kind": "file",
"associated_datafile": "Physical Activity and BMI.csv"
},
{
"name": "De Grootste Leugenaar",
"path": "The Biggest Liar.jasp",
"description": "Creativiteit testscores en een rangorde in een liegwedstrijd <br><br> Het voorbeeldbestand in JASP laat zien hoe Spearman's en Kendall's correlatie kunnen worden toegepast. <br><br> <i>Fictieve data van Andy Field.<\/i>",
"kind": "file",
"associated_datafile": "The Biggest Liar.csv"
},
{
"name": "Titanic",
"path": "Titanic.jasp",
"description": "Leeftijd, kabineklasse, en overlevingstatus van 1313 passagiers op de Titanic. <br><br> Het voorbeeldbestand in JASP laat zien hoe een logistische regressie kan worden toegepast. <br><br> <i>Dataset in R.<\/i>",
"kind": "file",
"associated_datafile": "Titanic.csv"
}
],
"debug": false
},
{
"name": "5. Frequenties",
"path": "5. Frequencies",
"description": "",
"kind": "folder",
"children": [
{
"name": "Dansende Katten en Honden",
"path": "Dancing Cats and Dogs.jasp",
"description": "Het aantal katten en honden die hebben geleerd te dansen, getraind door een van de twee types van conditioneren <br><br> Het voorbeeldbestand in JASP laat zien hoe een log-lineaire analyse kan worden toegepast. <br><br> <i>Fictieve data van Andy Field.<\/i>",
"kind": "file",
"associated_datafile": "Dancing Cats and Dogs.csv"
},
{
"name": "Dansende Katten",
"path": "Dancing Cats.jasp",
"description": "Het aantal katten dat heeft geleerd te dansen, getraind door een van de twee types van conditioneren <br><br> Het voorbeeldbestand in JASP laat zien hoe een chi-kwadraat toets van onafhankelijkheid kan worden toegepast. <br><br> <i>Fictieve data van Andy Field.<\/i>",
"kind": "file",
"associated_datafile": "Dancing Cats.csv"
},
{
"name": "Doodstraf",
"path": "Death Penalty.jasp",
"description": "Beslissingen van de rechtbank over de doodstraf (ja of nee) verdeeld op ras van de aangeklaagde (i.e., wit of zwart) en het ras van het slachtoffer (i.e., wit of zwart). <br><br> Het voorbeeldbestand in JASP laat zien hoe een Bayesiaanse log-lineaire analyse kan worden toegepast. <br><br> <i>Data van Radelet & Pierce (1991).<\/i>",
"kind": "file",
"associated_datafile": "Death Penalty.csv"
},
{
"name": "Emily Rosa",
"path": "Emily Rosa.jasp",
"description": "Correcte en incorrecte beslissingen van Therapeutic Touch beoefenaars in Emily Rosa's beroemde experiment. \"In de eerste trial konden de participanten de locatie van de beoefenaars hand in 70 (47%) van de 150 gevallen juist localiseren.\" <br><br> Het voorbeeldbestand in JASP laat zien hoe een Bayesiaanse binomiale toets kan worden toegepast. <br><br> <i>Dataset gereconstrueerd van de samengevatte informatie van Rosa et al. (1998).<\/i>",
"kind": "file",
"associated_datafile": "Emily Rosa.csv"
},
{
"name": "Gezondheidsgewoontes",
"path": "Health Habits.jasp",
"description": "fysieke activiteiten en fruitconsumptie van 1184 studenten. <br><br> Het voorbeeldbestand in JASP laat zien hoe een chi-kwadraat toets van onafhankelijkheid kan worden toegepast.<br><br> <i>Data van Moore, McCabe, & Craig.<\/i>",
"kind": "file",
"associated_datafile": "Health Habits.csv"
},
{
"name": "Hongerige Zombies",
"path": "Hungry Zombies.jasp",
"description": "Het antwoord van 12 zombies op de vraag: \"Hoeveel honger ervaar je op dit moment?\" <br><br> Het voorbeeldbestand in JASP laat zien hoe een Bayesiaanse binomiale toets kan worden toegepast.<br><br> <i>Fictieve data van E.J. Wagenmakers.<\/i>",
"kind": "file",
"associated_datafile": "Hungry Zombies.csv"
},
{
"name": "Listerism",
"path": "Listerism.jasp",
"description": "De herstelstatus van patienten behandeld met Lister's methode of normaal verband. <br><br> Het voorbeeldbestand in JASP laat zien hoe Bayesiaanse contingency tables kunnen worden toegepast. <br><br> <i>Dataset gereconstrueerd aan de hand van de samenvattende informatie van MacAlister (1881) en gerapporteerd in Jamil et al. (2017).<\/i>",
"kind": "file",
"associated_datafile": "Listerism.csv"
},
{
"name": "Herinnering aan Stress-Situaties",
"path": "Memory of Life Stresses.jasp",
"description": "Het aantal gerapporteerde stress-situaties (opgeteld over alle participanten) die voorkwamen in de maanden voor het interview. <br><br> Het voorbeeldbestand in JASP laat zien hoe een multinomiale toets kan worden toegepast. <br><br> <i>Subset van de data gerapporteerd in Uhleman et al. (1974) aangeboden door Haberman (1978).<\/i>",
"kind": "file",
"associated_datafile": "Memory of Life Stresses.csv"
},
{
"name": "MOOC Bias",
"path": "MOOC Bias.jasp",
"description": "Het responspercentage van MOOC docenten op vragen gesteld met acht verschillende identiteitsconstructen [i.e., geslacht (man, vrouw) x ras (Wit, Indiaas, Zwart, Chinees)]. <br><br> Het voorbeeldbestand in JASP laat zien hoe een chi-kwadraat toets van onafhankelijkheid kan worden toegepast.<br><br> <i>Data van Baker et al. (2018).<\/i>",
"kind": "file",
"associated_datafile": "MOOC Bias.csv"
},
{
"name": "Zonnebrandcreme",
"path": "Sun Block Lotions.jasp",
"description": "Reacties van 20 participanten op de vraag: \"Welke van deze twee zonnebrandcremes is beter?\" <br><br> Het voorbeeldbestand in JASP laat zien hoe een binomiale toets kan worden toegepast. <br><br> <i>Fictieve data van Moore, McCaib, & Craig (2012).<\/i>",
"kind": "file",
"associated_datafile": "Sun Block Lotions.csv"
},
{
"name": "Driezijdige Munt",
"path": "Three-Sided Coin.jasp",
"description": "Het aantal keren dat beide experimentele munten op hun rand terecht kwamen (uit 1000 gooien). <br><br> Het voorbeeldbestand in JASP laat zien hoe een Bayesiaanse binomiale toets, die gebruik maakt van samenvattingsstatistiek, kan worden toegepast.<br><br> <i>Data verzameld door Matthew Parker.<\/i>",
"kind": "file"
}
],
"debug": false
},
{
"name": "6. Factor",
"path": "6. Factor",
"description": "",
"kind": "folder",
"children": [
{
"name": "G Factor",
"path": "G Factor.jasp",
"description": "Charles Spearman's data van leerlingen hun schoolcijfers en sensorisch onderscheidingsvermogen. <br><br> Het voorbeeldbestand in JASP laat zien hoe een exploratorische factoranalyse kan worden toegepast. <br><br> <i>Data gerapporteerd in Spearman (1904).<\/i>",
"kind": "file",
"associated_datafile": "G Factor.csv"
}
],
"debug": false
},
{
"name": "7. Audit",
"path": "7. Audit",
"description": "",
"kind": "folder",
"children": [
{
"name": "Testen van de Interne Systemen",
"path": "controlTestBayesian.jasp",
"description": "Een fictieve populatie bestaande uit 100 observaties uit interne systemen en hun relevante criteria. <br><br> Het voorbeeldbestand in JASP laat zien hoe de Bayesiaanse audit workflow kan worden toegepast. <br><br> <i>Gegevensset gebruikt in R-package jfa<\/i>",
"kind": "file",
"associated_datafile": "controlTest.csv"
},
{
"name": "Testen voor Overwaarderingen",
"path": "substantiveTestBayesian.jasp",
"description": "Een fictieve populatie bestaande uit 3500 transacties. <br><br> Het voorbeeldbestand in JASP laat zien hoe de Bayesiaanse audit workflow kan worden toegepast. <br><br> <i>Gegevensset gebruikt in R-package jfa<\/i>",
"kind": "file",
"associated_datafile": "BuildIt_Monetary.csv"
},
{
"name": "Plannen en Selecteren van een Steekproef",
"path": "planningAndSelectingBayesian.jasp",
"description": "Een fictieve populatie bestaande uit 3500 transacties. <br><br> Het voorbeeldbestand in JASP laat zien hoe de Bayesiaanse planning en de selectie kan worden toegepast. <br><br> <i>Gegevensset gebruikt in R-package jfa<\/i>",
"kind": "file",
"associated_datafile": "BuildIt_Monetary.csv"
},
{
"name": "Evalueren van een Steekproef",
"path": "evaluationBayesian.jasp",
"description": "Een fictieve steekproef bestaande uit 60 transacties. <br><br> Het voorbeeldbestand in JASP laat zien hoe de Bayesiaanse evaluatie kan worden toegepast. <br><br> <i>Gegevensset gebruikt in R-package jfa<\/i>",
"kind": "file",
"associated_datafile": "auditSample.csv"
},
{
"name": "Vaststellen van de Wet van Benford",
"path": "sinoForest.jasp",
"description": "Jaarrekening van het rapport van Sino Forest Corporation uit 2010. <br> <br> Het voorbeeldbestand in JASP toont het gebruik van een analyse met behulp van de wet van Benford. <br> <br> <i> Gegevensset gebruikt in R-package benford.analysis <\/i>",
"kind": "file",
"associated_datafile": "sinoForest.csv"
},
{
"name": "BuildIt Binary",
"path": "BuildIt_Binary.jasp",
"description": "BuildIt's audit populatie bestaande uit 3500 transacties. <br><br> Het voorbeeldbestand in JASP laat zien hoe de Bayesiaanse audit workflow kan worden toegepast. <br><br> <i>Gegevensset gebruikt in R-package jfa<\/i>",
"kind": "file",
"associated_datafile": "BuildIt_Monetary.csv"
}
],
"debug": false
},
{
"name": "8. Bain",
"path": "8. Bain",
"description": "",
"kind": "folder",
"children": [
{
"name": "One Sample T-Test",
"path": "bainOneSample.jasp",
"description":"Dit JASP-bestand toont een Bain T-Toets voor Eén Gemiddelde met behulp van de Sesamstraat gegevens. <br> <br> <i> Gegevensset opgenomen in het bain R-pakket. <\ / I>",
"kind": "file",
"associated_datafile": "sesame.csv"
},
{
"name": "Welch's T-Test",
"path": "bainIndependentSamples.jasp",
"description":"Dit JASP-bestand toont een Bain Welch's T-Toets met behulp van de Sesamstraat gegevens. <br> <br> <i> Gegevensset opgenomen in het bain R-pakket. <\ / I>",
"kind": "file",
"associated_datafile": "sesame.csv"
},
{
"name": "Paired Samples T-Test",
"path": "bainPairedSamples.jasp",
"description":"Dit JASP-bestand toont een Bain Gepaarde T-Toets toets met behulp van de Sesamstraat gegevens. <br> <br> <i> Gegevensset opgenomen in het bain R-pakket. <\ / I>",
"kind": "file",
"associated_datafile": "sesame.csv"
},
{
"name": "ANOVA",
"path": "bainAnova.jasp",
"description":"Dit JASP-bestand toont een Bain ANOVA toets met behulp van de Sesamstraat gegevens. <br> <br> <i> Gegevensset opgenomen in het bain R-pakket. <\ / I>",
"kind": "file",
"associated_datafile": "sesame.csv"
},
{
"name": "ANCOVA",
"path": "bainAncova.jasp",
"description":"Dit JASP-bestand toont een Bain ANCOVA toets met behulp van de Sesamstraat gegevens. <br> <br> <i> Gegevensset opgenomen in het bain R-pakket. <\ / I>",
"kind": "file",
"associated_datafile": "sesame.csv"
},
{
"name": "Regressie",
"path": "bainRegression.jasp",
"description": "Dit JASP-bestand toont een Bain regressie met behulp van de Sesamstraat gegevens. <br> <br> <i> Gegevensset opgenomen in het bain R-pakket. <\ / I>",
"kind": "file",
"associated_datafile": "sesame.csv"
}
],
"debug": false
},
{
"name": "9. Ontdek Verdelingen",
"path": "9. Discover Distributions",
"description": "",
"kind": "folder",
"children": [
{
"name": "Distributions",
"path": "Normal distribution.jasp",
"description": "Synthetische gegevensset van variabelen gegenereerd uit verschillende waarschijnlijkheidsverdelingen. <br> <br> Het voorbeeld JASP-bestand toont de normale verdeling. <br> <br> <i> Fictieve gegevens gecreëerd door JASP Team. <\ / I>",
"kind": "file",
"associated_datafile": "Distributions.csv"
}
]
},
{
"name": "10. Machine Learning",
"path": "10. Machine Learning",
"description": "",
"kind": "folder",
"children": [
{
"name": "Iris Bloemen",
"path": "iris.jasp",
"description": "Dit beroemde iris gegevensbestand (door Fisher of Anderson) geeft de maten (in centimeters) van de variabelen kelkbladlengte en breedte, en bloembladlengte en breedte respectievelijk, voor 50 bloemen van alle 3 soorten irissen. Deze soorten zijn Iris setosa, Iris versicolor, en Iris virginica. <br><br> <i>Dataset in R.<\/i>",
"kind": "file",
"associated_datafile": "iris.csv"
},
{
"name": "Telco's Overstappende Klanten",
"path": "telcoCustomerChurn.jasp",
"description": "Telecomdata van 7043 klanten van een telefoonprovider. Variabelen varieren van persoonlijke beschrijvingen tot subscriptiekosten en geven zo informatie over overstapgedrag van klanten. <br><br> <i>Publiek beschikbaar via https://www.kaggle.com/blastchar/telco-customer-churn.<\/i>",
"kind": "file",
"associated_datafile": "telcoCustomerChurn.csv"
},
{
"name": "Studentcijfers",
"path": "studentGrades.jasp",
"description": "De data bevat informatie van 357 middelbare scholieren in Portugal (Cortez & Silva, 2008). <br><br> <i>Publiek beschikbaar via https://www.kaggle.com/dipam7/student-grade-prediction<\/i>",
"kind": "file",
"associated_datafile": "studentGrades.csv"
},
{
"name": "Wijnsoorten",
"path": "wine.jasp",
"description": "De resultaten van chemische analyse van wijnen die worden ontwikkeld in een specifieke regio in Italië. Drie soorten wijn zijn gebruikt in de 178 monsters, en de resultaten van 13 chemische analyses zijn gerapporteerd voor iedere monster. <br><br> <i>Dataset in R.<\/i>",
"kind": "file",
"associated_datafile": "wine.csv"
}
],
"debug": false
},
{
"name": "11. Meta-Analyse",
"path": "11. Meta-Analysis",
"description": "",
"kind": "folder",
"children": [
{
"name": "BCG-Vaccin",
"path": "BCG Vaccine.jasp",
"description": "Toetsstatistiek van studies die de effectiviteit van het BCG-Vaccin onderzochten. <br><br> Het voorbeeldbestand in JASP laat zien hoe een vast-effect en willekeurig-effect meta-analyse kan worden toegepast. <br><br> <i>Data aangeboden door Raoul Grasman.<\/i>",
"kind": "file",
"associated_datafile": "BCG Vaccine.csv"
}
],
"debug": false
},
{
"name": "12. Netwerk Analyse",
"path": "12. Network Analysis",
"description": "",
"kind": "folder",
"children": [
{
"name": "BFI Netwerk",
"path": "BFI Network.jasp",
"description": "Reacties van 2800 participanten op 25 Big Five Inventory items. <br><br> Het voorbeeldbestand in JASP laat zien hoe een netwerk analyse kan worden toegepast. <br><br> <i>Dataset in R.<\/i>",
"kind": "file",
"associated_datafile": "BFI Network.csv"
}
],
"debug": false
},
{
"name": "13. Betrouwbaarheid",
"path": "13. Reliability",
"description": "",
"kind": "folder",
"children": [
{
"name": "Angst voor Statistiek",
"path": "Fear of Statistics.jasp",
"description": "Antwoorden van 2571 studenten op een SPSS Angstvragenlijst. <br> <br> Het voorbeeld-JASP-bestand toont het gebruik van een betrouwbaarheidsanalyse. <br> <br> <i> Fictieve gegevens van Andy Field. <\ / i>",
"kind": "file",
"associated_datafile": "Fear of Statistics.csv"
}
],
"debug": false
},
{
"name": "14. SEM",
"path": "14. SEM",
"description": "",
"kind": "folder",
"children": [
{
"name": "Politieke Democratie",
"path": "Political Democracy.jasp",
"description": "Indicatoren van industrialisatie in 1960, en politieke democratie in 1960 en 1965. <br><br> Het voorbeeldbestand in JASP laat zien hoe structural equation modeling kan worden toegepast. <br><br> <i>Dataset in R.<\/i>",
"kind": "file",
"associated_datafile": "Political Democracy.csv"
}
],
"debug": false
},
{
"name": "15. Overig",
"path": "15. Miscellaneous",
"description": "",
"kind": "folder",
"children": [
{
"name": "Anscombe's Kwartet",
"path": "Anscombe's Quartet.jasp",
"description": "Een klassiek voorbeeld van het nut van het visualiseren van data. <br><br> Het voorbeeldbestand in JASP laat zien hoe data grondig kan worden geinspecteerd met grafieken in plaats van statistische uitvoer. <br><br> <i>Fictieve data van Anscombe (1973).<\/i>",
"kind": "file",
"associated_datafile": "Anscombe's Quartet.csv"
},
{
"name": "Missing Data",
"path": "Missing Data.jasp",
"description": "Synthetische data met missende waardes. <br><br> Het voorbeeldbestand in JASP laat zien hoe een XXX kan worden toegepast. Missende waardes.<br><br> <i>Fictieve data van Alexander Ly.<\/i>",
"kind": "file",
"associated_datafile": "Missing Data.csv"
},
{
"name": "De Lengte van Presidenten",
"path": "Presidents' Height.jasp",
"description": "De lengte van presidenten van de VS en hun aandeel van de populariteitsstemming. <br><br> Het voorbeeldbestand in JASP laat zien hoe een interval - nulhypothese kan worden toegepast. <br><br> <i>Subset van de data gerapporteerd in Stulp et al. (2015).<\/i>",
"kind": "file",
"associated_datafile": "Presidents' Height.csv"
}
],
"debug": false
},
{
"name": "Debug Dataset (JASP Team, 2017)",
"path": "../debug.csv",
"description": "For testing. Readme: is.gd/jaspdata",
"kind": "file",
"children": ["NULL"],
"debug": true
}
]
}
|
---
abstract: 'Regional adversarial attacks often rely on complicated methods for generating adversarial perturbations, making it hard to compare their efficacy against well-known attacks. In this study, we show that effective regional perturbations can be generated without resorting to complex methods. We develop a very simple regional adversarial perturbation attack method using cross-entropy sign, one of the most commonly used losses in adversarial machine learning. Our experiments on ImageNet with multiple models reveal that, on average, $76\%$ of the generated adversarial examples maintain model-to-model transferability when the perturbation is applied to local image regions. Depending on the selected region, these localized adversarial examples require significantly less $L_p$ norm distortion (for $p \in \{0, 2, \infty\}$) compared to their non-local counterparts. These localized attacks therefore have the potential to undermine defenses that claim robustness under the aforementioned norms.'
bibliography:
- '2020\_04.bib'
---
Introduction {#Introduction}
============
1[0]{} at (0, 1) [No localization]{}; (russell) at (2.5, 1) [![(Top) An input image and its adversarial counterpart created with IFGS. (Center and bottom) Perturbation localization grids illustrated with black-gray images and adversarial examples generated by IFGS when the perturbation is only applied to the grey areas in the localization grids. $L_p$ norms of the perturbation are provided under each image. All of the adversarial examples were generated using AlexNet and successfully transfer to ResNet-50.[]{data-label="fig:adv_sq_fr"}](image_examples/3133_org.png "fig:"){width="2.3cm"}]{}; at (2.5, 1 + 1.4) [Original image]{}; (whitehead) at (5.5, 1) [![(Top) An input image and its adversarial counterpart created with IFGS. (Center and bottom) Perturbation localization grids illustrated with black-gray images and adversarial examples generated by IFGS when the perturbation is only applied to the grey areas in the localization grids. $L_p$ norms of the perturbation are provided under each image. All of the adversarial examples were generated using AlexNet and successfully transfer to ResNet-50.[]{data-label="fig:adv_sq_fr"}](image_examples/3133_noloc.png "fig:"){width="2.3cm"}]{}; at (5.5, 1 + 1.4) [Adversarial image]{}; at (5.5, 1 - 1.4) [$L_0=0.99$]{}; at (5.5, 1 - 1.65) [$L_2=6.63$]{}; at (5.5-0.05, 1 - 1.9) [$L_{\infty}=0.07$]{};
(-1, 1 -2.2) – (7, 1 -2.2);
1[-3.25]{} at (0, 1) [Perturbation\
localization\
masks\
(Center square)]{}; (russell) at (2, 1) [![(Top) An input image and its adversarial counterpart created with IFGS. (Center and bottom) Perturbation localization grids illustrated with black-gray images and adversarial examples generated by IFGS when the perturbation is only applied to the grey areas in the localization grids. $L_p$ norms of the perturbation are provided under each image. All of the adversarial examples were generated using AlexNet and successfully transfer to ResNet-50.[]{data-label="fig:adv_sq_fr"}](localization_masks/c1.png "fig:"){width="1.7cm"}]{}; (whitehead) at (4, 1) [![(Top) An input image and its adversarial counterpart created with IFGS. (Center and bottom) Perturbation localization grids illustrated with black-gray images and adversarial examples generated by IFGS when the perturbation is only applied to the grey areas in the localization grids. $L_p$ norms of the perturbation are provided under each image. All of the adversarial examples were generated using AlexNet and successfully transfer to ResNet-50.[]{data-label="fig:adv_sq_fr"}](localization_masks/c2.png "fig:"){width="1.7cm"}]{}; (whitehead) at (6, 1) [![(Top) An input image and its adversarial counterpart created with IFGS. (Center and bottom) Perturbation localization grids illustrated with black-gray images and adversarial examples generated by IFGS when the perturbation is only applied to the grey areas in the localization grids. $L_p$ norms of the perturbation are provided under each image. All of the adversarial examples were generated using AlexNet and successfully transfer to ResNet-50.[]{data-label="fig:adv_sq_fr"}](localization_masks/c3.png "fig:"){width="1.7cm"}]{};
1[-5.1]{} at (0, 1) [Adversarial\
examples]{}; (russell) at (2, 1) [![(Top) An input image and its adversarial counterpart created with IFGS. (Center and bottom) Perturbation localization grids illustrated with black-gray images and adversarial examples generated by IFGS when the perturbation is only applied to the grey areas in the localization grids. $L_p$ norms of the perturbation are provided under each image. All of the adversarial examples were generated using AlexNet and successfully transfer to ResNet-50.[]{data-label="fig:adv_sq_fr"}](image_examples/3133_c1.png "fig:"){width="1.7cm"}]{}; at (2, 1-1.1) [$L_0=0.16$]{}; at (2, 1-1.35) [$L_2=2.37$]{}; at (2-0.05, 1-1.6) [$L_{\infty}=0.02$]{}; (whitehead) at (4, 1) [![(Top) An input image and its adversarial counterpart created with IFGS. (Center and bottom) Perturbation localization grids illustrated with black-gray images and adversarial examples generated by IFGS when the perturbation is only applied to the grey areas in the localization grids. $L_p$ norms of the perturbation are provided under each image. All of the adversarial examples were generated using AlexNet and successfully transfer to ResNet-50.[]{data-label="fig:adv_sq_fr"}](image_examples/3133_c2.png "fig:"){width="1.7cm"}]{}; at (4, 1-1.1) [$L_0=0.28$]{}; at (4, 1-1.35) [$L_2=2.49$]{}; at (4-0.05, 1-1.6) [$L_{\infty}=0.02$]{}; (whitehead) at (6, 1) [![(Top) An input image and its adversarial counterpart created with IFGS. (Center and bottom) Perturbation localization grids illustrated with black-gray images and adversarial examples generated by IFGS when the perturbation is only applied to the grey areas in the localization grids. $L_p$ norms of the perturbation are provided under each image. All of the adversarial examples were generated using AlexNet and successfully transfer to ResNet-50.[]{data-label="fig:adv_sq_fr"}](image_examples/3133_c3.png "fig:"){width="1.7cm"}]{}; at (6, 1-1.1) [$L_0=0.44$]{}; at (6, 1-1.35) [$L_2=6.52$]{}; at (6-0.05, 1-1.6) [$L_{\infty}=0.10$]{};
(-1, 1 -1.9) – (7, 1 -1.9);
1[-8.05]{} at (0, 1) [Perturbation\
localization\
masks\
(Random location)]{}; (russell) at (2, 1) [![(Top) An input image and its adversarial counterpart created with IFGS. (Center and bottom) Perturbation localization grids illustrated with black-gray images and adversarial examples generated by IFGS when the perturbation is only applied to the grey areas in the localization grids. $L_p$ norms of the perturbation are provided under each image. All of the adversarial examples were generated using AlexNet and successfully transfer to ResNet-50.[]{data-label="fig:adv_sq_fr"}](localization_masks/r1.png "fig:"){width="1.7cm"}]{}; (whitehead) at (4, 1) [![(Top) An input image and its adversarial counterpart created with IFGS. (Center and bottom) Perturbation localization grids illustrated with black-gray images and adversarial examples generated by IFGS when the perturbation is only applied to the grey areas in the localization grids. $L_p$ norms of the perturbation are provided under each image. All of the adversarial examples were generated using AlexNet and successfully transfer to ResNet-50.[]{data-label="fig:adv_sq_fr"}](localization_masks/r2.png "fig:"){width="1.7cm"}]{}; (whitehead) at (6, 1) [![(Top) An input image and its adversarial counterpart created with IFGS. (Center and bottom) Perturbation localization grids illustrated with black-gray images and adversarial examples generated by IFGS when the perturbation is only applied to the grey areas in the localization grids. $L_p$ norms of the perturbation are provided under each image. All of the adversarial examples were generated using AlexNet and successfully transfer to ResNet-50.[]{data-label="fig:adv_sq_fr"}](localization_masks/r3.png "fig:"){width="1.7cm"}]{};
1[-9.9]{} at (0, 1) [Adversarial\
examples]{}; (russell) at (2, 1) [![(Top) An input image and its adversarial counterpart created with IFGS. (Center and bottom) Perturbation localization grids illustrated with black-gray images and adversarial examples generated by IFGS when the perturbation is only applied to the grey areas in the localization grids. $L_p$ norms of the perturbation are provided under each image. All of the adversarial examples were generated using AlexNet and successfully transfer to ResNet-50.[]{data-label="fig:adv_sq_fr"}](image_examples/3133_f1.png "fig:"){width="1.7cm"}]{}; at (2, 1-1.1) [$L_0=0.17$]{}; at (2, 1-1.35) [$L_2=9.31$]{}; at (2-0.05, 1-1.6) [$L_{\infty}=0.23$]{}; (whitehead) at (4, 1) [![(Top) An input image and its adversarial counterpart created with IFGS. (Center and bottom) Perturbation localization grids illustrated with black-gray images and adversarial examples generated by IFGS when the perturbation is only applied to the grey areas in the localization grids. $L_p$ norms of the perturbation are provided under each image. All of the adversarial examples were generated using AlexNet and successfully transfer to ResNet-50.[]{data-label="fig:adv_sq_fr"}](image_examples/3133_f2.png "fig:"){width="1.7cm"}]{}; at (4, 1-1.1) [$L_0=0.24$]{}; at (4, 1-1.35) [$L_2=9.28$]{}; at (4-0.05, 1-1.6) [$L_{\infty}=0.24$]{}; (whitehead) at (6, 1) [![(Top) An input image and its adversarial counterpart created with IFGS. (Center and bottom) Perturbation localization grids illustrated with black-gray images and adversarial examples generated by IFGS when the perturbation is only applied to the grey areas in the localization grids. $L_p$ norms of the perturbation are provided under each image. All of the adversarial examples were generated using AlexNet and successfully transfer to ResNet-50.[]{data-label="fig:adv_sq_fr"}](image_examples/3133_f3.png "fig:"){width="1.7cm"}]{}; at (6, 1-1.1) [$L_0=0.44$]{}; at (6, 1-1.35) [$L_2=8.01$]{}; at (6-0.05, 1-1.6) [$L_{\infty}=0.16$]{};
Recent advancements in the field of machine learning (ML) — more specifically, in deep learning (DL) — have substantially increased the adoption rate of automated systems in everyday life [@Alexnet; @resnet; @resnext]. However, since their inception, these systems have been criticized for their lack of *interpretability*: it is often difficult or impossible to know precisely *why* an ML model produces a specific response for a given input, yet such information is highly relevant in many settings [@interpretation_fragile; @saliency_unreliability]. One manifestation of this shortcoming of current ML theory to understand DL models is the phenomenon of *adversarial examples* [@LBFGS], which has recently received much attention in the research community. Adversarial examples are data points specifically crafted by an adversary in order to force machine learning models into making mistakes. Often, these artificial examples are visually indistinguishable from natural data points, making it almost impossible for humans to detect them and calling into question the generalization ability of deep neural networks (DNN) [@schmidt2018adversarially; @ilyas2019adversarial].
Formally, adversarial examples are usually defined as follows [@LBFGS; @PGD_attack]. Given an ML model $f$ and an input $\bm{X}$, an adversarial example $\tilde{\bm{X}}$ satisfies (1) $\|\bm{X} - \tilde{\bm{X}}\|_p \leq \varepsilon$ for some chosen $L_p$ norm and perturbation budget $\varepsilon > 0$ and (2) $f(\bm{X}) \neq f(\tilde{\bm{X}})$. In other words, the perturbed input $\tilde{\bm{X}}$ must be “close” to the original input $\bm{X}$ as measured by an $L_p$ norm and the classifier $f$ must output different labels for $\bm{X}$ and $\tilde{\bm{X}}$. However, for sufficiently small values of $\varepsilon$, the two inputs are indistinguishable and should belong to the same class. Hence, the existence of adversarial examples for very small perturbation budgets indicates a failure of DL models to accurately capture the data manifold. Interestingly, depending on the attack used, adversarial examples can be highly *transferable*: an adversarial sample $\tilde{\bm{X}}$ that fools a certain classifier $f$ can also fool completely different classifiers trained for the same task [@DBLP:journals/corr/PapernotMG16; @cheng2019improvinge_black_black_box]. This so-called *transferability*, i.e., the degree to which an adversarial sample can fool other models, is a popular metric for assessing the effectiveness of a particular attack.
Through the generations of research in computer vision it was established that certain regions of images are more important for the identification of an object of interest than others [@moravev_image_parts_important; @schmid1997local_image_parts_important; @lowe_SIFT; @sun2014deep_face_parts_important; @guided_backprop; @grad_cam]. As such, research on localized adversarial attacks also shows that adversarial perturbation applied to these *important* regions may change the prediction faster and with less $L_p$ perturbation than attacks that apply the perturbation to the entire image [@one_pixel_attack; @LAVAN; @xu2018structured_new_local_adv_attack; @zajac2019adversarial_frame]. However, analyses to prevent adversarial examples often do not evaluate robustness against such regional attacks. Adversarial defenses are often studied exclusively against well-understood attacks such as FGS [@Goodfellow-expharnessing], JSMA [@JSMA], IFGS [@IFGS], Carlini & Wagner’s Attack [@CW_Attack], PGD [@PGD_attack], and BPDA [@athalye2018_obfuscated], where these attacks apply their perturbations to the entire image based on the magnitude of the loss gradient for each pixel and according to the $L_p$ norm constraints they set. We believe this lack of evaluation against regional attacks is because (1) regional attacks are often studied in permissive white-box settings which do not represent real-world scenarios and (2) the proposed attacks usually come with a completely new and complicated way of generating adversarial examples, thus making it not straightforward to apply these attacks to different datasets, especially not locally, as opposed to well-understood attacks.
In this work, we show that so-called “global” adversarial attacks can be easily modified to become localized attacks. As such, different from previous research efforts on localized perturbation, our study does not propose a novel attack. Instead, we introduce a general method for localizing the perturbations generated by existing non-localized attacks. We achieve this by multiplying the original perturbations by a simple binary mask (as shown in \[fig:adv\_sq\_fr\]), restricting the perturbation to specific image regions. We analyze both the transferability and the $L_p$ norm properties of the crafted adversarial examples, finding that the localized examples are about as effective as the examples generated by the original attacks (in terms of transferability), and with the localized versions often requiring significantly less $L_p$ distortion. The implementation of the proposed method is publicly available.[^1]
The finding that we can significantly reduce the required $L_p$ distortion while maintaining similar levels of effectiveness potentially undermines many existing defenses — certified or not — since these usually guarantee robustness against specific $L_p$ perturbation budgets [@wong2017provable; @croce2018provable; @andriushchenko2019provably; @ghiasi2020breaking_certified_defenses]. Reducing the required distortion attacks below such thresholds could render these defenses ineffective.
Framework {#Framework}
=========
**Data** Adversarial examples are mainly studied on MNIST [@lecun1998gradient], CIFAR [@CIFAR], or ImageNet [@ILSVRC15:rus]. However, as the field of adversarial machine learning evolved, due to shortcomings in terms of color channels and image sizes, the MNIST and CIFAR datasets are not deemed to be suitable for studies that represent real-world scenarios where adversarial examples pose a threat [@DBLP:journalsCarliniW17]. Following this observation, we use images taken from the test set of the ImageNet dataset in order to generate adversarial examples.
**Models** Although convolutional architectures were already used in the work of @lecun1998gradient, it was the success of AlexNet in 2012 that popularized DNN architectures [@Alexnet]. Recent research in the field of adversarial robustness also revealed AlexNet to be one of the more robust architectures [@su2018robustness_18_imagenet_models_evaluation]. Following the success of AlexNet, VGG [@VGG] architectures were proposed with smaller convolutional kernel sizes. Thanks to their simple architecture, VGG architectures are still popular today in many computer vision approaches. In order to overcome problems with vanishing gradients in deep architectures, @resnet proposed ResNet architectures, introducing the usage of residual layers. These residual architectures were later expanded upon and are currently some of the most frequently used architectures for solving a variety of problems in the field of deep learning [@resnext; @resnext_video]. Given the history of the aforementioned architectures in the field of adversarial machine learning, as well as in other deep learning areas, we opted for the use of AlexNet, VGG-16, and ResNet-50 in our experiments.
Experimental Setup {#Experimental Setup}
==================
**Generating adversarial examples** @DBLP:journalsCarliniW17 demonstrated the fragility of adversarial examples generated by single-step attacks and argued that iterative attacks should be used for evaluating novel defenses. Iterative attacks calculate and add perturbation to the input iteratively according to the rule $$\begin{aligned}
\bm{X}_{n+1} = \bm{X}_{n} + \bm{P}_{n} \,,\end{aligned}$$ where $\bm{X}_{n}$ and $\bm{P}_{n}$ represent the input and the perturbation generated at the $n$th iteration, respectively. In this study we generate the perturbation as follows: $$\begin{aligned}
&\bm{P}_{n} = \alpha \, \text{sign} \big( \nabla_x J(g(\theta, \bm{X}_{n})_c) \big) \,,\end{aligned}$$ where $\nabla_x J(g(\theta, \bm{X}_{n})_c)$ represents the gradient with respect to $\bm{X}$ obtained with the cross-entropy loss ($J$) when targeting the class $c$. We use $\alpha=0.004$ as the perturbation multiplier which approximately corresponds to changing the pixel values of images by $1/255$ at each iteration and perform this attack for $250$ iterations. Typically, adversarial attacks such as FGS, IFGS, and PGD enforce a constraint on the magnitude $\|\bm{X} - \tilde{\bm{X}}\|_p$ of the perturbation. However, in order to make a valid comparison between adversarial examples in terms of $L_0$, $L_{2}$, and $L_{\infty}$ norms, we only enforce a discretization constraint, thus ensuring that the produced adversarial examples can be represented as valid images (i.e., the pixel values of $\tilde{\bm{X}}$ lie within the range $[0,1]$, as can be expected from regular images).
**Localizing adversarial perturbation** In a previous research effort, we successfully used the Hadamard product to select target pixels for generating adversarial examples in the context of semantic segmentation [@ozbulak2019impact]. In order to localize the perturbation to selected regions, we employ a similar approach in this research effort, making use of $$\begin{aligned}
\bm{X}_{n+1} = \bm{X}_{n} + \bm{P}_{n} \odot \bm{L} \,,\end{aligned}$$ where $\bm{L}$ is a *localization mask*, i.e., a binary tensor of the same shape as the input. In this tensor, regions where the perturbation needs to be applied are set to $1$ while the remainder is set to $0$.
(4,4) (0.1,0.1)(0,1)[4]{}[(1,0)[3]{}]{} (0.1,0.1)(1,0)[4]{}[(0,1)[3]{}]{}
(0.3,0.55)[$52\%$]{} (1.3,0.55)[$59\%$]{} (2.25,0.55)[$100\%$]{}
(0.3,1.55)[$60\%$]{} (1.25,1.55)[$100\%$]{} (2.3,1.55)[$56\%$]{}
(0.25,2.55)[$100\%$]{} (1.3,2.55)[$73\%$]{} (2.3,2.55)[$66\%$]{}
(-0.3,2.3) (-0.3,1.25) (-0.3,0.05)
(0.12,3.3)[AlexNet]{} (1.12,3.3)[VGG-16]{} (2.12,3.3)[ResNet-50]{}
(-0.75,0.75) (0.75,3.75)[Target Model]{} (-0.5,-0.5)[(a) $17\%$ of pixels selected]{}
(4,4) (0.1,0.1)(0,1)[4]{}[(1,0)[3]{}]{} (0.1,0.1)(1,0)[4]{}[(0,1)[3]{}]{}
(0.3,0.55)[$67\%$]{} (1.3,0.55)[$65\%$]{} (2.25,0.55)[$100\%$]{}
(0.3,1.55)[$70\%$]{} (1.25,1.55)[$100\%$]{} (2.3,1.55)[$63\%$]{}
(0.25,2.55)[$100\%$]{} (1.3,2.55)[$76\%$]{} (2.3,2.55)[$67\%$]{}
(-0.3,2.3) (-0.3,1.25) (-0.3,0.05)
(0.12,3.3)[AlexNet]{} (1.12,3.3)[VGG-16]{} (2.12,3.3)[ResNet-50]{}
(-0.75,0.75) (0.75,3.75)[Target Model]{} (-0.5,-0.5)[(b) $28\%$ of pixels selected]{}
(4,4) (0.1,0.1)(0,1)[4]{}[(1,0)[3]{}]{} (0.1,0.1)(1,0)[4]{}[(0,1)[3]{}]{}
(0.3,0.55)[$78\%$]{} (1.3,0.55)[$77\%$]{} (2.25,0.55)[$100\%$]{}
(0.3,1.55)[$83\%$]{} (1.25,1.55)[$100\%$]{} (2.3,1.55)[$75\%$]{}
(0.25,2.55)[$100\%$]{} (1.3,2.55)[$78\%$]{} (2.3,2.55)[$75\%$]{}
(-0.3,2.3) (-0.3,1.25) (-0.3,0.05)
(0.12,3.3)[AlexNet]{} (1.12,3.3)[VGG-16]{} (2.12,3.3)[ResNet-50]{}
(-0.75,0.75) (0.75,3.75)[Target Model]{} (-0.5,-0.5)[(c) $45\%$ of pixels selected]{}
[llcc|cc|cc|cc|cc|cc]{} & Source: & & &\
& Target: & & & & & &\
& Norm: & $L_2$ & $L_{\infty}$ & $L_2$ & $L_{\infty}$ & $L_2$ & $L_{\infty}$ & $L_2$ & $L_{\infty}$ & $L_2$ & $L_{\infty}$ & $L_2$ & $L_{\infty}$\
& $7.35$ & $0.07$ & $6.39$ & $0.05$ & $6.91$ & $0.07$ & $3.62$ & $0.02$ & $6.79$ & $0.07$ & $3.76$ & $0.02$\
& & $(5.37)$ & $(0.08)$ & $(4.50)$ & $(0.06)$ & $(4.17)$ & $(0.05)$ & $(3.16)$ & $(0.04)$ & $(4.31)$ & $(0.06)$ & $(2.20)$ & $(0.02)$\
& & $6.55$ & $0.15$ & $5.33$ & $0.11$ & $4.01$ & $0.10$ & $3.41$ & $0.09$ & $3.54$ & $0.09$ & $2.79$ & $0.06$\
& & $(4.36)$ & $(0.14)$ & $(3.52)$ & $(0.10)$ & $(2.64)$ & $(0.09)$ & $(2.77)$ & $(0.10)$ & $(2.54)$ & $(0.09)$ & $(2.23)$ & $(0.07)$\
& & $6.47$ & $0.11$ & $6.30$ & $0.10$ & $5.01$ & $0.10$ & $3.68$ & $0.06$ & $4.50$ & $0.09$ & $3.70$ & $0.06$\
& & $(4.48)$ & $(0.11)$ & $(4.45)$ & $(0.11)$ & $(2.99)$ & $(0.08)$ & $(3.05)$ & $(0.07)$ & $(2.93)$ & $(0.08)$ & $(3.09)$ & $(0.08)$\
& & $6.80$ & $0.10$ & $6.46$ & $0.09$ & $6.71$ & $0.11$ & $3.92$ & $0.05$ & $6.64$ & $0.11$ & $4.65$ & $0.07$\
& & $(4.48)$ & $(0.10)$ & $(4.33)$ & $(0.09)$ & $(3.79)$ & $(0.08)$ & $(3.07)$ & $(0.06)$ & $(3.90)$ & $(0.08)$ & $(3.54)$ & $(0.07)$\
& & $9.86$ & $0.18$ & $10.1$ & $0.20$ & $6.07$ & $0.16$ & $4.64$ & $0.12$ & $4.77$ & $0.13$ & $4.32$ & $0.11$\
& & $(8.37)$ & $(0.20)$ & $(7.94)$ & $(0.21)$ & $(3.74)$ & $(0.14)$ & $(3.61)$ & $(0.15)$ & $(2.88)$ & $(0.12)$ & $(2.90)$ & $(0.11)$\
& & $8.92$ & $0.13$ & $8.63$ & $0.13$ & $6.71$ & $0.15$ & $4.50$ & $0.08$ & $5.68$ & $0.12$ & $4.85$ & $0.10$\
& & $(6.60)$ & $(0.13)$ & $(6.52)$ & $(0.14)$ & $(4.04)$ & $(0.12)$ & $(2.96)$ & $(0.08)$ & $(3.25)$ & $(0.09)$ & $(3.44)$ & $(0.10)$\
& & $8.44$ & $0.12$ & $7.23$ & $0.09$ & $7.79$ & $0.14$ & $5.44$ & $0.08$ & $7.02$ & $0.12$ & $5.78$ & $0.09$\
& & $(5.72)$ & $(0.13)$ & $(4.94)$ & $(0.11)$ & $(4.17)$ & $(0.09)$ & $(3.89)$ & $(0.09)$ & $(3.90)$ & $(0.09)$ & $(3.79)$ & $(0.08)$\
& & $8.11$ & $0.15$ & $7.41$ & $0.13$ & $5.20$ & $0.13$ & $4.43$ & $0.10$ & $4.59$ & $0.10$ & $3.81$ & $0.08$\
& & $(5.63)$ & $(0.16)$ & $(4.63)$ & $(0.14)$ & $(3.14)$ & $(0.11)$ & $(3.30)$ & $(0.12)$ & $(2.65)$ & $(0.09)$ & $(2.92)$ & $(0.09)$\
& & $6.82$ & $0.10$ & $7.51$ & $0.11$ & $5.97$ & $0.12$ & $4.29$ & $0.07$ & $5.50$ & $0.11$ & $4.35$ & $0.07$\
& & $(4.99)$ & $(0.12)$ & $(4.54)$ & $(0.11)$ & $(3.55)$ & $(0.10)$ & $(2.91)$ & $(0.07)$ & $(3.14)$ & $(0.09)$ & $(3.02)$ & $(0.08)$\
& & $7.42$ & $0.10$ & $6.76$ & $0.09$ & $7.21$ & $0.12$ & $4.61$ & $0.06$ & $7.39$ & $0.12$ & $5.04$ & $0.07$\
& & $(4.80)$ & $(0.11)$ & $(4.20)$ & $(0.09)$ & $(3.98)$ & $(0.09)$ & $(3.41)$ & $(0.07)$ & $(4.03)$ & $(0.08)$ & $(3.53)$ & $(0.07)$\
\[tbl:exp\_results\_ldist\]
**Perturbation regions** In this study, we evaluate the use of three different perturbation regions, each with three different settings. These regions are (1) randomly selected pixels, (2) center square pixels, and (3) outer frame pixels. For (1), we randomly select $\{45\%, 28\%, 17\% \}$ of all pixels, where these percentages approximately correspond to a center square with a side length of $\{90, 120, 150\}$ pixels and an outer frame with a width of $\{20, 34, 58\}$ pixels, respectively. Thus, the number of selected pixels for all regions in each of the three different settings is virtually the same. Visual examples of the localization masks are provided in \[fig:pert\_localiztion\_masks\] in \[appA\].
**Calculating $L_p$ distances** We calculate $L_p$ distances ($p = 0, 2, \infty$) between genuine images and their adversarial counterparts, similar to calculations in @JSMA and @DBLP:journalsCarliniW17. A detailed description of these calculations for our settings is also provided in \[appA\].
Experiments {#Experiments}
===========
We first analyze model-to-model transferability (also called black-box transferability) for adversarial examples with localized perturbation. For each model-to-model pair, we generate $2,000$ adversarial examples that transfer from the source model to the target model. Using the same initial images as these adversarial examples do, we now apply perturbation to nine different regions (i.e., three regions, with each region coming with three different settings). In \[fig:localized\_transferability\], we present the percentage of adversarial examples that transfer from model to model when localized perturbation is applied, as opposed to performing the adversarial attack without any localization constraints. We see that a large portion of adversarial examples maintains model-to-model transferability when perturbation is applied to local regions.
For the adversarial examples that maintain model-to-model transferability, \[tbl:exp\_results\_ldist\] provides exhaustive details on the mean and standard deviation of the $L_2$ and $L_\infty$ properties of the produced adversarial examples. $L_0$ norms are omitted from this table because adversarial examples with regional perturbation almost always have reduced mean $L_0$ norms (\[fig:percentage\_of\_adv\_with\_less\_lp\_norm\] and \[tbl:exp\_results\_l0\] in \[appB\]). Adversarial perturbation applied to the center square of an image reduces the mean $L_2$ norm while it increases the mean $L_{\infty}$ norm. However, with additional experiments, we discover that $43\%$ of the individual adversarial examples with localized perturbation have lower $L_{\infty}$ distances than their non-locally perturbed counterparts, showing that localized perturbation nevertheless reduces the $L_{\infty}$ norm for a large number of cases. The detailed breakdown of this analysis can be found in \[appB\].
Another important observation we make is the difference in perturbation for different regions. As can be seen, not all regions are equally important when it comes to manipulating the prediction of a DNN with adversarial perturbation. We clearly observe adversarial perturbation applied to the center square being more influential than perturbation in other regions. Surprisingly, applying perturbation to randomly selected pixels requires less distortion than applying it to the frame of an image, further highlighting the differences between *important* and *unimportant* regions. Allowing perturbation in a more condensed area versus a more expanded area provides different results for the center square region and the other two regions. Increasing the number of selected pixels in the center square region also increases the $L_2$ norm of the perturbation, while doing so for frame and random pixels reduces the aforementioned norm.
Conclusion and Future Directions {#Conclustion and Future Directions}
================================
We have proposed a simple and general method for localizing perturbations generated by existing adversarial attacks to specific image regions. Our method is experimentally confirmed to be effective, maintaining high black-box transferability at distortion levels that are significantly lower than the distortion levels required by existing attacks. The reduction in the amount of perturbation achieved by our method raises the concern that existing adversarial defenses may be undermined, since these are usually designed to be effective only against non-local attacks requiring larger perturbation budgets.
Our main priority for future work is (1) to investigate to what extent our localization method can fool state-of-the-art adversarial defenses as well as (2) to more precisely identify regions of importance where this localized perturbation can be made more effective, linking the observations made in this study to the interpretability of DNNs.
Experimental Details {#appA}
====================
1[0]{} at (0, 1) [Center square\
localization]{}; (a) at (2, 1) [![The localization masks used in this study. The given percentages correspond to the number of selected pixels compared to the total number of available pixels.[]{data-label="fig:pert_localiztion_masks"}](localization_masks/c1.png "fig:"){width="1.8cm"}]{}; at (2, 1-1.15) [$16.1\%$]{}; (b) at (4, 1) [![The localization masks used in this study. The given percentages correspond to the number of selected pixels compared to the total number of available pixels.[]{data-label="fig:pert_localiztion_masks"}](localization_masks/c2.png "fig:"){width="1.8cm"}]{}; at (4, 1-1.15) [$28.6\%$]{}; (c) at (6, 1) [![The localization masks used in this study. The given percentages correspond to the number of selected pixels compared to the total number of available pixels.[]{data-label="fig:pert_localiztion_masks"}](localization_masks/c3.png "fig:"){width="1.8cm"}]{}; at (6, 1-1.15) [$44.8\%$]{};
1[-2.5]{} at (0, 1) [Random\
localization]{}; (russell) at (2, 1) [![The localization masks used in this study. The given percentages correspond to the number of selected pixels compared to the total number of available pixels.[]{data-label="fig:pert_localiztion_masks"}](localization_masks/r1.png "fig:"){width="1.8cm"}]{}; at (2, 1-1.15) [$17.0\%$]{}; (whitehead) at (4, 1) [![The localization masks used in this study. The given percentages correspond to the number of selected pixels compared to the total number of available pixels.[]{data-label="fig:pert_localiztion_masks"}](localization_masks/r2.png "fig:"){width="1.8cm"}]{}; at (4, 1-1.15) [$28.0\%$]{}; (whitehead) at (6, 1) [![The localization masks used in this study. The given percentages correspond to the number of selected pixels compared to the total number of available pixels.[]{data-label="fig:pert_localiztion_masks"}](localization_masks/r3.png "fig:"){width="1.8cm"}]{}; at (6, 1-1.15) [$45.0\%$]{};
1[-5]{} at (0, 1) [Frame\
localization]{}; (russell) at (2, 1) [![The localization masks used in this study. The given percentages correspond to the number of selected pixels compared to the total number of available pixels.[]{data-label="fig:pert_localiztion_masks"}](localization_masks/f1.png "fig:"){width="1.8cm"}]{}; at (2, 1-1.15) [$17.0\%$]{}; (whitehead) at (4, 1) [![The localization masks used in this study. The given percentages correspond to the number of selected pixels compared to the total number of available pixels.[]{data-label="fig:pert_localiztion_masks"}](localization_masks/f2.png "fig:"){width="1.8cm"}]{}; at (4, 1-1.15) [$28.0\%$]{}; (whitehead) at (6, 1) [![The localization masks used in this study. The given percentages correspond to the number of selected pixels compared to the total number of available pixels.[]{data-label="fig:pert_localiztion_masks"}](localization_masks/f3.png "fig:"){width="1.8cm"}]{}; at (6, 1-1.15) [$45.0\%$]{};
1[1.3]{} at (0, 1) [No localization]{}; at (2, 1) [Center]{}; at (4, 1) [Frame]{}; at (6, 1) [Random]{};
1[0]{} (a) at (0, 1) [![$L_0$, $L_2$, and $L_{\infty}$ distances between the initial images and their adversarial counterparts for the adversarial examples that originate from the same initial image but that were perturbed using different localization methods. All of the adversarial examples successfully transfer to models they are not originated from.[]{data-label="fig:additional_examples"}](app_samples/2079_noloc.png "fig:"){width="1.8cm"}]{}; at (0, 1-1.1) [$L_0=0.96$]{}; at (0, 1-1.4) [$L_2=3.25$]{}; at (0-0.06, 1-1.7) [$L_{\infty}=0.02$]{}; (a) at (2, 1) [![$L_0$, $L_2$, and $L_{\infty}$ distances between the initial images and their adversarial counterparts for the adversarial examples that originate from the same initial image but that were perturbed using different localization methods. All of the adversarial examples successfully transfer to models they are not originated from.[]{data-label="fig:additional_examples"}](app_samples/2079_90cr.png "fig:"){width="1.8cm"}]{}; at (2, 1-1.1) [$L_0=0.15$]{}; at (2, 1-1.4) [$L_2=0.83$]{}; at (2-0.06, 1-1.7) [$L_{\infty}=0.01$]{}; (b) at (4, 1) [![$L_0$, $L_2$, and $L_{\infty}$ distances between the initial images and their adversarial counterparts for the adversarial examples that originate from the same initial image but that were perturbed using different localization methods. All of the adversarial examples successfully transfer to models they are not originated from.[]{data-label="fig:additional_examples"}](app_samples/2079_90fr.png "fig:"){width="1.8cm"}]{}; at (4, 1-1.1) [$L_0=0.17$]{}; at (4, 1-1.4) [$L_2=3.72$]{}; at (4-0.06, 1-1.7) [$L_{\infty}=0.03$]{}; (c) at (6, 1) [![$L_0$, $L_2$, and $L_{\infty}$ distances between the initial images and their adversarial counterparts for the adversarial examples that originate from the same initial image but that were perturbed using different localization methods. All of the adversarial examples successfully transfer to models they are not originated from.[]{data-label="fig:additional_examples"}](app_samples/2079_90rand.png "fig:"){width="1.8cm"}]{}; at (6, 1-1.1) [$L_0=0.16$]{}; at (6, 1-1.4) [$L_2=1.14$]{}; at (6-0.06, 1-1.7) [$L_{\infty}=0.01$]{};
1[-3]{} (a) at (0, 1) [![$L_0$, $L_2$, and $L_{\infty}$ distances between the initial images and their adversarial counterparts for the adversarial examples that originate from the same initial image but that were perturbed using different localization methods. All of the adversarial examples successfully transfer to models they are not originated from.[]{data-label="fig:additional_examples"}](app_samples/3659_noloc.png "fig:"){width="1.8cm"}]{}; at (0, 1-1.1) [$L_0=0.99$]{}; at (0, 1-1.4) [$L_2=10.5$]{}; at (0-0.06, 1-1.7) [$L_{\infty}=0.12$]{}; (a) at (2, 1) [![$L_0$, $L_2$, and $L_{\infty}$ distances between the initial images and their adversarial counterparts for the adversarial examples that originate from the same initial image but that were perturbed using different localization methods. All of the adversarial examples successfully transfer to models they are not originated from.[]{data-label="fig:additional_examples"}](app_samples/3659_90cr.png "fig:"){width="1.8cm"}]{}; at (2, 1-1.1) [$L_0=0.16$]{}; at (2, 1-1.4) [$L_2=3.51$]{}; at (2-0.06, 1-1.7) [$L_{\infty}=0.05$]{}; (b) at (4, 1) [![$L_0$, $L_2$, and $L_{\infty}$ distances between the initial images and their adversarial counterparts for the adversarial examples that originate from the same initial image but that were perturbed using different localization methods. All of the adversarial examples successfully transfer to models they are not originated from.[]{data-label="fig:additional_examples"}](app_samples/3659_90fr.png "fig:"){width="1.8cm"}]{}; at (4, 1-1.1) [$L_0=0.17$]{}; at (4, 1-1.4) [$L_2=25.4$]{}; at (4-0.06, 1-1.7) [$L_{\infty}=0.55$]{}; (c) at (6, 1) [![$L_0$, $L_2$, and $L_{\infty}$ distances between the initial images and their adversarial counterparts for the adversarial examples that originate from the same initial image but that were perturbed using different localization methods. All of the adversarial examples successfully transfer to models they are not originated from.[]{data-label="fig:additional_examples"}](app_samples/3659_90rand.png "fig:"){width="1.8cm"}]{}; at (6, 1-1.1) [$L_0=0.17$]{}; at (6, 1-1.4) [$L_2=7.02$]{}; at (6-0.06, 1-1.7) [$L_{\infty}=0.09$]{};
1[-6]{} (a) at (0, 1) [![$L_0$, $L_2$, and $L_{\infty}$ distances between the initial images and their adversarial counterparts for the adversarial examples that originate from the same initial image but that were perturbed using different localization methods. All of the adversarial examples successfully transfer to models they are not originated from.[]{data-label="fig:additional_examples"}](app_samples/7153_noloc.png "fig:"){width="1.8cm"}]{}; at (0, 1-1.1) [$L_0=0.99$]{}; at (0, 1-1.4) [$L_2=8.80$]{}; at (0-0.06, 1-1.7) [$L_{\infty}=0.10$]{}; (a) at (2, 1) [![$L_0$, $L_2$, and $L_{\infty}$ distances between the initial images and their adversarial counterparts for the adversarial examples that originate from the same initial image but that were perturbed using different localization methods. All of the adversarial examples successfully transfer to models they are not originated from.[]{data-label="fig:additional_examples"}](app_samples/7153_90cr.png "fig:"){width="1.8cm"}]{}; at (2, 1-1.1) [$L_0=0.16$]{}; at (2, 1-1.4) [$L_2=2.91$]{}; at (2-0.06, 1-1.7) [$L_{\infty}=0.03$]{}; (b) at (4, 1) [![$L_0$, $L_2$, and $L_{\infty}$ distances between the initial images and their adversarial counterparts for the adversarial examples that originate from the same initial image but that were perturbed using different localization methods. All of the adversarial examples successfully transfer to models they are not originated from.[]{data-label="fig:additional_examples"}](app_samples/7153_90fr.png "fig:"){width="1.8cm"}]{}; at (4, 1-1.1) [$L_0=0.17$]{}; at (4, 1-1.4) [$L_2=5.97$]{}; at (4-0.06, 1-1.7) [$L_{\infty}=0.07$]{}; (c) at (6, 1) [![$L_0$, $L_2$, and $L_{\infty}$ distances between the initial images and their adversarial counterparts for the adversarial examples that originate from the same initial image but that were perturbed using different localization methods. All of the adversarial examples successfully transfer to models they are not originated from.[]{data-label="fig:additional_examples"}](app_samples/7153_90rand.png "fig:"){width="1.8cm"}]{}; at (6, 1-1.1) [$L_0=0.13$]{}; at (6, 1-1.4) [$L_2=0.44$]{}; at (6-0.06, 1-1.7) [$L_{\infty}=0.01$]{};
1[-9]{} (a) at (0, 1) [![$L_0$, $L_2$, and $L_{\infty}$ distances between the initial images and their adversarial counterparts for the adversarial examples that originate from the same initial image but that were perturbed using different localization methods. All of the adversarial examples successfully transfer to models they are not originated from.[]{data-label="fig:additional_examples"}](app_samples/2955_noloc.png "fig:"){width="1.8cm"}]{}; at (0, 1-1.1) [$L_0=0.99$]{}; at (0, 1-1.4) [$L_2=11.9$]{}; at (0-0.06, 1-1.7) [$L_{\infty}=0.16$]{}; (a) at (2, 1) [![$L_0$, $L_2$, and $L_{\infty}$ distances between the initial images and their adversarial counterparts for the adversarial examples that originate from the same initial image but that were perturbed using different localization methods. All of the adversarial examples successfully transfer to models they are not originated from.[]{data-label="fig:additional_examples"}](app_samples/2955_120cr.png "fig:"){width="1.8cm"}]{}; at (2, 1-1.1) [$L_0=0.28$]{}; at (2, 1-1.4) [$L_2=6.98$]{}; at (2-0.06, 1-1.7) [$L_{\infty}=0.12$]{}; (b) at (4, 1) [![$L_0$, $L_2$, and $L_{\infty}$ distances between the initial images and their adversarial counterparts for the adversarial examples that originate from the same initial image but that were perturbed using different localization methods. All of the adversarial examples successfully transfer to models they are not originated from.[]{data-label="fig:additional_examples"}](app_samples/2955_120fr.png "fig:"){width="1.8cm"}]{}; at (4, 1-1.1) [$L_0=0.25$]{}; at (4, 1-1.4) [$L_2=4.82$]{}; at (4-0.06, 1-1.7) [$L_{\infty}=0.05$]{}; (c) at (6, 1) [![$L_0$, $L_2$, and $L_{\infty}$ distances between the initial images and their adversarial counterparts for the adversarial examples that originate from the same initial image but that were perturbed using different localization methods. All of the adversarial examples successfully transfer to models they are not originated from.[]{data-label="fig:additional_examples"}](app_samples/2955_120rand.png "fig:"){width="1.8cm"}]{}; at (6, 1-1.1) [$L_0=0.27$]{}; at (6, 1-1.4) [$L_2=4.39$]{}; at (6-0.06, 1-1.7) [$L_{\infty}=0.04$]{};
1[-12]{} (a) at (0, 1) [![$L_0$, $L_2$, and $L_{\infty}$ distances between the initial images and their adversarial counterparts for the adversarial examples that originate from the same initial image but that were perturbed using different localization methods. All of the adversarial examples successfully transfer to models they are not originated from.[]{data-label="fig:additional_examples"}](app_samples/6483_noloc.png "fig:"){width="1.8cm"}]{}; at (0, 1-1.1) [$L_0=0.99$]{}; at (0, 1-1.4) [$L_2=7.06$]{}; at (0-0.06, 1-1.7) [$L_{\infty}=0.06$]{}; (a) at (2, 1) [![$L_0$, $L_2$, and $L_{\infty}$ distances between the initial images and their adversarial counterparts for the adversarial examples that originate from the same initial image but that were perturbed using different localization methods. All of the adversarial examples successfully transfer to models they are not originated from.[]{data-label="fig:additional_examples"}](app_samples/6483_120cr.png "fig:"){width="1.8cm"}]{}; at (2, 1-1.1) [$L_0=0.28$]{}; at (2, 1-1.4) [$L_2=4.39$]{}; at (2-0.06, 1-1.7) [$L_{\infty}=0.06$]{}; (b) at (4, 1) [![$L_0$, $L_2$, and $L_{\infty}$ distances between the initial images and their adversarial counterparts for the adversarial examples that originate from the same initial image but that were perturbed using different localization methods. All of the adversarial examples successfully transfer to models they are not originated from.[]{data-label="fig:additional_examples"}](app_samples/6483_120fr.png "fig:"){width="1.8cm"}]{}; at (4, 1-1.1) [$L_0=0.28$]{}; at (4, 1-1.4) [$L_2=6.08$]{}; at (4-0.06, 1-1.7) [$L_{\infty}=0.08$]{}; (c) at (6, 1) [![$L_0$, $L_2$, and $L_{\infty}$ distances between the initial images and their adversarial counterparts for the adversarial examples that originate from the same initial image but that were perturbed using different localization methods. All of the adversarial examples successfully transfer to models they are not originated from.[]{data-label="fig:additional_examples"}](app_samples/6483_120rand.png "fig:"){width="1.8cm"}]{}; at (6, 1-1.1) [$L_0=0.28$]{}; at (6, 1-1.4) [$L_2=4.51$]{}; at (6-0.06, 1-1.7) [$L_{\infty}=0.04$]{};
1[-15]{} (a) at (0, 1) [![$L_0$, $L_2$, and $L_{\infty}$ distances between the initial images and their adversarial counterparts for the adversarial examples that originate from the same initial image but that were perturbed using different localization methods. All of the adversarial examples successfully transfer to models they are not originated from.[]{data-label="fig:additional_examples"}](app_samples/4842_noloc.png "fig:"){width="1.8cm"}]{}; at (0, 1-1.1) [$L_0=0.99$]{}; at (0, 1-1.4) [$L_2=11.6$]{}; at (0-0.06, 1-1.7) [$L_{\infty}=0.13$]{}; (a) at (2, 1) [![$L_0$, $L_2$, and $L_{\infty}$ distances between the initial images and their adversarial counterparts for the adversarial examples that originate from the same initial image but that were perturbed using different localization methods. All of the adversarial examples successfully transfer to models they are not originated from.[]{data-label="fig:additional_examples"}](app_samples/4842_150cr.png "fig:"){width="1.8cm"}]{}; at (2, 1-1.1) [$L_0=0.44$]{}; at (2, 1-1.4) [$L_2=3.80$]{}; at (2-0.06, 1-1.7) [$L_{\infty}=0.03$]{}; (b) at (4, 1) [![$L_0$, $L_2$, and $L_{\infty}$ distances between the initial images and their adversarial counterparts for the adversarial examples that originate from the same initial image but that were perturbed using different localization methods. All of the adversarial examples successfully transfer to models they are not originated from.[]{data-label="fig:additional_examples"}](app_samples/4842_150fr.png "fig:"){width="1.8cm"}]{}; at (4, 1-1.1) [$L_0=0.45$]{}; at (4, 1-1.4) [$L_2=18.2$]{}; at (4-0.06, 1-1.7) [$L_{\infty}=0.32$]{}; (c) at (6, 1) [![$L_0$, $L_2$, and $L_{\infty}$ distances between the initial images and their adversarial counterparts for the adversarial examples that originate from the same initial image but that were perturbed using different localization methods. All of the adversarial examples successfully transfer to models they are not originated from.[]{data-label="fig:additional_examples"}](app_samples/4842_150rand.png "fig:"){width="1.8cm"}]{}; at (6, 1-1.1) [$L_0=0.45$]{}; at (6, 1-1.4) [$L_2=18.26$]{}; at (6-0.06, 1-1.7) [$L_{\infty}=0.32$]{};
(4,4) (0.1,0.1)(0,1)[4]{}[(1,0)[3]{}]{} (0.1,0.1)(1,0)[4]{}[(0,1)[3]{}]{}
(0.3,0.55)[$99\%$]{} (1.3,0.55)[$99\%$]{} (2.45,0.55)
(0.3,1.55)[$99\%$]{} (1.45,1.55) (2.3,1.55)[$99\%$]{}
(0.45,2.55) (1.3,2.55)[$99\%$]{} (2.3,2.55)[$99\%$]{}
(-0.3,2.3) (-0.3,1.25) (-0.3,0.05)
(0.12,3.3)[AlexNet]{} (1.12,3.3)[VGG-16]{} (2.12,3.3)[ResNet-50]{}
(-0.75,0.75) (0.75,3.75)[Target Model]{} (-0.5,-0.5)[(a) $17\%$ of pixels selected]{}
(4,4) (0.1,0.1)(0,1)[4]{}[(1,0)[3]{}]{} (0.1,0.1)(1,0)[4]{}[(0,1)[3]{}]{}
(0.3,0.55)[$99\%$]{} (1.3,0.55)[$99\%$]{} (2.45,0.55)
(0.3,1.55)[$99\%$]{} (1.45,1.55) (2.3,1.55)[$99\%$]{}
(0.45,2.55) (1.3,2.55)[$99\%$]{} (2.3,2.55)[$99\%$]{}
(-0.3,2.3) (-0.3,1.25) (-0.3,0.05)
(0.12,3.3)[AlexNet]{} (1.12,3.3)[VGG-16]{} (2.12,3.3)[ResNet-50]{}
(-0.75,0.75) (0.75,3.75)[Target Model]{} (-0.5,-0.5)[(b) $28\%$ of pixels selected]{}
(4,4) (0.1,0.1)(0,1)[4]{}[(1,0)[3]{}]{} (0.1,0.1)(1,0)[4]{}[(0,1)[3]{}]{}
(0.3,0.55)[$99\%$]{} (1.3,0.55)[$99\%$]{} (2.45,0.55)
(0.3,1.55)[$99\%$]{} (1.45,1.55) (2.3,1.55)[$99\%$]{}
(0.45,2.55) (1.3,2.55)[$99\%$]{} (2.3,2.55)[$99\%$]{}
(-0.3,2.3) (-0.3,1.25) (-0.3,0.05)
(0.12,3.3)[AlexNet]{} (1.12,3.3)[VGG-16]{} (2.12,3.3)[ResNet-50]{}
(-0.75,0.75) (0.75,3.75)[Target Model]{} (-0.5,-0.5)[(c) $45\%$ of pixels selected]{}
(4,4) (0.1,0.1)(0,1)[4]{}[(1,0)[3]{}]{} (0.1,0.1)(1,0)[4]{}[(0,1)[3]{}]{}
(0.3,0.55)[$82\%$]{} (1.3,0.55)[$85\%$]{} (2.45,0.55)
(0.3,1.55)[$77\%$]{} (1.45,1.55) (2.3,1.55)[$84\%$]{}
(0.45,2.55) (1.3,2.55)[$77\%$]{} (2.3,2.55)[$81\%$]{}
(-0.3,2.3) (-0.3,1.25) (-0.3,0.05)
(0.12,3.3)[AlexNet]{} (1.12,3.3)[VGG-16]{} (2.12,3.3)[ResNet-50]{}
(-0.75,0.75) (0.75,3.75)[Target Model]{} (-0.5,-0.5)[(a) $17\%$ of pixels selected]{}
(4,4) (0.1,0.1)(0,1)[4]{}[(1,0)[3]{}]{} (0.1,0.1)(1,0)[4]{}[(0,1)[3]{}]{}
(0.3,0.55)[$80\%$]{} (1.3,0.55)[$79\%$]{} (2.45,0.55)
(0.3,1.55)[$78\%$]{} (1.45,1.55) (2.3,1.55)[$79\%$]{}
(0.45,2.55) (1.3,2.55)[$80\%$]{} (2.3,2.55)[$76\%$]{}
(-0.3,2.3) (-0.3,1.25) (-0.3,0.05)
(0.12,3.3)[AlexNet]{} (1.12,3.3)[VGG-16]{} (2.12,3.3)[ResNet-50]{}
(-0.75,0.75) (0.75,3.75)[Target Model]{} (-0.5,-0.5)[(b) $28\%$ of pixels selected]{}
(4,4) (0.1,0.1)(0,1)[4]{}[(1,0)[3]{}]{} (0.1,0.1)(1,0)[4]{}[(0,1)[3]{}]{}
(0.3,0.55)[$77\%$]{} (1.3,0.55)[$76\%$]{} (2.45,0.55)
(0.3,1.55)[$74\%$]{} (1.45,1.55) (2.3,1.55)[$68\%$]{}
(0.45,2.55) (1.3,2.55)[$80\%$]{} (2.3,2.55)[$74\%$]{}
(-0.3,2.3) (-0.3,1.25) (-0.3,0.05)
(0.12,3.3)[AlexNet]{} (1.12,3.3)[VGG-16]{} (2.12,3.3)[ResNet-50]{}
(-0.75,0.75) (0.75,3.75)[Target Model]{} (-0.5,-0.5)[(c) $45\%$ of pixels selected]{}
(4,4) (0.1,0.1)(0,1)[4]{}[(1,0)[3]{}]{} (0.1,0.1)(1,0)[4]{}[(0,1)[3]{}]{}
(0.3,0.55)[$32\%$]{} (1.3,0.55)[$40\%$]{} (2.45,0.55)
(0.3,1.55)[$28\%$]{} (1.45,1.55) (2.3,1.55)[$41\%$]{}
(0.45,2.55) (1.3,2.55)[$52\%$]{} (2.3,2.55)[$43\%$]{}
(-0.3,2.3) (-0.3,1.25) (-0.3,0.05)
(0.12,3.3)[AlexNet]{} (1.12,3.3)[VGG-16]{} (2.12,3.3)[ResNet-50]{}
(-0.75,0.75) (0.75,3.75)[Target Model]{} (-0.5,-0.5)[(a) $17\%$ of pixels selected]{}
(4,4) (0.1,0.1)(0,1)[4]{}[(1,0)[3]{}]{} (0.1,0.1)(1,0)[4]{}[(0,1)[3]{}]{}
(0.3,0.55)[$28\%$]{} (1.3,0.55)[$49\%$]{} (2.45,0.55)
(0.3,1.55)[$34\%$]{} (1.45,1.55) (2.3,1.55)[$49\%$]{}
(0.45,2.55) (1.3,2.55)[$49\%$]{} (2.3,2.55)[$47\%$]{}
(-0.3,2.3) (-0.3,1.25) (-0.3,0.05)
(0.12,3.3)[AlexNet]{} (1.12,3.3)[VGG-16]{} (2.12,3.3)[ResNet-50]{}
(-0.75,0.75) (0.75,3.75)[Target Model]{} (-0.5,-0.5)[(b) $28\%$ of pixels selected]{}
(4,4) (0.1,0.1)(0,1)[4]{}[(1,0)[3]{}]{} (0.1,0.1)(1,0)[4]{}[(0,1)[3]{}]{}
(0.3,0.55)[$34\%$]{} (1.3,0.55)[$45\%$]{} (2.45,0.55)
(0.3,1.55)[$34\%$]{} (1.45,1.55) (2.3,1.55)[$50\%$]{}
(0.45,2.55) (1.3,2.55)[$62\%$]{} (2.3,2.55)[$55\%$]{}
(-0.3,2.3) (-0.3,1.25) (-0.3,0.05)
(0.12,3.3)[AlexNet]{} (1.12,3.3)[VGG-16]{} (2.12,3.3)[ResNet-50]{}
(-0.75,0.75) (0.75,3.75)[Target Model]{} (-0.5,-0.5)[(c) $45\%$ of pixels selected]{}
**Perturbation regions** In Figure \[fig:pert\_localiztion\_masks\], we provide visualizations of the selected localization masks, where the given percentages correspond to the proportion of selected pixels out of all available pixels.
Note that for the perturbation localized on the image frame, unlike @zajac2019adversarial_frame, we do not expand the size of the image. We simply exercise the perturbation on the selected outermost pixels.
**Calculating $L_p$ distances** Between initial images of size $224 \times 224$ and their adversarial counterparts, we calculate $L_0$, $L_2$, and $L_{\infty}$ distances as follows: $$\begin{aligned}
L_{0}(\bm{X}, \bm{\tilde{X}}) & = \frac{\sum_{i}^{224} \sum_{j}^{224} \mathds{1}_{\{\bm{X}_{i,j} - \bm{\tilde{X}}_{i,j} \neq 0\}}}{224 \times 224} \,, \\
L_{2}(\bm{X}, \bm{\tilde{X}}) & = ||\bm{X} - \bm{\tilde{X}}||_2 \,,\\
L_{\infty}(\bm{X}, \bm{\tilde{X}}) & = \max(|\bm{X} - \bm{\tilde{X}}|) \,,\end{aligned}$$ where $\bm{X}$ and $\bm{\tilde X}$ represent an initial image and its adversarial counterpart, respectively. In this framework, an $L_{\infty}$ norm of $1$ means that the added perturbation changed a pixel from black to white (i.e., $0$ to $255$), or vice versa. An $L_0$ norm of $1$ means all pixels are modified by the adversarial perturbation.
Additional Experimental Results {#appB}
===============================
In Figure \[fig:additional\_examples\], we provide a number of qualitative examples, showing the $L_0$, $L_2$, and $L_{\infty}$ norms of adversarial perturbation generated using various localization settings. All of the examples presented in Figure \[fig:additional\_examples\] are generated using AlexNet and transfer to ResNet-50.
For the experiments discussed in the main paper, Figure \[fig:percentage\_of\_adv\_with\_less\_lp\_norm\] provides the percentage of adversarial examples that have lower $L_p$ norm than their counterparts generated with “global” perturbation. Our experiments show that regional perturbation almost always leads to lower $L_0$ norms compared to non-regional perturbation, whereas in the case of $L_2$ and $L_{\infty}$ norms, this depends on the initial image-target class combination.
For the sake of completeness, In \[tbl:exp\_results\_l0\] we provide the exhaustive details of $L_0$ norms of adversarial perturbations for the experiment described in the main paper. Since the perturbation region is what is controlled in this experiment, the resulting perturbations have much less $L_0$ deviation compared to $L_2$ or $L_{\infty}$.
[llcccccc]{} & Source: & & &\
& Target: & VGG-16 & ResNet-50 & AlexNet & ResNet-50 & AlexNet & VGG-16\
& Norm: & & &\
& $0.93$ & $0.94$ & $0.90$ & $0.84$ & $0.89$ & $0.83$\
& & $(0.08)$ & $(0.07)$ & $(0.07)$ & $(0.11)$ & $(0.10)$ & $(0.10)$\
& & $0.15$ & $0.15$ & $0.15$ & $0.15$ & $0.15$ & $0.14$\
& & $(0.01)$ & $(0.01)$ & $(0.01)$ & $(0.01)$ & $(0.01)$ & $(0.01)$\
& & $0.27$ & $0.28$ & $0.27$ & $0.26$ & $0.27$ & $0.26$\
& & $(0.01)$ & $(0.01)$ & $(0.01)$ & $(0.03)$ & $(0.01)$ & $(0.03)$\
& & $0.43$ & $0.43$ & $0.43$ & $0.40$ & $0.43$ & $0.41$\
& & $(0.02)$ & $(0.02)$ & $(0.02)$ & $(0.04)$ & $(0.02)$ & $(0.04)$\
& & $0.16$ & $0.16$ & $0.16$ & $0.16$ & $0.16$ & $0.16$\
& & $(0.01)$ & $(0.01)$ & $(0.01)$ & $(0.01)$ & $(0.01)$ & $(0.01)$\
& & $0.27$ & $0.27$ & $0.27$ & $0.26$ & $0.27$ & $0.26$\
& & $(0.01)$ & $(0.01)$& $(0.01)$& $(0.02)$& $(0.01)$& $(0.02)$\
& & $0.43$ & $0.43$ & $0.43$ & $0.42$ & $0.43$ & $0.42$\
& & $(0.02)$ & $(0.02)$& $(0.02)$& $(0.04)$& $(0.04)$& $(0.03)$\
& & $0.16$ & $0.16$ & $0.16$ & $0.16$ & $0.16$ & $0.15$\
& & $(0.01)$ & $(0.01)$& $(0.01)$& $(0.01)$& $(0.01)$& $(0.01)$\
& & $0.28$ & $0.28$ & $0.28$ & $0.27$ & $0.28$ & $0.27$\
& & $(0.01)$ & $(0.01)$& $(0.01)$& $(0.02)$& $(0.01)$& $(0.02)$\
& & $0.44$ & $0.43$ & $0.43$ & $0.41$ & $0.43$ & $0.41$\
& & $(4.80)$ & $(0.11)$ & $(4.20)$ & $(0.09)$ & $(3.98)$ & $(0.09)$\
\[tbl:exp\_results\_l0\]
[^1]: ` `
|
Q:
On error no prevent default - reload page not using AJAX
I have the following code to load data via AJAX:
$().ready(function() {
$('a:not(.flags a)').filter(function() {
return this.hostname && this.hostname === location.hostname;
}).addClass('internal_link');
$(document).on('click', '.internal_link', function(e) {
var url = $(this).attr('href');
$.ajax({
url: url,
dataType: 'json',
success: function(data) {
contentWrapper = $('<div />').html(data.content);
$(contentWrapper).find('a').filter(function() {
return this.hostname && this.hostname === location.hostname;
}).addClass('internal_link');
document.title = data.meta_title;
$('#articlecontent').fadeOut(400, function()
{
$(this).fadeOut('slow').html(contentWrapper.html()).fadeIn('slow');
});
$('nav li a').removeClass('selected');
$('#nav_'+data.code).addClass('selected');
$('meta[name=keywords]').attr('keywords', data.meta_keys);
$('meta[name=description]').attr('description', data.meta_desc);
$("html, body").animate({ scrollTop: 0 }, "slow");
},
error: function(jqXHR, exception) {
if (jqXHR.status === 0) {
alert('Not connect.\n Verify Network.');
} else if (jqXHR.status == 404) {
alert('Requested page not found. [404]');
} else if (jqXHR.status == 500) {
alert('Internal Server Error [500].');
} else if (exception === 'parsererror') {
alert('Requested JSON parse failed.');
} else if (exception === 'timeout') {
alert('Time out error.');
} else if (exception === 'abort') {
alert('Ajax request aborted.');
} else {
alert('Uncaught Error.\n' + jqXHR.responseText);
}
}
});
e.preventDefault();
});
});
I've prepared my PHP output to display in error Requested JSON parse failed. for testing purposes. At the moment when AJAX error occur at the moment I display alert what for normal user is useless. When I don't display any error using alert, user won't know what is going on. Maybe I'm wrong but the best would be in that case simple "unprevent default" what mean site should be reloaded not using AJAX.
I've already seen for example Best way to remove an event handler in jQuery? but when I add at the beginning of error function:
$(document).off('click', '.internal_link');
it makes that I have to click again on the link to reload page not using AJAX.
Also when I added in this function
return true;
the site isn't reloaded not using AJAX.
Is there any way to do that?
A:
Ajax is asynchronous, so when the error handler fires it's too late to start removing the preventDefault or the event handler, but you could just redirect with javascript instead as these look like they are anchors.
Something like
$(document).ready(function () {
var links = $('a:not(.flags a)').filter(function () {
return this.hostname && this.hostname === location.hostname;
});
links.on('click', function (e) {
e.preventDefault();
var url = this.href;
$.ajax({
url: url,
dataType: 'json',
success: function (data) {
// success handler
},
error: function (jqXHR, exception) {
window.location.href = url; // redirect here
}
});
});
});
|
Q:
Parse string to int when string contains a number + extra characters
Using Python, how can/should I parse a string that has a number, followed by other characters, to an int? The specific problem I am trying to solve is parsing the first number out of a string containing a number followed by an arbitrary amount of other characters, including, possibly other numbers, which I am not interested in.
For example, if the string is "12//1" I need to get just the 12 to an integer.
A:
If you want to extract the digits in the string:
int(''.join(c for c in s if c.isdigit()))
A:
I would use this regular expression:
import re
try:
print int(re.compile("(\d+)").match('12//').group(1))
except:
print "there was no number"
It will extract all digits and strops at the first nondigit character.
\d means single digit, \d+ means match at least one digit and (\d+) together means put what have you found in a group 1.
A:
Looks like a job for itertools.takewhile:
>>> from itertools import takewhile
>>> s = '12//'
>>> int(''.join(takewhile(str.isdigit, s)))
12
|
// Using two different methods for highlighting due to limitations of 'highlight.js'
// Add controls to report data to show/hide/reveal items.
function bindControls() {
var dig_iframe = $('#dig-iframe').contents();
// Click into report data to reveal locations in Combined CSS.
dig_iframe.find('#report-tabs').on('click', '.property-list li, #specificity-table tr', function() {
var $trigger = $(this);
var clicked_item = "declaration";
if ( $trigger[0].nodeName == "TR" ) {
clicked_item = "selector";
}
if ( $trigger.hasClass("active") ) {
$trigger.removeClass("active");
dig_iframe.find(".js-css-reset").click();
} else {
if ( clicked_item == "declaration") {
if ( dig_iframe.find(".property-list li.active").length > 0 ) {
dig_iframe.find(".property-list li").removeClass("active");
dig_iframe.find(".js-css-reset").click();
}
var item_text = $trigger.find(".property-list__item").text();
dig_iframe.find("#css-code .declaration").each(function(){
if ( item_text == ($(this).text()).trim() ) {
$(this).addClass("highlight")
}
})
} else {
if ( dig_iframe.find("#specificity-table tr.active").length > 0 ) {
dig_iframe.find("#specificity-table tr.active").removeClass("active");
dig_iframe.find(".js-css-reset").click();
}
var item_text = $(this).find(".selector").text();
dig_iframe.find("#css-code .selector").each(function(){
if ( item_text == $(this).text() ) {
$(this).addClass("highlight")
}
})
}
$(this).addClass("active");
dig_iframe.find(".ruleset, .group").hide();
dig_iframe.find(".highlight").each(function(){
$(this).closest(".group").fadeIn("fast");
$(this).closest(".ruleset").fadeIn("fast");
});
dig_iframe.find(".js-css-reset").removeClass("btn--disabled");
}
});
}
|
1. Automatic detection of table relationships. Like PowerPivot if you import multiple tables from the same source Power Query now detects the relationships and brings them over to the Power Pivot Data Model automatically.
Like this:
I want to draw your attention to a contest that we run: the Power BI Demo Contest. All you need to do is create a short video of something cool you built using Power BI and share it. You could win great prizes!
The first two packages essentially contain some script tasks with complete samples on how to work with Piq, SQOOP and Hadoop jobs respectively. The other packages use the components provided and provide a quick start on getting data from Azure Blob Storage and getting data into Azure Blog Storage using SSIS. |
Genomic features of human limb specific enhancers.
To elucidate important cellular and molecular interactions that regulate patterning and skeletal development, vertebrate limbs served as a model organ. A growing body of evidence from detailed studies on a subset of limb regulators like the HOXD cluster or SHH, reveals the importance of enhancers in limb related developmental and disease processes. Exploiting the recent genome-wide availability of functionally confirmed enhancer dataset, this study establishes regulatory interactions for dozens of human limb developmental genes. From these data, it appears that the long-range regulatory interactions are fairly common during limb development. This observation highlights the significance of chromosomal breaks/translocations in human limb deformities. Transcriptional factor (TF) analysis predicts that the differentiation of early nascent limb-bud into future territories entail distinct TF interaction networks. Conclusively, an important motivation for annotating the human limb specific regulatory networks is to pave way for the systematic exploration of their role in disease and evolution. |
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