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Version: 2021.3
AppCallbacks class
Universal Windows Platform Player Settings
Universal Windows Platform: WinRT API in C# scripts
It is possible to use WinRT API directly in Unity scripts. However there are limitations and requirements for this:
• Scripts must be written in C#
• API compatibility level must be set to .NET 4.6 or .NET Standard 2.0 in the player settings
• Because the same script code is also used by Unity Editor (which always uses Mono), all code that uses WinRT API must be under ENABLE_WINMD_SUPPORT define
Below is an example for getting advertising using WinRT API directly:
using UnityEngine;
public class WinRTAPI : MonoBehaviour
{
void Update()
{
auto adId = GetAdvertisingId();
// ...
}
string GetAdvertisingId()
{
#if ENABLE_WINMD_SUPPORT
return Windows.System.UserProfile.AdvertisingManager.AdvertisingId;
#else
return "";
#endif
}
}
AppCallbacks class
Universal Windows Platform Player Settings
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How to run One Million users
Scaling up to load testing with a million users on Flood
In a previous post we detailed some considerations around planning for high concurrency in your tests. In this post, we'll detail how to run a high concurrency test on Flood IO and get you on the way to a million concurrent users.
The Million User Scenario
A common use case we see for Flood IO is the testing of mobile HTTP based RESTful APIs.
In these JMeter and Gatling scenarios we load test a simple HTTP endpoint that serves a JSON response of approx. 6.4KB for the purpose of this example. The load test simulates active users polling a server from a mobile device every 60 seconds.
Baseline a single node
For any test, especially high concurrency tests, you should baseline performance from a single node to make sure that Gatling or JMeter JVM performance is not impacting the results. We provide a shared grid node for you to baseline and observe this behaviour.
Response Time
If you start to see an unexplained 'wobble' in response time as you ramp up concurrent users, you should at first be suspicious of your test plan (concurrency, request rate, network throughput) and the test tool itself.
We automatically capture verbose GC logs from running tests and can help you detect any JVM performance issues. We also flag any grid which is running hot in terms of CPU and Memory to help you detect any performance bottlenecks on the grid.
Memory
If you find your test plan is memory intensive, you can opt to scale up the size of your individual grid nodes. We provide two sizes.
Our m3.xlarge nodes will provide you with 8GB JVMs for JMeter or Gatling with the following parameters: -Xms8192m -Xmx8192m -XX:NewSize=2048m -XX:MaxNewSize=2048m
Pay 10% extra and scale up to our m3.2xlarge nodes which provide you with 20GB JVMs with the following parameters: -Xms20480m -Xmx20480m -XX:NewSize=5120m -XX:MaxNewSize=5120m
Transaction Rate
Our reporting engine can easily sustain around 60K requests per minute and beyond without delay on each node.
At much higher transaction rates you may see some delay in the reporting of your results. You can avoid this lag by __double_underscoring a proportion of transaction names to mark them as background transactions. These then get ignored by our reporting engine.
Take for example this scenario in JMeter
The control sample is the only sample which is reported. For each control sample, we generated an additional 999 background load samples.
On an example 10 node grid we reported on 80,000 requests per minute. Extrapolate the background load (80_000 * 1_000 / 60) and this would be approx. 1.3M requests per second which is well above most use cases we've seen on Flood IO.
Network Throughput
Each grid node is capable of around 100 Mbps network throughput or more.
If you have a 10 node grid that would be more than 1 Gbps. You should always estimate the network throughput your test is going to generate, especially for tests which don't cache requests or have large response bodies, for example downloading PDFs or binaries. Then simply scale out with the number of grid nodes required.
Start Your Grid
Once you are happy with a single node's results and have nice flat response times, it's time to scale out.
Our plans don't restrict you in the number of users or how many tests you run on a grid. You simply spin up as many nodes as your plans permit and use those nodes as you wish. On a Pro plan you can start 1 grid with 10 nodes in any region. On a Team plan you can start 10 grids each with 20 nodes in any of the 8 supported regions across the globe. You can also Host Your Own AWS nodes for even greater savings.
A single grid with 20 nodes at 10K users per node will let you test 200K users from one region.
Spread that load out around the globe and you can be chasing 1M users within minutes.
Start load testing now
It only takes 30 seconds to create an account, and get access to our free-tier to begin load testing without any risk.
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Security
All you need about 7 steps of Cyber Kill Chain
Rezarta Meni
July 27, 2021
This year began with the promise of a brighter future, but it looks like it will be a long way ahead. If you look at the 2021 statistics, you will notice that most of them are showing the fact that cybersecurity risks are increasing as a result of COVID-19 and the work-from-home approach, making that one of the most serious challenges that businesses face daily. Ignoring cybersecurity risks has been proven to be one of the costliest mistakes, but on the other hand, it is almost impossible to eliminate those. The battle between cyber dark side criminals and security professionals is never-ending. As a result, having defense tactics in place in this dangerous battleground may be the most effective way to mitigate those. In this case, the Cyber Kill Chain can be helpful. But what is it, why, and for what you can use this approach? Let's figure it out in this article. 📑 Table of Contents What is the Cyber Kill Chain? How does the Cyber Kill Chain Work? The Cyber Kill Chain Gaps...
Is the security of credit cards indeed as strong as we expect?
Darina Shramko
July 12, 2021
Image source - asiancsbank.com It is difficult to imagine a modern person who does not use Visa or MasterCard cards . More and more people prefer cashless payments . Paying bills, shopping online, and booking flights can all be done in seconds, all thanks to credit cards. However, are we thinking about the algorithms used in credit cards ? To protect yourself from the actions of intruders , you need to find out how the payment was made. So how do bank cards work? Let's figure it out together. This article also: a practical guide for holders of bank cards of payment systems Visa, MasterCard, etc.; a functional safety guide for bank customers and employees. 📑 Table of contents: Bank credit card structure Credit card readers Chip EVM Card authentication Payer verification Transaction authorization Contactless payments Conclusion Disclaimer: This article discusses technologies that should be used to protect funds in bank accounts. Any use of these methods for hacking or unauthorized...
Must 15 “Do not do on Internet” rules for 2021
Ozair Malik
August 1, 2021
A 21- year old student of Kings College London, running for student union president , found out about the importance of Internet safety rules the hard way. A week before Election Day, his witty opponents found his objectionable pictures in his past social media posts that were vulgar and referenced drug use. This dreadful incident crashed his political career. The doomed candidate withdrew his candidature, providing an open playing field to his opponents. Alas, he is not the only victim of lousy internet surfing habits . A lot many people have suffered such losses due to their careless posting on social media. Moreover, many people have been exposed to hacks, scams, identity thefts, and physical harm at the hands of bad actors present online. Since the Internet is a public space and unsafe surfing can be very hazardous for you and your loved ones. While you are browsing the Internet, you must protect yourself because it is highly unregulated. Table of Contents Minimize Giving Out...
23 DIY privacy and security settings for your Windows
Rakesh Naik
August 1, 2021
Imagine someone stole your computer and now has access to all your sensitive information just because you weren’t careful enough to secure it on your computer. You wouldn’t like that, would you? In this article, we work on just how you can prevent such a breach of sensitive information that might be personal or of professional importance. In this article, we look at 23 different ways , which were tried and tested by your truly, that helps you improve the privacy of your Windows 10 PC . The exciting thing about all these methods is that you can implement these yourself on your computer and require no additional software installation whatsoever. Windows has always been a very important part of daily life for a lot of people around the world and has continued to remain the most popular operating system in the world. Windows is also the operating system with the greatest number of vulnerabilities making it quite easy to exploit user information and compromise their accounts. Just last...
The enigma & the benefits of the deep web. How to safely access the deep web yourself from home and precautions to keep you safe
Rakesh Naik
July 28, 2021
The Deep web is and always has been an enigma to regular users of the internet. The deep web is almost like the oceans of Earth; while only 10% has been explored so far, what is unexplored is even more shocking and vast. The deep web is mostly known as the worst place for internet users to visit due to the myriad of crimes and illegal activities that can take place to victimise these users. The deep web is where governments hide secrets that they don’t want anyone to uncover. But, recently, a good side of the deep web has begun to show up; a twinkle of light in the otherwise dark world. In this article, we explore this aspect of the deep web, where it can be used to your advantage without causing any harm to yourself or the people around you. I also detail a few steps through which you too can access the deep web from your own computer, along with a few precautions for you to follow. 📑 Table of Contents Breaking the enigma of the deep web The deep web issues Deep web: A new hope...
55 Ways to Save Money on Internet Safety: The DEFINITIVE Guide
Dean Chester
July 27, 2021
Have you ever said to yourself: “Man, I wish I could afford all those pricey tools for Internet safety”? I know I have. Some may say that Web security is not something to save money on. I say, it absolutely is. Do you want to know why? Then jump straight into my newest guide on how to save money on Internet safety! But that’s not all! In the end, you’ll find a bonus chapter on how to save even more money by using your Net security tools! Use the table of contents below for your convenience: How to Save Money by Using Free Versions Save by Setting Up Your Browser Wisely Increasing Your Cost Efficiency Free & Simple Tweaks You Should Do Save More on Internet Safety: Super-Secret Bonus Chapter How to Save Money by Using Free Versions 1. Use a free secure email address You got to start with your privacy somewhere, so why not with your email security? Gmail is far from safe, so we’d better find another provider. Luckily, there are alternatives that are secure and free, sometimes even...
Everything You Need to Know About SIEM with the Top 5 SIEM Solutions on the Market in 2021
Rakesh Naik
July 25, 2021
Do you run a business and are worried about its security? Or are you an InfoSec professional looking to expand your knowledge? Well, you're in luck! In this article, I discuss a security solution known as SIEM that is made to improve the security of any enterprise. 📑 Table of Contents What is SIEM? How Does SIEM Software Work? Need for SIEM Software Incident Detection Compliance with Regulations Incident Management Benefits and Drawbacks of SIEM Software Benefits of SIEM Drawbacks of SIEM What to Look for in a Good SIEM Software Real-Time Monitoring Scaling Threat Detection Response Times User Interface Integration Log Management Reporting How to Successfully Implement SIEM Software Requirements Gathering Correlation Rules Test Runs Data Collection Incident Response Plan Further SIEM Refining Top SIEM Tools on the Market SolarWinds Security Event Manager Splunk Enterprise SIEM McAfee ESM LogRhythm IBM QRadar Conclusion What is SIEM? Security Information and Event Management is...
Why Covid19' is a game-changer in the whole cybersecurity domain?
Hamna Imran
July 25, 2021
It might surprise you that Telephone-operated Crime Survey for England and Wales (TCSEW) estimated a significant increase in physical crimes during April and May 2020 compared with a two-month average in the pre-lockdown period. While the falling trend might be observed across the majority of crime types like theft offenses and domestic burglary. The survey indicates a rise in computer misuse offenses during April and May. As hackers who progress on chaos visualized the outbreak as a way to infiltrate people's devices and steal information that could be manipulated and resold on the Dark web. In March 2019, the World Health Organization pronounced the coronavirus that causes COVID-19 a pandemic. A declaration that leads to a massive number of companies asking employees to work from home. However, millions of workers signing in remotely to corporate networks lead to another threat, Cyberattacks. Hence sharing my knowledge on this topic is a necessity to me as a cyber researcher. In...
Introduction to Identity Management and why it is crucial to protect your digital identity in 2021
Nihad Hassan
July 25, 2021
Image Source – freepik.com Have you ever think that your digital identity will be protected by a third party in 2021? The recent attacks on the supply chain of IT service providers prove that we as humans are still the weakest part of our identity protection from theft or misuse, but we can expect an expansion of Identity authentication services already. 📑 Table of contents: Why IAS become increasingly important? Introduction to Identity and Access Management (IAM)? Conclusion Why IAS become increasingly important? Since the start of the COVID19 disease, identity and access management have become more critical. Enterprises worldwide were forced to adopt the work-from-home model to continue working during the general lockdown; the massive shift of the workforce to become remote has increased cyber threats against users' credentials. On the other hand, the digital transformation which accelerated during the pandemic has boosted the importance of identity management . According to...
What is HTTPS, and how It relates to TLS and SSL? Does HTTPS really protect you against cyber threats?
Hamna Imran
July 25, 2021
Are you also one of those people who think that the green lock in the URL has superpowers to protect you from all the viruses? Well, let me surprise you today and hurl a new perspective. Do yourself a favor by reading the expert advice. 📑 Table of Contents What is HTTPS? Difference between HTTP and HTTPS How to identify whether a website is using HTTPS? Why must HTTPS be used? Working of HTTPS What is SSL/TLS? HTTPS relationship with TLS and SSL Does HTTPS protect you from attacks? Potential threats Expert advice on being safe from attacks while using HTTPS Conclusion What is HTTPS? “Hyper text transfer protocol” is abbreviated as HTTPS . It is a secure HTTP extension. It is used by websites that install and configure SSL/TLS certificates to establish a secure connection with the server. Encryption: Encrypt the transmitted data to protect it from spyware. This means that when users browse the site, no one can "eavesdrop" on their conversations, track their actions on different pages,...
How to host your own Threat Intelligence server and filling it with data?
Hamna Imran
July 24, 2021
Ever received a link through email that took you to a suspicious website? Well, if your answer is No, You are fortuitous enough because you could have lost a lot of personal information. According to a Cybercrime report, most cyberattacks begin with a simple email. Above 90 percent of unbeaten hacks and data breaches stem from phishing emails that beguile the recipients to click a link, open a document, or forward information to someone which they shouldn't. People are the weakest link in the security chain, says Kathy Hughes Being associated with Cyber Security, I am compelled to agree with him. Approximately 66 billion legal emails are sent on a daily basis. Unfortunately, an average of 303 billion illicit emails or malicious also spams inboxes. This information clearly shows the importance of monitoring spam emails while on their way to corporate users’ inboxes. As cyber threats evolve and new ones pop up every other day, it is evident that cybersecurity analysts have to step up as...
Artificial Intelligence in Cyber Warfare: The End of Humanity Imminent?
Rakesh Naik
July 21, 2021
The development of full artificial intelligence could spell the end of the human race. It would take off on its own, and re-design itself at an ever-increasing rate. Humans, who are limited by slow biological evolution, couldn't compete, and would be superseded.” – Stephen Hawking Cyberwarfare is a new form of warfare waged through computers , enhanced software, the internet as well as malware to further national agendas and improve the international game of power. With the improvement of technology, the means of war have also changed with better and more efficient “ weapons " being used in cyberspace. The latest player in the world of cyberwarfare is Artificial Intelligence that adds to the efficiency of such cyberattacks. AI eliminates the human element and allows a high-performance system to take care of all the details of cyberspace attacks. While AI integrated warfare has many benefits, we need to also stay informed of the drawbacks of the technology. AI potentially has the...
Social media safety rules for 2021
Dean Chester
July 12, 2021
How much time do you spend on social media? 2, 3, or even more hours a day? Meanwhile, posting and communicating on social networking websites are not just bells and whistles, they often put our safety and privacy at risk. But how to stay secure and improve your social media safety? In order to do this, you have to learn all possible risks of social media and know useful practical tips on how to protect your private data on social networks. In this guide, I will show you how to use social media safely and secure your accounts. Let’s dive right in. Why social networks are not safe? Top threats of social media Security tips for social media privacy and safety How to stay safe on Facebook? How to protect your data on Instagram? How to guard yourself on Twitter? Why social networks are not safe? Taking into consideration current statistics and news about social network safety, it becomes evident that privacy and security on social media are far beyond the simple usage of a VPN service ...
What's My IP Address
Dean Chester
July 8, 2021
Caution! You are not protected! Hide your IP from ISPs, hackers, snoopers and other "prying eyes". If you care about your privacy, but you don’t know how to do it, read hide my IP guide and learn how a VPN will help to keep yourself private online. Hide your IP IP Address Guide DNS Leak Check What’s my router IP? How to check torrent IP? WebRTC Leak Check What do you need to know about your IP address? Once a gadget "goes out" to the global network, it is assigned with the unique number that indicates the geo-location of the gadget’s owner. It contains a certain combination of numbers which is individual for all network visitors. This number that serves to uniquely identify is called an IP address. What is it for? That’s simple! In order to perform connections between the rest of the digital world, one is required to have an IP address assigned by an Internet Service Provider (ISP). It’s worth noting that they should be personal, individual for all netizens. As you can see from the...
Internet Privacy: Expectations vs. Reality
Dean Chester
July 7, 2021
Welcome, privacy enthusiasts! We are glad to see you again at COOLTECHZONE.COM . And today, we’d like to talk to you about something that is very important to understand to fully make use of a VPN. On the other hand, this thing is seldom discussed. It is, of course, myths and misconceptions about VPN technology. Without further delay, let’s get into it! Table of contents: Why there are so many VPN misconceptions Myths truth about VPNs: Reality check How to choose a VPN that won’t disappoint you My conclusion Why there are so many VPN misconceptions One of the most surprising things for me in my line of work was, I have to admit it, how many people actually care about their online privacy and safety. I’ve met quite a few “laypeople” who were legitimately concerned about their cybersecurity and surveillance their governments and private companies alike put them under, and would like to hide their real IP addresses to up their privacy. However, it was not all that positive. I can safely...
In-Depth Guide to De-Googling: Delete Google, Gmail, YouTube accounts
Dean Chester
July 7, 2021
Hello, ladies and gentlemen, and welcome to another CoolTechZone guide! Though our website is mainly dedicated to reviewing and comparing various and best VPN services , we realize that virtual private network technologies are just one asset, albeit a very important one, of Internet privacy and security. So in our today’s guide, I’ll tell you about another topic: deleting your Google accounts and finding alternatives to Google services. But wait, you’re probably saying, why would anyone do that? Well, you’re about to find out in the very next section of this guide. If you feel like you know the basics already and want to get into the juicy bits, just use this quick navigation menu to skip ahead to whatever chapter you want: What de-googling is and why you should consider it How to quit Google services and best alternatives to them Conclusion What de-googling is and why you should consider it Cutting oneself off from Google and its many services completely or partially is a known...
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Is There an Age Limit for Mobility Scooters?
Mobility Scooters: Everything You Need to Know
What is a Mobility Scooter?
A mobility scooter is a battery-powered vehicle designed to provide personal transportation for people with mobility issues. They are typically used by individuals who have difficulty walking or standing for long periods of time, and can offer a greater degree of independence and freedom than traditional wheelchairs.
Is There an Age Limit for Mobility Scooters?
The age limit for mobility scooters varies depending on the country and the specific scooter model. In general, most mobility scooters are designed for adults, and some may have a minimum age requirement of 18 years old. However, there are also some mobility scooters specifically designed for children, and these may have a lower age limit.
Mobility Scooters
Types of Mobility Scooters and Their Benefits
There are three main types of mobility scooters:
• Travel scooters: These are the most common type of mobility scooter and are designed for use both indoors and outdoors. They are typically lightweight and easy to disassemble for transport.
• Heavy-duty scooters: These scooters are designed for heavier users and offer a higher weight capacity than travel scooters. They are also typically more powerful and have a longer range.
• Bariatric scooters: These scooters are designed for the heaviest users and offer the highest weight capacity. They are also typically the most expensive type of mobility scooter.
Benefits of using a mobility scooter:
• Increased mobility and independence
• Reduced pain and fatigue
• Improved quality of life
• Greater participation in social activities
Factors to Consider When Choosing the Right Scooter
When choosing a mobility scooter, there are a number of factors to consider, including:
• Your needs and abilities: Consider your level of mobility, your weight, and the terrain you will be using the scooter on.
• The size and weight of the scooter: Make sure the scooter is the right size for you and that you can easily lift and transport it.
• The range of the scooter: Consider how far you will need to travel on a single charge.
• The features of the scooter: Some scooters have additional features, such as a basket, lights, or a horn.
• The price of the scooter: Mobility scooters can range in price from a few hundred dollars to several thousand dollars.
Conclusion
Mobility scooters can offer a great way to improve your mobility and independence. When choosing a mobility scooter, it is important to consider your needs and abilities, the size and weight of the scooter, the range of the scooter, the features of the scooter, and the price of the scooter.
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%0 Journal Article %A Tso, Cho-Lea %A Shintaku, Peter %A Chen, James %A Liu, Qinghai %A Liu, Jason %A Chen, Zugen %A Yoshimoto, Koji %A Mischel, Paul S. %A Cloughesy, Timothy F. %A Liau, Linda M. %A Nelson, Stanley F. %T Primary Glioblastomas Express Mesenchymal Stem-Like Properties %D 2006 %R 10.1158/1541-7786.MCR-06-0005 %J Molecular Cancer Research %P 607-619 %V 4 %N 9 %X Glioblastoma is the most common and aggressive primary brain cancer. Recent isolation and characterization of brain tumor-initiating cells supports the concept that transformed neural stem cells may seed glioblastoma. We previously identified a wide array of mesenchymal tissue transcripts overexpressed in a broad set of primary glioblastoma (de novo) tumors but not in secondary glioblastoma (derived from lower-grade) tumors, low-grade astrocytomas, or normal brain tissues. Here, we extend this observation and show that a subset of primary glioblastoma tumors and their derived tumor lines express cellular and molecular markers that are associated with mesenchymal stem cells (MSC) and that glioblastoma cell cultures can be induced to differentiate into multiple mesenchymal lineage-like cell types. These findings suggest either that a subset of primary glioblastomas derive from transformed stem cells containing MSC-like properties and retain partial phenotypic aspects of a MSC nature in tumors or that glioblastomas activate a series of genes that result in mesenchymal properties of the cancer cells to effect sustained tumor growth and malignant progression. (Mol Cancer Res 2006;4(9):607–19) %U https://mcr.aacrjournals.org/content/molcanres/4/9/607.full.pdf
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Saturday, April 6, 2013
SSRS AX 2012: Why and how is a Parameter added to report
If we look at the Simple SSRS report we created using dataset CustTableSRS (use below internal link for more details), we observe that while rendering the report - we had to enter a value in the parameters tab. i.e, Value for CustGroup.
So how and why does this value appear?
How does this parameter appear:
The answer can be found if we go to AOT in Dynamics Ax Client. Open the query CustTableSRS which we used as a Dataset for our report.
In the CustTableSRS AxQuery, we find several nodes. Lets concentrate on the DataSources node.
And in the Datasources node, we can find the CustTable from which the data into the report has be rendered from. And we can also see the Fields, AccountNum & CustGroup, which were displayed in the report.
Now if you look at Ranges, we see that CustGroup lies here. That means, the query has a range and is defined by CustGroup.
And this is how the CustGroup parameter is shown and is required while rendering the report.
Why does the parameter appear:
The basic reason, or should say purpose of the CustGroup parameter is - it acts as a filter. If you select CustGroup as 20, all the records with CustGroup as 20. And if you select any other value in CustGroup, all the related fields are shown.
But the actual and main reason for the need of parameter in report is a performance and efficiency reason. Because, we could have defined our own filter in the report to filter the data to any particular scenario. But then what we would have done is we would load all the data and then filter on that data that is on the SSRS server.
But by using the range on the query, means that, the AOT transfers the data after applying the range on the data and then send it to the SSRS server to be rendered on the report. So that way less data is transferred across. So that is the advantage and proper use of Ranges, a.k.a parameters for reports.
Internal links:
SSRS Ax 2012: How to create a simple SSRS report - Link
Information collected from:
AX2009 SSRS 2 The Case of the Mysterious Parameter - Link
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What strength does Ambien CR come in?
AMBIEN CR is available as extended-release tablets containing 6.25 mg or 12.5 mg of zolpidem tartrate for oral administration. Tablets are not scored. AMBIEN CR 6.25 mg tablets are pink, round, bi-convex, and debossed with A~ on one side.
What is the difference between Ambien and Ambien CR?
KNOW THE DIFFERENCE BEFORE YOU GO
It is important that you talk with your doctor to figure out which formulation is right for you. AMBIEN is a sleep aid that helps you fall asleep each night. AMBIEN CR has a dual purpose. It helps you fall asleep and also helps you stay asleep each night.
What is the highest amount of Ambien you can take?
Ambien, Edluar, and generic formulations:
• Starting dosage: 5 mg for women and 5 mg or 10 mg for men, taken right before bedtime. …
• Dosage increases: Your doctor may increase your dosage to 10 mg per day if the 5 mg dose is not effective.
• Maximum dosage: 10 mg once per day taken right before bedtime.
IT IS INTERESTING: You asked: Does serotonin make you calm?
How long does it take for Ambien CR to start working?
Ambien works relatively quickly, and it remains in the body for a short period of time. It has a rapid onset of action within 30 minutes, with peak effects reached within 1–2.5 hours for most people, depending on whether the person took an immediate- or extended-release version of the drug.
What is zolpidem 12.5 mg used for?
Zolpidem is used to treat a certain sleep problem (insomnia) in adults. It helps you fall asleep faster and stay asleep longer, so you can get a better night’s sleep. It may also reduce the number of times you wake up during the night. Zolpidem belongs to a class of drugs called sedative-hypnotics.
Why do doctors not want to prescribe Ambien?
Doctors generally are reluctant to prescribe sleeping pills due to risk of addiction and side effects, she says. For those who are suffering from long-term sleeplessness, consider visiting a sleep specialist, which may require a referral based on individual insurance plans.
Can I take 2 Ambien 10mg?
The total dose of AMBIEN should not exceed 10 mg once daily immediately before bedtime. AMBIEN should be taken as a single dose and should not be readministered during the same night. The recommended initial doses for women and men are different because zolpidem clearance is lower in women.
Can you take 20 mg of zolpidem?
The total dose of Zolpidem Tartrate Tablets should not exceed 10 mg once daily immediately before bedtime. Zolpidem Tartrate Tablets should be taken as a single dose and should not be readministered during the same night.
IT IS INTERESTING: What does a dopamine receptor agonist do?
Does Ambien shorten your life?
A new study has linked popular sleeping pills such as Ambien and Restoril with a nearly five-fold increased risk of early death. Researchers at Scripps Health, a nonprofit health system in San Diego, estimate that in 2010, sleeping pill use may have contributed to up to 500,000 “excess deaths” in the United States.
Why Ambien is bad for you?
Although Ambien is classified as a sedative, this drug can give the user a rush of energy and euphoria when it is abused at high doses. However, misusing this drug can result in extreme drowsiness, confusion, and clumsiness, all of which increase the risk of falls, fractures, and other accidental injuries.
What happens if you take Ambien and stay awake?
Ambien inhibits natural brain activity, inducing drowsiness to the point of intense sedation and calmness. People who take Ambien and force themselves to stay awake are much more likely to perform unconscious actions and not remember them.
How long will Ambien keep you asleep?
Do not take it with or after a meal because it will not work as quickly. Do not take a dose of this drug unless you have time for a full night’s sleep of at least 7 to 8 hours.
Is Ambien sleep good sleep?
Zolpidem, commonly known as Ambien, slows down activity in the brain, allowing you to sleep. The immediate release form dissolves right away, helping you fall asleep fast. The extended release version has two layers — the first helps you fall asleep, and the second dissolves slowly to help you stay asleep.
IT IS INTERESTING: Is there a supplement for serotonin?
Can I take 2 12.5 mg Ambien?
Do not increase your dose, take it more often, or use it for longer than prescribed. Do not take more than 12.5 milligrams a day. Women are usually prescribed a lower dose because the drug is removed from the body more slowly than in men.
How many mg of zolpidem is safe?
Adults—5 milligrams (mg) for women and 5 or 10 mg for men once a day at bedtime. Your doctor may increase your dose as needed. However, do not take more than 10 mg per day. Take only 1 dose a night as needed.
Does Ambien dissolve in water?
The free base of zolpidem is insoluble in water; zolpidem tartrate is slightly soluble in water (23 g/l at 20 °C), practically insoluble in dichloromethane, sparingly soluble in methanol [3].
Psychopharmacy
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Diabetes Care for
Children & Young People
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Does nutrition burnout impact children and young people with diabetes and their carers?
Paula Chinchilla
Nutrition therapy is recommended for all children and young people with diabetes, and it should be adapted to cultural, religious, ethnic and family traditions, as well as the cognitive and psychosocial circumstances of the child and their family. Nutrition tasks involved in diabetes management, such as carbohydrate counting and following healthy eating recommendations, can be demanding and complex for some families, and this can lead to diabetes distress and burnout. There is no term that specifically describes “nutrition burnout”, but rather “diabetes burnout” as a whole. This article reviews the role that healthcare professionals and the support system of the young person with diabetes play in avoiding distress and/or burnout related to nutrition tasks.
The term “diabetes distress” has been defined by the American Diabetes Association (ADA; 2021) as:
“…significant negative psychological reactions related to emotional burdens and worries specific to an individual’s experience in having to manage a severe, complicated, and demanding chronic disease such as diabetes.”
Diabetes distress has been found to be more prevalent and persistent than major depressive disorder, and it can have a huge impact on diabetes management (Rariden, 2019). Diabetes burnout is a state of physical or emotional exhaustion caused by the continuous distress of diabetes, as well as efforts to self-manage it. People with diabetes (PWD) may feel that, despite their best efforts, their blood glucose levels are unpredictable and disappointing; this often leads to feeling helpless and disengaged from diabetes self-management (Polonsky, 1999). People with diabetes burnout can feel disheartened with the continual effort required to manage diabetes. This state of mind can be temporary or impact continuously. Healthcare professionals (HCPs) can describe people with diabetes burnout as “difficult”, “non-compliant”, or “unmotivated”, while they are actually struggling with following the long list of tasks that are necessary to manage diabetes (Abdoli et al, 2020).
People with diabetes burnout can disengage from nutrition tasks, such as carbohydrate counting or eating healthily, among other diabetes-related tasks. They can present with eating disorders or risk-taking behaviours and, furthermore, it might be hard to engage them in attending clinics and discussing their diabetes management (Polonsky, 1999).
The best way to avoid diabetes burnout is to regularly screen for diabetes-specific distress, so that advice and support can be offered by the diabetes team in a timely manner.
Nutrition burnout
Unlike “diabetes burnout”, there is not a specific term that describes “nutrition burnout”. Yet this is very important for dietitians to consider, as often PWD can be struggling solely with the tasks involved in nutrition therapy, rather than their diabetes as a whole.
One of the key approaches of nutritional therapy when living with type 1 diabetes (T1D) and using intensive insulin therapy is to match the insulin dose to carbohydrate intake, in line with individualised insulin-to-carbohydrate ratios (level 3 carbohydrate counting [CC]). It is recommended that this is taught from diagnosis to all children and young people (CYP) with diabetes (NICE, 2016).
Carbohydrate counting
CC aims to improve glycaemic control and gives flexibility of food choices (Tascini et al, 2018). However, CC can be difficult for families, and the education should be adapted to their culture, preferences, capacities and understanding.
In a study by Fortin et al (2017), which involved adults with T1D, there was a relationship between the level of confidence in doing CC with the education level. In the same study, participants who had depression found that CC was harder to perform in their daily lives. According to the study, the factors that made CC difficult were the impression that glucose levels were fluctuating even with CC and that CC complicates the management of diabetes (Fortin et al, 2017).
Common barriers for CYP that can impact adherence to CC include peer influences, social context and depression (Borus and Laffel, 2010).
Intervention strategies should address the individual’s goals and expectations of using CC as part of intensive insulin therapy, emphasise problem solving to manage the challenges of dining out and changes in daily routines, and provide practical and applicable CC resources (Leung et al, 2014).
CC is not the only task that PWD should consider in their daily routines. The fat and protein content in meals has also shown to have an impact in insulin dosing decisions (Figure 1).
Role of healthcare professionals in avoiding nutrition burnout
PWD should be routinely assessed for diabetes distress, especially when complications arise (ADA, 2019). Routine monitoring and discussing diabetes burnout with individuals with T1D have also been suggested to improve psychosocial wellbeing and diabetes outcomes (Abdoli et al, 2021).
One such method could be dietitians teaming up with psychologists to explore if different aspects of the distress are related to nutrition tasks. If this is done in a timely manner, it could prevent burnout in CYP with T1D. Parental anxiety can also have a direct and negative effect on diabetes management and health outcomes (Sundberg et al, 2017). This is why it may be important to consider assessing parental diabetes distress too.
For example, if using the Problem Areas In Diabetes (PAID) Scale for Children (PAID-C; Evans et al, 2019) or PAID for Teenagers PAID-T; Shapiro et al, 2018) and parents’ version questionnaires, some of the statements can be related to nutrition tasks. These questionnaires have been adapted from the PAID scale by Welch et al (1996) for use with adolescents, children and their parents.
The PAID-T and parent-of-teenager version (P-PAID-T) are valid and reliable measures for use in adolescents and their parents. The PAID-T has a three-factor structure of diabetes distress, including the day-to-day burden of managing diabetes tasks (regimen-specific distress) and the perception that one’s family or friends are unsupportive with regard to diabetes management (family and friends distress).
The PAID-C and the parent version (P-PAID-C) show unique factor structures given the developmental differences between the two age groups (Evans et al, 2019). If the child, adolescent or parent answers that some of those related statements are a problem, the HCP can find ways to help. If statements that can be related to nutrition tasks are a problem for the PWD or parents, the HCP can discuss links between emotions and behaviour. Techniques including exploration, identifying feelings, reflection, normalisation and double reflection are suggested. Assessing for distorted beliefs or unrealistic goals and proposing a focused plan which is targeted, attainable, short-duration and with minor modifications is recommended (Rariden, 2019). Table 1 gives suggestions of identifying problem areas in diabetes related to nutrition tasks and suggestions of support to families.
Language matters when speaking about nutrition
HCPs should lead conversations with PWD to identify the connection between their emotions and the hurdles of diabetes management. In starting such conversations, an HCP should consider their approach and use of language, as PWD can find reassurance in feeling they are supported.
Good use of language – including verbal, written and non-verbal – can lower anxiety, build confidence, educate and help to improve self-care (NHS England, 2018). Often, when messages received from a number of different sources, including the media, people around them and HCPs, are perceived negatively, this can lead to feelings of shame, guilt and resentment in the PWD.
PWD often feel criticised or judged by others, including their HCP, regarding their food choices and eating habits (Doherty et al, 2020), so it is important that they feel encouraged to express their concerns in a safe, non-judgemental environment (Odiase et al, 2020).
The PDPEAS (Paediatric Diabetes: Positive Eating, Activity, Self) working group, comprising psychologists and dietitians, has created some helpful resources for CYP with diabetes and their carers (Children and Young People’s North West Diabetes Network, 2021). The working group suggests promoting principles of connected eating to change current nutritional messages delivered through diabetes education. This way CYP living with T1D are encouraged to develop or maintain a healthier relationship with food and their bodies.
Health literacy and language barriers when speaking about nutrition
Health literacy is a person’s ability to understand and apply health-related information and their ability to navigate the health system (World Health Organization, 2013).
After a diabetes appointment, the PWD and/or their carers need to remember everything that took place and was said during the consultation. They then need to apply what they have learnt when they go back home. This could be challenging for a person who has not clearly understood the message that their HCP has tried to convey to them, and this might impact on their self-care and health outcomes (Odiase et al, 2020).
The HCP should analyse if the information was understood, find different ways of explaining nutritional therapy and make adjustments to accommodate individual differences in learning style. CC might include a lot of calculations and also the understanding of the relationship between insulin and foods.
Some techniques and suggestions are highlighted in Box 1 to help PWD feel confident in completing diabetes-related tasks (Misra-Hebert and Isaacson, 2012). Building confidence and understanding can decrease the chances of the person feeling distressed by the tasks.
Dealing with nutrition-related tasks after diagnosis
In the local diabetes clinic, data were collected from 18 newly diagnosed children with diabetes (ages 8–18 years) and their families. They were asked about how they were coping with nutrition tasks after being diagnosed with T1D:
• 40% of the respondents said that the diabetes management task hardest to apply was CC, followed by glucose monitoring and insulin application.
• 22% of the families reported having felt tired or exhausted of making decisions around mealtimes.
• 28% reported having felt that they “can’t be bothered” to use CC.
• 33% of the families have felt worried or anxious about eating outside home (restaurants, school and activities).
• 33% of families have felt angry or upset when CC has not resulted in high or low blood glucose levels.
The families were also asked about the support from the diabetes team in adapting the healthy eating recommendations to their traditions and lifestyle:
• 50% of the families felt “completely supported”.
• All families responded they felt supported to some extent.
The families also shared the different ways they make nutrition-related tasks, such as CC, adapt to their individual lifestyle. Some of the answers are shared below:
“Having a booklet in my lunch box that everyone can see and record my carb count in, at school and home.”
“Using carb-counting apps.”
“Eating similar food portions and learning to memorise the carbohydrate content.”
“Calculate carbohydrates in favourite recipes and dishes using apps.”
“Do a list of favourite takeout menus and the carb content and keep it on the phone.”
For future research, it would be helpful to consider the level of involvement and support of caregivers in those CYP with nutrition burnout. These families would most likely benefit from more contact with the diabetes team.
Eating disorders in CYP with type 1 diabetes
CYP with diabetes appear to have a greater incidence of depression, anxiety, psychological distress and eating disorders (ED) compared to their peers without diabetes (Delamater et al, 2018). There is also an increased risk of ED in CYP with elevated levels of diabetes distress, high HbA1c and body dissatisfaction (Araia et al, 2020).
Diabetes itself could be a risk factor for developing ED, due to the required behaviours related to diet, including the emphasis on dietary management (type, quantity and quality of foods eaten, as well as timing of food intake); possible dietary restraints (restriction of food intake and adoption of dietary rules); focus on weight at diabetes clinic appointments and weight changes before and after diagnosis; the effect of diabetes on self-image and family interaction and other nutrition-related issues (Coleman and Caswell, 2020). By screening for diabetes distress and burnout in nutrition-related tasks (Table 1), HCPs can also detect any signs of eating disorders.
Role of carers in avoiding “nutrition burnout”
Parents and carers of pre-school children can find nutrition-related tasks very challenging due to “normal” food-related issues, such as seeking independence, transient food preferences, variable appetite, food refusal and behavioural resistance (Patton et al, 2008).
Children can recognise parental stress and quickly learn to use their diabetes as a way of getting their favourite foods. It is important for parents to ask themselves, “If my child did not have T1D, would I say no to this request?” (Sundberg et al, 2017). HCPs should work together with parents and facilitate helping techniques when the nutrition-related tasks have been causing distress in the family.
A failure to find the balance in responsibility for diabetes care between the parent and the CYP can lead to increased diabetes distress for all family members (Law et al, 2012). Channelling a pathway towards independence in dietary self-management, through better sharing of adolescent–parent responsibilities for diabetes care, with a timely transfer from parent-dominated to adolescent-dominated self-care, is a crucial foundation for good health-related diabetes outcomes.
Sociodemographic family factors, such as single-parent households or higher family density (more young people than adults in the household), lower family income and ethnic minority status, are associated with less optimal parental involvement in diabetes management (including nutrition-related tasks) and greater risk of poor diabetes management (Delamater et al, 2018).
The involvement of the parents and carers, as well as the school, in nutrition-related tasks can positively impact how the CYP with diabetes copes with their daily routines. Knowing that the tasks are not solely on the person’s shoulders and that support can be found in decision making can allow for the person to feel comforted with a rest from continuous health demands, and thus taking a step away from feeling burnt out.
Conclusion
Even though “nutrition burnout” is not an established term, it is important for HCPs to work together with CYP with diabetes and their carers to avoid stress related to nutrition-related tasks. The HCP should evaluate distress and use appropriate language, considering health literacy and language barriers, to give education about nutrition. It would be helpful to create a tool for CYP with T1D and their carers to evaluate nutrition burnout solely, or as a major component of diabetes burnout, and put into practice different ways of avoiding and dealing with it.
Acknowledgements
Children’s and Young People Diabetes Care Module, Birmingham City University and the collaborating clinical and academic module team.
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McGill DE, Levitsky LL (2016) Management of hypoglycemia in children and adolescents with type 1 diabetes mellitus. Curr Diab Rep 16: 88
Misra-Hebert AD, Isaacson JH (2012) Overcoming health care disparities via better cross-cultural communication and health literacy. Cleve Clin J Med 79: 127–33
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Polonsky, WH (1999) Diabetes Burnout: What to Do When You Can’t Take It Anymore. American Diabetes Association, Virginia, USA
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Sundberg F, Barnard K, Cato A et al (2017) ISPAD Guidelines. Managing diabetes in preschool children. Pediatr Diabetes 18: 499–517
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std::sub_match<BidirIt>::compare
From cppreference.com
< cpp | regex | sub match
int compare( const sub_match& m ) const;
(1) (since C++11)
int compare( const string_type& s ) const;
(2) (since C++11)
int compare( const value_type* c ) const;
(3) (since C++11)
1) Compares two sub_match directly by comparing their underlying character sequences. Equivalent to str().compare(m.str()).
2) Compares a sub_match with a std::basic_string. Equivalent to str().compare(s).
3) Compares a sub_match with a null-terminated sequence of the underlying character type pointed to by s. Equivalent to str().compare(c).
This function is infrequently used directly by application code. Instead, one of the non-member comparison operators are used.
Contents
[edit] Parameters
m - a reference to another sub_match
s - a reference to a string to compare to
c - a pointer to a null-terminated character sequence of the underlying value_type to compare to
[edit] Return value
A value less than zero if this sub_match is less than the other character sequence, zero if the both underlying character sequences are equal, greater than zero if this sub_match is greater than the other character sequence.
[edit] Example
[edit] See also
compares two strings
(public member function of std::basic_string<CharT,Traits,Allocator>) [edit]
converts to the underlying string type
(public member function) [edit]
compares two sub_match objects
(function template) [edit]
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What Is the Difference between CEREC and Traditional Crowns?
What Is the Difference between CEREC and Traditional Crowns?
Mar 01, 2022
Do you require restoration over a front tooth because it has weakened from decay or infections and is no longer fully functional? Visiting a dentist is the best way to start your journey on the therapeutic process because you may find it challenging to determine what kind of restoration you need. Although dentists will offer you different solutions of the cuff, you may not have sufficient knowledge of which restorative material best suits your requirements.
If your damaged or weakened tooth can be preserved, the dentist recommends you have a dental crown placed over the tooth for protection against further damage. If you are unaware of what dental crowns are, these restorations are protective covers for the damaged or weakened tooth sitting over it like a snug hat. Getting a dental crown over the tooth restores the tooth’s appearance, shape, size, and strength, restoring its functionality to ensure you can use it for over a decade.
The dentist may provide information you can either have traditional crowns made from metal, porcelain, or porcelain fused to metal if you wish. However, traditional crowns require at least two visits to the dentist’s office spanning over three weeks to get your dental crown. If you think the procedure of getting traditional dental crowns is cumbersome, the dentist offers CEREC crowns near you as an alternative option promising to complete the entire process in a few hours. The dentist also guides you on the dental crown procedure to educate you on restorative material you can select.
What Precisely Are CEREC Crowns?
Dentistry advances in technologies are making life much easier currently than earlier. In the past, if you had a damaged tooth only option available before you were to select traditional crowns provided by many dentists. While the reliability of conventional crowns remains undisputed, the time taken for creating them is lengthy, requiring you to wait for at least three weeks before you can have the restoration of your tooth. Aggravating the matter even further were temporary crowns placed over your prepared teeth to protect them.
The duration of time needed to get dental crowns perhaps encouraged researchers in dental technology to develop the Chairside Economical Restoration of Esthetic Ceramics, the acronym of which is CEREC that allows the dentist in Laguna Beach to provide you with a dental crown within a few hours. Instead of waiting for weeks for your permanent crown can presently walk into the office of the Laguna Beach dentist and leave the dentist’s office in a couple of hours with your new CEREC crown over your tooth.
CEREC crown restorations are completed by the Laguna Beach dentist in a single visit. You still have to undergo the teeth preparation process to reshape your tooth for the CEREC crown. However, you receive freedom from wearing temporary crowns because the dentist asks you to wait in the reception area as they fabricate your crown right there in the dental clinic near you.
After tooth preparation, you don’t have to provide impressions of your teeth using the traditional putty. Instead, the dentist takes digital impressions of your teeth using intraoral cameras for CEREC crowns. The intraoral scanner also captures 3D images of your teeth that are more accurate than traditional impressions. After capturing the photos, the dentist transfers the images to a computer.
Your CEREC crown is prepared in the dentist’s office using a milling machine from a block of porcelain. You can have traditional crowns made from metals, porcelain fused to metal, gold, or stainless steel. However, with CEREC crowns, your options are limited because you can only get all-porcelain crowns providing the best color match to other types of crowns. CEREC crowns are an excellent choice if you have metal allergies and want the restoration for a front tooth.
The Durability of CEREC Crowns
CEREC crowns in Laguna Beach are also durable like traditional crowns, so long as you have them from an experienced dental professional like the Laguna Beach dentist. Any dental restoration in your mouth is just as durable as the care you give it after placement. Therefore you must provide proper attention to the dental restoration by brushing twice a day, flossing at least once, and getting six-monthly exams and cleanings from your dentist to ensure the repair over your teeth is functioning excellently.
If you need a damaged or decayed front tooth restored with dental crowns but are not willing to endure the traditional crown process, please visit Laguna Family Dentistry, providing CEREC crowns for your front teeth in one visit.
Sleep Strips
Interested in improving your quality of sleep? Try our Sleep Strips! They help you improve the quality of your sleep through nasal breathing.
Purchase Sleep Strips
|
DVT SystemVerilog IDE User Guide
Rev. 20.1.20, 25 June 2020
Chapter 11. File Templates
Whenever you create a new file using the New File Wizard, you can pick a file template.
A file template is a code template with the context set to File Content. For more details see Code Templates.
|
Effect on renal function of tenofovir co-administered with either efavirenz or boosted lopinavir or boosted atazanavir: the Swiss HIV Cohort Study
Details
Serval ID
serval:BIB_001B7B9E709F
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Abstract (Abstract): shot summary in a article that contain essentials elements presented during a scientific conference, lecture or from a poster.
Collection
Publications
Institution
Title
Effect on renal function of tenofovir co-administered with either efavirenz or boosted lopinavir or boosted atazanavir: the Swiss HIV Cohort Study
Title of the conference
13th International Workshop on Adverse Drug Reactions and Co-morbidities in HIV
Author(s)
Schaefer J., Fux C., Bucher H.C., Bernasconi E., Vernazza P., Weber R., Cavassini M., Battegay M., Calmy A., Furrer H., Young J.
Address
Rome, Italy, July 14-16, 2011
ISBN
1359-6535
Publication state
Published
Issued date
2011
Peer-reviewed
Oui
Volume
16
Series
Antiviral therapy
Pages
A17-A18
Language
english
Notes
Publication type : Meeting Abstract
Abstract
Reduced re'nal function has been reported with tenofovir disoproxil fumarate (TDF). It is not clear whether TDF co-administered with a boosted protease inhibitor (PI) leads to a greater decline in renal function than TDF co-administered with a non-nucleoside reverse transcriptase inhibitor (NNRTI).Methods: We selected ail antiretroviral therapy-naive patients in the Swiss HIV Cohort Study (SHCS) with calibrated or corrected serum creatinine measurements starting antiretroviral therapy with TDF and either efavirenz (EFV) or the ritonavir-boosted PIs, lopinavir (LPV/r) or atazanavir (ATV/r). As a measure of renal function, we used the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to estimate the glomerular filtration rate (eGFR). We calculated the difference in eGFR over time between two therapies using a marginal model for repeated measures. In weighted analyses, observations were weighted by the product of their point of treatment and censoring weights to adjust for differences both in the sort of patients starting each therapy and in the sort of patients remaining on each therapy over time.Results: By March 2011, 940 patients with at least one creatinine measurement on a first therapy with either TDF and EFV (n=484), TDF and LPVlr (n=269) or TDF and ATV/r (n=187) had been followed for a median of 1. 7, 1.2 and 1.3 years, respectively. Table 1 shows the difference in average estimated GFR (eGFR) over time since starting cART for two marginal models. The first model was not adjusted for potential confounders; the second mode! used weights to adjust for confounders. The results suggest a greater decline in renal function during the first 6 months if TDF is used with a PI rather than with an NNRTI, but no further difference between these therapies after the first 6 months. TDF and ATV/r may lead to a greater decline in the first 6 months than TDF and LPVlr.Conclusions: TDF co-administered with a boosted PI leads to a greater de cline in renal function over the first 6 months of therapy than TDF co-administered with an NNRTI; this decline may be worse with ATV/r than with LPV/r.
Keywords
,
Web of science
Create date
23/09/2011 16:20
Last modification date
20/08/2019 13:22
Usage data
|
Additional Arguments and Parameters
Overview
Teaching: 10 min
Exercises: 0 min
Questions
• How do I specify arguments that don’t require input values?
• How do I refer to runtime parameters?
Objectives
• Learn how to add additional options to a command.
• Learn how to reference runtime parameters.
Sometimes tools require additional command line options that don’t correspond exactly to input parameters.
In this example, we will wrap the Java compiler to compile a java source file to a class file. By default, “javac” will create the class files in the same directory as the source file. However, CWL input files (and the directories in which they appear) may be read-only, so we need to instruct “javac” to write the class file to the designated output directory instead.
arguments.cwl
#!/usr/bin/env cwl-runner
cwlVersion: v1.0
class: CommandLineTool
label: Example trivial wrapper for Java 9 compiler
hints:
DockerRequirement:
dockerPull: openjdk:9.0.1-11-slim
baseCommand: javac
arguments: ["-d", $(runtime.outdir)]
inputs:
src:
type: File
inputBinding:
position: 1
outputs:
classfile:
type: File
outputBinding:
glob: "*.class"
arguments-job.yml
src:
class: File
path: Hello.java
Now create a sample Java file and invoke cwl-runner providing the tool wrapper and the input object on the command line:
$ echo "public class Hello {}" > Hello.java
$ cwl-runner arguments.cwl arguments-job.yml
[job arguments.cwl] /tmp/tmpwYALo1$ docker \
run \
-i \
--volume=/home/peter/work/common-workflow-language/v1.0/examples/Hello.java:/var/lib/cwl/stg8939ac04-7443-4990-a518-1855b2322141/Hello.java:ro \
--volume=/tmp/tmpwYALo1:/var/spool/cwl:rw \
--volume=/tmp/tmpptIAJ8:/tmp:rw \
--workdir=/var/spool/cwl \
--read-only=true \
--user=1001 \
--rm \
--env=TMPDIR=/tmp \
--env=HOME=/var/spool/cwl \
openjdk:9.0.1-11-slim \
javac \
-d \
/var/spool/cwl \
/var/lib/cwl/stg8939ac04-7443-4990-a518-1855b2322141/Hello.java
Final process status is success
{
"classfile": {
"size": 416,
"location": "/home/example/Hello.class",
"checksum": "sha1$2f7ac33c1f3aac3f1fec7b936b6562422c85b38a",
"class": "File"
}
}
Here we use the arguments field to add an additional argument to the command line that isn’t tied to a specific input parameter.
arguments: ["-d", $(runtime.outdir)]
This example references a runtime parameter. Runtime parameters provide information about the hardware or software environment when the tool is actually executed. The $(runtime.outdir) parameter is the path to the designated output directory. Other parameters include $(runtime.tmpdir), $(runtime.ram), $(runtime.cores), $(runtime.outdirSize), and $(runtime.tmpdirSize). See the Runtime Environment section of the CWL specification for details.
Key Points
• Use the arguments section to describe command line options that do not correspond exactly to input parameters.
• Runtime parameters provide information about the environment when the tool is actually executed.
• Runtime parameters are referred under the runtime namespace.
|
Ir para o conteúdo principal
Conserte seus objetos
Direito de executar reparos
Loja
Ajuda
Editando passo 2 —
Tipo de Passo:
Arraste para reorganizar
Samsung just brought the biggest contender to the Camera Bump Contest—the one you didn't know was happening—and now it's over! Everybody go home.
Technically you could make a bigger bump, but at some point it just becomes a thicker phone body with no bump at all. Crazy talk, we know.
Here's a nifty visual comparison with the iPhone 11 Pro Max with its raised triple bump, and the Note10+5G with its single Martinsville Speedway bump.
Our unit might be defective—we couldn't find anywhere to plug in our headphones. And the Bixby button is gone, so who are we supposed to loudly complain to?
Suas contribuições são licenciadas pela licença de código aberto Creative Commons.
|
Fedora setup: installing software
As any Linux distro is as good as it's software repositories, in my experience Fedora is really good. During install you get the option to enable some pre-defined third-party repositories, but I prefer to start with just the official Fedora repositories (mirrors.fedoraproject.org) and only add and/or enable other repositories if I need them. I also prefer using the traditional RPM packages over the Fedora flatpak versions. I still don't feel comfortable with containerized applications and if I wanted a flatpak oriented operating system, I would be on Fedora Silverblue and not on Fedora Workstation.
I don't have a lot of software needs as I usually get by with a browser, editor and terminal as a developer, but I do have some favorite applications that I install with either dnf in the terminal or the Gnome Software Center. The first 2 are GUI applications for reading (and both in the Software Center):
Both NewsFlash (and it's predecessor FeedReader) and Foliate I discovered when I used elementary OS in 2019/2020 before I switched to Fedora 33, but I had to install it from Flathub. The packaged Fedora versions are both up-to-date and look great on Gnome.
The next ones are command line applications that I install with dnf:
I mostly use git and ssh on the command line, but those are already preinstalled. These other ones I use every once in a while. I use syncthing as cross-platform sharing/backup of important documents between several of my computers and lynx to access gopherspace; newsboat is something I use to curate RSS articles quickly and to automate some experimental stuff.
For the last 2 I first need to add their third-party repository, so I can get automatic updates:
Although I used to use Firefox as my main browser for 15 years, I switched to Brave in 2020, as I wasn't happy where Firefox was going and I wanted to get rid of my dependency on the Firefox account for browser synching. VSCodium/VSCode is also something I started using recently and replaces Sublime Text that I used for 10 years.
One of the things I have been contemplating for a while, is to also install an email client like Evolution or Thunderbird or Geart. I've been using them occiasonaly, but somehow I have a hard time re-adjusting. In the mean time I use the 'Install as application' feature in Chromium-based browsers for my webmail clients, so they open as a separate window and look like a desktop application. I do the same for other applications like Mastodon and Element until I find a good native desktop client.
So, I don't use a lot of software and I don't try out a lot anymore, but I do check in every once a while to see what's recommended through Gnome through the Sofware Center or Apps for Gnome
|
Knowledge Base
Intel’s Haswell 4th Generation Processors for Socket LGA 1150 Guide
By April 3, 2020 No Comments
Intel’s Haswell processors succeeded the Sandy Bridge and Ivy Bridge micro-architectures and, since then, have paved the way for Broadwell and Skylake micro-architectures. Haswell processors were announced in 2013 and subsequently launched globally. Haswell CPUs were primarily designed to improve the performance and power savings features of processors working with Intel 8-Series and 9-Series chipsets. Haswell CPUs are compatible with motherboards that have Intel’s Socket LGA 1150.
Haswell Vs Ivy Bridge
Every time Intel releases a new micro-architecture, naturally it is always compared with its preceding version and in this case, Haswell is pitted against Ivy Bridge. Compared to Ivy Bridge processors, Haswell processors have as much as 8% higher vector processing performance, single threaded performance has increased by as much as 6% and so has multi-threaded performance. Sequential CPU performance too has increased by 6%. The average improvement in performance of Haswell processors as compared to Ivy Bridge is around 3%.
There are many features of Ivy Bridge that have been brought forward to Haswell processors. It still features a 22nm manufacturing process, 3D tri-gate transistors, micro-operation cache with storage for 1.5 K micro-operations, 14- to 19-stage instruction pipeline, dual-channel DDR3 memory, and 16 PCI Express 3.0 lanes among others.
There are certain new features in Haswell comparable to Ivy Bridge. Haswell processors come with a larger core with a fourth arithmetic logic unit, second brand prediction unit, third address generation unit, higher cache bandwidth, deeper buffers, and better memory controllers.
Full List of Haswell Processors
If you are looking for a processor capable of playing the latest games at maximum settings, you could do worse than a Haswell chip. Overclocking is possible up to 4.7GHz, although it will be much more stable at around 4.4GHz.
Below is the full list of Haswell processors:
Core i7 ExtremeCore i7Core i5Core i3PentiumCeleron
5960X4790K4690K4370G3470G1850
5930K479046904360G3460G1840
5820K4790S4690S4350G3450G1830
4790T4690T4340G3440G1820
4785T4670K4330G3430G1840T
477146704370TG3420G1820T
4770K4670S4360TG3460TG1820TE
47704670R4350TG3450T
4770S4670T4330TG3440T
4770R45904340TEG3420T
4770T4590S4330TEG3320TE
4770TE4590T4170G3260
4765T45704160G3258
4570S4150G3250
4570R4130G3240
4570T4170TG3220
4570TE4160TG3260T
44604150TG3250T
4460S4130TG3240T
4460TG3220T
4440
4440S
4430
4430S
|
DynArray problem Pdox DOS
DynArray problem Pdox DOS
Post by Jan Theo Bakk » Wed, 02 Nov 1994 23:30:46
Does anyone know a fast way to determine whether an element of a
dynamic array does NOT exist? IsAssigned and Not IsAssigned are not
enough I think, because no difference is made between the presence
of an element and the contents of the element. Also, combinations with
isblank etc. don't work. They result in a cancel/debug BECAUSE the
element does not exist. Only thing I think of is a FOR-loop over the
array.
Thanks,
Jan Theo
DynArray problem Pdox DOS
Post by DCarl » Fri, 04 Nov 1994 09:39:11
Quote:(Jan Theo Bakker) writes:
A combination in the right order should work for you. I'm not sure if
you've given enough info but try:
IF NOT ISASSIGNED(myArray["SomethingHere"]) OR
ISBLANK(myArray["SomethingHere"]) THEN
..........;Code here if dynarray is not assigned or is blank
ENDIF
Does this not work for you?
Can* Corporation
DynArray problem Pdox DOS
Post by ABrons » Fri, 04 Nov 1994 13:06:12
Quote:(Jan Theo Bakker) writes:
>Does anyone know a fast way to determine whether an element of a
>dynamic array does NOT exist? IsAssigned and Not IsAssigned are not
>enough I think, because no difference is made between the presence
>of an element and the contents of the element. Also, combinations with
>isblank etc. don't work. They result in a cancel/debug BECAUSE the
>element does not exist. Only thing I think of is a FOR-loop over the
>array.
The isassigned function is *exactly* the way to do it, as in
isassigned(dynarray["tag"]). This works because there is no way to create
a dynarray element without also assigning it a value, so the problem you
speak of does not exist.
--Aaron
DynArray problem Pdox DOS
Post by FrontM » Fri, 04 Nov 1994 22:08:02
Quote:(Jan Theo Bakker) writes:
Does anyone know a fast way to determine whether an element of a
dynamic array does NOT exist? IsAssigned and Not IsAssigned are not
enough I think, because no difference is made between the presence
of an element and the contents of the element. Also, combinations with
isblank etc. don't work. They result in a cancel/debug BECAUSE the
element does not exist. Only thing I think of is a FOR-loop over the
array.
=========================
ISASSIGNED & ISBLANK are it, but can be used effectively. ISASSIGNED will
return false if the element has not been assigned at all (does not exist),
but will return True if the element exists but is blank. ISBLANK can then
be used to determine the status of its contents -- I do it all the time.
So you might use:
IF ISASSIGNED(X["This One"]) AND NOT ISBLANK(X["This One"])
THEN DO_THIS_THING
ELSE
IF ISASSIGNED(X["This One"])
THEN DO_THAT_THING
ENDIF
DR
1. PDOX 4.0 for DOS and PDOX for Windows
I cut my database teeth on Paradox for DOS but am now having to enter
the Windows era. Unfortunately, the newer versions of Paradox for
Windows (7, 8, 9) do not have the ability to record scripts from key
strokes and mouse clicks as was possible in the DOS versions. I found
this old feature very useful for quickly producing scripts and for
learning the syntax and commands of PAL. Are there any early Windows
versions of Paradox that retain the Record Script feature and is there
any place I can get copies of the program and manuals? If so, it would
be of immense value to me while I'm on the steep part of the learning
curve with ObjectPAL.
Many thanks for any help that you can provide.
Randy Linder
2. Forced to Strictly SQL ... YUCK!
3. PDOX 4.5 DOS to PDOX 8 WIN95....?
4. LONDON - Sybase Server Development - Unix/CShell Scripting - Equity Derivatives - Front Office - ￡30k to ￡50k + to 30%
5. ADO and Oracle BLOBs
6. PDOX DOS programmer needs help understanding PDOX 7
7. Incorrect Query results - Urgent
8. DOS PDOX 3.5 conversion to PDOX WINDOWS, Need conversion Utilites
9. PDOX 7-EXECUTING DOS BATCH FILE FROM PDOX FORM
10. Question: pdox(dos) vs. pdox(win)
11. pdox(dos) vs. pdox(win)
12. PDOX DOS .SC -> PDOX 4.5 WINDOWS
|
Adspecs and case, 1996.
3 3 c m
40cm
actual image size: 32cm x 25cm
Adspecs and case, 1996.
© Science Museum / Science & Society Picture Library
Description
A pair of adaptive spectacles invented by Joshua D Silver, profesor of physics at Oxford University. Spectacles have been in use in the West for at least 700 years. The earliest had convex lenses, and were designed to beworn by people with long sight, to help them focus on nearby objects. Later, concave spectacle lenses were made for people with short sight. In 1784 Benjamin Franklin (1706-1790) invented 'bifocals' - spectacles split into two parts, each with a different focal length. Adaptive spectacles are designed to allow the wearer to manually adjust the power of each lens to their own requirements.
Image Ref.
10309165
buy a print
Select size
Select finish
How many prints?
£20.00
buy a framed print
buy a canvas
buy a framed canvas
|
A fork of Gitea (see branch `mj`) adding Majority Judgment Polls 𐄷 over Issues and Merge Requests. https://git.mieuxvoter.fr
You can not select more than 25 topics Topics must start with a letter or number, can include dashes ('-') and can be up to 35 characters long.
229 lines
7.6 KiB
// Copyright 2020 The Gitea Authors. All rights reserved.
// Use of this source code is governed by a MIT-style
// license that can be found in the LICENSE file.
package repo
import (
"bytes"
"errors"
"fmt"
"net/http"
"strings"
"code.gitea.io/gitea/models"
"code.gitea.io/gitea/modules/auth"
"code.gitea.io/gitea/modules/context"
"code.gitea.io/gitea/modules/convert"
"code.gitea.io/gitea/modules/graceful"
"code.gitea.io/gitea/modules/log"
"code.gitea.io/gitea/modules/migrations"
"code.gitea.io/gitea/modules/notification"
repo_module "code.gitea.io/gitea/modules/repository"
"code.gitea.io/gitea/modules/setting"
api "code.gitea.io/gitea/modules/structs"
"code.gitea.io/gitea/modules/util"
)
// Migrate migrate remote git repository to gitea
func Migrate(ctx *context.APIContext, form api.MigrateRepoOptions) {
// swagger:operation POST /repos/migrate repository repoMigrate
// ---
// summary: Migrate a remote git repository
// consumes:
// - application/json
// produces:
// - application/json
// parameters:
// - name: body
// in: body
// schema:
// "$ref": "#/definitions/MigrateRepoOptions"
// responses:
// "201":
// "$ref": "#/responses/Repository"
// "403":
// "$ref": "#/responses/forbidden"
// "422":
// "$ref": "#/responses/validationError"
//get repoOwner
var (
repoOwner *models.User
err error
)
if len(form.RepoOwner) != 0 {
repoOwner, err = models.GetUserByName(form.RepoOwner)
} else if form.RepoOwnerID != 0 {
repoOwner, err = models.GetUserByID(form.RepoOwnerID)
} else {
repoOwner = ctx.User
}
if err != nil {
if models.IsErrUserNotExist(err) {
ctx.Error(http.StatusUnprocessableEntity, "", err)
} else {
ctx.Error(http.StatusInternalServerError, "GetUser", err)
}
return
}
if ctx.HasError() {
ctx.Error(http.StatusUnprocessableEntity, "", ctx.GetErrMsg())
return
}
if !ctx.User.IsAdmin {
if !repoOwner.IsOrganization() && ctx.User.ID != repoOwner.ID {
ctx.Error(http.StatusForbidden, "", "Given user is not an organization.")
return
}
if repoOwner.IsOrganization() {
// Check ownership of organization.
isOwner, err := repoOwner.IsOwnedBy(ctx.User.ID)
if err != nil {
ctx.Error(http.StatusInternalServerError, "IsOwnedBy", err)
return
} else if !isOwner {
ctx.Error(http.StatusForbidden, "", "Given user is not owner of organization.")
return
}
}
}
remoteAddr, err := auth.ParseRemoteAddr(form.CloneAddr, form.AuthUsername, form.AuthPassword, ctx.User)
if err != nil {
if models.IsErrInvalidCloneAddr(err) {
addrErr := err.(models.ErrInvalidCloneAddr)
switch {
case addrErr.IsURLError:
ctx.Error(http.StatusUnprocessableEntity, "", err)
case addrErr.IsPermissionDenied:
ctx.Error(http.StatusUnprocessableEntity, "", "You are not allowed to import local repositories.")
case addrErr.IsInvalidPath:
ctx.Error(http.StatusUnprocessableEntity, "", "Invalid local path, it does not exist or not a directory.")
default:
ctx.Error(http.StatusInternalServerError, "ParseRemoteAddr", "Unknown error type (ErrInvalidCloneAddr): "+err.Error())
}
} else {
ctx.Error(http.StatusInternalServerError, "ParseRemoteAddr", err)
}
return
}
gitServiceType := convert.ToGitServiceType(form.Service)
if form.Mirror && setting.Repository.DisableMirrors {
ctx.Error(http.StatusForbidden, "MirrorsGlobalDisabled", fmt.Errorf("the site administrator has disabled mirrors"))
return
}
var opts = migrations.MigrateOptions{
CloneAddr: remoteAddr,
RepoName: form.RepoName,
Description: form.Description,
Private: form.Private || setting.Repository.ForcePrivate,
Mirror: form.Mirror,
AuthUsername: form.AuthUsername,
AuthPassword: form.AuthPassword,
AuthToken: form.AuthToken,
Wiki: form.Wiki,
Issues: form.Issues,
Milestones: form.Milestones,
Labels: form.Labels,
Comments: true,
PullRequests: form.PullRequests,
Releases: form.Releases,
GitServiceType: gitServiceType,
}
if opts.Mirror {
opts.Issues = false
opts.Milestones = false
opts.Labels = false
opts.Comments = false
opts.PullRequests = false
opts.Releases = false
}
repo, err := repo_module.CreateRepository(ctx.User, repoOwner, models.CreateRepoOptions{
Name: opts.RepoName,
Description: opts.Description,
OriginalURL: form.CloneAddr,
GitServiceType: gitServiceType,
IsPrivate: opts.Private,
IsMirror: opts.Mirror,
Status: models.RepositoryBeingMigrated,
})
if err != nil {
handleMigrateError(ctx, repoOwner, remoteAddr, err)
return
}
opts.MigrateToRepoID = repo.ID
defer func() {
if e := recover(); e != nil {
var buf bytes.Buffer
fmt.Fprintf(&buf, "Handler crashed with error: %v", log.Stack(2))
err = errors.New(buf.String())
}
if err == nil {
repo.Status = models.RepositoryReady
if err := models.UpdateRepositoryCols(repo, "status"); err == nil {
notification.NotifyMigrateRepository(ctx.User, repoOwner, repo)
return
}
}
if repo != nil {
if errDelete := models.DeleteRepository(ctx.User, repoOwner.ID, repo.ID); errDelete != nil {
log.Error("DeleteRepository: %v", errDelete)
}
}
}()
if _, err = migrations.MigrateRepository(graceful.GetManager().HammerContext(), ctx.User, repoOwner.Name, opts); err != nil {
handleMigrateError(ctx, repoOwner, remoteAddr, err)
return
}
log.Trace("Repository migrated: %s/%s", repoOwner.Name, form.RepoName)
ctx.JSON(http.StatusCreated, repo.APIFormat(models.AccessModeAdmin))
}
func handleMigrateError(ctx *context.APIContext, repoOwner *models.User, remoteAddr string, err error) {
switch {
case models.IsErrRepoAlreadyExist(err):
ctx.Error(http.StatusConflict, "", "The repository with the same name already exists.")
case models.IsErrRepoFilesAlreadyExist(err):
ctx.Error(http.StatusConflict, "", "Files already exist for this repository. Adopt them or delete them.")
case migrations.IsRateLimitError(err):
ctx.Error(http.StatusUnprocessableEntity, "", "Remote visit addressed rate limitation.")
case migrations.IsTwoFactorAuthError(err):
ctx.Error(http.StatusUnprocessableEntity, "", "Remote visit required two factors authentication.")
case models.IsErrReachLimitOfRepo(err):
ctx.Error(http.StatusUnprocessableEntity, "", fmt.Sprintf("You have already reached your limit of %d repositories.", repoOwner.MaxCreationLimit()))
case models.IsErrNameReserved(err):
ctx.Error(http.StatusUnprocessableEntity, "", fmt.Sprintf("The username '%s' is reserved.", err.(models.ErrNameReserved).Name))
case models.IsErrNameCharsNotAllowed(err):
ctx.Error(http.StatusUnprocessableEntity, "", fmt.Sprintf("The username '%s' contains invalid characters.", err.(models.ErrNameCharsNotAllowed).Name))
case models.IsErrNamePatternNotAllowed(err):
ctx.Error(http.StatusUnprocessableEntity, "", fmt.Sprintf("The pattern '%s' is not allowed in a username.", err.(models.ErrNamePatternNotAllowed).Pattern))
case models.IsErrMigrationNotAllowed(err):
ctx.Error(http.StatusUnprocessableEntity, "", err)
default:
err = util.URLSanitizedError(err, remoteAddr)
if strings.Contains(err.Error(), "Authentication failed") ||
strings.Contains(err.Error(), "Bad credentials") ||
strings.Contains(err.Error(), "could not read Username") {
ctx.Error(http.StatusUnprocessableEntity, "", fmt.Sprintf("Authentication failed: %v.", err))
} else if strings.Contains(err.Error(), "fatal:") {
ctx.Error(http.StatusUnprocessableEntity, "", fmt.Sprintf("Migration failed: %v.", err))
} else {
ctx.Error(http.StatusInternalServerError, "MigrateRepository", err)
}
}
}
|
FANDOM
Rhinopomastus
6015438708 38bb5c4a79 b
Common Scimitarbill (Rhinopomastus cyanomelas)
Scientific Classification
Kingdom Animalia
Phylum Chordata
Class Aves
Order Bucerotiformes
Family Phoeniculidae
Genus Rhinopomastus
Rhinopomastus or scimitarbills (also spelt scimitar-bills), is a genus of wood hoopoes. They are often classified in the family Phoeniculidae; however, genetic studies show that they diverged from the true woodhoopoes about 10 million years ago and so they are sometimes placed in a family of their own, the Rhinopomastidae.
They are smaller than most woodhoopoes and their bills are strongly curved like a scimitar, giving them their name. They are mostly glossy black in colour with a few white markings on the wings. While other woodhoopoes are gregarious birds which gather in flocks, the scimitarbills are usually seen alone or in pairs.
They feed mainly on insects and other invertebrates, which they find by using their bills to probe into holes and crevices. They are acrobatic birds, well-adapted for clambering through trees. The eggs are laid in a tree cavity.
Species
Black Scimitarbill (Stephens, 1826) (Rhinopomastus aterrimus)
Common Scimitarbill (Vieillot, 1819) (Rhinopomastus cyanomelas)
Abyssinian Scimitarbill (Rüppell, 1845) (Rhinopomastus minor)
Gallery
Community content is available under CC-BY-SA unless otherwise noted.
|
5
I'm still learning Drupal, and I was trying to use hook_form_alter() to resize a text field added from a module. My problem is that I don't think I'm indentifying the element correctly.
Here's the element code:
<input type="text" class="form-text form-autocomplete" value="" size="60" id="edit-2" name="2" maxlength="128" autocomplete="OFF">
Here's my module code:
/**
* Implements hook_form_alter().
*/
if ($form_id == 'edit-2') {
$form['text'] = array(
'#type' => 'text',
'#size' => 25,
);
}
I'm not sure what to do; any suggestions would be helpful.
Thanks!
9
The HTML id has nothing to do with $form_id.
$form_id is the name of the whole form. In most cases, it is the name of the function that generates the form unless hook_forms() is used.
Instead of checking the $form_id with an if condition, it is often easier to implement the more specific hook_form_FORM_ID_alter() hook. So if the form_id is BLA, you can directly create a function yourmodule_form_BLA_alter(&$form, &$form_state)and don't need to mess with $form_id at all.
There are exception when this doesn't work or isn't practically, but it most cases, it is recommended to use that hook (It's a performance improvement too, because your function will just be called for that specific form and not every single form in Drupal).
If you are not sure what $form_id is, implement hook_form_alter() and put a drupal_set_message($form_id) in there. That should then print all form ids of the page you are on, allowing you to easily pick the one you want to change.
About the name of the form element, you can't guess that from the HTML in most cases, because unless #tree is set to TRUE, the names are flattened, so it might be $form['some_fieldset']['example'] in the $form structure and just name="example" in HTML.
So, to find the element you want to change, there are two ways.
a) Look at the source code of the function that defines the form structure.
b) Use dpm($form) (requires devel.module).
I prefer the second method, and this is usually the second step after figuring out the $form_id, if I don't know exactly what I want to do. dpm() prints complex array/object structures in a very nice and browseable way. That is actually something you should get used to all the time when you work with Drupal. Don't just guess things. You're going to be wrong pretty often. Instead, if there are any variables that you want to use but don't know the exact structure of them, add a dpm($var), load the page/trigger the action and then you can exactly see what you are working with.
Edit:
The last problem is that right now, your code does completely replace that form element. Instead, you only want to override the #size property, like this:
$form['finder_form'][2]['#size'] = 25;
|improve this answer|||||
• Thank you so much Berdir. I can't thank you enough. I pretty much had to google everything you said but it gave me the tools to get close to solving the problem. I'm not there yet though. I got to the part where I get an array from dpm($form) but I'm not sure to actually identify what is the element itself that I modifying. Its basically a text search box, but I can't seem to find any names that resemble it at all. Any tips of narrowing down what I want to modify? – Lostsoul Jun 22 '11 at 2:39
• In my function I tried to add something like this: $form['2'] = array( '#type' => 'textfield', '#size' => 25, ); } but its actually not modifying the existing search bar, but adding a second one, which makes me think I am not identifying the element correctly. – Lostsoul Jun 22 '11 at 2:44
• I saw in the dpm command, there was an element named 2(under the finder_form element which I think is the one I need). under "2", there was a bunch of options that looked like they were correct for the element I am trying to modify, but no luck. – Lostsoul Jun 22 '11 at 2:45
• I managed to figure it out. 2 was the correct element but it was under another element, so I added: $form['finder_form']['2'] = array( '#type' => 'textfield', '#size' => 25, ); } and it worked. Right now I'm using an actual value for size, is there a way to make it relative so if a person has a larger/smaller screen it always looks good? – Lostsoul Jun 22 '11 at 3:13
• sorry, last question..alot of my fucntionality is gone(it was an autocomplete search field)...does this mean I have to add all the elements I want back into my module above? or is there a way for it to only modify what I tell it to change? – Lostsoul Jun 22 '11 at 3:15
3
The problem is that you are looking at the HTML produced by Drupal, to decide which is the identifier of the form field that you want to modify.
• hook_form_alter(), hook_form_FORM_ID_alter(), and hook_form_BASE_FORM_ID_alter() (introduced in Drupal 7) don't directly alter the HTML output produced from Drupal; they alter an array containing the values described in Form API Quickstart Guide, Form API Reference (for Drupal 7, there are Form generation and Form API Reference).
• The form you are trying to alter could contain a form field that is contained in another form field; this normally happens with form fields that are part of a field set. The structure of the form array used by the form API is difficult to interpret basing on the HTML output.
What you would need to do is to
• find out the module that creates the form field you are trying to alter
• find out the form building function that generates the form containing that form field
• read the array containing the description of the form field you need to alter
Once you have done it, you can create the implementation of the hook that will allow you to alter that form field.
If the form builder function is, for example, path_admin_form() and your module is mymodule.module, then you can implement mymodule_form_path_admin_form(&$form, &$form_state).
|improve this answer|||||
1
First you want to look for the form in HTML of the loaded page.
<form class="node-form node-article-form" enctype="multipart/form-data" action="/cruzr/node/226/edit?destination=admin/workbench" method="post" id="article-node-form" accept-charset="UTF-8"><div><div class="form-item form-type-textfield form-item-title">
</form>
Here the ID is 'article-node-form'.
Then you want to use the HOOK_form_FORM_ID_alter() callback function.
|improve this answer|||||
0
1 For a quick answer I'd use the html. The form tag tells you
<form action="/yhivebook/class/917/1503856800?XDEBUG_SESSION_START=10676" method="post" id="yhivebook-booking-form"
2 In hook_form_alter the 3rd parameter is the form_id
function views_megarow_form_alter(&$form, &$form_state, $form_id) {
3 Any function with $form_state has it in
$form_state['build_info']['form_id']
Point your debugger there.
For example, submitting the form with the form id will work.
drupal_form_submit($form_state['build_info']['form_id'], $form_state);
|improve this answer|||||
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ShippingApiLevelModuleController
public class ShippingApiLevelModuleController
extends BaseModuleController
java.lang.Object
com.android.tradefed.testtype.suite.module.BaseModuleController
com.android.tradefed.testtype.suite.module.ShippingApiLevelModuleController
Führen Sie Tests durch, wenn das Gerät die folgenden Bedingungen erfüllt:
• Wenn min-api-level definiert ist:
• Das Gerät wird mit der min-api-level oder höher ausgeliefert.
• Wenn vsr-min-api-level definiert ist:
• Das Gerät wird mit der Stufe vsr-min-api-level oder höher ausgeliefert.
• Das Anbieter-Image implementierte die Funktionen für die vsr-min-api-level oder höher.
Zusammenfassung
Öffentliche Bauträger
ShippingApiLevelModuleController ()
Öffentliche Methoden
IModuleController.RunStrategy shouldRun ( IInvocationContext context)
Methode zur Entscheidung, ob das Modul ausgeführt werden soll oder nicht.
Öffentliche Bauträger
ShippingApiLevelModuleController
public ShippingApiLevelModuleController ()
Öffentliche Methoden
sollteRun
public IModuleController.RunStrategy shouldRun (IInvocationContext context)
Methode zur Entscheidung, ob das Modul ausgeführt werden soll oder nicht.
Parameter
context IInvocationContext : der IInvocationContext des Moduls
Kehrt zurück
IModuleController.RunStrategy RunStrategy#RUN , wenn das Modul ausgeführt werden soll, andernfalls IModuleController.RunStrategy.FULL_MODULE_BYPASS .
Würfe
DeviceNotAvailableException wenn das Gerät nicht verfügbar ist
|
Arthritis Gout Joint Pain
Gout: Disease of the Kings
Hand surgeon John M. Erickson, MD answers your questions about the disease called Gout.
Gout is a common type of inflammatory arthritis typically presenting with a red, hot, swollen, extremely painful joint. Gout frequently affects joints in the big toe, ankle or knee but can happen elsewhere. Gout can also involve the fingers, wrist and elbow. A “gout attack” usually starts suddenly and the pain increases rapidly. Because of the skin redness, warmth, and pain intensity, gout attacks can be difficult to distinguish from infection.
What is gout?
A gout attack is caused when uric acid normally circulating in the blood deposits in joints or soft tissues and forms crystals. When the body reacts to the crystals it creates a painful inflammatory reaction. Uric acid is naturally produced in the body. It is a normal breakdown product of a chemical in many foods called purines. Our bodies remove uric acid through the urine. Gout occurs when there is either too much uric acid produced in the body or too little being removed by the kidneys. Gout attacks can cause joint damage over time. Bumps or nodules of uric acid can develop around the joints in long-term gout; these nodules are called tophi.
Doctors have known about gout for many centuries. Historically, gout was thought to be a disease of only the wealthy or royal class, and it was called the “disease of the kings.” Overindulgence in diets rich in meats, seafood, and alcohol has long been associated with gout, and the people who could afford such a lifestyle were the people typically affected. We now know that this is because animal proteins such as red meat, pork, oily fish, and shellfish are high in purines. Additionally, alcohol reduces the metabolism of uric acid and can make problems with gout more significant.
What are the risk factors for gout?
Gout occurs more often in males than females. Other risk factors for gout are family history, purine-rich diets, alcoholism, kidney disease, obesity, diabetes, dehydration, use of chemotherapy drugs, and use of some diuretic medications (water pills). Food products with added fructose and sugary drinks can also increase the risk of gout. Occasionally, trauma and surgery can bring on a gout attack.
How is gout treated?
Treatment of acute gout attacks typically involves rest, splinting, and anti-inflammatory medications. Naproxen and ibuprofen are examples of common over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs) used in the treatment of gout. Indomethacin and prednisone are stronger prescription anti-inflammatory medications. Colchicine is another commonly prescribed medicine for gout attacks. A corticosteroid injection into the joint (cortisone shot) can also be used to reduce the inflammation from gout. Gout attacks usually last for a few days, and prompt treatment can make the symptoms go away sooner.
How is gout prevented?
Attacks of gout can lead to joint damage over time, therefore prevention of gout attacks is important. Treatment of gout involves decreasing the uric acid level in the diet and/or increasing the excretion of uric acid in urine. There are several lifestyle changes which can reduce the risk of a gout attack, including:
1. Stay hydrated and drink adequate amounts of water to flush the uric acid through the kidneys.
2. Limit the intake of animal meats high in purines such as beef, pork, oily fish, and shellfish to reduce the production of uric acid. Organ meats such as liver, kidneys, and sweetbreads are especially high in purines.
3. Limit the intake of alcohol.
4. Limit the intake of processed foods such as refined flour, sugary drinks, and food products with added fructose. Instead, choose foods with complex carbohydrates such as whole grains, fresh fruits and vegetables. Choose dairy products such as low-fat milk and yogurt.
If diet and lifestyle changes are not enough to control the gout attacks, preventative medications may be needed. Most doctors recommend starting a medication to reduce uric acid in the blood if patients have more than two gout attacks in a year. These medications include allopurinol, probenacid, and febuxostat. Primary care physicians often prescribe these medications and monitor the uric acid level with blood tests. These medications are meant to treat an acute gout attack and are designed to prevent gout attacks long-term. Please talk to your doctor if you have questions about gout.
Dr. John M. Erickson is a hand and upper extremity specialist at the Raleigh Hand Center. He trained in orthopedic surgery at the University of Michigan and completed a hand surgery fellowship at Vanderbilt University. He19 is an active member of the American Society for Surgery of the Hand (ASSH).
You may also like
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/* Copyright (C) 2001,2002,2003,2004 Michael Rubinstein This file is part of the L-function package L. This program is free software; you can redistribute it and/or modify it under the terms of the GNU General Public License as published by the Free Software Foundation; either version 2 of the License, or (at your option) any later version. This program is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU General Public License for more details. Check the License for details. You should have received a copy of it, along with the package; see the file 'COPYING'. If not, write to the Free Software Foundation, Inc., 59 Temple Place - Suite 330, Boston, MA 02111-1307, USA. */ #include "L.h" #include "Lcommandline_values_zeros.h" //-----functions-------------------------------------------------------------- void compute_values(Double x,Double y,const char *return_type,const char *file_name,Double x3,Double y3,Long count) { fstream file; Complex s,u; Double x2,y2; //cout << setprecision(DIGITS3); if(strcmp(file_name,"")) //i.e. if a file_name has been provided... { file.open(file_name, ios::in); if(!file.is_open()) { cout << endl << "FAILED TO FIND THE FILE: " << file_name<< endl; exit(1); } while (!file.eof()) { file >> x2; file >> y2; s=Complex(x2,y2); if(!file.eof()) switch(current_L_type) { case 1: u=int_L.value(s,global_derivative,return_type); //global_derivative specifies which derivative to compute. Default is 0 which //is just the plain L-value cout << real(u) << " " << imag(u) << endl; //cout << imag(s) << " " << abs(u)<< endl; break; case 2: u=Double_L.value(s,global_derivative,return_type); cout << real(u) << " " << imag(u) << endl; break; case 3: u=Complex_L.value(s,global_derivative,return_type); cout << real(u) << " " << imag(u) << endl; break; } } file.close(); } else // else use the x and y provided { Long n=0; s=Complex(x,y); //#pragma omp sections { do{ n++; cout << setprecision(DIGITS); if(count>0)cout << real(s) << " " << imag(s) <<" "; cout << setprecision(DIGITS3); switch(current_L_type) { case 1: u=int_L.value(s,global_derivative,return_type); cout << real(u) << " " << imag(u) << endl; //cout << imag(s) << " " << abs(u)<< endl; break; case 2: u=Double_L.value(s,global_derivative,return_type); cout << real(u) << " " << imag(u) << endl; break; case 3: u=Complex_L.value(s,global_derivative,return_type); cout << real(u) << " " << imag(u) << endl; break; } s=s+Complex(x3-x,y3-y)/(double)count; } while(n0, we look for the first //count zeros (starting at t1 not yet implemented) using steps of no smaller //than step_size. //if count >0 then t2 is not used, so it's value is irrelevant. void compute_zeros(Double x, Double y,Double step_size, Long count,int rank, bool test_explicit_formula) { if(current_L_type==1){ if(count==0) int_L.find_zeros(x,y,step_size); //else int_L.find_zeros_via_gram(x,count,step_size); else int_L.find_zeros_via_N(count,false,step_size,rank,test_explicit_formula); //else int_L.find_zeros_elaborate(x,count,step_size); } if(current_L_type==2){ if(count==0) Double_L.find_zeros(x,y,step_size); //else Double_L.find_zeros_via_gram(x,count,step_size); else Double_L.find_zeros_via_N(count,false,step_size,rank,test_explicit_formula); //else Double_L.find_zeros_elaborate(x,count,step_size); } if(current_L_type==3){ if(count==0) Complex_L.find_zeros(x,y,step_size); //Complex_L.find_zeros_via_gram(x,count,step_size); Complex_L.find_zeros_via_N(count,true,step_size,rank,test_explicit_formula); } } //find the zeros of the function obtained by interpolating L and L2. Assumes //they are of the same quasi degree and have same number of dirichlet //coefficients. The interpolated L-function has all its basic data as t times the //data of the first L-function and (1-t) times the data of the second L-function. //does not work with integer L_functions since interpolation gives at least doubles void L_interpolate(Double x, Double y,Double step_size, int n) { double t; char message_stamp[300]; ostrstream os2(message_stamp,300); t=0; do{ os2.seekp(0); os2 << t << ends; if(current_L_type==2){ Double_L3=Double_L*(1-t)+Double_L2*t; Double_L3.find_zeros(x,y,step_size,"cout",message_stamp); } if(current_L_type==3){ Complex_L3=Complex_L*(1-t)+Complex_L2*t; Complex_L3.find_zeros(x,y,step_size,"cout",message_stamp); } t=t+1./n; }while(t<=1); }
|
US4600833A - Solid state image sensing device with a color filter - Google Patents
Solid state image sensing device with a color filter Download PDF
Info
Publication number
US4600833A
US4600833A US06475402 US47540283A US4600833A US 4600833 A US4600833 A US 4600833A US 06475402 US06475402 US 06475402 US 47540283 A US47540283 A US 47540283A US 4600833 A US4600833 A US 4600833A
Authority
US
Grant status
Grant
Patent type
Prior art keywords
filter
color
layer
surface
coloring
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
US06475402
Inventor
Hiroshi Shibata
Hiroyasu Toyoda
Hidefumi Nakata
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Mitsubishi Electric Corp
Original Assignee
Mitsubishi Electric Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Grant date
Links
Images
Classifications
• HELECTRICITY
• H01BASIC ELECTRIC ELEMENTS
• H01LSEMICONDUCTOR DEVICES; ELECTRIC SOLID STATE DEVICES NOT OTHERWISE PROVIDED FOR
• H01L27/00Devices consisting of a plurality of semiconductor or other solid-state components formed in or on a common substrate
• H01L27/14Devices consisting of a plurality of semiconductor or other solid-state components formed in or on a common substrate including semiconductor components sensitive to infra-red radiation, light, electromagnetic radiation of shorter wavelength, or corpuscular radiation and specially adapted either for the conversion of the energy of such radiation into electrical energy or for the control of electrical energy by such radiation
• H01L27/144Devices controlled by radiation
• H01L27/146Imager structures
• H01L27/14601Structural or functional details thereof
• H01L27/1462Coatings
• H01L27/14621Colour filter arrangements
• HELECTRICITY
• H01BASIC ELECTRIC ELEMENTS
• H01LSEMICONDUCTOR DEVICES; ELECTRIC SOLID STATE DEVICES NOT OTHERWISE PROVIDED FOR
• H01L31/00Semiconductor devices sensitive to infra-red radiation, light, electromagnetic radiation of shorter wavelength or corpuscular radiation and adapted either for the conversion of the energy of such radiation into electrical energy or for the control of electrical energy by such radiation; Processes or apparatus peculiar to the manufacture or treatment thereof or of parts thereof; Details thereof
• H01L31/02Details
• H01L31/0216Coatings
• H01L31/02161Coatings for devices characterised by at least one potential jump barrier or surface barrier
• H01L31/02162Coatings for devices characterised by at least one potential jump barrier or surface barrier for filtering or shielding light, e.g. multicolour filters for photodetectors
Abstract
A solid state image sensing device comprises a photosensitive semiconductor element having a plurality of photocells on a surface thereof. A protective layer is disposed on the photosensitive semiconductor element, and an inorganic layer is disposed on the protective layer. A plurality of color filter layers each comprising a coloring agent having a color absorption characteristic are mixed into a portion of the inorganic layer in locations overlying the photocell, and a surface protective coating is disposed on a surface of the color filter layers.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a solid state image sensing device comprising a photosensitive semiconductor element having photocells on a major surface thereof and a colored filter disposed on a major surface of the photosensitive semiconductor element.
2. Description of the Prior Art
In one of conventional designs of color image sensing devices as shown in FIG. 1, there is adhesively attached onto the front of an electron tube type image pickup tube 1, for example, sold under the name of "SACHICON", a color filter 2 consisting of a glass plate and a color coating mounted on the glass plate and comprising gelatin as its predominant component and bearing a checker pattern of the three primary colors. In FIG. 1, a lens is denoted by 3, a cathode by C and a grid by G. In another conventional type of image sensing device, the electron tube of FIG. 1 is replaced by a photosensitve semiconductor element having a substantial number of photocells and a filter carrying a color coating of the three primary colors on a glass plate is attached onto a surface of the semiconductor element in the same manner as in FIG. 1. Yet another type of conventional image sensing device is adapted such that a deposit of gelatin is formed on a major surface of a semiconductor element and desired coloring agents are mixed into the gelatin deposit for the buildup of a color filter having a checker pattern of the three primary colors.
The conventional image sensing devices described above, more particularly, the image sensing devices having the color filter on the major surface of the photosensitive semiconductor element will now be discussed in more detail with reference to FIGS. 2 and 3.
As indicated in FIG. 2, there are formed in a check pattern on a major surface 11a of a silicon substrate 11 a plurality of photocells 12R, 12B and 12G, typically, in the form of well known photodiodes. To complete a semiconductor element 10, a passivation layer 14 of typically PSG film is grown over the major surface 11a of the silicon substrate 11. In FIG. 2, a field oxide layer is denoted by 13, red, blue and green color photocells by 12R, 12B and 12G, respectively.
Subsequently, a water-soluble and photosensitive resin such as gelatin is applied over a major surface 10a of the photosensitive semiconductor element 10 and the resin is removed except on regions thereof where the red color photocells 12R are desired to be formed. Immersing a red dye in the remaining water-soluble photosensitive resin on the major surface 10a of the photosensitive semiconductor element 10 results in developing red color filter layers 15.
An isolation layer 16 is then disposed over the photosensitve semiconductor element 10 bearing the red color filter layers 15 embedded therein. In a manner similar to the manner of developing the red color filter layers 15, a blue dye is immersed into the regions of the water-soluble photosensitive resin on a surface of the isolation layer 16 which correspond to the blue color photocells 12B, thus forming blue color filter layers 17.
Furthermore, another isolation layer 18 is disposed and green color filter layers which each comprises in combination the water-soluble photosensitive resin and a green dye immersed therein are formed in regions of an upper surface of the isolation layer corresponding to the green positions where the green color photocells 12G are to be developed, in the same manner as with the development of the red color filter layers 15 and the blue color filter layers 17.
The last step to complete a solid state image sensing device of a cross-sectional view as shown in FIG. 3 is to dispose a surface protective coating 20 at the uppermost surface of the resulting device. It is noted that the red color filter layers 15, the blue color filter layers 17 and the green color filter layers 19 define as a whole a checker pattern of the three primary colors as is clear from FIG. 4 schematically showing its plan view.
The conventional solid image sensing devices as discussed above are, however, unsatisfactory in the following respects: (a) desired colors are not readily available since the predominant component of the red, blue and green color filter layers 15, 17 and 19, i.e., gelatin is albuminous, in other words, highly sensitive to heat and easily soluble in water or chemicals with a great possibility of blurring and difference in color during dying; (b) the gelatin material in the laminated structure as the predominant component would become molten and reduce in thickness in the event cleaning is done too much on the device prior to patterning for the setup of the red, blue and green color filter layers 15, 17 and 19; and (c) if cleaning is simplified to circumvent this problem, then dust and other pollutants would be left and cause a deficiency in the resulting pattern. Especially, such organic layers are liable to degenerate upon exposure to ultraviolet radiation, thus deteriorating operation life and reliability of the color image sensing device.
SUMMARY OF THE INVENTION
The principal object of the present invention is to provide an improved image sensing device which overcomes the shortcomings of the conventional devices as outlined above and particularly ensures excellent properties in resistance to heat and humidity, operation life and reliability through the disposition of color filters containing coloring agents selected from metals, sulfur or inorganic compounds on a major surface of a photosensitive body.
These objects and other objects, features, aspects and advantages of the present invention will become more apparent from the following detailed description of the present invention when taken in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic cross-sectional view of a vacuum tube type color image sensing device;
FIG. 2 is a schematic cross-sectional view of a photosensitive semiconductor element;
FIG. 3 is a schematic cross-sectional view of the conventional solid state image sensing device;
FIG. 4 is a schematic plan view of the solid state image sensing device; and
FIGS. 5A to 5E are schematic cross-sectional views for explaining the steps of disposing a glass coating, disposing a resist pattern and mixing a red coloring agent; mixing a blue coloring agent; effecting thermal treatment and disposing a protective layer, separatively.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
A specific embodiment of the present invention will be explained with respect to FIGS. 5A to 5E. Referring first to FIG. 5A, there are formed over a major surface 11a of a silicon substrate 11 a plurality of photosensitive cells 12R, 12B and 12G, for example, photodiodes, in a checker pattern, as is seen from FIG. 2. In the following description, the photosensitive elements so formed in the illustrated embodiment are collectively called a photosensitive semiconductor element 10. A layer of SiO2 or a glass layer of typically SiO2, B2 O3 and K2 O is grown over the whole of a major surface of the semiconductor element 10, using the conventional CVD (Chemical Vapor Deposition) method or plasma CVD method.
The next step is to apply a deposit of resist material 22a over the whole of an upper surface of the glass coating 21 and perforate the resist deposit 22a at only limited portions where red color photocells 12R are to be developed, by using the conventional photolithography, as seen in FIG. 5B. An oxide containing Na2 O, K2 O, ZnO, CdS and Se is then mixed as a coloring agent into the glass coating 21 by ion beam implantation or sputtering. Satisfactory red color filter regions 23 were obtained when the metals and compounds were diffused into the glass material with the following compositions: SiO2 58%, B2 O3 4.0%, Na2 O 3.5%, K2 O 15.5%, ZnO 18.0%, CdS 1.2% and Se 0.44%.
After removal of the whole of the resist deposit 22a which has been used for deposition of the red color filter regions 23, a fresh deposit of resist material 22b is applied and the limited portions thereof where green filter regions 24 or green color photocells 12G are desired to be formed are subsequently perforated with the photolithography in the same manner as described above with respect to the development of the red color filter regions 23. Ion beam implantation or sputtering is carried out to diffuse an oxide containing Na2 O, K2 O, CaO, ZnO, CdS and S into the glass coating 21, resulting in the growth of the green color filter regions 24 having a glass composition of SiO2 60%, B2 O3 4%, Na2 O 3.0%, K2 O 18.0%, CaO 11.0%, ZnO 4.0%, CdS 0.6% and S 0.2%. This exemplary composition contributes toward enriched performance of the green color filter regions.
Similarly, when blue color filter regions are to be formed, the resist deposit 22b used in developing the green color filter regions 24 is wholly removed in advance and a fresh resist coating 22c is applied again as indicated in FIG. 5D. This step of applying the resist coating is followed by the photolithography by which only the limited portions thereof where blue photocells 12B are to be formed are perforated. The subsequent step of ion implantation or sputtering introduces an oxide containing Fe, Al, Mg, Co, etc., into the glass coating 21 as a coloring agent. This results in developing blue color filter regions 25.
Thereafter, the resist coating 22c which has been used for the development of the blue color filter regions is wholly removed. To deepen coloring in the respective colors, the glass coating 21 is subjected to themal treatment, so that there is built in the glass coating 21 a colored filter structure 30 composed of the individual red, green and blue filter regions 23, 24, and 25. In other words, a coloring agent containing other metals or metal oxides is added to the glass material containing SiO2, B2 O3 and K2 O) so that the three primary colors are formed in the colored filter structure 30 or complementary colors thereof may be developed through proper choice of the coloring agent.
The solid state image sensing device is completed after positioning a membrane of protective material 26 over the whole of an upper surface of the colored filter structure 30 to secure stability of the colored filter structure 30 as depicted in FIG. 5E.
It is generally known in the art that coloring agents are applied by diffusing such metals as Cr, Mn, Fe, Co, Ni, Ce, Nd and so forth in the form of oxides. Other metal materials, for example, Cu, Ag, Au and Se, are available and inorganic compounds such as CdS and CdSe are further available for the purpose of the present invention. It is also possible to effect coloring through combination with those additives.
Whereas in the above illustrated embodiment the colored filter structure 30 is built as an integral component on the major surface of the photosensitive semiconductor element 10, it is obvious that the photosensitive semiconductor element 10 and the colored filter structure may be manufactured, separately, and then bonded together to complete a solid state image sensing device while keeping the same advantageous features as in the above embodiments.
That is, as shown in FIG. 6, a glass coating 21 is disposed over a surface of a transparent plate 28 (typically glass) as in the previous embodiment and metal oxides are added to the glass coating 21 to color the same into individual colors, providing a checker filter structure composed of a plurality of red color filter regions 23, a like plurality of green color filter regions 24 and a like plurality of blue color filter regions 25. The colored filter structure 30 is covered with a protective membrane 26. Formed in a checker pattern over a major surface of a silicon substrate 11 are a plurality of photosensitive elements 12R, 12G and 12B, typically, in the form of photodiodes. A passivation layer 14 and a flattening resin layer 27 are disposed on the resulting photosensitive element to complete the manufacture of a photosensitive semiconductor element 10. Thereafter, the rear of the colored filter structure 30, that is, the rear of the transparent plate 28 is abutted against the front of the resin layer 27 on the photosensitive semiconductor element 10 for bonding such that the individual ones of the filter regions 23, 24 and 25 of the colored filter structure 30 face the individual ones of the photocells 12R, 12G and 12B of the photosensitive semiconductor element 10. This step finishes the manufacture of a solid state image sensing device.
As compared with the conventional coloring method using an organic dye including gelatin as its base material, the benefits of the present invention featuring the provision of the colored filter structure containing the coloring agents selected from metals, sulphur or inorganic compounds on the major surface of the photosensitive elements are as follows: moisture resistance is higher than that of gelatin because the base material is glass; the filter structure acts as a protective layer for the (photosensitive) semiconductor element; resistance to light is higher; and less discoloration takes place for prolonged use. Another benefit is stable and optimum coloring because precise amounts of the coloring agents may be diffused through the use of ion implantation or sputtering during the manufacture of the solid state image sensing device.
Although the present invention has been described and illustrated in detail, it is clearly understood that the same is by way of illustration and example only and is not to be taken by way of limitation, the spirit and scope of the present invention being limited only by the terms of the appended claims.
Claims (12)
What is claimed is:
1. A solid state image sensing device, comprising:
a photosensitive semiconductor element having at least one photocell on a surface thereof;
a transparent inorganic layer disposed on said surface to cover the photocell; and
at least one colored filter having inorganic coloring agents contained in regions of said inorganic layer in a position overlying said photocell.
2. A solid state image sensing device, comprising:
a photosensitive semiconductor element having at least one photocell on a surface thereof,
a protective layer disposed on said surface,
an inorganic layer disposed on said protective layer,
a color filter layer comprising an inorganic coloring agent having a color absorption characteristic, said coloring agent sputtered into a portion of said inorganic layer in a location overlying said photocell, and
a surface protective coating disposed on a surface of said color filter layer.
3. A device in accordance with claim 2 wherein said inorganic layer comprises a glass layer having as its predominant component a material selected from the group consisting of SiO2 and B2 O3, or a silicon nitride layer containing Si3 N4 as its predominant component.
4. A device in accordance with claim 2 wherein said coloring agent includes a transition element selected from the group consisting of Cr, Fe, Co and Ni.
5. A device in accordance with claim 2 wherein said coloring agent comprises a colloidal coloring agent selected from the group consisting of Cu, Ag, Au, Se and S.
6. A device in accordance with claim 2 wherein said coloring agent comprises
a coloring agent selected from the group consisting of CdS and combined CdS and CdSe.
7. A device in accordance with claim 2 wherein said coloring agent comprises in combination a transition element selected from the group consisting of Cr, Fe, Co and Ni, a colloidal coloring agent selected from the group consisting of Ca, Ag, Au, Se and S and an inorganic coloring agent selected from the group consisting of CdS and combined CdS and CdSe.
8. A solid state image sensing device comprising:
a photosensitve semiconductor element having a plurality of photocells disposed in a checker pattern on a surface thereof and divided into at least three groups,
a protective layer disposed on said surface of said photosensitive semiconductor element,
an inorganic layer disposed on said protective layer,
colored filter structure comprising first, second and third filter layers,
said first filter layers including a first coloring agent mixed into regions of said inorganic layer corresponding to said photocells in the first of said at least three groups, said second filter layers including a second coloring agent mixed into regions of said inorganic layer corresponding to said photocells in the second of said at least three groups, said third filter layers including a third coloring agent mixed into regions of said inorganic layer corresponding to said photocells in the third of said at least three groups, and
a surface protective coating disposed on a surface of said colored filter structure.
9. A device in accordance with claim 8 wherein said first filter layers are red color filter layers, said second filter layers are green color filter layers, and said third filter layers are blue color filter layers.
10. A device in accordance with claim 8 wherein
said inorganic layer comprises a glass layer containing as its predominant component a material selected from the group consisting of SiO2 and B2 O3 or a silicon nitride layer containing SiN4 as its predominant component.
11. A device in accordance with claim 8 wherein
said inorganic layer comprises a glass layer containing SiO2 as its predominant component, said first coloring agent in said first filter layers comprises an oxide selected from the group consisting of Na2 O, K2 O, ZnO, CdS, and Se, said second coloring agent in said second filter layers comprises an oxide selected from the group consisting of Na2 O, K2 O, CaO, ZnO, CdS, and S, and said third coloring agent in said third filter layers comprises an oxide selected from the group consisting of Fe, Al, Mg, and Co.
12. The device of claim 2, wherein said color filter layers are subjected to thermal treatment to deepen the colors of the inorganic coloring agents.
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US4755666A (en) * 1986-06-16 1988-07-05 Sanyo Electric Co., Ltd. Photosensor frame
US4776671A (en) * 1985-11-28 1988-10-11 Nissha Printing Co., Ltd. High property, high precision color filter and method for manufacturing the same
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US4855817A (en) * 1986-07-15 1989-08-08 Kabushiki Kaisha Toshiba Color image sensor with optical diffusion members covering sets of color filters and separated by light shields to obtain accurate color reproduction
US4988168A (en) * 1987-06-25 1991-01-29 International Business Machines Corporation TFT LCD device having color filter layer decal
US5258608A (en) * 1990-11-29 1993-11-02 Nec Corporation Solid-state imaging device with anti-reflective layers of amorphous silicon and insulating silicon
US5321250A (en) * 1991-11-12 1994-06-14 Nec Corporation Solid state image pickup device with optical filter free from age deterioration
US5377046A (en) * 1993-01-21 1994-12-27 Ryan Screen Printing Inc. Indicator viewing angle enhancer
US5452138A (en) * 1991-07-31 1995-09-19 Texas Instruments Incorporated Deformable mirror device with integral color filter
US5945722A (en) * 1997-05-02 1999-08-31 National Semiconductor Corporation Color active pixel sensor cell with oxide color filter
WO1999047900A1 (en) * 1998-03-18 1999-09-23 Intel Corporation Using duv curing to form a protective coating for color filters
US6111247A (en) * 1997-12-08 2000-08-29 Intel Corporation Passivation protection of sensor devices having a color filter on non-sensor portion
US6642963B1 (en) * 1998-06-29 2003-11-04 Intel Corporation Silylation layer for optical devices
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Cited By (26)
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US4700080A (en) * 1984-07-31 1987-10-13 Canon Kabushiki Kaisha Color photosensor utilizing color filters
US4776671A (en) * 1985-11-28 1988-10-11 Nissha Printing Co., Ltd. High property, high precision color filter and method for manufacturing the same
US4755666A (en) * 1986-06-16 1988-07-05 Sanyo Electric Co., Ltd. Photosensor frame
US4855817A (en) * 1986-07-15 1989-08-08 Kabushiki Kaisha Toshiba Color image sensor with optical diffusion members covering sets of color filters and separated by light shields to obtain accurate color reproduction
US4988168A (en) * 1987-06-25 1991-01-29 International Business Machines Corporation TFT LCD device having color filter layer decal
EP0307233A3 (en) * 1987-09-11 1990-03-21 Canon Kabushiki Kaisha Photoelectric converting apparatus
EP0307233A2 (en) * 1987-09-11 1989-03-15 Canon Kabushiki Kaisha Photoelectric converting apparatus
US5081347A (en) * 1987-09-11 1992-01-14 Canon Kabushiki Kaisha Photoelectric converting apparatus with reflection-prevention section
US5258608A (en) * 1990-11-29 1993-11-02 Nec Corporation Solid-state imaging device with anti-reflective layers of amorphous silicon and insulating silicon
US5452138A (en) * 1991-07-31 1995-09-19 Texas Instruments Incorporated Deformable mirror device with integral color filter
US5321250A (en) * 1991-11-12 1994-06-14 Nec Corporation Solid state image pickup device with optical filter free from age deterioration
US5377046A (en) * 1993-01-21 1994-12-27 Ryan Screen Printing Inc. Indicator viewing angle enhancer
US5945722A (en) * 1997-05-02 1999-08-31 National Semiconductor Corporation Color active pixel sensor cell with oxide color filter
US6111247A (en) * 1997-12-08 2000-08-29 Intel Corporation Passivation protection of sensor devices having a color filter on non-sensor portion
US6207947B1 (en) * 1998-03-18 2001-03-27 Intel Corporation Using DUV curing to form a protective coating for color filters
WO1999047900A1 (en) * 1998-03-18 1999-09-23 Intel Corporation Using duv curing to form a protective coating for color filters
US6642963B1 (en) * 1998-06-29 2003-11-04 Intel Corporation Silylation layer for optical devices
US20050082627A1 (en) * 2003-10-01 2005-04-21 Hoon Jang CMOS image sensor and manufacturing method thereof
US7129108B2 (en) 2003-10-01 2006-10-31 Dongbu Electronics Co., Ltd. CMOS image sensor and manufacturing method thereof
US20080296713A1 (en) * 2006-01-03 2008-12-04 Byoung Su Lee Image Sensor with Color Filters and Method of Manufacturing the Same
US20130140436A1 (en) * 2006-03-14 2013-06-06 Sony Corporation Color Filter Array, Imaging Device, and Image Processing Unit
US20080073736A1 (en) * 2006-09-26 2008-03-27 Dongbu Hitek Co., Ltd. Image sensor and method of fabricating the same
US7695995B2 (en) * 2006-09-26 2010-04-13 Dongbu Hitek Co., Ltd. Image sensor and method of fabricating the same
DE102007043452B4 (en) * 2006-09-26 2013-06-27 Dongbu Hitek Co., Ltd. A method for manufacturing an image sensor
US20080153194A1 (en) * 2006-12-23 2008-06-26 Jeong Seong Hee Method for manufacturing image sensor
US20110248155A1 (en) * 2010-04-12 2011-10-13 National Cheng Kung University Distributed filtering and sensing structure and optical device containing the same
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Putting our DNA clocks back
October 14, 2012 • 3:02 am
By Matthew Cobb
One of the most important tools in evolutionary biology over the last thirty or so years has been the development of the ‘molecular clock’, which is a technique for measuring how long ago two organisms (or taxa or species) separated on the ‘tree of life’. This approach has been incredibly powerful, and underlies much of our understanding of the rate of evolution, linking fossil and molecular data – all the figures from the excellent Timetree.org are based on the molecular clock. But now it appears that in our lineage at least, the clock may not have been ticking quite so fast as we thought, and some recalibration is going to be necessary.
The basic assumption behind the molecular clock is that mutations – changes in DNA – occur at a constant rate over time, and that the number of differences between two groups can therefore be turned into a figure based on the time since the two diverged. This phenomenon was first noticed in 1962 by Linus Pauling and Emile Zuckerkandl looking at differences in haemoglobin genes, then explicitly turned into a hypothesis the following year by Margoliash, before being fully developed in the 1970s by Allan Wilson. (It is in fact a bit more complicated, as the average generation time of a species has to be taken into account – the shorter the generation time, the higher the mutation rate.)
There are some important provisos to the clock – any stretch of DNA that is subject to selection, for example, is not going to be a very useful source of clock data, as genetic differences will tend to be removed by selection; many genes that are vital to organismal function are therefore highly conserved, showing few differences between groups. For this reason, scientists tend to use either ‘synonymous changes’ in DNA – these are ‘silent’ differences that do not cause any change in gene function (protein structure, gene regulation, or whatever) – or to use stretches of non-coding DNA, which appear to be not subject to natural selection and to evolve ‘neutrally’, just accumulating mutations with time.
The sources of spontaneous mutations are well-known – mistakes in the cellular machinery during copying of DNA, electromagnetic radiation, mutagenic chemicals (most of them completely natural), and so on. These spontaneous mutations are important not only for calibrating the clock, but above all for providing the raw material for evolution by natural selection. The whole infinite variety of life is the consequence of mutations, which have then been filtered through the sieve of natural selection, over vast periods of time.
The molecular clock has been particularly important in helping to calibrate and understand the wealth of fossils relating to human evolution that have been discovered over the past decades. In fact, fossil dates have been used to help calibrate the clock data, and as a result the mutation rate that has generally been used for humans and other apes has been about 1 mutation per year per billion bases of DNA. However, new results from massive programmes of DNA sequencing have revealed that this assumed rate is probably much higher than what has actually been taking place in our gonads.
A review by Aylwun Scally and Richard Durbin, recently published in Nature Reviews Genetics, reveals that over the last decade, nine studies have come out with substantially lower mutation rates, suggesting our clocks have been running far too fast. These studies have looked at mutation rates across the whole genome, and have focused on particular genes, including one study of over 14,000 people. They all suggest that the actual mutation rate is about half that previously estimated. To put this into perspective, a study of 78 families from Iceland (mother, father, child) found that on average, a baby has 36 spontaneous mutations that are not present in either parent. Depending on where you grew up – presence of natural radiation etc – the number of spontaneous mutations in your genes is probably not too far different.
So what happens when this new, lower, figure is plugged into our estimates of divergence times for the various twigs and branches on the tangled bank of recent human evolution? Because the clock is now thought to be ticking more slowly than we originally estimated, the divergence times are being put back. So, for example, the human/Neanderthal split was estimated at between 272,000-435,000 years ago. The new figure would appear to be something more like 400,000-600,000 years.
This removes an odd discrepancy, as previous estimates of human/Neanderthal divergence using mitochondrial DNA (mtDNA is found in the tiny mitochondria of our cells, which are inherited maternally, and which are involved only in the generation of energy) had come up with a figure 0f 500,000-600,000 years ago. So both nuclear DNA and mtDNA now give a similar estimate – we split from our Neanderthal cousins about half a million years ago. Not that that stopped us mating with them and getting some of their genes… In terms of the time when we left Africa (based on genetic differences between non-African and African populations), that figure used to be put at around 70,000 years ago; it now appears to have been substantially earlier, perhaps 90,000-130,000 years ago.
This useful table assembled by Ann Gibbons in her excellent Science magazine piece summarises the changes, and their links with the fossils:
A lot of unknowns remain – in particular the issue of estimating generation time in prehistoric populations, as well as the lack of population-level data for prehistoric groups (e.g. Neanderthals or Denisovans). But the increasing richness of molecular data are producing ever more refined estimates of our past. And that is the power of science – nothing is taken as fixed, knowledge changes and increases, in a uniquely progressive way, enabling us to revise and refine our understanding, and even to reject what we previously thought to be true. Indeed, there is grandeur in this view of life.
References (both hidden behind pay walls, sadly):
Aylwyn Scally and Richard Durbing (2012) Revising the human mutation rate: implications for the understanding human evolution. Nature Reviews Genetics 13:745-753.
Ann Gibbons (2012) Turning back the clock” slowing the pace of prehistory. Science 338:189-191.
You can also learn more by listening to the Science magazine podcast item about this.
28 thoughts on “Putting our DNA clocks back
1. Cool.
Although – “we split from our Neanderthal cousins about half a billion years ago.”
You meant “million,” right?
2. This removes an odd discrepancy, as previous estimates of human/Neanderthal divergence using mitochondrial DNA (mtDNA is found in the tiny mitochondria of our cells, which are inherited maternally, and which are involved only in the generation of energy) had come up with a figure 0f 500,000-600,000 years ago. So both nuclear DNA and mtDNA now give a similar estimate – we split from our Neanderthal cousins about half a billion years ago.
I think you mean half a million years ago.
3. I don’t think the human-chimp split can really be dated from fossils: before 4 Mya certainly, but how much before is rather a guess. However the suggested split of 34-46 Mya is AIUI not only well before when we thought humans and orangutans split, but before old world monkeys split off from the apes. So something is not right there. Does this suggest a significant slow-down in the clock somewhere between 0.6 Mya and 4 Mya?
1. Ann Gibbons’ table shows the dates one would estimate assuming the mutation rate (either the old or the revised one) was constant. However you are correct that the implied orang speciation is far too ancient, and one of the things we discuss is a slowdown in mutation rate during great ape evolution, to reconcile these estimates. There is some debate about how big the slowdown was and what caused it. We also discussed this in the gorilla genome paper earlier this year (http://www.nature.com/nature/journal/v483/n7388/full/nature10842.html), which is open access.
1. So, if the DNA clock is variable-speed…is there any hope of further calibrating it in order to figure out what rate it was running at at a particular point in time?
b&
1. We might be able to get (e.g. from fossils) a better estimate of how long a typical generation was at some point in the past, which is relevant to this discussion. In theory we might also be able to use ancient DNA samples to measure mutation rates within the last hundred thousand years or so – e.g. if we could extract DNA from a family of fossil individuals. But outside that timeframe it is difficult to see how we could ever measure past mutation rates directly. The uncertainty is something we are just going to have to handle in the context of evolutionary models.
1. Thanks — makes sense.
Sounds like, for the time being, we should accept increasingly-widening error bars on the data with increasing age, and hope for the error bars to tighten in the future…but never for them to get as tight as one might hope for.
Still, it’s an amazing tool!
And I imagine that, even when the error bars are very wide, it’s still useful for comparative analysis. That is, you might not be able to pin down with much certainty when a particular event happened, but you should still be able to be confident that it happened earlier than / later than / contemporaneously with another event.
Cheers,
b&
4. Regarding Out-of-Africa migration, the re-calibrated DNA clock is in much better agreement with both the archaeological evidence and the palaeolinguistic inference accumulated.
For the Neanderthals split, it’s not just archaeology: palaeoanthropology and geology would have to have been wrong about too many things to account for such large a discrepancy by errors or bias on their side only.
Colleagues who specialise in these older periods (I don’t) tended to keep their nerve and wait for geneticists to come around with better data and better dating. As just happened.
Not for the first time, by the way. Early, uncalibrated, radiocarbon dates tended to throw a monkey wrench into the works of consolidated relative sequences by favouring shorter chronologies. Then tree-ring calibration came about, leaving the most vocal proponents of short chronologies with egg on their face.
5. Whoa, this is very useful for Ardipithecus. They didn’t fit very well with chimps being only at 4.5-5 m.y. from us.
6. I was always uneasy with the 5 million year divergence time for Human-Chimp given by the molecular clock. I assume Scally and Durbing use theoretical fixation rates for neutral mutations. However, the new estimates seem to be based on DNA segments with few bases, such that a sample size of 14,000 may mean little in terms of statistical precision. A few studies involving unsuspected selected loci could have biased the estimate downwards. Certainly, the question is not closed.
Just an aside: it seems that Nature is an example of the left hand not knowing what the right hand is doing. Nature endorsed the ENCODE assertion that the genome is 80% ‘functional’ and then publishes the present paper whose cornerstone premise seems to be that very little of the genome is functional. One is prompted to believe that biochemists – and Nature editors — are a most heterogeneous group of the very competent and the very incompetent.
1. How do they find a part of the genome that they think is “selection neutral”? Are there really parts hanging around that have no sequence-dependent function? If so wouldn’t they be lost? And won’t synonymous mutations in coding regions change tRNA usage and translation efficiency and thus not really be neutral?
2. A few studies involving unsuspected selected loci could have biased the estimate downwards. Certainly, the question is not closed.
Just an aside: it seems that Nature is an example of the left hand not knowing what the right hand is doing. Nature endorsed the ENCODE assertion that the genome is 80% ‘functional’ and then publishes the present paper whose cornerstone premise seems to be that very little of the genome is functional.
Yeah question not closed…and seem to be more open than ever with the ENCODE results. Seems like our idea of gene conservation (and where it needs to take place) has just been lit up. Interestingly molecular clocks have always been fodder for creationists because of how…hmm unscientific it seemed (ie fossil dating/sequence pretty much determined/calibrated molecular clock values since there was little genetic data.) Now we are getting some in-depth genetic data but a long ways to go in reconciling the two disciplines. Have there been any recent studies between phyla to determine breaks from very ancient ancestors?
7. Yet another example of how science is guaranteed to always be worng…
…but it’s also guaranteed to also always converge on the truth.
Or, in other words, science has phenomenal accuracy, though the precision will always leave something to be desired.
Religion, on the other hand, has unbelievable precision and no accuracy whatsoever.
I’ll have to keep an eye on TimeTree to see how they incorporate these new findings….
Cheers,
b&
8. great post but the last bit is not accurate.
mtDNA is found in the tiny mitochondria of our cells, which are inherited maternally, and which are involved only in the generation of energy
e.g., metabolism and apoptosis.
9. And that is the power of science – nothing is taken as fixed, knowledge changes and increases..
But.. so many millions of lies told at so many dinner parties.
1. That depends. Did your dinner-party conversation include a reasonable indication of the scope of the error bars?
Even if you happen to know the exact standard figures, it’s rhetorically not a bad idea to round everything to one or two significant figures and prepend everything with “about,” unless the precision is the point you’re trying to make.
For example, I’ll state that the universe is about a baker’s dozen billion years old; that the Sun is about a third of the age of the Universe, and that life began sometime fairly early after the Earth had cooled, probably sometime in the first half-billion years after it had coalesced. Dinosaurs died out a few score million years ago, but the last common ancestor of the mammals lived before then, at about a hundred million years ago.
There are a number of advantages. First, it saves you should you misremember or if there are later refinements. It also emphasizes the provisional nature of all such measurements, and it makes the point that it’s the scale that matters more than the precision.
If the age of the universe is later refined to be estimated at 13.62 BYA instead of 13.75 BYA, no big deal. But if it’s later revised to 5,773 years old…well, then we’ve got a problem.
Cheers,
b&
10. It pushes back the divergence time between African/non-Africans to before the emergence of behaviorally modern humans (without even mentioning the Khoisan!) This is making things warm for those who claim a genetic change was responsible for the behavioral change. hehehe.
11. You see, this is where I think I can see where the creatnists (did a really good typo there – cretinists)are coming from. I read that (and will read it properly, promise!) but the scale is too huge and immense – it’s just hard for me to understand and my eyes were glazing over about halfway down. However, I am happy to accept that there are people who know more about these things than me and I am very glad they are doing the research, even if I personally don’t quite get it. It’s a bit like my lodger who asked me how to cook a joint of gammon – his eyes were glazing over by the time I’d got to “…and then you stick the cloves into the diamonds you’ve cut into the fat”. He was happy to accept my expertise and knowledge (yes I did cook it in the end) I hope that makes sense? But whilst I think most creatonists would be happy to accept advice on cooking from me, they WON’T accept the evidence that is given to them by people who know more about evolution than they do!
12. Whoa, you appear to have accumulated a “trackback/pingback” from some spammer/ scammer. Quite what that means, and what if anything can be done about it, I’m not sure. But that link looks more spammy than a serving of “Spam, Spam, sausage, egg and Spam”, with extra Spam.
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+ <h1 id="message-grouping">Message Grouping</h1>
+<p>Message groups are sets of messages that have the following
+characteristics:</p>
+<ul>
+<li><p>Messages in a message group share the same group id, i.e. they have
+same group identifier property (<code>JMSXGroupID</code> for JMS,
+<code>_AMQ_GROUP_ID</code> for Apache ActiveMQ Artemis Core API).</p>
+</li>
+<li><p>Messages in a message group are always consumed by the same
+consumer, even if there are many consumers on a queue. They pin all
+messages with the same group id to the same consumer. If that
+consumer closes another consumer is chosen and will receive all
+messages with the same group id.</p>
+</li>
+</ul>
+<p>Message groups are useful when you want all messages for a certain value
+of the property to be processed serially by the same consumer.</p>
+<p>An example might be orders for a certain stock. You may want orders for
+any particular stock to be processed serially by the same consumer. To
+do this you can create a pool of consumers (perhaps one for each stock,
+but less will work too), then set the stock name as the value of the
+_AMQ_GROUP_ID property.</p>
+<p>This will ensure that all messages for a particular stock will always be
+processed by the same consumer.</p>
+<blockquote>
+<p><strong>Note</strong></p>
+<p>Grouped messages can impact the concurrent processing of non-grouped
+messages due to the underlying FIFO semantics of a queue. For example,
+if there is a chunk of 100 grouped messages at the head of a queue
+followed by 1,000 non-grouped messages then all the grouped messages
+will need to be sent to the appropriate client (which is consuming
+those grouped messages serially) before any of the non-grouped
+messages can be consumed. The functional impact in this scenario is a
+temporary suspension of concurrent message processing while all the
+grouped messages are processed. This can be a performance bottleneck
+so keep it in mind when determining the size of your message groups,
+and consider whether or not you should isolate your grouped messages
+from your non-grouped messages.</p>
+</blockquote>
+<h2 id="using-core-api">Using Core API</h2>
+<p>The property name used to identify the message group is <code>"_AMQ_GROUP_ID"</code>
+(or the constant <code>MessageImpl.HDR_GROUP_ID</code>). Alternatively, you can set
+<code>autogroup</code> to true on the <code>SessionFactory</code> which will pick a random
+unique id.</p>
+<h2 id="using-jms">Using JMS</h2>
+<p>The property name used to identify the message group is <code>JMSXGroupID</code>.</p>
+<pre><code> // send 2 messages in the same group to ensure the same
+ // consumer will receive both
+ Message message = ...
+ message.setStringProperty("JMSXGroupID", "Group-0");
+ producer.send(message);
+
+ message = ...
+ message.setStringProperty("JMSXGroupID", "Group-0");
+ producer.send(message);
+</code></pre><p>Alternatively, you can set <code>autogroup</code> to true on the
+<code>ActiveMQConnectonFactory</code> which will pick a random unique id. This can
+also be set in the JNDI context environment, e.g. <code>jndi.properties</code>.
+Here's a simple example using the "ConnectionFactory" connection factory
+which is available in the context by default</p>
+<pre><code>java.naming.factory.initial=org.apache.activemq.artemis.jndi.ActiveMQInitialContextFactory
+connectionFactory.myConnectionFactory=tcp://localhost:61616?autoGroup=true
+</code></pre><p>Alternatively you can set the group id via the connection factory. All
+messages sent with producers created via this connection factory will
+set the <code>JMSXGroupID</code> to the specified value on all messages sent. This
+can also be set in the JNDI context environment, e.g. <code>jndi.properties</code>.
+Here's a simple example using the "ConnectionFactory" connection factory
+which is available in the context by default:</p>
+<pre><code>java.naming.factory.initial=org.apache.activemq.artemis.jndi.ActiveMQInitialContextFactory
+connectionFactory.myConnectionFactory=tcp://localhost:61616?roupID=Group-0
+</code></pre><h2 id="example">Example</h2>
+<p>See the [examples](examples.md} chapter for an example which shows how message groups are configured and used with JMS and via a connection factory.</p>
+<h2 id="clustered-grouping">Clustered Grouping</h2>
+<p>Using message groups in a cluster is a bit more complex. This is because
+messages with a particular group id can arrive on any node so each node
+needs to know about which group id's are bound to which consumer on
+which node. The consumer handling messages for a particular group id may
+be on a different node of the cluster, so each node needs to know this
+information so it can route the message correctly to the node which has
+that consumer.</p>
+<p>To solve this there is the notion of a grouping handler. Each node will
+have its own grouping handler and when a messages is sent with a group
+id assigned, the handlers will decide between them which route the
+message should take.</p>
+<p>There are 2 types of handlers; Local and Remote. Each cluster should
+choose 1 node to have a local grouping handler and all the other nodes
+should have remote handlers- it's the local handler that actually makes
+the decision as to what route should be used, all the other remote
+handlers converse with this. Here is a sample config for both types of
+handler, this should be configured in the <em>broker.xml</em>
+file.</p>
+<pre><code><grouping-handler name="my-grouping-handler">
+ <type>LOCAL</type>
+ <address>jms</address>
+ <timeout>5000</timeout>
+</grouping-handler>
+
+<grouping-handler name="my-grouping-handler">
+ <type>REMOTE</type>
+ <address>jms</address>
+ <timeout>5000</timeout>
+</grouping-handler>
+</code></pre><p>The <em>address</em> attribute refers to a <a href="#clusters.address">cluster connection and the address
+it uses</a>, refer to the clustering section on how to
+configure clusters. The <em>timeout</em> attribute referees to how long to wait
+for a decision to be made, an exception will be thrown during the send
+if this timeout is reached, this ensures that strict ordering is kept.</p>
+<p>The decision as to where a message should be routed to is initially
+proposed by the node that receives the message. The node will pick a
+suitable route as per the normal clustered routing conditions, i.e.
+round robin available queues, use a local queue first and choose a queue
+that has a consumer. If the proposal is accepted by the grouping
+handlers the node will route messages to this queue from that point on,
+if rejected an alternative route will be offered and the node will again
+route to that queue indefinitely. All other nodes will also route to the
+queue chosen at proposal time. Once the message arrives at the queue
+then normal single server message group semantics take over and the
+message is pinned to a consumer on that queue.</p>
+<p>You may have noticed that there is a single point of failure with the
+single local handler. If this node crashes then no decisions will be
+able to be made. Any messages sent will be not be delivered and an
+exception thrown. To avoid this happening Local Handlers can be
+replicated on another backup node. Simple create your back up node and
+configure it with the same Local handler.</p>
+<h2 id="clustered-grouping-best-practices">Clustered Grouping Best Practices</h2>
+<p>Some best practices should be followed when using clustered grouping:</p>
+<ol>
+<li><p>Make sure your consumers are distributed evenly across the different
+nodes if possible. This is only an issue if you are creating and
+closing consumers regularly. Since messages are always routed to the
+same queue once pinned, removing a consumer from this queue may
+leave it with no consumers meaning the queue will just keep
+receiving the messages. Avoid closing consumers or make sure that
+you always have plenty of consumers, i.e., if you have 3 nodes have
+3 consumers.</p>
+</li>
+<li><p>Use durable queues if possible. If queues are removed once a group
+is bound to it, then it is possible that other nodes may still try
+to route messages to it. This can be avoided by making sure that the
+queue is deleted by the session that is sending the messages. This
+means that when the next message is sent it is sent to the node
+where the queue was deleted meaning a new proposal can successfully
+take place. Alternatively you could just start using a different
+group id.</p>
+</li>
+<li><p>Always make sure that the node that has the Local Grouping Handler
+is replicated. These means that on failover grouping will still
+occur.</p>
+</li>
+<li><p>In case you are using group-timeouts, the remote node should have a
+smaller group-timeout with at least half of the value on the main
+coordinator. This is because this will determine how often the
+last-time-use value should be updated with a round trip for a
+request to the group between the nodes.</p>
+</li>
+</ol>
+<h2 id="clustered-grouping-example">Clustered Grouping Example</h2>
+<p>See the <a href="examples.html">examples</a> chapter for an example of how to configure message groups with a ActiveMQ Artemis Cluster.</p>
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+ <h1 id="messaging-concepts">Messaging Concepts</h1>
+<p>Apache ActiveMQ Artemis is an asynchronous messaging system, an example of <a href="http://en.wikipedia.org/wiki/Message_oriented_middleware" target="_blank">Message
+Oriented
+Middleware</a> ,
+we'll just call them messaging systems in the remainder of this book.</p>
+<p>We'll first present a brief overview of what kind of things messaging
+systems do, where they're useful and the kind of concepts you'll hear
+about in the messaging world.</p>
+<p>If you're already familiar with what a messaging system is and what it's
+capable of, then you can skip this chapter.</p>
+<h2 id="messaging-concepts">Messaging Concepts</h2>
+<p>Messaging systems allow you to loosely couple heterogeneous systems
+together, whilst typically providing reliability, transactions and many
+other features.</p>
+<p>Unlike systems based on a <a href="http://en.wikipedia.org/wiki/Remote_procedure_call" target="_blank">Remote Procedure
+Call</a> (RPC) pattern,
+messaging systems primarily use an asynchronous message passing pattern
+with no tight relationship between requests and responses. Most
+messaging systems also support a request-response mode but this is not a
+primary feature of messaging systems.</p>
+<p>Designing systems to be asynchronous from end-to-end allows you to
+really take advantage of your hardware resources, minimizing the amount
+of threads blocking on IO operations, and to use your network bandwidth
+to its full capacity. With an RPC approach you have to wait for a
+response for each request you make so are limited by the network round
+trip time, or <em>latency</em> of your network. With an asynchronous system you
+can pipeline flows of messages in different directions, so are limited
+by the network <em>bandwidth</em> not the latency. This typically allows you to
+create much higher performance applications.</p>
+<p>Messaging systems decouple the senders of messages from the consumers of
+messages. The senders and consumers of messages are completely
+independent and know nothing of each other. This allows you to create
+flexible, loosely coupled systems.</p>
+<p>Often, large enterprises use a messaging system to implement a message
+bus which loosely couples heterogeneous systems together. Message buses
+often form the core of an <a href="http://en.wikipedia.org/wiki/Enterprise_service_bus" target="_blank">Enterprise Service
+Bus</a>. (ESB). Using
+a message bus to de-couple disparate systems can allow the system to
+grow and adapt more easily. It also allows more flexibility to add new
+systems or retire old ones since they don't have brittle dependencies on
+each other.</p>
+<h2 id="messaging-styles">Messaging styles</h2>
+<p>Messaging systems normally support two main styles of asynchronous
+messaging: <a href="http://en.wikipedia.org/wiki/Message_queue" target="_blank">message queue</a>
+messaging (also known as <em>point-to-point messaging</em>) and <a href="http://en.wikipedia.org/wiki/Publish_subscribe" target="_blank">publish
+subscribe</a> messaging.
+We'll summarise them briefly here:</p>
+<h3 id="the-message-queue-pattern">The Message Queue Pattern</h3>
+<p>With this type of messaging you send a message to a queue. The message
+is then typically persisted to provide a guarantee of delivery, then
+some time later the messaging system delivers the message to a consumer.
+The consumer then processes the message and when it is done, it
+acknowledges the message. Once the message is acknowledged it disappears
+from the queue and is not available to be delivered again. If the system
+crashes before the messaging server receives an acknowledgement from the
+consumer, then on recovery, the message will be available to be
+delivered to a consumer again.</p>
+<p>With point-to-point messaging, there can be many consumers on the queue
+but a particular message will only ever be consumed by a maximum of one
+of them. Senders (also known as <em>producers</em>) to the queue are completely
+decoupled from receivers (also known as <em>consumers</em>) of the queue - they
+do not know of each other's existence.</p>
+<p>A classic example of point to point messaging would be an order queue in
+a company's book ordering system. Each order is represented as a message
+which is sent to the order queue. Let's imagine there are many front end
+ordering systems which send orders to the order queue. When a message
+arrives on the queue it is persisted - this ensures that if the server
+crashes the order is not lost. Let's also imagine there are many
+consumers on the order queue - each representing an instance of an order
+processing component - these can be on different physical machines but
+consuming from the same queue. The messaging system delivers each
+message to one and only one of the ordering processing components.
+Different messages can be processed by different order processors, but a
+single order is only processed by one order processor - this ensures
+orders aren't processed twice.</p>
+<p>As an order processor receives a message, it fulfills the order, sends
+order information to the warehouse system and then updates the order
+database with the order details. Once it's done that it acknowledges the
+message to tell the server that the order has been processed and can be
+forgotten about. Often the send to the warehouse system, update in
+database and acknowledgement will be completed in a single transaction
+to ensure <a href="http://en.wikipedia.org/wiki/ACID" target="_blank">ACID</a> properties.</p>
+<h3 id="the-publish-subscribe-pattern">The Publish-Subscribe Pattern</h3>
+<p>With publish-subscribe messaging many senders can send messages to an
+entity on the server, often called a <em>topic</em> (e.g. in the JMS world).</p>
+<p>There can be many <em>subscriptions</em> on a topic, a subscription is just
+another word for a consumer of a topic. Each subscription receives a
+<em>copy</em> of <em>each</em> message sent to the topic. This differs from the
+message queue pattern where each message is only consumed by a single
+consumer.</p>
+<p>Subscriptions can optionally be <em>durable</em> which means they retain a copy
+of each message sent to the topic until the subscriber consumes them -
+even if the server crashes or is restarted in between. Non-durable
+subscriptions only last a maximum of the lifetime of the connection that
+created them.</p>
+<p>An example of publish-subscribe messaging would be a news feed. As news
+articles are created by different editors around the world they are sent
+to a news feed topic. There are many subscribers around the world who
+are interested in receiving news items - each one creates a subscription
+and the messaging system ensures that a copy of each news message is
+delivered to each subscription.</p>
+<h2 id="delivery-guarantees">Delivery guarantees</h2>
+<p>A key feature of most messaging systems is <em>reliable messaging</em>. With
+reliable messaging the server gives a guarantee that the message will be
+delivered once and only once to each consumer of a queue or each durable
+subscription of a topic, even in the event of system failure. This is
+crucial for many businesses; e.g. you don't want your orders fulfilled
+more than once or any of your orders to be lost.</p>
+<p>In other cases you may not care about a once and only once delivery
+guarantee and are happy to cope with duplicate deliveries or lost
+messages - an example of this might be transient stock price updates -
+which are quickly superseded by the next update on the same stock. The
+messaging system allows you to configure which delivery guarantees you
+require.</p>
+<h2 id="transactions">Transactions</h2>
+<p>Messaging systems typically support the sending and acknowledgement of
+multiple messages in a single local transaction. Apache ActiveMQ Artemis also supports
+the sending and acknowledgement of message as part of a large global
+transaction - using the Java mapping of XA: JTA.</p>
+<h2 id="durability">Durability</h2>
+<p>Messages are either durable or non durable. Durable messages will be
+persisted in permanent storage and will survive server failure or
+restart. Non durable messages will not survive server failure or
+restart. Examples of durable messages might be orders or trades, where
+they cannot be lost. An example of a non durable message might be a
+stock price update which is transitory and doesn't need to survive a
+restart.</p>
+<h2 id="messaging-apis-and-protocols">Messaging APIs and protocols</h2>
+<p>How do client applications interact with messaging systems in order to
+send and consume messages?</p>
+<p>Several messaging systems provide their own proprietary APIs with which
+the client communicates with the messaging system.</p>
+<p>There are also some standard ways of operating with messaging systems
+and some emerging standards in this space.</p>
+<p>Let's take a brief look at these:</p>
+<h3 id="java-message-service-jms">Java Message Service (JMS)</h3>
+<p><a href="http://en.wikipedia.org/wiki/Java_Message_Service" target="_blank">JMS</a> is part of
+Oracle's JEE specification. It's a Java API that encapsulates both message
+queue and publish-subscribe messaging patterns. JMS is a lowest common
+denominator specification - i.e. it was created to encapsulate common
+functionality of the already existing messaging systems that were
+available at the time of its creation.</p>
+<p>JMS is a very popular API and is implemented by most messaging systems.
+JMS is only available to clients running Java.</p>
+<p>JMS does not define a standard wire format - it only defines a
+programmatic API so JMS clients and servers from different vendors
+cannot directly interoperate since each will use the vendor's own
+internal wire protocol.</p>
+<p>Apache ActiveMQ Artemis provides a fully compliant JMS 1.1 and JMS 2.0 API.</p>
+<h3 id="system-specific-apis">System specific APIs</h3>
+<p>Many systems provide their own programmatic API for which to interact
+with the messaging system. The advantage of this it allows the full set
+of system functionality to be exposed to the client application. API's
+like JMS are not normally rich enough to expose all the extra features
+that most messaging systems provide.</p>
+<p>Apache ActiveMQ Artemis provides its own core client API for clients to use if they
+wish to have access to functionality over and above that accessible via
+the JMS API.</p>
+<h3 id="restful-api">RESTful API</h3>
+<p><a href="http://en.wikipedia.org/wiki/Representational_State_Transfer" target="_blank">REST</a>
+approaches to messaging are showing a lot interest recently.</p>
+<p>It seems plausible that API standards for cloud computing may converge
+on a REST style set of interfaces and consequently a REST messaging
+approach is a very strong contender for becoming the de-facto method for
+messaging interoperability.</p>
+<p>With a REST approach messaging resources are manipulated as resources
+defined by a URI and typically using a simple set of operations on those
+resources, e.g. PUT, POST, GET etc. REST approaches to messaging often
+use HTTP as their underlying protocol.</p>
+<p>The advantage of a REST approach with HTTP is in its simplicity and the
+fact the internet is already tuned to deal with HTTP optimally.</p>
+<p>Please see <a href="rest.html">Rest Interface</a> for using Apache ActiveMQ Artemis's RESTful interface.</p>
+<h3 id="stomp">STOMP</h3>
+<p><a href="http://stomp.github.io/" target="_blank">Stomp</a> is a very simple text protocol for
+interoperating with messaging systems. It defines a wire format, so
+theoretically any Stomp client can work with any messaging system that
+supports Stomp. Stomp clients are available in many different
+programming languages.</p>
+<p>Please see <a href="interoperability.md">Stomp</a> for using STOMP with Apache ActiveMQ Artemis.</p>
+<h3 id="amqp">AMQP</h3>
+<p><a href="http://en.wikipedia.org/wiki/AMQP" target="_blank">AMQP</a> is a specification for
+interoperable messaging. It also defines a wire format, so any AMQP
+client can work with any messaging system that supports AMQP. AMQP
+clients are available in many different programming languages.</p>
+<p>Apache ActiveMQ Artemis implements the <a href="https://www.oasis-open.org/committees/tc_home.php?wg_abbrev=amqp" target="_blank">AMQP
+1.0</a>
+specification. Any client that supports the 1.0 specification will be
+able to interact with Apache ActiveMQ Artemis.</p>
+<h2 id="high-availability">High Availability</h2>
+<p>High Availability (HA) means that the system should remain operational
+after failure of one or more of the servers. The degree of support for
+HA varies between various messaging systems.</p>
+<p>Apache ActiveMQ Artemis provides automatic failover where your sessions are
+automatically reconnected to the backup server on event of live server
+failure.</p>
+<p>For more information on HA, please see <a href="ha.html">High Availability and Failover</a>.</p>
+<h2 id="clusters">Clusters</h2>
+<p>Many messaging systems allow you to create groups of messaging servers
+called <em>clusters</em>. Clusters allow the load of sending and consuming
+messages to be spread over many servers. This allows your system to
+scale horizontally by adding new servers to the cluster.</p>
+<p>Degrees of support for clusters varies between messaging systems, with
+some systems having fairly basic clusters with the cluster members being
+hardly aware of each other.</p>
+<p>Apache ActiveMQ Artemis provides very configurable state-of-the-art clustering model
+where messages can be intelligently load balanced between the servers in
+the cluster, according to the number of consumers on each node, and
+whether they are ready for messages.</p>
+<p>Apache ActiveMQ Artemis also has the ability to automatically redistribute messages
+between nodes of a cluster to prevent starvation on any particular node.</p>
+<p>For full details on clustering, please see <a href="clusters.html">Clusters</a>.</p>
+<h2 id="bridges-and-routing">Bridges and routing</h2>
+<p>Some messaging systems allow isolated clusters or single nodes to be
+bridged together, typically over unreliable connections like a wide area
+network (WAN), or the internet.</p>
+<p>A bridge normally consumes from a queue on one server and forwards
+messages to another queue on a different server. Bridges cope with
+unreliable connections, automatically reconnecting when the connections
+becomes available again.</p>
+<p>Apache ActiveMQ Artemis bridges can be configured with filter expressions to only
+forward certain messages, and transformation can also be hooked in.</p>
+<p>Apache ActiveMQ Artemis also allows routing between queues to be configured in server
+side configuration. This allows complex routing networks to be set up
+forwarding or copying messages from one destination to another, forming
+a global network of interconnected brokers.</p>
+<p>For more information please see <a href="core-bridges.html">Core Bridges</a> and <a href="diverts.html">Diverting and Splitting Message Flows</a>.</p>
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Sur la présence en Méditerranée de Garveia franciscana (Torrey 1902) (Cnidaria, Hydroida) = Occurrence of Garveia franciscana in the Mediterranean Sea
Morri, C. (1982). Sur la présence en Méditerranée de Garveia franciscana (Torrey 1902) (Cnidaria, Hydroida) = Occurrence of Garveia franciscana in the Mediterranean Sea. Cah. Biol. Mar. 23(4): 381-391
In: Cahiers de Biologie Marine. Station Biologique de Roscoff: Paris. ISSN 0007-9723, more
Peer reviewed article
Available in Author
Keywords
Marine; Brackish water
Author Top
• Morri, C.
Abstract
Garveia franciscana (Torrey) has been found to be common in two coastal lagoons in the Northern Adriatic, Italy, in salinities between 20 and 30 per mil. G. franciscana is a cosmopolitan tropical to temperate brackish species living in meso-polyhaline shallow waters. It requires some water movement and high concentrations of organic matter in the bottom sediments. Its presence in the Northern Adriatic can be interpreted as an example of so-called "sub-atlanticism" of the Northern Adriatic, or simply as an accidental introduction by ships. A critical comparison with the other Mediterranean species of the genus, G. grisea (Motz-Kossowska, 1905), is provided; and the morphology and ecology of both the species are considered.
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| By: Kristin Lewotsky, Contributing Editor
Factories today leverage increasing levels of intelligence to improve the flexibility, throughput, and quality of manufacturing. For an example, look no further than the growing level of integration between machine vision and motion control in the manufacturing world. Combining the two technologies creates a more flexible, dynamic environment. The machine vision system becomes more effective, the motion system becomes more adaptable, and the production environment as a whole demonstrates greater functionality.
In the words of Nate Holmes, R&D group manager for motion and vision product lines at National Instruments (Austin, Texas), the vision system provides information, while the motion system takes action. Integration of the two technologies can be split into three classes: motion assisted machine vision (synergistic integration), vision-assisted motion control (synchronized integration), and vision-guided motion. They are listed in order of increasing levels of integration, which also implies increased complexity. There is a payoff for that complexity, though. Higher levels of integration increase product quality and production efficiency, while reducing production cost.
“Combining vision with motion allows you to have more flexible dynamic environment,” says Darrell Paul, marketing supervisor for product marketing at Omron Industrial Automation (Hoffman Estates, Illinois). “The motion system is able to provide more functionality inside the motion than ever before. So, at the same time you might be doing motion-guided vision, you could also be doing inspection and code reading.
In a palletizing operation, for example, the vision system could detect the layers of packaging already on the pallet. This would enable it to stack additional items in the correct orientation and sequence. And that is just the start. “It can then go back to the line and be able to see a package running on the conveyor,” says Paul. “It can actively lock in the position of that package and guide the motion control system to pick up the package without having to use any additional encoders on the system to do it.”
Before we launch into a discussion of integrated machine vision and motion control systems, it is important to note that a large number of variations exist in the hardware, software, and architecture. Some systems use a PLC and dedicated motion controller while others use a PC-based soft-motion platform. The colors of light, camera resolutions, and types of cameras themselves vary widely from system to system. This discussion includes some basic examples but be aware that they are not, by any means, comprehensive.
Motion-assisted vision
For decades, machine vision has been a fixture in the industrial environment. The technology is used for a variety of inspection tasks, from determining presence or absence of an object to checking dimensions to assessing quality. Is a part flawed? Is the bottle label on straight? Is the plastic the correct color? Machine vision systems can answer these questions very rapidly, over extended durations, and often very accurately. How accurately depends upon a number of factors, including system design, lighting, and how well the imager can see the parts. This is where motion systems can help.
Motion control technology can improve the performance of vision systems by optimizing positioning for best results. Motion axes can be used to place parts in front of the image sensor or transfer the image sensor over the parts. The technology can reposition parts to better illuminate the area of interest or change lighting conditions. It can change the orientation of the part or the camera to capture a sequence of images from different angles.
The classic example of motion-assisted vision is a web- or conveyor-based system that moves the product or web in front of a camera at constant velocity. The camera may be free running and capturing images continually or it may be triggered by a hardware sensor or a software trigger. The image processing algorithm may need to know the speed of the conveyor and the two systems may need to operate on a common time basis. The level of integration is minimal, however.
Vision-assisted motion
In vision-assisted motion, the vision system provides input to enable the motion system to perform a task such as ejecting bad parts. These types of tasks require synchronized operation between the vision system and the motion system. The sensor of the vision system triggers the camera to capture an image, which is stored in the buffer for processing. The trigger is also sent to the motion system so that the motion controller can register the position of the part. The vision system analyzes the image. When it detects a faulty part, it sends a signal to the motion system, which uses its knowledge of the part location to enable the actuator to eject the failed product.
For example, consider a system for separating green tomatoes from ripe tomatoes in a ketchup processing line. The tomatoes ride up a conveyor and cascade off the end in a single line (see figure 1). A line-scan camera captures the image and triggers the motion system to capture the position of a given tomato. If analysis determines that the tomato is green, the vision system sends a signal to the motion system. The controller on the motion system tracks the motion of the green tomato, and when the green tomato is in front of the actuator, commands a move to direct the tomato to a different conveyor.
Figure 1
Figure 1: in this vision-based sorting application, the vision system sends a trigger to the camera to capture an image and to the motion system to monitor the location of the tomatoes. When the image sensor detects an unripe tomato, it sends a signal to the motion system. The motion controller tracks the position of the item in question to enable an actuator to be commanded to reject the part. (Image courtesy of Kingstar)
These types of sorting applications require tight synchronization between the vision and motion systems. In particular, the analysis and decision to reject the part needs to take place quickly enough that the motion system is commanded to act before the part reaches the actuator. The image resolution and complexity of the algorithm need to be low enough that analysis can be completed in time.
The performance of the communication system needs to be analyzed to confirm that latency and jitter do not interfere with image processing.
Vision-guided motion
At the next level of integration, the vision system provides feedback to the motion system, helping it to close the control loop (see figure 2). As in the case of synchronized motion, a sensor in the vision system triggers the camera to capture an image of the part. The vision system, (frequently the camera), calculates the position of the part in pixel space, then converts that to the physical location in real-world coordinates. The motion controller uses this information to generate a trajectory for the actuator. The approach dramatically increases the functionality of the motion system.
“Vision-guided motion compensates for non-rigid tooling,” says Paul. “You could have a part appear anywhere on a conveyor, and the system with the vision will be able to find that part and pick it up or inspect it or perform whatever operation it is supposed to do. You don't necessarily need to be presenting that part in a rigid fixture as you would in the past. And you don’t need to pay for that tooling either. So it’s an engineering cost reduction as well as an increase in flexibility.”
Figure 2
Figure 2: Block diagram of a vision-guided motion system shows the role of the vision system in delivering data to the trajectory generator at cycle times on the order of 0.5 to 1 s. The trajectory generator delivers setpoints about every millisecond, while the control loop for the actuator operates on 50 µs cycle times. (Image courtesy of National Instruments)
Vision-guided motion is distinct from synchronized motion. In synchronized integration, the vision system helps the motion system decide whether to move. In vision-guided motion, the vision system helps the motion system decide where to move. Using vision-guided motion, a system can locate and assemble parts fed to it in random orientations. This eliminates the need for fixtures or special positioning equipment, reducing cost and complexity as well as speeding changeovers. Switching to a new product involves a software change rather than retooling.
Consider an application in which a silicone bead is applied by an extruder head to the edge of pieces of fabric. The system consists of a conveyor moving at a fixed speed, an overhead-mounted vision system, and an extrusion head mounted downstream on a linear slide controlled by a rotary servo motor (see figure 3). The fabric pieces are placed on the conveyor in random orientations. As they pass under the vision system, it captures an image and processes the data to calculate position and angle of the piece. Coordinate transformation software built into the smart camera transforms the image location from pixel space to its physical location in the real-world coordinate system. The motion controller uses this information to calculate the tool trajectory required to apply an even bead of silicone to the edge of the fabric.
Figure 3
Figure 3: This freeform edge-tracking system uses vision-guided motion to apply a bead of silicone to the edge of a series of cloth parts placed on a conveyor in random orientation. The overhead camera captures the image and performs a coordinate transformation before passing the data to the motion controller. The controller commands an extrusion head mounted on a servo-motor-driven linear slide to apply the silicone. The camera system also performs an inspection step simultaneously with part acquisition to enable the system to reject any defective blanks. (Image courtesy of ORMEC)
Another example involves CNC table cutters used to cut parts out of 4’ x 8’ metal blanks. In conventional systems, the blanks are placed on the work surface using a crane. As a result, they cannot be precisely aligned. Instead, the machine must acquire the edge mechanically before it begins cutting parts from the blank in a relative coordinate system. To maximize yield, the machine is programmed to cut a pattern of nested parts. Because the orientation of the blanks varies, parts along the perimeter may project over the edge and be incomplete. Vision-guided motion provides a solution to this problem.
With the introduction of image-based feedback, the tool set no longer needs to acquire the edge of the blank mechanically. Instead, the vision system captures an image of the blank and converts its position from pixel space to real-world coordinates. The motion system modifies the trajectory for the tool had so that it cuts the maximum number of complete parts from the blank. This approach enables the system to compensate for a blank that is cocked, offset, or otherwise misaligned. It increases yield and throughput.
Vision-guided motion is an effective approach but does present some challenges. As with synchronized integration, timing is essential. The processing frame rate needs to be synchronized to the motion loop rate. Communications latency should be carefully scrutinized to ensure that it is acceptable within the constraints of the position loop of the equipment.
The biggest issue is that the system only determines the trajectory at the beginning of the move and does not receive further input to modify performance. If there is an error in the coordinate transformation, the system cannot correct. As a result, the performance of the system depends on both the transformation and also on the precision, accuracy, and repeatability of the motion system.
Visual servoing
Visual servoing, or visual servo control, provides a way to avoid the possible errors introduced by vision-guided motion systems. In visual servo control, the system uses vision input both as guidance and as closed-loop feedback (see figure 4). Instead of providing input only for initial trajectory planning, the vision system provides continuous images to enable the motion system to target the part. The approach can be used to obtain highly accurate performance from less expensive equipment.
Figure 4
Figure 4: in the visual servo control scheme known as dynamic look and move, the vision system generates position setpoints directly, eliminating the need for a separate trajectory generator. This cuts the cycle time significantly. (Image courtesy of National Instruments)
A more sophisticated approach to visual servo control is known as direct servo. In this type of system, machine vision replaces conventional motion feedback devices such as encoders. The standard configuration features two cameras: an overhead camera to image actuator and target used to generate position setpoints, and a camera mounted on the actuator itself that delivers position feedback (see figure 5).
Figure 5
Figure 5: Direct servo control uses two cameras to deliver guidance and feedback. The first camera (bottom) images both actuator and target, using the data to generate position setpoints, replacing the trajectory generator. The second camera (top), mounted on the actuator, closes the position feedback loop. This camera replaces the conventional motion feedback system of encoder or similar. (Image courtesy of National Instruments)
Challenges of integrating motion and vision
The integration of vision and motion brings big benefits, but it is not always easy. Both systems are complex. They frequently are provided by different vendors. This can make interoperability a challenge because the two systems need to be synchronized. The higher the level of integration, the tighter the synchronization required.
As previously discussed, adding vision means that the vision system and motion control tasks need to be completed in the same cycle. Achieving this goal requires a comprehensive evaluation of the task. Start by determining timing - how fast is the part moving? How much time is available to process the image and determine an action? Can the vision system deliver this response rate before the part reaches the actuator?
A number of factors can present timing issues. Adding digital filters can impact data analysis. “Vision tools can slow you down if you are not careful,” says Sam Rubin, senior systems engineer at ORMEC Systems Group (Rochester, New York). “The camera may need to use digital filtering to improve image contrast. Because these filters process the image pixel by pixel, they take time. All of a sudden, an inspection that would run at 1 ms starts running at 50 ms and then it may end up being too slow for the machine rate required.” Reducing the area being imaged and analyzed to the minimum possible region-of-interest can help speed the process.
Particularly in the case of vision-guided motion and visual servoing, uninterrupted high-speed communications is essential. There was a time when the two systems would be kept separate and communicate over a high-speed data link. This has the potential to introduce latencies as a result of fixed offset and jitter. “If I'm going to be counting bottles and I can only count them so fast because I have to allow for non-deterministic latencies,” says Matt Edwards, solutions architect/director consulting at IntervalZero (Waltham, Massachusetts). “I have to schedule for worst case.” As a result of the latency issue, machine builders and integrators increasingly run both machine vision and motion control on the same computing platform using a real-time operating system (RTOS) and shared memory. “Now, I can shorten those latencies and make things more deterministic and the system operates quicker because it’s all in one box and there are no sporadic latencies that I have to account for,” says Edwards. “Now, the whole process can go faster.”
A number of pitfalls exist in the integration of motion and vision. The first is mission creep. A vision system can perform multiple tasks while guiding motion, including inspection and barcode reading. It is important to ensure that these additions do not cause the vision system processing time to exceed the cycle time of the equipment.
It is important to remember that the vision system will be tuned and integrated to address a specific set of tasks and conditions. Boosting the speed may shrink the cycle time beyond the ability of the vision system to keep up.
Paths to success
More and more OEM machine builders are integrating machine vision into their motion systems. In part, that is due to a concerted push in industry toward usability. Smart cameras incorporate automatic coordinate transformation and calibration routines. Many feature autofocus and integrated lighting. For OEMs and end-users trying to put together a system with synergistic integration, it has never been easier to add in machine vision. Even with higher levels of integration, a new generation of products integrating both motion and vision in one device simplifies device commissioning.
“You're finding higher success in applications,” says Nick Tebeau, director of sales for Leoni Engineering Products and Services (Lake Orion, Michigan). “And what that means is that companies who may not have wanted to get involved in the past with integrating these technology platforms out of fear of being unsuccessful are now finding themselves much more comfortable. Support is more readily available because the number of trusted integrators has grown throughout North America. And there’s better training such as the AIA CVP training that really enable these different companies to become educated into the proper way of getting started.”
Despite the array of modern tools, organizations pursuing higher levels of integration should still consider working with an integrator, or at the very least tapping their vendors for help. “Systems are becoming a lot easier but understanding the basics of the motion and the vision system and marrying the two together can still be challenging,” says Bill Catalano, vice-president of marketing and sales at ORMEC Systems Group (Rochester, New York). “In this resource restricted time that we live in, working with an integrator or vendor can give organizations an edge.”
Acknowledgments
Thanks go to Andy Long of CYTH Systems and Nate Holmes of National Instruments for useful conversations and background material.
|
undefined method `goals_against' for #<YAML::Object:0x5584864>
Hi all,
I have a serialized object (of class Goals) in my statistics table. I
store it in the value row of statitics
When I do:
goals = Statistic.find(1).value.goals_against I get
undefined method `goals_against' for #<YAML::Object:0x5584864>
(goals_against is a member of Goals)
Someone knows why this happens?
Thanks
Stijn
Would you share your model definitions and the code that you use to create/save the statistic and goals instances?
Craig
Thanks for the reply,
Please find the models, database and class definition below.
I try to get the goals object like this
@statistics = @event.statistics.find(:all, :include
=> :statistic_definition)
goals_a = @statistics.first.value.goals_against
=> undefined method `goals_against' for #<YAML::Object:0x579cbec>
The YAMLvalue in the database is:
--- !ruby/object:Goals
goals:
1: 2
goals_against: 2
goals_for: 2
version: 1
The model:
class Statistic < ActiveRecord::Base
belongs_to :event
belongs_to :statistic_definition
serialize :value
end
statitics table
id int(11)
value text
event_id int(11)
statistic_definition_id int(11)
The object I serialize
class Goals
attr_accessor :goals
attr_accessor :goals_for
attr_accessor :goals_against
attr_accessor :penalty_for
attr_accessor :penalty_against
def initialize(goals, goals_against, penalty_for = nil,
penalty_against = nil)
@version = 1
@goals = goals
set_goals_for()
@goals_against = goals_against.to_i
unless penalty_for.nil?
@penalty_for = penalty_for.to_i
@penalty_against = penalty_against.to_i
end
end
private
def set_goals_for
@goals_for = 0
@goals.each_value {|value| @goals_for += value.to_i }
end
end
I tried something a bit simpler just to see if it would work. Here’s what I did.
• create a new rails app (rails blah)
• create the databases (rake db:create:all)
• generate a Statistic model with a value column of type text (script/generate model statistic value:text)
• run migrations (rake db:migrate)
• create a non-ActiveRecord class named Goals with one attributed named goals_against
• run the Rails console (script/console) and do the following:
Statistic.create! :value => Goals.new(3)
=> #<Statistic id: 2, value: #<Goals:0x1928960 @goals_against=3>, created_at: “2008-04-17 13:22:10”, updated_at: “2008-04-17 13:22:10”>
stat = Statistic.find :first
=> #<Statistic id: 2, value: #<Goals:0x1911ddc @goals_against=3>, created_at: “2008-04-17 13:22:10”, updated_at: “2008-04-17 13:22:10”>
stat.value.goals_against
=> 3
I didn’t have any problems along the way. Other than using simpler models/classes, nothing jumps out at me as to what you might have done that’s causing your problem.
Here’s the source code.
class Statistic < ActiveRecord::Base
serialize :value
end
class Goals
attr_accessor :goals_against
def initialize(goals_against)
@goals_against = goals_against
end
end
Here’s the generated schema from db/schema.rb.
ActiveRecord::Schema.define(:version => 1) do
create_table “statistics”, :force => true do |t|
t.text “value”
t.datetime “created_at”
t.datetime “updated_at”
end
end
Let me know how it goes and if there’s anything more I can do.
Regards,
Craig
Many thanks for the help.
I have found some strange behavior:
I use understanding code to first insert a then read a Goals object
from the database
stat = Statistic.new
stat.event_id = 1
stat.statistic_definition_id = 1
stat.value = Goals.new({1 => 1, 2 => 2}, 1)
stat.save
@statistics = @event.statistics.find(:all, :include
=> :statistic_definition)
goals_a = @statistics.first.value.goals_against
When I use above code the deserialization works as it should.
The next time, when I only get the Goals object out of the database
(and not insert it first), deserialization fails. It seems that I have
to insert and read the object in the same request otherwise
deserialization fails.
This sounds very weird and I have no idea what causes this.
Regards,
Stijn
I found out something more. When I do:
Goals.new({1 => 1, 2 => 2}, 1)
@statistics = @event.statistics.find(:all, :include
=> :statistic_definition)
goals_a = @statistics.first.value.goals_against
it works.
@statistics = @event.statistics.find(:all, :include
=> :statistic_definition)
goals_a = @statistics.first.value.goals_against
I get undefined method `goals_against' for #<YAML::Object:0x539a954>
Can it be that the deserializer doesn't know the Goals object somehow
by default? I put the Goals class file in my Lib directory.
Regards,
Stijn
When I do
it also works. I thus just have to use the Goals class
In the example that I created, I put the Goals class in app/models even though it’s not an ActiveRecord model. Does putting your Goals class in app/models make a difference?
Regards,
Craig
Hi Craig,
Putting it in the apps/model solves the problem. I though tough you
should put all your classes in the lib dir.
regards,
Stijn
I’ve used the lib dir only once for a very simple rake task, but my impression is that code in the lib dir should be available to the rest of the app. If I have a chance to do a little learning, I’ll report back.
Craig
|
US6198767B1 - Apparatus for color component compression - Google Patents
Apparatus for color component compression Download PDF
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US6198767B1
US6198767B1 US08/411,127 US41112795A US6198767B1 US 6198767 B1 US6198767 B1 US 6198767B1 US 41112795 A US41112795 A US 41112795A US 6198767 B1 US6198767 B1 US 6198767B1
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Diane Marie Mauersberg
Agnes Yee Ngai
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MediaTek Inc
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• HELECTRICITY
• H04ELECTRIC COMMUNICATION TECHNIQUE
• H04NPICTORIAL COMMUNICATION, e.g. TELEVISION
• H04N11/00Colour television systems
• H04N11/04Colour television systems using pulse code modulation
• H04N11/042Codec means
• H04N11/044Codec means involving transform coding
• HELECTRICITY
• H04ELECTRIC COMMUNICATION TECHNIQUE
• H04NPICTORIAL COMMUNICATION, e.g. TELEVISION
• H04N19/00Methods or arrangements for coding, decoding, compressing or decompressing digital video signals
• H04N19/10Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding
• H04N19/102Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding characterised by the element, parameter or selection affected or controlled by the adaptive coding
• H04N19/132Sampling, masking or truncation of coding units, e.g. adaptive resampling, frame skipping, frame interpolation or high-frequency transform coefficient masking
• HELECTRICITY
• H04ELECTRIC COMMUNICATION TECHNIQUE
• H04NPICTORIAL COMMUNICATION, e.g. TELEVISION
• H04N19/00Methods or arrangements for coding, decoding, compressing or decompressing digital video signals
• H04N19/10Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding
• H04N19/169Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding characterised by the coding unit, i.e. the structural portion or semantic portion of the video signal being the object or the subject of the adaptive coding
• H04N19/186Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding characterised by the coding unit, i.e. the structural portion or semantic portion of the video signal being the object or the subject of the adaptive coding the unit being a colour or a chrominance component
• HELECTRICITY
• H04ELECTRIC COMMUNICATION TECHNIQUE
• H04NPICTORIAL COMMUNICATION, e.g. TELEVISION
• H04N19/00Methods or arrangements for coding, decoding, compressing or decompressing digital video signals
• H04N19/42Methods or arrangements for coding, decoding, compressing or decompressing digital video signals characterised by implementation details or hardware specially adapted for video compression or decompression, e.g. dedicated software implementation
• H04N19/423Methods or arrangements for coding, decoding, compressing or decompressing digital video signals characterised by implementation details or hardware specially adapted for video compression or decompression, e.g. dedicated software implementation characterised by memory arrangements
• HELECTRICITY
• H04ELECTRIC COMMUNICATION TECHNIQUE
• H04NPICTORIAL COMMUNICATION, e.g. TELEVISION
• H04N19/00Methods or arrangements for coding, decoding, compressing or decompressing digital video signals
• H04N19/50Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using predictive coding
• H04N19/587Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using predictive coding involving temporal sub-sampling or interpolation, e.g. decimation or subsequent interpolation of pictures in a video sequence
• HELECTRICITY
• H04ELECTRIC COMMUNICATION TECHNIQUE
• H04NPICTORIAL COMMUNICATION, e.g. TELEVISION
• H04N19/00Methods or arrangements for coding, decoding, compressing or decompressing digital video signals
• H04N19/60Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using transform coding
• H04N19/61Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using transform coding in combination with predictive coding
Abstract
A method of encoding interlaced, full motion digital video image data. The digital video image data has two interlaced fields per frame with luminance and chrominance components, where the chrominance components are uncorrelated between adjacent fields. The method encompasses applying one field of chrominance information to both luminance fields of a frame. This encodes chrominance components at one quarter the spatial resolution of the luminance components.
Description
FIELD OF THE INVENTION
This invention relates to video encoders, especially video encoders intended to encode and further compress video signals, e.g., discrete cosine transform encoded video signals. The invention relates especially to dynamically partitionable digital video processors for digital video signal encoding. A dynamically partitionable digital video processor, as used herein, means a processor that can function as an n unit processor, e.g., a four byte wide processor, and as n 1-unit processors, e.g., as four one-byte wide processors. The method, apparatus, and system of the invention are useful compressing video signals, as in encoding broadcast signals, cablecast signals, and digital network signals, as well as in high definition television, interactive television, multimedia, video on demand, video conferencing, and digital video recording. The method and apparatus of the invention specifically relates to a method of encoding digital video image data having luminance and chrominance components, where the chrominance components are encoded at one quarter the spatial resolution of the luminance components.
BACKGROUND OF THE INVENTION
The Moving Picture Experts' Group (MPEG) MPEG-2 Draft Standard is a compression/decompression standard for digital video applications. The standard describes an encoding method that results in substantial bandwidth reduction by a subjective lossy compression followed by a lossless compression. The encoded, compressed digital video data is subsequently decompressed and decoded in an MPEG-2 Draft Standard compliant decoder.
The MPEG-2 Draft Standard is described in, e.g., C. A. Gonzales and E. Viscito, “Motion Video Adaptive Quantization In The Transform Domain,” IEEE Trans Circuits Syst Video Technol, Volume 1, No. 4, December 1991, pp. 374-378, E. Viscito and C. A. Gonzales, “Encoding of Motion Video Sequences for the MPEG Environment Using Arithmetic Coding,” SPIE, Vol. 1360, pp. 1572-1576, (1990), D. LeGall, “MPEG: A Video Compression Standard for Multimedia Applications,” Communications of the ACM, Vol. 34, No. 4, (April 1991), pp. 46-58, S. Purcell and D. Galbi, “C Cube MPEG Video Processor,” SPIE, v. 1659, (1992) pp. 24-29, and D. J. LeGall, “MPEG Video Compression Algorithm,” Signal Process Image Commun, v. 4, n. 2, (1992), pp. 129-140, among others.
The MPEG-2 Draft Standard specifies a very high compression technique that achieves compression not achievable with intraframe coding alone, while preserving the random access advantages of pure intraframe coding. The combination of frequency domain intraframe encoding and interpolative/predictive interframe encoding of the MPEG-2 Draft Standard result in a balance between intraframe encoding alone and interframe encoding alone.
The MPEG-2 Draft Standard exploits temporal redundancy for motion compensated interpolative and predictive encoding. That is, the assumption is made that “locally” the current picture can be modelled as a translation of the picture at a previous and/or future time. “Locally” means that the amplitude and direction of the displacement are not the same everywhere in the picture.
MPEG-2 Draft Standard specifies predictive and interpolative interframe encoding and frequency domain intraframe encoding. It has block based motion compensation for the reduction of temporal redundancy, and Discrete Cosine Transform based compression for the reduction of spatial redundancy. Under MPEG-2 Draft Standard motion compensation is achieved by predictive coding, interpolative coding, and Variable Length Coded motion vectors. The information relative to motion is based on 16×16 blocks and is transmitted with the spatial information. It is compressed with Variable Length Codes, such as Huffman codes.
The MPEG-2 Draft Standard provides temporal redundancy reduction through the use of various predictive and interpolative tools. This is illustrated in FIG. 1. FIG. 1 shows three types of frames or pictures, “I” Intrapictures, “P” Predicted Pictures, and “B” Bidirectional Interpolated Pictures.
The “I” Intrapictures provide moderate compression, and are access points for random access, e.g., in the case of video tapes or CD ROMS. As a matter of convenience, one “I” Intrapicture is provided approximately every half second. The “I” Intrapicture only gets information from itself. It does not receive information from any “P” Predicted Pictures or “B” Bidirectional Interpolated Pictures. Scene cuts preferably occur at “I” Intrapictures.
“P” Predicted Pictures are coded with respect to a previous picture. “P” Predicted Pictures are used as the reference for future pictures, both “P” and “B” pictures.
“B” Bidirectional Coded pictures have the highest degree of compression. They require both a past picture and a future picture for reconstruction. “B” bidirectional pictures are never used as a reference.
Motion compensation goes to the redundancy between pictures. The formation of “P” Predicted Pictures from “I” Intrapictures and of “B” Bidirectional Coded Pictures from a pair of past and future pictures is a key feature of the MPEG-2 Draft Standard technique.
The motion compensation unit under the MPEG-2 Draft Standard is the Macroblock unit. The MPEG-2 Draft Standard Macroblocks are 16×16 pixel macroblocks. Motion information consists of one vector for forward predicted macroblocks, one vector for backward predicted macroblocks, and two vectors for bidirectionally predicted macroblocks. The motion information associated with each 16×16 macroblock is coded differentially with respect to the motion information present in the reference macroblock. In this way a 16×16 macroblock of pixels is predicted by a translation of a 16×16 macroblock of pixels from a past or future picture.
The difference between the source pixels and the predicted pixels is included in the corresponding bit stream. The decoder adds the correction term to the block of predicted pixels to produce the reconstructed block.
As described above and illustrated in FIG. 1, each 16×16 pixel block of a “P” Predicted Picture can be coded with respect to the closest previous “I” Intrapicture, or with respect to the closest previous “P” Predicted Picture.
Further, as described above and illustrated in FIG. 1, each 16×16 pixel block of a “B” Bidirectional Picture can be coded by forward prediction from the closest past “I” or “P” Picture, by backward prediction from the closest future “I” or “P” Picture, or bidirectionally, using both the closest past “I” or “P” picture and the closest “future “I” or “P” picture. Full bidirectional prediction is the least noisy prediction.
Motion information is sent with each 16×16 pixel block to show what part of the reference picture is to be used as a predictor.
As noted above, motion vectors are coded differentially with respect to motion vectors of the previous adjacent block. Variable Length Coding is used to code the differential motion vector so that only a small number of bits are needed to code the motion vector in the common case, where the motion vector for a block is nearly equal to the motion vector for a preceding block.
Spatial redundancy is the redundancy within a picture. Because of the block based nature of the motion compensation process, described above, it was desirable for the MPEG-2 Draft Standard to use a block based method of reducing spatial redundancy. The method of choice is the Discrete Cosine Transformation, and Discrete Cosine Transform coding of the picture. Discrete Cosine Transform coding is combined with weighted scalar quantization and run length coding to achieve still further levels of compression.
The Discrete Cosine Transformation is an orthogonal transformation. orthogonal transformations, because they have a frequency domain interpretation, are filter bank oriented. The Discrete Cosine Transformation is also localized. That is, the encoding process samples on an 8×8 spatial window which is sufficient to compute 64 transform coefficients or sub-bands.
Another advantage of the Discrete Cosine Transformation is that fast encoding and decoding algorithms are available. Additionally, the sub-band decomposition of the Discrete Cosine Transformation is sufficiently well behaved to allow effective use of psychovisual criteria.
After transformation, many of the frequency coefficients are zero, especially the coefficients for high spatial frequencies. These coefficients are organized into a zig-zag, as shown in FIG. 2, and converted into run-amplitude (run-level) pairs. Each pair indicates the number of zero coefficients and the amplitude of the non-zero coefficient. This is coded in a Variable Length Code.
Discrete Cosine Transformation encoding is carried out in the three stages as shown in FIG. 2. The first stage is the computation of the Discrete Cosine Transformation coefficients. The second step is the quantization of the coefficients. The third step is the conversion of the quantized transform coefficients into {run-amplitude} pairs after reorganization of the data into zig-zag scanning order.
Quantization enables very high degrees of compression, and a high output bit rate, and retains high picture quality.
Quantization can be adaptive, with “I” Intrapictures having fine quantization to avoid “blocking.” This is important because “I” Intrapictures contain energy at all frequencies. By way of contrast, “P” and “B” pictures contain predominantly high frequency energy and can be coded at a coarser quantization.
The MPEG-2 Draft Standard specifies a layered structure of syntax and bit stream. The bit stream is separated into logically distinct entities to prevent ambiguities and facilitate decoding. The six layers are shown in Table 1, below
TABLE 1
MPEG-2 Draft Standard Layers
Layer Purpose
Sequence Layer Random Access Unit and Context
Group of Pictures Layer Random Access Unit and Video
Coding
Picture Layer Primary Coding Unit
Slice Layer Resynchronization Unit
Macroblock Layer Motion Compensation Unit
Block Layer DCT Unit
Encoding can be accomplished by hardware or by software. Hardware encoding is generally faster than software encoding. However, even hardware encoding is slow, given the bit rate of a video image and the narrow bandwidth of the transmission medium. One reason for this is the many steps required in forming the Discrete Cosine Transform, and calculating all of its coefficients.
OBJECTS OF THE INVENTION
It is one object of the invention to provide a system that increases the speed of the encoding process, especially the Discrete Cosine Transform encoding process.
It is still another object of the invention to reduce the clock cycles required for encoding a picture.
SUMMARY OF THE INVENTION
These and other objects of the invention are attained by the digital signal encoder system of the invention. The system is useful for receiving the pre-processed, partially encoded but uncompressed macroblock and forming the discrete cosine transform thereof. The processor of the invention works in conjunction with other elements of the encoder system including a quantizer, a variable length code encoder, and a FIFO data output buffer to provide an integrated system.
The processor of the invention is utilized in a digital video encoder processor for discrete cosine transform encoding. The discrete cosine transform encoding includes the encoding steps of (1) determining the discrete cosine transform field or frame type, (2) addressing individual pixels as either (i) vertically adjacent pixels on consecutive Odd and Even field lines, or (ii) vertically adjacent pixels on consecutive Odd field lines, then consecutive Even field lines; or (iii) vertically adjacent pixels on consecutive Even field lines, then consecutive Odd field lines. These subtractions may be performed between (i) consecutive lines, (ii) odd lines, or (iii) even lines. The next step is finding the smallest variance of the above subtractions to determine the discrete cosine transform coding type. The subtractions are carried out in a dynamically partitionable processor having a plurality of datapaths. The datapaths are partitionable by the action of running opcode into (i) a single wide datapath, and (ii) a plurality of narrow datapaths for calculating the absolute value of the difference between two pixels, and accumulating the results of the subtraction.
According to a further exemplification of the invention there is provided a method of memory management in a digital image encoder to minimize memory bandwidth demands during encoding. The method is used with motion video data having temporal and spatial redundancy where chrominance and luminance data are stored temporarily. According to the method disclosed chrominance and luminance data are stored in separate locations in memory. The luminance data is fetched from memory and is the only image data used for motion estimation. The chrominance data is fetched from memory in a chrominance-luminance pair for image reconstruction. The reconstructed image is stored in memory, and fetched from memory for motion estimation.
According to a still further exemplification of the invention there is provided a method of encoding digital video image data having luminance and chrominance components, where the chrominance components are encoded at one quarter the spatial resolution of the luminance components.
And, according to a still further embodiment of our invention, there is provided a method of Discrete Cosine Transformation of a digital video image. In the disclosed method the Field Variance and Frame Variance are calculated. When the Field Variance is less than the Frame Variance Field Discrete Cosine Transform type transformation is performed. Alternatively, when the Frame Variance is less than the Field Variance, then a Frame Discrete Cosine Transform transformation is performed.
According to a still further embodiment of our invention, there is provided a method for encoding bitstream headers where templates for the bitstream header are stored in a buffer. The templates being addressable by programmable instructions, and the processor has a status register containing a bit for each header type. The status register is modifiable during the encoding process with a data pattern indicating the headers needed for encoding with the bitstream. In this way when a bit is set to 1 the predefined header type is generated and shipped to the bitstream, the header being generated by processing the header buffer template entries associated with the header type.
According to a still further embodiment of our invention, there is provided a method of encoding a low frame rate digital video source image to a high frame rate digital video target image in an encoder, where repeat fields are introduced into a high frame rate digital video intermediate image.
THE FIGURES
FIG. 1 shows the relationship of the Intraframe, the Predicted Frames, and the Bidirectional Frames to form a Group of Pictures.
FIG. 2 is a flow chart of three stages of discrete cosine transform encoding.
FIG. 3 is a block diagram of the dynamically partitionable digital video encoder processor of the invention.
FIG. 4 shows the subtraction of pixels, e.g., between consecutive lines, between odd lines, and between even lines.
DETAILED DESCRIPTION OF THE INVENTION
Every pixel in a digital video picture is represented by 1 byte of luminance and 1 byte of chrominance information. This is specified in the 4:2:2 MPEG standard. With a maximum picture size of 720 by 480 pixels and a transmission rate of 30 pictures per second, storage of the video image requires a large amount of memory. Moreover, a high bandwidth is required to transmit a video image across a transmission medium. Digital video compression is introduced to lower the memory and transmission medium bandwidth requirements. The end result of compression is a digital video image with less data bytes than the original picture but with as much information as possible.
The Processor
One step in video compression is to determine the quantization value per segment of the picture. The concept of quantization is to reduce the value of each pixel in the segment by a stepsize so that as many zeros as possible are created. In general, as the result of subsequent compression and encoding techniques, zeros require less data bits to represent. The value of the quantization factor or constant is selected based upon a human vision model. The selection of the quantization value requires computation that involves every pixel in the segment. There are 256 bytes of luminance data per macroblock in the 4:2:2 MPEG standard. To involve every pixel would require 256 operations. To speed up the computation, the operations are carried out in parallel.
The processor 11 of the invention has an instruction store 21 where microcode is stored. The processor 11 has a four byte wide arithmetic and logical unit 31 that is comprised of four one byte ALU's, 33, 35, 37, and 39. The processor 11 has a two level set of general purpose working registers, 41, a group of special purpose registers, 43, an instruction address stack, and a condition register, 45.
The processor 31 can perform four byte wide arithmetic and logical operations in the pipelines ALU 31. The pipelined ALU, 31, is made up of four individual one byte ALUs, 33, 35, 37, and 39. These four specialized arithmetic and logical units, ALUs, 33, 35, 37, and 39, are the core of the arithmetic and logic operations. Processor operations occur in four pipelined cycles:
1. FETCH,
2. DECODE,
3. EXECUTE, and
4. WRITE BACK.
Microcode instructions are first fetched from the instruction store, 21, and then decoded. The ALU controller, 30, provides data/control signals from the register/memory interface unit, 47, and the instruction fetch/decode unit, 23, respectively, through the ALU control unit, 30, to the ALUs, 33, 35, 37, and 39, based on the decoded instruction and the results of the previous instructions for data pipelining.
The processor, 11, can operate on either register/memory data from the register/memory interface unit, 47, or pixel data sent to the processor, 11, on dedicated pixel buses, 49. Branch/loop instructions are performed by a separate branch/loop processor unit, 25.
Data is processed by the ALUs, 33, 35, 37, and 39, in the EXECUTE cycle and stored to registers/memory, 41, 43, and 45, during the WRITE BACK cycle through the register/memory interface unit, 47. The processor, 11, can access a two level set of general purpose working registers, 41, and a group of special purpose registers, 43, internal to the processor, 11. A pixel bus, 49, is also provided for access to the registers/memory from external sources. A block diagram of the processor, 11, is shown in FIG. 3.
Each instruction is 27 bits wide. There are several instruction formats defined for this processor. A typical instruction has an opcode, a mode bit, destination field, and 2 source fields. The opcode is used to indicate what function is to be performed by the processor.
The mode bit tells the processor how to operate on the instruction. The two modes are “UNI” and “LP”. “UNI” mode operates as one four byte operation. While “LP” mode (LOGICAL PARTITION) operates as four one byte operations independent of each other. The source fields specify the location of the inputs to the operations. The destination field specifies the location to store the result of the operations.
The arithmetic and logical function unit, 31, consists of four 1 byte standalone arithmetic and logical units (ALUs), 33, 35, 37, and 39. The carry out of the high order bit of each unit propagates to the next higher order unit if the instruction specifies a 4 byte operation.
In each arithmetic and logical unit, there is an accumulation function. The accumulator per ALU is 16 bits wide. An add accumulate instruction is architected that permits the accumulation of the addition results with the previous data in the accumulator. The add circuitry allows two 8 bit inputs to be added to a 16 bit accumulator. This function permits accumulation of up to 256 bits of input data.
There are eight 8 by 8 multipliers installed in the processor, two per ALU. A 32 by 32 multiplication operation is also architected into the processor.
A subset of the 32 by 32 multiplication is the 32 by 16 multiplication. Two 8 by 8 multipliers in each unit are joined to form an 8 by 16 multiplier. In addition the two 8 by 16 multipliers of adjacent units are joined to form a single 16 by 16 multiplier. The input operands are parsed to allow H×L and L×L multiplications. The result of the two 16 by 16 multiplications are combined to form the 32 by 16 multiplication. This design allows the maximum reuse of circuitry.
One compression technique employed in MPEG2 is Discrete Cosine Transform (DCT) coding. This process is used to convert spatial domain image data into frequency domain image data. The picture image is fed to the DCT process in small subset of 8 by 8 pixels. An 8×8 block of pixels is defined as a macroblock.
If consecutive lines of pixels are used to feed the DCT process, this technique is defined as frame DCT type. Alternatively, if every other line of pixel image data is concatenated to form the 8 by 8 DCT input then this technique is defined as field DCT type. In general if there is motion between the two fields of a picture, as often occurs in interlaced pictures, then the pixel data has large differences between consecutive lines. If there is no motion between fields then there is very little variance between consecutive lines of pixel data. Typically the lower the pixel variance the higher the compression efficiency that can be achieved.
The encoder determines the DCT type, e.g. field or frame, by calculating the variances of the input pixel image. The input is fetched according to the address modes set by the set addressing mode instruction. This instruction sets one of the 6 unique address modes. ‘Mode 1’ will address two vertically adjacent pixels on consecutive Odd and Even field lines in the macroblock. ‘Mode 2’ will first address two vertically adjacent pixels on consecutive Odd field lines, then switch to consecutive Even field lines. ‘Mode 3’ will first address two vertically adjacent pixels on consecutive Even field lines, then switch to consecutive Odd field lines. Modes 4, 5, and 6 are identical to Modes 1,2, and 3 respectively, expect that one pixel in each of the Odd or Even lines of the macroblock is addressed, instead of two. The one pixel addressing modes are not used in the DCT type calculation.
The DCT type calculation involves three different subtractions: subtraction between consecutive lines, subtraction between the odd lines and subtraction between the even lines as shown in FIG. 4.
The smallest variance of the above subtractions is used to determine the DCT coding type. This pixel variance calculation is computation intensive involving every pixel. There are 256 pixels every macroblock, requiring 128 subtractions and 128 additions for the frame DCT calculation, and another 128 subtractions and 128 additions for the field DCT calculation. In a final step, the totals of the four accumulated values are added using an accumlator sum instruction, ACCSUM. A compare instruction is needed to determine which variance is smaller frame DCT or field DCT. In processors used heretofore this decision will require 512 calculations. In the processor of the instant invention, the mode bit is used to specify 4 calculations to be carried out in one cycle. The number of cycles required to perform this calculation is improved by a factor of four, resulting in one hundred twenty eight cycles required to perform the calculation. With the combination of the subtract absolute (SUBABS) and add accumulator (ADDACC) instructions, only 64 cycles are required.
Only two instructions are needed to calculate the variances. The instructions are SUBABS and ADDACC. These two instructions form a subroutine and are looped until all pixels in the macroblock have been used. The loop is used once for the frame DCT calculation and once again for the field DCT calculation. The SUBABS instruction is used to calculate the absolute value of the difference between two pixels. The ADDACC instruction is used to accumulate the results of the SUBABS instruction.
By pipelining the result of the SUBABS into the input of the ADDACC, intermediate memory read or write instructions are not needed. In this mode of operation, the above instructions improve performance by reducing the cycles required per calculation.
The processor, 11, of the invention is utilized in a digital video encoder processor for discrete cosine transform encoding. The discrete cosine transform encoding includes the encoding steps of (1) determining the discrete cosine transform field or frame type, (2) addressing individual pixels as either (i) vertically adjacent pixels on consecutive Odd and Even field lines, or (ii) vertically adjacent pixels on consecutive Odd field lines, then consecutive Even field lines; or (iii) vertically adjacent pixels on consecutive Even field lines, then consecutive Odd field lines. These subtractions may be performed between (i) consecutive lines, (ii) odd lines, or (iii) even lines. The next step is finding the smallest variance of the above subtractions to determine the discrete cosine transform coding type. The subtractions are carried out in a dynamically partitionable processor having a plurality of datapaths, 33, 35, 37, 39. The datapaths 33, 35, 37, 39, are partitionable by the action of running opcode into (i) a single wide datapath, 31, and (ii) a plurality of narrow datapaths, 33, 35, 37, 39, for calculating the absolute value of the difference between two pixels, and accumulating the results of the subtraction.
Another compression technique following calculation of the DCT coefficients is quantization. Quantization is a process to determine the stepsize per macroblock. Stepsize is based on the light intensity variances of the macroblock. The average of intensity of the macroblock is first calculated. Variances of each block are then determined. The smallest variance is used to select the stepsize for the macroblock. In the processor described herein, the average intensity can be calculated by ADDACC and shift instructions. The ADDACC instruction forms a subroutine of one instruction and is looped until all of the pixels in the 8 by 8 block are used. The accumulated result is divided by 64 via a shift right instruction.
The LP mode option is used for performance improvement. The addition of all luminance pixels is performed by the four ALUs, 33, 35, 37, and 39, in parallel. The average of each group is then calculated by performing a SHIFT RIGHT on the result.
The variance intensity is calculated by the SUBABS and ADDACC instructions. The SUBABS is used to determine the difference of each pixel data from the average of the block. ADDACC is used to accumulate the differences in each block. The smallest accumulation among the four blocks is used to determine the stepsize of the macroblock. By choosing LP mode, the computation of the four blocks is carried out simultaneously.
The architecture of the instructions in the processor, 11, and the execution unit design allows the dynamic partition of a single four byte dataflow to operate as one four byte dataflow unit or as four one byte execution units. The dynamic partitionable capability enhances the processor output, thereby providing a system that increases the speed of the encoding process, especially the Discrete Cosine Transform encoding process, and reducing the clock cycles required for encoding a picture.
Method and Apparatus for Color Conversion
The MPEG 2 standard specifies that the video input source is either 422 or 420 format. In the YUV color space, most of the high frequency components are concentrated in the Y component. However, human visual acuity is lowest in the high frquency chrominance components, and highest in the low frequency luminance components. For this reason, high compression of video sources can be obtained if the video sources are compressed from RGB to 422 or 420 color format. The color conversion to 420 requires reduction in both the horizontal and vertical dimensions, producing chrominance components that are one quarter the spatial resolution of the luminance components.
In progressive video, there is no motion between fields. A linear filter can be used to reduce the chrominace components. In interlaced full motion video, there is time difference, and thus motion between two fields in a frame structure picture. Because the chrominance components of two adjacent fields are very uncorrelated, a linear filter will create artifacts. Therefore motion compensation must be considered in the chrominance reduction.
Only the chrominance components of one field are used in the invention described herein. One field of chrominance information is applied to both luminance fields. No chrominance motion compensation is needed in this method. By eliminating one field, the vertical components are also reduced. Since all horizontal components of a field are within the time interval, there is no motion and a linear filter is used to reduce the horizontal components.
Color reduction is achieved by this economical filter and enhances video compression.
Field and Frame Encoding
One form of image compression is achieved by removal of redundant data called spatial redundancies. This form of redundancy occurs due to correlated information between adjacent pixel data.
In interlaced full motion video, there is a time difference between fields and thus there is motion between adjacent fields. This motion creates a discontinuity between adjacent lines within a frame.
The MPEG2 standard allows the use of Field and Frame Discrete Cosine Transform types to achieve better compression. Frame processing works better when there is little or no motion. There are more lines in the Frame format, thus there is more correlation for increased compressibility. However Field format processing works better in vertical detail motion. In such cases the field data is more correlated than the frame data.
The Discrete Cosine Transform Type decision, i.e., the Field or Frame decision, is calculated for every macroblock. The encoding method of the invention is based on the observation that if the two fields of the picture are from different times, then the data between the adjacent lines within a field will generally be closer in value than the data of adjacent lines within the frame.
The encoder calculates the total differences between adjacent lines of the Frame structure of the macroblock and then of adjacent lines of a Field structure within the macroblock. If the Field total variance is less, then Field Discrete Cosine Transform type is chosen. If however, the Frame total variance is less, then a Frame Discrete Cosine Transform type is chosen.
The Frame variance is calculated by the summation of the absolute differences between adjacent lines in the frame structure. It is assumed the lines in the frame structure are numbered in ascending order such as 1,2,3 etc. The Frame variance is the summation of the absolute differences of line 1 and 2, line 3 and 4, etc.
The Field variance is calculated in two parts: Field1 and Field2. Field1 is the summation of the absolute differences between adjacent odd lines in the frame structure. With the same numbering scheme as above, the Field1 variance is the summation of the absolute differences of line 1 and 3, line 5 and 7, etc. Field2 is calculated in the similar fashion with the exception the even line numbers are used. Field2 variance is the summation of the absolute differences of line 2 and 4, line 6 and 8, etc.
If the frame variance is less than Field1 plus Field2, as above, then Frame Discrete Cosine Transform is chosen. Otherwise the Field Discrete Cosine Transform is selected.
Generation of the MPEG Header
Bitstream headers, as defined in the MPEG2 Standard, contain information concerning the attached bitstream. The syntax of the header must be precise, as it is used to inform the decoder how to reconstruct the encoded picture. The usage of headers are application dependent. A flexible design is needed to allow easy adaptation to specific application requirements. Performance is also important so that valuable time is not taken away from the picture encoding.
In the encoder of our invention, a pre-loaded template is used in combination with a set of programmable instructions to generate the header bitstream. A 190×27 bits on-chip header buffer contains the templates for header types specified in the MPEG2 standard, MP@ML. This buffer is initialized from an external processor at the power on reset time.
Each header type occupies several entries in the buffer. The header generator of the invention contains a status register, writable by the processorof the invention, that works with the header buffer. The status register contains a bit for each header type. During the encoding process, the status register is modified with a data pattern indicating the header types needed. When a “ship header” command is issued, the header generator processes the status register from left to right, one bit at a time. When a bit is set to 1, the predefined header type is generated and shipped to the bitstream. The header is generated by processing the header buffer template entries associated with the header type.
Each entry in the header buffer contains the following fields:
1. valid,
2. length,
3. command, and
4. data.
During initialization all valid bits are set “off”. The valid bit is only set by microcode when the associated data is needed in the bitstream per application. During “ship header” processing the contents of the “data” field are put into the bitstream if the “valid” field is “on”.
The “length” field is loaded during the initialization process. It is used to indicate the length of data in the “data” field to be shipped to the bitstream when the “valid” bit is “on”.
There are three bits in the “command” field. The “command” field is used to inform the header generator of the processor of the location of data, how to generate the data, and how much data to be inserted into the bitstream. The “command” codes are defined as follows:
001 ship content of data field into bitstream
010 concatenate 20 bits of zeros with the content of data field & ship into bitstream
011 ship next 64 bytes of data in data buffer into bitstream
100 ship macroblock data into bitstream
101 ship content of two consecutive data entries into the bitstream
110 ship content of data field into bitstream and reset valid bit
111 ship user data into bitstream
The 000 code is undefined
Contents of data field is initialized by the external processor. It can later be modified by microcode.
The content of the header buffer is writable by either the external or the internal processor. This provides flexibility. The internal processor, that is, the processor of the invention, only has to set up a few registers when the ship header command is issued. The processor is freed to process other work while the header hardware builds and ships the header into the bitstream, thus improving performance.
Memory Organization
Temporal redundancies are redundant image information over time, i.e., data that is similar or repeats itself from frame to frame over time. Motion estimation is a process used to reduce temporal redundancies of video images. Motion estimation is a process of determining the movement of objects within an image sequence. Removal of temporal redundancies is also a key part of the MPEG2 standard. However the standard does not specify the method to accomplish Motion Estimation. The MPEG2 standard only specifies the headers, bit stream architecture, and protocols necessary to allow MPEG2 compliant decoding.
Motion estimation creates three challenges for the encoder: memory bandwidth, computation requirement, and noise. According to our invention, regional block matching is used for motion estimation. Regional block matching involves segmentation of a frame into smaller regions and searching for the displacement which produces a best match among possible regions in a reference frame. The size of a frame is defined as 720 rows of pixels horizontally by 480 lines of pixels vertically as defined in the MPEG2 standard. Since the amount of data per picture is too large to be included inside the encoder chip, it is stored in an external memory. Three main steps are required for motion estimation function: data retrieval from memory, data computation, and prediction selection.
The amount of data retrieved from external memory is directly proportional to the search window. A large search window provides a high probability of finding a closer match within a large amount of data, and therefore creates a bigger demand on memory bandwidth. The opposite is true for a small search window, which creates less of a demand on memory bandwidth, but has a lower probability of finding a closer match.
To maximize memory bandwidth, the encoder memory control system and method of the invention include luminance and chrominance pair (uv pair) storing, separate luminance and chrominace locations, memory access prioritization and physically distinct memories for luminance and chrominance.
Luminance and chrominance data are stored in separate locations. Motions occur in both luminance and chrominance data. However luminance and chrominance movements track each other. To minimize computation requirements, only luminance data is used in motion estimation. When pixel data is retrieved from external memory, the memory access time depends on Column Address Select (CAS) and Row Address Select (RAS) times. Longer delays are needed for each new RAS access than an adjacent CAS within a RAS. For this reason, the luminance data is stored separately from the chrominance data. This maximizes adjacent CAS during motion estimation. The chrominance data is sent to the memory control in UV pairs and is stored and fetched from the DRAM in this manor to save memory bandwidth when processing a picture store or a macroblock (MB) fetch.
As defined in the MPEG2 standard, a picture is divided into smaller subimages or macroblocks. The macroblocks are coded independently of one another. A macroblock is defined as 16 pixels horizontally and 16 lines vertically. It is further defined that the pel unit in the macroblock could either be full or half pel. Let x and y be adjacent pixels in a picture, half pel is defined as
(x+y)/2
where / is division with rounding
To form 16 pixels in half unit, the encoder has to retrieve 17 bytes from external memory. With an input memory bus design four bytes wide, five memory accesses are needed to retrieve 17 bytes of data. However, only 1 byte in the last access is useful. This applies to luminance and chrominance data (u and v). By storing the u and v in pairs, only nine memory accesses are needed for 1 line of chrominance data. By way of comparison, ten memory accesses are needed if Luminance and chrominance (u and v) are stored in separate memory locations.
In the encoder, the input images are accumulated until enough data is saved to start encoding. Data is then fetched from the external memory during the encoding process. The image is reconstructed from the encoded data. This reconstructed image is also saved in external memory. The reconstructed image in external memory will then be retrieved later as reference data for motion estimation in subsequent pictures. A piece of pixel data is stored and fetched several times during the encoding process. To minimize conflicts, the external memory in the encoder of the invention is physically separated into different segments. Each segment has its own controls and data path such that several memory segments can operate simultaneously. The segments are selected based on their data flow in the encoder. The input image is saved in one memory segment and the reconstructed image is saved in another memory segment.
When performing the task of fetching and storing reconstructed reference data, the DRAM saves bandwidth by prioritizing the memory accesses. The encoding parameters for the picture, such as picture type, IP or IPB mode, dual prime, and the number of reference fields, help to predict the number of fetches each unit in the refinement search path will have per macroblock. With the number of fetches per unit predicted, the memory control executes a DRAM fetch and store pattern for that picture. Patterns for all of the different encoding scenarios are predetermined and mapped into a state machine to provide maximum data flow through the chip. Maximum data flow is achieved by mapping out DRAM fetches and stores so that each unit may receive data when it will need it, and the reference data is stored back to DRAM when it has been determined that the refinement units will be busy with previously fetched data. Memory accesses are streamlined as much as possible to prevent pauses in processing a macroblock due to units having to wait for the memory control to finish another fetch or a macroblock store before receiving their data.
The combination of the above features maximizes the bandwidth and miminizes the memory requirement for our encoder design.
While the invention has been described with respect to certain preferred embodiments and exemplifications, it is not intended to limit the scope of the invention thereby, but solely by the claims appended hereto.
Claims (1)
We claim:
1. In a method of encoding interlaced, full motion digital video image data having two interlaced fields per frame with luminance and chrominance components, where the chrominance components are uncorrelated between adjacent fields, the improvement comprising applying one field of chrominance information to both luminance fields of a frame, thereby encoding chrominance components at one quarter the spatial resolution of the luminance components.
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US20030061610A1 (en) * 2001-03-27 2003-03-27 Errico James H. Audiovisual management system
US20030076448A1 (en) * 2001-10-19 2003-04-24 Hao Pan Identification of replay segments
US20030121040A1 (en) * 2001-07-02 2003-06-26 Ferman A. Mufit Audiovisual management system
US20030182620A1 (en) * 2002-03-19 2003-09-25 James Errico Synchronization of video and data
US20040073918A1 (en) * 2002-09-30 2004-04-15 Ferman A. Mufit Automatic user profiling
US20040197088A1 (en) * 2003-03-31 2004-10-07 Ferman Ahmet Mufit System for presenting audio-video content
US20040255150A1 (en) * 2000-04-07 2004-12-16 Sezan Muhammed Ibrahim Audiovisual information management system
US20050060641A1 (en) * 1999-09-16 2005-03-17 Sezan Muhammed Ibrahim Audiovisual information management system with selective updating
EP1667463A2 (en) * 2004-12-06 2006-06-07 Sony Corporation Video signal processing device and video signal transfer method
US20060174277A1 (en) * 2004-03-04 2006-08-03 Sezan M I Networked video devices
US20060282856A1 (en) * 2005-03-04 2006-12-14 Sharp Laboratories Of America, Inc. Collaborative recommendation system
US20070209047A1 (en) * 2006-03-03 2007-09-06 Sharp Laboratories Of America, Inc. Method and system for configuring media-playing sets
US20070211950A1 (en) * 2006-03-08 2007-09-13 Masato Shima VLC Technique for Layered Video Coding Using Distinct Element Grouping
US7647340B2 (en) 2000-06-28 2010-01-12 Sharp Laboratories Of America, Inc. Metadata in JPEG 2000 file format
US8028314B1 (en) * 2000-05-26 2011-09-27 Sharp Laboratories Of America, Inc. Audiovisual information management system
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US20050060641A1 (en) * 1999-09-16 2005-03-17 Sezan Muhammed Ibrahim Audiovisual information management system with selective updating
US20050141864A1 (en) * 1999-09-16 2005-06-30 Sezan Muhammed I. Audiovisual information management system with preferences descriptions
US20050131727A1 (en) * 1999-09-16 2005-06-16 Sezan Muhammed I. Audiovisual information management system with user identification
US20050120033A1 (en) * 1999-09-16 2005-06-02 Sezan Muhammed I. Audiovisual information management system with identification prescriptions
US7197709B2 (en) 1999-09-16 2007-03-27 Sharp Laboratories Of America, Inc. Audiovisual information management system with multiple user identifications
US7194688B2 (en) 1999-09-16 2007-03-20 Sharp Laboratories Of America, Inc. Audiovisual information management system with seasons
US20050120034A1 (en) * 1999-09-16 2005-06-02 Sezan Muhammed I. Audiovisual information management system with advertising
US7181691B2 (en) 1999-09-16 2007-02-20 Sharp Laboratories Of America, Inc. Audiovisual information management system with presentation service
US20050091165A1 (en) * 1999-09-16 2005-04-28 Sezan Muhammed I. Audiovisual information management system with usage preferences
US20050091685A1 (en) * 1999-09-16 2005-04-28 Sezan Muhammed I. Audiovisual information management system
US20050091686A1 (en) * 1999-09-16 2005-04-28 Sezan Muhammed I. Audiovisual information management system with seasons
US7194687B2 (en) 1999-09-16 2007-03-20 Sharp Laboratories Of America, Inc. Audiovisual information management system with user identification
US7178107B2 (en) 1999-09-16 2007-02-13 Sharp Laboratories Of America, Inc. Audiovisual information management system with identification prescriptions
US20050188328A1 (en) * 1999-09-16 2005-08-25 Sezan Muhammed I. Audiovisual information management system with presentation service
US20040268390A1 (en) * 2000-04-07 2004-12-30 Muhammed Ibrahim Sezan Audiovisual information management system
US20040268383A1 (en) * 2000-04-07 2004-12-30 Sezan Muhammed Ibrahim Audiovisual information management system
US20040261095A1 (en) * 2000-04-07 2004-12-23 Sezan Muhammed Ibrahim Audiovisual information management system
US20040255150A1 (en) * 2000-04-07 2004-12-16 Sezan Muhammed Ibrahim Audiovisual information management system
US20040268389A1 (en) * 2000-04-07 2004-12-30 Sezan Muhammed Ibrahim Audiovisual information management system
US20040267805A1 (en) * 2000-04-07 2004-12-30 Sezan Muhammed Ibrahim Audiovisual information management system
US8028314B1 (en) * 2000-05-26 2011-09-27 Sharp Laboratories Of America, Inc. Audiovisual information management system
US7647340B2 (en) 2000-06-28 2010-01-12 Sharp Laboratories Of America, Inc. Metadata in JPEG 2000 file format
US8020183B2 (en) 2000-09-14 2011-09-13 Sharp Laboratories Of America, Inc. Audiovisual management system
US20020059584A1 (en) * 2000-09-14 2002-05-16 Ferman Ahmet Mufit Audiovisual management system
US20030061610A1 (en) * 2001-03-27 2003-03-27 Errico James H. Audiovisual management system
US7904814B2 (en) 2001-04-19 2011-03-08 Sharp Laboratories Of America, Inc. System for presenting audio-video content
US20020180774A1 (en) * 2001-04-19 2002-12-05 James Errico System for presenting audio-video content
US20030121040A1 (en) * 2001-07-02 2003-06-26 Ferman A. Mufit Audiovisual management system
US20060083304A1 (en) * 2001-10-19 2006-04-20 Sharp Laboratories Of America, Inc. Identification of replay segments
US20030076448A1 (en) * 2001-10-19 2003-04-24 Hao Pan Identification of replay segments
US7653131B2 (en) 2001-10-19 2010-01-26 Sharp Laboratories Of America, Inc. Identification of replay segments
US20050271269A1 (en) * 2002-03-19 2005-12-08 Sharp Laboratories Of America, Inc. Synchronization of video and data
US20030182620A1 (en) * 2002-03-19 2003-09-25 James Errico Synchronization of video and data
US7853865B2 (en) 2002-03-19 2010-12-14 Sharp Laboratories Of America, Inc. Synchronization of video and data
US8214741B2 (en) 2002-03-19 2012-07-03 Sharp Laboratories Of America, Inc. Synchronization of video and data
US7793205B2 (en) 2002-03-19 2010-09-07 Sharp Laboratories Of America, Inc. Synchronization of video and data
US20050271146A1 (en) * 2002-03-19 2005-12-08 Sharp Laboratories Of America, Inc. Synchronization of video and data
US20040073918A1 (en) * 2002-09-30 2004-04-15 Ferman A. Mufit Automatic user profiling
US7657907B2 (en) 2002-09-30 2010-02-02 Sharp Laboratories Of America, Inc. Automatic user profiling
US20040197088A1 (en) * 2003-03-31 2004-10-07 Ferman Ahmet Mufit System for presenting audio-video content
US20060174277A1 (en) * 2004-03-04 2006-08-03 Sezan M I Networked video devices
US8776142B2 (en) 2004-03-04 2014-07-08 Sharp Laboratories Of America, Inc. Networked video devices
US8356317B2 (en) 2004-03-04 2013-01-15 Sharp Laboratories Of America, Inc. Presence based technology
US20090317052A1 (en) * 2004-03-04 2009-12-24 Sharp Laboratories Of America, Inc. Networked video devices
EP1667463A2 (en) * 2004-12-06 2006-06-07 Sony Corporation Video signal processing device and video signal transfer method
EP1667463A3 (en) * 2004-12-06 2011-07-20 Sony Corporation Video signal processing device and video signal transfer method
US20060282856A1 (en) * 2005-03-04 2006-12-14 Sharp Laboratories Of America, Inc. Collaborative recommendation system
US8949899B2 (en) 2005-03-04 2015-02-03 Sharp Laboratories Of America, Inc. Collaborative recommendation system
US8689253B2 (en) 2006-03-03 2014-04-01 Sharp Laboratories Of America, Inc. Method and system for configuring media-playing sets
US20070209047A1 (en) * 2006-03-03 2007-09-06 Sharp Laboratories Of America, Inc. Method and system for configuring media-playing sets
US8116371B2 (en) * 2006-03-08 2012-02-14 Texas Instruments Incorporated VLC technique for layered video coding using distinct element grouping
US20070211950A1 (en) * 2006-03-08 2007-09-13 Masato Shima VLC Technique for Layered Video Coding Using Distinct Element Grouping
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Titanium(III) chloride
From Wikipedia, the free encyclopedia
Jump to: navigation, search
Titanium(III) chloride
Beta-TiCl3-chain-from-xtal-3D-balls.png
Beta-TiCl3-chains-packing-from-xtal-3D-balls-B.png
β-TiCl3 viewed along the chains
TiCl3.jpg
TiCl3 solution
Names
Other names
titanium trichloride
titanous chloride
Identifiers
3D model (Jmol)
ChemSpider
ECHA InfoCard 100.028.845
EC Number 231-728-9
RTECS number XR1924000
UNII
Properties
TiCl3
Molar mass 154.225 g/mol
Appearance red-violet crystals
hygroscopic
Density 2.64 g/cm3
Melting point 425 °C (797 °F; 698 K) (decomposes)
Boiling point 960 °C (1,760 °F; 1,230 K)
very soluble
Solubility soluble in acetone, acetonitrile, certain amines;
insoluble in ether and hydrocarbons
+1110.0·10−6 cm3/mol
1.4856
Hazards
Main hazards Corrosive
Safety data sheet External MSDS
Related compounds
Other anions
Titanium(III) fluoride
Titanium(III) bromide
Titanium(III) iodide
Other cations
Scandium(III) chloride
Chromium(III) chloride
Vanadium(III) chloride
Related compounds
Titanium(IV) chloride
Titanium(II) chloride
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YesYN ?)
Infobox references
Titanium(III) chloride is the inorganic compound with the formula TiCl3. At least four distinct species have this formula; additionally hydrated derivatives are known. TiCl3 is one of the most common halides of titanium and is an important catalyst for the manufacture of polyolefins.
Structure and bonding[edit]
In TiCl3, each Ti atom has one d electron, rendering its derivatives paramagnetic, i.e. the substance is attracted into a magnetic field. The trihalides of hafnium and zirconium: in these heavier metals engage in metal-metal bonding. Solutions of titanium(III) chloride are violet, which arises from excitations of its d-electron. The colour is not very intense since the transition is forbidden by the Laporte selection rule.
Four solid forms or polymorphs of TiCl3 are known. All feature titanium in an octahedral coordination sphere. These forms can be distinguished by crystallography as well as by their magnetic properties, which probes exchange interactions. β-TiCl3 crystallizes as brown needles. Its structure consists of chains of TiCl6 octahedra that share opposite faces such that the closest Ti—Ti contact is 2.91 Å. This short distance indicates strong metal-metal interactions (See Figure in upper right). The three violet "layered" forms, named for their color and their tendency to flake, are called alpha, gamma, and delta. In α-TiCl3, the chloride anions are hexagonal close-packed. In γ-TiCl3, the chlorides anions are cubic close-packed. Finally, disorder in shift successions, causes an intermediate between alpha and gamma structures, called the delta (δ) form. The TiCl6 share edges in each form, with 3.60 Å being the shortest distance between the titanium cations. This large distance between titanium cations precludes direct metal-metal bonding. In contrast, direct Zr-Zr bonding is indicated in zirconium(III) chloride. The difference between the Zr(III) and Ti(III) materials is attributed in part to the relative radii of these metal centers.[1]
Synthesis and reactivity[edit]
TiCl3 is produced usually by reduction of titanium(IV) chloride. Older reduction methods used hydrogen:[2]
2 TiCl4 + H2 → 2 HCl + 2 TiCl3
It is conveniently reduced with aluminium and sold as a mixture with aluminium trichloride, TiCl3·AlCl3. This mixture can be separated to afford TiCl3(THF)3.[3] The complex adopts a meridional structure.[4]
Its hydrate can be synthesised by dissolving titanium in aqueous hydrochloric acid.
2 Ti + 6 HCl + 6 H2O → 2 TiCl3(H2O)3 + 3 H2
TiCl3 forms a variety of coordination complexes, most of which are octahedral. The light-blue crystalline adduct TiCl3(THF)3 forms when TiCl3 is treated with tetrahydrofuran.[5]
TiCl3 + 3 C4H8O → TiCl3(OC4H8)3
An analogous dark green complex arises from complexation with dimethylamine. In a reaction where all ligands are exchanged, TiCl3 is a precursor to the tris acetylacetonate complex.
The more reduced titanium(II) chloride is prepared by the thermal disproportionation of TiCl3 at 500 °C. The reaction is driven by the loss of volatile TiCl4:[6]
2 TiCl3 → TiCl2 + TiCl4
The ternary halides, such as A3TiCl6, have structures that depend on the cation (A+) added.[7] Caesium chloride treated with titanium(II) chloride and hexachlorobenzene produces crystalline CsTi2Cl7. In these structures Ti3+ exhibits octahedral coordination geometry.[8]
Applications[edit]
TiCl3 is the main Ziegler-Natta catalyst, responsible for most industrial production of polypropylene. The catalytic activities depend strongly on the polymorph and the method of preparation.[9]
Laboratory use[edit]
TiCl3 is also a reagent in organic synthesis, useful for reductive coupling reactions, often in the presence of added reducing agents such as zinc. It reduces oximes to imines.[10] Titanium trichloride can reduce nitrate to ammonium ion thereby allowing for the sequential analysis of nitrate and ammonia.[11] Slow deterioration occurs in air-exposed titanium trichloride, often resulting in erratic results, e.g. in reductive coupling reactions.[12]
Safety[edit]
TiCl3 and most of its complexes are typically handled under air-free conditions to prevent reactions with oxygen and moisture. Depending on the method for its preparation, samples of TiCl3 can be relatively air stable or pyrophoric.[2][13]
References[edit]
1. ^ Greenwood, Norman N.; Earnshaw, Alan (1997). Chemistry of the Elements (2nd ed.). Butterworth-Heinemann. ISBN 0-08-037941-9.
2. ^ a b T. R. Ingraham, K. W. Downes, P. Marier, "Titanium(III) Chloride" Inorganic Syntheses, 1960, vol 6, pp. 52–56. doi: 10.1002/9780470132371.ch16
3. ^ Jones, N. A.; Liddle, S. T.; Wilson, C.; Arnold, P. L. (2007). "Titanium(III) Alkoxy-N-heterocyclic Carbenes and a Safe, Low-Cost Route to TiCl3(THF)3". Organometallics. 26: 755–757. doi:10.1021/om060486d.
4. ^ Handlovic, M.; Miklos, D.; Zikmund, M. "The structure of trichlorotris(tetrahydrofuran)titanium(III)" Acta Crystallographica 1981, volume B37(4), 811-14.doi:10.1107/S056774088100438X
5. ^ Manzer, L. E.; Deaton, Joe; Sharp, Paul; Schrock, R. R. (1982). "Tetrahydrofuran Complexes of Selected Early Transition Metals". Inorg. Synth. 21: 137. doi:10.1002/9780470132524.ch31.
6. ^ Holleman, A. F.; Wiberg, E. "Inorganic Chemistry" Academic Press: San Diego, 2001. ISBN 0-12-352651-5.
7. ^ Hinz, D.; Gloger, T. & Meyer, G. (2000). "Ternary halides of the type A3MX6. Part 9. Crystal structures of Na3TiCl6 and K3TiCl6". Zeitschrift für Anorganische und Allgemeine Chemie. 626 (4): 822–824. doi:10.1002/(SICI)1521-3749(200004)626:4<822::AID-ZAAC822>3.0.CO;2-6.
8. ^ Jongen, L. & Meyer, G. (2004). "Caesium heptaiododititanate(III), CsTi2I7". Zeitschrift für Anorganische und Allgemeine Chemie. 630 (2): 211–212. doi:10.1002/zaac.200300315.
9. ^ Kenneth S. Whiteley,T. Geoffrey Heggs, Hartmut Koch, Ralph L. Mawer, Wolfgang Immel, "Polyolefins" in Ullmann's Encyclopedia of Industrial Chemistry 2005, Wiley-VCH, Weinheim. doi:10.1002/14356007.a21_487
10. ^ Lise-Lotte Gundersen, Frode Rise, Kjell Undheim, José Méndez-Andino, "Titanium(III) Chloride" in Encyclopedia of Reagents for Organic Synthesis doi:10.1002/047084289X.rt120.pub2
11. ^ "Determining Ammonium & Nitrate ions using a Gas Sensing Ammonia Electrode". Soil and Crop Science Society of Florida, Vol. 65, 2006, D.W.Rich, B.Grigg, G.H.Snyder
12. ^ Fleming, M. P; McMurry, J. E. "Reductive Coupling of Carbonyls to Alkenes: Adamantylideneadamantane". Org. Synth. ; Coll. Vol., 7, p. 1
13. ^ Pohanish, Richard P. & Greene, Stanley A. (2009). Wiley Guide to Chemical Incompatibilities (3 ed.). John Wiley & Sons. p. 1010. ISBN 9780470523308.
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Installation
Using jQuery#
<script type="text/javascript">
$.getScript("//cnstrc.com/js/cust/<your_custom_bundle_name>.js", function () {
$("#query").constructorAutocomplete({
key: "<your_api_key>",
});
});
</script>
To install with jQuery, use this code snippet. In this example, #query is the DOM selector of your search box, and <your_api_key> can be found on your dashboard.
Using HTML/JavaScript#
<script
type="text/javascript"
src="https://cnstrc.com/js/cust/<your_custom_bundle_name>.js"
></script>
<script>
const inputElement = document.querySelector("#query");
const autocomplete = new ConstructorioAutocomplete(inputElement, {
key: "<your_api_key",
});
</script>
To install with HTML/JavaScript, use this code snippet.
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Maven Target Set
Maven brought the idea of standard project directory tree structures and standardized project lifecycles to the world of Java project builds. With Ant you have to specify everything about the build, with Maven everything is standardized. Ant has the benefit of being completely general, Maven has the benefit of convention. Gant sits with Ant, it is a gneral mechanism for scripting Ant tasks using Groovy rather than XML. Using a dynamic programming language means that it is possible to write complete target sets that can be included. So we don’t have to use a completely different framework to harness the power of convention. Examples of prepackaged target sets are gant.targets.Clean and gant.targets.Maven. These are, in effect, mixins that can be used to create build specifications.
An example:
includeTargets << gant.targets.Maven
maven.groupId = 'org.codehaus.gant'
maven.artifactId = 'gant'
maven.version = '1.2.1-SNAPSHOT'
maven.javaCompileProperties = [source: '1.5', target: '1.5', debug: 'true']
maven.deployURL = 'https://dav.codehaus.org/repository/gant'
maven.deploySnapshotURL = 'https://dav.codehaus.org/snapshots.repository/gant'
setDefaultTarget install
The Maven target set imports the targets: initialize, compile, test-compile, test, package, install, and deploy. We can add any other targets just as we might in any Gant file.
An alternative way of writing this is:
includeTargets ** gant.targets.Maven * [
groupId: 'org.codehaus.gant',
artifactId: 'gant',
version: '1.2.1-SNAPSHOT',
javaCompileProperties: [source: '1.5', target: '1.5', debug: 'true'],
deployURL: 'https://dav.codehaus.org/repository/gant',
deploySnapshotURL: 'https://dav.codehaus.org/snapshots.repository/gant'
]
setDefaultTarget install
With either of the above, we can see what targets are available using the -p (or -T) option:
|> gant -p
clean Action the cleaning.
clobber Action the clobbering. Do the cleaning first.
compile Compile the source code in src/main to target/classes.
deploy Deploy the artefact: copy the artefact to the remote repository https://dav.codehaus.org/snapshots.repository/gant.
initialize Ensure all the dependencies can be met and set classpaths accordingly.
install Install the artefact into the local repository.
package Package the artefact as a jar in target/classes.
site Create the website.
test Run the tests using the junit unit testing framework.
test-compile Compile the test source code in src/test to target/test-classes.
Default target is install.
NB The site target does not work as yet. Note that the comments explain as much as possible about the action inclusing sources and targets where known. The above example is for building Gant itself – the 1.0.1-SNAPSHOT version.
For those people who prefer to use Test’N’Groove rather than JUnit for unit tests, simply specify the testFramework property to be ‘testng’. So for example, the ADS Package build file is:
includeTargets ** gant.targets.Maven * [
groupId: 'org.devjavasoft',
artifactId: 'ads',
version: '3.1.0',
javaCompileProperties: [source: '1.6', target: '1.6', debug: 'true'],
testFramework: 'testng'
]
cleanPattern << '**/*~'
setDefaultTarget test
NB The Maven target set automatically pulls in the Clean target so we can use the standard Gant clean support features. Checking the available targets for the above Gant file:
|> gant -p
clean Action the cleaning.
clobber Action the clobbering. Do the cleaning first.
compile Compile the source code in src/main to target/classes.
deploy Deploy the artefact: copy the artefact to the remote repository .
initialize Ensure all the dependencies can be met and set classpaths accordingly.
install Install the artefact into the local repository.
package Package the artefact as a jar in target/classes.
site Create the website.
test Run the tests using the testng unit testing framework.
test-compile Compile the test source code in src/test to target/test-classes.
Default target is test.
Note that the test target tells us which unit test framework is being used. Groovy’s GString in action.
What about dependencies? Simply add to the compileDependencies or testDependencies property, for example:
maven.testDependencies << [groupId: 'org.testng', artifactId: 'testng', version: '5.8', scope: 'test', classifier: 'jdk15']
A dependency is a hash with keys for all the attributes required by the Maven dependency resolution system. During completion of the initialize target all specified dependencies will be checked for presence in the standard Maven local repository or downloaded if not present. Although we have presented the example of downloading TestNG here, you don’t need it for using Test’N’Groove since this dependency is automatically added when testFramework is set to ‘testng’.
Currently the list of amendable properties is:
groupId: ''
artifactId: ''
version: ''
sourcePath: 'src'
mainSourcePath: '${properties.sourcePath}${System.properties.'file.separator'}main'
testSourcePath: '${properties.sourcePath}${System.properties.'file.separator'}test'
targetPath: 'target' ,
mainCompilePath: '${properties.targetPath}${System.properties.'file.separator'}classes'
testCompilePath: '${properties.targetPath}${System.properties.'file.separator'}test-classes'
testReportPath: '${properties.targetPath}${System.properties.'file.separator'}test-reports'
metadataPath: '${properties.mainCompilePath}${System.properties.'file.separator'}META-INF'
javaCompileProperties: [source: '1.3', target: '1.3', debug: 'false']
groovyCompileProperties: [:]
compileClasspath: []
testClasspath: []
compileDependencies: []
testDependencies: []
testFramework: 'junit'
testFrameworkVersion: '3.8.2'
testFrameworkClassifier: 'jdk15'
packaging: 'jar'
deployURL: ''
deploySnapshotURL: ''
deployId: 'dav.codehaus.org' ,
manifest: [:] ,
manifestIncludes: [] ,
Options for testFramework are currently ‘junit’ and ‘testng’. Options for packaging are currently ‘jar’ and ‘war’ (but the war packaging has not been tested).
NB The Maven target set is a work in progress. Currently it seems to work for simple Maven structured projects, but it does not yet have all the plugin control facilities of Maven itself. If you find anything that is missing or doesn’t work, please create a JIRA issue.
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IC 1848: The Soul Nebula
Stars are forming in the Soul of the Queen of Aethopia. More specifically, a large star forming region called the Soul Nebula can be found in the direction of the constellation Cassiopeia, who Greek mythology credits as the vain wife of a King who long ago ruled lands surrounding the upper Nile river. The Soul Nebula houses several open clusters of stars, a large radio source known as W5, and huge evacuated bubbles formed by the winds of young massive stars. Located about 6,500 light years away, the Soul Nebula spans about 100 light years and is usually imaged next to its celestial neighbor the Heart Nebula (IC 1805). The featured image appears mostly red due to the emission of a specific color of light emitted by excited hydrogen gas.
from NASA http://ift.tt/1Rcu039
via IFTTT
Northern Pluto
Gaze across the frozen canyons of northern Pluto in this contrast enhanced color scene, imaged last July by the New Horizons spacecraft. Currently known as Lowell Regio, the region has been informally named for Percival Lowell, founder of the Lowell Observatory. Also famous for his speculation that there were canals on Mars, in 1906 Lowell started the search that ultimately led to Pluto’s discovery. Pluto’s North Pole itself is above and left of center in the the frame. The pale bluish floor of the broad canyon on the left is about 70 kilometers (45 miles) wide, running vertically toward the south. Higher elevations take on a yellowish hue. New Horizon’s measurements have determined that in addition to nitrogen ice, methane ice is abundant across northern Pluto’s Lowell Regio.
from NASA http://ift.tt/1TFkkD3
via IFTTT
The Tarantula Nebula
The Tarantula Nebula is more than a thousand light-years in diameter, a giant star forming region within nearby satellite galaxy the Large Magellanic Cloud, about 180 thousand light-years away. The largest, most violent star forming region known in the whole Local Group of galaxies, the cosmic arachnid sprawls across this spectacular composite view constructed with space- and ground-based image data. Within the Tarantula (NGC 2070), intense radiation, stellar winds and supernova shocks from the central young cluster of massive stars, cataloged as R136, energize the nebular glow and shape the spidery filaments. Around the Tarantula are other star forming regions with young star clusters, filaments, and blown-out bubble-shaped clouds In fact, the frame includes the site of the closest supernova in modern times, SN 1987A, at the lower right. The rich field of view spans about 1 degree or 2 full moons, in the southern constellation Dorado. But were the Tarantula Nebula closer, say 1,500 light-years distant like the local star forming Orion Nebula, it would take up half the sky.
from NASA http://ift.tt/1XPFyyp
via IFTTT
Highest, Tallest, and Closest to the Stars
Fans of planet Earth probably recognize its highest mountain, the Himalayan Mount Everest, on the left in this 3-panel skyscape of The World at Night. Shrouded in cloud Everest’s peak is at 8,848 meters (29,029 feet) elevation above sea level. In the middle panel, stars trail above volcanic Mauna Kea forming part of the island of Hawaii. Festooned with astronomical observatories, its summit lies a mere 4,168 meters above sea level. Still, measured from its base starting below the ocean’s surface, Mauna Kea is over 10,000 meters tall, making it Earth’s tallest mountain from base to summit. At right, beneath the arc of the Milky Way is the Andean mountain Chimborazo in Ecuador. The highest equatorial mountain, the Chimborazo volcano’s peak elevation is 6,268 meters above sea level. But rotating planet Earth is a flattened sphere (oblate spheroid) in shape, its equatorial diameter greater than its diameter measured pole to pole. Sitting nearly on top of Earth’s greatest equatorial bulge, Chimborazo’s peak is the farthest point on the planet’s surface from the center, over 2,000 meters farther from the center of the Earth than Everest’s peak. That makes Chimborazo’s summit the place on Earth’s surface closest to the stars.
from NASA http://ift.tt/1XOFjnl
via IFTTT
USA’s Northeast Megalopolis from Space
Can you identify a familiar area in the northeast USA just from nighttime lights? It might be possible because many major cities are visible, including (right to left) New York, Philadelphia, Baltimore, Washington, Richmond and NorfolkBoston of the USA’s Northeast megalopolis is not pictured. The featured image was taken in 2012 from the International Space Station. In the foreground are two Russian cargo ships with prominent solar panels. This Northeast megalopolis of the USA contains almost 20 percent of the people of the USA but only about 2 percent of the land area. Also known also as the Northeast Corridor and part of the Eastern Seaboard, about 10 percent of the world’s largest companies are headquartered here. The near continuity of the lights seem to add credence to the 1960s-era prediction that the entire stretch is evolving into one continuous city.
from NASA http://ift.tt/1QxN7Ei
via IFTTT
A Supernova through Galaxy Dust
Telescopes around the world are tracking a bright supernova that occurred in a nearby dusty galaxy. The powerful stellar explosion was first noted earlier this month. The nearby galaxy is the photogenic Centaurus A, visible with binoculars and known for impressive filaments of light-absorbing dust that cross its center. Cen A is featured here in a high-resolution archival Hubble Space Telescope image, with an inset image featuring the supernova taken from the ground only two days after discovery. Designated SN2016adj, the supernova is highlighted with crosshairs in the inset, appearing just to the left of a bright foreground star in our Milky Way Galaxy. This supernova is currently thought to be of Type IIb, a stellar-core-collapse supernova, and is of high interest because it occurred so nearby and because it is being seen through a known dust filament. Current and future observations of this supernova may give us new clues about the fates of massive stars and how some elements found on our Earth were formed.
from NASA http://ift.tt/1Q8JuoZ
via IFTTT
M82: Galaxy with a Supergalactic Wind
What’s lighting up the Cigar Galaxy? M82, as this irregular galaxy is also known, was stirred up by a recent pass near large spiral galaxy M81. This doesn’t fully explain the source of the red-glowing outwardly expanding gas, however. Evidence indicates that this gas is being driven out by the combined emerging particle winds of many stars, together creating a galactic superwind. The featured photographic mosaic highlights a specific color of red light strongly emitted by ionized hydrogen gas, showing detailed filaments of this gas. The filaments extend for over 10,000 light years. The 12-million light-year distant Cigar Galaxy is the brightest galaxy in the sky in infrared light, and can be seen in visible light with a small telescope towards the constellation of the Great Bear (Ursa Major).
from NASA http://ift.tt/20NADOn
via IFTTT
Where Your Shadow Has Company
Want to take a relaxing interstellar vacation? Consider visiting Kepler-16b, a world in a binary star system. In fact Kepler-16b is the first discovered circumbinary planet. It was detected in a wide 229 day orbit around a close pair of cool, low-mass stars some 200 light-years away. The parent stars eclipse one another in their orbits, observed as a dimming of starlight. But Kepler-16b itself was discovered by following the additional very slight dimming produced during its transits. Like sci-fi planet Tatooine of Star Wars fame, two suns would set over its horizon. Still, Kepler 16b is probably not a Tatooine-like terrestrial desert world. Instead, Kepler 16b is thought to be a cold, uninhabitable planet with about the mass of Saturn and a gaseous surface … so plan to dress accordingly. Or, choose another Visions of the Future vacation destination.
from NASA http://ift.tt/1TwmINu
via IFTTT
NGC 2403 in Camelopardalis
Magnificent island universe NGC 2403 stands within the boundaries of the long-necked constellation Camelopardalis. Some 10 million light-years distant and about 50,000 light-years across, the spiral galaxy also seems to have more than its fair share of giant star forming HII regions, marked by the telltale reddish glow of atomic hydrogen gas. The giant HII regions are energized by clusters of hot, massive stars that explode as bright supernovae at the end of their short and furious lives. A member of the M81 group of galaxies, NGC 2403 closely resembles another galaxy with an abundance of star forming regions that lies within our own local galaxy group, M33 the Triangulum Galaxy. Spiky in appearance, bright stars in this colorful galaxy portrait of NGC 2403 are in the foreground, within our own Milky Way.
from NASA http://ift.tt/1PWr22G
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Hitomi Launches
On February 17 at 5:45pm JST this H-IIA rocket blasted skyward from JAXA’s Tanegashima Space Center located off the southern coast of Japan, planet Earth. Onboard was the ASTRO-H X-ray astronomy satellite, now in orbit. Designed to explore the extreme cosmos from black holes to massive galaxy clusters, the satellite observatory is equipped with four cutting-edge X-ray telescopes and instruments sensitive to photon energies from 300 to 600,000 electron volts. By comparison, visible light photon energies are 2 to 3 electron volts. Following a tradition of renaming satellites after their successful launch, ASTRO-H has been newly dubbed “Hitomi”, inspired by an ancient legend of dragons. Hitomi means “the pupil of the eye”.
from NASA http://ift.tt/1Qo1pqI
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Automation Icon
Automation
Life is too nice to do things twice.
5 Stories
All Topics
Arthur Busser padok.fr
Getting started with GitHub Actions
In this post Arthur covers the core concepts, the question “Should you use GitHub Actions?”, and a step-by-step tutorial to build a functional CI/CD pipeline using GitHub Actions.
If you are already using GitHub to host your project’s source code, getting started with GitHub Actions is effortless. The fact that it integrates fully with the entire GitHub ecosystem means your team can double down on using the platform as a significant part of your software development process.
Overall, my opinion is that GitHub Actions is worth a try. Whether this is the automation system best suited for your team depends on your specific needs.
Vue.js n8n.io
An "open source" alternative to Zapier
n8n (a numeronym for “nodemation”) is a node-based workflow automation tool. The reason for the square quotes around “open source” is because it has a Commons Clause attached to its Apache 2.0 license, which means you can do anything you want with the source code except make money with it. Since n8n itself is built on open source tech such as TypeScript and Vue.js, this is a nice touch by the author in the FAQ:
As n8n itself depends on and uses a lot of other Open Source projects it is only fair and in our interest to also help them. So it is planed to contribute a certain percentage of revenue/profit every month to these projects. How much exactly is not decided yet.
An "open source" alternative to Zapier
0:00 / 0:00
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write a simulator that reads a memory trace and simulates the action of a virtual memory system with a single level page table.
Your task is to write a simulator that reads a memory trace and simulates the action of a virtual memory system with a single level page table. Your memory system should keep track of which pages are loaded into memory. • As it processes each memory event from the trace, it should check to see if the correspond-ing page is loaded. • If not, it should choose a victim page in memory to replace. • If the victim page to be replaced is dirty, it must be saved to disk before replacement. • Finally, the new page is loaded into memory from disk, and the page table is updated. This is just a simulation of the page table, so you do not actually need to read and write data from disk. When a simulated disk read or write occurs, simply increment a counter to keep track of disk reads and writes, respectively. You must implement the following page replacement algorithms: • FIFO: Replace the page that has been resident in memory longest. • LRU: Replace the page that has been resident in memory oldest.
find the cost of your paper
Complete independent research and review two (2) to three (3) online end-user license agreements.
Complete independent research and review two (2) to three (3) online end-user license agreements. Compare and contrast each EULA with each other. In your response, please consider the following: ·….
Write a SQL query that identifies the number of prescriptions grouped by drug name.
ALY6030 Final Project Assignment – Pharmacy Claims Due End of Week 6 Background: The excel file “ALY 6030 Final Project Data Set.xlsx” contains sample pharmacy claims for made-up members of….
Create a JavaFX program to allow a user to query the Northwind database.
Create a JavaFX program to allow a user to query the Northwind database. You should be able to perform the following functionality using the program: Print order total (not….
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Bienvenido a Java Mexico
Java México es una comunidad de desarrolladores mexicanos en el lenguaje Java.
Este sitio es colaborativo, automáticamente al registrarte obtienes un Blog para compartir tus conocimientos o información acerca del lenguaje. Antes de publicar en tu blog o los foros por favor lee los lineamientos de publicación.
Para dudas y problemas con respecto al lenguaje Java puedes visitar los Foros de Discusión.
También puedes responder nuestra encuesta para saber en que estado vives!
Harvesting verticles parte 1.
> ¿Qué es Vert.x?
Es una plataforma orientada a crear aplicaciones web, empresariales, móviles, que es poliglota, simple, escalable, concurrente, o por lo menos es lo que dice la portada de la pagina del proyecto, también puedes ver lo que dice wikipedia al respecto y dentro de la documentación comentan también este teman. Y la versión resumida
Episodio 5 de la temporada 1 - ViveCodigo.org – Coding Dojo (Codebreak)
Esta vez en la entrega de Vivecodigo les presentamos nuevamente un coding dojo, en el cual se desarrollo un juego llamada code breaker con algunos destacados invitados.
La dinámica fue pasar una a uno para ir desarrollando el juego, el cual fue en base Test-driven development (TDD) por lo cual cada uno de los invitados pudo aportar elementos para el desarrollo de esta solución.
Al concluir se platico sobre la dinámica y las dificultades que existieron, con lo cual pudieron realizar una retrospectiva de lo que mas les agrado y no de este coding dojo, en base a l esfuerzo y las ideas que apostaron cada uno de ellos.
Un video sin duda muy entretenido y con elementos enriquecedores.
Espero disfruten este contenido. Sigan enviándonos sus comentarios tambien nos pueden seguir en nuestro feed de vivecodigo.org.
Probar una cadena de llamadas con Mockito
Como @neodevelop explica en esta entrada: http://www.javamexico.org/blogs/neodevelop/pruebas_de_unidad_con_mockito... se puede probar con Mockito si un metodo fue llamado o no utilizando verify(objeto).nombreDelMetodo();
Utilice varias veces esa comprobación hasta que me fallo recientemente en un escenario como el siguiente: quería ver si mi nuevo método PhoneManager.getPhone(id) estaba invocando el método Profile.getPhone()
// FAIL
// prueba que el getter getPhone fue invocado:
class PhoneManagerTest {
@InjectMocks PhoneManager phoneManager;
@Mock Profile profile;
...
@Test
public void testGetPhone() {
Assert.assertEquals("(55) 5658-1111", phoneManager.getContactPhone(1));
Mockito.verify(profile).getPhone();
}
El problema es que profile no es un atributo de PhoneManager sino que es obtenido con una cadena de llamadas como esta:
Profile profile = phoneManager.getAccountAdapter().getProfileService().getProfileById(id);
Preprocesadores para desarrollar las páginas Web y PreprocessJS
Hace algunos dias, platicando con algunos desarrolladores que nunca habian programado una página web dinamica con algunas de las tecnologias mas comunes para realizarlas, me pregunto uno de ellos, ¿en si como funcionaba un JSP ó un PHP ó un ASP o un GSP ...? .
La respuesta que le di fue desde luego algo minimalista, por que se que esas tecnologias funcionan gracias a los framewroks y a los lenguages subyacentes que permiten crear el contenido dinámico de las páginas web, plus los servidores web (apache, tomcat, jboss, websphere, iis etc.) que permiten las conexiones en internet via sockets y el protocolo TCP/IP.
Y lo que de una o de otra forma le comente es que esos lenguages de scripting en gran medida(hablando en la capa de desarrollo de aplicaciones web) preprocesaban archivos que tienen incrustado HTML, Javascript y un lenguaje de alto nivel como Java, Groovy, C#, Vb.Net, o más propietarios como el PHP que es (C syntaxis like).
Java para principiantes (Ambito o alcance de las variables en Java)
Hola a todos, en mi blog quiero ayudar a varios jóvenes que se inician en el mundo de la programación en Java, así que he creado algunos post que quiero compartir con ustedes, esto con el fin de obtener críticas y consejos para mejorarlo, sin más preámbulo acá esta el artículo:
El alcance de las variables es una de las consultas que más se presentan en los blogs, adicionalmente son la causa de dolores de cabeza de algunos desarrolladores novatos, por lo tanto, hemos creado este post con el fin de explicar de una forma clara cual debe ser el comportamiento de las variables locales, globales, de clase de método etc.
Inicialmente crearemos una clase con el siguiente código:
public class EjemploAmbito {
//Declaración de variable de clase
private int edad;
//Declaración del método main
public static void main(String[] args) {
EjemploAmbito ambito = new EjemploAmbito();
ambito.setEdad(25);
System.out.println("La edad es " + ambito.getEdad());
}
//Declaración del getter de edad
public int getEdad() {
return edad;
}
//Declaración del setter de edad
Entorno de desarrollo IDE o editor de texto?
Siempre había pensado que era mucho mejor trabajar en un IDE, pues me permite crear las interfaces gráficas con mayor facilidad, sin embargo mi visión del universo de la programación estaba muy sesgada, pues la mayor parte de mi tiempo programando he usado los entornos de desarrollo.
Pues bien, aunque en la encuesta los vencedores fueron los IDE, y entiendo el por que, me sorprendió la cantidad de votos que tuvieron los procesadores de texto minimalistas, (les pido perdonen mi entusiasmo, este blog tiene pocas semanas de creado, para mi 47 votos son un número enorme!!) , y fue así como consulte a varios de los programadores que los usan para que me explicaran las ventajas que tienen y por que los eligieron.
En primer lugar, la mayoría de los desarrolladores que usan estos programas tienen una gran inclinación por el desarrollo web, y claro, tanto Gedit como Sublime Text manejan HTML5 y CSS3; es cierto que Netbeans y Eclipse han expandido sus fronteras buscando que los desarrolladores los elijan no solo para trabajar en Java sino también para trabajar en HTML, PHP, Ruby etc. Pero créanme que a los desarrolladores web no se los ganan tan fácil.
Creación de un archivo JAR usando JarOutputStream
Creación de un archivo JAR usando JarOutputStream
Alguna vez trate de generar un JAR desde mi aplicacion, pero no lo logre en ese momento, por otros motivos me encontre con la clase JarOutputStream la cual me permite hacer eso, generar un JAR indicandole los paquetes y clases que contendra e inclusive creandole el archivo manifiesto.
Hoy les traigo un sencillo ejemplo de como podemos crear un JAR indicando la carpeta que contiene los archivos .class.
Imagenes
Codigo
package clases;
import java.awt.BorderLayout;
import java.awt.event.ActionEvent;
import java.awt.event.ActionListener;
import java.awt.event.ItemEvent;
import java.awt.event.ItemListener;
import java.io.BufferedInputStream;
import java.io.File;
import java.io.FileInputStream;
import java.io.FileOutputStream;
23a. reunión de @springhispano, @grailsmx, @artesano_soft y @scalamug
El pasado 26 de Septiembre se llevo a cabo la 23a. reunión de la comunidad, en donde tuvimos la presencia de Alvaro Videla(@old_sound), un desarrollador Erlang que esta trabajando en RabbitMQ y es autor del libro RabbitMQ in Action.
En esta sesión Alvaro nos comparte su experiencia en la charla: "Scaling applications with RabbitMQ"
Esta reunión fue llevada hasta ustedes por Makingdevs que adicionalmente obsequio libros de "RabbitMQ in action" y además regalo una libreta personalizada a los participantes de la reunión así que no te pierdas la próxima reunión.
Leer mas:http://springhispano.org/?q=node/3099
Episodio 4 de la temporada 1 – Erlang con Alvaro Videla – @old_sound
Bienvenidos sean a esta nueva emisión del podcast el episodio numero 4 de la temporada numero 1.
Alvaro Videla (@old_sound) es un desarrollado uruguayo muy experimentado que esta actualmente esta trabajando en RabbitMQ y en RabbitMQ Simulator, además es el autor del libro de “RabbitMQ in action”; aprovechando su visita a México tuvimos la oportunidad de entrevistarlo para que nos hablará acerca de su trayectoria y también del lenguaje de programación Erlang.
Es interesante conocer la historia de Alvaro, así como también, ver la facilidad con la que expresa el paradigma con el que se maneja Erlang, el cual en propias palabras de Alvaro, es único aunque Erlang entre en la categoría de lenguajes funcionales.
Una conversación muy entretenida, informativa y enriquecedora, no se lo pierdan.
¡Espero lo disfruten! y apreciamos mucho cualquier comentario que nos puedan dejar, pronto mas capítulos de la temporada 01.
Programar es...
Programar es ...
1. Vivir constantemente presionado.
2. Tener 0 vida social (o muy poca).
3. Repetir rutina tras rutina (jeje).
4. Conocer gente extraña...
5. Muchas horas sin dormir en casa ...
6. Reuniones aburridas...
7. Enojos constantes...
8. Querer replantear nuestra vida...
"¿que hubiera sido de mi vida si hubiera sido futbolista?"
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Special Feature: Using Essential Oils to activate the mind
Special Feature: Using Essential Oils to activate the mind
Special Feature
Memory and Essential Oils
Oils to activate the mind
Our sense of smell is not redundant
THE ACUITY of the olfactory system in early humans was more developed than in today’s population. Modern chemical life has done much to anaesthetise our smell sense and render it more or less redundant.
Yet the human brain can remember more than 50,000 different scents; and every one of these individually shaped smell molecules has to fit like a jigsaw into its own exact space on the olfactory bulb.
Before the man-made chemical world held sway, plants provided most of the smell signatures, which were read discerningly by early peoples to determine certain outcomes.
Even if today’s humans are unaware of it, plant and human pheromones can profoundly affect us subliminally, driving our feelings, actions and habits.
As evolution took shape, smell became relatively less crucial for survival and accordingly the part of the human brain responsible for smell and primitive emotions became less important.
The new, supposedly superior, brain evolved over the primitive ‘old brain’ structures, developing and heightening both old and newly advanced senses and modifying instincts and emotions by the development of mind.
This brain development also created a larger memory storage capacity, expanding to include everything in the vast and complex human experience.
Instinct is the nose of the mind
- Delphine de Girardin
The past comes alive
The act of smelling a plant immediately sets the mind to work, transporting the scent here and there; a catalysing complex theatre throughout the brain as old memories and old connections are recognised.
Memories, as well as smell, are stored in the Limbic system of the brain.
This is why memories, imagination and old sentiments are more readily reached through smell than through any other channel.
We become aware of memories and store them from the very first day of our existence and relate them to specific situations and moods.
We each have our own personal connection to every smell. A certain pleasant smell during a memorable childhood experience can be relived many years later when the same smell is smelt again and the same sense of wellbeing is felt.
We can choose to consciously recollect certain smells to intensify old memories, but we are not at the mercy of odour memories.
We can reprogram our smell memory computer in order to enhance our lives. This is where using essential oils comes into play. They support intellectual activity by supporting our memory.
Smell memory the strongest
Is the elephant’s legendary long memory due to its extraordinary dependence upon its long nose?
Studies show that long-term odour memory is stronger than visual memory, partly because of our primitive, self-preservation instincts; but also because a subconscious smell connection uses less stimulus discrimination than does conscious sight.
There are more innate preconceptions with smell evaluations that are often irrational and inclined to stimulus generalisation.
The physical and emotional features of human nature are slower to learn, but also slower to forget.
Learned associative smell, which is employed in aversion therapy and positive reinforcement, leaves a lasting impression and smells can be useful therapeutically to recall memory even in cases of amnesia or comatose conditions.
Plant smells help evoke memories
Memory is a very complex process involving far more of the brain than scientists initially thought.
The concept and function of memory involves more than the temporary or permanent, planned or incidental recall; it includes the expansion of memory itself, the increasing capacity to remember and to do so independently and consciously improving our human intelligence.
Essential oils enervate the brain and the entire central nervous system; the smells of basil, peppermint and rosemary have the ability to stimulate not just recall, but the mental powers of memorisation and concentration.
Essential oils evoke and enhance intellectual, emotional and physical faculties of awareness and discrimination, according to character of the oil employed to a corresponding feature of human nature and elsewhere in the body.
Reinforced learning when stimulated
The limbic system is a set of interconnected pathways in the brain related to the hippocampus and some primitive areas of the cerebrum having to do with smell, memory, oral movements linked to feeding and primitive exploratory behaviour, fundamental drives for survival and emotional and visceral responses.
The limbic brain also contains the ‘pleasure centre’; which reinforces learning when stimulated.
It works in tandem with the hippocampus where it forms the control centre, coordinating all sensory input into a coherent whole.
The hippocampus is located deep within the brain, behind the eyes and between the ears and pulsates a mysterious theta brain-wave rhythm that signals its functioning in modifying emotion and processing memory.
This is why using essential oils can have such direct and efficacious effects in changing to positive mind states.
Memory storage unit
The hippocampus has a primary role in processing events and experiences into memories, but it is not the only or final repository of long-term memory.
Memory processing and storage also occurs elsewhere in previously unsuspected areas of the brain.
When a particular sensory stimulus enters the same area of the brain, entire collections of mutually stimulating neurons assemble, into similar and dependable patterns; according to the continual stimulus reinforcement, making memory initially possible.
The important central switchboard of the limbic system and hippocampus connects and coordinates into a coherent whole the different stimuli from the different brain locations: sounds in the auditory cortex, images in the visual cortex.
In this manner, the hippocampus serves as a kind of transit station in which memories linger for an extended state between short-term and long-term memory.
Odour or smell memory does not necessarily engage other brain areas involved in the memory process, unless smell occurs coincidental with auditory, visual or thought stimuli and processes.
The more it coincides, the more likely it is to be remembered, retained in the short to long term memory complex to be processed first through the limbic system and hippocampus.
Interestingly, the hippocampus is also the part of the brain with the greatest degree of plasticity and appears to be absolutely necessary for making new memories or creating new neural pathways.
It appears to be very important in converting things that are ‘in your mind’ at the moment (in short-term memory) into things that you will remember for the long run (long-term memory).
If we didn’t have the hippocampus we couldn’t live in the present: we would be stuck in the past of old memories.
Increase your memory recall
Aromatherapy is extremely useful in compensating for any dysfunction in the memory as it not only affect a person’s mood but can also prove powerful enough to evoke memories that we are happy to recall.
Rosemary in particular has been found to increase blood circulation around the body and to the brain, providing an excellent stimulant that enables the memory to function more sharply. It is also an aroma that can help relieve stress and relax worries. When our central nervous system is calm and centred, we are better able to access deeper memories that are meaningful to process so we might progress forward with our lives.
Memory recall is accelerated when a past event is associated with a smell. That’s why a whiff of a certain scent can send us back in time and carry with it images and feelings associated with that event. Next time we need assistance to access some elusive fact, aromatherapy can trigger your memory.
Rosemary, for instance, has a long history of increasing memory, concentration and creativity, while Japanese research has confirmed it to be a brain stimulant. Other mental stimulants are sage, basil and bay laurel.
Rose serves our memory by allowing us to embrace our grief process and let go of the pain that could entrap our hearts for too long.
Jasmine deeply relaxes and removes us from the intense emotional attachment to past hurtful memories.
Inhale one of the recommended essential oils while studying for a test or attending a class and when you need to recall the information, simply smell the same scent.
For many people the scent of certain plants can revive memories with a vividness that nothing else can equal, for the sense of smell can be extraordinarily evocative, bringing back pictures as sharp as photographs of scenes that and left the conscious mind.
- Delphine de Girardin
Oils for Memory
Rosemary, sage, bergamot, clary sage, cypress, peppermint, basil, bay, juniper, lemon, rose, jasmine are very efficacious. In general though, all essential are capable of stimulating memory and brain receptivity.
Essence of Tinderbox in new light
We discover ourselves to be that light which has no apparent source, yet is the Source of everything.
FOREMOST, Tinderbox prescribes to the underlying principal that all people inherently contain within them a spark of the divine, and that we are all biologically programmed to spiritually evolve.
We are born for illumination, even if we are unaware of this intrinsic human impulse, just like a plant, we are all growing towards the light. At the Tinderbox we are wholly supportive of your journey to Self-awakening and hope that we have something inspirational to offer you as help along the ongoing path; something that encourages you to tend lovingly to the emerging story of your life.
Yes we do make a high quality range of artisanal herbal products with much care and good intention. However that is not all that Tinderbox is about; we very much strive to promote the holistic lifestyle whereby all aspects of the human being: physical, emotional, mental and spiritual are honoured. Indeed the products are based on the belief that all human beings are their own healers by nature and that they just need to look within to discover the wherewithal in order for healing to begin.
Tinderbox is about transformation; we create pure botanical products that promote a positive shift in your life in some small or significant way, each item mindfully designed to heal the whole person, to nurture, soothe, relax, indulge and elevate the mood and consciousness of the individual. Real healing is about transformation, about making us whole again and a return to whom we truly are.
Tinderbox - harnessing the wisdom and vitality of plants for human transformation.
A new day dawns @tinderbox.com.au
Tinderbox is an ever evolving, well-spring of creativity that flows continually, adapting and adjusting to ‘the sea of change’ that is a reality when working with plants.
The rough edges of an old recipe might be refined; a discontinued bottle may catalyse a fresh start; or we awaken new spirit in an existing product with a change of look.
Today we celebrate our new website at tinderbox.com.au which showcases our artwork, proudly displays our products and provides a plethora of information about the plant world.
You can also follow what inspires our staff on facebook and let the Tinderbox Sparks take you behind the scenes of our Balingup workshop.
We invite you to ride the winds of change with us. We hope you enjoy the journey as much as we will.
Download .pdf version
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Rätsel des Alltags
Warum wird beim Versenden einer SMS immer die Nummer übertragen, während man sie aber bei Telefongesprächen mit dem Handy unterdrücken kann?
»Da die SMS-Technik ursprünglich nicht kommerziell verwendet werden sollte, wurde sie technisch sehr einfach aufgebaut. Deshalb muss man heute auf beim Telefonieren übliche Zusatzfunktionen wie die Unterdrückung der Rufnummer verzichten. Das sehen auch die GSM-Standards vor, auf die sich die Mobilfunkanbieter 1990 weltweit geeinigt haben.«
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PoS - Proceedings of Science
Volume 236 - The 34th International Cosmic Ray Conference (ICRC2015) - Cosmic Ray Physics: Theory, Models and Simulations
On the primary model to explain the relation between a rigidity-dependent spectral hardening of proton and helium spectra and
J. Huang
Full text: pdf
Published on: August 18, 2016
DOI: https://doi.org/10.22323/1.236.0546
How to cite
Metadata are provided both in "article" format (very similar to INSPIRE) as this helps creating very compact bibliographies which can be beneficial to authors and readers, and in "proceeding" format which is more detailed and complete.
Open Access
Creative Commons LicenseCopyright owned by the author(s) under the term of the Creative Commons Attribution-NonCommercial-ShareAlike.
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Just JavaScript - Parameters, and Destructuring
Written by Ian Elliot
Monday, 05 March 2018
Article Index
Just JavaScript - Parameters, and Destructuring
Rest, Default Parameters, Destructuring
There are many ways in which JavaScript's approach is different from standard, run of the mill, class-based languages, but some of them go unnoticed. Take the whole subject of parameter passing - JavaScript does it different.
This is an extract from the book Just JavaScript by Ian Elliot.
Buy Now: from your local Amazon
Just JavaScript
An Idiomatic Approach
JustJavaScriptSmall
A Radical Look At JavaScript
Most books on JavaScript either compare it to the better known class based languages such as Java or C++ and even go on to show you how to make it look like the one of these.
Just JavaScript is an experiment in telling JavaScript's story "just as it is" without trying to apologise for its lack of class or some other feature. The broad features of the story are very clear but some of the small details may need working out along the way - hence the use of the term "experiment". Read on, but don't assume that you are just reading an account of Java, C++ or C# translated to JavaScript - you need to think about things in a new way.
Just JavaScript is a radical look at the language without apologies.
Contents
1. JavaScript – Essentially Different
2. In The Beginning Was The Object
3. Real World Objects
4. The Function Object
Extract - The Function Object
Extract - Function Object Self Reference
5. The Object Expression
6. Function Scope, Lifetime & Closure
7. Parameters, Returns and Destructuring
Extract - Parameters, and Destructuring
8. How Functions Become Methods
9. Object Construction
Extract: - Object Factories ***NEW!
10. The Prototype
Extract - ES2015 Class and Extends
11. Inheritance and Type
12. The Search For Type
13. Property Checking
Buy Now: from your local Amazon
Also by Ian Elliot
JavaScript Async: Events, Callbacks, Promises and Async Await
Just jQuery: The Core UI
Just jQuery: Events, Async & AJAX
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<ASIN:1871962560>
<ASIN:1871962501>
<ASIN:1871962528>
In this short chapter we look at some of the more practical aspects of using Functions in JavaScript. There is nothing deep and philosophical about the ways that we can use JavaScript’s functions but it does give you some idea of how powerful the idea that “every thing is an object” and the weak typing are.
Object Parameters
Another big difference between JavaScript and most other languages is that parameters in functions and return values can be objects of any type – in fact it is easier to forget ideas of type and simply regard parameters as objects.
This has the effect of also removing any ideas of function signature i.e. the types of the parameters and hence of function overloading. If you are familiar with languages where both of these ideas are central to object oriented programming this will seem to be a big loss however what you have in return is the idea that a function can be written to deal with any objects that happen to be passed to it.
For example in other languages you might well have to write a function to add two integers and another to add two floats. If you want a function that works with both integers and floats then you have to invent generics and deal all of the complications that this brings. In JavaScript you can simply write:
function add(a,b){
return a+b;
}
and use the function to add two integers or two decimal valued numbers or even two strings although in this case the result is concatenation rather than addition. What is more you can pass any two objects to the add function without generating any compile time error. For example:
alert(add({},{}));
There are no restrictions on what sort of object you can pass to a function as a parameter and no restriction on what the function can return.
This freedom can seem like an invitation to chaos but in there are many simplifications that also result. For example, there is no need to event the complex subject of generics because all JavaScript functions are generic.
The whole idea of typeless programming is taken up in later chapters but this is where it first makes itself felt.
Arguments Object
The fact that parameters are objects is a powerful feature but, as mentioned in an earlier chapter, in fact the entire parameter list is an object.
Every function, apart from arrow functions, has a local arguments object which contains all of the parameter values passed to the function in something that looks like an Array. What is more the function declaration does not determine what can be passed to the function at the point of use.
That is function declarations do not need to specify any parameters at all and you can call any function with any list of arguments you care to use.
For example:
function sum(){
var total=0;
for(var i=0;i<arguments.length;i++){
total+=arguments[i];
}
return total;
}
which will add any number of parameters you care to specify. Notice that the declaration does not specify anything at all, not event their number, about the parameters that the function expects. You can call it using:
alert(sum(1,2,3,4));
or with any number of parameters of any type.
The arguments list is processed by the JavaScript engine to produce an object that is like an Array.
This is really all we need to write any function and indeed other languages struggle to provide this level of flexibility.
So why do we have a parameter list in function declarations?
The simple answer is to make JavaScript functions look more like functions in other languages and to make simple functions easier to write. Any parameter list that you specify in the declaration is used to deconstruct the arguments object into named local variables.
For example:
function sum(a,b,c){
}
unpacks the first three parameters you pass into a, b and c respectively. If you pass fewer than three then any parameters that do not have values are undefined. If you pass more than three then only the first three values are used in the local variables but of course all of the values are still available in the arguments object.
This unpacking or destructuring of the arguments object really is a good way to think about how parameters work in JavaScript. For example there is a two way connection between the parameter variables and the arguments object. If you change the arguments object then the value in the variable changes and vice versa.
For example:
function myFunction(a){
alert(a);
arguments[0]=1;
alert(a);
a=2;
alert(arguments[0]);
}
MyFunction(0);
displays 0, 1 2 and changing arguments changes the associated parameters and vice versa.
Strict Mode
The association between arguments and parameters is broken in strict mode. Any changes to arguments do not change the parameters and vice versa.
Passing An Array To arguments - Spread
If parameters are passed to functions in the arguments array you might be thinking if you can bypass the comma separated list of parameters and simply pass an Array that is used as arguments.?
You can but only if you call the array using either the apply method that every Function object has or you are prepared to use some new syntax introduced with ES2015.
First to pass a parameter array in almost any version of JavaScript you can use apply:
function sum(a,b){
return a+b;
};
var args=[1,2];
sum.apply(null,args);
This passes the args array to the function as the arguments object which is then unpacked into the usual parameters.
Using the ES2015 spread operator … you can write the above as:
function sum(a,b){
return a+b;
};
var args=[1,2];
sum(...args);
The spread operator will unbundle any iterable object like an array and it works in function arguments, elements of array literals and object expressions where key value pairs are needed.
Last Updated ( Monday, 05 March 2018 )
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%0 Journal Article %T Factors associated with the no-reflow phenomenon following percutaneous intervention of saphenous vein coronary bypass grafts %J ARYA Atherosclerosis Journal %I Cardiovascular research institute, Isfahan University of Medical Sciences %Z 1735-3955 %A Hashemi-Jazi, Mohammad %A Hosseini, Sayed Mojtaba %A Gholamrezaei, Ali %D 2017 %\ 10/02/2017 %V 13 %N 5 %P 221-229 %! Factors associated with the no-reflow phenomenon following percutaneous intervention of saphenous vein coronary bypass grafts %K Angioplasty %K Coronary Artery Bypass %K No-Reflow Phenomenon %K Percutaneous Coronary Intervention %K Saphenous Vein %R %X BACKGROUND: We investigated clinical and procedural factors associated with the no-reflow phenomenon following percutaneous coronary intervention (PCI) of the saphenous-vein grafts (SVG). METHODS: A cross-sectional study was done on patients who had undergone PCI of the SVG. Patients’ medical documents were reviewed for demographic, clinical, laboratory, and procedural data. Slow/no-reflow was defined based on the thrombolysis in myocardial infarction (TIMI) grade (0 to 2). Univariate and multiple logistic regression analyses were performed to investigate factors associated with slow/no-reflow and P < 0.050 was considered as significant. RESULTS: A total of 205 patients were studied (81% man, mean ± standard deviation of age was 66.8 ± 9.6 years). Slow/no-reflow was found in 38 (18.5%) patients. High diastolic blood pressure (P = 0.010), leukocytosis (P = 0.017), diffuse lesions (P = 0.007), degenerated SVG (P < 0.001), proximal lesions (P < 0.001), thrombosis (P = 0.013), and lower number of used stents during procedure (P = 0.032) were associated with slow/no-reflow in unadjusted analyses. Factors independently associated with slow/no-reflow were pre-procedural high diastolic blood pressure with odds ratio (OR) = 3.858 [95% confidence interval (95% CI), 1.157-12.860], degenerated SVG with OR = 5.901 (95% CI: 1.883-18.492), proximal lesions with OR = 5.070 (95% CI: 1.822-14.113), pre-intervention TIMI grade with OR = 0.618 (95% CI: 0.405-0.942), number of used stents for PCI with OR = 0.074 (95% CI: 0.011-0.481) for > 1 stent, and length of stents used for PCI with OR = 0.100 (95% CI: 0.019-0.529) for > 30 mm stents. CONCLUSION: This study on the clinical and procedural factors associated with the slow/no-reflow phenomenon following PCI of the SVG can be used in risk estimation of this serious complication and tailoring preventive strategies to at-risk patients. %U https://arya.mui.ac.ir/article_10598_b602cc33882d90518756f90565f5b745.pdf
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Cough Drop
A cough drop is medicinal tablet designed to deliver active ingredients which suppress or relieve the cough reflex. They are made just like hard candies; ingredients are mixed together, they are cooked, cooled, and packaged. First developed during the eighteenth century, cough drops have become a significant part of the $2 billion cough and cold market.
Background
Anyone who has gotten sick knows the sensation of a cough. It is a natural reflex that helps protect the body from infections. It plays an important role in clearing the throat and other air passages of secretions and irritating particles. These particles include dust, food, liquids, and mucus. A cough occurs in three distinct steps. It typically begins with a deep breath which draws air into the lungs. The vocal cords spontaneously close thereby sealing the windpipe. Next, the air is compressed by the tightening of the expiratory muscles. The vocal cords are suddenly opened and the air trapped in the lungs is rapidly expelled along with any foreign debris in the windpipe.
Coughs associated with colds can be either productive or nonproductive. A productive cough helps clear the respiratory passages of the lung. A nonproductive cough is brought on by a minor irritation and has a limited benefit. It is the nonproductive cough that cough drops are designed to sooth or suppress.
The are two types of active ingredients in a nonprescription cough drop including expectorants and cough suppressants. An expectorant is a material that aids in the removal of phlegm from the respiratory tract. It works by blocking the sensory nerves that are involved in triggering a cough. While many expectorants are available, data about their functionality is not. Some clinicians even question whether expectorants are effective. Antitussives, which are cough suppressants, work in a variety of ways affecting either the lungs, muscles, or brain.
History
Using syrups and herbal teas to control coughing has been known since antiquity. An ancient Hebrew text suggests the use of goat's milk for this reason. In the second century, Galen was perhaps the first to report an effective cough suppressant. Cough drops originally developed from candy. The first hard candies were produced during the fourth century. Since sugar was so expensive, these products were typically a luxury item available only to the rich. Over the years, sugar crops were planted in North America and throughout the world. Sugar refiners were established, and the price of sugar was reduced, making it available to everyone by the eighteenth century.
While the active ingredients in a cough drop were known for centuries, it was not until the nineteenth century that the cough drop was born. One of the first mass-produced cough drops was the Smith Brothers cough drop. According to the company, James Smith was operating a restaurant when a journeyman introduced him to a formula for a cough candy. He mixed up a batch in his kitchen and was able to quickly sell them. Demand for his product grew and he began advertising in 1852. He enlisted the aid of his two sons who helped mix batches and sell them on the streets of Poughkeepsie, New York. They inherited the business in 1866 when James Smith died, and renamed the company Smith Brothers. During this time, they sold their cough drops in large glass bowls. To prevent imitators, they developed a unique package in 1872 that was filled at the factory. In 1922, menthol cough drops were introduced. Over the years, a variety of manufacturers have developed their own cough drop formulas. Each one has tried to improve the flavor and efficacy of their product.
Raw Materials
Cough drops have two categories of ingredients. One type makes up most of the cough drop while the other is the active, or functional, ingredients. The major portion of cough drops is made up of ingredients found in typical hard candy recipes. The essential ingredients include sugar, corn syrup, acids, colors, and flavors. Sugar is a disaccharide compound called sucrose. It is obtained primarily from sugarcane or sugar beets by an extraction process. In a cough drop recipe, sugar crystals are usually used. Sugar is responsible for the physical structure of the cough drop along with its sweet taste and mouthfeel.
Corn syrup is a main component of cough drops. It is a mixture of sugars that is composed of polysaccharides, dextrose, and maltose. The main reason it is used is to control the crystallization of sugar. It also provides some sweetness and body to the cough drop. Additionally, it reduces the formation of dust from sugar during the blending stage.
To increase the visual appeal of the cough drop various dyes are added. In the United States, these dyes are strictly regulated by the government. Some that are allowed in food products include red dye #40, yellow dye #5, yellow dye #6, and blue dye #1. Natural colorants like caramel coloring are also used. Using only these colorants, the most popular cough drop colors, red and blue, can be produced.
To cover the taste of the active ingredients, various flavoring ingredients are put into cough drop recipes. Both artificial and natural flavors are used. Artificial flavors are mixtures of aromatic chemicals like methyl anthranilate and ethyl caporate. Natural flavors are derived from fruits, berries, and honey. Acids such as citric, lactic, tartaric, and malic acid are also included to modify the flavor.
Various active ingredients can be included in a cough drop recipe. As mentioned previously, these can be either expectorants or antitussives. Some common ingredients are volatile oils such as menthol or eucalyptus oil. Volatile oils, or essential oils, are obtained from parts of a plant through extraction or distillation processes. Menthol is typically isolated from the Mentha arvensis plant or distilled from peppermint oil. It may also be synthetically produced. Menthol has a cooling effect in the mouth that helps to relieve irritation. It is also thought to work as an expectorant. Eucalyptus oil is isolated from the eucalyptus plant. It is believed to have a medicinal effect functioning as an expectorant and a relief agent for minor mouth and throat irritations. Recently, companies have been including zinc in their cough drops. Certain evidence suggests that zinc may be beneficial in fighting symptoms of a cold. Vitamin C is another ingredient that has been included in some brands of cough drops. Other ingredients that may be found are herbals such as echinacea or ginko biloba. Peppermint oil, camphor, and sodium citrate have also been used.
Design
Cough drops, or lozenges, are usually sold as small, hard candy pieces that slowly release their medicine as they melt in the mouth. Chemically speaking, they are a supersaturated solution of water molecules, sugar, and corn syrup. They can be either grained (opaque) or nongrained (clear). While all cough drops are designed to sooth and relieve coughing, some have added ingredients to help fight colds, freshen breath, or clear nasal congestion. Certain cough drops have reduced active ingredients and are created specifically for children. There are a wide variety of flavors, the most popular of which are cherry, honey, and menthol.
The Manufacturing
Process
The basic steps in producing a cough drop are mixing, cooking, cooling-working, forming, cooling, and packaging. Most manufacturers
Much like the manufacture of candy, the basic steps in producing a cough drop are mixing, cooking, cooling-working, forming, cooling, and packaging.
Much like the manufacture of candy, the basic steps in producing a cough drop are mixing, cooking, cooling-working, forming, cooling, and packaging.
have an automated production line connected by a conveyor system.
Mixing
• 1 In this manufacturing step, the ingredients are combined in a large, stainless steel container by compounding personnel. Water is usually pumped directly in to the tank. The sugar, corn syrup, and certain other ingredients are then mixed until they are ready to be cooked.
Cooking
• 2 To produce the cough drop, the moisture level of the mixture must be reduced. Some cough drops have a moisture content as low as 0.5%. There are three types of cookers that are employed. Batch cooking involves a direct-fire cooker. In this method, the heat is applied to the mixture from below and the moisture evaporates into the air. Quicker methods use either a semicontinuous cooker or a continuous cooker that operates under low pressure conditions. In the semicontinuous process, the cough drop mixture is first boiled under atmospheric pressure and then pumped into a second kettle that is a vacuum chamber. It is then rapidly cooked and drawn off for working. Continuous cookers use a scraped-surface heat-exchanger which can cook the cough drop within a few seconds.
Cooling and working
• 3 After cooking, the cough drop mixture is conveyored to cooling slabs. It is cooled to facilitate incorporation of ingredients such as color, flavors, and active ingredients. The cooling slabs are composed of steel and have a built-in circulating water system. Candy plows are also involved. They move the mixture around so some of the hotter areas come in contact with the cooler surface of the slabs. As it cools, the mixture becomes plasticized and it looks like a workable mass similar to dough.
• 4 At this point, the rest of the cough drop ingredients are added. They are poured onto the batch and machines pull and twist the mass, working the ingredients throughout. When everything is adequately combined, the batch is split off and sent through a sizing machine. These devices roll the batch into a cylindrically shaped mass and reduce the diameter to a suitable size. From here, the mass is fed into the forming machines.
Forming
• 5 Various forming machines are available. Typically, cough drops are tablet-shaped products. The cylindrical mass runs through this machine and is cut into smaller pieces. These pieces are then put into a die and stamped to produce the desired shape. The cough drops are then ejected from the die and moved to the finishing phases of production.
Cooling and packaging
• 6 The formed cough drops are rapidly cooled to ensure that they maintain their shape. This is done on a conveyor belt that is equipped with rapidly blowing air jets. From the cooling area, the cough drops are put into packaging. Many manufacturers wrap each cough drop in a wax paper package to prevent them from absorbing moisture from the air. A number of these are then put into a larger bag for final sales. Other manufacturers do not individually wrap their cough drops, but store them in a bulk package. These are typically a wax-coated box that is sealed. To prevent them from sticking together, bulk packaged cough drops are often coated.
Quality Control
As with all food and drug processing facilities, quality control begins by monitoring the characteristics of the incoming ingredients. These ingredients are taken to a quality control lab where they are tested to ensure they meet specifications. Tests include evaluation of the ingredient's physical properties such as appearance, color, odor, and flavor. Certain chemical properties of the ingredients may also be evaluated. Each manufacturer has their own tests that help certify that the incoming ingredients will produce a consistent cough drop. In addition to ingredient checks, the packaging is also inspected to ensure it meets the set specifications.
After production, the characteristics of the final product such as appearance, flavor, texture, and odor are also carefully monitored. The usual test methods involve comparing the final product to an established standard. For example, to make sure the flavor is correct, a random sample may be taken and compared to some set standard. Other qualities such as appearance, texture, and odor may be evaluated by sensory panels, a group of specialists that are trained to determine small differences. In addition to sensory tests, other instrumental measurements are taken.
The Future
Cough drop recipes have changed little since they were first introduced. Most of the advancements have come in the design of the cookers and other processing equipment. It is expected that future improvements aimed at increasing the speed of production will continue to be found. Another area that will be expanded will be the addition of novel ingredients that may provide multiple benefits to the consumer. For example, some cough drop marketers have introduced vitamin C-containing products. These cough drops are intended not only to sooth a cough, but also relieve some of the symptoms of a cold.
Where to Learn More
Books
Alikonis, J. Candy Technology. Westport, CT: AVI Publishing Co., 1979.
Covington, T. Handbook of Nonprescription Drugs. Washington, DC: American Pharmaceutical Association, 1993.
Mathlouthi, M. and P. Reiser, eds. Sucrose: Properties and Applications. London: Blackie and Sons, Ltd., 1995.
Periodicals
Friedman, M. "As Temperatures Drop, Cough Remedies Flourish." Adweek (February, 1989).
Slezak, M. "Warm Weather Cools Cough and Cold Sales." Supermarket News (March 6, 1995).
Perry Romanowski
User Contributions:
Comment about this article, ask questions, or add new information about this topic:
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Cough Drop forum
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[MOL] Tamoxifen [00447] Medicine On Line
[Date Prev][Date Next][Thread Prev][Thread Next][Date Index][Thread Index]
[MOL] Tamoxifen
Tamoxifen has a beneficial effect in approximately 50% of women with
metastatic breast cancer. It reduces cancer recurrence and mortality rates
in stage I and II disease and reduces the risk of new primary cancer in the
other breast. The possibility that the drug may prevent or delay the
development of breast cancer in healthy women with a family history of the
disease has prompted the initiation of large-scale, double-blind controlled
trials of tamoxifen (20 mg/kg/day) in the United States, the United
Kingdom, Italy, and Australia. The US clinical trial, begun in 1992, is the
most ambitious and controversial trial ever undertaken by the National
Cancer Institute (NCI). This $68 million trial is being conducted by the
National Surgical Adjuvant Breast and Bowel Project (NSABP), a group headed
for years by Bernard Fisher at the University of Pittsburgh.
NSABP had signed up some 11,000 healthy women aged 35 to 78 and was
attempting to recruit another 5000 -- half of whom were to receive
tamoxifen for 5 years, and half to receive placebo, with follow-up for 7
years -- when NCI suspended the trial. Government audits had turned up
irregularities in NSABP data (in particular, data concerning the merits of
lumpectomy versus mastectomy). As a result, NCI suspended all NSABP
clinical trials, including the tamoxifen study, and forced the resignation
of Fisher and his deputy, Carol Redmond. Currently NSABP is installing a
new data auditing system, forming a new management team, and electing new
leaders. [Anderson C. Science. 1994; 263:1679. Marshall E. Science. 1994;
264:1524-1527.]
Some of the best tamoxifen data are from a large trial coordinated by NSABP
(the B-14 trial) involving a dozen centers and nearly 3000 patients with
hormone-sensitive, nonmetastatic breast cancer. Tamoxifen was shown to
reduce the incidence of new breast cancer by about 40% and to reduce
cholesterol levels and prevent bone loss. It was also shown to increase the
risk of endometrial cancer (Oncolink-NCI-PDQ), deep-vein thrombosis, and
possibly ocular degeneration. Most cases of endometrial cancer were
detected early enough to treat, but there were some deaths. However, the
increase in mortality was more than offset by the decrease in mortality
from breast cancer. [Fisher B et al. J Natl Cancer Inst. 1994; 86:527-537.]
A number of other clinical trials also found that tamoxifen increased the
risk of endometrial cancer. In a Swedish study involving 1372 subjects
randomized to tamoxifen or placebo, endometrial cancer developed in 23
women in the tamoxifen group compared with 4 in the placebo group during
9-year follow-up. A British study of 111 subjects enrolled in the UK Pilot
Breast Cancer Prevention trial found that tamoxifen- treated women had more
uterine abnormalities than patients in the placebo group (39% had a
thickened endometrium, compared with 10% of placebo subjects, and 16% had
atypical hyperplasia, compared with none in the placebo group). [Kedar RP
et al. Lancet. 1994;1318-1324.] There is also evi-dence that tamoxifen may
increase the risk of gastrointestinal cancer and damage the fetus when
taken during pregnancy.
An NCI panel has imposed two conditions on the current NSABP trial:
stronger warnings about uterine cancer and annual endometrial testing for
all participants. Patients are urged to see their physicians promptly if
they experience any menstrual irregularities, abnormal vaginal discharge,
change in vaginal discharge, or pelvic pain or pressure. The drug is still
indicated for the treatment of breast cancer, but the NCI emphasizes that
tamoxifen should not be taken as a breast cancer preventive outside of a
clinical trial. Nevertheless, physicians are already prescribing tamoxifen
as a prophylactic agent for women with a family history of breast cancer.
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paramvi's blog
By paramvi, history, 15 months ago, In English,
Hi, so this problem was asked in one of the job hiring contest which is over now. So the problem is as follows:
Cool numbers are defined as numbers having digits only 2 and 5. So example of cool digits are 2, 5, 22, 25, 225, while 12, 23, 221 are not cool numbers because all their digits are not from {2, 5}. Let f(k) be defined as the function having value as a cool number greater than or equal to k. For a given pair of { L, R }, I need to evaluate ( f(L)+f(L+1)+....+f(R) ). Constraints of L, R {1<=L<=R<=10^9}
How can I solve the above problem. Any hint or approach is appreciated.
Read more »
• Vote: I like it
• -5
• Vote: I do not like it
By paramvi, 3 years ago, In English,
We need to find all numbers between i,j which have 'D' as it's lowest common divisor(LCD). By LCD 'D' of n, I mean there don't exist any number 1<d<D, which divides n.
Constraints : 1<=i<=j<=2*10^9; 1<=D<=2*10^9;
If the constraints hadn't been that much large, it can be trivially solved using sieve of Eratosthenes.
Solution to this problem is appreciated.
Example : lets i,j,D have values 4,16,5 respectively.
So the answer will be following set of numbers: 5. Here 10,15 are not in the answer because 10 is divisible by 5 as well as 2, which is less than 5. Same for 15. Hope it clarify the doubts.
Read more »
By paramvi, 4 years ago, In English,
Hello guys. I need help in cracking a problem. I was trying to do this problem but my answer is coming out to be incorrect. Can you guys please help me in solving this problem.
My Solution.
Let's say number of tiles required at the end of the i-1'th iteration is tile_n. We will store how much area is left in the each of the "tile_n" tiles.
Now for i'th tile in the input, I will go through each of the "tile_n" tiles (stored) and will check if area of the any one of the "tile_n" tiles is greater than i'th tile.
if yes
Let's say it is the j'th tile.
I will check whether or not area of the j'th tile is a multiple of i'th tile. (this is so because we want to cut the proper tile from the j'th tile)
else
I will add another tile, tiles_n=tiles_n+1
and repeat.
Clearly my solution is lagging somewhere. Can please someone correct my algo. or explain me what to do in this problem.
Read more »
|
Seasonal Affective Disorder
Do you experience mood changes at specific times of the year? If so, you may be experiencing a type of depression known as Seasonal Affective Disorder (SAD). SAD is caused by changes in seasons and it begins and ends at the same times each year. For most people, SAD begins late fall and continues into the winter months. Some people experience symptoms of SAD in the spring and summer months as well.
SAD is a subtype of depression so its symptoms are similar to major depressive disorder. Some of these symptoms include: tiredness or low energy, appetite changes, weight gain, oversleeping, having difficulty concentrating etc.
Even though it is unclear what the specific causes of SAD are, it is thought to be related to changes in biological clock. The internal clock may be disrupted by reduced sunlight in the fall and winter months leading to Depressive symptoms.
If feel you are experiencing symptoms of winter blues that have been persistent over several days, see your doctor. You may be suffering from SAD. This is especially important if you are experiencing changes in sleep pattern or appetite or you are feeling hopeless or having suicidal thoughts.
There are effective treatments for SAD. These may include light therapy, medications and psychotherapy. Light therapy includes sitting a few feet from a special light box. This ensures that you are exposed to bright light that mimics natural outdoor light. Though research on light therapy is limited, it is first line treatment for fall onset SAD and its effective for relieving symptoms for most people.
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How to connect react JS with database
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Reading Time: 4 minutes
Introduction
In modern web applications, you may want to add a database to save and fetch data. As a result, you will get exemption from the risk of losing the necessary data and information. No matter how often you restart your app or refresh your web browser, you will discover the actual data flowing in the manually created database.
You have to make an effortless combination between the applied web technologies and database systems to get the spontaneous transformation of data. If you used the react JS in developing your front-end user interface, you need to connect it with the submitted database. The database can be either of SQL (MySQL) or NoSQL (MongoDB).
How to connect react JS with a database? You for sure need to master this essential method to accomplish your job precisely. Integrating React JS with the database is very simple. There is no need for writing a hundred lines of codes to do so. You have to follow easy steps to get started. Are you determined to grab this skill? If so, you can stay tuned till the end as it will benefit you in no time. We’re going to break down everything in a digestible manner. Let’s dive into the context!
How to connect react JS with a database?
React is the most-used front-end JavaScript library. It offers some extraordinary and user-friendly features and advantages to develop functional web applications overnight. This technology is easy to navigate, versatile, and favorable for new developers. The demand for react JS in web applications is above the mark. It’s comprehensively used to create multi-functional, dynamic, and data-driven websites.
So it’s crucial to combine react JS with the database. But you couldn’t connect react JS with the database directly. You have to connect the front end with the backend first. Then you need to connect the backend with the database. However, let’s explore the accurate approach of connecting react JS with database:
Create a database:
As you’re going to connect the database with your front-end technology, you need to create a database at first carefully. You may opt for the MySQL database management system to have flawless data manipulation convenience. To host MySQL, you need to install a XAMMP server on your system. Then you can open up the database console in order to create a new database.
Create a server connection:
Now it’s time to create a server connection for the database. In this step, you can create two different folders in the main application folder. One folder will contain the front-end files and another will serve the backend structure. Then you need to create a config folder in the server folder. It’s time to create a db.js file inside the config file. Write the following code:
Const mysql = require (‘mysql’)
Const db = mysql.createConnection({
host: “localhost”,
user: “root”,
password: “—“,
database: “posts”
})
module.exports = db
Define the endpoints:
Once you’ve completed the previous steps successfully, it’s time to define the endpoints CRUD app. You need to create an index.js file to define all the backend logic in order to get, update, delete, and sort the queries. This step needs some lines of code as well.
const connection = require(‘../util/connection’);
async function getAll() {
const sql = “SELECT * FROM tableName”;
const [rows] = await connection.promise().query(sql);
return rows;
exports.getAll = getAll;
Create the react app and define the frontend:
You’ve already done the database and server connection steps. Now you have to get ready for creating your react application. To be a well-versed front-end developer, you must have rock-solid expertise in creating react applications. Once you will complete the app creation, you need to define the frontend to make a superb connection.
Integrate the frontend and backend together:
We said earlier that you have to connect front with backend, and it’s high time to do so. You need to use a backend language such as Node.js, PHP, Python, etc build an API. The API will make connections between front-end and back-end segments to offer you a fast and secure database management system.
The simple method of connecting react JS with database
You may have heard people are talking about an easy method of connection. But it hardly works. You will encounter a security problem if you try this unrecognized method. In this approach, you have to write a dummy code statement. You need some database packages or drivers to move towards. The code will connect the driver to the database and run queries if the environment becomes supportive.
You will be interacting with the database directly through this process. It’s easy but not safe. If you become unable to acquire your goal in this process, you must switch to the previous one. Otherwise, you have to store your data in memory for a certain time. You will keep losing your valuable data unless you integrate a secured database with your react application.
Conclusion
By this time, you’ve known the method of connecting react JS with the database. You can follow the steps to combine either SQL or NoSQL database with your react application. But keep in mind that you have to write the correct and authentic code. Furthermore, your system must support both the react and database modules. If you’re new to this task, it may take time to get everything ready. But a professional developer can manage it within a short time without any issue.
However, you need to try steadily if you encounter any obstacles. You will become proficient in integrating your react application with the database if you do it several times. In order to work with web technologies professionally, you need to become well-versed in this procedure as soon as possible. How to connect react JS with a database? We hope you will never ask anyone this question from now.
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18
The title says most of it. Say I have a Windows PE (x86, 32bit) binary (just so we have case to discuss), the imports list will usually only show the imports found in the import directory. The attributes it shows are address of the function, name and library from which it got imported as shown in this screenshot snippet:
Screenshot of import tab in IDA Pro
Is there a way for me through scripting (IDC or Python, I don't care too much), to add imports of my own to the list and, for example, have them point (the address attribute) to code such as this (highlighted line)?:
Dynamically imported function in IDA Pro
I.e. the line would in such case look like:
0DCBA987 GetLongPathNameW kernel32.dll
or even just
0DCBA987 GetLongPathNameW ???
assuming the above call GetProcAddress would be at address 0DCBA987.
The advantage to me would be readability. But it would also yield a more comprehensive list of imports (and consequently xrefs) as some functions are frequently imported dynamically due to their availability in the various Windows versions.
It should be quite trivial given a certain binary to figure out all xrefs to candidate functions that retrieve the imported function's address (such as GetProcAddress) and then walk their calls to find which function was imported. The DLL part may be more complicated to find out, but it could be left empty or entered manually. But I didn't find a function that would allow me to add imports. Is there a way?
• 2
Interesting question, that would be useful when analyzing a program from a memory dump. Having the ability to edit the Imports would add cross-references and make the analysis easier. – ekse May 30 '13 at 9:17
• 4
If you haven't seen it you should check out reiat.py. It does most of what you discussed except adding to the import tabs. – alexanderh May 30 '13 at 19:58
• @alexanderh: hadn't, although I saw some of the other repos you have on Bitbucket before. Do you have any idea how to get that last step done? – 0xC0000022L May 30 '13 at 20:42
• 1
@0xC0000022L No, I do not. I'll try to take a crack at it this weekend. My email is in the source code. Feel free to email the sample if you can share it. Stupid side note, the comment "GetLongPathNameW" can be used to gather non-commented cross-references via hot-key X. Not useful for automated analysis but still helpful. – alexanderh May 31 '13 at 22:09
• You could try updating import_node (exported from the SDK's nalt.hpp), but it's unclear if IDA re-reads those netnodes every time it redraws the list of imports. – Jason Geffner Mar 24 '15 at 17:43
13
I don't know if many people know this, but IDA uses some kind of a trick to decide if a segment is an imports segment, and handles it completely different.
IDA uses a few segment properties to treat a segment as an imports segment. for example, naming a segment .idata, or setting the segment's class to XTRN will immediately make it an imports segment. such segments won't display the usual code/data listings, function definitions and most of the other stuff we're used to in the Code View.
More specifically, adding code to those segments will be hidden in IDA, which will refuse displaying any assembly in those segments. A nice Anti-IDA trick I'd say :)
Instead, they'll only display name definitions, offsets and comments. Once an offset is assigned a name of an API stored in IDA's database, IDA will get the API's prototype and other info, assign type definition and comments.
IIRC These APIs will also be shown in the imports window but i'm not sure what exactly triggers this. it might also depend on IDA versions and other import-related PE properties.
EDIT
It's been more than three years and obviously I couldn't find the script then, and I just went over some old code of mine and were able to reconstruct what I did in that script, and here is the gist of it:
import idaapi
import idc
for import_rva, import_name in LIST_OF_IMPORTS:
ea = imagebase + import_rva
if idaapi.get_segm_class(getseg(ea)) == "XTRN":
print("import is already inside an XTRN segment, "
"assuming it's correctly named")
continue
elif idaapi.get_segm_class(getseg(ea-1)) == "XTRN":
print("Import is just below an import segment, "
"extending segment to include this additional import")
# shrinking it's current segment
# WARNING: this assumes current import is at the top of its segment
# otherwise we'll have to SPLIT the import's current segment
# and to that I say CBA aka left as an exercise to the reader
idaapi.set_segm_start(ea, SegStart(ea)+4, 0)
# expanding it's new segment
idaapi.set_segm_end(ea-1, SegEnd(ea-1)+4, 0)
else:
print("Creating new segment for import")
idc.AddSeg(ea, ea+4, 0, 1, 4, 0)
idc.SetSegClass(ea, "XTRN")
# renaming import to API name. This will make IDA add type
# information and automatic comments for any function it's
# familiar with
idc.MakeName(ea, import_name)
# Making it an offset to have IDA show it as an import instead
# of hiding it
idc.MakeDword(ea)
| improve this answer | |
• @Nirlzr: by all means, I'd be curious to see this answer fleshed out a bit. Thanks. – 0xC0000022L May 31 '13 at 21:56
• @Nirlzr: any news concerning the mentioned script? – 0xC0000022L Jun 7 '13 at 14:49
• 2
@0xC0000022L: Terribly sorry! I'm currently in reserve duty and I can't get to stuff I have at work. didn't forget about it. – NirIzr Jun 7 '13 at 15:36
• 3
@0xC0000022L I know it's been a long time (and that's an understatement), but I've edited my answer to include the script) – NirIzr Oct 21 '16 at 3:28
8
+150
if adding an extra import section to the PE file is an acceptable option
use tools like iidking and add an import section with all the imports that are resolved dynamically
use add cross referances dialog or idc add_dref() to add cross references to them
code for demo
#include <stdio.h>
#include <windows.h>
#pragma comment(lib , "user32.lib")
DWORD (WINAPI * MyGetShortPathName)(LPCTSTR,LPTSTR,DWORD);
int main (void) {
MessageBox(NULL,"testing add import" , "Test", MB_OK);
char modname[MAX_PATH] = {0};
GetModuleFileName(NULL,modname,MAX_PATH);
printf("%s\n",modname);
HMODULE hMod = LoadLibrary("kernel32.dll");
if(hMod) {
*(FARPROC *)&MyGetShortPathName = GetProcAddress(hMod,"GetShortPathNameA");
if(MyGetShortPathName) {
MyGetShortPathName(modname,modname,MAX_PATH);
printf("%s\n",modname);
}
}
return 0;
}
compiled and executed
C:\codesnips\addimp\addimp.exe
C:\CODESN~1\addimp\addimp.exe
unmodified imports
00412000 GetCurrentThread KERNEL32
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
00412130 MessageBoxA USER32
exe modified with iidking and an import GetShortPathNameA added in the extra import section
C:\codesnips\addimp>fc /b addimp.exe modaddimp.exe
Comparing files addimp.exe and MODADDIMP.EXE
000000E6: 04 05 no of section
00000131: 90 A0
00000160: F4 00
00000161: 47 90
00000164: 3C 50
00000278: 00 2E .
00000279: 00 49 I
0000027A: 00 49 I
0000027B: 00 44 D
0000027C: 00 4B K
0000027D: 00 69 I
0000027E: 00 6E N
0000027F: 00 67 G
00000281: 00 02 vsize
00000285: 00 90
00000286: 00 01
00000289: 00 02
0000028D: 00 5E
0000028E: 00 01
0000029C: 00 20
0000029F: 00 E0
ida imports window copy paste of modified exe
00412000 GetCurrentThread KERNEL32
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
00412130 MessageBoxA USER32
00419058 GetShortPathNameA kernel32
double clicked 419058 -> open view -> open subviews -> crooss referances-> add cross refernces
Up P sub_401000+89 call ds:GetProcAddress (data xref)
or idc command
add_dref(0x401089,0x419058,53);
AddCodeXref(0x419058,0x401089,53);
AddImports
compiling these three lines into a plugin will add the Desired import into the first module's import
void idaapi run(int) {
nodeidx_t index = import_node.alt1st();
unsigned long value = import_node.altval(index);
netnode(value).supset(0x410004,"GetShortPathNameA\0");
}
the idc file to create Segment
#include <idc.idc>
static main()
{
auto addr;
addr = 0x410000;
SegCreate(addr,addr+0x200,0,1,3,2);
SetSegmentType(addr,SEG_XTRN);
MakeDword(addr+4);
MakeName(addr+4,"GetShortPathNameA");
}
open an exe / run idc / plugin / close and save database / reopen database to see the added imports in imports tab of first module
edit
windows -> reset desktop works the same ways as closing and opening the database so that eleiminates closing and opening of database
| improve this answer | |
• Thanks for the answer! Unfortunately this won't work for some unpacked executables or when dealing with position independent code. – alexanderh Mar 25 '15 at 14:19
• can you elaborate or post / point to a sample where this doesn't seem to work ? – blabb Mar 25 '15 at 18:54
• I might be mistaken but your example would not work on samples that are missing the portable executable header. Examples of these would be shellcode, injected DLLs that zero out the header, or position independent code ( no header and resolves symbols address by traversing PEB for kernel32.dll). Sure, a PE header could be added but this isn't always a feasible approach because it relies on having and modifying the binary. – alexanderh Mar 25 '15 at 20:41
• if you are convinced about the reasoning i am fine with that but my thought process is like this if ida has enough information to retirieve and create the original imports then it should be capable of finding this too. the original query seemed to imply that the pe is available and didn't say anything about non availabilty of the original pe so i posted this approach with a caveat if modifying the exe is acceptable if your new requiremnts are about mucking with an idb standlaone then i dont have any idea – blabb Mar 26 '15 at 5:34
• I understand your thought process but it still doesn't answer how to add the imports to the import tab via IDC or Python in IDA. Which is the original request. Check out NirIzr answer it is the closest. – alexanderh Mar 26 '15 at 15:45
5
If you can not add something to the imports viewer you can write your own. Here is the simple example (it is slightly modified example referenced at this hexblog entry and located here with added double-click functionality, added columns, removed exports and fixed bug for a case of unknown origin of the imported function). See the function BuildImports for creating additional imports (manual_func1 and manual_func2)
import idaapi
import idautils
from idaapi import PluginForm
from PySide import QtGui, QtCore
class ImpExpForm_t(PluginForm):
def imports_names_cb(self, ea, name, ord):
self.items.append((ea, '' if not name else name, ord))
# True -> Continue enumeration
return True
def BuildImports(self):
tree = {}
nimps = idaapi.get_import_module_qty()
for i in xrange(0, nimps):
name = idaapi.get_import_module_name(i)
if not name:
name = "unknown"
# Create a list for imported names
self.items = []
# Enum imported entries in this module
idaapi.enum_import_names(i, self.imports_names_cb)
if name not in tree:
tree[name] = []
tree[name].extend(self.items)
tree["manually_added"] = [(0x01, "manual_func1", 3), (0x02, "manual_func2",4)]
return tree
def PopulateTree(self):
# Clear previous items
self.tree.clear()
# Build imports
root = QtGui.QTreeWidgetItem(self.tree)
root.setText(0, "Imports")
for dll_name, imp_entries in self.BuildImports().items():
imp_dll = QtGui.QTreeWidgetItem(root)
imp_dll.setText(0, dll_name)
for imp_ea, imp_name, imp_ord in imp_entries:
item = QtGui.QTreeWidgetItem(imp_dll)
item.setText(0, "%s" % imp_name)
item.setText(1, "0x%08x" % imp_ea)
item.setText(2, "0x%08x" % imp_ord)
def dblclick(self, item):
try:
idaapi.jumpto(int(item.text(1).encode("ascii", "ignore"), 16))
except:
print "Can not jump"
def OnCreate(self, form):
"""
Called when the plugin form is created
"""
# Get parent widget
self.parent = self.FormToPySideWidget(form)
# Create tree control
self.tree = QtGui.QTreeWidget()
self.tree.setColumnCount(4)
self.tree.setHeaderLabels(("Names","Address", "Ordinal", "Source"))
self.tree.itemDoubleClicked.connect(self.dblclick)
self.tree.setColumnWidth(0, 100)
# Create layout
layout = QtGui.QVBoxLayout()
layout.addWidget(self.tree)
self.PopulateTree()
# Populate PluginForm
self.parent.setLayout(layout)
def OnClose(self, form):
"""
Called when the plugin form is closed
"""
global ImpExpForm
del ImpExpForm
print "Closed"
def Show(self):
"""Creates the form is not created or focuses it if it was"""
return PluginForm.Show(self,
"Imports / Exports viewer",
options = PluginForm.FORM_PERSIST)
# --------------------------------------------------------------------------
def main():
global ImpExpForm
try:
ImpExpForm
except:
ImpExpForm = ImpExpForm_t()
ImpExpForm.Show()
# --------------------------------------------------------------------------
main()
| improve this answer | |
• Thanks, I have used the viewer approach before. An issue I have found is that once the IDB is closed the viewer and the data is gone. It would be cool to find something a little more permanent. – alexanderh Mar 25 '15 at 20:50
• 1
You can use OnClose to save the data for example. It will require a bit more development, but it is still easy – w s Mar 25 '15 at 20:53
• Generally speaking you have some better alternatives. First of all, you can store the script itself in the script window (File-->Script command has an interface for that) - this will allow to keep all your latest additions with the idb. You can also use OnClose and store your data in a file with name derived from the name of the idb which can be obtained by idautils.GetIdbPath. You can also store the data in the custom node of the idb. – w s Mar 26 '15 at 7:30
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/* * segment.c - NILFS segment constructor. * * Copyright (C) 2005-2008 Nippon Telegraph and Telephone Corporation. * * This program is free software; you can redistribute it and/or modify * it under the terms of the GNU General Public License as published by * the Free Software Foundation; either version 2 of the License, or * (at your option) any later version. * * This program is distributed in the hope that it will be useful, * but WITHOUT ANY WARRANTY; without even the implied warranty of * MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the * GNU General Public License for more details. * * You should have received a copy of the GNU General Public License * along with this program; if not, write to the Free Software * Foundation, Inc., 51 Franklin St, Fifth Floor, Boston, MA 02110-1301 USA * * Written by Ryusuke Konishi * */ #include #include #include #include #include #include #include #include #include #include #include #include #include "nilfs.h" #include "btnode.h" #include "page.h" #include "segment.h" #include "sufile.h" #include "cpfile.h" #include "ifile.h" #include "segbuf.h" /* * Segment constructor */ #define SC_N_INODEVEC 16 /* Size of locally allocated inode vector */ #define SC_MAX_SEGDELTA 64 /* Upper limit of the number of segments appended in collection retry loop */ /* Construction mode */ enum { SC_LSEG_SR = 1, /* Make a logical segment having a super root */ SC_LSEG_DSYNC, /* Flush data blocks of a given file and make a logical segment without a super root */ SC_FLUSH_FILE, /* Flush data files, leads to segment writes without creating a checkpoint */ SC_FLUSH_DAT, /* Flush DAT file. This also creates segments without a checkpoint */ }; /* Stage numbers of dirty block collection */ enum { NILFS_ST_INIT = 0, NILFS_ST_GC, /* Collecting dirty blocks for GC */ NILFS_ST_FILE, NILFS_ST_IFILE, NILFS_ST_CPFILE, NILFS_ST_SUFILE, NILFS_ST_DAT, NILFS_ST_SR, /* Super root */ NILFS_ST_DSYNC, /* Data sync blocks */ NILFS_ST_DONE, }; /* State flags of collection */ #define NILFS_CF_NODE 0x0001 /* Collecting node blocks */ #define NILFS_CF_IFILE_STARTED 0x0002 /* IFILE stage has started */ #define NILFS_CF_SUFREED 0x0004 /* segment usages has been freed */ #define NILFS_CF_HISTORY_MASK (NILFS_CF_IFILE_STARTED | NILFS_CF_SUFREED) /* Operations depending on the construction mode and file type */ struct nilfs_sc_operations { int (*collect_data)(struct nilfs_sc_info *, struct buffer_head *, struct inode *); int (*collect_node)(struct nilfs_sc_info *, struct buffer_head *, struct inode *); int (*collect_bmap)(struct nilfs_sc_info *, struct buffer_head *, struct inode *); void (*write_data_binfo)(struct nilfs_sc_info *, struct nilfs_segsum_pointer *, union nilfs_binfo *); void (*write_node_binfo)(struct nilfs_sc_info *, struct nilfs_segsum_pointer *, union nilfs_binfo *); }; /* * Other definitions */ static void nilfs_segctor_start_timer(struct nilfs_sc_info *); static void nilfs_segctor_do_flush(struct nilfs_sc_info *, int); static void nilfs_segctor_do_immediate_flush(struct nilfs_sc_info *); static void nilfs_dispose_list(struct nilfs_sb_info *, struct list_head *, int); #define nilfs_cnt32_gt(a, b) \ (typecheck(__u32, a) && typecheck(__u32, b) && \ ((__s32)(b) - (__s32)(a) < 0)) #define nilfs_cnt32_ge(a, b) \ (typecheck(__u32, a) && typecheck(__u32, b) && \ ((__s32)(a) - (__s32)(b) >= 0)) #define nilfs_cnt32_lt(a, b) nilfs_cnt32_gt(b, a) #define nilfs_cnt32_le(a, b) nilfs_cnt32_ge(b, a) /* * Transaction */ static struct kmem_cache *nilfs_transaction_cachep; /** * nilfs_init_transaction_cache - create a cache for nilfs_transaction_info * * nilfs_init_transaction_cache() creates a slab cache for the struct * nilfs_transaction_info. * * Return Value: On success, it returns 0. On error, one of the following * negative error code is returned. * * %-ENOMEM - Insufficient memory available. */ int nilfs_init_transaction_cache(void) { nilfs_transaction_cachep = kmem_cache_create("nilfs2_transaction_cache", sizeof(struct nilfs_transaction_info), 0, SLAB_RECLAIM_ACCOUNT, NULL); return (nilfs_transaction_cachep == NULL) ? -ENOMEM : 0; } /** * nilfs_destroy_transaction_cache - destroy the cache for transaction info * * nilfs_destroy_transaction_cache() frees the slab cache for the struct * nilfs_transaction_info. */ void nilfs_destroy_transaction_cache(void) { kmem_cache_destroy(nilfs_transaction_cachep); } static int nilfs_prepare_segment_lock(struct nilfs_transaction_info *ti) { struct nilfs_transaction_info *cur_ti = current->journal_info; void *save = NULL; if (cur_ti) { if (cur_ti->ti_magic == NILFS_TI_MAGIC) return ++cur_ti->ti_count; else { /* * If journal_info field is occupied by other FS, * it is saved and will be restored on * nilfs_transaction_commit(). */ printk(KERN_WARNING "NILFS warning: journal info from a different " "FS\n"); save = current->journal_info; } } if (!ti) { ti = kmem_cache_alloc(nilfs_transaction_cachep, GFP_NOFS); if (!ti) return -ENOMEM; ti->ti_flags = NILFS_TI_DYNAMIC_ALLOC; } else { ti->ti_flags = 0; } ti->ti_count = 0; ti->ti_save = save; ti->ti_magic = NILFS_TI_MAGIC; current->journal_info = ti; return 0; } /** * nilfs_transaction_begin - start indivisible file operations. * @sb: super block * @ti: nilfs_transaction_info * @vacancy_check: flags for vacancy rate checks * * nilfs_transaction_begin() acquires a reader/writer semaphore, called * the segment semaphore, to make a segment construction and write tasks * exclusive. The function is used with nilfs_transaction_commit() in pairs. * The region enclosed by these two functions can be nested. To avoid a * deadlock, the semaphore is only acquired or released in the outermost call. * * This function allocates a nilfs_transaction_info struct to keep context * information on it. It is initialized and hooked onto the current task in * the outermost call. If a pre-allocated struct is given to @ti, it is used * instead; otherwise a new struct is assigned from a slab. * * When @vacancy_check flag is set, this function will check the amount of * free space, and will wait for the GC to reclaim disk space if low capacity. * * Return Value: On success, 0 is returned. On error, one of the following * negative error code is returned. * * %-ENOMEM - Insufficient memory available. * * %-ENOSPC - No space left on device */ int nilfs_transaction_begin(struct super_block *sb, struct nilfs_transaction_info *ti, int vacancy_check) { struct nilfs_sb_info *sbi; struct the_nilfs *nilfs; int ret = nilfs_prepare_segment_lock(ti); if (unlikely(ret < 0)) return ret; if (ret > 0) return 0; sbi = NILFS_SB(sb); nilfs = sbi->s_nilfs; down_read(&nilfs->ns_segctor_sem); if (vacancy_check && nilfs_near_disk_full(nilfs)) { up_read(&nilfs->ns_segctor_sem); ret = -ENOSPC; goto failed; } return 0; failed: ti = current->journal_info; current->journal_info = ti->ti_save; if (ti->ti_flags & NILFS_TI_DYNAMIC_ALLOC) kmem_cache_free(nilfs_transaction_cachep, ti); return ret; } /** * nilfs_transaction_commit - commit indivisible file operations. * @sb: super block * * nilfs_transaction_commit() releases the read semaphore which is * acquired by nilfs_transaction_begin(). This is only performed * in outermost call of this function. If a commit flag is set, * nilfs_transaction_commit() sets a timer to start the segment * constructor. If a sync flag is set, it starts construction * directly. */ int nilfs_transaction_commit(struct super_block *sb) { struct nilfs_transaction_info *ti = current->journal_info; struct nilfs_sb_info *sbi; struct nilfs_sc_info *sci; int err = 0; BUG_ON(ti == NULL || ti->ti_magic != NILFS_TI_MAGIC); ti->ti_flags |= NILFS_TI_COMMIT; if (ti->ti_count > 0) { ti->ti_count--; return 0; } sbi = NILFS_SB(sb); sci = NILFS_SC(sbi); if (sci != NULL) { if (ti->ti_flags & NILFS_TI_COMMIT) nilfs_segctor_start_timer(sci); if (atomic_read(&sbi->s_nilfs->ns_ndirtyblks) > sci->sc_watermark) nilfs_segctor_do_flush(sci, 0); } up_read(&sbi->s_nilfs->ns_segctor_sem); current->journal_info = ti->ti_save; if (ti->ti_flags & NILFS_TI_SYNC) err = nilfs_construct_segment(sb); if (ti->ti_flags & NILFS_TI_DYNAMIC_ALLOC) kmem_cache_free(nilfs_transaction_cachep, ti); return err; } void nilfs_transaction_abort(struct super_block *sb) { struct nilfs_transaction_info *ti = current->journal_info; BUG_ON(ti == NULL || ti->ti_magic != NILFS_TI_MAGIC); if (ti->ti_count > 0) { ti->ti_count--; return; } up_read(&NILFS_SB(sb)->s_nilfs->ns_segctor_sem); current->journal_info = ti->ti_save; if (ti->ti_flags & NILFS_TI_DYNAMIC_ALLOC) kmem_cache_free(nilfs_transaction_cachep, ti); } void nilfs_relax_pressure_in_lock(struct super_block *sb) { struct nilfs_sb_info *sbi = NILFS_SB(sb); struct nilfs_sc_info *sci = NILFS_SC(sbi); struct the_nilfs *nilfs = sbi->s_nilfs; if (!sci || !sci->sc_flush_request) return; set_bit(NILFS_SC_PRIOR_FLUSH, &sci->sc_flags); up_read(&nilfs->ns_segctor_sem); down_write(&nilfs->ns_segctor_sem); if (sci->sc_flush_request && test_bit(NILFS_SC_PRIOR_FLUSH, &sci->sc_flags)) { struct nilfs_transaction_info *ti = current->journal_info; ti->ti_flags |= NILFS_TI_WRITER; nilfs_segctor_do_immediate_flush(sci); ti->ti_flags &= ~NILFS_TI_WRITER; } downgrade_write(&nilfs->ns_segctor_sem); } static void nilfs_transaction_lock(struct nilfs_sb_info *sbi, struct nilfs_transaction_info *ti, int gcflag) { struct nilfs_transaction_info *cur_ti = current->journal_info; WARN_ON(cur_ti); ti->ti_flags = NILFS_TI_WRITER; ti->ti_count = 0; ti->ti_save = cur_ti; ti->ti_magic = NILFS_TI_MAGIC; INIT_LIST_HEAD(&ti->ti_garbage); current->journal_info = ti; for (;;) { down_write(&sbi->s_nilfs->ns_segctor_sem); if (!test_bit(NILFS_SC_PRIOR_FLUSH, &NILFS_SC(sbi)->sc_flags)) break; nilfs_segctor_do_immediate_flush(NILFS_SC(sbi)); up_write(&sbi->s_nilfs->ns_segctor_sem); yield(); } if (gcflag) ti->ti_flags |= NILFS_TI_GC; } static void nilfs_transaction_unlock(struct nilfs_sb_info *sbi) { struct nilfs_transaction_info *ti = current->journal_info; BUG_ON(ti == NULL || ti->ti_magic != NILFS_TI_MAGIC); BUG_ON(ti->ti_count > 0); up_write(&sbi->s_nilfs->ns_segctor_sem); current->journal_info = ti->ti_save; if (!list_empty(&ti->ti_garbage)) nilfs_dispose_list(sbi, &ti->ti_garbage, 0); } static void *nilfs_segctor_map_segsum_entry(struct nilfs_sc_info *sci, struct nilfs_segsum_pointer *ssp, unsigned bytes) { struct nilfs_segment_buffer *segbuf = sci->sc_curseg; unsigned blocksize = sci->sc_super->s_blocksize; void *p; if (unlikely(ssp->offset + bytes > blocksize)) { ssp->offset = 0; BUG_ON(NILFS_SEGBUF_BH_IS_LAST(ssp->bh, &segbuf->sb_segsum_buffers)); ssp->bh = NILFS_SEGBUF_NEXT_BH(ssp->bh); } p = ssp->bh->b_data + ssp->offset; ssp->offset += bytes; return p; } /** * nilfs_segctor_reset_segment_buffer - reset the current segment buffer * @sci: nilfs_sc_info */ static int nilfs_segctor_reset_segment_buffer(struct nilfs_sc_info *sci) { struct nilfs_segment_buffer *segbuf = sci->sc_curseg; struct buffer_head *sumbh; unsigned sumbytes; unsigned flags = 0; int err; if (nilfs_doing_gc()) flags = NILFS_SS_GC; err = nilfs_segbuf_reset(segbuf, flags, sci->sc_seg_ctime); if (unlikely(err)) return err; sumbh = NILFS_SEGBUF_FIRST_BH(&segbuf->sb_segsum_buffers); sumbytes = segbuf->sb_sum.sumbytes; sci->sc_finfo_ptr.bh = sumbh; sci->sc_finfo_ptr.offset = sumbytes; sci->sc_binfo_ptr.bh = sumbh; sci->sc_binfo_ptr.offset = sumbytes; sci->sc_blk_cnt = sci->sc_datablk_cnt = 0; return 0; } static int nilfs_segctor_feed_segment(struct nilfs_sc_info *sci) { sci->sc_nblk_this_inc += sci->sc_curseg->sb_sum.nblocks; if (NILFS_SEGBUF_IS_LAST(sci->sc_curseg, &sci->sc_segbufs)) return -E2BIG; /* The current segment is filled up (internal code) */ sci->sc_curseg = NILFS_NEXT_SEGBUF(sci->sc_curseg); return nilfs_segctor_reset_segment_buffer(sci); } static int nilfs_segctor_add_super_root(struct nilfs_sc_info *sci) { struct nilfs_segment_buffer *segbuf = sci->sc_curseg; int err; if (segbuf->sb_sum.nblocks >= segbuf->sb_rest_blocks) { err = nilfs_segctor_feed_segment(sci); if (err) return err; segbuf = sci->sc_curseg; } err = nilfs_segbuf_extend_payload(segbuf, &sci->sc_super_root); if (likely(!err)) segbuf->sb_sum.flags |= NILFS_SS_SR; return err; } /* * Functions for making segment summary and payloads */ static int nilfs_segctor_segsum_block_required( struct nilfs_sc_info *sci, const struct nilfs_segsum_pointer *ssp, unsigned binfo_size) { unsigned blocksize = sci->sc_super->s_blocksize; /* Size of finfo and binfo is enough small against blocksize */ return ssp->offset + binfo_size + (!sci->sc_blk_cnt ? sizeof(struct nilfs_finfo) : 0) > blocksize; } static void nilfs_segctor_begin_finfo(struct nilfs_sc_info *sci, struct inode *inode) { sci->sc_curseg->sb_sum.nfinfo++; sci->sc_binfo_ptr = sci->sc_finfo_ptr; nilfs_segctor_map_segsum_entry( sci, &sci->sc_binfo_ptr, sizeof(struct nilfs_finfo)); if (inode->i_sb && !test_bit(NILFS_SC_HAVE_DELTA, &sci->sc_flags)) set_bit(NILFS_SC_HAVE_DELTA, &sci->sc_flags); /* skip finfo */ } static void nilfs_segctor_end_finfo(struct nilfs_sc_info *sci, struct inode *inode) { struct nilfs_finfo *finfo; struct nilfs_inode_info *ii; struct nilfs_segment_buffer *segbuf; if (sci->sc_blk_cnt == 0) return; ii = NILFS_I(inode); finfo = nilfs_segctor_map_segsum_entry(sci, &sci->sc_finfo_ptr, sizeof(*finfo)); finfo->fi_ino = cpu_to_le64(inode->i_ino); finfo->fi_nblocks = cpu_to_le32(sci->sc_blk_cnt); finfo->fi_ndatablk = cpu_to_le32(sci->sc_datablk_cnt); finfo->fi_cno = cpu_to_le64(ii->i_cno); segbuf = sci->sc_curseg; segbuf->sb_sum.sumbytes = sci->sc_binfo_ptr.offset + sci->sc_super->s_blocksize * (segbuf->sb_sum.nsumblk - 1); sci->sc_finfo_ptr = sci->sc_binfo_ptr; sci->sc_blk_cnt = sci->sc_datablk_cnt = 0; } static int nilfs_segctor_add_file_block(struct nilfs_sc_info *sci, struct buffer_head *bh, struct inode *inode, unsigned binfo_size) { struct nilfs_segment_buffer *segbuf; int required, err = 0; retry: segbuf = sci->sc_curseg; required = nilfs_segctor_segsum_block_required( sci, &sci->sc_binfo_ptr, binfo_size); if (segbuf->sb_sum.nblocks + required + 1 > segbuf->sb_rest_blocks) { nilfs_segctor_end_finfo(sci, inode); err = nilfs_segctor_feed_segment(sci); if (err) return err; goto retry; } if (unlikely(required)) { err = nilfs_segbuf_extend_segsum(segbuf); if (unlikely(err)) goto failed; } if (sci->sc_blk_cnt == 0) nilfs_segctor_begin_finfo(sci, inode); nilfs_segctor_map_segsum_entry(sci, &sci->sc_binfo_ptr, binfo_size); /* Substitution to vblocknr is delayed until update_blocknr() */ nilfs_segbuf_add_file_buffer(segbuf, bh); sci->sc_blk_cnt++; failed: return err; } static int nilfs_handle_bmap_error(int err, const char *fname, struct inode *inode, struct super_block *sb) { if (err == -EINVAL) { nilfs_error(sb, fname, "broken bmap (inode=%lu)\n", inode->i_ino); err = -EIO; } return err; } /* * Callback functions that enumerate, mark, and collect dirty blocks */ static int nilfs_collect_file_data(struct nilfs_sc_info *sci, struct buffer_head *bh, struct inode *inode) { int err; err = nilfs_bmap_propagate(NILFS_I(inode)->i_bmap, bh); if (unlikely(err < 0)) return nilfs_handle_bmap_error(err, __func__, inode, sci->sc_super); err = nilfs_segctor_add_file_block(sci, bh, inode, sizeof(struct nilfs_binfo_v)); if (!err) sci->sc_datablk_cnt++; return err; } static int nilfs_collect_file_node(struct nilfs_sc_info *sci, struct buffer_head *bh, struct inode *inode) { int err; err = nilfs_bmap_propagate(NILFS_I(inode)->i_bmap, bh); if (unlikely(err < 0)) return nilfs_handle_bmap_error(err, __func__, inode, sci->sc_super); return 0; } static int nilfs_collect_file_bmap(struct nilfs_sc_info *sci, struct buffer_head *bh, struct inode *inode) { WARN_ON(!buffer_dirty(bh)); return nilfs_segctor_add_file_block(sci, bh, inode, sizeof(__le64)); } static void nilfs_write_file_data_binfo(struct nilfs_sc_info *sci, struct nilfs_segsum_pointer *ssp, union nilfs_binfo *binfo) { struct nilfs_binfo_v *binfo_v = nilfs_segctor_map_segsum_entry( sci, ssp, sizeof(*binfo_v)); *binfo_v = binfo->bi_v; } static void nilfs_write_file_node_binfo(struct nilfs_sc_info *sci, struct nilfs_segsum_pointer *ssp, union nilfs_binfo *binfo) { __le64 *vblocknr = nilfs_segctor_map_segsum_entry( sci, ssp, sizeof(*vblocknr)); *vblocknr = binfo->bi_v.bi_vblocknr; } struct nilfs_sc_operations nilfs_sc_file_ops = { .collect_data = nilfs_collect_file_data, .collect_node = nilfs_collect_file_node, .collect_bmap = nilfs_collect_file_bmap, .write_data_binfo = nilfs_write_file_data_binfo, .write_node_binfo = nilfs_write_file_node_binfo, }; static int nilfs_collect_dat_data(struct nilfs_sc_info *sci, struct buffer_head *bh, struct inode *inode) { int err; err = nilfs_bmap_propagate(NILFS_I(inode)->i_bmap, bh); if (unlikely(err < 0)) return nilfs_handle_bmap_error(err, __func__, inode, sci->sc_super); err = nilfs_segctor_add_file_block(sci, bh, inode, sizeof(__le64)); if (!err) sci->sc_datablk_cnt++; return err; } static int nilfs_collect_dat_bmap(struct nilfs_sc_info *sci, struct buffer_head *bh, struct inode *inode) { WARN_ON(!buffer_dirty(bh)); return nilfs_segctor_add_file_block(sci, bh, inode, sizeof(struct nilfs_binfo_dat)); } static void nilfs_write_dat_data_binfo(struct nilfs_sc_info *sci, struct nilfs_segsum_pointer *ssp, union nilfs_binfo *binfo) { __le64 *blkoff = nilfs_segctor_map_segsum_entry(sci, ssp, sizeof(*blkoff)); *blkoff = binfo->bi_dat.bi_blkoff; } static void nilfs_write_dat_node_binfo(struct nilfs_sc_info *sci, struct nilfs_segsum_pointer *ssp, union nilfs_binfo *binfo) { struct nilfs_binfo_dat *binfo_dat = nilfs_segctor_map_segsum_entry(sci, ssp, sizeof(*binfo_dat)); *binfo_dat = binfo->bi_dat; } struct nilfs_sc_operations nilfs_sc_dat_ops = { .collect_data = nilfs_collect_dat_data, .collect_node = nilfs_collect_file_node, .collect_bmap = nilfs_collect_dat_bmap, .write_data_binfo = nilfs_write_dat_data_binfo, .write_node_binfo = nilfs_write_dat_node_binfo, }; struct nilfs_sc_operations nilfs_sc_dsync_ops = { .collect_data = nilfs_collect_file_data, .collect_node = NULL, .collect_bmap = NULL, .write_data_binfo = nilfs_write_file_data_binfo, .write_node_binfo = NULL, }; static size_t nilfs_lookup_dirty_data_buffers(struct inode *inode, struct list_head *listp, size_t nlimit, loff_t start, loff_t end) { struct address_space *mapping = inode->i_mapping; struct pagevec pvec; pgoff_t index = 0, last = ULONG_MAX; size_t ndirties = 0; int i; if (unlikely(start != 0 || end != LLONG_MAX)) { /* * A valid range is given for sync-ing data pages. The * range is rounded to per-page; extra dirty buffers * may be included if blocksize < pagesize. */ index = start >> PAGE_SHIFT; last = end >> PAGE_SHIFT; } pagevec_init(&pvec, 0); repeat: if (unlikely(index > last) || !pagevec_lookup_tag(&pvec, mapping, &index, PAGECACHE_TAG_DIRTY, min_t(pgoff_t, last - index, PAGEVEC_SIZE - 1) + 1)) return ndirties; for (i = 0; i < pagevec_count(&pvec); i++) { struct buffer_head *bh, *head; struct page *page = pvec.pages[i]; if (unlikely(page->index > last)) break; if (mapping->host) { lock_page(page); if (!page_has_buffers(page)) create_empty_buffers(page, 1 << inode->i_blkbits, 0); unlock_page(page); } bh = head = page_buffers(page); do { if (!buffer_dirty(bh)) continue; get_bh(bh); list_add_tail(&bh->b_assoc_buffers, listp); ndirties++; if (unlikely(ndirties >= nlimit)) { pagevec_release(&pvec); cond_resched(); return ndirties; } } while (bh = bh->b_this_page, bh != head); } pagevec_release(&pvec); cond_resched(); goto repeat; } static void nilfs_lookup_dirty_node_buffers(struct inode *inode, struct list_head *listp) { struct nilfs_inode_info *ii = NILFS_I(inode); struct address_space *mapping = &ii->i_btnode_cache; struct pagevec pvec; struct buffer_head *bh, *head; unsigned int i; pgoff_t index = 0; pagevec_init(&pvec, 0); while (pagevec_lookup_tag(&pvec, mapping, &index, PAGECACHE_TAG_DIRTY, PAGEVEC_SIZE)) { for (i = 0; i < pagevec_count(&pvec); i++) { bh = head = page_buffers(pvec.pages[i]); do { if (buffer_dirty(bh)) { get_bh(bh); list_add_tail(&bh->b_assoc_buffers, listp); } bh = bh->b_this_page; } while (bh != head); } pagevec_release(&pvec); cond_resched(); } } static void nilfs_dispose_list(struct nilfs_sb_info *sbi, struct list_head *head, int force) { struct nilfs_inode_info *ii, *n; struct nilfs_inode_info *ivec[SC_N_INODEVEC], **pii; unsigned nv = 0; while (!list_empty(head)) { spin_lock(&sbi->s_inode_lock); list_for_each_entry_safe(ii, n, head, i_dirty) { list_del_init(&ii->i_dirty); if (force) { if (unlikely(ii->i_bh)) { brelse(ii->i_bh); ii->i_bh = NULL; } } else if (test_bit(NILFS_I_DIRTY, &ii->i_state)) { set_bit(NILFS_I_QUEUED, &ii->i_state); list_add_tail(&ii->i_dirty, &sbi->s_dirty_files); continue; } ivec[nv++] = ii; if (nv == SC_N_INODEVEC) break; } spin_unlock(&sbi->s_inode_lock); for (pii = ivec; nv > 0; pii++, nv--) iput(&(*pii)->vfs_inode); } } static int nilfs_test_metadata_dirty(struct nilfs_sb_info *sbi) { struct the_nilfs *nilfs = sbi->s_nilfs; int ret = 0; if (nilfs_mdt_fetch_dirty(sbi->s_ifile)) ret++; if (nilfs_mdt_fetch_dirty(nilfs->ns_cpfile)) ret++; if (nilfs_mdt_fetch_dirty(nilfs->ns_sufile)) ret++; if (ret || nilfs_doing_gc()) if (nilfs_mdt_fetch_dirty(nilfs_dat_inode(nilfs))) ret++; return ret; } static int nilfs_segctor_clean(struct nilfs_sc_info *sci) { return list_empty(&sci->sc_dirty_files) && !test_bit(NILFS_SC_DIRTY, &sci->sc_flags) && sci->sc_nfreesegs == 0 && (!nilfs_doing_gc() || list_empty(&sci->sc_gc_inodes)); } static int nilfs_segctor_confirm(struct nilfs_sc_info *sci) { struct nilfs_sb_info *sbi = sci->sc_sbi; int ret = 0; if (nilfs_test_metadata_dirty(sbi)) set_bit(NILFS_SC_DIRTY, &sci->sc_flags); spin_lock(&sbi->s_inode_lock); if (list_empty(&sbi->s_dirty_files) && nilfs_segctor_clean(sci)) ret++; spin_unlock(&sbi->s_inode_lock); return ret; } static void nilfs_segctor_clear_metadata_dirty(struct nilfs_sc_info *sci) { struct nilfs_sb_info *sbi = sci->sc_sbi; struct the_nilfs *nilfs = sbi->s_nilfs; nilfs_mdt_clear_dirty(sbi->s_ifile); nilfs_mdt_clear_dirty(nilfs->ns_cpfile); nilfs_mdt_clear_dirty(nilfs->ns_sufile); nilfs_mdt_clear_dirty(nilfs_dat_inode(nilfs)); } static int nilfs_segctor_create_checkpoint(struct nilfs_sc_info *sci) { struct the_nilfs *nilfs = sci->sc_sbi->s_nilfs; struct buffer_head *bh_cp; struct nilfs_checkpoint *raw_cp; int err; /* XXX: this interface will be changed */ err = nilfs_cpfile_get_checkpoint(nilfs->ns_cpfile, nilfs->ns_cno, 1, &raw_cp, &bh_cp); if (likely(!err)) { /* The following code is duplicated with cpfile. But, it is needed to collect the checkpoint even if it was not newly created */ nilfs_mdt_mark_buffer_dirty(bh_cp); nilfs_mdt_mark_dirty(nilfs->ns_cpfile); nilfs_cpfile_put_checkpoint( nilfs->ns_cpfile, nilfs->ns_cno, bh_cp); } else WARN_ON(err == -EINVAL || err == -ENOENT); return err; } static int nilfs_segctor_fill_in_checkpoint(struct nilfs_sc_info *sci) { struct nilfs_sb_info *sbi = sci->sc_sbi; struct the_nilfs *nilfs = sbi->s_nilfs; struct buffer_head *bh_cp; struct nilfs_checkpoint *raw_cp; int err; err = nilfs_cpfile_get_checkpoint(nilfs->ns_cpfile, nilfs->ns_cno, 0, &raw_cp, &bh_cp); if (unlikely(err)) { WARN_ON(err == -EINVAL || err == -ENOENT); goto failed_ibh; } raw_cp->cp_snapshot_list.ssl_next = 0; raw_cp->cp_snapshot_list.ssl_prev = 0; raw_cp->cp_inodes_count = cpu_to_le64(atomic_read(&sbi->s_inodes_count)); raw_cp->cp_blocks_count = cpu_to_le64(atomic_read(&sbi->s_blocks_count)); raw_cp->cp_nblk_inc = cpu_to_le64(sci->sc_nblk_inc + sci->sc_nblk_this_inc); raw_cp->cp_create = cpu_to_le64(sci->sc_seg_ctime); raw_cp->cp_cno = cpu_to_le64(nilfs->ns_cno); if (test_bit(NILFS_SC_HAVE_DELTA, &sci->sc_flags)) nilfs_checkpoint_clear_minor(raw_cp); else nilfs_checkpoint_set_minor(raw_cp); nilfs_write_inode_common(sbi->s_ifile, &raw_cp->cp_ifile_inode, 1); nilfs_cpfile_put_checkpoint(nilfs->ns_cpfile, nilfs->ns_cno, bh_cp); return 0; failed_ibh: return err; } static void nilfs_fill_in_file_bmap(struct inode *ifile, struct nilfs_inode_info *ii) { struct buffer_head *ibh; struct nilfs_inode *raw_inode; if (test_bit(NILFS_I_BMAP, &ii->i_state)) { ibh = ii->i_bh; BUG_ON(!ibh); raw_inode = nilfs_ifile_map_inode(ifile, ii->vfs_inode.i_ino, ibh); nilfs_bmap_write(ii->i_bmap, raw_inode); nilfs_ifile_unmap_inode(ifile, ii->vfs_inode.i_ino, ibh); } } static void nilfs_segctor_fill_in_file_bmap(struct nilfs_sc_info *sci, struct inode *ifile) { struct nilfs_inode_info *ii; list_for_each_entry(ii, &sci->sc_dirty_files, i_dirty) { nilfs_fill_in_file_bmap(ifile, ii); set_bit(NILFS_I_COLLECTED, &ii->i_state); } } /* * CRC calculation routines */ static void nilfs_fill_in_super_root_crc(struct buffer_head *bh_sr, u32 seed) { struct nilfs_super_root *raw_sr = (struct nilfs_super_root *)bh_sr->b_data; u32 crc; crc = crc32_le(seed, (unsigned char *)raw_sr + sizeof(raw_sr->sr_sum), NILFS_SR_BYTES - sizeof(raw_sr->sr_sum)); raw_sr->sr_sum = cpu_to_le32(crc); } static void nilfs_segctor_fill_in_checksums(struct nilfs_sc_info *sci, u32 seed) { struct nilfs_segment_buffer *segbuf; if (sci->sc_super_root) nilfs_fill_in_super_root_crc(sci->sc_super_root, seed); list_for_each_entry(segbuf, &sci->sc_segbufs, sb_list) { nilfs_segbuf_fill_in_segsum_crc(segbuf, seed); nilfs_segbuf_fill_in_data_crc(segbuf, seed); } } static void nilfs_segctor_fill_in_super_root(struct nilfs_sc_info *sci, struct the_nilfs *nilfs) { struct buffer_head *bh_sr = sci->sc_super_root; struct nilfs_super_root *raw_sr = (struct nilfs_super_root *)bh_sr->b_data; unsigned isz = nilfs->ns_inode_size; raw_sr->sr_bytes = cpu_to_le16(NILFS_SR_BYTES); raw_sr->sr_nongc_ctime = cpu_to_le64(nilfs_doing_gc() ? nilfs->ns_nongc_ctime : sci->sc_seg_ctime); raw_sr->sr_flags = 0; nilfs_write_inode_common(nilfs_dat_inode(nilfs), (void *)raw_sr + NILFS_SR_DAT_OFFSET(isz), 1); nilfs_write_inode_common(nilfs->ns_cpfile, (void *)raw_sr + NILFS_SR_CPFILE_OFFSET(isz), 1); nilfs_write_inode_common(nilfs->ns_sufile, (void *)raw_sr + NILFS_SR_SUFILE_OFFSET(isz), 1); } static void nilfs_redirty_inodes(struct list_head *head) { struct nilfs_inode_info *ii; list_for_each_entry(ii, head, i_dirty) { if (test_bit(NILFS_I_COLLECTED, &ii->i_state)) clear_bit(NILFS_I_COLLECTED, &ii->i_state); } } static void nilfs_drop_collected_inodes(struct list_head *head) { struct nilfs_inode_info *ii; list_for_each_entry(ii, head, i_dirty) { if (!test_and_clear_bit(NILFS_I_COLLECTED, &ii->i_state)) continue; clear_bit(NILFS_I_INODE_DIRTY, &ii->i_state); set_bit(NILFS_I_UPDATED, &ii->i_state); } } static int nilfs_segctor_apply_buffers(struct nilfs_sc_info *sci, struct inode *inode, struct list_head *listp, int (*collect)(struct nilfs_sc_info *, struct buffer_head *, struct inode *)) { struct buffer_head *bh, *n; int err = 0; if (collect) { list_for_each_entry_safe(bh, n, listp, b_assoc_buffers) { list_del_init(&bh->b_assoc_buffers); err = collect(sci, bh, inode); brelse(bh); if (unlikely(err)) goto dispose_buffers; } return 0; } dispose_buffers: while (!list_empty(listp)) { bh = list_entry(listp->next, struct buffer_head, b_assoc_buffers); list_del_init(&bh->b_assoc_buffers); brelse(bh); } return err; } static size_t nilfs_segctor_buffer_rest(struct nilfs_sc_info *sci) { /* Remaining number of blocks within segment buffer */ return sci->sc_segbuf_nblocks - (sci->sc_nblk_this_inc + sci->sc_curseg->sb_sum.nblocks); } static int nilfs_segctor_scan_file(struct nilfs_sc_info *sci, struct inode *inode, struct nilfs_sc_operations *sc_ops) { LIST_HEAD(data_buffers); LIST_HEAD(node_buffers); int err; if (!(sci->sc_stage.flags & NILFS_CF_NODE)) { size_t n, rest = nilfs_segctor_buffer_rest(sci); n = nilfs_lookup_dirty_data_buffers( inode, &data_buffers, rest + 1, 0, LLONG_MAX); if (n > rest) { err = nilfs_segctor_apply_buffers( sci, inode, &data_buffers, sc_ops->collect_data); BUG_ON(!err); /* always receive -E2BIG or true error */ goto break_or_fail; } } nilfs_lookup_dirty_node_buffers(inode, &node_buffers); if (!(sci->sc_stage.flags & NILFS_CF_NODE)) { err = nilfs_segctor_apply_buffers( sci, inode, &data_buffers, sc_ops->collect_data); if (unlikely(err)) { /* dispose node list */ nilfs_segctor_apply_buffers( sci, inode, &node_buffers, NULL); goto break_or_fail; } sci->sc_stage.flags |= NILFS_CF_NODE; } /* Collect node */ err = nilfs_segctor_apply_buffers( sci, inode, &node_buffers, sc_ops->collect_node); if (unlikely(err)) goto break_or_fail; nilfs_bmap_lookup_dirty_buffers(NILFS_I(inode)->i_bmap, &node_buffers); err = nilfs_segctor_apply_buffers( sci, inode, &node_buffers, sc_ops->collect_bmap); if (unlikely(err)) goto break_or_fail; nilfs_segctor_end_finfo(sci, inode); sci->sc_stage.flags &= ~NILFS_CF_NODE; break_or_fail: return err; } static int nilfs_segctor_scan_file_dsync(struct nilfs_sc_info *sci, struct inode *inode) { LIST_HEAD(data_buffers); size_t n, rest = nilfs_segctor_buffer_rest(sci); int err; n = nilfs_lookup_dirty_data_buffers(inode, &data_buffers, rest + 1, sci->sc_dsync_start, sci->sc_dsync_end); err = nilfs_segctor_apply_buffers(sci, inode, &data_buffers, nilfs_collect_file_data); if (!err) { nilfs_segctor_end_finfo(sci, inode); BUG_ON(n > rest); /* always receive -E2BIG or true error if n > rest */ } return err; } static int nilfs_segctor_collect_blocks(struct nilfs_sc_info *sci, int mode) { struct nilfs_sb_info *sbi = sci->sc_sbi; struct the_nilfs *nilfs = sbi->s_nilfs; struct list_head *head; struct nilfs_inode_info *ii; size_t ndone; int err = 0; switch (sci->sc_stage.scnt) { case NILFS_ST_INIT: /* Pre-processes */ sci->sc_stage.flags = 0; if (!test_bit(NILFS_SC_UNCLOSED, &sci->sc_flags)) { sci->sc_nblk_inc = 0; sci->sc_curseg->sb_sum.flags = NILFS_SS_LOGBGN; if (mode == SC_LSEG_DSYNC) { sci->sc_stage.scnt = NILFS_ST_DSYNC; goto dsync_mode; } } sci->sc_stage.dirty_file_ptr = NULL; sci->sc_stage.gc_inode_ptr = NULL; if (mode == SC_FLUSH_DAT) { sci->sc_stage.scnt = NILFS_ST_DAT; goto dat_stage; } sci->sc_stage.scnt++; /* Fall through */ case NILFS_ST_GC: if (nilfs_doing_gc()) { head = &sci->sc_gc_inodes; ii = list_prepare_entry(sci->sc_stage.gc_inode_ptr, head, i_dirty); list_for_each_entry_continue(ii, head, i_dirty) { err = nilfs_segctor_scan_file( sci, &ii->vfs_inode, &nilfs_sc_file_ops); if (unlikely(err)) { sci->sc_stage.gc_inode_ptr = list_entry( ii->i_dirty.prev, struct nilfs_inode_info, i_dirty); goto break_or_fail; } set_bit(NILFS_I_COLLECTED, &ii->i_state); } sci->sc_stage.gc_inode_ptr = NULL; } sci->sc_stage.scnt++; /* Fall through */ case NILFS_ST_FILE: head = &sci->sc_dirty_files; ii = list_prepare_entry(sci->sc_stage.dirty_file_ptr, head, i_dirty); list_for_each_entry_continue(ii, head, i_dirty) { clear_bit(NILFS_I_DIRTY, &ii->i_state); err = nilfs_segctor_scan_file(sci, &ii->vfs_inode, &nilfs_sc_file_ops); if (unlikely(err)) { sci->sc_stage.dirty_file_ptr = list_entry(ii->i_dirty.prev, struct nilfs_inode_info, i_dirty); goto break_or_fail; } /* sci->sc_stage.dirty_file_ptr = NILFS_I(inode); */ /* XXX: required ? */ } sci->sc_stage.dirty_file_ptr = NULL; if (mode == SC_FLUSH_FILE) { sci->sc_stage.scnt = NILFS_ST_DONE; return 0; } sci->sc_stage.scnt++; sci->sc_stage.flags |= NILFS_CF_IFILE_STARTED; /* Fall through */ case NILFS_ST_IFILE: err = nilfs_segctor_scan_file(sci, sbi->s_ifile, &nilfs_sc_file_ops); if (unlikely(err)) break; sci->sc_stage.scnt++; /* Creating a checkpoint */ err = nilfs_segctor_create_checkpoint(sci); if (unlikely(err)) break; /* Fall through */ case NILFS_ST_CPFILE: err = nilfs_segctor_scan_file(sci, nilfs->ns_cpfile, &nilfs_sc_file_ops); if (unlikely(err)) break; sci->sc_stage.scnt++; /* Fall through */ case NILFS_ST_SUFILE: err = nilfs_sufile_freev(nilfs->ns_sufile, sci->sc_freesegs, sci->sc_nfreesegs, &ndone); if (unlikely(err)) { nilfs_sufile_cancel_freev(nilfs->ns_sufile, sci->sc_freesegs, ndone, NULL); break; } sci->sc_stage.flags |= NILFS_CF_SUFREED; err = nilfs_segctor_scan_file(sci, nilfs->ns_sufile, &nilfs_sc_file_ops); if (unlikely(err)) break; sci->sc_stage.scnt++; /* Fall through */ case NILFS_ST_DAT: dat_stage: err = nilfs_segctor_scan_file(sci, nilfs_dat_inode(nilfs), &nilfs_sc_dat_ops); if (unlikely(err)) break; if (mode == SC_FLUSH_DAT) { sci->sc_stage.scnt = NILFS_ST_DONE; return 0; } sci->sc_stage.scnt++; /* Fall through */ case NILFS_ST_SR: if (mode == SC_LSEG_SR) { /* Appending a super root */ err = nilfs_segctor_add_super_root(sci); if (unlikely(err)) break; } /* End of a logical segment */ sci->sc_curseg->sb_sum.flags |= NILFS_SS_LOGEND; sci->sc_stage.scnt = NILFS_ST_DONE; return 0; case NILFS_ST_DSYNC: dsync_mode: sci->sc_curseg->sb_sum.flags |= NILFS_SS_SYNDT; ii = sci->sc_dsync_inode; if (!test_bit(NILFS_I_BUSY, &ii->i_state)) break; err = nilfs_segctor_scan_file_dsync(sci, &ii->vfs_inode); if (unlikely(err)) break; sci->sc_curseg->sb_sum.flags |= NILFS_SS_LOGEND; sci->sc_stage.scnt = NILFS_ST_DONE; return 0; case NILFS_ST_DONE: return 0; default: BUG(); } break_or_fail: return err; } /** * nilfs_segctor_begin_construction - setup segment buffer to make a new log * @sci: nilfs_sc_info * @nilfs: nilfs object */ static int nilfs_segctor_begin_construction(struct nilfs_sc_info *sci, struct the_nilfs *nilfs) { struct nilfs_segment_buffer *segbuf, *prev; __u64 nextnum; int err, alloc = 0; segbuf = nilfs_segbuf_new(sci->sc_super); if (unlikely(!segbuf)) return -ENOMEM; if (list_empty(&sci->sc_write_logs)) { nilfs_segbuf_map(segbuf, nilfs->ns_segnum, nilfs->ns_pseg_offset, nilfs); if (segbuf->sb_rest_blocks < NILFS_PSEG_MIN_BLOCKS) { nilfs_shift_to_next_segment(nilfs); nilfs_segbuf_map(segbuf, nilfs->ns_segnum, 0, nilfs); } segbuf->sb_sum.seg_seq = nilfs->ns_seg_seq; nextnum = nilfs->ns_nextnum; if (nilfs->ns_segnum == nilfs->ns_nextnum) /* Start from the head of a new full segment */ alloc++; } else { /* Continue logs */ prev = NILFS_LAST_SEGBUF(&sci->sc_write_logs); nilfs_segbuf_map_cont(segbuf, prev); segbuf->sb_sum.seg_seq = prev->sb_sum.seg_seq; nextnum = prev->sb_nextnum; if (segbuf->sb_rest_blocks < NILFS_PSEG_MIN_BLOCKS) { nilfs_segbuf_map(segbuf, prev->sb_nextnum, 0, nilfs); segbuf->sb_sum.seg_seq++; alloc++; } } err = nilfs_sufile_mark_dirty(nilfs->ns_sufile, segbuf->sb_segnum); if (err) goto failed; if (alloc) { err = nilfs_sufile_alloc(nilfs->ns_sufile, &nextnum); if (err) goto failed; } nilfs_segbuf_set_next_segnum(segbuf, nextnum, nilfs); BUG_ON(!list_empty(&sci->sc_segbufs)); list_add_tail(&segbuf->sb_list, &sci->sc_segbufs); sci->sc_segbuf_nblocks = segbuf->sb_rest_blocks; return 0; failed: nilfs_segbuf_free(segbuf); return err; } static int nilfs_segctor_extend_segments(struct nilfs_sc_info *sci, struct the_nilfs *nilfs, int nadd) { struct nilfs_segment_buffer *segbuf, *prev; struct inode *sufile = nilfs->ns_sufile; __u64 nextnextnum; LIST_HEAD(list); int err, ret, i; prev = NILFS_LAST_SEGBUF(&sci->sc_segbufs); /* * Since the segment specified with nextnum might be allocated during * the previous construction, the buffer including its segusage may * not be dirty. The following call ensures that the buffer is dirty * and will pin the buffer on memory until the sufile is written. */ err = nilfs_sufile_mark_dirty(sufile, prev->sb_nextnum); if (unlikely(err)) return err; for (i = 0; i < nadd; i++) { /* extend segment info */ err = -ENOMEM; segbuf = nilfs_segbuf_new(sci->sc_super); if (unlikely(!segbuf)) goto failed; /* map this buffer to region of segment on-disk */ nilfs_segbuf_map(segbuf, prev->sb_nextnum, 0, nilfs); sci->sc_segbuf_nblocks += segbuf->sb_rest_blocks; /* allocate the next next full segment */ err = nilfs_sufile_alloc(sufile, &nextnextnum); if (unlikely(err)) goto failed_segbuf; segbuf->sb_sum.seg_seq = prev->sb_sum.seg_seq + 1; nilfs_segbuf_set_next_segnum(segbuf, nextnextnum, nilfs); list_add_tail(&segbuf->sb_list, &list); prev = segbuf; } list_splice_tail(&list, &sci->sc_segbufs); return 0; failed_segbuf: nilfs_segbuf_free(segbuf); failed: list_for_each_entry(segbuf, &list, sb_list) { ret = nilfs_sufile_free(sufile, segbuf->sb_nextnum); WARN_ON(ret); /* never fails */ } nilfs_destroy_logs(&list); return err; } static void nilfs_free_incomplete_logs(struct list_head *logs, struct the_nilfs *nilfs) { struct nilfs_segment_buffer *segbuf, *prev; struct inode *sufile = nilfs->ns_sufile; int ret; segbuf = NILFS_FIRST_SEGBUF(logs); if (nilfs->ns_nextnum != segbuf->sb_nextnum) { ret = nilfs_sufile_free(sufile, segbuf->sb_nextnum); WARN_ON(ret); /* never fails */ } if (atomic_read(&segbuf->sb_err)) { /* Case 1: The first segment failed */ if (segbuf->sb_pseg_start != segbuf->sb_fseg_start) /* Case 1a: Partial segment appended into an existing segment */ nilfs_terminate_segment(nilfs, segbuf->sb_fseg_start, segbuf->sb_fseg_end); else /* Case 1b: New full segment */ set_nilfs_discontinued(nilfs); } prev = segbuf; list_for_each_entry_continue(segbuf, logs, sb_list) { if (prev->sb_nextnum != segbuf->sb_nextnum) { ret = nilfs_sufile_free(sufile, segbuf->sb_nextnum); WARN_ON(ret); /* never fails */ } if (atomic_read(&segbuf->sb_err) && segbuf->sb_segnum != nilfs->ns_nextnum) /* Case 2: extended segment (!= next) failed */ nilfs_sufile_set_error(sufile, segbuf->sb_segnum); prev = segbuf; } } static void nilfs_segctor_update_segusage(struct nilfs_sc_info *sci, struct inode *sufile) { struct nilfs_segment_buffer *segbuf; unsigned long live_blocks; int ret; list_for_each_entry(segbuf, &sci->sc_segbufs, sb_list) { live_blocks = segbuf->sb_sum.nblocks + (segbuf->sb_pseg_start - segbuf->sb_fseg_start); ret = nilfs_sufile_set_segment_usage(sufile, segbuf->sb_segnum, live_blocks, sci->sc_seg_ctime); WARN_ON(ret); /* always succeed because the segusage is dirty */ } } static void nilfs_cancel_segusage(struct list_head *logs, struct inode *sufile) { struct nilfs_segment_buffer *segbuf; int ret; segbuf = NILFS_FIRST_SEGBUF(logs); ret = nilfs_sufile_set_segment_usage(sufile, segbuf->sb_segnum, segbuf->sb_pseg_start - segbuf->sb_fseg_start, 0); WARN_ON(ret); /* always succeed because the segusage is dirty */ list_for_each_entry_continue(segbuf, logs, sb_list) { ret = nilfs_sufile_set_segment_usage(sufile, segbuf->sb_segnum, 0, 0); WARN_ON(ret); /* always succeed */ } } static void nilfs_segctor_truncate_segments(struct nilfs_sc_info *sci, struct nilfs_segment_buffer *last, struct inode *sufile) { struct nilfs_segment_buffer *segbuf = last; int ret; list_for_each_entry_continue(segbuf, &sci->sc_segbufs, sb_list) { sci->sc_segbuf_nblocks -= segbuf->sb_rest_blocks; ret = nilfs_sufile_free(sufile, segbuf->sb_nextnum); WARN_ON(ret); } nilfs_truncate_logs(&sci->sc_segbufs, last); } static int nilfs_segctor_collect(struct nilfs_sc_info *sci, struct the_nilfs *nilfs, int mode) { struct nilfs_cstage prev_stage = sci->sc_stage; int err, nadd = 1; /* Collection retry loop */ for (;;) { sci->sc_super_root = NULL; sci->sc_nblk_this_inc = 0; sci->sc_curseg = NILFS_FIRST_SEGBUF(&sci->sc_segbufs); err = nilfs_segctor_reset_segment_buffer(sci); if (unlikely(err)) goto failed; err = nilfs_segctor_collect_blocks(sci, mode); sci->sc_nblk_this_inc += sci->sc_curseg->sb_sum.nblocks; if (!err) break; if (unlikely(err != -E2BIG)) goto failed; /* The current segment is filled up */ if (mode != SC_LSEG_SR || sci->sc_stage.scnt < NILFS_ST_CPFILE) break; nilfs_clear_logs(&sci->sc_segbufs); err = nilfs_segctor_extend_segments(sci, nilfs, nadd); if (unlikely(err)) return err; if (sci->sc_stage.flags & NILFS_CF_SUFREED) { err = nilfs_sufile_cancel_freev(nilfs->ns_sufile, sci->sc_freesegs, sci->sc_nfreesegs, NULL); WARN_ON(err); /* do not happen */ } nadd = min_t(int, nadd << 1, SC_MAX_SEGDELTA); sci->sc_stage = prev_stage; } nilfs_segctor_truncate_segments(sci, sci->sc_curseg, nilfs->ns_sufile); return 0; failed: return err; } static void nilfs_list_replace_buffer(struct buffer_head *old_bh, struct buffer_head *new_bh) { BUG_ON(!list_empty(&new_bh->b_assoc_buffers)); list_replace_init(&old_bh->b_assoc_buffers, &new_bh->b_assoc_buffers); /* The caller must release old_bh */ } static int nilfs_segctor_update_payload_blocknr(struct nilfs_sc_info *sci, struct nilfs_segment_buffer *segbuf, int mode) { struct inode *inode = NULL; sector_t blocknr; unsigned long nfinfo = segbuf->sb_sum.nfinfo; unsigned long nblocks = 0, ndatablk = 0; struct nilfs_sc_operations *sc_op = NULL; struct nilfs_segsum_pointer ssp; struct nilfs_finfo *finfo = NULL; union nilfs_binfo binfo; struct buffer_head *bh, *bh_org; ino_t ino = 0; int err = 0; if (!nfinfo) goto out; blocknr = segbuf->sb_pseg_start + segbuf->sb_sum.nsumblk; ssp.bh = NILFS_SEGBUF_FIRST_BH(&segbuf->sb_segsum_buffers); ssp.offset = sizeof(struct nilfs_segment_summary); list_for_each_entry(bh, &segbuf->sb_payload_buffers, b_assoc_buffers) { if (bh == sci->sc_super_root) break; if (!finfo) { finfo = nilfs_segctor_map_segsum_entry( sci, &ssp, sizeof(*finfo)); ino = le64_to_cpu(finfo->fi_ino); nblocks = le32_to_cpu(finfo->fi_nblocks); ndatablk = le32_to_cpu(finfo->fi_ndatablk); if (buffer_nilfs_node(bh)) inode = NILFS_BTNC_I(bh->b_page->mapping); else inode = NILFS_AS_I(bh->b_page->mapping); if (mode == SC_LSEG_DSYNC) sc_op = &nilfs_sc_dsync_ops; else if (ino == NILFS_DAT_INO) sc_op = &nilfs_sc_dat_ops; else /* file blocks */ sc_op = &nilfs_sc_file_ops; } bh_org = bh; get_bh(bh_org); err = nilfs_bmap_assign(NILFS_I(inode)->i_bmap, &bh, blocknr, &binfo); if (bh != bh_org) nilfs_list_replace_buffer(bh_org, bh); brelse(bh_org); if (unlikely(err)) goto failed_bmap; if (ndatablk > 0) sc_op->write_data_binfo(sci, &ssp, &binfo); else sc_op->write_node_binfo(sci, &ssp, &binfo); blocknr++; if (--nblocks == 0) { finfo = NULL; if (--nfinfo == 0) break; } else if (ndatablk > 0) ndatablk--; } out: return 0; failed_bmap: err = nilfs_handle_bmap_error(err, __func__, inode, sci->sc_super); return err; } static int nilfs_segctor_assign(struct nilfs_sc_info *sci, int mode) { struct nilfs_segment_buffer *segbuf; int err; list_for_each_entry(segbuf, &sci->sc_segbufs, sb_list) { err = nilfs_segctor_update_payload_blocknr(sci, segbuf, mode); if (unlikely(err)) return err; nilfs_segbuf_fill_in_segsum(segbuf); } return 0; } static int nilfs_copy_replace_page_buffers(struct page *page, struct list_head *out) { struct page *clone_page; struct buffer_head *bh, *head, *bh2; void *kaddr; bh = head = page_buffers(page); clone_page = nilfs_alloc_private_page(bh->b_bdev, bh->b_size, 0); if (unlikely(!clone_page)) return -ENOMEM; bh2 = page_buffers(clone_page); kaddr = kmap_atomic(page, KM_USER0); do { if (list_empty(&bh->b_assoc_buffers)) continue; get_bh(bh2); page_cache_get(clone_page); /* for each bh */ memcpy(bh2->b_data, kaddr + bh_offset(bh), bh2->b_size); bh2->b_blocknr = bh->b_blocknr; list_replace(&bh->b_assoc_buffers, &bh2->b_assoc_buffers); list_add_tail(&bh->b_assoc_buffers, out); } while (bh = bh->b_this_page, bh2 = bh2->b_this_page, bh != head); kunmap_atomic(kaddr, KM_USER0); if (!TestSetPageWriteback(clone_page)) inc_zone_page_state(clone_page, NR_WRITEBACK); unlock_page(clone_page); return 0; } static int nilfs_test_page_to_be_frozen(struct page *page) { struct address_space *mapping = page->mapping; if (!mapping || !mapping->host || S_ISDIR(mapping->host->i_mode)) return 0; if (page_mapped(page)) { ClearPageChecked(page); return 1; } return PageChecked(page); } static int nilfs_begin_page_io(struct page *page, struct list_head *out) { if (!page || PageWriteback(page)) /* For split b-tree node pages, this function may be called twice. We ignore the 2nd or later calls by this check. */ return 0; lock_page(page); clear_page_dirty_for_io(page); set_page_writeback(page); unlock_page(page); if (nilfs_test_page_to_be_frozen(page)) { int err = nilfs_copy_replace_page_buffers(page, out); if (unlikely(err)) return err; } return 0; } static int nilfs_segctor_prepare_write(struct nilfs_sc_info *sci, struct page **failed_page) { struct nilfs_segment_buffer *segbuf; struct page *bd_page = NULL, *fs_page = NULL; struct list_head *list = &sci->sc_copied_buffers; int err; *failed_page = NULL; list_for_each_entry(segbuf, &sci->sc_segbufs, sb_list) { struct buffer_head *bh; list_for_each_entry(bh, &segbuf->sb_segsum_buffers, b_assoc_buffers) { if (bh->b_page != bd_page) { if (bd_page) { lock_page(bd_page); clear_page_dirty_for_io(bd_page); set_page_writeback(bd_page); unlock_page(bd_page); } bd_page = bh->b_page; } } list_for_each_entry(bh, &segbuf->sb_payload_buffers, b_assoc_buffers) { if (bh == sci->sc_super_root) { if (bh->b_page != bd_page) { lock_page(bd_page); clear_page_dirty_for_io(bd_page); set_page_writeback(bd_page); unlock_page(bd_page); bd_page = bh->b_page; } break; } if (bh->b_page != fs_page) { err = nilfs_begin_page_io(fs_page, list); if (unlikely(err)) { *failed_page = fs_page; goto out; } fs_page = bh->b_page; } } } if (bd_page) { lock_page(bd_page); clear_page_dirty_for_io(bd_page); set_page_writeback(bd_page); unlock_page(bd_page); } err = nilfs_begin_page_io(fs_page, list); if (unlikely(err)) *failed_page = fs_page; out: return err; } static int nilfs_segctor_write(struct nilfs_sc_info *sci, struct the_nilfs *nilfs) { int ret; ret = nilfs_write_logs(&sci->sc_segbufs, nilfs); list_splice_tail_init(&sci->sc_segbufs, &sci->sc_write_logs); return ret; } static void __nilfs_end_page_io(struct page *page, int err) { if (!err) { if (!nilfs_page_buffers_clean(page)) __set_page_dirty_nobuffers(page); ClearPageError(page); } else { __set_page_dirty_nobuffers(page); SetPageError(page); } if (buffer_nilfs_allocated(page_buffers(page))) { if (TestClearPageWriteback(page)) dec_zone_page_state(page, NR_WRITEBACK); } else end_page_writeback(page); } static void nilfs_end_page_io(struct page *page, int err) { if (!page) return; if (buffer_nilfs_node(page_buffers(page)) && !PageWriteback(page)) { /* * For b-tree node pages, this function may be called twice * or more because they might be split in a segment. */ if (PageDirty(page)) { /* * For pages holding split b-tree node buffers, dirty * flag on the buffers may be cleared discretely. * In that case, the page is once redirtied for * remaining buffers, and it must be cancelled if * all the buffers get cleaned later. */ lock_page(page); if (nilfs_page_buffers_clean(page)) __nilfs_clear_page_dirty(page); unlock_page(page); } return; } __nilfs_end_page_io(page, err); } static void nilfs_clear_copied_buffers(struct list_head *list, int err) { struct buffer_head *bh, *head; struct page *page; while (!list_empty(list)) { bh = list_entry(list->next, struct buffer_head, b_assoc_buffers); page = bh->b_page; page_cache_get(page); head = bh = page_buffers(page); do { if (!list_empty(&bh->b_assoc_buffers)) { list_del_init(&bh->b_assoc_buffers); if (!err) { set_buffer_uptodate(bh); clear_buffer_dirty(bh); clear_buffer_nilfs_volatile(bh); } brelse(bh); /* for b_assoc_buffers */ } } while ((bh = bh->b_this_page) != head); __nilfs_end_page_io(page, err); page_cache_release(page); } } static void nilfs_abort_logs(struct list_head *logs, struct page *failed_page, struct buffer_head *bh_sr, int err) { struct nilfs_segment_buffer *segbuf; struct page *bd_page = NULL, *fs_page = NULL; struct buffer_head *bh; if (list_empty(logs)) return; list_for_each_entry(segbuf, logs, sb_list) { list_for_each_entry(bh, &segbuf->sb_segsum_buffers, b_assoc_buffers) { if (bh->b_page != bd_page) { if (bd_page) end_page_writeback(bd_page); bd_page = bh->b_page; } } list_for_each_entry(bh, &segbuf->sb_payload_buffers, b_assoc_buffers) { if (bh == bh_sr) { if (bh->b_page != bd_page) { end_page_writeback(bd_page); bd_page = bh->b_page; } break; } if (bh->b_page != fs_page) { nilfs_end_page_io(fs_page, err); if (fs_page && fs_page == failed_page) return; fs_page = bh->b_page; } } } if (bd_page) end_page_writeback(bd_page); nilfs_end_page_io(fs_page, err); } static void nilfs_segctor_abort_construction(struct nilfs_sc_info *sci, struct the_nilfs *nilfs, int err) { LIST_HEAD(logs); int ret; list_splice_tail_init(&sci->sc_write_logs, &logs); ret = nilfs_wait_on_logs(&logs); nilfs_abort_logs(&logs, NULL, sci->sc_super_root, ret ? : err); list_splice_tail_init(&sci->sc_segbufs, &logs); nilfs_cancel_segusage(&logs, nilfs->ns_sufile); nilfs_free_incomplete_logs(&logs, nilfs); nilfs_clear_copied_buffers(&sci->sc_copied_buffers, err); if (sci->sc_stage.flags & NILFS_CF_SUFREED) { ret = nilfs_sufile_cancel_freev(nilfs->ns_sufile, sci->sc_freesegs, sci->sc_nfreesegs, NULL); WARN_ON(ret); /* do not happen */ } nilfs_destroy_logs(&logs); sci->sc_super_root = NULL; } static void nilfs_set_next_segment(struct the_nilfs *nilfs, struct nilfs_segment_buffer *segbuf) { nilfs->ns_segnum = segbuf->sb_segnum; nilfs->ns_nextnum = segbuf->sb_nextnum; nilfs->ns_pseg_offset = segbuf->sb_pseg_start - segbuf->sb_fseg_start + segbuf->sb_sum.nblocks; nilfs->ns_seg_seq = segbuf->sb_sum.seg_seq; nilfs->ns_ctime = segbuf->sb_sum.ctime; } static void nilfs_segctor_complete_write(struct nilfs_sc_info *sci) { struct nilfs_segment_buffer *segbuf; struct page *bd_page = NULL, *fs_page = NULL; struct the_nilfs *nilfs = sci->sc_sbi->s_nilfs; int update_sr = (sci->sc_super_root != NULL); list_for_each_entry(segbuf, &sci->sc_write_logs, sb_list) { struct buffer_head *bh; list_for_each_entry(bh, &segbuf->sb_segsum_buffers, b_assoc_buffers) { set_buffer_uptodate(bh); clear_buffer_dirty(bh); if (bh->b_page != bd_page) { if (bd_page) end_page_writeback(bd_page); bd_page = bh->b_page; } } /* * We assume that the buffers which belong to the same page * continue over the buffer list. * Under this assumption, the last BHs of pages is * identifiable by the discontinuity of bh->b_page * (page != fs_page). * * For B-tree node blocks, however, this assumption is not * guaranteed. The cleanup code of B-tree node pages needs * special care. */ list_for_each_entry(bh, &segbuf->sb_payload_buffers, b_assoc_buffers) { set_buffer_uptodate(bh); clear_buffer_dirty(bh); clear_buffer_nilfs_volatile(bh); if (bh == sci->sc_super_root) { if (bh->b_page != bd_page) { end_page_writeback(bd_page); bd_page = bh->b_page; } break; } if (bh->b_page != fs_page) { nilfs_end_page_io(fs_page, 0); fs_page = bh->b_page; } } if (!NILFS_SEG_SIMPLEX(&segbuf->sb_sum)) { if (NILFS_SEG_LOGBGN(&segbuf->sb_sum)) { set_bit(NILFS_SC_UNCLOSED, &sci->sc_flags); sci->sc_lseg_stime = jiffies; } if (NILFS_SEG_LOGEND(&segbuf->sb_sum)) clear_bit(NILFS_SC_UNCLOSED, &sci->sc_flags); } } /* * Since pages may continue over multiple segment buffers, * end of the last page must be checked outside of the loop. */ if (bd_page) end_page_writeback(bd_page); nilfs_end_page_io(fs_page, 0); nilfs_clear_copied_buffers(&sci->sc_copied_buffers, 0); nilfs_drop_collected_inodes(&sci->sc_dirty_files); if (nilfs_doing_gc()) { nilfs_drop_collected_inodes(&sci->sc_gc_inodes); if (update_sr) nilfs_commit_gcdat_inode(nilfs); } else nilfs->ns_nongc_ctime = sci->sc_seg_ctime; sci->sc_nblk_inc += sci->sc_nblk_this_inc; segbuf = NILFS_LAST_SEGBUF(&sci->sc_write_logs); nilfs_set_next_segment(nilfs, segbuf); if (update_sr) { nilfs_set_last_segment(nilfs, segbuf->sb_pseg_start, segbuf->sb_sum.seg_seq, nilfs->ns_cno++); set_nilfs_sb_dirty(nilfs); clear_bit(NILFS_SC_HAVE_DELTA, &sci->sc_flags); clear_bit(NILFS_SC_DIRTY, &sci->sc_flags); set_bit(NILFS_SC_SUPER_ROOT, &sci->sc_flags); nilfs_segctor_clear_metadata_dirty(sci); } else clear_bit(NILFS_SC_SUPER_ROOT, &sci->sc_flags); } static int nilfs_segctor_wait(struct nilfs_sc_info *sci) { int ret; ret = nilfs_wait_on_logs(&sci->sc_write_logs); if (!ret) { nilfs_segctor_complete_write(sci); nilfs_destroy_logs(&sci->sc_write_logs); } return ret; } static int nilfs_segctor_check_in_files(struct nilfs_sc_info *sci, struct nilfs_sb_info *sbi) { struct nilfs_inode_info *ii, *n; __u64 cno = sbi->s_nilfs->ns_cno; spin_lock(&sbi->s_inode_lock); retry: list_for_each_entry_safe(ii, n, &sbi->s_dirty_files, i_dirty) { if (!ii->i_bh) { struct buffer_head *ibh; int err; spin_unlock(&sbi->s_inode_lock); err = nilfs_ifile_get_inode_block( sbi->s_ifile, ii->vfs_inode.i_ino, &ibh); if (unlikely(err)) { nilfs_warning(sbi->s_super, __func__, "failed to get inode block.\n"); return err; } nilfs_mdt_mark_buffer_dirty(ibh); nilfs_mdt_mark_dirty(sbi->s_ifile); spin_lock(&sbi->s_inode_lock); if (likely(!ii->i_bh)) ii->i_bh = ibh; else brelse(ibh); goto retry; } ii->i_cno = cno; clear_bit(NILFS_I_QUEUED, &ii->i_state); set_bit(NILFS_I_BUSY, &ii->i_state); list_del(&ii->i_dirty); list_add_tail(&ii->i_dirty, &sci->sc_dirty_files); } spin_unlock(&sbi->s_inode_lock); NILFS_I(sbi->s_ifile)->i_cno = cno; return 0; } static void nilfs_segctor_check_out_files(struct nilfs_sc_info *sci, struct nilfs_sb_info *sbi) { struct nilfs_transaction_info *ti = current->journal_info; struct nilfs_inode_info *ii, *n; __u64 cno = sbi->s_nilfs->ns_cno; spin_lock(&sbi->s_inode_lock); list_for_each_entry_safe(ii, n, &sci->sc_dirty_files, i_dirty) { if (!test_and_clear_bit(NILFS_I_UPDATED, &ii->i_state) || test_bit(NILFS_I_DIRTY, &ii->i_state)) { /* The current checkpoint number (=nilfs->ns_cno) is changed between check-in and check-out only if the super root is written out. So, we can update i_cno for the inodes that remain in the dirty list. */ ii->i_cno = cno; continue; } clear_bit(NILFS_I_BUSY, &ii->i_state); brelse(ii->i_bh); ii->i_bh = NULL; list_del(&ii->i_dirty); list_add_tail(&ii->i_dirty, &ti->ti_garbage); } spin_unlock(&sbi->s_inode_lock); } /* * Main procedure of segment constructor */ static int nilfs_segctor_do_construct(struct nilfs_sc_info *sci, int mode) { struct nilfs_sb_info *sbi = sci->sc_sbi; struct the_nilfs *nilfs = sbi->s_nilfs; struct page *failed_page; int err, has_sr = 0; sci->sc_stage.scnt = NILFS_ST_INIT; err = nilfs_segctor_check_in_files(sci, sbi); if (unlikely(err)) goto out; if (nilfs_test_metadata_dirty(sbi)) set_bit(NILFS_SC_DIRTY, &sci->sc_flags); if (nilfs_segctor_clean(sci)) goto out; do { sci->sc_stage.flags &= ~NILFS_CF_HISTORY_MASK; err = nilfs_segctor_begin_construction(sci, nilfs); if (unlikely(err)) goto out; /* Update time stamp */ sci->sc_seg_ctime = get_seconds(); err = nilfs_segctor_collect(sci, nilfs, mode); if (unlikely(err)) goto failed; has_sr = (sci->sc_super_root != NULL); /* Avoid empty segment */ if (sci->sc_stage.scnt == NILFS_ST_DONE && NILFS_SEG_EMPTY(&sci->sc_curseg->sb_sum)) { nilfs_segctor_abort_construction(sci, nilfs, 1); goto out; } err = nilfs_segctor_assign(sci, mode); if (unlikely(err)) goto failed; if (sci->sc_stage.flags & NILFS_CF_IFILE_STARTED) nilfs_segctor_fill_in_file_bmap(sci, sbi->s_ifile); if (has_sr) { err = nilfs_segctor_fill_in_checkpoint(sci); if (unlikely(err)) goto failed_to_write; nilfs_segctor_fill_in_super_root(sci, nilfs); } nilfs_segctor_update_segusage(sci, nilfs->ns_sufile); /* Write partial segments */ err = nilfs_segctor_prepare_write(sci, &failed_page); if (err) { nilfs_abort_logs(&sci->sc_segbufs, failed_page, sci->sc_super_root, err); goto failed_to_write; } nilfs_segctor_fill_in_checksums(sci, nilfs->ns_crc_seed); err = nilfs_segctor_write(sci, nilfs); if (unlikely(err)) goto failed_to_write; if (sci->sc_stage.scnt == NILFS_ST_DONE || nilfs->ns_blocksize_bits != PAGE_CACHE_SHIFT) { /* * At this point, we avoid double buffering * for blocksize < pagesize because page dirty * flag is turned off during write and dirty * buffers are not properly collected for * pages crossing over segments. */ err = nilfs_segctor_wait(sci); if (err) goto failed_to_write; } } while (sci->sc_stage.scnt != NILFS_ST_DONE); sci->sc_super_root = NULL; out: nilfs_segctor_check_out_files(sci, sbi); return err; failed_to_write: if (sci->sc_stage.flags & NILFS_CF_IFILE_STARTED) nilfs_redirty_inodes(&sci->sc_dirty_files); failed: if (nilfs_doing_gc()) nilfs_redirty_inodes(&sci->sc_gc_inodes); nilfs_segctor_abort_construction(sci, nilfs, err); goto out; } /** * nilfs_segctor_start_timer - set timer of background write * @sci: nilfs_sc_info * * If the timer has already been set, it ignores the new request. * This function MUST be called within a section locking the segment * semaphore. */ static void nilfs_segctor_start_timer(struct nilfs_sc_info *sci) { spin_lock(&sci->sc_state_lock); if (sci->sc_timer && !(sci->sc_state & NILFS_SEGCTOR_COMMIT)) { sci->sc_timer->expires = jiffies + sci->sc_interval; add_timer(sci->sc_timer); sci->sc_state |= NILFS_SEGCTOR_COMMIT; } spin_unlock(&sci->sc_state_lock); } static void nilfs_segctor_do_flush(struct nilfs_sc_info *sci, int bn) { spin_lock(&sci->sc_state_lock); if (!(sci->sc_flush_request & (1 << bn))) { unsigned long prev_req = sci->sc_flush_request; sci->sc_flush_request |= (1 << bn); if (!prev_req) wake_up(&sci->sc_wait_daemon); } spin_unlock(&sci->sc_state_lock); } /** * nilfs_flush_segment - trigger a segment construction for resource control * @sb: super block * @ino: inode number of the file to be flushed out. */ void nilfs_flush_segment(struct super_block *sb, ino_t ino) { struct nilfs_sb_info *sbi = NILFS_SB(sb); struct nilfs_sc_info *sci = NILFS_SC(sbi); if (!sci || nilfs_doing_construction()) return; nilfs_segctor_do_flush(sci, NILFS_MDT_INODE(sb, ino) ? ino : 0); /* assign bit 0 to data files */ } struct nilfs_segctor_wait_request { wait_queue_t wq; __u32 seq; int err; atomic_t done; }; static int nilfs_segctor_sync(struct nilfs_sc_info *sci) { struct nilfs_segctor_wait_request wait_req; int err = 0; spin_lock(&sci->sc_state_lock); init_wait(&wait_req.wq); wait_req.err = 0; atomic_set(&wait_req.done, 0); wait_req.seq = ++sci->sc_seq_request; spin_unlock(&sci->sc_state_lock); init_waitqueue_entry(&wait_req.wq, current); add_wait_queue(&sci->sc_wait_request, &wait_req.wq); set_current_state(TASK_INTERRUPTIBLE); wake_up(&sci->sc_wait_daemon); for (;;) { if (atomic_read(&wait_req.done)) { err = wait_req.err; break; } if (!signal_pending(current)) { schedule(); continue; } err = -ERESTARTSYS; break; } finish_wait(&sci->sc_wait_request, &wait_req.wq); return err; } static void nilfs_segctor_wakeup(struct nilfs_sc_info *sci, int err) { struct nilfs_segctor_wait_request *wrq, *n; unsigned long flags; spin_lock_irqsave(&sci->sc_wait_request.lock, flags); list_for_each_entry_safe(wrq, n, &sci->sc_wait_request.task_list, wq.task_list) { if (!atomic_read(&wrq->done) && nilfs_cnt32_ge(sci->sc_seq_done, wrq->seq)) { wrq->err = err; atomic_set(&wrq->done, 1); } if (atomic_read(&wrq->done)) { wrq->wq.func(&wrq->wq, TASK_UNINTERRUPTIBLE | TASK_INTERRUPTIBLE, 0, NULL); } } spin_unlock_irqrestore(&sci->sc_wait_request.lock, flags); } /** * nilfs_construct_segment - construct a logical segment * @sb: super block * * Return Value: On success, 0 is retured. On errors, one of the following * negative error code is returned. * * %-EROFS - Read only filesystem. * * %-EIO - I/O error * * %-ENOSPC - No space left on device (only in a panic state). * * %-ERESTARTSYS - Interrupted. * * %-ENOMEM - Insufficient memory available. */ int nilfs_construct_segment(struct super_block *sb) { struct nilfs_sb_info *sbi = NILFS_SB(sb); struct nilfs_sc_info *sci = NILFS_SC(sbi); struct nilfs_transaction_info *ti; int err; if (!sci) return -EROFS; /* A call inside transactions causes a deadlock. */ BUG_ON((ti = current->journal_info) && ti->ti_magic == NILFS_TI_MAGIC); err = nilfs_segctor_sync(sci); return err; } /** * nilfs_construct_dsync_segment - construct a data-only logical segment * @sb: super block * @inode: inode whose data blocks should be written out * @start: start byte offset * @end: end byte offset (inclusive) * * Return Value: On success, 0 is retured. On errors, one of the following * negative error code is returned. * * %-EROFS - Read only filesystem. * * %-EIO - I/O error * * %-ENOSPC - No space left on device (only in a panic state). * * %-ERESTARTSYS - Interrupted. * * %-ENOMEM - Insufficient memory available. */ int nilfs_construct_dsync_segment(struct super_block *sb, struct inode *inode, loff_t start, loff_t end) { struct nilfs_sb_info *sbi = NILFS_SB(sb); struct nilfs_sc_info *sci = NILFS_SC(sbi); struct nilfs_inode_info *ii; struct nilfs_transaction_info ti; int err = 0; if (!sci) return -EROFS; nilfs_transaction_lock(sbi, &ti, 0); ii = NILFS_I(inode); if (test_bit(NILFS_I_INODE_DIRTY, &ii->i_state) || nilfs_test_opt(sbi, STRICT_ORDER) || test_bit(NILFS_SC_UNCLOSED, &sci->sc_flags) || nilfs_discontinued(sbi->s_nilfs)) { nilfs_transaction_unlock(sbi); err = nilfs_segctor_sync(sci); return err; } spin_lock(&sbi->s_inode_lock); if (!test_bit(NILFS_I_QUEUED, &ii->i_state) && !test_bit(NILFS_I_BUSY, &ii->i_state)) { spin_unlock(&sbi->s_inode_lock); nilfs_transaction_unlock(sbi); return 0; } spin_unlock(&sbi->s_inode_lock); sci->sc_dsync_inode = ii; sci->sc_dsync_start = start; sci->sc_dsync_end = end; err = nilfs_segctor_do_construct(sci, SC_LSEG_DSYNC); nilfs_transaction_unlock(sbi); return err; } #define FLUSH_FILE_BIT (0x1) /* data file only */ #define FLUSH_DAT_BIT (1 << NILFS_DAT_INO) /* DAT only */ /** * nilfs_segctor_accept - record accepted sequence count of log-write requests * @sci: segment constructor object */ static void nilfs_segctor_accept(struct nilfs_sc_info *sci) { spin_lock(&sci->sc_state_lock); sci->sc_seq_accepted = sci->sc_seq_request; spin_unlock(&sci->sc_state_lock); if (sci->sc_timer) del_timer_sync(sci->sc_timer); } /** * nilfs_segctor_notify - notify the result of request to caller threads * @sci: segment constructor object * @mode: mode of log forming * @err: error code to be notified */ static void nilfs_segctor_notify(struct nilfs_sc_info *sci, int mode, int err) { /* Clear requests (even when the construction failed) */ spin_lock(&sci->sc_state_lock); if (mode == SC_LSEG_SR) { sci->sc_state &= ~NILFS_SEGCTOR_COMMIT; sci->sc_seq_done = sci->sc_seq_accepted; nilfs_segctor_wakeup(sci, err); sci->sc_flush_request = 0; } else { if (mode == SC_FLUSH_FILE) sci->sc_flush_request &= ~FLUSH_FILE_BIT; else if (mode == SC_FLUSH_DAT) sci->sc_flush_request &= ~FLUSH_DAT_BIT; /* re-enable timer if checkpoint creation was not done */ if (sci->sc_timer && (sci->sc_state & NILFS_SEGCTOR_COMMIT) && time_before(jiffies, sci->sc_timer->expires)) add_timer(sci->sc_timer); } spin_unlock(&sci->sc_state_lock); } /** * nilfs_segctor_construct - form logs and write them to disk * @sci: segment constructor object * @mode: mode of log forming */ static int nilfs_segctor_construct(struct nilfs_sc_info *sci, int mode) { struct nilfs_sb_info *sbi = sci->sc_sbi; struct the_nilfs *nilfs = sbi->s_nilfs; int err = 0; nilfs_segctor_accept(sci); if (nilfs_discontinued(nilfs)) mode = SC_LSEG_SR; if (!nilfs_segctor_confirm(sci)) err = nilfs_segctor_do_construct(sci, mode); if (likely(!err)) { if (mode != SC_FLUSH_DAT) atomic_set(&nilfs->ns_ndirtyblks, 0); if (test_bit(NILFS_SC_SUPER_ROOT, &sci->sc_flags) && nilfs_discontinued(nilfs)) { down_write(&nilfs->ns_sem); err = nilfs_commit_super( sbi, nilfs_altsb_need_update(nilfs)); up_write(&nilfs->ns_sem); } } nilfs_segctor_notify(sci, mode, err); return err; } static void nilfs_construction_timeout(unsigned long data) { struct task_struct *p = (struct task_struct *)data; wake_up_process(p); } static void nilfs_remove_written_gcinodes(struct the_nilfs *nilfs, struct list_head *head) { struct nilfs_inode_info *ii, *n; list_for_each_entry_safe(ii, n, head, i_dirty) { if (!test_bit(NILFS_I_UPDATED, &ii->i_state)) continue; hlist_del_init(&ii->vfs_inode.i_hash); list_del_init(&ii->i_dirty); nilfs_clear_gcinode(&ii->vfs_inode); } } int nilfs_clean_segments(struct super_block *sb, struct nilfs_argv *argv, void **kbufs) { struct nilfs_sb_info *sbi = NILFS_SB(sb); struct nilfs_sc_info *sci = NILFS_SC(sbi); struct the_nilfs *nilfs = sbi->s_nilfs; struct nilfs_transaction_info ti; int err; if (unlikely(!sci)) return -EROFS; nilfs_transaction_lock(sbi, &ti, 1); err = nilfs_init_gcdat_inode(nilfs); if (unlikely(err)) goto out_unlock; err = nilfs_ioctl_prepare_clean_segments(nilfs, argv, kbufs); if (unlikely(err)) goto out_unlock; sci->sc_freesegs = kbufs[4]; sci->sc_nfreesegs = argv[4].v_nmembs; list_splice_tail_init(&nilfs->ns_gc_inodes, &sci->sc_gc_inodes); for (;;) { err = nilfs_segctor_construct(sci, SC_LSEG_SR); nilfs_remove_written_gcinodes(nilfs, &sci->sc_gc_inodes); if (likely(!err)) break; nilfs_warning(sb, __func__, "segment construction failed. (err=%d)", err); set_current_state(TASK_INTERRUPTIBLE); schedule_timeout(sci->sc_interval); } if (nilfs_test_opt(sbi, DISCARD)) { int ret = nilfs_discard_segments(nilfs, sci->sc_freesegs, sci->sc_nfreesegs); if (ret) { printk(KERN_WARNING "NILFS warning: error %d on discard request, " "turning discards off for the device\n", ret); nilfs_clear_opt(sbi, DISCARD); } } out_unlock: sci->sc_freesegs = NULL; sci->sc_nfreesegs = 0; nilfs_clear_gcdat_inode(nilfs); nilfs_transaction_unlock(sbi); return err; } static void nilfs_segctor_thread_construct(struct nilfs_sc_info *sci, int mode) { struct nilfs_sb_info *sbi = sci->sc_sbi; struct nilfs_transaction_info ti; nilfs_transaction_lock(sbi, &ti, 0); nilfs_segctor_construct(sci, mode); /* * Unclosed segment should be retried. We do this using sc_timer. * Timeout of sc_timer will invoke complete construction which leads * to close the current logical segment. */ if (test_bit(NILFS_SC_UNCLOSED, &sci->sc_flags)) nilfs_segctor_start_timer(sci); nilfs_transaction_unlock(sbi); } static void nilfs_segctor_do_immediate_flush(struct nilfs_sc_info *sci) { int mode = 0; int err; spin_lock(&sci->sc_state_lock); mode = (sci->sc_flush_request & FLUSH_DAT_BIT) ? SC_FLUSH_DAT : SC_FLUSH_FILE; spin_unlock(&sci->sc_state_lock); if (mode) { err = nilfs_segctor_do_construct(sci, mode); spin_lock(&sci->sc_state_lock); sci->sc_flush_request &= (mode == SC_FLUSH_FILE) ? ~FLUSH_FILE_BIT : ~FLUSH_DAT_BIT; spin_unlock(&sci->sc_state_lock); } clear_bit(NILFS_SC_PRIOR_FLUSH, &sci->sc_flags); } static int nilfs_segctor_flush_mode(struct nilfs_sc_info *sci) { if (!test_bit(NILFS_SC_UNCLOSED, &sci->sc_flags) || time_before(jiffies, sci->sc_lseg_stime + sci->sc_mjcp_freq)) { if (!(sci->sc_flush_request & ~FLUSH_FILE_BIT)) return SC_FLUSH_FILE; else if (!(sci->sc_flush_request & ~FLUSH_DAT_BIT)) return SC_FLUSH_DAT; } return SC_LSEG_SR; } /** * nilfs_segctor_thread - main loop of the segment constructor thread. * @arg: pointer to a struct nilfs_sc_info. * * nilfs_segctor_thread() initializes a timer and serves as a daemon * to execute segment constructions. */ static int nilfs_segctor_thread(void *arg) { struct nilfs_sc_info *sci = (struct nilfs_sc_info *)arg; struct the_nilfs *nilfs = sci->sc_sbi->s_nilfs; struct timer_list timer; int timeout = 0; init_timer(&timer); timer.data = (unsigned long)current; timer.function = nilfs_construction_timeout; sci->sc_timer = &timer; /* start sync. */ sci->sc_task = current; wake_up(&sci->sc_wait_task); /* for nilfs_segctor_start_thread() */ printk(KERN_INFO "segctord starting. Construction interval = %lu seconds, " "CP frequency < %lu seconds\n", sci->sc_interval / HZ, sci->sc_mjcp_freq / HZ); spin_lock(&sci->sc_state_lock); loop: for (;;) { int mode; if (sci->sc_state & NILFS_SEGCTOR_QUIT) goto end_thread; if (timeout || sci->sc_seq_request != sci->sc_seq_done) mode = SC_LSEG_SR; else if (!sci->sc_flush_request) break; else mode = nilfs_segctor_flush_mode(sci); spin_unlock(&sci->sc_state_lock); nilfs_segctor_thread_construct(sci, mode); spin_lock(&sci->sc_state_lock); timeout = 0; } if (freezing(current)) { spin_unlock(&sci->sc_state_lock); refrigerator(); spin_lock(&sci->sc_state_lock); } else { DEFINE_WAIT(wait); int should_sleep = 1; prepare_to_wait(&sci->sc_wait_daemon, &wait, TASK_INTERRUPTIBLE); if (sci->sc_seq_request != sci->sc_seq_done) should_sleep = 0; else if (sci->sc_flush_request) should_sleep = 0; else if (sci->sc_state & NILFS_SEGCTOR_COMMIT) should_sleep = time_before(jiffies, sci->sc_timer->expires); if (should_sleep) { spin_unlock(&sci->sc_state_lock); schedule(); spin_lock(&sci->sc_state_lock); } finish_wait(&sci->sc_wait_daemon, &wait); timeout = ((sci->sc_state & NILFS_SEGCTOR_COMMIT) && time_after_eq(jiffies, sci->sc_timer->expires)); if (nilfs_sb_dirty(nilfs) && nilfs_sb_need_update(nilfs)) set_nilfs_discontinued(nilfs); } goto loop; end_thread: spin_unlock(&sci->sc_state_lock); del_timer_sync(sci->sc_timer); sci->sc_timer = NULL; /* end sync. */ sci->sc_task = NULL; wake_up(&sci->sc_wait_task); /* for nilfs_segctor_kill_thread() */ return 0; } static int nilfs_segctor_start_thread(struct nilfs_sc_info *sci) { struct task_struct *t; t = kthread_run(nilfs_segctor_thread, sci, "segctord"); if (IS_ERR(t)) { int err = PTR_ERR(t); printk(KERN_ERR "NILFS: error %d creating segctord thread\n", err); return err; } wait_event(sci->sc_wait_task, sci->sc_task != NULL); return 0; } static void nilfs_segctor_kill_thread(struct nilfs_sc_info *sci) { sci->sc_state |= NILFS_SEGCTOR_QUIT; while (sci->sc_task) { wake_up(&sci->sc_wait_daemon); spin_unlock(&sci->sc_state_lock); wait_event(sci->sc_wait_task, sci->sc_task == NULL); spin_lock(&sci->sc_state_lock); } } static int nilfs_segctor_init(struct nilfs_sc_info *sci) { sci->sc_seq_done = sci->sc_seq_request; return nilfs_segctor_start_thread(sci); } /* * Setup & clean-up functions */ static struct nilfs_sc_info *nilfs_segctor_new(struct nilfs_sb_info *sbi) { struct nilfs_sc_info *sci; sci = kzalloc(sizeof(*sci), GFP_KERNEL); if (!sci) return NULL; sci->sc_sbi = sbi; sci->sc_super = sbi->s_super; init_waitqueue_head(&sci->sc_wait_request); init_waitqueue_head(&sci->sc_wait_daemon); init_waitqueue_head(&sci->sc_wait_task); spin_lock_init(&sci->sc_state_lock); INIT_LIST_HEAD(&sci->sc_dirty_files); INIT_LIST_HEAD(&sci->sc_segbufs); INIT_LIST_HEAD(&sci->sc_write_logs); INIT_LIST_HEAD(&sci->sc_gc_inodes); INIT_LIST_HEAD(&sci->sc_copied_buffers); sci->sc_interval = HZ * NILFS_SC_DEFAULT_TIMEOUT; sci->sc_mjcp_freq = HZ * NILFS_SC_DEFAULT_SR_FREQ; sci->sc_watermark = NILFS_SC_DEFAULT_WATERMARK; if (sbi->s_interval) sci->sc_interval = sbi->s_interval; if (sbi->s_watermark) sci->sc_watermark = sbi->s_watermark; return sci; } static void nilfs_segctor_write_out(struct nilfs_sc_info *sci) { int ret, retrycount = NILFS_SC_CLEANUP_RETRY; /* The segctord thread was stopped and its timer was removed. But some tasks remain. */ do { struct nilfs_sb_info *sbi = sci->sc_sbi; struct nilfs_transaction_info ti; nilfs_transaction_lock(sbi, &ti, 0); ret = nilfs_segctor_construct(sci, SC_LSEG_SR); nilfs_transaction_unlock(sbi); } while (ret && retrycount-- > 0); } /** * nilfs_segctor_destroy - destroy the segment constructor. * @sci: nilfs_sc_info * * nilfs_segctor_destroy() kills the segctord thread and frees * the nilfs_sc_info struct. * Caller must hold the segment semaphore. */ static void nilfs_segctor_destroy(struct nilfs_sc_info *sci) { struct nilfs_sb_info *sbi = sci->sc_sbi; int flag; up_write(&sbi->s_nilfs->ns_segctor_sem); spin_lock(&sci->sc_state_lock); nilfs_segctor_kill_thread(sci); flag = ((sci->sc_state & NILFS_SEGCTOR_COMMIT) || sci->sc_flush_request || sci->sc_seq_request != sci->sc_seq_done); spin_unlock(&sci->sc_state_lock); if (flag || !nilfs_segctor_confirm(sci)) nilfs_segctor_write_out(sci); WARN_ON(!list_empty(&sci->sc_copied_buffers)); if (!list_empty(&sci->sc_dirty_files)) { nilfs_warning(sbi->s_super, __func__, "dirty file(s) after the final construction\n"); nilfs_dispose_list(sbi, &sci->sc_dirty_files, 1); } WARN_ON(!list_empty(&sci->sc_segbufs)); WARN_ON(!list_empty(&sci->sc_write_logs)); down_write(&sbi->s_nilfs->ns_segctor_sem); kfree(sci); } /** * nilfs_attach_segment_constructor - attach a segment constructor * @sbi: nilfs_sb_info * * nilfs_attach_segment_constructor() allocates a struct nilfs_sc_info, * initializes it, and starts the segment constructor. * * Return Value: On success, 0 is returned. On error, one of the following * negative error code is returned. * * %-ENOMEM - Insufficient memory available. */ int nilfs_attach_segment_constructor(struct nilfs_sb_info *sbi) { struct the_nilfs *nilfs = sbi->s_nilfs; int err; if (NILFS_SC(sbi)) { /* * This happens if the filesystem was remounted * read/write after nilfs_error degenerated it into a * read-only mount. */ nilfs_detach_segment_constructor(sbi); } sbi->s_sc_info = nilfs_segctor_new(sbi); if (!sbi->s_sc_info) return -ENOMEM; nilfs_attach_writer(nilfs, sbi); err = nilfs_segctor_init(NILFS_SC(sbi)); if (err) { nilfs_detach_writer(nilfs, sbi); kfree(sbi->s_sc_info); sbi->s_sc_info = NULL; } return err; } /** * nilfs_detach_segment_constructor - destroy the segment constructor * @sbi: nilfs_sb_info * * nilfs_detach_segment_constructor() kills the segment constructor daemon, * frees the struct nilfs_sc_info, and destroy the dirty file list. */ void nilfs_detach_segment_constructor(struct nilfs_sb_info *sbi) { struct the_nilfs *nilfs = sbi->s_nilfs; LIST_HEAD(garbage_list); down_write(&nilfs->ns_segctor_sem); if (NILFS_SC(sbi)) { nilfs_segctor_destroy(NILFS_SC(sbi)); sbi->s_sc_info = NULL; } /* Force to free the list of dirty files */ spin_lock(&sbi->s_inode_lock); if (!list_empty(&sbi->s_dirty_files)) { list_splice_init(&sbi->s_dirty_files, &garbage_list); nilfs_warning(sbi->s_super, __func__, "Non empty dirty list after the last " "segment construction\n"); } spin_unlock(&sbi->s_inode_lock); up_write(&nilfs->ns_segctor_sem); nilfs_dispose_list(sbi, &garbage_list, 1); nilfs_detach_writer(nilfs, sbi); }
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UI libraries / InstantSearch Android / Widgets
Signature
FilterRangeConnector(
filterState: FilterState,
attribute: Attribute,
bounds: ClosedRange<T>?,
range: ClosedRange<T>?
)
About this widget
Filter Numeric Range is a filtering view made to filter between two numeric values. The most common interface for this is a slider.
The Android View and Compose UI code samples (part of the Android widget showcase repository on GitHub) illustrate the use of sliders.
Examples
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class MyActivity : AppCompatActivity() {
val searcher = HitsSearcher(
applicationID = ApplicationID("YourApplicationID"),
apiKey = APIKey("YourSearchOnlyAPIKey"),
indexName = IndexName("YourIndexName")
)
val price = Attribute("price")
val groupID = FilterGroupID(price)
val primaryBounds = 0..15
val initialRange = 0..15
val filters = filters {
group(groupID) {
range(price, initialRange)
}
}
val filterState = FilterState(filters)
val range = FilterRangeConnector(
filterState = filterState,
attribute = price,
range = initialRange,
bounds = primaryBounds
)
val connection = ConnectionHandler(range, searcher.connectFilterState(filterState))
override fun onCreate(savedInstanceState: Bundle?) {
super.onCreate(savedInstanceState)
val view: NumberRangeView<Int> = MyNumberRangeView(textLabel) // your `NumberRangeView<T>` implementation
connection += range.connectView(view)
searcher.searchAsync()
}
override fun onDestroy() {
super.onDestroy()
connection.disconnect()
searcher.cancel()
}
}
Low-level API
If you want to fully control the Filter Numeric Range components and connect them manually, use the following components:
• Searcher: The Searcher that handles your searches.
• FilterState: The current state of the filters.
• FilterRangeViewModel: The logic applied to the numeric ranges.
• NumberRangeView: The view that renders the numeric range filter.
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class MyActivity : AppCompatActivity() {
val searcher = HitsSearcher(
applicationID = ApplicationID("YourApplicationID"),
apiKey = APIKey("YourSearchOnlyAPIKey"),
indexName = IndexName("YourIndexName")
)
val filterState = FilterState()
val attribute = Attribute("price")
val viewModel = FilterRangeViewModel<Int>()
val connection = ConnectionHandler()
override fun onCreate(savedInstanceState: Bundle?) {
super.onCreate(savedInstanceState)
val view: NumberRangeView<Int> = MyNumberRangeView(textLabel) // your `NumberRangeView<T>` implementation
connection += searcher.connectFilterState(filterState)
connection += viewModel.connectFilterState(filterState, attribute)
connection += viewModel.connectView(view)
searcher.searchAsync()
}
override fun onDestroy() {
super.onDestroy()
connection.disconnect()
searcher.cancel()
}
}
Compose UI
InstantSearch provides the NumberRangeState as a state model, which is an implementation of the NumberRangeView interface. You need to connect NumberRangeState to the FilterRangeConnector or FilterRangeViewModel like any other NumberRangeView implementation.
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class MyActivity : AppCompatActivity() {
val searcher = HitsSearcher(
applicationID = ApplicationID("YourApplicationID"),
apiKey = APIKey("YourSearchOnlyAPIKey"),
indexName = IndexName("YourIndexName")
)
val price = Attribute("price")
val groupID = FilterGroupID(price)
val primaryBounds = 0..15
val initialRange = 0..15
val filters = filters {
group(groupID) {
range(price, initialRange)
}
}
val filterState = FilterState(filters)
val sliderState = NumberRangeState<Int>()
val range = FilterRangeConnector(
filterState = filterState,
attribute = price,
range = initialRange,
bounds = primaryBounds
)
val connections = ConnectionHandler(range)
init {
connections += searcher.connectFilterState(filterState)
connections += range.connectView(sliderState)
}
override fun onCreate(savedInstanceState: Bundle?) {
super.onCreate(savedInstanceState)
setContent {
MyRangeSlider(sliderState) // your own UI composable to display range and bounds as `Range<T>`
}
searcher.searchAsync()
}
fun Range<Int>.toClosedFloatRange(): ClosedFloatingPointRange<Float> {
return min.toFloat()..max.toFloat()
}
override fun onDestroy() {
super.onDestroy()
connections.disconnect()
searcher.cancel()
}
}
Parameters
filterState
type: FilterState
Required
The FilterState that will hold your filters.
attribute
type: Attribute
Required
The attribute to filter.
bounds
type: ClosedRange<T>?
Optional
The limits of the acceptable range within which values are coerced.
range
type: ClosedRange<T>?
Optional
The range of values within the bounds.
View
view
type: NumberRangeView
Required
The view that renders the numeric range filter.
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val view = MyNumberRangeView(textLabel)
range.connectView(view)
// Example of `NumberRangeView<T>` implementation
class MyNumberRangeView(val view: TextView) : NumberRangeView<Int> {
override var onRangeChanged: Callback<Range<Int>>? = null
private var bounds: Range<Int>? = null
override fun setBounds(bounds: Range<Int>?) {
this.bounds = bounds
view.text = bounds?.let {
"Bounds: ${it.min} to ${it.max}"
} ?: "No bounds"
}
override fun setRange(range: Range<Int>?) = Unit
}
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Rogamarga
Cite.png
Roga marga means pathways of disease progression and manifestations. It is essential to know the path of progression and manifestation of the disease to plan the protocol for its management. Roga marga is a place of vitiation of body channels (kha vaigunya). The disease can be cured, if the exact site of vitiation is targeted. Through the applicability of roga marga, the recurrence of the disease may be reduced. [Cha.Sa.Chikitsa Sthana 15/36-37] The specific medicines for specific receptors can be developed. [Cha.Sa. Sutra Sthana 4/22]
Acharya Charaka has explained roga marga as under.[1] [Cha.Sa.Sutra Sthana 11/48]
1. Three roga margas viz. external (bahya), middle (madhyama) and internal (abhyantara)
2. Each roga marga has set of structural / physiological entities.
3. List of diseases of roga marga
This article describes the physiological and pathological aspects of rogamarga with their importance in therapeutics.
Contributors
Section/Chapter/topic Concepts/Rogamarga
Authors Bhojani M. K. 1,
Dwivedi Rambabu 2,
Vyas Mahesh3,
Bhatted Santoshkumar4
Reviewer Basisht G.5,
Editor Deole Y.S.6
Affiliations 1 Department of Sharir Kriya, All India Institute of Ayurveda, New Delhi, India
2 Former Dean, Institute of Post Graduate Teaching & Research in Ayurveda, Jamnagar, India
3 Department of Samhita Siddhanta, All India Institute of Ayurveda, New Delhi, India
4 Department of Panchakarma, All India Institute of Ayurveda, New Delhi, India
5 Rheumatologist, Orlando, Florida, U.S.A.
6 Department of Kayachikitsa, G. J. Patel Institute of Ayurvedic Studies and Research, New Vallabh Vidyanagar, Gujarat, India
Correspondence emails meera.samhita@aiia.gov.in,
carakasamhita@gmail.com
Publisher Charak Samhita Research, Training and Development Centre, I.T.R.A., Jamnagar, India
Date of publication: March 30, 2023
DOI 10.47468/CSNE.2023.e01.s09.133
Significance
As an important phase of pathogenesis (samprapti), the vitiated dosha travel and settle at the suitable places. [Madhu Kosha commentary on Madhava Nidana Sarvaroga Nidana Adhyaya][2] This is termed as prasara and sthana samshraya. It can be said that for both of these phases, roga marga plays a vital role. Also, the movement of dosha (dosha gati) mentioned as normal (prakriti) and abnormal (vaikrita) are with the same nomenclature viz. koshtha, shakha, marma-asthi-sandhi. This shows the significance of roga marga from physiological view point (prakrita gati of dosha).
Roga marga also contributes to the prognosis of the diseases. [Chakrapani commentary on Cha. Su. 11/48][3]
Further, roga marga is explained for precise treatment. [Madhukosha Commentary on Madhava Nidana Sarvaroga Nidana Adhyaya][4]
Etymology
1. Roga :
The word roga is derived from the root ‘ruj’ which means unpleasant, discomfort or pain, to break or disintegrate.
It is evident that roga is the outcome of the disintegration of equilibrium of dosha (or dhatusamyata) – Homeostasis, which culminates into pain – physical or psychological. [Arundatta on A.H.Nidana Sthana 1/1][5]
2. Marga :
The Sanskrit word marga means to go along, or path. [Shabda Kalpadrum][6] Marga is derived from the Sanskrit verb ‘mruj’ that means purified channel or route. The dictionary meanings of the word marga are path, way, manner, mode, methods, process, indicative of how pathogenesis is to take place. [Sir. M.M. Williams][7]
Rogamarga can be understood as the way of disease occurrence, progression and recurrence as well. The word Roga marga maybe understood as ‘A weak spot’ or ‘Costus specious’.
Textbook of Pathology by Boyd quotes “The science of pathology seeks to determine the cause of disease, to discover how disease injures the patient, to describe the lesions produced, to follow how the lesions change as disease progresses, to understand how disease produces secondary effects in the patient, and to record how the lesions heal as the patient recovers.” [8]
Definition
The external pathway of disease is called bahya roga marga.[9] [Hemadri and Arunadatta on A.H. Sutra Sthana 12/45] By this meaning, abhyantara (internal) and madhyama (medial) roga marga will be interpreted as internal and medial pathway of disease respectively.
These definitions suggest the appearance of clinical features can be representing a particular roga marga. However, in some cases the pathogenesis can be different with different pathways. For example, carbuncles due to diabetes (prameha pitika) appearing in the bahya roga marga, needs additional treatments besides other diseases which occur in bhaya roga marga.[10] Hence, it can be interpreted that the dosha samprapti can travel to any roga marga during the process.
Movement of dosha and pathways of diseases (roga marga vis-a-vis dosha gati)
Three types of movements of dosha are mentioned. [Cha. Sa.Sutra Sthana 17/113] The same are termed as three types of roga marga viz. shakha, koshtha and marma asthi sandhi.[11] [Cha.Sa.Sutra Sthana 11/48]
These are the different movements of dosha. As these gati are further classified into prakrita (normal) and vaikrita (abnormal), the healthy channels will render the passage for dosha and when the same channels are weaker/vulnerable, they act as ‘roga marga’.
Diseases observed in each roga marga
Diseases occurring in different rogamarga are tabulated as under:
Table 1: Diseases in different roga marga
Diseases occurring in bahya roga marga Diseases occurring in madhyama roga marga Diseases occurring in abhyantara roga marga Diseases occurring in bahya and abhyantara roga marga
Diseases like goitre, pimples, boil, warts, granuloma etc. which are manifested on the body and can be accessed easily and palpable Diseases involving the pathology of the vital organs like hemiplegia, facial paralysis etc., diseases of cardiovascular system, diseases of urinary system, diseases of joints Diseases like fever, diarrhoea, vomiting, cholera, constipation, diseases of abdomen, splenic disorders, cough, dyspnoea, hiccough etc. which are caused due to indigestion Skin diseases having acute spread like erysepelas, oedema, abdominal tumours, piles and abscess
Anatomical aspects
Certain exemplary organs are grouped under different roga margas. The organic implications of each rogamarga can be discussed as follows.
Bahya rogamarga (external pathway)
This includes body components like twak (skin), rakta dhatu (blood), and other similar body constituents. [Cha.Sa.Sutrasthana 11/48] It is similar to a branch of tree.[12]
Thus, to show the remoteness of these structures, they have been termed as shakha. These are the structures seen one after another in a sequence. Rasa, rakta, mamsa, meda, majja pertaining to the internal structures like liver, spleen, brain etc. should not come under bahya roga marga. For example, hrdayagata rasa dhatu, yakrita gata rakta dhatu should come under abhyantara roga marga. The accessory appendages of skin like hair, nails, tactile cells, sebaceous glands etc. should be considered under bahya roga marga. Mammary glands, ext. ear, tonsils, adenoids should also be considered under bahya roga marga. Thus, looking to the structures and diseases allotted to bahya rogamarga, it is evident that this marga has entities, which are superficial (compared to the madhyama roga marga) and these entities are the first line of contact with the external stimulus and hence the pathology occurring is easily diagnosed and approachable. The madhyama roga marga includes marma (vital organs) like heart, brain, kidneys, bones, joints, ligaments, tendons. [Cha.Sa.Sutra Sthana 11/48]
Madhyama rogamarga (medial pathway)
The grouping of structures of madhyama roga marga is quite different from that of other roga-marga. Although these organs are not connected with each other, they perform vital functions of the body and any damage to them will give rise to serious consequences.
Abhyantara rogamarga (internal pathway)
The abhyantara roga marga is termed as koshtha. It includes the gastrointestinal tract and all visceral organs. While enumerating koshthangas basti, hridaya and vrikka included in them. These will be included in abhyantara roga marga. But in text these organs and diseases related to them are ascribed to madhyama roga marga, which maybe explained as under.
Koshthanga are mainly responsible for nutrition and excretion of mala. Hridaya is considered a koshthanga for; it is responsible for nutrition and excretion of blood impurities. Same is the case with vrikka and basti. But the reason for not considering these organs under koshtha may be that the structural disorders of any of the organs may influence the material flowing through them but not the organs of mahasrotas. In case of the diseases related to abhyantara roga marga, there may be indirect influence on the vahana dravya of these organs. eg. rakta mutrata in pittaja jwara, hridaya ashuddhi in ama jwara, bahu mutrata in ajirna etc. Thus, being influenced by koshtha and their diseases, these might have been included in koshthanga. But when the point of roga marga comes, these organs are to be studied under madhyama roga marga as is in the texts.
Physiological aspect of roga-marga
Physiologically, the various organs occurring in a particular roga marga are inter-connected. This could be explained as under:
Table 2: Peculiarities of roga marga
Roga marga Important physiological aspect Other peculiarities
Abhyantara roga marga It is the prime site of jatharagni and concerned with digestion, absorption and excretion,
• It has the mula sthana of the dosha. [Su.Sa.Sutra Sthana 21/6]
• The koshthanga are in the abhyantara rogamarga
Bahya roga marga It is the site of dhatwagni, responsible for the dhatu nirmana
• As the nutrition is processed through abhyantara roga marga, at least two roga margas are functionally interlinked; and many cause and effect phenomena can be observed in these two margas.
Madhyam roga marga It includes organs such as sira, hridaya and basti, other marmas, asthi-sandhi etc.
• These organs have nothing in common either physiologically nor have anatomical continuity.
• They are the main seats of prana according to ayurveda
• They have large quantity of blood circulation.
• These organs are interlinked with each other pathologically, as the pathology of one affects the other.
Pathological understanding of roga marga vs. disease pathways
In a normal body, as such, there will be no rogamarga for the dosha to travel. The healthy srotas/organs are rendered weak by the intake of nidana sevana and this renders the srotas weak, which is termed as khavaigunya. This results in directing the samprapti and spread of disease. Such weak srotas/ organs becomes rogamarga.
Roga margas have crucial role to play in the samprapti of a disease. The very definition of samprapti brings forth two things. One is that, the accumulated and spreading dosha virtually reaches each and every part of the body and the general channel of flow is rasayani. [ A.H. Nidana Sthana 1/23]
Along with it, this subject has been emphasized for sadhyasahdyata i.e. prognosis, according to Chakrapani and for therapeutic application according to madhukoshakara. This points towards the pathological importance of roga marga.
Role of roga-marga in various stages of samprapti
• Sub clinical or formative stages :
Of the six stages, accumulaton (chaya), aggravation (prakopa), spread (prasara) are sub-clinical. The symptoms manifested in chaya stage are imprecise, depending on invoved dosha. Prakopa avastha exhibits the symptomatology but not disease. In the prasara avastha, when the spread of the morbid doshas starts, the manifestation at roga marga comes into picture. Albeit, as the accumulation (chaya avastha) occurs at the root (mula / utpatti sthana) of the dosha, the involvement of roga marga maybe inferred from accumulation stage (chaya avastha) itself.
• Clinical stage :
A list of diseases are mentioned under a particular roga marga. So, it can be said that roga marga plays significant role in the clinical stages viz. sthana samshraya and vyakti avastha.
Roga marga is the site of kha-vaigunya which later on cultivates for interaction of dosh and dushya. [Su.Sa.Sutra Sthana 24/10] Kha-vaigunya plays directive role for the pathology to spread in different srotas (systems).
Sthanasamshraya avastha is an important transition stage between the sub clinical and the clinical stages; wherein the structural lesions begin to occur alongwith the functional disturbances, which leads to localization of the pathology.
• In the vyakti avastha, the outcome of the interaction of dosha-dushya is revealed. According to respected Vaidya Shiva Charan Dhyani, in the book “Nidana Panchaka”, at this stage, (i) completion of dosha dushya sammurcchana (ii) Srotodusti and its features and (iii) lakshana sammuchaya of diseases, are manifested.[13]
• Though the dosha dushya sammurcchana is initiated in the previous stage, its completion is achieved in vyakti avastha. The sroto dushti occurs at roga-marga
• Complicated clinical (post clinical) stage :
Bheda stage is considered as the advanced clinical stage. In this stage, the disease (vyadhi) may become chronic or progressive and leads to other diseases. In this phase, the roga vriddhi takes place. Advancement of disease (roga vriddhi) takes place by different modes, which are listed briefly as follows:
1. In the same organ, sthanantara swarupa roga vriddhi :
In skin disorders and other contagious diseases, due to anatomical continuity in skin, the pathogens can travel in the same organ. E.g visarpa. [Cha.Sa.Chikitsa Sthana 21/15]
2. Dhatugata swarupa roga vriddhi :
The transfer of disease or samprapti from one dhatu to another is also the manifestation of roga vriddhi (dhatu gatatva). Dhatugata vyadhi and dhatugata vata are explained to get a clear idea. Apart from the dhatugatatva of dosha, it is explained in certain other contexts also. They are the following :
1. Dhatugatatva of jwara (the morbid dosha causing fever penetrates into deeper tissues) [Cha. Sa. Chikitsa sthana 3/ 70-83], [Su.Sa.Uttara Tantra 29/83-89]
2. Dhatugatatva of kushtha (the morbid dosha causing skin diseases penetrates into deeper tissues) [Su. Sa. Nidana Sthana 5/20-27]
3. Dhatugatatva of masurika (the morbid dosha causing chicken pox penetrates into deeper tissues) [Ma. Ni. 54 / 14-23]
4. Dhatugatatva of visha vega (the poison penetrates into deeper tissues) [A.Hr.Uttara tantra 19/26] [Su.Sa. Kalpa Sthana 4/39]
5. The examples of dhatugatatva given in skin diseases (kushtha) can be taken as a model for understanding the symptomatology of dhatugatatva of kapha dominant diseases. Likewise, dhatugatatva of jwara for pittaja vyadhis and dhatugatatva described in vatavyadhi for vata dominant disorders.
3. Nidanarthakara swarupa roga vriddhi :
Sometimes one disease may become nidana for the other disease. This is also a kind of roga-vriddhi. Eg., Jwara to raktapitta (the heat of the fever causes bleeding disorders), pratishyaya to kasa (coryza causes coughing), kasa to swasha (Coughing may lead to asthama kind of breathlessness), atisara to grahani (Diarrhoea causes sprue syndrome), grahani to arsha (Sprue syndrome may cause piles), etc. [Cha.Sa.Nidana Sthana 8/17-19]
4. Vyadhisankara swarupa roga vriddhi :
Vyadhi sankara means the occurance of 2-3 diseases at a time. Sometimes, the disease itself subsides after producing some other disease and sometimes it persists and becomes more troublesome.
e.g. Pratishyaya and kasa (coryza and coughing together),. [Cha.Sa.Nidana Sthana 8/22]
5. Upadrava swarupa roga vriddhi : [Cha.Sa. Chikitsa Sthana 21/40]
Upadrava also signifies roga vrddhi. In a vigunita sthana, dosha dushya sammurcchana takes place. If it is not treated at early stage and nidana sevana continued then this dosha dushya melaka becomes more virulent and travels to other places and produces upadrava. eg. Upadrava of udara roga (obstinate abdominal diseases including ascites) are chhardi (vomiting), atisara (diarrhoea), shwasa (dyspnoea), kasa (cough), trishna (morbid thirst), hikka (hiccup), aruchi (anorexia) etc. [Cha.Sa.Chikitsa Sthana 13/49]
6. Roga vriddhi in same srotas in a sequential order :
Roga initiates from sroto mula or a part of srotas and spreads to whole srotas, if nidana parivarjana is not done and chikitsa not applied. eg. Nasal Polyp leads to Bronchitis, which in turn may lead to asthma.
7. Roga vriddhi according to dosha sthana :
The best example given to study this is in Jwara Prakarana of Sushruta Uttara Sthana. [Nibandha Sangraha commentary by Dalhana on Su.Sa. Uttara tantra 39/ 51-52]
• Satata jwara in amashaya (In continuous fever, the morbid doshas are in the stomach)
• Anyedhyushka in hridaya (In intermittent fever, the morbid doshas are in the heart / heart region)
• Trutiyaka in kantha (In tertian fever, the morbid doshas are in the throat / throat region)
• Chaturthaka in sandhi (In quartan type of fever the morbid doshas are in the joints)
In this way, looking at the different procedures of roga vriddhi, it is evident that roga marga plays a definite role in the roga vriddhi, which may take place in the same roga marga or in other roga marga.
The inter-connectedness of the different roga marga
Dosha can move from one marga to another. The movement of the dosha from internal pathway towards other marga will be clear in most of the diseases. But in the case of external pathways, the movement of dosha from shakha towards koshtha is not so easy. The reason may be that the diseases of the internal pathway produce many symptoms externally. But the diseases of the external pathway generally may not have any serious symptoms and signs pertaining to internal or medial pathway. The reason for this can be given in the following paras.
1. Body due to its defense mechanism generally tries to push out the factors, which are not suitable to it. If the koshtha is filled with such morbid factors, in order to defend the organs of koshtha from any type of damage they are pushed to other margas if not expelled out. This is done preferably through the marga of poshana. The causes of movement of the doshas from koshtha to shakha have been mentioned by acharya Charak. [Cha.Sa.Sutra Sthana 28/31]
2. The same case is not found in the diseases of external pathways. Because the morbid dosha will not be able to move back to koshtha easily. This is because the viloma gati of dosha will have to take place here. This sort of movement is possible only with the co-operation of the srotas. The causes of movement of doshas from shakha to koshtha, mentioned by acharya Charak, plays role for this. [Cha.Sa.Sutra Sthana 28/32] Thus, compared to abhyantar rogamarga, the diseases of bahya roga marga takes longer duration.
The movement of the morbid factors in the diseases of medial pathways will be of different type. In these diseases, the movement of the dosha will be from one organ to the other organ of the same roga marga. In diseases like amavata, vatarakta, etc. which are related with the joints coming under medial pathway, signs and symptoms of the malfunction of heart (hridaya) or bladder (basti) or both etc. will be present. In the same way, the involvement of the heart may produce signs and symptoms related with extrenal pathway in their premonitory stage (purvarupavastha). Prameha and rajayakshma, which are the diseases of medial pathway, may be quoted as examples. In these disorders, excessive growth of hair, nails etc. are observed in premonitory stage.
It can be said that most of the diseases of external pathway originate from colon (pakwashayottha). In the diseases of external pathway apart from the external treatment (bahya chikitsa or bahirparimarjana chikitsa), virechana is preferred. It is only through suitable virechana dravyas, skin diseases are treated successfully.
Virechana have special influence on colon (pakwashaya). Thus, the disorders, which subside by means of virechana, the diseases of external pathways may be said to originate from colon (pakwashayottha).
Rogamarga related to prognosis
The purpose for describing roga-marga is to know prognosis (sukha sadhyatvadi jnanartham). [Chakrapani on Cha.Sa.Sutra Sthana 11/48] [Chakrapani on Cha.Sa.Sutra Sthana 10/12] [Chakrapani on Cha.Sa.Sutra Sthana 10/15,16] [Cha.Sa.Sutra Sthana 10/18,19] The contribution of roga marga to prognosis depends on the robustness of the site.[Chakrapani on Cha.Sa. Chikitsa Sthana 30/327]
Rogamarga for precise treatment
Roga marga is explained in view of precise treatment for diseases occurring in a particulat rogamarga. [Madhukosha on Madhava Nidana, Sarvaroga Nidana Adhyaya Shloka No.10]
As koshtha/abhyantar roga-marga is the place of jatharagni, all its diseases manifest due to poor agni (agnimandya or agni dushti), resulting into ama. Vamana and virechana maybe the line of treatment for shodhana purpose for the diseases occurring here, depending on the classification of origin from stomach (amashaya samuttha) and colon (pakwashaya samuttha vyadhi).
In the diseases of external pathways, dhatwagnimandya will be prominent. Snehana-swedana will be of use for bringing the dosha from shakha to koshtha and removal through the nearby orifice. Virechana and raktamokshana are one of the best shodhana measures for the diseases of external patways. In addition, kshara, and agnikarma can also be applied for the diseases.
For the diseases of medial pathway, prana and vyana vayu are found to be involved. Basti and nasya maybe more beneficial. As the diseases of madhyama roga marga are generally originated from colon (pakwashayottha) and due to obstructed vayu, basti maybe the first line of treatment. Basti is capable of preventing and overcoming the afflictions of marma, asthi sandhi etc. [Cha. Sa. Siddhi Sthana 9/ 7] Additionally, the diseases of head like facial paralysis (ardita), neck stiffness (manyastambha), hemiplegia (pakshaghata), etc. can be treated with nasya.
Similarly, shamana aushadha may also be categorized as acting specifically on a particular roga marga.
Roga marga : a special type of classification of diseases
Some of the expert ayurvedic physicians believe that the description of roga marga denotes special type of disease classification. Such a classification is exceptional in comparison to systemic classification of disease. The systemic classification does not give any contribution in the field of prognosis and management. Whereas it is not so in the case of ayurvedic classification of diseases in terms of roga marga. The systemic classification is based on the anatomical and physiological continuity, whereas not always the organs of a particular roga marga have anatomical attachment. e.g. madhyama roga marga. The connection between the organs of a particular marga is evident pathologically, hence termed as roga marga.
Contemporary approach
The contemporary approach to understand the body and the pathogenesis of any disease is analytical. Whereas that of ayurveda is holistic and comprehensive. With this basic difference, it maybe said that such a concept of ‘rogamarga’ is also unique in Ayurveda, where different set of diseases are said to occur under a single rogamarga. Further, the prognostic approach of contemporary medical science is not based on the systems involved; whereas this concept of rogamarga is also having significance for the prognosis.
Current researches
Thesis
• Bhojani Meera et al: A study on Nirdesha Chatushka of Charaka Samhita and applied aspect of Trayo-Rogamarga, MD Thesis, 2003, IPGT&RA, Jamnagar : A detailed description on the concept of rogamarga and doshagati is explained. A clinical trial is done on the patients of tamaka shwasa and pravahika, based on the concept of rogamarga. It was found that the line of treatment for the diseases occurring in a single rogamarga maybe similar and for the abhyantara rogamarga, the treatment maybe focused on jatharagni centered (correction of the digestion).
Articles
• Vilas Kad, Tushar Auti. A review on trividha rogamarga & its role in manifestation of disease. Ayurpharm Int J Ayur Alli Sci. 2015;4(2):29-34[14]
• Jyoti Devangamath Et Al: Crucial Role Of Rogamarga To Understand Vyadhi. International Ayurvedic medical Journal {online} 2016 {cited 2016 July} Available from: http://www.iamj.in/posts/images/upload/1291_1296.pdf[12]
• Asharani Amitkumar Kore : Concept Of Dosha-Gati With Special Reference To Kshaya-Sthan-Vruddhi Gati; IAMJ: Volume 3; Issue 2; February- 2015[15]
• Kore Asharani Amitkumar, Concept of Urdhav-Adho-Tiryak Gati of Dosha ; UJAHM 2015, 03 (05): Page 7-9;[16]
• Dr. Kulkarni. Pratibha et al., Rogamarga and Dosha Gati ; wjpmr, 2016,2(6), 97-99;[17]
• Pushpa Tuppad. Conceptual study of Rogamarga. J Ayurveda Integr Med Sci 2022;3:53-58;[18]
• These studies have derived the important role played by roga marga in the pathogenesis of the disease, its prognosis and the line of management. The dosha gati in its vikrita avastha is through the roga marga.
Send us your suggestions and feedback on this page.
References
1. Agnivesha , Dridhbala , Charaka , Charaka Samhita , Sutrasthana , Taistraishaniya Adhyaya , 11/48 , reprinted 2020 , Chaukhamba Surbharati Prakashana , Varanasi , Page No. 77
2. Madhavakara ,Madhav Nidana with Madhukosha commentary by Vijayrakshita and Shreekanthadatta revised and edited by Prof. Yadunanda Upadhyaya ,Sarvaroganidana Adhyaya , 1/10 , Page No. 60
3. Chakrapani commentary on Charaka istraishSamhita Sutrasthana , Tistraishaniya Adhyaya, 11/48reprinted 2020 , Chaukhamba Surbharati Prakashana , Varanasi , Page No.
4. Madhavakara ,Madhav Nidana with Madhukosha commentary by Vijayrakshita and Shreekanthadatta revised and edited by Prof. Yadunanda Upadhyaya ,Sarvaroganidana Adhyaya , 1/4 , Page No. 21
5. Arundatta commentary on Ashtang Hridaya edited by Pt. Hari Sadashiv Sastri Paradkar , Nidanasthana , Sarvaroganidana , 1/1 , reprinted 2018, Chaukhamba Sanskrit Sansthan , Varanasi , Page No. 440
6. Radhakantadeva, Vasu, v. and Vasu, h. (1886).Shabdakalpadrumah , Page No. 708
7. Monier-Williams, m. (1899). A Sanskrit-English dictionary , Page. No. 812
8. Boyd, William. "Text-book of Pathology." (1953).
9. Hemadri commentary on Ashtang Hridaya edited by Pt. Hari Sadashiv Sastri Paradkar , Sutrasthana , Doshabhediya Adhyaya, 12/45 , reprinted 2018, Chaukhamba Sanskrit Sansthan , Varanasi , Page No. 200
10. Bhojani Meera Et Al: A study on Nirdesha Chatushka of Charaka Samhita and applied aspect of Trayo-Rogamarga, MD Thesis, 2003, IPGT&RA, Jamnagar
11. Agnivesha , Dridhbala , Charaka , Charaka Samhita , Sutrasthana , Kiyantashirasiya Adhyaya, 17/112-113 , reprinted 2020 , Chaukhamba Surbharati Prakashana , Varanasi , Page No. 105
12. 12.0 12.1 Jyoti Devangamath Et Al: Crucial Role Of Rogamarga To Understand Vyadhi. International Ayurvedic medical Journal {online} 2016 {cited 2016 July} Available from: http://www.iamj.in/posts/images/upload/1291_1296.pdf
13. Vaidya Shivacharana Dhyani.Nidana Panchaka. Chaukhambha Surabharati prakashana.Varanasi. 2022, 58.
14. Vilas Kad, Tushar Auti. A review on trividha rogamarga & its role in manifestation of disease. Ayurpharm Int J Ayur Alli Sci. 2015;4(2):29-34
15. Asharani Amitkumar Kore Concept Of Dosha-Gati With Special Reference To Kshaya-Sthan-Vruddhi Gati IAMJ: Volume 3; Issue 2; Pages-628-6333
16. Kore Ashrani , CONCEPT OF URDHAV-ADHO-TIRYAK GATI OF DOSHA, UJAHM 2015, 03 (05): Page 7-9
17. Kulkarni Pratibha et .al. Roga Marga and Dosha Gati , World Journal of Pharmaceutical and Medical Research , 2016,2(6), 97-99.
18. Pushpa Tuppad, Conceptual study of Rogamarga. J Ayu Int Med Sci. 2022;7(3):53-58 Available From : https://jaims.in/jaims/article/view/1793
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modelStudio - perks and features
Hubert Baniecki
2020-07-15
The modelStudio() function computes various (instance and dataset level) model explanations and produces an interactive, customisable dashboard. It consists of multiple panels for plots with their short descriptions. Easily save and share the HTML dashboard with others. Tools for model exploration unite with tools for EDA (Exploratory Data Analysis) to give a broad overview of the model behavior.
Let’s use HR dataset to explore modelStudio parameters:
train <- DALEX::HR
train$fired <- as.factor(ifelse(train$status == "fired", 1, 0))
train$status <- NULL
head(train)
DALEX::HR dataset
gender age hours evaluation salary fired
male 32.58 41.89 3 1 1
female 41.21 36.34 2 5 1
male 37.71 36.82 3 0 1
female 30.06 38.96 3 2 1
male 21.10 62.15 5 3 0
male 40.12 69.54 2 0 1
Prepare HR_test data and a ranger model for the explainer:
# fit a ranger model
library("ranger")
model <- ranger(fired ~., data = train, probability = TRUE)
# prepare validation dataset
test <- DALEX::HR_test[1:1000,]
test$fired <- ifelse(test$status == "fired", 1, 0)
test$status <- NULL
# create an explainer for the model
explainer <- DALEX::explain(model,
data = test,
y = test$fired)
# start modelStudio
library("modelStudio")
modelStudio parameters
instance explanations
Pass data points to the new_observation parameter for instance explanations such as Break Down, Shapley Values and Ceteris Paribus Profiles. Use new_observation_y to show their true labels.
new_observation <- test[1:3,]
rownames(new_observation) <- c("John Snow", "Arya Stark", "Samwell Tarly")
true_labels <- test[1:3,]$fired
modelStudio(explainer,
new_observation = new_observation,
new_observation_y = true_labels)
grid size
Achieve bigger or smaller modelStudio grid with facet_dim parameter.
# small dashboard with 2 panels
modelStudio(explainer,
facet_dim = c(1,2))
# large dashboard with 9 panels
modelStudio(explainer,
facet_dim = c(3,3))
animations
Manipulate time parameter to set animation length. Value 0 will make them invisible.
# slow down animations
modelStudio(explainer,
time = 1000)
# turn off animations
modelStudio(explainer,
time = 0)
more calculations means more time
Decrease N and B parameters to lower the computation time or increase them to get more accurate empirical results.
# faster, less precise
modelStudio(explainer,
N = 200, B = 5)
# slower, more precise
modelStudio(explainer,
N = 500, B = 15)
no EDA mode
Don’t compute the EDA plots if they are not needed. Set the eda parameter to FALSE.
modelStudio(explainer,
eda = FALSE)
progress bar
Hide computation progress bar messages with show_info parameter.
modelStudio(explainer,
show_info = FALSE)
viewer or browser?
Change viewer parameter to set where to display modelStudio. Best described in r2d3 documentation.
modelStudio(explainer,
viewer = "browser")
parallel computation
Speed up modelStudio computation by setting parallel parameter to TRUE. It uses parallelMap package to calculate local explainers faster. It is really useful when using modelStudio with complicated models, vast datasets or many observations are being processed.
All options can be set outside of the function call. How to use parallelMap.
# set up the cluster
options(
parallelMap.default.mode = "socket",
parallelMap.default.cpus = 4,
parallelMap.default.show.info = FALSE
)
# calculations of local explanations will be distributed into 4 cores
modelStudio(explainer,
new_observation = test[1:16,],
parallel = TRUE)
additional options
Customize some of the modelStudio looks by overwriting default options returned by the ms_options() function. Full list of options.
# set additional graphical parameters
new_options <- ms_options(
show_subtitle = TRUE,
bd_subtitle = "Hello World",
line_size = 5,
point_size = 9,
line_color = "pink",
point_color = "purple",
bd_positive_color = "yellow",
bd_negative_color = "orange"
)
modelStudio(explainer,
options = new_options)
All visual options can be changed after the calculations using ms_update_options().
old_ms <- modelStudio(explainer)
old_ms
# update the options
new_ms <- ms_update_options(old_ms,
time = 0,
facet_dim = c(1,2),
margin_left = 150)
new_ms
update observations
Use ms_update_observations() to add more observations with their local explanations to the modelStudio.
old_ms <- modelStudio(explainer)
old_ms
# add new observations
plus_ms <- ms_update_observations(old_ms,
explainer,
new_observation = test[101:102,])
plus_ms
# overwrite old observations
new_ms <- ms_update_observations(old_ms,
explainer,
new_observation = test[103:104,],
overwrite = TRUE)
new_ms
DALEXtra
Use explain_*() functions from the DALEXtra package to explain various models.
Bellow basic example of making modelStudio for a mlr model using explain_mlr().
library(DALEXtra)
library(mlr)
# fit a model
task <- makeClassifTask(id = "task", data = train, target = "fired")
learner <- makeLearner("classif.ranger", predict.type = "prob")
model <- train(learner, task)
# create an explainer for the model
explainer_mlr <- explain_mlr(model,
data = test,
y = test$fired,
label = "mlr")
# make a studio for the model
modelStudio(explainer_mlr)
References
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http://www.cs.uregina.ca/Links/class-info/330/Shell/TCSH/shell.html
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Today in Science History - Quickie Quiz
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Frustrate Quotes (5 quotes)
It usually develops that after much laborious and frustrating effort the investigator of environmental physiology succeeds in proving that the animal in question can actually exist where it lives. It is always somewhat discouraging for an investigator to realize that his efforts can be made to appear so trite, but this statement does not belittle the ecological physiologist. If his data assist the understanding of the ways in which an animal manages to live where it does, he makes an important contribution to the study of distribution, for the present is necessarily a key to the past.”
From 'The role of physiology in the distribution of terrestrial vertebrates', collected in C.L. Hubbs (ed.), Zoogeography: Publ. 51 (1958), 84.
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Since 1957, influenza epidemics have continued to be a major, serious, and intractable health problem, as frustrating to an action and control orientated epidemiologist as poliomyelitis has been gratifying.
(1971). As quoted in Nancy J. Cox, 'Prevention and Control of Influenza', The Lancet 2000 (Dec 1999), 354.
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The question is not whether “big is ugly,” “small is beautiful,” or technology is “appropriate.” It is whether technologists will be ready for the demanding, often frustrating task of working with critical laypeople to develop what is needed or whether th
Technology Review (Feb 1980).
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They who clamor loudest for freedom are often the ones least likely to be happy in a free society. The frustrated, oppressed by their shortcomings, blame their failure on existing restraints. Actually, their innermost desire is for an end to the “free for all.” They want to eliminate free competition and the ruthless testing to which the individual is continually subjected in a free society.
In The True Believer: Thoughts on the Nature of Mass Movements (1951), 32.
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You must have short range goals to keep you from being frustrated by short-range failures.
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Carl Sagan Thumbnail In science it often happens that scientists say, 'You know that's a really good argument; my position is mistaken,' and then they would actually change their minds and you never hear that old view from them again. They really do it. It doesn't happen as often as it should, because scientists are human and change is sometimes painful. But it happens every day. I cannot recall the last time something like that happened in politics or religion. (1987) -- Carl Sagan
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Web Technologies - Scipy
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Lesson Description
Lession - #316 Scipy-linalg
SciPy is assembled utilizing the advanced ATLAS LAPACK and BLAS libraries. It has extremely fast linear algebra capabilities. These direct variable based math schedules expect an item that can be changed over into a two-dimensional array. The result of these schedules is likewise a two-dimensional array.
SciPy.linalg versus NumPy.linalg
A scipy.linalg contains every one of the capacities that are in numpy.linalg. Moreover, scipy.linalg likewise has a few other high level capacities that are not in numpy.linalg. One more benefit of utilizing scipy.linalg over numpy.linalg is that it is constantly gathered with BLAS/LAPACK support, while for NumPy this is discretionary. In this manner, the SciPy adaptation may be quicker relying upon how NumPy was installed.
Univariate Spline
It is a 1-D smoothing spline that fits a given group of data points. The scipy. interpolate. UnivariateSpline is used to fit a spline y = spl(x>
of degree k to the provided x, y data. s specifies the number of knots by specifying a smoothing condition.
Python is a computer programming language often used to build websites and software, automate tasks, and conduct data analysis. Python is a general-purpose language, meaning it can be used to create a variety of different programs and isn't specialized for any specific problems.
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C 36
OS 9-69
sc *\O
O I.
NANCE
TYPES
ROCKETS
AND
LAUNCHERS
ALL
FEBRUARY 1944
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THE ORDNANCE SCHOOL
ABERDEEN PROVING GROUND, MARYLAND
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THE COMMAND AND STAFF COLLEGE
LIBRARY
Class Symbol
M 614?"G9-B X...Q..d.\)...lL.,
Accession Number A.
edient pending the me imormation contained herein in an K wwxl wi approved War Department manual.
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ORDNANCE SCHOOL TEXT No. 9-69 OS 9-69 THE ORDNANCE SCHOOL Aberdeen Proving Ground, February 1944
r>
DOWNGRADED-AT 3 YEHR INTERVALSDECLSSSjnED AFTER 12 DOD DIH 5200.10
ROCKETS AND LAUNCHERS, ALL TYPES
Prepared under the direction of the Commandant, The Ordnance School
CONTENTS CHAPTER 1. General 2. 2.36" Rockets 3. 3.25" Target Rockets 4. 4.5" Rockets and Launchers 5. 7.2" Rockets and Launchers 6. 8" Rockets 7. 10" Rockets Paragraph 1 10 61 65 94 —113 114 Page 3 9 50 52 90 111 112
-1-
JUL 131948
PRELIMINARY
PRINTING
for limited distribution and subject to correction. Students are urged to add material as it becomes available and make whatever corrections a r e necessary. Blank pages for this purpose are avail able in sections concerned with new items.
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ROCKETS AND LAUNCHERS,
ALL TYPES
CHAPTER 1-GENERAL
1 PURPOSE
This text is published for use in courses at The Ordnance School. 2 SCOPE Chapter 1 covers material common to all rockets, such as the theory of flight, the history of rockets, and their advantages and disadvantages. Succeeding chapters are concerned with the various standard and development rockets, with a chapter assigned to each size of rocket. 3 REFERENCES Information included in this text has been secured from the following publications: a. Standard Nomenclature List S-9, Rockets, All Types, and Components. b. Training Circular No. 104, Antitank Rocket, 2.36", M6 and M7, and Launcher, dated 15 December 1942. c. Technical Manuals: TM 9-390, Target Rocket Projector, Ml; TM 9-393, 4.5-Inch A r t i l l e r y Rocket Launcher, T35, and 4.5-Inch H.E. Rocket, M8;TM 9-395,4.5" Rocket Materiel. d. Minutes of the O r d n a n c e Technical Committee.
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4 HISTORY OF ROCKETS a. The rocket has from early times attracted attention for military purposes, first in Asia and later in Europe and America. No great progress was made until the beginning of experiments by a William Congreve. Congreve extended the work of General Desaguliers, who was in charge of the famous Woolwich laboratory in England. Congreve set himself the task of producing a rocket capable of carrying an incendiary or explosive charge a n d having a range up to 2 miles. After some preliminary trials he was given permission to utilize the Royal Laboratory to construct rockets of his own design. The results obtained were so promising t h a t in 1805 Sir Sydney Smith's expedition against B o u l o g n e included boats especially fitted f o r salvo firing of rockets. Rough weather prevented their use on that occasion, but the following year they were used against -the same place and, although deflected by a strong wind from the fortifications, which were their objec tive, they did, considerable damage in the town itself. b. In 1812 t h e Field Rocket Brigade was formed and was ordered to join the Allies before Leipzig. Captain Bogue of the Horse Artillery, the only English officer present, was made the commander. The effect of the rockets on this occasion — the first time they had ever been used in European
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ROCKETS
GENERAL
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anced forces is setup which can result in movement of the tube. F i g u r e 1 illustrates such an arrangement in its simplest aspect and indicates how a rocket secures propulsion. It will be noted that the pressure is applied in all directions (at the moment of maxi mum pressure of the gas). The arrows indicate the forces exercised by the pressure, and the length of each ar row indicates the magnitude of each force. The forces near the open end of the tube are smaller, because the gas has less pressure at that point. The forces acting on the walls of the tube cancel
« •
land warfare — was very marked. The Rocket Brigade also distinguished itself 3 years later at Waterloo. c. During most of the 1 9 t h century, rockets carried an important share of artillery functions, although they did not come within measurable distance of superseding artillery, as Congreve in his enthusiasm had pre dicted. With the development of rifling, breechloading, independent recoil, and smokeless powder, the a d v a n t a g e s claimed for rockets were discounted, and they were declared obsolete by the end of the century. d. One of the first American proponents of rockets was Edwin Taylor, who, prior to and during the SpanishAmerican War, advocated the use of rockets to propel shells filled with dy namite and nitroglycerine. At t h a t time these charges were too sensitive to withstand the high acceleration pro duced by a gun. e. At the beginning of World War II, little interest was shown in rockets by the armed forces of this country. With the development of a successful antiaircraft rocket by the British, however, research was begun on a large scale. Work in the Ordnance Department on rockets as military projectiles using available modern pro pellants was begun on a small scale at Aberdeen Proving Ground, Maryland, by Col. L. A. Skinner in 1932. Much of the basic information which he secured has been of great assistance in the large-scale development which com menced in October 1942.
5 THEORY OF FLIGHT
* A
NO MOVEMENT
B
B
A
t
t
W
T
t
<ll
*
%
LINE OF MOVEMENT
FIG. 1
B
each other, and the tube moves forward as a result of the force applied to the closed end of the tube. When the gas has escaped from the tube and the pres sure outside the tube is the same as the pressure inside the tube, no force remains to move the tube forward. b. Semiclosed end.— It is ap parent that with the open-end tube the gas escapes rapidly, making a high pressure difficult to attain or main tain. By partially closing one end, a new situation occurs, as diagrammed in figure 2. (The pressure of the gas,
t^
A
1
A.
B
a. Method of propulsion.— If, in a system of forces acting against each other, the forces are unbalanced (i.e., one of the forces is greater than the other), movement will proceed in the direction of the greater force. If gas is placed under pressure in a tube closed at one end, a system of unbal
" LINE OF MOVEMENT FIG. 2
acting as a force against the walls of the tube, is now, for the sake of ex planation, e v e r y w h e r e equal). The forces acting against the walls cancel each other as before. In addition, the
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forces acting against the semiclosed end B of the rocket cancel the forces acting against an equal area of the fully closed end A. Since the tube is parti ally c l o s e d , a greater pressure is achieved and the resulting force on the effective area of end A is greater than h e r e t o f o r e . The force acting against the end A may be measured in terms of the area of the aperture in the end B and the pressure of the gas. The smaller the aperture, the greater the pressure of the gas, but at the same time, the smaller the aperture, the greater the force applied to the effec tive area of the end A. A great many complications enter the theory of flight at this point, but, for the sake of a basic explanation, they will be ignored. c. Introduction of the nozzle.— (1) Forward half.— By tapering the end
ROCKETS GENERAL
should be as long as possible in order to secure the maximum forward thrust and should diverge as rapidly as pos sible, but not so rapidly as to allow the flow of gas to leave the surface of the walls.
6 DESIGN
a. Terminology.— A rocket con sists, in general, of several compo nents. (See fig. 6.) The explosive head is the forward part of the complete round that contains the explosive charge. The motor is the tube that contains the propellant, which upon ignition pro duces the necessary gases. The fins are the attachments that stabilize the rocket in flight. The nozzle is the exit vent for the motor gases. The explo sive head is usually placed at the front end of the rocket. The motor is attached to the base of the head. The nozzle is at the rear end of the motor, and the fins are attached externally at the same place. This terminology is not used to designate the component parts of any particular standard rocket but is r e served for discussions of rockets in general. b_. Explosive head.— Explosive heads for the various standard rockets differ considerably in shape but always have a streamlined appearance. c. Motor.— The motor for all standard rockets is a tube. The walls of the tube have sufficient strength to withstand the anticipated pressures resulting from the burning of the pro pellant. A balance must be struck be tween the weight of the motor (the thick ness of its walls) and the pressure that is to be achieved. A maximum pressure is desirable, but excessive motor weight w i l l materially reduce the effective flight of the rocket. d. Nozzle. — The development of the most efficient nozzle is still in process. At present the nozzle is a smooth piece in the form of a venturi. The forward curve is smooth and has a long radial distance. The rear por
B to the rear, the pressure of the gas is not changed, but a smooth, nonturbu lent flow of escaping gas is created. This tapered sectionforms the forward half of the nozzle. (2) Rear half.— If an extension which expands from the aperture is added to the nozzle, a system of forces which give a forward thrust to the tube is set up. Figure 4 illustrates how this is accomplished. There are prac-
T
I K
T
B
'LINE OF MOVEMENT FIG. 4
tical limits to the length of this ex pansion as well as to the angle at which the expansion develops. In general, it may be said that the expanding part
-5
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ROCKETS
GENERAL
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(3) Lack of recoil is an im portant consideration, for it gives wide latitude in the selection of mounts and missiles. The mount may be of more e. Fins. — The fins vary in shape delicate construction than is possible with a gun of equal caliber; missiles with the different rockets. that cannot withstand gun acceleration f. Propellant.— T h e develop can be projected rocket fashion. Ab _ ment of a suitable propellant for rockets sence of recoil has also permitted the has been a difficult process. At present development of sensitive and efficient a propellant powder in stick form is fuzes. used. This powder, which is ballistite, burns slowly and evenly, providing the (4) Of tremendous importance maximum allowable pressure. The rate in considering the advantages of rockets at which the powder burns (which is a are the ease and cheapness of manu determining factor of pressure) is de facture of the launcher in comparison termined by many factors. One of these with the complexity and high cost of a is the diameter of the nozzle, which gun. The rocket launcher is simply a regulates the rate of escape of the gas. guide and consists either of a tube or If the gas fails to escape at the proper parallel tracks. rate, the pressure within the motor increases. As this internal pressure b. Advantages of rockets.—The builds up, the rate of burning of the advantages of rockets, then, may be propellant will increase, further in summarized as follows: creasing the pressure until the wall strength of t h e motor is exceeded. (1) Absence of recoil. The composition and the rate of burn ing of the propellant, then, affect not (2) Accelerations that are not only the design of the nozzle but also excessive and that are easily controlled. the thickness of the motor. It may be seen that the balance to be achieved be (3) Need for only a light,-in tween the various components is a deli expensive, easily mass-manufactured cate one. guide launcher.
7 ADVANTAGES AND LIMITATIONS
tion of the venturi develops at an angle of approximately 20°, the limit best suited to secure the maximum thrust.
a. A p p l i c a t i o n s of rockets. (1) Rockets are of great importance because they produce no recoil. The lack of recoil permits their use on airplanes and small boats and on light tanks, cars, motorcycles a n d other vehicles incapable of withstanding large recoil forces. It also permits t h e firing if grenades and explosive charges from a tube held in the hands. (2) Another feature of rockets that gives them military importance is the relative lightness of the projector in comparison with a gun firing ammuni tion of equal weight. This permits fire to be delivered from areas to which guns and howitzers cannot be transported.
c. Limitations of rockets.— The following disadvantages limit the appli cation of rockets. (1) The dangers resulting from the blast of the gases escaping through the nozzle. (2) Decreased accuracy in com parison with a gun. 8 USES At the present time there are five kinds of rockets. They are classi fied for use as follows: a Antitank.-The antitank rock et is fired from the shoulder for effec tive action against armored vehicles and hard-surfaced materials.
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ROCKETS
GENERAL
b. Antiaircraft t a r g e t rocket. This rocket is fired from a special launcher to simulate the flight of low flyirig aircraft in order to provide anti aircraft gun crews with a more accu r a t e one epti on of combat firing. c. Artillery and aircraft artil lery.— This rocket is used in much the same manner as artillery in general and with the same mission. As air craft artillery, it is fired from planes against other planes and from planes against ground targets. d. P r a c t i c e . — These rockets are fired to simulate the firing of highexplosive rockets, to which they cor respond, without the danger or expense of firing the latter. _§_. Chemical.— These rockets project smoke and other chemical agents. 9 ROCKETS a. Listing.—The following rock ets are issued to the service:* b. Characteristics.— A l l t h e above r o c k e t s are projected from launchers with either rails or a tube to serve as a guide. As the function of rockets vary, their design varies a c cordingly, but all have the m o t o r , nozzle, and fins at the r e a r . c. Painting.— The rockets hav ing a high-explosive content are painted olive drab;those having inert heads are painted blue. Painting will be discussed in more detail in the section devoted to each particular rocket. d. Packing.— Packing will be discussed in the sections devoted to each particular rocket. e. General safety precautions. (1) A distinctive feature of rockets is the blast at the base of the launcher when the rocket is being projected. Person nel are warned to stay clear of the blast area, for this blast is highly destructive.
(2) All rockets should be stored at a temperature that does not exceed (1) Rocket, H.E., AT, 2.36", the temperature range specified for the M6A1. rocket. No rounds should be left ex posed to the direct rays of the sun for (2) R o c k e t , practice, 2.36", any length of time in order to avoid M7A1. heating the powder to a temperature above that at which the rocket is d e (3) Rocket, target, A.A., 3.25", signed to operate. Local conditions M2. will govern the type of storage place (4) R o c k e t , H.E., 4.5", M8 that is supplied. The several tem w/Fuze, P.D., M4. perature limits have been carefully (5) Rocket, practice, 4.5", M9 determined for these rounds, and these limits should not be exceeded. w/dummy fuze.
*The nomenclature of the rockets listed is correct and complete. However, in the interest of brevity it will be shortened throughout the following dis cussions. Modifications are occurring rapidly, and therefore the above list is subject to change. -7-
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ROCKETS GENERAL
i—
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CHAPTER 2-2.36" ROCKETS
SECTION I ROCKET, H.E., AT, 2.36", M6A1 10 GENERAL a. Description.— The antitank rocket, 2.36", M6A1, is both an off ensive and defensive weapon. In both types of action, it is used primarily to fire upon hostile armored vehicles which come within effective range. It is e s s e n tially a weapon of opportunity. It is 21.6" long and weighs 3.5 lb. It has a relatively low r a t e of fire and a d i s tinctive flash discharge. Its muzzle velocity is approximately 265 f t . / s e c . The maximum range is 700 yd., but the rocket is comparatively inaccurate at ranges over 300 yd. In the hands of trained personnel, it is a powerful supporting weapon at short ranges with limited fields of fire. It is highly ef fective against all known types of m e dium tanks. b. Tactical use.— (1) Offensive action.— Being both highly mobile and effective against pill-box and mecha nized defenses, t h e antitank rocket, 2.36", M6A1, is a valuable weapon to be c a r r i e d by landing forces, raiding groups, tank-hunting p a r t i e s , and m o torized reconnaissance units. It is capable of delivering harassing fire against an a r e a target from ranges as great as 600 yd. and so is extremely valuable in attacks on vehicular biv ouacs and halted or disabled armored vehicles and for use in ambushes. (2) Defensive action.— T h e f o r e most use of this weapon is that of a d e fensive weapon against the attack of mechanized forces. It should always be conserved for this emergency p u r pose. Whenever time permits, rocket teams will be assigned a definite place in t h e antimechanized defense of a weapon, unit, or installation; and if natural cover is not available, twoman-typefox holes will be dug for each rocket team. In the event of a s u r p r i s e -9
M6A1 ROCKET
attack, r o c k e t e e r s must maneuver themselves in the most favorable po sition to direct their fire against the nearest hostile vehicle. The antitank rocket is valuable in the following d e fensive situations: the close-in defense of crew-served weapons;the protection of motorized columns on the march and at temporary h a l t s ; the protection of minefields, wire entanglements, obser vation and command posts; and the defense of all r e a r - a r e a installations of all a r m s and services within the range of hostile mechanized forces. (3) Miscellaneous.— In addition to the above uses as an antitank p r o jectile, this rocket can also be used in a stationary emplacement for demoli tion or as an antitank mine or a booby trap. c. Effect.- (1) The rocket will penetrate 3" of homogeneous-steel a r mor plate at all ranges and at angles of impact as low as 30°. The force of the detonation is so great that the metal of the armor plate is raised to a state of incandescence and heated particles of the metal fly from the back of the plate in a cone-shaped spray. Tins' spray has antipersonnel effect as far as 30 yd. and usually causes any ammunition which it strikes to detonate. (2) Against masonry and struc tural steel, the rocket has a powerful blast a n d shattering effect. It will penetrate up to 9" of pine timber, but its continuing spray is not as effective as in the penetration of armor plate. Ground impact will n o t ordinarily cause detonation at high angles of im pact. At low angles of impact, the blast effect is similar to that of the 75-mm high-explosive shell. Impact against water will never cause deto nation.
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M6A1
ROCKET
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11 ROCKET LAUNCHER, M1A1
a. General.—The 2.36" antitank rocket launcher, M1A1, is an electri cally operated weapon of the open-tube type. It is fired from the shoulder in the standing, kneeling, sitting, or prone positions. The tube has a smooth bore and is approximately 54.5" long. It is 2.37" in internal diameter and weighs 13.26 lb. b. Description.— (1) Attached to the left side of the barrel are the front and rear sights. The rear sight is a peep sight;the front sight consists of three studs for ranges of 100, 200, and 300 yd. Intermediate or greater ranges, lead, and windage must be esti mated by the firer. (2) Ahead of the front sight and secured to the tube by a screw and nut is a flash deflector of conical wire screen with a mounting clamp which overlaps the muzzle end of the launcher. The flash deflector deflects particles of unburned powder which might fly back in the face of the firer. (3) The hand grip consists of the left and right trigger grips attached to the trigger support. The trigger support a c c o m m o d a t e s the trigger guard, trigger, and the lower and up per trigger-switch contacts. The trig ger is pinned at its upper end to the trigger support and is free to pivot.
M6A1 ROCKET
(4) The stock h a s a narrow vertical slot by means of which it slips over the stock support, to which it is attached by screws. In the bottom of the stock there are two vertical cylin drical compartments f o r accommo dating four batteries. The two batteries in the rear compartment are in actual use; the two batteries in the front com partment are spares. Eveready 791-A batteries are issued initially. When replacement is necessary, two separate cells of the battery BA-42 type can be used if the Eveready batteries are not available. The batteries are kept in po sition by a hasp assembly which fits on the bottom of the stock and is kept closed by a spring-actuated hasp catch which engages the stock pin. (5) On the left side of the stock is a small electric lamp for testing the electric circuit and battery. The lamp is connected parallel with the firing mechanism, and it lights when the trig ger is squeezed, regardless of whether the rocket is in the launcher or not. A spare lamp is carried in a circular compartment on the right side of the stock, under the circuit indicator cover. (6) The face guard, pressed on the barrel above the stock and held in position by its own tension, protects the firer's face from the heat in the tube.
BAR CONTACT BATTERY SPRING LOWER TRIGGER SWITCH CONTACT
FIGURE 7. - ROCKET LAUNCHER, M1A1
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M6A1 ROCKET
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13 BODY AND OGIVE ASSEMBLY
(7) At the rear of the barrel is a spring-actuated tail-latch assembly. The function of the latch is to engage notches on the tail of the rocket and hold it in position for firing. T h e breech guard at the breech end of the barrel facilitates loading of the rocket, protects the tail-latch assembly, pre vents distortion of the end of the bar rel, and prevents entry of dirt and foreign material when the end of the launcher rests on the ground. £. Electrical functioning (see fig. 7)."^- (1) When the t r i g g e r i s squeezed, it presses the bar contact against the lower trigger-swtich con tact to complete the electric circuit. (2) The battery spring in the base of the stock contacts the batteries and is connected by wire to the stock support to complete the electric circuit. From the rear of the stock to the in sulated contact springs, the barrel is wound with bracing wire. The two con tact springs, one on each side of the tube, serve as connecting points for the contact wire leading from the rocket. In this manner, the circuit is completed. The electric current passes through the rocket and sets off an electric ig niter which ignites the p r o p e l l i n g charge. (3) When the pressure on the trigger is released, the trigger spring forces the trigger to the forward posi tion and the electric circuit is broken.
12 ROCKET COMPONENTS
This assembly (see fig. 6) com prises the head of the rocket. Taken by itself, it has the general appearance of a boattailed artillery projectile. It consists of a body, ogive, and body union. a. Body.- This (see fig. 8) is a steel cup, 4.11" long, with a diameter of 2.23" at its forward open end and
JJ
FIG. 8 -BODY
n
with walls 0.087" thick. The rear half of the body is slightly tapered, and in the rear face is punched a hexa gonal hole, 1.06" across the flats. Into this hole is fitted the body union. An external longitudinal groove, 0.175" wide and 0.037" deep, is pressed 0.385" to the rear of the forward end of the body. b. Ogive.— The ogive (see fig. 9) is a cone, 4-1/2" in height and 2.245" in diameter. The walls of the cone are 0.031" thick and are bulged out t o form a flange approximately 1/2" wide at the base. This flange fits over the open end of the body and acts as the forward bearing surface of the rocket in its travel through the launcher. The flange is clinched securely into
The M6A1 rocket is 21.62" long and consists of a body and ogive a s sembly, complete with explosive com ponents, and a stabilizer and fuze a s sembly, complete with explosive and propellant c o m p o n e n t s . The total weight of the rocket is divided between these two component assemblies, the former weighing 1.57 lb., the latter, 1.82 lb. In the following paragraphs each component will be described. The explosive components will be discussed separately.
F I G . « -OGIVE
the groove in the forward outer sur face of the body. Four depressions
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are formed in the ogive just above the flange. These depressions rest on the upper rim of the body. c_. Body union.— The body union (see fig. 10) is a cylindrical component open at both ends. It is 0.78" in height and 1.25" in diameter. At the forward end, the body union is reduced to 1.058" in external diameter for a distance of 0.25" and is tapered internally. This allows the union to fit into the hexagonal hole in the rear of the body, where,
M6A1 ROCKET
(a) Stabilizer tube.— This com ponent (see fig. 6) is made of steel tubing 6.322"long and 1.060"in internal diameter with walls 0.095" thick. The forward rim of the tube is chamfered; the rear 0.44" of the tube is externally threaded. (b) Fuze body.— This component (see fig. 11) is a thick-walled cup, cut away on its forward part to form a
after insertion, it is crimped into place. The central hole of the union is threaded to seat the stabilizer-tube assembly. 14 STABILIZER ASSEMBLY a. Functions.— The stabilizer assembly has the following functions: (1) To house the fuze and pro pellant. This part of the rocket is called the "motor," i.e., the part that does the propelling. (2) To house the electric firing attachment. (3) To serve as an escape vent for the propellant gases.
threaded projection 0.93" in diameter. The center section of the body is 1.25" in diameter; the rear section is 1.061" in diameter to allow a forced-fit joint in the forward end of the stabilizer tube. The over-all length is 2.317", and the central hole is 1.772" deep and 0.500" in diameter. At the point where the forward projection begins, the central hole widens to a diameter of 0.68". From this point forward, the central hole is internally threaded to sr Jt fuze components. A hole 0 . 0 8 9" in di ameter is drilled transversely through the fuze body just above the long axis of the body that intersects the central fuze body hole.
(c) Safety pin.—This component is inserted in the transverse hole men tioned in (b), above, where it restrains (4) To stabilize the rocket in the firing pin of the fuze. Upon removal of the pin, the fuze is armed. When the its flight. safety pin is removed, DO NOT DROP b. Components. — The stabilizer assembly consists of the stabilizer-tube THE ROCKET. assembly, fin assembly, electric wiring (d) Fuze.— 1 The fuze (see _ and connections, and trap assembly. The fig. 6) consists of a steel firing pin and components are described in the follow a firing-pin spring. The firing pin is ing subparagraphs. roughly cylindrical in shape and has a (1) Stabilizer-tube a s s e m b l y . point 0.31" long protruding from the flat This component (see fig. 6) consists forward face. The firing pin slips into of a stabilizer tube, a fuze body, a the central cavity of the fuze body, where it is held in a rearward position safety pin, and a fuze. -13
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M6A1 ROCKET
by the firing-pin spring. A circum ferential groove, 0.045" deep, midwaydown the length of the firing pin, r e ceives the safety pin when the latter is in place. The safety pin, when in this groove, holds the firing pin securely in a rearward position. When the safety pin is removed, the firing pin is free to move forward, restrained only by the action of the firing-pin spring. Drop ping the rocket as little as 4' will pro vide sufficient impact for the firing pin to overcome the tension of the spring and cause the rocket to be detonated. Therefore, when the safety pin is r e moved, it is necessary to take every precaution not to drop the rocket. 2 Below and in line with the firing pin and spring is the M18 detona tor assembly and the explosive charge. The detonator assembly consists of an aluminum detonator cup, 0.342" deep, 0.190" in diameter, and crimped at both ends. It is housed in a brass detonator holder that screws into the internally threaded opening of the fuze body. A brassbooster cup, 0.480"deep, 0.530"in diameter, and externally threaded on the rim, is screwed into place in the fuze body after the detonator holder is fitted. The booster cup and the detonator holder are separated by an onionskin disk and a detonator-holder retaining disk. The second disk is made of alu minum and seals, in turn, the detonator holder in place in the fuze body. The lower or unthreaded external half of the booster cup extends beyond the fuze body, and, when the stabilizer assembly is screwed into the rocket body, the booster cup fits into a recess in the explosive charge. (2) Fin assembly.— The fin as sembly, which guides the rocket in flight, (see fig. 12) consists of six steel fins and the nozzle. Each fin is attached to the nozzle by two spot welds on the lower flange. (a) The fins are made of sheet steel 0.041" thick and 5-1/2" long. The fins are flanged at top and bottom in the
shape shown in figure 12. In the upper edge of each fin is cut a notch 1-2/3"
/- '.V.'.
JECTION AA
F I C 12 -FIN ASSEMBLY
from the leading edge. This notch is kept free of paint and is tinned with solder. On the side surface of each fin, an area 1/8" in diameter is treated similarly. All external surfaces of the fin assembly except the tinned sur faces of the fins, which are keptfree as electric contacts, are coated with olivedrab lacquer enamel. (b) The nozzle is a steel cup internally threaded at the forward end. The rear face of the cup narrows and continues t o t h e rear, forming the nozzle proper. The internal surface of the rear half of the nozzle is curved smoothly, as illustrated in figure 13, and is given a fine finish. The forward
half of the nozzle is 1.49" in diameter; the rear half is 0.687"in diameter. In ternal surfaces of the nozzle are coated with a light coat of priming paint. (3) Electric wiring and attach ments.— This component ignites the propellant and is an electric squib with two insulated lead wires of unequal
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length. The squib is thrust up into the stabilizer tube so that its forward end is approximately 5-1/2" forward of the rear end of the nozzle. Both lead wires, one 18-3/4" long, the other 6-3/4"long, extend rearward out of the nozzle. The short length is stripped sufficiently at its free end to allow it to be soldered to a tinned spot on one of the fins. The longer length of wire is wrapped twice about the under projection of one of the fins. The last 6-1/2" of the wire are laid bare, and a 1/2" length is folded back twice upon itself. Over this node of wire is wrapped a 6" length of 1/2" b l a c k tape. This taping facilitates grasping the end of the wire. The wire is then spiraled to take up its slack, and the free end is reversed and taped lightly (with cellulose tape) to the rear end of a fin (see fig. 6). When the rocket is loaded into the launcher, the wire is torn from the tape and its bared length engaged in the launcher clips. (4) Trap assembly.— The trap assembly, which holds the propellant in the best burning position, consists of a steel trap body and a trap ring, shaped as illustrated in figure 14, the trap ring being staked to the trap body. The assembly is either cadmium or zinc plated. (a) The trap body is made of steel and has eight equally spaced ribs. (b) The trap ring is made of steel.
TRAP BODY
M6A1 ROCKET
c. Assembly.— The fuze body is inserted" in t h e forward end of the stabilizer tube and is held in place by the tight fit required. A silver-solder ring is slipped down the tube and, upon heating, melts and seals the internal joint between fuze body and tube. Fol lowing this, a dome-shaped disk i s slipped down the tube, convex side up, and pressed flat against the fuze body. The disk is a safety factor; it removes the possibility of propellant flames or gases working through or around the fuze body to cause premature function ing of the rocket. The firing pin is in serted and the safety pin run through the transverse hole and the firing-pin groove. The detonator holder, with detonator, i s screwed into the fuze body, followed by disks and the booster cup. The propellant is inserted in the tube. The trap assembly is screwed into the large opening of the nozzle, where it rests on the rim just below the internal threads. Then the fin a s sembly is screwed onto the rear threads of the stabilizer tube. Pettman cement is applied to the threads of the nozzle to waterproof the thread mesh. The rear end of the nozzle is closed with a chipboard disk, which is notched to provide for the passage of the lead wires.
15 EXPLOSIVE COMPONENTS
TRAP RING
FIG. 14 TRAP ASSEMBLY
a. Propellant.— The propellant consists of five sticks of ballistite, each 0.36" in diameter and 4.15" long. The -rocket is not loaded by weight but by length of powder stick — the purpose being to keep the pressure for various rounds at a relatively constant value. On the average, however, the propellant weighs approximately 61-1/2 grams. The propellant and its components are loaded as follows: A spacer tube, made of kraft paper, 1" in diameter and 3/4" long, is slipped into the stabilizer tube, coming to rest against the flattened disk. The five propellant sticks are slipped into the tube, coming to rest upon the rim of the spacer. When the
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M6A1 ROCKET
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After the round is inserted in the con tainer, the cover is sealed in place by means of a strip of 2" adhesive tape 20-1/2" long. This strip is olive drab in color and has the designation of the rocket (Rocket, H.E., A.T., 2.36", M6A1) marked on it in yellow figures and letters. b. Packing box— (1) The packing box (see fig. 15) is 18-2/3" x 13-1/2" x 24-1/2" and is sturdily constructed of 3/4" lumber reinforced by end and top cleats. Two 16" lengths of manila rope are securely attached to opposite sides of the box and serve as carrying handles. The box is stained a light brown, and all the exposed metal parts are painted with light-brown lusterless enamel. The box has identifying marking (see fig. 15) in black paint. (2) The 20 loaded containers are i n s e r t e d in the compartments (formed in the box by fiberboard di viders) so that adjacent containers are tail end up and nose end up, respec tively. 18 SAFETY PRECAUTIONS a. The safety pin should be re moved only after the nose of the rocket is placed in the launcher. b. The rocket is sensitive and will function if dropped on its nose upon a hard surface from a height of 4'. Do not remove the safety pin except as ex plained above. Even when still in the packing containers the rockets must not be subjected to rough handling. c. Rockets which have been un packed but not fired should be returned to their original packing containers. The safety pin and the nozzle disk must be in place. The fiber container should be resealed with the adhesive tape. d. Rockets should be stored in a dry, cool place. They should not be stored where temperatures exceed 120 F., and they should not be exposed to the direct rays of the sun. e. Face guard and gloves must be worn when the rocket is fired.
nozzle is screwed onto the stabilizer tube, the propellant sticks rest on the rim of the trap ring and are held se curely in place. b. O t h e r e x p l o s i v e compo nents.— The body contains the explosive charge, and in the fuze body are the M18 detonator and the booster. The detonator consists of an upper detona tor charge of 0.98 grains of lead azide and a detonator pellet of 1.26 grains of tetryl. The booster charge is a pellet of tetryl weighing 1.86 grains. 16 PAINTING AND MARKING a. Painting.— All external sur faces of the complete rocket are coated with o l i v e - d r a b ammunition paint. Those surfaces previously mentioned as being unpainted remain so. b. Marking.— Just below the joint of ogive and body, the name of the round, the lot number, the manu facturer's initials, and the month and year of loading are marked circum ferentially with yellow marking ink. All the letters and figures are 3/8" high. Sample marking: ROCKET, H.E., A.T., M6A1 Lot 1234-56, P.A. 9-43 17 PACKING T h e M6A1 rocket i s packed one per individual fiber container, M87 (see fig. 15). Twenty such loaded con tainers are packed in a wooden packing box. The box, complete with contents, weighs approximately 136 lb. and is equipped with two rope handles to facil itate its handling. a. Container, M87.— This con tainer follows the standard design for fiber containers, consisting of a cylin drical tube and cover of laminated asphalt-filled c h i p b o a r d . The con tainer is 22-1/2" long and 2-3/4" in diameter. The tube and cover are each closed at one end with a terneplate end plate. A plywood support ring rests on a chipboard spacer at the lower end of the tube. It prevents the nose of the rocket from touching the end plate.
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M6A1 ROCKET
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M7A1 ROCKET
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SECTION II
ROCKET, PRACTICE, 2.36", M7A1
(2) Marking.— In the same posi tion as on the M6A1 H.E. rocket, the nomenclature of the round, the lot num ber, and month and year of manufacture appear in white marking ink. d. Packing.— (1) The practice rocket is packed in the same manner and in the same container as the M6A1 rocket (see par. 17). The sealing strip for the container is light blue, and the appropriate nomenclature is stenciled in white. (2) Twenty c o n t a i n e r s a r e packed into the wooden packing box in the same manner as the H.E. M6A1 round. The packing box is identical but is marked to correspond with the con tents. In addition, a 3" blue band en circles the box when the contents are practice rockets. Blue paint is also applied to the vertical cleats at each end of the box. e. Precautions.— T h e s a m e precautions described in paragraph 18 must be exercised in the storage and handling of the practice rocket. How ever, since there is no bursting charge or firing mechanism, the removal of the safety pin does not arm the M7A1 rocket.
19 GENERAL
The M7A1 rocket (see'fig. 15) is similar in design and construction to the M6A1 rocket, lacking only an explosive charge. It has the same dimensions, weight, and trajectory a s t h e H.E. rocket. It is fired in the same ranges as the M6A1 without the cost or danger incidental to firing the H.E. round. a. Weight rod.— A steel rod, 5.33" l o n g , 0.75" in diameter, a n d threaded at one end, is fitted into the fuze body. This rod makes up for the weight of the explosive charge and fuze present in the M6A1 rocket. All other components of the M7A1 practice round are similar to the components of the M6A1 rocket. b. Use.— After ithasbeenfired, the practice rocket, M7A1, may be used again as a dummy round in teaching methods of loading and handling. c. Painting and marking. (1) Painting.— All external surfaces of the M7A1 practice rocket, are coated with blue lacquer enamel. Fin sur faces serving as contact points for the igniter system are left unpainted and are tinned with solder.
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M7A1 ROCKET
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M6A3 ROCKET
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SECTION III ROCKET, H.E., AT, 2.36", M6A3
20 REASONS FOR CHANGE
• a. Change in ogive. —The design of the conical ogive of the M6A1 rocket proved to be undesirable for several reasons. First, the ogive tended to telescope on impact. This resulted in poor transmission of the impact force to the fuze, allowing a variation in the time interval between impact of the rocket and functioning of the fuze in successively fired rockets. Secondly, on impact at angles of 20° or more the conical ogive tended to shear off at the joint of ogive and body. This shearing had a serious effect on penetration of the target. The major difficulty with the conical ogive was that it failed to provide f o r a uniform, satisfactory penetration of the target by all rockets. b. Change in tail a s s e m b l y With the contemplated addition of a hemispherical ogive it was realized that the center of pressure of the rocket would be moved forward and that the rocket would have a definite wobble through its trajectory unless the tail assembly were improved. For this reason it was decided to redesign the tail assembly. A circular assembly was the design finally accepted. c. Redesignationof model num ber.— The North African theater has renovated the M6A1 and M7A1 rockets and assigned the model number M6A2 to the renovated rounds. Although the Ordnance Department did not officially recognize this designation, it was felt that the M6A2 designation should not be applied to any new ammunition because of possible confusion and misunder standing. For this reason the designa tion M6A3 and M7A3 (see section IV) have been applied.
21 HEMISPHERICAL OGIVE a. Description.— T h e o g i v e , made of sheet steel, has the shape il lustrated in figure 17. It is 4-9/16" long and 2.245" in diameter at the flange. The hemisphere is curved on a 1" radius. b. Effectiveness.- With the hemispherical ogive, the fuze of the rocket has been found to function in an average of 875 microseconds compared to an average of 1250 microseconds in the M6A1 with a conical ogive. Pene
tration has been uniformly improved. The improvements in functioning and penetration are due to the even trans mission of impact force through the straight sides of t h e hemispherical ogive. On angle impacts, the M6A3 has resisted shearing and has maintained a fast fuze action and uniformly high penetration. 22 TAIL ASSEMBLY a. Description of fin.— The new type of fin used on the M6A3 rocket has the shape illustrated in figure 18. Each of the four fins required in the complete assembly is made of .025" sheet steel. The broad blade of the fin is 2-5/16" long and curved over an arc of 90°. b. A s s e m b l y - Each fin is joined to the other by welding with an overlap
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of approximately 1/2". lne oases 01 the fins are spot welded to the nozzle. rough the upright section of one of Jfour fins is a small hole. This hole (for insertion of one qf the ignition |es. In the blade of each fin is a lsverse groove which is continuous the grooves in the other three fins le complete assembly. This groove is tinned and serves as a contact point with the electrical s y s t e m of the launcher.
DECLASSIFIED ffectlveness.—
M6A3 ROCKET
The M6A3 c. Efi rocket with the circular fin has slightly better ballistic qualities than the M6A1 rocket had with the old-style tall as sembly. Considering that the center of pressure has been moved forward, this is a marked improvement. 23 OTHER CHANGES There are no other changes in the M6A3 rocket. In all other respects it is similar to the M6A1 rocket.
1
1 1
SLOT
TAIL ASSEMBLY FIG.-18 TAIL ASSEMBLY
SECTION IV ROCKET, PRACTICE, 2.36», M7A3
24 CHANGES The M7A3 rocket has all the changes mentioned above in the M6A3
rocket. It is the practice counterpart of the M6A3 and has the same ballistic qualities.
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M6A3 SOCKET
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1
ROCKET. HE.. A.T..M6A3
a. x tn ui z <
DETAIL OF MARKING
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M7A3
ROCKET
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-23-
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M7A3 ROCKET
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M7A3 ROCKET
T12 ROCKET
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SECTION V ROCKET, H ^ . , AT, 2.36", T12
25 RSSON FOR DEVELOPMENT •The M6A1 rocket has been used widely!In combat, and its deficiencies have been noted. The development work on the T12 was started so that all the de ficiencies of the earlier rockets might be corrected. The T12 rocket retains all the good qualities of the M6A3. Specifically, t h e new performance characteristics are: a. Greater stability in flight and a consequent greater accuracy. b. Safe operation through a greater temperature range. c. A bore-safe fuze — the most important change in the T12.
(1) Motor assembly.— (a) Tail. The tail is a seamless steel tube 7.50" long and approximately 1.330" In di ameter. The rear end of the tube is curved in a venturi. The throat at its narrowest point is .433" in diameter. The central internal portion of the tail is approximately 1.06" in diameter. The forward internal .75" of the tail is threaded. The outer rear sur face of the t a i l seats the tail as sembly. (b) Rein ring.— This circular steel band is shrunk onto the tail at the threaded forward end. It strengthens this end of the tail.
(c) T r a p and trap-base as sembly.— The trap and trap-base as d. Detonation of the rocket on sembly consists of the trap and trap ground impact for use against per-' base. The trap is a star-shaped de sonnel. This involves the employment vice made of steel. The central por tion has a .125" hole, and from it r a of a more sensitive fuze. diate five spokes, 72° apart and .51" long. The trap is fitted onto the trap 26 GENERAL base. The trap base is a disk 1.0" in a. Appearance.— See figure 21. diameter and .06" thick. A spindle 21/32" high and .271" in diameter pro b. General data.— jects from the center of one face. The last 7/32" of the spindle is reduced in Length, over-all 17.16" max. diameter to .123". Onto this section Length of head 8-1/4" of the spindle is fitted the trap. The Length of motor 7.5" end is peened to hold the trap in Length of fin 3-15/16" place. The complete trap and trapExplosive charge 220 gxn. base assembly is soldered to the sur 50-50 cast pentolite 214 gm. face of the fuze body. The propellant 10-90 cast pentolite 6gm. hangs on the trap and is thus rigidly Propellant (approx.) ~ 63 gm. held in the motor. Weight of complete rocket — 3.72 lb. c. Components.— T h e M6A3 (d) Igniter.— No information on head and the T12 head are identical. this item is available at present. Several other components, including the fuze, are new. The fuze will be (e) Propellant.—The propellant discussed in a separate paragraph; the in the T12 motor Is the same as that components of the new motor and fin used in the M6A3. It consists of five assembly will be discussed in the fol sticks of ballistite, each approximately 4.15" long and .375" in over-all di
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T12 ROCKET
T12 ROCKET
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T12 ROCKET
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T 1 2
"* •
- •
ROCKET
ameter. Through each stick runs an axial hole .125" in diameter. The rocket isgROt loaded by weight, as is explained ii^paragraph 15, but it weighs approxi mately 63 gm. (2) Fin assembly.— This a s sembly consists of six fins, six fin brackets (one of which is slightly dif ferent from the other five), rivets, and a fin ring. The six brackets are spot welded onto the tail surface of the motor. The fins are held in place be tween the brackets by rivets passing through the holes in the brackets and the fin hole. The fin is free to rotate 120° and is checked from further move ment by a slanted surface on the back of the fin. The fins are held in place along the motor by a fin ring. This ring is a circular band and is removed when the rocket is placed in the launcher. 27 FUZE, ROCKET, 2.36% T7 a. General.— The T7 fuze was developed to meet the need for a safer, faster functioning fuze. (See fig. 21.) Shortly to be standardized, it will be used in the T12 and the T23 rockets'. The major difference between the T7 fuze and the fuze used in the M6A1 rocket is that the T7 is of the "bore-riding" pin type similar to the M52 mortar fuze. Because of this bore-riding feature, the T7 fuze is bore safe and yet suffers no reductipn in effectiveness. b. Action.— (1) The safety pin passing through the firing pin holds the latter securely in place. The slider spring presses 'forward against t h e shoulder of the slider. The slider, which is slotted on its forward rim, hooks into a groove in the inner end of the arming pin, holding the arming pin in position. (2) When the safety pin is with drawn, the firing pin is still held se curely in place by the arming pin. Upon set-back, however, the slider is forced to the rear against the tension of the slider spring. This permits the arm
ing pin, disengaged from the slider, to be forced out by the compression of the arming-pin spring until the arming-pin cup strikes the wall of the launcher. (3) As long as the rocket r e mains in the launcher, the arming pin is held partly in the firing pin, holding the latter in position. (4) When the rocket has cleared the launcher, the arming pin with its attached cup and the arming-pin spring are expelled. The firing pin is now free to move. The firing-pin spring is an "anti-creep11 factor, preventing the fir ing pin from contacting-the detonator except on impact. (5) On impact, the firing pin, is driven into the detonator by inertia, exploding it. The detonation passes through the booster, where it is ampli fied, and the function of the fuze is complete. c. Explosive components. (1) Detonator, M18.— This is the same detonator as that assembled with the M6A3 rocket. (2) Booster.— This is the same booster as that used with the M6A3 rocket. d. Safety devices.— This fuze has several safety devices, most of which have been mentioned above. They are as follows: (1) Safety pin.— This component holds the firing pin firmly in place and makes the fuze safe up to the shear point of the safety pin. This shear point will rarely be exceeded. (2) Slider. — T h i s component, under tension of the slider spring,, holds the arming pin in place. The slider may be forced to the rear if sufficient ac celeration could be simulated. Even in a free fall of l f to 2* this accelera tion would not be approximated and the slider would stay in its forward position.
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DECLASSIFIED
T12 ROCKET (3) Arming pin.— This compo nent makes the fuze bore safe, since it does not permit the firing pin to move forward until the rocket is clear of the launcher and the arming-pin assemblyexpelled. (4) Firing-pin spring.— T h i s spring prevents premature detonation of the rocket. Without the spring, the firing pin could move forward by creep action and set off the detonator. 28 BALLISTICS a. Range.— The rocket has the same range as the M6A3, but its effec tive range has been slightly increased by the new fin assembly. b. Penetration.— On angles of impact up to 30° the T12 rocket will penetrate the armor of any known enemy tank. c_. Effective fragmentation r a dius.— No information available. d. Muzzle velocity.— No infor mation available. e_. Launcher employed.— T h e M1A1 and M9 launchers a r e used to fire this rocket. 29 PAINTING AND MARKING a. Painting.— All external s u r faces of the rocket except the tinned notches of the fins are coated with olivedrab lacquer enamel. b. Marking.— In two circum ferential lines just below the flange on the rocket head is stenciled the fol lowing information: ROCKET, H.E., AT, T12 LOT 0000-0000.00-00
month and year of manufacture and the initials of the manufacturer. 30 PACKING One T12 rocket is packed in a fiber container, T l . Twenty loaded containers are packed in a wooden pack ing box (see fig. 22). a. Fiber container, Tl.— This container is generally similar to all fiber containers. It is 18-3/8"long and 2-15/16" in diameter. The cover fits over the inner wall of the body and is held in place by a strip of yellow ad hesive tape. The yellow sealing strip is 2" x 20-3/4" and is marked with 1/4" black characters as follows: ROCKET, AT, 2.36", T12 The rocket is inserted in the container, ogive first, coming to rest on a ringshaped plywood support in the bottom of the tube. b. Packing box.— The packing box is generally similar to the packing box for the M6A1 rocket. The lid. of the box is hinged on the side, and there is a single hinge and hasp. This box differs from the box for the M6A1 by the addi tion of stenciled Ammunition Identifi cation Code designation. The volume of the new box has been reduced to 3.25 cu. ft. Packing-box data No. of rounds contained 20 Volume 3.25 cu. ft. Total weight Dimensions - - 20-1/8" x 19-1/8" x 14" No. of carrying handles 2 31 SAFETY PRECAUTIONS All the safety precautions ob served in handling the M6A1 rocket must be followed in handling the T12. In addition, the fuze of the T12 rocket is more sensitive to set-back, and a fall of 2' to 3* will cause the round to explode.
All,the.-figures and letters are 3/8" ^ " ' ' a r e ^applied with yellow m a r k
ing ink. The lot number includes the
-27
DECLASSIFIED
T12 ROCKET
DECLASSIFIED
FIBER CONTAINER, T|
DESIGNATION ROCKET, AT. 2.36, TI2 ROCKET, PRACTICE A.T.,2.36,T23
COLOR OF SEALING STRIP YELLOW LIGHT BLUE
B
B
A-INSERT A. I.C. CODE. B-INSERT "H.E.,A.T.,2.36 IN.,TI2" OR "PRACTICE, AT., 2 . 3 6 IN.,T23" AS APPLICABLE. C-INSERT GROSS WEIGHT. D-INSERT LOT NUMBER.
FIGURE 22. - PACKING OF THE T12 AND T23 ROCKETS
DECLASSIFIED
-28
__
NOTES
DECLASSIFIED
-29-
DECLASSIFIED
NOTES
D E C L A S S I F I E D
DECLASSIFIED
-OCKET SECTION VI
ROCKET, PRACTICE, 2 3 6 % T 2 3
3 2 UgSO N FOR DEVELOPMENT ieT23 practice rocket wasde to provide an inert rocket trajectory identical to that of H.E. AT rocket. The T23 is the practice counterpart of the T12 and may be used in training to simulate the action of the T12. The T23 prac tice rocket uses all the components of the T12 except afuze and high-explosive head content. A weight bar is intro duced that is equal to the weight of the fuze, and an inert composition fills the charge cavity. The T23 has the same type and weight of propellant as the T12 and is fired in the same manner and from the same launchers. 33 GENERAL a. Appearance.— T h e r o c k e t has the same general appearance as the T12 rocket. (See fig. 23.) b. General data.—• The practice rocket, T23, has the same weight and dimensions as the T12. (See par. 26b, section V.) c. Components.— With the ex ception of the two components listed below, the T23 is identical to the T12. (!) Weight rod.— This compo nent is a steel cylinder 1.150" long and .495" in diameter. A transverse hole .080' in diameter is drilled through the rod .935" from one end. The two rims of the rod are slightly chamfered to insure a tight fit of the rod in the fuze body. The rod is positioned so that the transverse hole is inline with the holes in the fuze body, thus permitting easy insertion of the safely pin. (2) Charge (inert).— Approxi mately .49 1b. of filler is poured into
the head, where it hardens. The filler is 60 percent plaster of paris and 40 percent zinc stearate. The cone of the T23 practice rocket causes the filler to adopt the same shape as the pentolite* in the T12 rocket, m the M7A1 and M7A3 rockets the cone is not present. 34 PAINTING AND MASKING a. Painting. — The Tl 2 motor is used and is painted olive drab. The head of the T23 is coated with blue lacquer enamel. b. Marking.— In two circum ferential lines just below the body flange is stenciled 1he following: ROCKET, PRAC, AT, T23 .LOT 0000-0000.0-00 All letters and figures are 3/8" high and are stenciled with white marking ink. 35 PACKING The T23 rocket is packed in much the same manner as the T13 (see fig. 22). There are obvious differences in nomenclature, and the adhesive seal ing strip on the container is blue instead of yellow. A 3" blue band is painted ground the packing box to identify the contents as practice ammunition. 36 SAFETY PRECAUTIONS Safely precautions similar to those exercised with the T12 H.E. AT rocket must be enforced during handling of the T23 practice rocket. This will familiarize personnel with -the proper handling of the T12 when they are called upon to handle and fire it.
-31
DECLASSIFIED
T23 ROCKET
DECLASSIFIED
T23 ROCKET
DECLASSIFIED'
DECLASSIFIED
-32
DECLASSIFIED
DECLASSIFIED
SECTION VII ROCKET, SMOKE, WP, 2.36", T26 37 i REASON FOR DEVELOPMENT a. Whenever possible, a com plete series of rockets (high-explosive, prajttice, smoke, incendiary, and chem ical) is developed. This is the policy of the Ordnance Department and holds for all calibers of rockets. In some cases the development of certain items of the series is impracticable or would serve no tactical purpose. In any given caliber, all the rockets in the series must be designed with certain factors in mind. First, all the rockets must have the same trajectory. This is particu larly true of the 2.36" rockets that are fired f r o m t h e shoulder launcher. Secondly, in order to have similar tra jectories they must have equal weight and, in the case of the higher velocity rockets, as nearly identical contours as possible. Thirdly, they must have as nearly interchangeable components as possible so that additional manu facturing facilities will not be required. b. In line with this policy, the T26 WP rocket has been developed. Upon standardization this rocket will be assigned the model number M10. 38 GENERAL a. Appearance.— See figure 25. b. Motor.— The T26 s m o k e rocket makes use of the motor currently standard for the 2.36" rocket. At the present time this is the motor as sembled with the M6A1 rocket. The M6A1 motor is being replaced by the M6A3 motor, and the M6A3 motor will be replaced by the T12 motor when the T12 rocket is standardized and placed in production. This general statement concerning the use of t h e standard rocket motor for chemical rockets holds true for all 2.36" chemical rockets. c. Use. — Tactical requirements call for a smoke with harassing quali
-33
T26 ROCKET
ties. WP in smoke form has little effect upon the human body, but particles cause very severe burns. F o r t h e latter reason WP is an excellent smoke for use against enemy personnel both to blind them and to make them casualties. d. General data.— Length, over-all Length of head Diameter Diameter of head Weight of complete round WP charge Bursting charge 19-5/16" 5-1/2" 2.36" 2.30" 3.4 lb. 405 gm. 4 gm.
e_. Components.— The compo nents of the T26 chemical rocket are the motor assembly and the head as sembly. The head assembly will be discussed in the following paragraph.
39 HEAD ASSEMBLY
The head assembly consists of the container, the collar, the burster well, the bursting charge, the sealing cap, and the chemical charge. For the purpose of this description, the fuze body, the primer holder, and the primer will be considered as parts of the head assembly. They are actually modified components of the M6A1 motor as sembly. a. Container.— T h e container has the shape illustrated in figure 24.
DECHASSfBED
T26 ROCKET
DECLASSIFIED
ui
RI O
CVi ,
CO
,
--]
dARK ING
ig
CSJ i :
0
u. O
_J < UJ
a
t°-fe
| f%
DECLASSIFIED
-34
DECLASSIFIED
It is drawnfrom steel 0.49" thick and is curved at the forward end on a radius of .8". The rear end of the container, where curved, curves on a radius of 17/32". The center hole at the rear of the container i s 9.37" in diameter. b. Collar.— The collar is il lustrated in figure 26. It is threaded as shown and is 1-1/4" in greatest di ameter. It is made to seat in the cen tral hole of the container. The collar
T26 ROCKET
ameter and .125" deep. It is inserted in the well, open end up. f . Chemical charge. — W h i t e _ phosphorus is poured hot into the con tainer so that when the burster well is inserted there is a 1/2" dead space at bottom of the container. g. Fuze body.— The fuze bodyassembled with the M6A1 motor used with the T26 smoke rocket has the shape illustrated infigure27. It is a cylinder
is attached to the container by pouring silver solder through the joint. The fuze-body spacer slips over the threads of the collar and is held in place against the flat surfaces of the collar by the fuze body. It is a steel ring .938" in external diameter, .70" in internal diameter, and .119" thick. It seals the joint between the fuze body and the collar. c. Burster well.— The burster well is a rimmed tube 5-5/8" long and .4" in diameter for the greater part of its length. The closed end of the tube is sealed airtight. The upper 1/2" of the tube is shouldered to a diameter of .547". The rim is .045" wide and has a total diameter of .562". The burster well extends through the collar into the container with its rim resting on the inner rim of the collar. d. Bursting charge.— After the EC powder is poured into the burster well, the well is closed with a sealing cap. e. Sealing cap.— The s e a l i n g cap is a kraft-paper cup .360" in di-35
approximately 2.307" long and 1.25" in diameter. The forward portion, which seats the collar, is .935" in diameter. Aside from the taper in the front end of the fuze body and its lack of external threads on this surface, it is similar to the fuze body of the M6A1 rocket. h. Primer holder.—The primer holder has the shape shown in figure 28. It is screwed into the fuze body
and holds the primer in position to r e ceive the blow of the firing pin. It also acts as a firing-pin spring guide by holding the forward end of the firingpin spring in place. The primer holder
DECLASSIFIED
T26 ROCKET
DECLASSIFIED
e. The bursting charge defla grates, rupturing the head and igniting and scattering the chemical charge. The action of the rocket is completed.
4 1 BALLISTICS
is made of brass and is .60" in di ameter. The central hole, the primer seat, is .24" in diameter. The holder is 5/16" thick and the firing-pin spring guide is approximately 3/64" above the adjacent surface. In the lower surface of the holder are two positioning holes for screwing the holder into the fuze body. i_. Primer,— The primer is il lustrated in figure 29. It is held in place in the primer holder by staking the rim of the primer body on the upper rim of the primer holder. The as-
Range, effective Effective area covered by smoke Launcher employed
300 yd. M1A1 and M9
42 PAINTING AND MARKING a. Painting.— (1) Motor.— The motor is painted olive drab in t h e standard manner. (2) Head.— All exterior sur faces of the head are coated with bluegray lacquer. b. Marking. —A 1/2" yellow band is painted about the motor, l-l/2"from the nose. Centrally on the container, in three lines of yellow figures and letters, appears the following marking: (3/16" figures) ROCKET, 2.36INCH, T26 (3/4" figures) WP-SMOKE (3/8" figures) LOT 0000-0.0-00 43 PACKING No packing has been considered for this rocket as yet, but it may be safely assumed that the type of packing adopted for the M6A1 rocket will be closely followed. If twenty T26 rockets are packed in fiber containers, which are in turn loaded into a wooden packing box, the weight and dimensions of the loaded box will be nearly identical to the weight and dimensions of the loaded box of M6A1 rockets. 44 SAFETY PRECAUTIONS a. Do not remove the safety pin until the round is to be fired and its nose is in the launcher. b. After the safety pin has been removed, do not drop the rocket. A fall of I 1 can function the fuze.
PRIMER MIXTURE FIG. 2 9 PRIMER
sembled primer is .239" in diameter
at the base, .306" at the upper rim, and
.303" deep. The body and the anvil
are made of brass, and the primer cup
is an alloy of copper, silicon, and zinc.
The disk is lead foil, and the washer is
manila foil. The primer charge is .70
grains of primer mixture.
40 ACTION a. The rocket propels itself
from the launcher when the propellant
is ignited.
b. When the rocket reaches the
end of its trajectory or strikes the
target, the firing pin continues forward,
overcoming the resistance of the firing-
pin spring by inertia.
c. The firing pin drives into the primer, causing it to explode. d. The flame of the primer ig nites the bursting charge.
DECLASSIFIED
-36 -
NOTES
DECLASSIFIED
DECLASSIFIED
-37
NOTES
DECLASSIFIED
DECLASSIFIED
-38
DECLASSIFIED
c. Face guards and gloves must be worn when the rocket is fired. d. Burning particles of white phosphorus landing on the skin inilict serious burns. Personnel should ap proach burning rockets with extreme
T27 ROCKET
packed but not fired should be returned to their original packing containers. The safety pin and nozzle disk must be in place. f . Rockets should be stored in a _ cool, dry place. They should not be s t o r e d where temperatures exceed 120° F., and they should not be exposed to the direct rays of the sun.
care. e. Rockets which have been un
SECTION VIII
ROCKET, SMOKE, HC, 2.36", T27
45 REASON FOR DEVELOPMENT
In accordance with the policy outlined in paragraph 37 of section VII, the T27 HC rocket has been developed.
used to blind enemy fortifications or groups of enemy personnel but it is not as suitable for this purpose as WP smoke.
46 GENERAL d. General data.— a. Appearance. — It will be noted from figure 30 that the head of the T27 Length, over-all 18-5/16" rocket is shorter than the head of the Length of head 4-3/4" T26 rocket shown in figure 25. The HC Diameter - - 2.36" filler loaded into the T27 is denser Diameter of head 2.30" than the WP filler loaded into the T26. Weight of complete round 3.4 lb. Specifically, 450 gm. of HC are loaded HC charge 450 gm. 18 gm. into the shorter T27 head and 405 gm. First-fire charge of WP are loaded into the longer T26 head. In order that the two rockets e. Components.— The compo have identical weight, the difference in nents of the T27 HC rocket are the the head design was necessary motor assembly and the head assembly. The head assembly will be discussed in b. Motor.— The M6A1 rocket the following paragraph. motor with minor changes in the fuze body is used. See paragraph 38 of 47 HEAD ASSEMBLY The head assembly consists of section VII for a discussion of the motors to be used with this smoke the container and its chemical charge, the container cup, the first-fire charge, rocket in the future. the impregnated disk, the closure plate c. Use. — Tactical requirements and collar. For the purpose of this call for a smoke rocket for both offen description, the fuze body, the primer sive and defensive situations. HC smoke holder, the primer, and the fuze-body is a screening agent that has no effect spacer will be considered as compo upon the human body. For this reason nents of the head assembly. They are it can be used to cover the advance or actually modified components of the retreat of friendly troops. It may be the M6A1 motor assembly.
-39
DECLASSIFIED
T27 ROCKET
DECLASSIFIED
•p*.-'
CM
2
ARKI
X
a z
vO
^^^
[I.]
as
COS
u. O
DETAI
C D
00 cvi
LJ
Ufe
(J
a:
o
DECLASSIFIED
-40
DECLASSIFIED
a. Container.— The steel container is illustrated unassembled in figure 31. The forward end is curved
T27
ROCKET
to the collar in the M26 rocket. It is 1" in diameter and 3/4" thick. The central hole is 7/16" in diameter. The cham
\
"1
T"
Hs
ir
\T~
I i
^\—r i
J
2
0
> , 3 6
7
-1
1
I
"— i —
FIG. 3 2 COLLAR
FIG. 31 CONTAINER
on a radius of .8". The open rear end has a diameter of 2.30", and the wall thickness is .049". b. C h e m i c a l charge.— The chemical charge is approximately 450 gm. of HC mixture cast to leave space for the container cup. c. Container cup.— The con tainer cup is made of zinc .010" thick. It is 1-1/8" in diameter and 29/32"deep and has a rim with a diameter of 2.1". d. F i r s t - f i r e charge.— This charge is 18 gm. of starter mixture. The container cup, with the contained first-fire charge, is placed in the re cess formed in the chemical charge. e. Impregnated disk. — This disk, approximately 2.1" in diameter, is laid over the surface of the first-fire charge, the rim of the cup, and the adjoining chemical charge. It is held in place by a disk of adhesive plaster. f . Closure plate.— The closure _ plate is a steel disk 2.18" in diameter and .1225" thick. It has a central h o l e .615" in diameter and four equally spaced outer holes each 3/8" in di ameter. g. Collar.— The collar has the shape shown in figure 32. It is similar
fered rim is fitted in the central hole of the closure plate and silver solder poured over the juncture. The closure plate and colla^ assembly is then fitted over the disk of adhesive plaster. The rim of the container is then turned tightly over the plate, closing the head assembly. h. Fuze body.—This is the same fuze body as that assembled with the T26 rocket. i_. Primer holder.— This is the same component as that assembled with the T26 rocket. j . Primer.— This is the same primer as that assembled with the T26 rocket. k. Fuze-body spacer.— This is the same component as that used with the T26. It is assembled in the same way.
48 BALLISTICS
Range, effective Effective area covered by smoke Launcher employed
49 ACTION
300 yd. M1A1 and M9
a. The rocket propels itself from the launcher upon ignition of the propellant.
-41
DECLASSIFIED
T27 ROCKET
DECLASSIFIED
(3/8" figures) ROCKET, 2.36 INCH, T27 (3/4" figures) HC - SMOKE (3/8" figures) LOT 0000-0.0-00 51 PACKING No packing has yet been devel oped for this rocket, although the as sumed packing of the T26 outlined in section VII is applicable. 52 SAFETY PRECAUTIONS a. Do not remove the safety pin until the round is to be fired. b. After the wire has been r e moved, a fall of 1' can function the fuze. Do not drop the rocket after the safety pin has been removed. c. F ac e guard s and gl ove s must be worn when the rocket is fired. d. Rockets which have been un packed but not fired should be returned to their original packing containers. The safety pin and nozzle disk must be in place. e. Rockets should be stored in a dry, cool place. They should not be stored where temperatures e x c e e d 120° F., and they should not be exposed to the direct rays of the sun.
b. At the end of its trajectory, or upon striking the target, the firing pin continues forward, overcoming the resistance of the firing-pin spring byinertia. c. The firing pin drives into the primer, causing it to explode. d. The flame of the primer ig nites the first-fire charge. e. The burning first-fire charge ignites the HC mixture. The first smoke generated escapes through the holes in the closure plates. As the whole charge begins to burn, the container melts and the smoke escapes freely. The action of the rocket is completed. 50 PAINTING AND MARKING a. Painting.— (1) Motor.— The motor is coated with olive-drab lacquer. (2) Head assembly. — All ex ternal surfaces of the head assembly are coated with blue-gray lacquer. b. Marking.- A 1/2" band of yellow lacquer enamel is painted about the head, 1-1/2" from the nose. Cen trally on the head appear the following three lines of circumferential marking:
DECLASSIFIED
-42
DECLASSIFIED
N0TES
DECLASSIFIED
-43
NOTES
D E C L A S S I F I E D
DECLASSIFIED
-44
DECLASSIFIED
T31 ROCKET
SECTION IX ROCKET, INCENDIARY, 2.36", T31
53 REASON FOR DEVELOPMENT
In accordance with the policy outlined in paragraph 37 of section VII, tl|eT31 incendiary rocket has been de veloped.
e. Components.— The compo nents of the T31 incendiary rocket are the motor assembly and the head as sembly. The head assembly will be discussed in the following paragraph.
54 GENERAL 55 HEAD ASSEMBLY a. Appearance. — It will be noted The head assembly consists of from figure 33 that the body assembly the container, ring, collar, container of the T31 is shorter than the body a s cup and closure plate. For the purpose semblies of the T26 or T27 rockets. of this description, the fuze body, Since the incendiary charge of the T31 primer holder and primer w i l l be is denser than either HC or WP, the considered as parts of the head a s body of the T31 must be smaller in sembly. They are actually modified order not to exceed the total weight components of the M6A1 motor as sembly. The container has a chemical permitted for the rocket. charge, and the container cup has a b. Motor.- The M6A1 rocket first-fire charge. motor with minor changes in the fuze body is used. See paragraph 38 of a. Container.— T h e container section VII for a discussion of the is identical to the container of the T27 motors to be used with this incendiary rocket except that it is 4-1/8" long — rocket in the future. 5/8" shorter than the T27. c. Use.— Theoretically, there is widespread use for an incendiary rocket. It should prove effective against tanks, wooden dwellings, and in interior portions of fortifications. At the pres ent time however, it is doubtful whether this rocket will be standardized, since the incendiary charge which it carries is small. Initial production of t h e rockets has gone to interested service boards for testing. These tests will determine whether' or not it will be standardized. d. General data.— Length, over-all 17-11/16" Length of head 4-1/8" Diameter 2.36" Diameter of head 2.30" Weight of complete round 3.4 lb. Thermite charge (estimated) - 500 gm. First-fire charge 18 gm. b. Ring.- The ring is steel .06" thick, .25" wide, and 2.202"in diameter. It is spot welded at 45° intervals to the inside of the container, 5/16" from the open end. c. Collar.— The collar is iden tical to the T27 collar. It is assembled to the closure plate in the same way as the T27 collar and closure plate. d. Container cup. — This compo nent is identical to the T27 component. e. Closure plate. — This compo nent is identical to the T27 component. f . Fuze body.- The T26, T27, _ and T31 rockets use the same fuze body. g_. Primer holder.- The T26, T27, and T31 rockets use the same primer holder.
-45
DECLASSIFIED
T31 ROCKET
DECLASSIFIED
V YEAR ^-MONTH V MANUFACTURER'S INITIALS
z o
DETAIL OF MARKING
\ \
U—— r
\
UJ UJ U
PZc:
UJ—i"
CJ-J-G O|_.
a. o
<
DECLASSIFIED
-46
DECLASSIFIED
h. P r i m e r . - The T26,T27, and T31 rockets use the same primer. i_. Chemical charge.— Into the container is pressed a charge of ap proximately 500 gm. of thermite. j . First-fire c h a r g e . — The first-fire charge, pressed into the con tainer cup, consists of 18 gm. of firstfire composition.
T31 ROCKET
(2) Head.—All exterior surfaces of the head are coated with blue-gray lacquer . b. Marking.- A 1/2" band of purple lacquer enamel is painted about the head, 1-1/2" from the nose. Cen trally on the head appear the following three lines of circumferential marking: (3/8" figures) ROCKET, 2.36 INCH, T31 (3/4" figures) TH - INCENDIARY (3/8" figures) LOT 0000-0000.0-00 59 PACKING No packing has yet been devel oped for this rocket, although the as sumed packing of the T26 outlined in section VII is applicable. 60 SAFETY PRECAUTIONS a. Do not remove the safety pin until the round is to" be fired. b. After the pin has been r e moved, a fall of I 1 can function the fuze. Do not drop the rocket after the safety pin has been removed. c. Face guards and gloves must be worn when the rocket is fired. d. The heat generated by the thermite i s intense, and personnel should exercise care in approaching a burning rocket. e. Rockets which have been un packed but not fired should be returned to their original packing containers. The safety pin and nozzle disk must be in place. f . Rockets should be stored in _ a dry, cool place. They should not be stored where temperature e x c e e d s 120° F., and they should not be exposed to the direct rays of the sun.
56 BALLISTICS Range, effective 300 yd. Heat generated by rocket Burning time of charge Launcher employed M1A1 and M9
57 ACTION a. The rocket propels itself from the launcher upon ignition of the propellant. b. When the rocket reaches the end of its trajectory, or strikes the target, the firing pin continues for ward, overcoming the resistance of the firing-pin spring by inertia. c. The firing pin drives intc the primer, causing it to explode. d. The flare of t h e primer flashes through the central hole of the primer holder and ignites the firstfire charge. e. The first-fire charge burns and ignites the thermite charge, and the action of the rocket is complete. 58 PAINTING AND MARKING a. Painting.— (1) Motor.— The motor is painted olive drab in the stand ard manner.
-47
DECLASSIFIED
NOTES
DECLASSIFIED
-48
DECLASSIFIED
NOTES
DECLASSIFIED
-49
3.25" ROCKETS
DECLASSIFIED
CHAPTER 3-3.25" TARGET ROCKETS
61 GENERAL
The rocket, target, A.A., 3.25", M2 (see fig. 34), was designed for use as a high-speed target for firing p r a c tice with automatic antiaircraft weap ons. The rocket consists of a motor, a motor extension, a nose, and three plywood fins. T h e propellant is a solvent-extruded double-base powder (40 percent nitrocellulose) extruded into cylindrical sticks 5" long and 7/8" in diameter with a 5/16" hole through the center. The propelling charge is ig nited by an electric squib assembled within the rocket. This rocket is a direct copy of the British 3" U. P. pro jectile. 62 GENERAL DATA Length Diameter 59" 3.25"
Width across fins Weight Propelling charge Igniter (black powder) Muzzle velocity
24" 37.5 1b. 3.2 lb. 0.78 oz. 2,200 yd.
63 ROCKET, TARGET, FLARE, A.A.,
3.25", M2A1
When a flare is added to the M2 rocket for antiaircraft target practice at night, the resulting projectile is des ignated as the rocket, target, antiair craft, 3.25", M2A1. The flare burns for 15 to 20 seconds from the beginning of flight. 64 REFERENCES TM 4-236, Instructions for use of Rocket, Target, M2 by Antiaircraft Units; TM 9-390, Target Rocket Pro jector, Ml.
A
©Pip* Black powder ignition charge ©
w
©
Squib wires
(g) Propelling chorg. @ N°£Z'e. . . . (Note: Drawing show* only the mote combustion chamber.)
©
Inflating wether, • Cap
(§) Igniter bag \SJ/ » v © Tub* body
FIGURE 34. - ROCKET, TARGET, A .A., 3.25", M2
DECLASSIFIED
-50
DECLASSIFIED
NOTES
-51-
DECLASSIFIED
M8 ROCKET
DECLASSIFIED
CHAPTER 4-4.5" ROCKET AND LAUNCHERS
SECTION I ROCKET, H.E., 4.5", M8 of the plane. (See figs. 35 and 36.) Each launcher is a smooth-bore plas tic tube 4*9/16" in internal diameter and approximately 10' in length. At the breech end of each tube are three latches. One of these (1) holds the rocket in place in the launcher; the other two make electrical contact with the two contact rings (3) of the rocket. The two contact latches (2) are con nected by wires to the firing-selector box. This box, located in the cockpit of the plane, operates on the plane's electrical system. On each cluster there is a device which enables the pilot to jettison the launchers after the rockets are fired. (2) Operation. — The t r i g g e r , mounted on the joy stick of the plane, is connected to the firing-selector box. The box enables the pilot to fire each rocket singly or the entire group auto-
65 GENERAL a. Rocket.— The rocket, H.E., 4.5", M8 (see fig. 43) is a round of ammunition for use by ground forces against ground targets. The main issue of the rocket initially, however, will be to the Air Forces for use against ground targets. The round carries a relatively heavy explosive charge so situated as to provide for complete fragmentation of head and motor. For this reason the round has considerable fragmentation effect as well as the blast effect derived from the heavy charge. The M8 rocket, complete with theM4 fuze and auxiliary booster, is 33.19" long and weighs ap proximately 38 lb. b. L a u n c h e r . — (1) General. Since the rockets will be initially issued to the Air Forces, the launchers are being issued in clusters of three — one cluster to be mounted under each wing
FIGURE 35. - LAUNCHER, ROCKET, 4.5", 3-TUBE, A.C., T30. END VIEW
SHOWING LAUNCHER READY FOR
LOADING
FIGURE 36. - LAUNCHER, ROCKET, 4.5", 3-TUBE, A.C., T30. END VIEW SHOWING ROCKETS IN TUBE AND ELECTRICAL CONTACTS IN PLACE
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M4 FUZE
matically at 1/10 - second i n t e r v a l s . When the rockets are fired singly, the the selector determines the sequence of firing. When the trigger is pressed, a n electric current passes into the rocket through the two contact rings. This current initiates the igniter, which in turn initiates the rocket motor. c_. Issue.— It is contemplated that the M8 rocket will be used in either a single- or multiple -barreled launcher that will serve as an infantry accom panying weapon. The launcher a n d rocket will be generally similar in use and effect to the 105-mm howitzer and, as such, will prove an important adjunct to the fire power of infantry troops. No information is available concerning the organizational assignment of the weap on, but Ordnance personnel will see it in quantity in the near future. Famili arity with the ammunition, its action and functioning, and its fuzing and pack ing will prove invaluable in handling it properly in the" field. d. Reference.- SNL S-9 lists the rocket and gives pertinent data. 66 COMPONENTS The term "complete round" as applied to rockets includes the rocket head and fuze, the rocket motor and igniter, and all components required for proper functioning. 67 FUZE
pin. Through the release on set-back of a prisoned bail, the pin is freed, permitting the slider to move into the armed position. The fuze consists of a body, head, firing-pin assembly, slider assembly, related p a r t s , explosive components, and auxiliary booster. More than a general description of the various components is not included. The diagram of the fuze and the de scription of its action will give an ade quate acquaintance with the fuze. a. Body.— (1) The base (see fig. 37) is designed to screw into the shell adapter and is threaded for that purpose just below the shoulder. The forward end of the body has a circularledge to seat the head and to form a projection, or nose, over which the head fits and into which the two flash holes are drilled. The flash holes are parallel to each other and ente'r the body longitudinally. One flash hole (instantaneous) is 0.205" in diameter, widening at the top to 0.315" to seat the primer. The , second flash hole (delay), 0.325" in diameter for the lowest third of its length, is 0.445" wide for the upper two-thirds. These two flash holes open into a transverse hole, 0.380" in diameter and extending approxi mately 1-3/4" into the body. T h i s transverse hole houses the setting pin, which has the function of determining the instantaneous or delay action of the fuze. A third hole, parallel to the flash holes, 0.88"from the longitudinal axis of the body and 0.127" in diameter, con tains the retaining pin. This pin rides in an 0.127" circumferential groove in the setting pin, permitting the setting pin to rotate but not to move longitudi nally. In order to lock the setting pin in one of two positions, two notches, 180° apart, are formed in the setting pin. A ball bearing under spring tension fits in one of these notches. Some pressure is needed to rotate the setting pin. This disengages the ball and re -engages it in the opposite notch. The spring and ball fit into a hole (the
The M8 rocket differs from ammunition fired from cannon in that it does not rotate. To design a fuze that would be bore safe under these condi tions presented a problem that was suc cessfully solved by the development of the Fuze, P.D., M4. The M4 fuze is safe by reason of a slider that inter rupts the explosive train and moves out of its interrupting position only after forward acceleration of the rocket is complete. The slider is retained in the interrupting position by means of a
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FUZE
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Fig. 37 FUZE, ROCKET, P.D., M4
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114 FUZE
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^SLIDER SPRING SLIDER PLUG-i\ /-SETTING-PIN HOLE -LOCKING BALLS. SPRING RETAINING-PIN GROOVE -RETAINING PIN ARROWHEAD INDICATOR CIRCLE
COTTER PIN
RING
EVE
SET-BACK PIN BOOSTERrCUP CHARGE* rBOOSTER DISK \ ^SLIDER SET-BACK-PIN SPRING SET-BACK-PIN & SPRING HOLE
STRIKER
I. NO. 26 PRMER 2. PRIMER HOUSING
aLEADAZlOE
56. 7 a SET SCREW RELAY DISK RELAY WASHER FIRING-PIN ENTRYWAY CORK CUSHION DELAY ARMING PIN ARMING-PIN SPRING BOOY
9. PRMER COVER
10. DELAY-ELEMENT HOUSING 11. COMPRESSION CHAMBER 12. DELAY CHARGE 13. DELAY-ELEMENT PLUG 14. DELAY-RELAY CUP I S WASHER
FIGURE 37. FUZE, POINT DETONATING, M4
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M4 FUZE
DELAY ELEMENT
SUPERQUICK ELEMENT DELAY ARMING PIN LOCKING BALL
& SPRING
SET-BACK PIN DELAY-ARMING-PIN SPRING
SET-BACK-PIN SPRING
SETTING PIN FUNCTIONING HOLES RETAINING-PIN GROOVE LOCK PIN
LOCK-PIN SPRING
CLOSING-CUP CHARGE MI7 DETONATOR SLIDER PLUG FIGURE 38. - POSITION AND NOMENCLATURE
OF M4 ROCKET FUZE IN UNARMED POSITION
leading ifi^*ti$NtiJttthg-pin hole. This fourth hole is 0.645" from the longitu dinal axis of the body and is 0.250" in diameter. Both the locking-ball-and spring hole and the retaining-pin hole open on the body ledge, and both are radially alined. Diametrically oppo site these two holes and opening on the body ledge is the fifth hole, paralleling the flash holes. This hole is 0.185" in diameter for the lowest third of its length, opens sharply to 0.310", and is 0.373" for the upper half of its length. This hole houses the delay arming pin, which prevents movement of the slider. The delay-arming-pin hole opens into a second transverse hole, which is paral lel to and bel ow the setting-pin hole. Into this second horizontal hole, 0.5" in di
ameter and 2-1/4" deep, fits the slider. This hole is called the slider recess. (2) The body consists of an ob long portion with a dome-shaped por tion at one end. (See fig. 37.) The narrow faces of the oblong fit solidly against the sides of the dome, but be tween the wide faces of the oblong and the inner sides of the dome there are two open recesses. All the holes men tioned in the preceding paragraph are contained in the oblong portion. Leading at an angle of 45° from the wall of the upper end of the delay-arming-pin hole is a hole 0.195" in diameter that opens at its lower end into one of the recesses mentioned above as being between ob long and dome. This hole is referred to
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114 FUZE
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FIGURE 39. - PARTIAL ARMING OF M4 FUZE
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M4 FUZE
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jNjpURE 40. - SUPERQUICK FUNCTIONING OF M4 FUZE
FIGURE 39. - PARTIAL ARMING OF M4 FUZE
as the ball escape hole and is the only hole not formed at right angles. The ball escape hole intersects a sixth hole, parallel to the flash holes. This sixth hole, the set-back-pin-and-springhole, is 0.151" in diameter and extends down ward from the ledge formed on the upper side of the body. The set-back-pin-and springhole intersects none of the trans verse holes and is approximately 1-3/4" deep. (3) In the bottom surface of the fuze body there is a single central flash hole, or booster-closing-cup channel, 0.2" in diameter. A second hole, the lock-pin hole, is located 0.34" from
the closing-cup channel and opens into the slider recess. It houses the lock pin and lock-pin spring. After insertion of the pin and spring, the hole is closed at the bottom with a steel closing disk, 0.245" in diameter and 0.0329" thick. (4) The body is a malleable -iron casting given a good machine finish and cadmium plating. It weighs 1.7 lb. and has a maximum height of 2.51" and a maximum width of 3.21". b. Head.— The head is made of aluminum alloy and weighs 575 grains. It is cast to a shape which allows it to fit over the body projection and rest on
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M4
FUZE
FIGURE 4 1 . - DELAY FUNCTIONING OF M4 FUZE
the body ledge. The central hole, which fits over the body projection, is 0.998" in diameter. Immediately above this hole there is a shoulder which narrows the hole to 0.7". This upper hole houses the firing-pin assembly. The bottom of the head is a flat base that fits on the body ledge. Through the sides of the head are two holes, each threaded to take a commercial setscrew. These cone-pointed setscrews engage two holes, 5/32" wide and .1" deep, in the walls of the body projection and tighten the head onto the body. The base of the head, where it rests on the body ledge, closes the h o l e s leading downward
from the body ledge. c_. Booster.— The booster as sembly consists of a booster cup and a booster disk. The cup is aluminum al loy, weighs 261 grains, and is 1.123" in internal diameter and 1.288"in external diameter. The upper 0.3" of the inner wall is threaded to fit the lower projec tion of the fuze body, where, after being screwed on, it is secured by staking. The booster disk is onionskin paper that fits into the bottom of the cup and is inserted prior to loading of the booster pellet.
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the end of the slider and is held in place by the slider plug. The plug is a threaded steel cap which screws into the open end of the slider recess and holds the slider assembly in place. The outer face of the plug is slotted to take a screwdriver, and the opposite end is recessed in the same manner as the slider to seat the slider spring. The lock pin and lock-pin spring are housed in the lock-pin-spring hole described in a(3) above. Two-thirds of the way along its length, the lock pin has a 0.5" shoulder, 0.05" thick. This shoulder fits into the lock-spring hole. Below the shoulder, the pin is 0.120" in di ameter and 0.07" long to hold the lockpin spring in place. Above the shoulder, the pin is 0.20" long and 0.08" in di ameter. It is this longer and more slender portion of the pin that engages the keyway of the slider and under the tension of the spring moves into the lock-pin recess, locking the slider in position. The lock-pin spring is made of steel music wire, has three free coils, and is held in place in the lockpin hole by the closing disk. The latter, described in a(3) above, is secured by crimping. i. Related p a r t s . - (1) Dowel pin.— This steel pin, 0.20" long and 0.125" in diameter, fits into matching holes drilled into the surfaces of the body ledge and the base of the head. It prevents rotary motion of either part in the same manner as the set screws prevent vertical motion of the parts. (2) Ring and pin.— A cotter pin, ring engaged, passes through a trans verse hole in the side of the body that intersects the set-back-pin hole. The cotter pin is fitted through an eye in the set-back pin when the latter is in its most forward position. The cotter pin then engages the hole in the opposite wall of the set-back-pin hole and enters an other shallow and narrow hole, opening on the body ledge. Prior to assembly of the head, a tool is inserted in this
d. Firing-pin assembly.— This assembly consists of the striker, two firing pins, and a shear wire. The striker i s an aluminum-alloy disk, 0.695" in diameter and 0.20" thick. Two holes pass through the faces of the disk, each hole shaped to seat a firing pin. The two holes are 0.220" apart and equidistant from the center of the striker. A diametric hole is drilled through the striker to house the shear wire. The shear wire, which is 1.15" long, 0.04" in diameter, and made of brass, passes through the shear-wire hole and through the walls of the firingpin recess in the head. The wire keeps the striker in place under the normal shocks incidental to handling. Each of the firing pins is nipple shaped and made of cadmium-plated steel. They extend 0.08" below the surface of the striker and are held in place in the striker by a 340° crimp of the striker metal. e. Slider assembly.— The a s sembly consists of the slider, slider spring, slider plug, lock pin, lockpin spring, and closing disk. The slider is a cadmium-plated steel rod, 0.408" in diameter, 1.47° long, and weighing 490 grains. One end is recessed to a depth of 0.15"to seat the slider spring. The wall of thg^o^gpsite end is key wayed on a curve1 (radius of 1.75") to provide a camming surface. This key way extends a little more than half the length of the slider. It is interrupted near the inner end by a hole, the lockpin recess, 0.093" in diameter. In this keyway the lock pin rides until it slips into the lock-pin recess. At a dis tance of 0.94" from the spring-recess end of the slider are drilled two con centric holes. The lower hole, 0.374" deep and 0.242" in diameter, houses the detonator assembly and is beveled outward at the bottom. Above it is a hole 0.152" in diameter drilled through the remaining thickness of the slider. This upper hole is the detonator flash hole. The slider spring, made of steel music wire, is seated in the recess at
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M4 FUZE hole and the ends of the cotter pin are bent down, so that the pin is secured in place. (3) Setting pin.— In addition to the circumferential groove and notches described in a(l) above, there is a set of holes drilled through the setting pin. These holes determine the func tioning of the fuze. The holes, three in all, are drilled through the pin at different angles and have the appear ance, in cross section, of a letter X with an additional leg, X \ . Each hole is 0.14" in diameter, and the two holes forming the X are approximately 1/16" apart at the surface of the pin. The parallel leg intersecting one leg of the X forms a common opening with the leg at the surface. The arrangement of the holes and their location beneath the instantaneous and delay flash holes permits selective functioning of the fuze by 180° rotation of the setting pin. g. Explosive components of in stantaneous and delay flash h o l e s . (1) Instantaneous -flash -hole c o m p o n e n t s . - The explosive components in the instantaneous flash hole consist of a No. 26 primer and a relay, both of which are held in place in the flash hole by a primer housing. The No. 26 primer, discussed in volume 1, is the standard cal..3O primer. The relay assembly consists of a charge of 1.54 grains of lead azide pressed into an aluminum cup under apressureof 5,000 lb./sq.in. The relay cup is 0.193" in diameter and 0.120" deep and has a slight rim. The charge fills the cup to a depth of 0.095". A relay disk of pink onionskin paper, 0.002" thick, is placed on the charge and covered with an aluminum relay washer of the same thickness. The cup is then closed with a 360° crimp, which exposes the pink disk. The primer is fitted into the primer housing, which is a brass cup, 0.313" in diameter, recessed to fit tightly over the primer and drilled at the bottom with a 0.10" hole to permit the firing pin to contact the primer. The relay assembly, pink side up, is fitted into the flash hole and rested on a diskshaped compressed-cork relay cushion that has been previously inserted and rests on the inner shoulder of the flash hole. The primer housing is then in serted, located on the upper shoulder, and secured by staking. (2) Delay-flash-hole c o m p o n e n t s . - The explosive components of the delay flash hole are all parts of the delay-element assembly. The two ma jor metal parts of this assembly are the primer cover and the delay-element housing. The former is similar to the primer housing in the instantaneous flash hole except that the walls are higher and are internally threaded at the rim. The primer cover is 0.44" in diameter and 0.395" high and is in ternally formed to seat the No. 26 primer and allow contact of the primer and firing pin. The delay-element hous i n g i s a brass member, internally shaped to seat several components of varying diameters. It is 0.835" long and 0.44" in diameter and is externally threaded to screw into t h e primer cover. The two metal components when screwed together slip readily into the flash hole, the exterior of the housing being shaped to match the internal shape of the lower flash hole. When the two components are fitted together, there is an internal void space between them that forms a compression chamber. Below this chamber in the housing is a long, narrow hole 0.425" deep andO.124" in diameter. At the bottom it narrows to a small concentric hole 0.045" long and0.051" in diameter. Loaded into this long hole successively are a delay-relay assembly, a delay charge, and a delayelement plug. The delay-element plug, which is nearest the compression cham ber, is a brass plug, 0.123" in diameter and 0.102" thick, having a conical hole of minimum diameter (on the lower face) of 0.027" and opening outward and up ward with a taper of 0.3" diameter per inch of length. This conical hole col
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M4 FUZE
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in diameter, and 0.343" deep. Into the cup is pressed 3.25 grains of tetryl under a pressure of 10,000 lb./sq.in. The assembly is fitted into its recess in the bottom of the head and secured with a 360° crimp. j_. B o o s t e r charge.— The booster assembly consists of a booster cup, booster-cup charge, and booster disk. The cup, made of aluminum alloy, is 1.288" in diameter, 1.17" deep, and threaded internally at the rim to screw onto the fuze body. The booster disk, onionskin paper 0.002" thick, is inserted in the bottom of the cup, and the booster charge of 329 grains of tetryl, in pellet form, is loaded into the cup. k. Auxiliary booster.— In order to make certain that a high-order deto nation of the explosive charge takes place, an auxiliary booster is fitted into the fuze-well cup. The auxiliary booster assembly fits readily into the cup and is held in place by the booster cup of the fuze when the fuze is screwed into the shell. (1) Components.— The Ml aux iliary booster consists of a tube as sembly, a bottom, and a charge. The tube assembly consists of a waterproof chipboard tube, 3-5/8" long, 2.65" in diameter, and having walls 0.15" thick; and an end plate, which is a steel disk grooved at the rim to allow it to be crimped over the rim of t h e tube. The bottom is a chipboard disk shaped like the nose plug and having a diameter across the rim of 2.50" and a smaller diameter of 2.10". The charge is 0.871b. of cast TNT or 0.84 lb. of flake TNT. (2) Assembly.— The end plate is crimped over one rim of the tube, and the charge is loaded. The bottom is fitted into the open end of the tube and the rim of the tube is roll-crimped to hold the bottom in place. The bottom is fitted with its rim against the charge. (3) Marking. — Stenciled in white 1/8" letters circumferentially about the end plate are the nomenclature and use
lects the flame of the primer from the compression chamber and presents it to the delay element as a concentrated spit of fire. The delay charge, below the delay-element plug, is approximately 1.23 grains of grade "A-5" Army black powder, compressed under a pressure of 60,000 lb./sq.in. The powder i s varied in quantity to give a 0.1-second delay. Below the delay charge is the delay-relay assembly. This assembly consists of an 0.77-grain charge of lead azide pressed into a delay-relay cup under a pressure of 25,000 lb./sq.in. The cup is 0.122" in diameter and0.155" deep and has an inward bulge in the base. After insertion of the lead azide, the walls are crimped inward at an angle of 45°. The flat portion of the bottom of the cup is coated with red N.R.C. compound, and the assembly is placed in the bottom of the long hole and compressed under a pressure of 60,000 lb./sq.in. before the compound is dry. This compression flattens the crimped walls of the cup. The delayelement plug, and all the components under it are held in place by means of a 45° circular crimp of t h e adjacent walls. To seal the joint between hous ing and primer cover, a copper washer is inserted. h. Slider explosive c o m p o nents. — The Ml7 detonator i s a s sembled in the slider. This is the same detonator assembled in the M53 P.D. fuze (see vol. 3). The detonator is in serted into the slider-detonator recess, coming to rest on a washer-shaped compressed-cork detonator c u s h i o n which has already been inserted and located on the inner shoulder of the recess. The colored end of the deto nator is flush with the counterboring at the large end of the detonator r e cess, and it is secured in place by crimping. i. Booster-closing-cup a s sembly7— T h i s explosive component consists of a booster closing cup and a booster-closing-cup charge. The cup is gilding metal, slightly rimmed, 0.19"
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of the booster -"AUXILIARY BOOSTER, Ml, FOR FUZE, ROCKET, P.D., M4." Across the middle of the end plate a r e stenciled i n white 3/16" letters the WQ.rds "THIS END UP," and below these words is the lot number of the booster. (4) Packing.— The Ml auxiliary booster is packed with the M4 fuze. (5) Weight.— T h e a u x i l i a r y booster weighs 0.971b. The fuze weighs 2.1 lb. The fuze and auxiliary booster together have a weight of 3.07 lb. L Marking and painting.— C i r cumferentially about the fuze and just above the shoulder are stamped in 1/8" letters and figures the name and model number of the fuze, the date (year and month) of loading, the loader's initials,, and the lot number. "FUZE, ROCKET, P.D., M4. 5-43, LOT P.A.-1-123" is a sample stamping. On either side of the setting-pin hole are stamped two a r r o w heads pointing toward the hole. These arrowheads are coated with red lacquer enamel. A circular depression to one side of the screwdriver slot in the ex posed end of the setting pin is coated similarly. Rotation of the pin through 180° places the red ball opposite one of the arrowheads, the latter being marked either "SQ" or "DELAY." m. Packing.— (1) General.—The M4 fuze and the Ml auxiliary booster are packed together in the M106 fiber container. Fifteen such containers a r e packed in a wooden packing box. (2) C o n t a i n e r , fiber, M106. Assembled, the container is 8-3/8"long and approximately 3-3/4" in diameter. It consists of a cylindrical body closed at one end by a steel end plate and at the other end by a cylindrical cover. The cover is closed at the free end by a steel end plate which, like the end plate for the body, bulges outward at the center. The walls of the body and cover are waterproofed chipboard. In side the body and closely interfitting are two chipboard tubes, both of whose lower rims are flush with the end plate. The intermediate tube is 5-25/32"high, and its upper rim is crimped into a steel ring. It is on this ring that the M4 fuze r e s t s . The second of the two tubes, the inner tube, which fits in side the intermediate tube, is 1-9/16" high. Into this tube fits the base of the auxiliary booster. Between the bottom surface of the auxiliary booster and the end plate is inserted a hair-felt disk, 1/4" thick, that protects the booster from sudden shock. Slipping easily in the intermediate tube is a spacer tube and disk. The spacer tube is 1 -1/2" high and is of a diameter to fit the lower fuze body. The disk is chipboard, 0.142" thick, and separates the fuze in the upper end of the container and the booster in the lower end of the container. Secured to the inside of the cover tube and in contact with the end plate is a disk of plywood called the support. A central hole in the support is 5/8" in diameter at the top and 1-1/2" in diameter at the bottom. The smaller end of the hole is located just below the center bulge of the end plate, and the nose of the fuze is inserted in the hole in the support. (3) Marking of container. — Em bossed circumferentially on the cover end plate is the nomenclature of the container - " C O N T A I N E R , M 1 0 6 . " Stenciled in white letters and figures 1/4" high are the l o t number, t h e packer's initials, and the month and year of packing. (4) Sealing strip for container. A strip of black adhesive tape, 2" x 25-1/2", is usedto seal the joint between the cover and the body of the container. In addition, the strip is lettered to a s sist in the identification of the container. On the sealing strip for the M106 fiber container, the nomenclature of the con tents (see fig. 42), their lot numbers, the packer's initials, and the month and year of packing appear in white letters and figures 1/4" high. *
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LJ
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11
•:
:-^btnu
NJ
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x
~Ir
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(5) Packing box. —Into the wood en packing box are loaded 15 fiber con tainers in vertical position. The box is sturdily constructed of heavy lumber, reinforced by end and top cleats. As in all boxes containing fuzes, the nails in this box are cement coated. Between each set of end cleats, a length of jute rope is fastened to facilitate the hand ling of the box.* The box is 22-3/16" x 12-11/16" x 9-7/8", and the cover is closed by means of toggles. Complete with contents, the box weighs 72.45 lb. The wooden exterior surfaces of the box are stained a light brown, and all hardware is coated with a lusterless light-brown enamel. Stenciled on the box in white is all the information shown in figure 42. n. Action.- (1) The first step in the action is the adjustment of the setting pin to provide for superquick *or delay action. This is accomplished by rotating the setting pin 180° to match up the red ball with the desired red arrowhead marked "SQ" or "DELAY." (2) The cotter pin and ring are removed by pulling. When the cotter pin is withdrawn, the pin is free to move rearward and is held in its forward po sition only by the action of the set-back spring. (3) When the rocket is fired, acceleration causes the set-back pin to move to the r e a r . The spring offers sufficient resistance to the rearward motion of the pin so that the pin reaches its most rearward position only after the rocket has cleared the launcher. In this feature lies the bore safety of the fuze. (4) Upon the completion of the rearward movement of the set-back pin, the escape ball (which is made of steel and is 0.187" in diameter) rolls r e a r ward in the ball escape hole, permitting the delay arming pin to be moved for ward by the tension of the arming-pin spring. The arming pin moves forward only when the forward acceleration of the rocket has been completed.
M4 FUZE
(5) When the lower end of the delay arming pin clears the inner end of the slider, the slider is moved by the tension of the slider spring. (6) The lock pin rides in the slider keyway and springs up into the lock-pin recess under tension of the lock-pin spring. The slider is thus locked into a position where the deto nator is in line with the booster closing cup below and the body flash hole above. The fuze is now armed. (7) On impact, the head of the fuze is crushed. The firing-pin a s sembly is driven to the rear, shearing the shear wire a n d initiating b o t h primers. It is important to note that, no matter what action of the fuze is pro vided, both the instantaneous and delay elements are exploded. (a) If the fuze has been set for instantaneous (SQ), both primers func tion. The relay charge is initiated, and its flame is transmitted down the in stantaneous flash hole, through the par allel leg of the >Cs in the setting pin, and through the body flash hole, where it initiates the M17 detonator in the sliderdetonator recess. This travel of the flame is, to all intents and purposes, instantaneous. While this process oc curs, the delay element has been func tioning, and in the event that a mal function occurs in the instantaneous element, the Ml7 detonator will function 0.1 sec. later. (b) If the fuze has been set for delay action, both primers function as in (a) above, but, since the setting pin has been rotated 180°, there is no way to transmit the relay flame through the setting pin. The flame from the primer in the delay element passes through the compression chamber and the delay element plug, causing the delay charge to begin to burn. This charge burns for 0.1 sec. and then ignites the de lay charge, w h i c h detonates. T h e detonating wave and the flame from
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ing on an 8" radius. The base is 0.52" thick, and a central hole 1.5" in di ameter is drilled and countersunk to a diameter of 1.74". The walls thicken at an angle of 15° from the base to a point 1.250" above. This makes the in terior surface of the shell entirely smooth and adds support to the base of the shell casing. The lower 0.81" of the outer walls is threaded to fit the rocket body. Above the threads is an unthreaded portion, 0.15" wide. In the face of the base is an annular groove whose diameter is 3.00". The groove is approximately 0.20" in width and depth. (2) Burster tube.— The burster tube is steel tubing, 15-1/2" long and 1-3/4" in external diameter, with a wall thickness of 0.120". The bottom of the tube is smoothly rounded. The burster tube fits snugly and is brazed in place in the countersunk lower central shell hole. (3) Shell adapter.—The adapter is a malleable-iron ring of a size to fit halfway into the shell nose. The upper outer surface1 of the adapter is curved to follow the contour of the shell body. The inner surface of the adapter is threaded to seat the fuze. In the wall of the adapter is a threaded hole, 0.25"
this explosion pass through the hole in the setting pin and initiate the Ml 7 detonator. (8) Initiation of the M17 deto nator causes detonation of the booster closing-cup charge. (9) The d e t o n a t i o n of t h e booster-closing-cup charge detonates the booster charge, and the function of the fuze is completed. o. Safety measure. —Anaccele ration of 100 gravities (1 gravity in terms of acceleration is 32 ft./sec./sec.; 100 gravities = 3,200 ft./sec./sec.) of short duration must be attained in the flight of the rocket to initiate arming of the fuze. Forward acceleration of the rocket has ceased at a point ap proximately 85'from the launcher, and at this point the fuze is armed and the rocket is ready to detonate upon impact. 68 SHELL ASSEMBLY a. Component parts. — The shell assembly (see fig. 45) consists of the shell, burster tube, shell adapter, set screw, fuze well cup, and shell plug. In the following subparagraphs these components will be described. (1) Shell.- The shell is either forged or made from tubing in the shape of a flat-based cup, curved in slightly
at the top and centrally drilled and countersunk in the base. It is 7.5" high and 4.5" in diameter at the base and has a wall thickness of 0.2". The forward opening is 3.375" in diameter. At a point 4.75" from the base, the walls curve inward toward the forward open
in diameter, that seats the setscrew. The adapter is fitted into the nose openin of the shell and welded into place. (4) Setscrew.— This is a simple commercial setscrew, slotted at one end, that locks the fuze when the latter is inserted in the adapter.
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M8 ROCKET
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M8 ROCKET
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b. The forward end is as fol lows: At a point, 0.187" from the inner edge of the rim, is a series of internal threads that fit the body to the shell as sembly. In the rear of the threads is an external groove and an internal bulge, the groove being approximately 1/2" deep. The internal bulge acts as a rest to hold the trap assembly in place. Two inches to the rear of the external groove is a second external groove, approxi mately 0.06" deep. This second groove is a safety device, for the body will shear at this point if excessive propel lant pressures develop. c. The rear end of the body, or the nozzle, is as follows: The nozzle begins at a point 5.721" from the rear face of the body. It is formed by an initial inward curve on a radius of 3/4", followed by an outward curve on a ra dius of 1-3/4". The two curves form a venturi. The outer end of the second curve flattens out at an angle of 15° from the longitudinal axis of the body. The throat of the venturi is 1.828" in diameter, and the rear face is 2.62" in diameter. The last internal 3-7/8" of the nozzle are given a machine finish
(5) Fuze well cup.— This cup is made of thin steel (0.012" thick) in the shape of a cylinder. It is 2.83" in di ameter, 4.67" deep, and is rimmed with a single thread at the open end. The single thread screws into the threading of the adapter and holds the cup in place. (6) Shell plug.- This plug is made of cast iron, plastic, or sheet metal. It is rimmed, slotted on the up per face, and threaded beneath the rim
to fit into the adapter. After the fuze well cup is inserted, and prior to ship ment, the shell plug is inserted; it is removed only to insert the fuze. b. P a i n t i n g and m a r k i n g . (1) Painting.— After the explosive is loaded into the shell, all external sur faces of the assembly, except the lower shell threads, are coated with luster less olive-drab paint. (2) Marking.— Circumferen tially about the shell and 5" below the shell plug, the lot number of the shell, the loader's initials or symbol, and the month and year of loading are stenciled in yellow 1/4" letters and figures.
69 BODY ASSEMBLY
a. The body is a tube 23.29" long and 4.5" in diameter through ap proximately four-fifths of its length. The body is open at its forward end and is formed into a nozzle in the last onefifth of its length. The central section of the body has no design peculiarities, but both ends deserve description.
of the finest quality. The outer edge of the nozzle seats the fin assembly. Extreme care is taken to keep the nozzle concentric with the central sec tion of the body, for a lack of concen tricity will cause a thrust of escaping gas that is not along the longitudinal axis of the body. Such a thrust would result in inaccuracy in the flight of the rocket.
66
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M8 ROCKET 70 TRAP ASSEMBLY and 0.20" thick, with a central hole 2-1/8" a. General. — The trap assembly in diameter. Radially about the plate is a wire cage housed in the rocket body a r e 10 equally spaced slots, each0.164" and providing a framework to hold the wide and approximately 0.62" deep. Into propellant in the proper position. these slots the trap wires are fitted, r e maining there by reason of their tension. b. Components.— The trap a s sembly consists of a trap ring, 10 trap c. Assembly. —Before the shell wires, and a trap plate. assembly is screwed into the body the (1) Trap ring.— The trap ring trap assembly is slipped, trap-ring end has the shape illustrated in figure 48. first, into the threaded end of the rocket It is made of steel, is rimmed, and has body until the trap plate comes to rest a 3.47" diameter a c r o s s the r i m and a on the internal bulge of the body. Screw ing the shell assembly into the body forces the trap plate against the bulge and holds the trap assembly in place. The trap wire heads extending above the surface of the trap plate fit into the an nular groove in the base of the shell. 71 FIN ASSEMBLY a. General.— The fin assembly for the M8 rocket is a unique arrange ment that opens and guides the rocket in flight only after the rocket has cleared the launcher. The fins of the assembly are held in place by a component that is expelled by the blast of the escaping gas. The fins continue to be held in place by the walls of the launcher, and, after clearing the bore, snap to their out stretched position. b. Components. - The fin as sembly consists of a fin collar, six fins, a fin retaining ring, and a fin retainer. (1) Fin collar.— This collar, 0.094" thick and made of cadmium- or zinc-plated steel, fits into the notched
central diameter of 2.47". The trap wires a r e run through the 10 equally spaced 0.16"-diameter holes. (2) Trap wires.— Each of the 10 trap wires is identical. E a c h i s abright basic-steel wire, 0.162" in diameter, with a small head on each end. Each head is 0.19" long. The wire from the base of one head to the base of the other is 16.88" long. One head is formed prior to insertion of the wire in the trap ring. The second is formed after insertion in the ring. (3) Trap plate.— This compo nent (see fig. 49) is 4.24" in diameter
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M8
ROCKET
outer edge of the nozzle. The section of the collar that fits over the nozzle notch is 2.630' in diameter and 0.706" deep. The collar then widens abruptly to a diameter of 3.500". Above the ledge thus formed are collar walls 0.562" high. A rim, 4.25" in diameter, extends out ward from the top of these walls. Six equally spaced slots, 0.085" wide, are cut from the ledge and wall in the upper section of the collar. Into these six slots the holed ends of the six fins are fitted. When the fins are in their r e tained position, they rest against the external portion of the collar wall that fits over the nozzle notch. In their flight position, they are forced back against the rim of the collar. (2) Fins. — There are six fins in the fin assembly, all identical, all made of zinc- or cadmium-plated steel, and all having the shape illustrated in figure 51. The fin is 4-1/8" long and 0.078"
after the fins have been fitted into the fin collar slots. The ring is then welded in six places to the internal ridge of the fin collar. (4) Fin retainer.— This compo nent is a thin cadmium- or zinc-plated steel washer having a maximum radius of 1-11/16". The central hole of the washer is 2-1/4" in diameter. The fin retainer has the shape illustrated in figure 52. There are six points A on
the perimeter of the retainer. Between each two points is a cam surface B. The fin retainer is inserted in the rear end of the fin collar, with the fins in their retained position. The points are placed next to the edges of the fins, and the retainer is rotated by engaging the notch C. This rotation cams the upper ends of the fins outward, locking them thick and has a maximum width of 13/16". into position. They remain in this po When the fin is in the retained position, sition until the retainer is expelled by the sloped end A rests against the outer the blast of the propellant gases and the wall of the nozzle, the flat surface D rocket clears the bore of the projector. rests on the lower outer wall of the fin collar, and the fin retaining ring passes through the hole B. In the flight posi 72 IGNITER ASSEMBLY a. General.— The igniter as tion, the fin has rotated 90° and the notch C fits against the upper rim of sembly~consists of an open fiber tube the collar. The end E of each fin is fitted into a plastic base. The base fitted through a slot in the fin collar houses a primer for percussion igni and is held in place by the fin retaining tion of the igniter and a ring that pro vides electrical contact for electrical ring. ignition of the igniter. Either method (3) Fin retaining ring.— The fin of ignition can be used. The igniter retaining ring is a length of 0.135" steel fits into the open end of the nozzle, wire bent into a circle 3-1/2" in di where it is secured with cement. When ameter. The ring is not completely the igniter is initiated, it ignites the closed, a 1/2" arc remaining open. The propellant, the gases of the latter blow ring is run through the hole in each fin ing the igniter from the nozzle.
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M8 ROCKET
b. Components.— T h e igniter (7) Contact-ring a s s e m b l y . — assembly consists of the tube, closing The contact ring is made of steel and is cup, squib assembly, primer, primer 2.128" in diameter with a central hole holder assembly, c u p , contact-ring 1.3" in diameter. To one face of the assembly, and igniter charge. ring are welded three studs similar to those welded to the undersurface of (1) Tube.— The tube is a c a r the primer holder. These studs are tridge-paper cylinder, 3.54" long and placed so that they will fit into the outer set of holes in the cup. 1.25" in diameter. Stenciled length wise in black letters and figures on the tube (keeping 7/8" at one end unlettered) (8) Igniter charge. — The igniter are the name and use of .the assembly. charge consists of 648 grains of grade A-l black powder. (2) Closing cup.— This compo c. Assembly. — The p r i m e r nent is a glazed paperboard cup 9/16" deep and approximately 1.16" in di holder assembly is fitted into the central cup hole so that the studs slip through ameter. The diameter is controlled by the inner set of holes in the cup. The the necessity for a snug fit between the closing cup and tube. (3) Squib assembly. — The squib is an electrical arrangement for igniting the charge and has two terminals at tached to the lead wires. (4) Primer. — The primer is a No. 28 cal..5O primer (see vol. 1). (5) P r i m e r - h o l d e r assembly. The primer holder is a steel cup with a wide rim. It is 0.24" deep and 0.3" in diameter. The rim is 0.8"in diameter. Equally spaced about the undersurface of the rim are welded three studs, normal to the r i m . The studs are each 0.19" long and 0.09" thick. (6) Cup. — The plastic cup seats all the other components of the igniter assembly, and the rim of the cup is c e mented to the nozzle. The cup is shaped as illustrated in figure 53. The central hole seats the primer holder assembly; the shallow annular groove seats the contact ring. The sleeve is slotted at one point to permit the terminal of one lead wire to be engaged in one of the contact-ring studs. The rim of the cup is chamfered to allow a close fit in the nozzle. In the base of the cup are six holes, each 0.006" in diameter a n d spaced as shown in figure 53. The studs fit through these holes.
FIG. S 3 - IGNITER ASSEMBLY
contact-ring assembly is fitted into the annular groove of the cup so that the studs slip through the outer set of holes in the cup. One terminal is engaged on one of the contact-ring studs; the second terminal of the squib assembly is en gaged on one of the primer -holder studs. All studs are then riveted so that all parts are up tight. The squib is held upright by the stiffness of the lead wires. The tube is slipped into the sleeve of the cup and secured with ce ment. The opening between cup and tube, where the terminal and lead wires exit, is securely sealed with cement. The igniter charge is poured into the tube, and the closing cup, its outer wall coated with cement, is pressed into place against the charge. The No. 28 primer is seated, and t h e annular
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M8 ROCKET
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before being fired. To remove the r e quired amount of propellant, the shell assembly is unscrewed from the body. The body is then set upright on a sturdy, level, surface. Because of the presence of the black-powder igniter bags, the re moval of the trap assembly must be undertaken with care. When the trap assembly has b e e n removed, three equidistant trap wires are unsprung from the trap plate after the propellingcharge holder has been unwound. (Do not remove sticks from those wires that hold the igniter-bag assemblies.) Re place trap wires and reassemble the round. 74 EXPLOSIVE CHARGE a. The bursting charge for the M8 rocket is approximately 4.3 lb. of cast TNT. The charge is poured into the shell assembly, completely filling the burster tube. In the casting opera tion a fuze well is formed in the shell charge. This well is 2.88" in diameter and 4.38" deep. b. To protect the b u r s t i n g charge in the burster tube from the high temperatures generated by the propel lant gases, an insulator tube is inserted and fire clay poured into the burster tube. The insulator tube, made of chip board, is 15-3/16" long and 1.49" in di ameter. The wall thickness is 0.08". After the inner and outer surfaces have been coated with acidproof black paint, the insulator tube is slipped into the burster tube, where it seats on the burster-tube bottom. The end of the insulator tube, extending above t h e burster tube, is pressed flat against the shell body. The fire clay is pressed into the burster-tube bottom to a depth of 1.28"under a pressure of 2501b./sq.in. 75 PAINTING AND MARKING a. Following the loading of the explosive into the shell assembly, the lot number, loader's initials or symbol, and the year and month of loading of the shell assembly are stenciled in 1/4" letters and figures on the shell. This
groove between primer and primer holder is sealed with red N.R.C. com pound. 73 PROPELLANT a. The propellant for the M8 rocket consists of 30 sticks of ballistite w h i c h i s a double -base propellant powder. Each stick is 5" long and 7/8" in diameter and has an axial hole 1/4" in diameter. Three sticks are on each trap wire, and there is sufficient clear ance between stick and wire to allow the burning of the inner stick wall simultaneously with the burning of the outer wall. The three sticks which run onto each trap wire do not occupy all the length of the wire. Motion is pre vented by an adhesive strip, the pro pelling-charge holder, 1" x 30", that is bound about the wires of the trap a s sembly with one edge against the sticks. b. Two igniter-bag assemblies are bound on two opposite columns of propellant. The bags assist the ignition of the propellant by catching the flame of the igniter and igniting themselves. This ignites the upper propellant sticks which otherwise might fail to ignite im mediately. The igniter-bag assembly consists of an igniter-bag charge of 333 grains of grade A-l black powder inclosed in a cotton bag sewn together from a 7-1/2" x 1-1/8"cloth. The ends of the bag are closed by 10" lengths of tying cord. This cord is also used to tie the bags to the propellant. c. When the rocket is fired in a temperature range of 20° to 90° F., a full propellant charge is used. When the rocket is fired in a temperature range of 50° to 130°F., three sticks of propel lant must be removed to avoid a danger ously excessive propellant pressure. This temperature overlap makes pos sible firings at the same range with either a full or a reduced charge. This i s advantageous in instances when rockets are prepared for firing then are subjected to a change in temperature
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lettering a p p e a r s circumferentially, 5" below the nose of the shell. b. Following assembly of shell and body, the nomenclature of the round and the lot number of the shell and body a r | stenciled on the body. They are stenciled in 1/2" letters and figures, anfi the letters and figures of the two lot numbers, etc., are 1/4" high. All of t h i s stenciling appears circum f erentially on the motor in such a posi tion that the lower line of characters is 12" from the nose of the shell. The nomenclature reads as follows: "ROCKET, H.E., 4.5-INCH, M8" c. All letters and figures are stenciled with yellow paint on the olive drab lacquer enamel that covers all ex ternal surfaces of the rocket. 76 PACKING a. General.— T h e c o m p l e t e round (except fuze), with nose plug, is packed in an individual fiber container. Three fiber containers (three rounds) are bolted together into a bundle. It is this bundle that personnel will see in the field, and they should be familiar with its apearance, weight, and di mensions. b. Container, fiber, 4.5", M97. This is the individual fiber container in which the rocket is packed. It follows the general design for fiber containers. It has an inner and outer tube and a cover tube. It is painted black and is reinforced at the ends with steel end plates. However, it has no nose sup port, since the rockets contained are unfuzed. The container is 32-1/16" long and 5-5/16" in diameter and weighs 39.5 lb. when loaded. The end plates have a center bulge and are embossed semicircularly with the nomenclature of the container in 1/4" letters and fig ures. After the rocket is packed in the container, the loader's initials and the lot number are stenciled on the end plate with white marking ink.
M8 ROCKET
c. Sealing strip.— A 2" x 38" strip of yellow adhesive tape is wrapped about the joint between cover and tube, sealing the joint and identifying the con tents of the container as high explosive. d. Bundle.— Three containers are placed, cover end up, in the lower clover-leaf end plate, and the bolt is run through the end plate and engaged in the upper end plate, where it is se cured, assembling the bundle. T h e complete bundle is 33" long, 10" high, and 135 lb.in weight. The shipping and identification plates have stamped on t h e m the information illustrated in figure 54. e. Box.— For oversea shipment two rockets in M97 containers a r e packed in a wooden packing box. The box is 36" x 13-5/8" x 13-5/8" and weighs, complete with contents, 90 lb. 77 SAFETY PRECAUTIONS Due care must be exercised in handling t h e s e rockets, because of their high-explosive content. It i s important that the rocket be protected against the direct rays of the sun and that it never be stored at temperatures above the maximum at which it can be fired. When the rocket is fuzed, further care must be taken with its handling; with the safety pin removed, the fuze must be handled as though armed. 78 BALLISTICS a. Range. - The maximum range of the M8 rocket assembled with the M4 fuze is 4,500 yd. b. Muzzle velocity.— 900ft/sec. c. Dispersion. — Fifty percent of a given number of rounds fired at maxi mum range will fall within a rectangle whose dimensions are 65 yd. x 130 yd. d. Pressure.— The motor p r e s sure, af90 u F., is 3000 lb./sq.in. with the basic charge. e. Miscellaneous.— To the M8 rocket body may be assembled a variety of heads, containing various chemical agents.
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M8 ROCKET
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DESIGNATION COLOR OF SEALING STRIP O & ROCKET, H.E., 4 5 INCH, MB.
C WITH OUT FUZE)
ROCKET PRACTICl
4 5 INCH, M9. WITHOUT FUZE) LIGHT BLUE
5 O
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M9 ROCKET
SECTION II
ROCKET, PRACTICE, 4.5", M9
79 GENERAL
a. Use.— The rocket, practice, 4.5", M9, is a companion round to the M8 high-explosive rocket. It has the same weight as the M8, is assembled with similar components, has the same ballistics, and lacks only the explosive charge and live fuze to be identical. Since it is similar in weight and has the same trajectory as theM8, it is used to give rocket crews training in handling and firing without the danger or expense incidental to the use of the M8 H.E. round. In addition, at short ranges, if the M9 is fired with the M4 fuze, the functioning of the fuze provides a suit able smoke puff for ranging purposes. At extreme ranges, the a u x i l i a r y booster may be assembled with the M4 fuze to provide a visible smoke puff. As an alternative, a bag of black powder placed below the M4 fuze will also pro duce a satisfactory smoke puff. TheM9 rocket, then, is valuable both for drill purposes and for simulating fire.
a.. Fuze, rocket, dummy, M6. The M6 fuze is a solid gray-iron cast ing having the same general external appearance and the same weight as the M4 fuze (assembled with the M8 rocket). A hollow space is formed in the bottom of the fuze when material is removed to adjust the weight of the fuze. The external and internal surfaces of the fuze are coaied with blue lacquer en amel, except the threads, which are lightly c o a t e d w i t h shell grease. Stamped circumferentially about t h e fuze, 1/4" above the shoulder and in 1/8" letters and figures, is the nomen clature of the fuze, "FUZE, ROCKET, DUMMY, M6." The- fuze is packed separately, but information concerning packing is not available. b. Inert filler.— Approximately 4.5 lb. of a mixture of 60 percent plaster of paris and 40 percent zinc stearate is poured into the shell assembly. A fuze well is formed in the same manner as the fuze well in the M8 rocket and has the same dimensions. 81 PAINTING AND MARKING a. Painting.— All external sur faces of the M9 rocket shell, except threads, are coated with light-blue lac quer enamel. Threads are lightly coated with shell grease. The body is coated with olive-drab lacquer enamel. b. Marking.— In the same posi tion as on the M8 appears the nomen clature of the round: "ROCKET, PRACTICE, 4.5-INCH, M9"
b. The launcher. — The M9 prac tice rocket is fired from the same types afol#«8fe«&©BA<as are employed to fire the M8 high-explosive rocket.
80 DESCRIPTION OF COMPONENTS
The M9 rocket is identical to the M8 H.E. rocket with the exception of a high-explosive charge and a live fuze. Substituted for these two com ponents is an inert shell filler and a dummy fuze. Both of these components are described in the following sub paragraphs.
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M9 ROCKET
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•NOSE PLUG SETSCREW SHELL ADAPTER
INERT FILLER SHELL
ROCKET,
LOTaunil •[Hj[;-nt!
PROPELLING-CHARGE HOLDER
• SHELL TUBE
PROPELLANT
IGNITER BAG
TRAP ASSEMBLY NOZZLE
FIN
IGNITER CHARGE - SQUIB FIN RETAINER
FIGURE 55. - ROCKET, PRACTICE, 4.5", M9
Below the nomenclature is t h e l o t number of the round. All lettering is in white, the nomenclature in 1/2" let ters and figures, the lot n u m b e r , loader's initials or symbol, and the month and year of loading in 1/4" lett e r s and figures. On the shell, 5" b e low the fuze opening, is stenciled in 1/2" white letters, the word "INERT," and immediately below this word, in
1/4" letters, is stenciled the lot number of the shell.
82 PACKING
Except for t h e sealing strip (which is light blue instead of yellow) and the appropriate change in nomencla ture, the M8 and M9 rockets are packed identically. As with the M8 rocket, the M9 is shipped unfuzed and with a nose plug inserted.
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SECTION III 4.5" ROCKET DEVELOPMENT
4.5" ROCKET
83 GENERAL Although the principles of operation of the various component parts of the 4.5" rockets have been retained throughout the course of their developmerit, minor changes in the design of some of t h e components have been made from time to time with a view to improving their functioning and the functioning of the complete assembly. A brief history of the development of these rockets is given below: si. Production was b e g u n in February 1943 on the design of shell (head) and body (motor) designated as the M8 and M9. During the course of manufacture and the ballistic acceptance tests of the metal parts, several weaknesses in design and materials were revealed. Many metal parts from different manufacturers failed in the ballist-ic tes&wbfn all other specifications had been met. It was decided in the latter part of June 1943 to discontinue mass production and to place the item in the development stage. „,, , n b. All p r o d u c 11 o n contracts were canceled, and a contract for hmited procurement was placed with the
•n „ J T ^ ^ J I J .
d. Tests on the M8A1 indicated that the base of the head was weak and, because of the large deflection under pressure, would not allow full advantage to be taken of the strength of the new motor. A new head was designed to overcome this difficulty. The round composed of this new head and the motor from the M8A1 was designated as the M8A2. The M8A1 round is now in production but will be superseded by the M8A2 as soon as the new head is in quantity production. The total procurement of the M8, M8A1, and M8A2 will be covered by the authorization mentioned in b. e. The round composed of the M8A2head and a high-strength motor is designated as the T22 rocket;the same head and motor with the head inertloaded for the practice round is desig nated as the T46 rocket. This round is capable of withstanding working pressures considerably in excess of the working pressures of the previously mentioned rounds, and it pro vides for an increased powder charge a n d ^ i n c r e a s e d f a c t o r of s a £ e t The
characteristics of the round are as
, „
follows:
Revere Copper and Brass Co. for a lot of 390,000, which would complete the limited procurement of 550,000 originally authorized. ' c. The design of the body (motor) was changed in July 1943 to provide for an increase in strength, particularly at the threaded end. An effort was made to use the existing shell (head), which had been manufactured for the M8 and M9, by machining new base threads. The round composed of the strengthened motor and the modified head was designated as the M8A1.
Designation: H.E. Practice
T22 T46
Length, w/M4A2 fuze or dummy fuze 32" Weight, each type 38-3/4 lb. High-explosive charge, w/M4A2 fuze - 4.3 1b. Propellant 4.75 lb. Velocity —^ 865 ft./sec. Temperature range 20° to 125° F. Maximum range (approx.) — 4,200 yd.
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4.5" ROCKET
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Standard charge (4.6 lb.) for normal temperature Low charge (4.2 lb.) for high temperature At 100° F. Elevation, mils 46 69 94 116 140 167 193 222 253 287 325 369 Area of impact, yd.
Range, At 70° F . yd. Elevation, mils 500 750 1,000 1,200 1,400 1,600 1,800 2,000 2,200 2,400 2,600 2,800 3,000 3,200 3,400 3,600 3,800 4,000 39 58 80 98 116 136 157 180 204 228 256 286 318 356 365 Area of impact, yd.
210 x 450
125 x 200
250 x 400
550
FIGURE 56. - FIRING TABLE FOR THE M8 AND M9 ROCKETS
84 FIRING TABLE
The firing table shown in figure 56 is derived from data computed by firing the rockets from a fixed proving ground launcher. For this reason the table may not be completely accurate for rockets fired from mobile mounts (see section V). In any event, the data compiled in the firing table is reason ably accurate and will serve its pur pose until superseded. Firing tables for all launchers will be made avail able when the launchers are issued. 85 TEMPERATURE RANGES The 4.5" rockets, M8 and M9, may be fired within temperature ranges of 20°to 120° F. The full charge maybe fired within a temperature range of 20° to 90° F . , and the reduced charge may be fired in a temperature range of 50° to 120° F. Figure 57 shows the r e
lation between the full and reduced charges for the low and high tempera ture ranges. A temperature of 20° F. for the full charge gives a pressure
PRESSURE
L
0 5O
'7=-.
80 120
PBESS
which corresponds to that obtained by the reduced charge at 50° F . This is a good minimum operating pressure. In addition to a minimum operating pres sure, there is a safe maximum. This maximum pressure is produced by the reduced charge at 120° F. Thus, the reduced charge is necessary between
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the temperatures of 90° and 120° F. in order to remain within the safe operat ing pressure. Below 50° F. the re duced charge will give pressures below the minimum operating value. Between 50° and 90° F., either charge will work satisfactorily. However, the full charge
4.5" ROCKET
will give a greater range than the re duced charge as indicated by the firing table given in figure 56. The overlap in temperature range gives a versatility in charges that is valuable tactically and provides a wide margin of safety in relation to operating pressured.
SECTION IV
ROCKET, FRAGMENTATION, 4.5", T29
86 GENERAL
The T29 rocket (see fig. 58) consists of a 20-lb. fragmentation bomb, M40, assembled to the M8 4.5" rocket
motor. The assembly is made possible by a special adapter. The M111A2 bomb fuze is used with the T29 at the present time.
FIGURE 58. - ROCKET, FRAGMENTATION, 4.5", T29
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DECLASSIFIED
NOTES
-78
NOTES
-79
M4A1 FUZE
DECLASSIFIED
SECTION V 4.5" ROCKET FUZE DEVELOPMENT
87 GENERAL
The M4 P.D. rocket fuze a s sembled with the M8 rocket has under gone change since its standardization. Two successive major changes resulted in the M4A1 and the M4A2 fuzes. These changes and the modified fuzes are dis cussed in the following paragraphs. 88 FUZE, P.D., M4A1 a. The principal changes in the .M4 fuze (see fig. 37) to produce the M4A1 fuze are as follows: (1) A different delay time has been provided. Approximately 40 per cent of the present production of M4A1 fuzes retain the .1-sec. delay found in the M4 fuze. Such fuzes are for ground use only. The remaining production quantities of the M4A1 fuze have a .015-sec. delay. This delay was r e quested by the Army Air Forces, and fuzes having this delay are for air use only. The short-delay charge consists of approximately .136 grain of Army black powder, grade A-5, compressed at a pressure of 60,000 lb./sq.in. The .1-sec. delay charge consists of 1.23 grains of a similar powder pressed under a similar pressure. The dimen sions of the delay-element housing de pend on the type of delay charge used. When the delay charge is inserted in the small central cavity, the long narrow hole below the compression chamber is 1.520" long; when the short-delay charge is inserted, the hole is .355" long. The difference in length of this hole is ob tained by increasing the length of the compression chamber. The different delay times will be included as part of the nomenclature of the fuze and will appear stamped on the fuze. Requests for the fuze should specify the delay time required.
(2) The walls of the fuze have been made thinner so as to reduce the total weight of the fuze. (3) With the use of the two-zone propellant in the modified M8 rocket, it was found necessary to reduce the spring tension so that a lower accel eration would arm the fuze. The M4 fuze required 160 G. to arm (in later production models this requirement was reduced to 100 G.); the M4A1 r e quires 100 G. to arm. b. Upon completion of the pres ent production program for the M4A1 fuze, it is contemplated that the fuze w i l l b e declared limited standard. Production of the M4A2 will begin on a large scale, and issues of the M4A1 will be made until stocks are exhausted.
89 FUZE, P.D., M4A2
The M4A2 rocket fuze (see fig. 60) differs from the M4 and M4A1 in the following respects: a. The body has been redesigned to seat a new type of setting pin. In the M4 and M4A1 fuzes when the setting pin was not rotated completely through 180°, the flash holes in the setting pin were not alined with the body flash hole and the delay and instantaneous flash holes; the setting pin presented a solid metal surface to the flame from either the super quick or delay elements, and the fuze would not function completely. When this condition existed, the rocket became a dud. To obviate this diffi culty, the arrangement illustrated in figure 60 was devised. An oblique hole, 5/32" in diameter, is drilled from the upper rim of the delay-arming-pin hole to the body flash hole. Into this
-80
&SCUSSIFIED
hole, at a 25° angle, is fitted the delay element. The flash from the delay element is thus certain to pass un obstructed through the body flash hole and set off the slider detonator no matter whether the setting pin is set correctly or not. b. The new setting pin is 1.33" long and has a single diagonal flash hole passing through the unslotted end. This flash hole is .218" in diameter and is set at angle of 28°.
M4A2 FUZE
c. The slider for t h e M4A2 fuze is made of aluminum, affecting a considerable reduction in weight. At the same time, the lockingpinhas been strengthened (see fig. 60). The combina tion of these two changes has done much to prevent malfunctions of the fuze during ricochet. In the M4 and M4A1 fuzes, the heavy slider occa sionally sheared the weaker locking pin and slid back into the unarmed position. Such a malfunction is unlikely to occur now. d. Another change is the use of a lead-brass forged body as a third alternative. This is in addition to the malleable-iron and gray-iron castings previously specified.
FIG 59 SETTING PIN
-81
DECLASSIFIED
M4A2
FUZE
-82
DECLASSIFIED
DECLASSIFIED
SECTION VI 4.5" ROCKET LAUNCHERS
90 GENERAL a. Launchers for rockets, 4.5" and larger, are of three general c l a s sifications. (1) Air-to-ground or air-to-air launchers are mounted on aircraft and are used to launch rockets at ground targets or at other aircraft. (2) Ground-to-ground launchers are mounted on vehicles or emplaced on the ground and are used to launch rock ets at ground targets. (3) Antiaircraft launchers are mounted on vehicles or emplaced on the ground and a r e used to launch rockets at aircraft. They are not used by the United States Army. b. There are three types of ground-to-ground launchers.
4.5* LAUNCHERS
Firing mechanism-Electric, p e r m i t ting single-round or ripple fire. Blast protection for crew Sighting equipment • Weight c_. Ripple fire.— Ripple fire r e fers to the setting of the firing mecha nism that permits the rockets to be launched one after another at short intervals. 92 LAUNCHER, ROCKET, MULTIPLE ARTILLERY, 4.5", T34 a. Description.— This ground to-ground launcher (see fig. 63), now under development, will be mounted on the turret of an M4 medium tank. It is of the expendable type, composed of 60 opaque plastic tubes which may be jettisoned at will. The rockets are fired electrically, either singly or in ripple fire. Elevation is from -5° to +30° by means of the elevating mecha nism of the gun in the turret. Traverse is accomplished by movement of the t u r r e t . A l l 4.5" ground-to-ground rockets may be used in this launcher. T h e launcher weighs approximately 1,800 lb. b. Principal characteristics. No. of tubes - 60 -5° to +30° Provided by rotating turret. None For indirect fire only.
91 LAUNCHER, ROCKET, MULTIPLE ARTILLERY, 4.5% T27 AND T27E1 a. D e s c r i p t i o n . — The T27 launcher (see figs. 61 and 62), designed to provide a light and highly mobile weapon of great fire power for ground to-ground use, is an eight-tube launcher. It maybe mounted on a 1-1/2-ton truck or assembled for ground fire at a se lected position. This weapon is in the development stage. A second pilot, which will be designated T27E1, is being designed for breakdown into two-man loads not exceeding 120 lb. each. b. Principal characteristics.
Elevation No. of tubes Elevation Traverse 8
Traverse
-5° to +45° • Provided by turning truck, or by shifting trail in ground fire.
-83
Firing mechanism- Electric, p e r m i t ting single-round or ripple fire.
DECLASSIFIED
T36 LAUNCHER
•Bfafcft
DECkASSIBED
Tank itself. b. Principal characteristics. No. of tubes Elevation 8 -5° to +45°
Sighting equipment—Tank equipment. Weight (approx.) 1,800 lb.
93 LAUNCHER, ROCKET, MULTIPLE ARTILLERY, 4.5", T36 a. D e s c r i p t i o n . — This is a ground-to-ground launcher with eight light steel tubes. It can be fired from the ground or installed on a 1/4-ton 4 x 4 truck. Firing is electrical, in single rounds or in ripple fire. Eleva tion is from -5° to +35°. When mounted in the 1/4-ton truck, the launcher is traversed by movement of the vehicle. When the launcher is used as a ground weapon, it can be traversed through 20°. This launcher is under development.
Traverse: Truck-mounted Provided by turn ing truck. Ground-emplaced 20° Firing mechanism-Electric, p e r m i t ting single-round or ripple fire. Blast protection Sighting equipment Weight
DECLASSIFIED
-84
DECLASSIFIED
T27 LAUNCHER
-85
DECLASSIFIED
T27 LAUNCHER
DECLASSIFIED
FIGURE 62. - T27 LAUNCHER MOUNTED ON 1-1/2-TON 6 X 6 PERSONNEL, CARRIER. TOP: FRONT, 45° ELEVATION. BOTTOM: THREE-QUARTER.' LEFT FRONT, -5° DEPRESSION
-86-
DECLASSIFIED
DECLASSIFIED
T34 LAUNCHER
FIGURE 63. - T34 LAUNCHER ON MEDIUM TANK, M4-TYPE<
-87
DECLASSIFIED
NOTES
NOTES
-89
7.2" ROCKETS
DECLASSIFIED
CHAPTER 5-7.2" ROCKETS AND LAUNCHERS
SECTION I ROCKET, H.E., 7.2", T14 94 ROCKET H.E., 7.2", T14 This rocket was designed to carry a powerful demolition charge. It is propelled by a fast-burning double base powder in extruded stick form. The muzzle velocity is approximately 920 ft./sec, and the maximum range is approximately 6,000 yd. The Fuze, Tl, and Fuze, Mk. 137 (Navy), are used with this rocket.
SECTION II ROCKET, CHEMICAL, 7.2", T15 95 ROCKET, CHEMICAL, 7.2", T15 The T15 rocket is similar to the T14 rocket except for substitution of a chemical-loaded head in place of the H.E. head used with the T14. The T15 weighs approximately 701b. The minimum range for this projectile is 500 yd. The Tl and Mk. 137 (Navy) fuzes are used.
SECTION III ROCKET, H.E., AT, 7.2", T16 96 ROCKET, H.E., AT, 7.21, T 17 This rocket is the same as the T14 rocket except that it has a high explosive antitank head.
SECTION IV ROCKET, PRACTICE, 7.2", T17
97 ROCKET, PRACTICE, 7.2", T 17 This is the T14 rocket with an
inert head substituted for the H.E. head on the T14.
DECLASSIFIED
-90
NOTES
-91
NOTES
-92
DECLASSIFIED
SECTION V ROCKET, CHEMICAL, 7.2", T21
T ROCKET
§8 REASON FOR DEVELOPMENT Military requirements exist for a methodof projecting a large-capacity chemical shell from a light, mobile, and portable mount or gun. The T21 rocket, capable of carrying a heavy chemical charge, is the first of the 7.2" series of rockets to approach stand ardization. The T24 7.2" H.E. rocket has been virtually dropped from de velopment; the modified Navy rocket, T37, is now serving as an interim type. 99 GENERAL a. Appearance.— See figure 64 and 65. b. General data.— Length, over-all (w/o fuze; 45.4" Length, over-all (w/fuze) 47.127" Length of head 17-3/8" Length of motor, including tail vanes 29.91" Diameter of motor 3.25" Diameter of head - - - 7.2" Weight of head (w/charge) - - 29.46 lb. Chemical charge 20.00 lb. Weight of motor (w/propellant) 20.54 lb. Propellant (approx.) 5.74 lb. Total weight of rocket 50.00 lb. Fuze Mk. 147 Muzzle velocity 600 ft./sec. Range (approx.) 3,500 yd. c. Use.— The T21 rocket car ries a 20-lb. charge of FS smoke. It is used for laying down heavy smoke screens in tactical situations. Fired from a multiple launcher, the rockets will cover a large area as a result of normal dispersion. d. C o m p o n e n t s . — The T21 chemical rocket consists of a chem ical head, a motor, and a tail assembly. The Mk. 147 fuze is assembled with -93
the rocket. The head, motor, tail as sembly, and fuze will be discussed in the following paragraphs. 100 HEAD The head consists of the con tainer, adapter, burster tube, burster charge, chemical charge, shipping plug, and connector. These components are described in the following paragraphs. a. Container.— The container is «. bulb-shaped steel tube, open at both ends. b. Adapter.— The adapter fits inside the flange on the forward end of the container and is brazed thereto. The wide, forward end of the adapter is internally threaded to seat the fuze. c. Burster tube.— The burster tube is made of steel, fits inside the adapter, and extends downward into the container. The flange on the upper rim of the tube rests on the internal flange of the adapter. The tube and the adapter are held together by a press fit and sealed with white lead paste. The rear end of the tube is closed. d. Burster charge.— The only information available concerning the burster charge is that it weighs 0.35 lb. e. C h e m i c a l charge.— The chemical charge is 20 lb.of FS smoke. f . Shipping plug.— The only in _ formation available concerning t h i s component is that it is screwed into the adapter after the chemical charge is loaded into the container and is r e moved only to fit the fuze. g . Connector.— The connector _ is a cylindrical steel plug which fits inside the rear end of the container and
DECLASSIFIED
T21 ROCKET
DECLASSIFIED
-94-
DECLASSIFIED
DECLASSIFIED
T21 ROCKET
o
-95
DECLASSIFIED
DECLASSIFIED
T21 ROCKET
is brazed thereto. The rear portion of the connector is threaded internally to seat the forward end of the motor body.
101 MOTOR a. A p p e a r a n c e . — Figure 64 gives a cross section of the riaotor and its components. b. Components. — T h e m o t o r consists of a motor body, shipping cap, venturi tube, grid, and the propellant assembly. In the following subpara graphs the first four of these compo nents will be described. The propel lant assembly will be discussed in a separate paragraph. (1) Motor body.— T h e motor body is a steel tube .11" thick and 28.935" long. It is tapered near the rear end. This taper commences ap proximately 7" from the rear end and ceases approximately 4"from that end. The rear portion of the body has a di ameter of 2.755". The forward end of the tube is externally threaded through 1" of its length and fits inside the con nector of the head.
(3) Venturi tube.— The venturi tube is shown in figure 67. It is slipped down through the large, open end of the motor body, and the end B is welded to the inner edge of the motor-body rim. The tube is steel and has the shape and dimensions illustrated in figure 67. The hole C is .125" in diameter and allows gas to escape into the space be tween tube and motor body. Gas in this cavity tends to equalize the pressure on both sides of the venturi tube and prevent its distortion.
(4) Grid.— The grid consists of four steel pieces, each notched as shown in A, figure 68. These four pieces are interlocked to form the assembly shown in B, figure 68. Each end of each piece is rounded to fit the internal surface of the motor body. The grid is dropped (2) Shipping cap. — The shipping down through the large opening in the motor body and comes to rest cross cap, made of drab-colored plastic, is shaped as shown in figure 66. The walls wise on the upper rim of the venturi.
A
a r e internally threaded to f i t t h e threaded end of the motor body. Two winglike projections on the upper sur face of the cap assist in screwing on the cap.
^ _
B
~I375~ (-.187
I \
c
1
•A
FIG.68 GRID
—2gMAX- -\
L
A
1
h-2.75 R U OC
102 PROPELLANT ASSEMBLY
This assembly is a part of the motor assembly, but for sake of sim plicity of presentation it is described in this separate paragraph. The pro pellant assembly consists of the pro pellant-powder assembly, closure disk, spring, igniter assembly, desiccant assembly, and tail plug. These compo-
DECLASSIFIED
-96
DECLASSIFIED
T21
ROCKET
nents are described in subparagraphs _ a through f below; in subparagraph g_, the assembly and functioning of the propellant are discussed. a. Propellant-powder assembly. This assembly consists of four sticks of propellant powder and four propellantpowder washers. Each of t h e four washers is cemented to one end of the four sticks. The propellant is ignited at its forward end rather than at its rear end as was the case in the p r e viously discussed rockets. (1) Propellant powder. —A stick of propellant powder is 20.5" long and has a 1" axial hole. The view in figure 69 shows the three longitudinal ridges on the surface of the stick. There are eight sets of three holes each in each stick. Figure 69 shows the relative position of one set of holes. These holes make the propellant stick burn more evenly.
r-|DIA.-24 HOLES
r
i
i
1
)
1
T" t
r> .9.
- 1 6
1 ; /
»
FIG. 70
SPRING
d. Igniter assembly.— The ig niter assembly consists of an igniter c a p , igniter holder, electric squib, and igniter charge. These igniter com ponents will be described in the fol lowing subparagraphs. (1) Igniter cap. — The igniter cap is 2.375"in diameter and3/8"deep. It is made of steel .0179" thick. (2) Igniter holder. —The igniter holder is made of clear plastic and has the shape and dimensions illus trated in figure 71. The electric squib is slipped into the axial hole of the ig niter holder. After the igniter charge is pouredinto the igniter cap, the holder is cemented to the cap (see fig. 64.)
FIG.69
PROPELLENT POWDER
(2) Propellant-powder washer. The washer is made of celluloid 1/8" thick. T h e external d i a m e t e r is 2-15/32", and the internal diameter is 1-3/64". b. Closure disk.— The closure disk is of black, hard fiber 3.03" in di ameter and 1/8" thick. c. Spring.— The spring is made of annealed steel and has the shape and dimensions shown in figure 70. The spring is welded to the face of the ig niter cap (see fig. 64).
FIG. 71 IGNITER HOLDER
(3) Electric s q u i b . - The squib is a commercial electric igniter with
-97
DECLASSIFIED
T21 ROCKET
DECLASSIFIED
and sets off the igniter charge. The flame of the igniter charge starts the inside and outside of the upper half of each propellant stick burning. The rapid burning of the sticks results in a high gas pressure that provides the motive power for the rocket.
103 TAIL ASSEMBLY
The tail assembly serves to stabilize the rocket in flight and as a contact point for the electric current (4) Igniter charge.— The ig that explodes the igniter. The tail as niter charge is black powder. sembly consists of two tail vanes, a front and rear shroud, and four fins. e. Desiccant assembly. — The The components a r e described a s desiccant assembly consists of three follows: 5" squares of cheesecloth bound into a bag. The bag contains 30 to 35 grains a. Tail vanes.— Each vane is of silica gel. This assembly absorbs made of steel and is shaped roughly like moisture and prevents the moisture a W. The curved middle portion A (see content of the propellant from becom fig. 72) is welded to the rear outer sur ing too high. face of the motor body. The feet of the vanes, labeled B, support the front and f . Tail plug.— The tail plug is rear shrouds. The rear shroud is _ black, hard fiber, 1/8" thick and 2.25" welded to end B", and the front shroud in diameter. Opposite each other on is riveted to end B' through the holes C. the rim of the plug are two small notches. g. Assembly and functioning. (l) Assembly.— The four propellant sticks with washers attached are in serted in the threaded end of the motor body, washer ends first, and rest on the grid. The igniter assembly is then inserted in the same end; the wires are drawn through the venturi tube. The projection on the igniter holder spaces the propellant sticks. The closure disk is fitted into the motor body, pressed down upon the spring, and cemented in place. The tension of the spring holds the igniter firmly against the propellant sticks, holding the latter in place. The desiccant assembly is placed in the venturi tube. The tail plug is inserted in the rear of the venturi tube with one igniter lead wire in eachnotch. The tail plug is cemented in place.
two plastic-coated lead wires, each 24" long. The free ends of the lead wires are stripped for a distance of 1". To each stripped end, 12" of insulated lead wire is bound with friction tape. The free ends and tha taped ends of each of these second lengths of wire are stripped for 3/4". One wire is attached to the terminal on the front shroud of the tail assembly, and the other is at tached to the rear-shroud terminal.
b. Front shroud.— The front shroud is a steel ring 7.20" in diameter and 1.94" high. Equally spaced about the ring are four pairs of holes. The front shroud is slipped over the feet of the vanes, and the holes in the shroud and in the feet are alined. Shroud and vanes are fastened by means of insu lated rivets. A terminal for one of the igniter lead wires is attached to the inner surface of the shroud.
c. Rear shroud. — The r e a r (2) Functioning. — When electric current is turned on, the squib explodes shroud is identical to the front shroud
DECLASSIFIED
-98 -
T21
ROCKET
except that it has no holes and is welded at three points to each vane foot. The rear shroud is assembled with a .12" gap between it and the front shroud. A t e r m i n i for the other igniter lead wire is attached to the inner surface of the shroud. vid. Fin. — The steel fins a r e welded to the outside of the motor body just forward of the taper. Area A is welded to the motor body, and end B is welded to blade C of an adjacent fin (see fig. 73). End D extends rearward along the motor body, and the edge E is welded to the outer surface of the rear shroud
guard and body in such a manner as to extend over and completely cover the body shoulder. (b) The shipping guard is r e moved. This is a brass cup with a rounded bottom that fits over the pro peller assembly and is held in place on the body shoulder by the shipping-guard tape. The removal of t h e shipping guard exposes the propeller assembly and the upper half of the body. (c) The safety wire is removed. On the safety wire is a white tag, 3"x 1". In black letters appears the following information:
REMOVE SAFETY WIRE over (obverse) REPLACE SAFETY WIRE IF ROUND IS UNFIRED 104 FUZE, MK. 147 (NAVY) a. General.— The Army pro cures this fuze from the Navy. It is 2.414" long and 1.750" in greatest di ameter (see fig. 74). The threads just below the shoulder engage those in the adapter of the T21 rocket. Into the bot tom of the fuze is screwed an adapter that seats the burster. This burster ruptures the case and scatters t h e chemical contents of the rocket. The fuze is made of cadmium-plated steel and weighs approximately 1/2 lb. with out the burster. b. Action. - (1) The fuze i s shipped with the components in the po sition shown in figure 74. After the fuze is screwed into the rocket, the fol lowing steps are taken prior to firing: (a) The shipping-guard tape is removed. This tape is wrapped in a clockwise direction over the shipping -99 over (reverse) The underlined words are in red. The removal of the safety wire permits movement of the set-back pellet when sufficient acceleration is gained. (2) When the rocket i s fired the set-back pellet moves to the rear against the tension of the set-back pellet spring. The propeller locking pin, which is staked to the pellet and extends through a hole in the body, moves to the rear with the pellet. This rearward movement of pellet and pin frees the propeller assembly and per mits it to rotate. (3) The propeller assembly be gins to spin. After 2.1 turns it has moved outward far enough so that the propeller lock pin on returning to its
DECLASSIFIED
T21 ROCKET
DECLASSIFIED
z
0.
Q ^ CO
D O O
X
LU
cc
_J
LU
UJ
LU Q.
<r
i i
z
X
Iddl
to
a.
O en a.
O oc
w
-100
DECLASSIFIED
DECLASSIFIED
forward position, cannot act as a posi tive lock. The fuze is not yet armed. The propeller assembly continues to rotate, and is unscrewed from the body. The assembly then rotates freely, for it is free of the body threads, which are riding in the groove next to the shoulder of the pin. The point of the firing pin has withdrawn into the central hole of the closure plate, freeing the shutter. The shutter can now move. (4) The shutter, cocked by the "mouse-trap" shutter spring, rotates clockwise until it is stopped by the closure-plate pin. In this position, the detonator assembly, housed in the cen tral shutter hole, is in line with the firing pin and the lead-cup charge. The shutter is locked in this position by a spring-actuated detent that moves into a recess in the closure plate. The fuze is now armed. (5) On impact, the propeller assembly is driven rearward and the firing-pin threads shear t h e b o d y threads. The firing pin drives into the detonator assembly, causing it to ex plode. This explosion is carried through the tetryl lead and the tetryl burster charge. The action of the fuze is com plete. c. Explosive c o m p o n e n t s . (1) Detonator assembly.— The compo nents of the detonator are an upper charge of .052 gm.of lead-azide prim ing mixture, an intermediate charge of .110 gm. of lead azide, and a lower charge of .070 gm. of tetryl. The up per end of the detonator is identified by a green disk; the lower end by a red disk. (2) Lead-cup charge. — The lead cup is cemented into place in the central
T21 ROCKET
hole of the lead-in disk .075 gm. of tetryl. The lead cup is made of aluminum and is .182" in diameter at the rim and .190" deep. d. Packing. — No information is available at present. §_. Marking. — No information is available at present. f . S a f e t y f e a t u r e s . - (1) T h e safety locking wire prevents movement of the set-back pellet until the wire is removed. (2) The set-back-pellet spring will compress completely only under a pellet pressure caused by an accelera tion of 40 gravities. (3) The propeller must rotate 2.1 turns before armd^gi (4) The firing pin must with draw completely before the shutter can snap over. 105 PAINTING AND MARKING a. Head. — The head is painted gray. About the nose of the head is painted a narrow yellow band, a n d stenciled on the head in yellow is the nomenclature of the rocket. b. Motor and t a i l assembly. All external surfaces of motor and tail assembly (except contact points in the latter) are painted olive drab with nonomenclature stenciled in yellow. c. Note.— Detailed information on a and b above is not available. 106 PACKING No information is available.
DECLASSIFIED
-101
T24
ROCKET
SECTION VI
ROCKET, H.E., 7.2", T24
107 REASON FOR DEVELOPMENT See paragraph 98 of the preceding section. 108 GENERAL The T24 rocket is identical to the T21 chemical rocket with the fol lowing exceptions: a. The head has been slightly redesigned, since the T24 carries a 21.60 lb. charge of high explosive. b. The fins in the tail assembly of the T21 rocket are not assembled with the T24 rocket. c. The head of the T24 rocket is painted olive drab with yellow lettering.
SECTION VII ROCKET, H.E., 7.2", T37 109 REASON FOR DEVELOPMENT Military requirements indicated a need for a rocket capable of carrying a heavy charge of high explosive. This heavy charge was to be used for breaching concrete emplacements, and the effect was to be achieved by blast. c. Components.- N e a r l y a l l the components of this rocket are obtained from the Navy. The T37 is patterned after a point-detonating Navy rocket of simple design. T h e T37 rocket has been redesigned to provide for a base-detonating fuze. The head is made of thin steel to give the maxi mum blast effect from the charge.
110 GENERAL a. Appearance.— See figure 75. The T37 is of modified Navy design / d. Propellant. — The propellant serving as an interim type. s/^s a N a v y double-base solventless powder. It is a single unperforated, b. Data.— cruciform stick. The outer edges of the stick a r e inhibited in manufacturing, Length (approx.) 36" and only the inner edges are permitted Length of container 20" to burn. Length of motor 16" Diameter of fin and container - - 7.2" 111 FUZE, B.D., MK. 146 Diameter of motor 3.25" This fuze is obtained from the Weight (approx.) 60 lb. Navyand is illustrated in cross section Weight of charge in figure 76. It is pressure operated Weight of propellant —-"—r 1 -:--»-->; g|id,i^'|qpatetiin the r e a r surface of the Velocity (approx.) 170ft. /set*. of'tnVWad.' The r e a r surface of the Range fuze extends intothe motor and is sub-
DECLASSIFIED
DECLASSIFIED
T37 ROCKET
DECLASSIFIED
-103
MK.146 FUZE
DECLASSIFIED
INLET SCREW
INLET SCREEN
PLUG
INLET CUP
ORIFICE
GASKET
DIAPHRAGM
HEAD
SHEAR WIRE ARMING PLUNGER FIRING PIN BODY LOCKING BALL BODY DETENT FIRING PIN SPRING
SHUTTER
SPRING
SHUTTER
LOCKING PIN FIRING PIN SHUTTER
-SHUTTER HINGE PIN
SPACER SLEEVE
BOOSTER (TETRYL)
LEAD-IN
(TETRYL)
MAGAZINE
.
SHUTTER
N
(UNARMED
posmoN)
FIRING PIN
SHUTTER LOCKING PIN
SHUTTER
SPRING
DETENT SECTION X - X
DETONATOR
FIGURE 76. - FUZE-, B.D., MK. 146
DECLASSIFIED
-104
DECLASSIFIED
jected to the pressure of the propellant gas. The action of the fuze is described as follows: a. Gas from the burning pro pellant seeps through the inlet screen, through the transverse hole in the inlet screw, and through t h e inlet-screw orifice. b. When sufficient gas p r e s sure is builtup in the pressure chamber, the diaphragm is depressed. c. Under the pressure of the diaphragm, the arming plunger is driven downward. Sufficient pressure must be exerted by the diaphragm on the arming plunger to cause the latter to shear the shear wire. d. When t h e arming plunger moves downward, the locking ball moves into the recess in the arming plunger. e. With the locking ball in the arming-plunger recess, the fir ing-pin body, under tension of the firing-pin
T37 ROCKET
spring, is forced upward, withdrawing the firing pin from its position in the shutter. When in the shutter, the firing pin prevents rotation of the shutter. f_. The shutter, no longer r e strained by the firing pin, is forced in a clockwise direction by the shutter spring, rotating on the shutter hinge pin. The shutter rotates until halted by the shutter locking pin and is locked in this position by the spring-actuated detent. g_. In this position of the shut ter, the shutter detonator is in line with the firing pin above and the lead-in below. h. On impact of t h e rocket, the firing pin continues forward by inertia, and drives into the detonator. The detonator i s exploded, and this explosion travels through the lead-in, into the booster. The booster explodes, setting off the rocket charge. T h e function of the fuze is completed.
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T40 LAUNCHER
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SECTION VIII
LAUNCHER, ROCKET, MULTIPLE ARTILLERY, 7.2", T40
112 MILITARY CHARACTERISTICS
a. T h e T40 is a ground-toground rocket launcher (see discussion of launchers, par. 90) having the fol lowing military characteristics: No. of tubes (max.) 20 Mounting M4-type tank turret Traverse By tank turret Elevation — -5° to +25° by turret gun mechanism Sighting Turret gun mechanism
Firing Electric — single mechanism -- •- round or ripple fire Armor plating Protection b. This launcher is used for the 7.2" rocket, Mk. VI (Navy). The mounting of the launcher will not interfere with waterproofing of the tank, and the launcher maybe jettisoned at any time. The armor plate on the bottom and sides serves to protect the rockets loaded on the rails against cal..30 ammunition.
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CHAPTER 6 - 8 " ROCKETS
ROCKETS
113 GENERAL T h e 8" rocket consists of a 100-lb. bomb assembled by means of an adapter to an M8, 4.5" motor. The fin assembly of the bomb replaces the
M8 tail assembly. A standard bomb fuze, slightly modified so that it will arm at the slow rocket velocity, will be used.
NOTES
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-ill
10" ROCKETS
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CHAPTER 7 - 1 0 " ROCKETS
SECTION I ROCKET, H.E., 10", T10
114 GENERAL The rocket, H.E., 10", T10, is a ground-to-ground projectile which can be used for demolition. When used for demolition purposes, the head is filled with TNT. Chemical may be substituted when it is desired to lay down gas. The rocket has fixed fins and is fired electrically. 115 PRINCIPAL CHARACTERISTICS Weight, total Length, over-all Muzzle velocity 210 lb. 53" 440 ft./sec.
Range (45° elevation) 2,200 yd. Weight of head (w/filler) 117 lb. Filler (TNT) 77 lb. Head 40 lb. Fuze (bomb, nose) MHO Motor: Length 23-1/2" Diameter 10" Propellant (double-base powder) 108 sticks Length, each stick 5" Outside diameter 7/8" Inside diameter • 1/4" Burning time .2 sec. Internal pressure - - 2,800 lb./sq. in.
SECTION II ROCKET, H.E., 10", T1OE1 (HIGH VELOCITY)
116 GENERAL
This rocket differs from the T10 in the following specifications. Total weight Muzzle velocity Maximum range 190 1b. 1,050 ft./sec. 5,000 yd.
Weight of head (w/filler) Filler (TNT) HeadFuze Propellant (double-base) powder)
68 lb. 40 1b. 28 1b. M4 162 sticks'
SECTION III ROCKET, H.E., AT, 10", T10E2
117 GENERAL
Rocket T10E2, differs from the T10 only in its weight (180 lb.) and the use of an H.E. AT head employing'the
hollow-charge principle. T h e head, ^wi|hotit filler, weighs 40 lb. The weight oYfnT TNT'filler is 35 lb.
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ROCKETfe AND LAUNCHERS, ALL TYPES • OS 9-69
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Biomedical Engineers
Biomedical Engineer Career, Salary and Education Information
What They Do: Biomedical engineers combine engineering principles with medical sciences to design and create equipment, devices, computer systems, and software.
Work Environment: Most biomedical engineers work in manufacturing, universities, hospitals, and research facilities of companies and educational and medical institutions. They usually work full time.
How to Become One: Biomedical engineers typically need a bachelor’s degree in biomedical engineering or bioengineering, or in a related engineering field. Some positions may require a graduate degree.
Salary: The median annual wage for biomedical engineers is $88,550.
Job Outlook: Employment of biomedical engineers is projected to grow 4 percent over the next ten years, about as fast as the average for all occupations. Increasing numbers of technologies and applications to medical equipment and devices, along with the medical needs of a growing and aging population, will require the services of biomedical engineers.
Related Careers: Explore occupations that share similar duties, skills, interests, education, or training with the occupation covered in the profile.
Following is everything you need to know about a career as a Biomedical Engineer with lots of details. As a first step, take a look at some of the following Biomedical Engineer jobs, which are real jobs with real employers. You will be able to see the very real job career requirements for employers who are actively hiring. The link will open in a new tab so that you can come back to this page to continue reading about the career:
Top 3 Biomedical Engineer Jobs
• Biomedical Engineer - DEX - Camarillo, CA
... biomedical medical equipment in a hospital * Strong communications and organizational skills. * Must have good attention to detail. Company Description DEX is an engineering , manufacturing and repair ...
• Director Clinical and Biomedical Engineering - Julia Edmunds Associates, Inc. - Seattle, WA
Director Clinical and Biomedical Engineering Seattle, Washington Our Client's highest priority continues to be on quality and safety for every patient. We are looking for a Leader possessing at least ...
• HICS Temporary - Clinical Engineering - Renown Health - Reno, NV
For Internal Employees Only Decontamination of equipment
See all Biomedical Engineer jobs
What Biomedical Engineers Do[About this section] [To Top]
Biomedical engineers combine engineering principles with medical and biological sciences to design and create equipment, devices, computer systems, and software used in healthcare.
Duties of Biomedical Engineers
Biomedical engineers typically do the following:
• Design biomedical equipment and devices, such as artificial internal organs, replacements for body parts, and machines for diagnosing medical problems
• Install, adjust, maintain, repair, or provide technical support for biomedical equipment
• Evaluate the safety, efficiency, and effectiveness of biomedical equipment
• Train clinicians and other personnel on the proper use of biomedical equipment
• Research the engineering aspects of the biological systems of humans and animals with life scientists, chemists, and medical scientists
• Prepare procedures, write technical reports, publish research papers, and make recommendations based on their research findings
• Present research findings to scientists, nonscientist executives, clinicians, hospital management, engineers, other colleagues, and the public
Biomedical engineers design instruments, devices, and software used in healthcare; develop new procedures using knowledge from many technical sources; or conduct research needed to solve clinical problems. They frequently work in research and development or quality assurance.
Biomedical engineers design electrical circuits, software to run medical equipment, or computer simulations to test new drug therapies. In addition, they design and build artificial body parts, such as hip and knee joints. In some cases, they develop the materials needed to make the replacement body parts. They also design rehabilitative exercise equipment.
The work of these engineers spans many professional fields. For example, although their expertise is based in engineering and biology, they often design computer software to run complicated instruments, such as three-dimensional x-ray machines. Alternatively, many of these engineers use their knowledge of chemistry and biology to develop new drug therapies. Others draw heavily on math and statistics to build models to understand the signals transmitted by the brain or heart. Some may be involved in sales.
The following are examples of specialty areas within the field of biomedical engineering:
Bioinstrumentation uses electronics, computer science, and measurement principles to develop instruments used in the diagnosis and treatment of medical problems.
Biomaterials is the study of naturally occurring or laboratory-designed materials that are used in medical devices or as implantation materials.
Biomechanics involves the study of mechanics, such as thermodynamics, to solve biological or medical problems.
Clinical engineering applies medical technology to optimize healthcare delivery.
Rehabilitation engineering is the study of engineering and computer science to develop devices that assist individuals recovering from or adapting to physical and cognitive impairments.
Systems physiology uses engineering tools to understand how systems within living organisms, from bacteria to humans, function and respond to changes in their environment.
Some people with training in biomedical engineering become postsecondary teachers.
Work Environment for Biomedical Engineers[About this section] [To Top]
Biomedical engineers hold about 19,800 jobs. The largest employers of biomedical engineers are as follows:
Medical equipment and supplies manufacturing 19%
Research and development in the physical, engineering, and life sciences 16%
Colleges, universities, and professional schools; state, local, and private 10%
Navigational, measuring, electromedical, and control instruments manufacturing 9%
Healthcare and social assistance 9%
Biomedical engineers work in teams with scientists, healthcare workers, or other engineers. Where and how they work depends on the project. For example, a biomedical engineer who has developed a new device designed to help a person with a disability to walk again might have to spend hours in a hospital to determine whether the device works as planned. If the engineer finds a way to improve the device, he or she might have to return to the manufacturer to help alter the manufacturing process to improve the design.
Biomedical Engineer Work Schedules
Biomedical engineers usually work full time on a normal schedule. However, as with employees in almost any engineering occupation, biomedical engineers occasionally may have to work additional hours to meet the needs of patients, managers, colleagues, and clients. Some biomedical engineers work more than 40 hours per week.
How to Become a Biomedical Engineer[About this section] [To Top]
Get the education you need: Find schools for Biomedical Engineers near you!
Biomedical engineers typically need a bachelor's degree in biomedical engineering or bioengineering, or in a related engineering field. Some positions may require a graduate degree.
Find a Degree:
Education for Biomedical Engineers
Biomedical engineering and traditional engineering programs, such as mechanical and electrical, are typically good preparation for entering biomedical engineering jobs. Students who pursue traditional engineering programs at the bachelor's level may benefit from taking biological science courses.
Students interested in becoming biomedical engineers should take high school science courses, such as chemistry, physics, and biology. They should also take math courses, including algebra, geometry, trigonometry, and calculus. Courses in drafting or mechanical drawing and in computer programming are also useful.
Bachelor's degree programs in biomedical engineering and bioengineering focus on engineering and biological sciences. Programs include laboratory- and classroom-based courses, in subjects such as fluid and solid mechanics, computer programming, circuit design, and biomaterials. Other required courses may include biological sciences, such as physiology.
Accredited programs also include substantial training in engineering design. Many programs include co-ops or internships, often with hospitals and medical device and pharmaceutical manufacturing companies, to provide students with practical applications as part of their study. Biomedical engineering and bioengineering programs are accredited by ABET.
Important Qualities for Biomedical Engineers
Analytical skills. Biomedical engineers must analyze the needs of patients and customers to design appropriate solutions.
Communication skills. Because biomedical engineers sometimes work with patients and frequently work on teams, they must express themselves clearly. They must seek others' ideas and incorporate those ideas into the problem-solving process.
Creativity. Biomedical engineers must be creative to come up with innovative and integrative advances in healthcare equipment and devices.
Math skills. Biomedical engineers use the principles of calculus and other advanced topics in math and statistics, for analysis, design, and troubleshooting in their work.
Problem-solving skills. Biomedical engineers typically deal with and solve problems in complex biological systems.
Advancement for Biomedical Engineers
Biomedical engineers typically receive greater responsibility through experience and more education. To lead a research team, a biomedical engineer generally needs a graduate degree. Biomedical engineers who are interested in basic research may become medical scientists.
Some biomedical engineers attend medical or dental school to specialize in various techniques or topical areas, such as using electric impulses in new ways to get muscles moving again. Some earn law degrees and work as patent attorneys. Others pursue a master's degree in business administration (MBA) and move into managerial positions. For more information, see the profiles on lawyers and architectural and engineering managers.
Biomedical Engineer Salaries[About this section] [More salary/earnings info] [To Top]
Salary Calculator
Entry Level Experienced
The median annual wage for biomedical engineers is $88,550. The median wage is the wage at which half the workers in an occupation earned more than that amount and half earned less. The lowest 10 percent earned less than $51,890, and the highest 10 percent earned more than $144,350.
The median annual wages for biomedical engineers in the top industries in which they work are as follows:
Navigational, measuring, electromedical, and control instruments manufacturing $101,960
Research and development in the physical, engineering, and life sciences $93,250
Medical equipment and supplies manufacturing $83,450
Healthcare and social assistance $75,030
Colleges, universities, and professional schools; state, local, and private $69,100
Biomedical engineers usually work full time on a normal schedule. However, as with employees in almost any engineering occupation, biomedical engineers occasionally may have to work additional hours to meet the needs of patients, managers, colleagues, and clients. About 1 in 5 biomedical engineers work more than 40 hours per week.
Job Outlook for Biomedical Engineers[About this section] [To Top]
Employment of biomedical engineers is projected to grow 4 percent over the next ten years, about as fast as the average for all occupations.
Biomedical engineers likely will see employment growth because of increasing possibilities brought by new technologies and increasing applications to medical equipment and devices. Smartphone technology and three-dimensional printing are examples of technology being applied to biomedical advances.
As the aging baby-boom generation lives longer and stays active, the demand for biomedical devices and procedures, such as hip and knee replacements, is expected to increase. In addition, as the public continues to become more aware of medical advances, increasing numbers of people will seek biomedical solutions to their health problems from their physicians.
Biomedical engineers work with scientists, other medical researchers, and manufacturers to address a wide range of injuries and physical disabilities. Their ability to work in different activities with workers from other fields is enlarging the range of applications for biomedical engineering products and services.
Employment projections data for Biomedical Engineers, 2018-28
Occupational Title Employment, 2018 Projected Employment, 2028 Change, 2018-28
Percent Numeric
Biomedical engineers 19,800 20,500 4 700
*Some content used by permission of the Bureau of Labor Statistics, U.S. Department of Labor.
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Enter the initial daily intake for the patient. If the daily intake is unknown, the auto-calculate will estimate the initial daily caloric intake based on weight management of the estimated ideal weight.CloseAny daily calorie recommendation is a starting recommendation. Please monitor the pets body weight and adjust as needed to achieve ideal weight.
“The American Heart Association recommends that men eat less than 36 grams of added sugar and that women consume less than 24 grams. However, for optimal weight loss, I tell my male clients to consume less than 20 grams of sugar per day and I tell the women to consume less than 15 grams.The easiest way to cut back on the sweet stuff is by consuming less sugary drinks and dressings. Cut the sugar, lose the fat, regain your health and life.” — Dr. Sean M. Wells, DPT, PT, OCS, ATC/L, CSCS
“Eating directly out of a box or bag (almost always leads to overeating. Serve your food on a plate or in a bowl to keep portion sizes in check and to get used to what one serving looks like. Also, when we take the time to sit down during meals versus standing or driving, we tend to feel more satisfied with our meal. In fact, research shows that you will eat up to 30% more food at the next meal if you ate standing up! Serve yourself, sit down, and enjoy!” — Jennifer McDaniel, MS, RDN, CSSD, LD, food and nutrition expert
Generally, foods that take more effort to chew – fruit, vegetables, lean meats, whole grains, etc. – require the body to burn more calories since more calories are required to digest them. It also results in the feeling of satiety for longer periods of time. Furthermore, certain foods like coffee, tea, chilies, cinnamon, and ginger have been found to increase the rate of calories burned due to the ingredients they contain.
They should help keep you from feeling deprived and bingeing on higher-calorie foods. For instance: honey has just 64 fat-releasing calories in one tablespoon. Eggs have just 70 calories in one hard-boiled egg, loaded with fat-releasing protein. Part-skim ricotta cheese has just 39 calories in one ounce, packed with fat-releasing calcium. Dark chocolate has about 168 calories in a one-ounce square, but it’s packed with fat releasers. And a University of Tennessee study found that people who cut 500 calories a day and ate yogurt three times a day for 12 weeks lost more weight and body fat than a group that only cut the calories. The researchers concluded that the calcium in low-fat dairy foods triggers a hormonal response that inhibits the body’s production of fat cells and boosts the breakdown of fat.
The value obtained from this equation is the estimated number of calories a person can consume in a day to maintain their body-weight assuming they remain at rest. This value is multiplied by an activity factor (generally 1.2-1.95) dependent on a person's typical levels of exercise in order to obtain a more realistic value for maintaining body-weight (since people are less likely to be at rest throughout the course of an entire day). 1 pound of body weight, or approximately 0.45 kg, equates to about 3,500 calories. As such, in order to lose 1 pound per week, it is recommended that 500 calories be shaved off the estimate of calories necessary for weight maintenance per day. For example, if a person has an estimated allotment of 2,500 calories per day to maintain body-weight, consuming 2,000 calories per day for one week would theoretically result in 3,500 calories (or 1 pound) lost during the period.
Swap giant dinner plates, bowls, and silverware for smaller versions, and pick up portion-sized packages of snacks instead of nomming straight from a full-size box or bag, says Cerderquist. You'll be eating less without even thinking about it. Another pro tip: stay away from protein bars. "It is amazing to see that an entire well-balanced meal can have the same amount of calories as many protein bars," she says. "But you are much more satisfied when having the variety of textures and flavors from a real meal."
So boiling it down even further: reduce calories, eat better, exercise, and most of all, remember it is a practice that has to be repeated over time – months or years. The fact that you'll have to work harder at maintenance than your never-overweight best friend is depressing, but it's worth coming to terms with. And, most important to remember, your brain (the organ behind all this, after all) is plastic, and it will respond to the changes you make – better than you think. And so will your body.
The weight loss calculator will then compute your daily Calorie consumption required to achieve approximately 1lb to 2lbs of fat loss a week. Many consider it unhealthy to adopt a calorie consumption of less than 1200 Calories a day and as such, if you can not lose weight at a recommended speed without dropping your calories below this level you may consider increasing your activity as an alternative.
We often think that if we can just discover the “right” combination of foods, we’ll magically lose weight or maintain what we’ve lost. There are low-fat diets, low-carb diets, low glycemic diets, Paleo diets, and a lot of iterations of all of these. Jensen points out that in fact there doesn’t seem to be any “right” diet, and there doesn’t seem to be any evidence that one particular diet will work better with an individual’s specific metabolism. “The big myth out there,” he says, “is that there’s a magical combination of foods – be it protein, vegetarian, and what have you – that’s going to be unique because of its unique interaction with your metabolism. We know pretty much that any diet will help you lose weight if you follow it. There’s no magic diet. The truth is that ALL Diets will work if you follow them.”
If this cycle has occurred more times than you'd like to admit, you’re not alone. Setting a weight-loss goal is easy to do, but following through on it is a different story. Which is why losing weight is consistently one of the most popular resolutions, but few of us actually accomplish it. In fact, one survey found that at the end of the first week of January, 30 percent of people have already called it quits.
Some popular beliefs attached to weight loss have been shown to either have less effect on weight loss as commonly believed or are actively unhealthy. According to Harvard Health, the idea of metabolism being the "key to weight" is "part truth and part myth" as while metabolism does affect weight loss, external forces such as diet and exercise have an equal effect.[44] They also commented that the idea of changing one's rate of metabolism is under debate.[44] Diet plans in fitness magazines are also often believed to be effective, but may actually be harmful by limiting the daily intake of important calories and nutrients which can be detrimental depending on the person and are even capable of driving individuals away from weight loss.[45]
Eating sugary foods might be satisfying in the moment, but they can increase your cravings for more sugary foods in the future — and that only leads to trouble. "Many foods high in added sugar are also higher in calories and fill you up less than lower-calorie, still-sweet alternatives like fruit," says Amy Gorin, MS, RDN, owner of Amy Gorin Nutrition in Jersey City, NJ. But there are still ways to satisfy your sweet tooth without ODing on sugar. "When you're baking, cut out some of the sugar in recipes by adding in vanilla extract or cinnamon, blend unsweetened cocoa powder into a smoothie instead of honey, top your French toast with unsweetened frozen fruit instead of syrup, and nosh on a slab of watermelon instead of cookies."
Be choosy about carbs. You can decide which ones you eat, and how much. Look for those that are low on the glycemic index (for instance, asparagus is lower on the glycemic index than a potato) or lower in carbs per serving than others. Whole grains are better choices than processed items, because processing removes key nutrients such as fiber, iron, and B vitamins. They may be added back, such as in “enriched” bread.
While the American College of Sports Medicine warns that women who eat less than 1,300 calories a day and men who eat less than 1,800 risk slowing down their metabolism over time. But a rev-up stage that only lasts two weeks is approved by doctors and isn’t as difficult as it seems. Our tester found the Mayo Clinic day pretty satisfying, and still had enough energy to hit the gym.
… that lists sugar, fructose, or corn syrup among the first four ingredients on the label. You should be able to find a lower-sugar version of the same type of food. If you can’t, grab a piece of fruit instead, especially if you show signs you’re eating too much sugar. Look for sugar-free varieties of foods such as ketchup, mayonnaise, and salad dressing. Also, avoid partially hydrogenated foods, and look for more than two grams of fiber per 100 calories in all grain products. Finally, a short ingredient list means fewer flavor enhancers and empty calories. Sounds impossible, but you can actually learn how to give up sugar without missing it.
Aerobic activity is the best way to create the calorie deficit you need to lose body mass, says WebMD. So focus on whatever kind of cardio you're interested in doing. Just because running or biking burns a lot of calories doesn't mean that's what you should do. So focus on cardio activities that interest you. You're more likely to keep returning to the activity if you like doing it, rather than if it feels like a chore.
She recommends setting aside time on Sunday to plan out the week ahead. “Planning is so important from an organization perspective,” says Delaney. “When it comes to organizing you really need to think about what’s important to you. I always tell people, don’t over-schedule. You don’t have to say yes to every single invitation. Think about what your week is going to look like and how you’re going to find time for what’s important.”
“The one trick I use now, which I should have been using all along, is the make dinner a no-carb meal. I’ll do a vegan protein and vegetables, and no bread. I think carbs are important and good energy, but when I don’t eat them at night, I wake up and I feel like my belly’s flat first thing in the morning.” — Carrie Underwood, who lost 30 pounds of baby weight in less than a year
The least intrusive weight loss methods, and those most often recommended, are adjustments to eating patterns and increased physical activity, generally in the form of exercise. The World Health Organization recommended that people combine a reduction of processed foods high in saturated fats, sugar and salt[11] and caloric content of the diet with an increase in physical activity.[12]
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Monitor the health of your community here
Trouble Breathing While Exercising
Trouble breathing while exercising may manifest as shortness of breath, wheezing, a barking type of cough or tightness of the throat. There are many reason why you might develop trouble breathing during exercise including having recently begun an exercise program, exercise-induced asthma or a hiatal hernia. You need to know when trouble breathing during exercise is something that requires immediate medical attention and when it does not.
Age
Age, lifestyle, general health and general physical condition all factor into situations where you may experience breathing difficulties while exercising. After age 30, the rate of air flow through the lungs begins to slowly decline, making it easier for you to become short of breath during physical exertion. The muscles of the diaphragm and those between the ribs become weaker through the lifespan, requiring them to work harder to provide maximum air flow. These natural changes with aging don't prevent you from exchanging enough air because in youth, there is "excess" lung capacity that you body draws on as you age.
• Age, lifestyle, general health and general physical condition all factor into situations where you may experience breathing difficulties while exercising.
• After age 30, the rate of air flow through the lungs begins to slowly decline, making it easier for you to become short of breath during physical exertion.
Lifestyle and Physical Condition
What is DOE in Medical Terms?
Learn More
If you've been maintaining a fairly sedentary lifestyle and are beginning an exercise routine or program, you may find yourself short of breath during your initial workouts. The same applies if you are changing your workout to include more aerobic activity; you may experience mild shortness of breath until your body begins to acclimate to the change in physical activity. If you are overweight or obese, exercise may result in mild shortness of breath.
Health
Your overall health is another important consideration for why you may experience trouble breathing while exercising and the reason why it is important to consult your health care provider before beginning any exercise program. Heart disease, respiratory disease and hypertension may warrant that you begin with short sessions more frequently rather than one long daily session until your body builds up tolerance to the new physical activity. Exercise-induced asthma is a condition that can be treated with the use of medication, allowing you to exercise without experiencing wheezing and gasping.
Considerations
Bronchitis and Exercise
Learn More
Shortness of breath due to age, lifestyle and physical condition is not unusual if that is the only symptom present. Symptoms such as chest pressure, pain or discomfort, wheezing in the absence of known diagnosis of asthma, breathing trouble that is severe or worsens with time, presence of a barking cough and tightness in the throat are all signals the need to be seen by a health care professional. If difficulty breathing occurs suddenly or you seem not to be getting enough air with your breaths, contact emergency services.
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tablet computer
Since tablets don’t have any keyboard, you should sort on digital keyboards that have various layouts and designs. 2-in-1 tablets come with a removable keyboard, however these models nonetheless fall wanting the laptop computer expertise because of their smaller size and more restrictive designs.
Windows 10
Processor – This is the chip that drives the tablet. A tablet with a quad-core processor will usually carry out better than a tablet with a twin-core processor.
This tablet features a 10.1-inch show, and is designed to be used as a cellular entertainment system. Google has stopped providing the Pixel C, its final Android-powered tablet/laptop computer. Its discontinuation marks an acknowledgment that there’s no interest in excessive-priced Android tablets. Increase your productivity within the area by adding an IP-sixty five rated full-measurement keyboard with customizable RGB backlight to your rugged tablet.
Small enough to slot in the hand however massive enough to display plenty of text at an honest size, tablets are meant to deliver the feeling of a guide or magazine to a pc. It usually signifies that it’s simple to tackle the go and travel with. In other eventualities, cellular might mean that, like many mobile units, the tablet is ready to have phone service, making it the identical as some other smartphone, besides a lot bigger.
• On the app aspect, the Microsoft store isn’t as wealthy as that of Android and iOS, nevertheless it adds to the compatibility the presence of assist for .exe programs, so we are able to set up any PC program that we all know.
• Archived from the original on January 9, 2017.
• “IDC releases Q2 tablet PC marketshare, Windows nonetheless trails iOS and Android”.
• According to a survey performed by the Online Publishers Association (OPA) now known as Digital Content Next (DCN) in March 2012, it discovered that 72% of tablet house owners had an iPad, whereas 32% had an Android tablet.
The battery within a laptop takes up a much smaller percentage of the house needed for its inner parts. Thus, even with the upper capacity battery offered by laptops, they don’t run as long as tablets. Many tablets can assist up to ten hours of internet usage before requiring a charge. In comparison, the common laptop only runs for about four to eight hours. Tablets rely solely on a touchscreen interface for enter, which might present challenges when you need to input text.
If you’re looking at iPads, all new iPads share the identical processor. Test to see how the tablet handles loading and closing apps, as well as switching in between open apps. Try out a graphically intensive sport (if one is on the market on the demo mannequin) to see how the tablet handles a high load.
The keyboard cowl additionally presents further screen safety and comes with a kickstand. Generally tablet computer systems have smaller screens than standard computer systems, which some individuals may find troublesome to use.
Lenovo Tab M7 Tablet (7-inch, 1gb, sixteen Gb, Wi-fi Only)
Not all apps are optimized for tablet use, however more and more are releasing tablet variations. Because of the low power necessities of their hardware parts, tablets are designed for effectivity. In reality, most of a tablet’s interior is taken up by the battery. Laptops, then again, use more powerful hardware.
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Single-Molecule Protein Identification by Sub-Nanopore Sensors
Link
Recent advances in top-down mass spectrometry enabled identification of intact proteins, but this technology still faces challenges. For example, top- down mass spectrometry suffers from a lack of sensitivity since the ion counts for a single fragmentation event are often low. In contrast, nanopore technology is exquisitely sensitive to single intact molecules, but it has only been successfully applied to DNA sequencing, so far. Here, we explore the potential of sub-nanopores for single-molecule protein identification (SMPI) and describe an algorithm for analyzing the electrical current blockade signal (nanospectrum) resulting from the translocation of a denaturated, linearly charged protein through a sub-nanopore. We further describe the first SMPI algorithm, compute the p-values of Protein-Nanospectrum Matches, and discuss the promise and computational limitations of the current SMPI technology.
Written by M. //
Web Statistics
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Brain Imaging and Behavior DOI 10.1007/s11682-013-9288-2
REVIEW ARTICLE
Diffusion tensor imaging and magnetic resonance spectroscopy in traumatic brain injury: a review of recent literature Kun-lin Xiong & Yong-shan Zhu & Wei-guo Zhang
# Springer Science+Business Media New York 2014
Abstract Concussion is the most common form of traumatic brain injury (TBI), but diagnosis remains controversial because the brain appears quite normal in conventional computed tomography and magnetic resonance imaging (MRI). These conventional tools are not sensitive enough to detect diffuse traumatic axonal injury, and cannot depict aberrations in mild TBIs. Advanced MRI modalities including diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS), make it possible to detect brain injuries in TBI. The purpose of this review is to provide the latest information regarding the visualization and quantification of important abnormalities in TBI and new insights into their clinical significance. Advanced imaging modalities allow the discovery of biomarkers of injury and the detection of changes in brain injury over time. Such tools will likely be used to evaluate treatment efficacy in research. Combining multiple imaging modalities would not only provide greater insight into the underlying physiological changes in TBI, but also improve diagnostic accuracy in predicting outcomes. In this review we present evidence of brain abnormalities in TBI based on investigations using MRI, including DTI and MRS. Our review provides a summary of some of the important studies published from 2002 to 2012 on the topic of MRI findings in head trauma. With the growing realization that even mild head injury can lead to neurocognitive deficits, medical imaging has assumed preeminence for detecting abnormalities associated with TBI. Advanced MRI modalities such as DTI and MRS have an important role in the diagnosis of lesions for TBI patients.
K.
Diffusion tensor imaging and magnetic resonance spectroscopy in traumatic brain injury: a review of recent literature.
Concussion is the most common form of traumatic brain injury (TBI), but diagnosis remains controversial because the brain appears quite normal in conv...
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FancyBox is a jQuery plugin which is used to open text, photos, etc as a modal dialog. The post explains how to integrate FancyBox with an ASP.NET MVC application.
Bundling
FancyBox is available as a Nuget package. The Nuget package has a stylesheet which it puts in the Content folder, associated images and sprites which it puts in the Content/FancyBox folder, and javascript which it puts in the Scripts folder.
To use FancyBox, include the styles as well as the scripts as follows:
The script can be bundled easily with the jQuery and bootstrap. This will reduce the number of round-trips to the server. However, the fancybox CSS should be bundled separately. This is because fancybox has associated images. There are some transforms which can be used to bundle the fancybox CSS along with other CSS. But, these techniques do not have adequate guidance from Microsoft. For more information on bundling FancyBox styles, please check the StackOverflow article.
Displaying text using FancyBox
FancyBox can be used to display text as modal dialog. The following HTML code snippet explains how to do this.
The div with fancy-text class be fancy-boxed. When the user clicks on the div, the div with ID moreInfo is shown as modal dialog. Clicking on the content will close the modal dialog. The javascript for fancy-boxing the div is shown below.
There are problems in iOS 8 when a div is made clickable. The iOS 8 browsers do not show the fancybox. To avoid the problem, use the onclick event handler as shown in the HTML code snippet to indicate that the div is clickable.
Slideshow of images using FancyBox
A set of images can be shown as a slideshow using FancyBox. The hyperlink should be marked with a rel attribute to denote that it is part of a gallery.
The above gallery can be fancy-boxed with the following Javascript code.
The cyclic attribute ensures that the gallery loops back to the beginning after the last photo is displayed. Some more adjustments need to be made to ensure that the navigation buttons stay visible. The default behavior of FancyBox is to allow the navigation button to become visible on hover. This does not work well on mobile devices. So, the navigation buttons should be made visible always.
There are two callback methods, onUpdate and afterClose, that needs to be handled to make the navigation buttons visible. onUpdate is fired when the window needs to be redrawn. afterClose is fired when the modal window is closed.
The .fancybox-nav class should be marked visible when the FancyBox is shown. The class should be marked hidden when the window is closed.
FancyBox integration with ASP.NET MVC application
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Medication Guide App
Technetium Tc 99m Teboroxime (Systemic)
VA CLASSIFICATION
Primary: DX201
Commonly used brand name(s): CardioTec.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).
Not commercially available in Canada.
Category:
Diagnostic aid, radioactive (cardiac disease)—
Indications
Accepted
Cardiac imaging, radionuclide
Myocardial infarction (diagnosis) and
Myocardial perfusion imaging, radionuclide—Technetium Tc 99m teboroxime is indicated in myocardial perfusion imaging to distinguish normal from abnormal myocardium in patients with suspected coronary artery disease (CAD) using rest and stress techniques. {01} {11} {12} {13} {14} {15} {19} {20} {21} {24} {25} {28} {29} {30} {31} {33}
Physical Properties
Nuclear data:
Radionuclide
(half-life)
Decay
constant
Mode
of
decay
Principal
photon
emissions
(keV)
Mean
number of
photons/
disintegration
(³0.01)
Tc 99m
(6.0 hr)
0.1151 h -1
Isomeric
transition to
Tc 99
Gamma
18
0.062
Gamma
140.5
0.891
Pharmacology/Pharmacokinetics
Mechanism of action/Effect:
The mechanisms for uptake and retention of technetium Tc 99m teboroxime by myocardial tissue are not well established. Unlike cationic thallous chloride Tl 201 and technetium Tc 99m sestamibi, technetium Tc 99m teboroxime has a neutral charge. Because of its neutral charge and high lipophilicity, the myocardial uptake of technetium Tc 99m teboroxime appears to occur by a passive diffusion process. The rate of passive uptake is determined by the membrane permeability of the drug, the surface area of the vascular beds to which it is exposed, the vascular and extravascular concentrations of the drug, and the rate of delivery of the drug. {38} While technetium Tc 99m teboroxime's mechanism of myocardial retention is less efficient than that of thallous chloride Tl 201 or technetium Tc 99m sestamibi, its myocardial extraction is higher. Its rapid myocardial washout allows early repeat studies following the application of a pharmacologic or physical intervention. {08} {09} {11} {12} {13} {16} {17} {23} {29} {30} {31}
Distribution:
Technetium Tc 99m teboroxime is rapidly cleared from blood after intravenous administration, with high myocardial extraction in proportion to myocardial perfusion even at extremely high flow rates. Myocardial uptake is apparent scintigraphically at 1 minute after injection. A significant amount of the initial myocardial activity is cleared by 20 to 30 minutes after administration. {01} {06} {07} {08} {10} {11} {16} {17} {30} {31} {33}
Liver uptake of technetium Tc 99m teboroxime becomes significant by 5 to 10 minutes after injection and has a slow clearance (half-life approximately 1.5 hours) that can impair visualization of the inferior left ventricular wall. {01} {06} {07} {08} {10} {17} {20} {28} {30} {31}
There is marked first-pass uptake of technetium Tc 99m teboroxime in the lungs with rapid subsequent clearance within the first 2 minutes after injection. This initial lung uptake may complicate first-pass radionuclide angiography image interpretation, since it results in lower ejection fractions, higher pulmonary transit times, higher calculated pulmonary blood volume indices, and poorer left ventricular border definition. {26} {38}
Protein binding:
Very low (<10%). {01} {23} {32}
Half-life:
Elimination (myocardium)—10 to 15 minutes. {08}
Note: A biexponential pattern of myocardial washout has been demonstrated in animals and man. About two-thirds of myocardial activity demonstrates an effective half-life of 5.2 minutes; the remaining one-third demonstrates an effective half-life of 3.8 hours. {10} {20} {24} {30} {38} At 10 minutes after injection, approximately 10.4±4.4% (mean) of the injected dose remains in the circulation. {01} {06} {07} {08} {10} {11} {16} {17} {30} {31} {33} {38}
Radiation dosimetry:
{01}{22}{38}
Mode of
administra-
tion
Estimated absorbed radiation dose*
Target organ
mGy/MBq
rad/mCi
Intravenous
Large intes-
tine, upper
0.033
0.12
Gallbladder wall
0.026
0.097
Large intestine,
lower
0.023
0.087
Small intestine
0.018
0.067
Liver
0.017
0.062
Ovaries
0.0098
0.036
Lungs
0.0076
0.028
Urinary bladder
wall
0.0074
0.027
Heart wall
0.0055
0.020
Kidneys
0.0055
0.020
Red marrow
0.0045
0.017
Spleen
0.0040
0.015
Brain
0.0034
0.012
Thyroid
0.0029
0.011
Testes
0.0028
0.010
Total body
0.0045
0.017
Effective dose: 0.013 mSv/MBq (0.048 rem/mCi) {17} {22}
* Assuming 6-hour gallbladder emptying; 2-hour urinary bladder void. {01} {22}
Elimination:
Hepatobiliary, mainly. Renal, 22±13% in 24 hours. {01} {02}
Precautions to Consider
Carcinogenicity
Long-term animal studies to evaluate carcinogenic potential of technetium Tc 99m teboroxime have not been performed. {33}
Mutagenicity
Decayed technetium Tc 99m teboroxime has not been shown to be mutagenic in a reversion test with bacteria, a chromosomal aberration assay, and an in vivo mouse micronucleus assay. {01} {33}
At high concentrations that were toxic to the cells and reduced growth to 33% or less relative to vehicle controls, technetium Tc 99m teboroxime was weakly positive for inducing forward mutations at the TK locus in L5178Y mouse lymphoma cells without metabolic activation. In the presence of metabolic activation, technetium Tc 99m teboroxime gave negative results in this assay. {01} {33}
Pregnancy/Reproduction
Pregnancy—
Tc 99m (as free pertechnetate) crosses the placenta. However, studies with technetium Tc 99m teboroxime have not been done in humans.
The possibility of pregnancy should be assessed in women of child-bearing potential. Clinical situations exist in which the benefit to the patient and fetus from information derived from radiopharmaceutical use outweighs the risks from fetal exposure to radiation. In these situations, the physician should use discretion and reduce the administered activity of the radiopharmaceutical to the lowest possible amount. {05}
Studies have not been done in animals. {01}
FDA Pregnancy Category C. {01} {33}
Breast-feeding
Although it is not known whether technetium Tc 99m teboroxime is distributed into breast milk, it is known that Tc 99m as free pertechnetate is distributed into breast milk. Because of the potential risk to the infant from radiation exposure, discontinuation of nursing for a period of 24 hours is recommended after administration of technetium Tc 99m–labeled radiopharmaceuticals. {01} {05}
Pediatrics
Although technetium Tc 99m teboroxime is used in children, there have been no specific studies evaluating safety and efficacy. When used in children, the diagnostic benefit should be judged to outweigh the potential risk of radiation. {01} {05}
Geriatrics
Appropriate studies on the relationship of age to the effects of technetium Tc 99m teboroxime have not been performed in the geriatric population. However, clinical trials and studies were conducted including older patients and geriatrics-specific problems that would limit the usefulness of this agent in the elderly are not expected. {02} {30}
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).
Risk-benefit should be considered when the following medical problem exists
Sensitivity to the radiopharmaceutical preparation
Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent or rare {01} {33}
Burning sensation at injection site
hypotension
metallic taste
nausea
numbness of hand and arm
swelling of face
Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Radiopharmaceuticals (Diagnostic).
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):
Description of use
Action in the body: Accumulation of radioactivity in myocardial cells as a function of relative blood flow
Differences in uptake of radioactivity can be visualized
Small amounts of radioactivity used in diagnosis; radiation dose received is relatively low and considered safe
Before having this test
» Conditions affecting use, especially:
Sensitivity to the radiopharmaceutical preparation
Pregnancy—Technetium Tc 99m (as free pertechnetate) crosses placenta; risk to fetus from radiation exposure as opposed to benefit derived from study should be considered
Breast-feeding—Not known if technetium Tc 99m teboroxime is distributed into breast milk, but Tc 99m as free pertechnetate is distributed into breast milk; temporary discontinuation of nursing is recommended to avoid any unnecessary absorbed radiation dose to the infant
Preparation for this test
Fasting for 4 to 8 hours before the stress/rest test
Other special preparatory instructions may also be given; patient should inquire in advance
General Dosing Information
Radiopharmaceuticals are to be administered only by or under the supervision of physicians who have had extensive training in the safe use and handling of radioactive materials and who are licensed by the Nuclear Regulatory Commission (NRC) or the appropriate Agreement State agency, if required, or, outside the U.S., the appropriate authority.
Fasting is usually recommended for 4 to 8 hours before the stress/rest test. {21} {38}
Technical factors such as tomographic reconstruction artifacts, patient movement, diaphragmatic attenuation, and breast attenuation in female patients may cause false-positive results (false perfusion defects). {16} {38}
In conjunction with exercise or pharmacologic vasodilatation stress testing, technetium Tc 99m teboroxime should be administered at the inception of a period of maximum stress that is continued for approximately 30 to 60 seconds after injection. {01} {11} {20} {31} {32} {38}
High liver extraction of technetium Tc 99m teboroxime may interfere with visualization of the inferior wall of the heart. Positioning the patient upright during image acquisition is helpful in minimizing the contribution of liver activity, since in the upright position the liver tends to drop downward, allowing better separation of the cardiac and hepatic activities. {11} {15} {20} {21}
For either rest or stress studies, imaging must begin within 2 to 5 minutes after injection of technetium Tc 99m teboroxime and must be completed within 5 to 10 minutes. After 5 minutes, differential washout of technetium Tc 99m teboroxime begins to introduce artifacts. If image acquisition takes too long, perfusion defects can become less apparent before acquisition is complete, resulting in an underestimation of the number and severity of ischemic segments. A significant amount of the initial myocardial activity is cleared by 20 to 30 minutes after administration. {01} {11} {30} {31} {38}
Rapid myocardial washout and early hepatic uptake necessitates use of rapid imaging protocols, and may require a multiple-headed single-photon emission computed tomography (SPECT) camera to complete image acquisition in 3 to 4 minutes. {10} {17} {28} {30} {38}
For studies performed in conjunction with pharmacologic stress testing
Pharmacologic stress, induced by intravenous adenosine or dipyridamole, may be preferred for stress/rest studies using technetium Tc 99m teboroxime since the patient can be infused while in position under the camera, thus eliminating delays between tracer injection and the start of image acquisition. {28} {30}
Technetium Tc 99m teboroxime is usually administered during the third minute of the 4- to 5-minute infusion of adenosine, or 2 minutes after the 4-minute dipyridamole infusion. {24} {29} {30}
Safety considerations for handling this radiopharmaceutical
Improper handling of this radiopharmaceutical may cause radioactive contamination. Guidelines for handling radioactive material have been prepared by scientific, professional, state, federal, and international bodies and are available to the specially qualified and authorized users who have access to radiopharmaceuticals. {18}
Parenteral Dosage Forms
TECHNETIUM Tc 99m TEBOROXIME INJECTION
Usual adult and adolescent administered activity
Cardiac imaging
Intravenous, 555 to 1110 megabecquerels (15 to 30 millicuries). {01}
Note: Due to the short residence time of technetium Tc 99m teboroxime in the myocardium, two separate injections are needed for a stress/rest perfusion study. {11}
When a stress study is to be performed prior to a rest study, it is recommended that an interval of 11/2 hours be allowed for the effects of exercise to dissipate. {01} {11} {12}
For same-day rest/stress studies, a combined dose of 1295 to 1850 megabecquerels (35 to 50 millicuries) is used. {01}
When a rest study is to be performed prior to a stress study, it is only necessary to wait until the residual myocardial activity clears. In most cases, the stress study may be performed in one hour. {01} {11}
Usual pediatric administered activity
Minimum dosage has not been established. {05}
Usual geriatric administered activity
See Usual adult and adolescent administered activity .
Strength(s) usually available
U.S.—
2 mg of cyclohexanedione dioxime, 2 mg of methyl boronic acid, 2 mg pentetic acid, 9 mg citric acid (anhydrous), 100 mg sodium chloride, 50 mg gamma cyclodextrin, and 50 mcg stannous chloride (anhydrous) in lyophilized form under nitrogen atmosphere, per 5-mL reaction vial (Rx) [CardioTec]
Note: Technetium Tc 99m teboroxime is a boronic acid technetium dioxime (BATO) derivative. {01} {08} {10} {11} {12}
Canada—
Not commercially available. {03}
Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from freezing. {01}
Note: Before radiolabeling, the kit is also stored at room temperature. {01}
Preparation of dosage form:
To prepare technetium Tc 99m teboroxime injection, an oxidant-free sodium pertechnetate Tc 99m solution is used.
During reconstitution, it is important that air is not added to the nitrogen atmosphere of the vial, since air will cause oxidation, thus decreasing the radiochemical purity of the compound. {11}
See manufacturer's package insert for complete instructions. {01}
Stability:
Product is stable (24-month shelf life before radiolabeling); U.S. package insert states that injection should be administered within 6 hours after preparation since it does not contain a preservative. {01} {05} {07} {31}
Incompatibilities:
If oxidants such as peroxides and hypochlorites are present in the sodium pertechnetate Tc 99m used for labeling, the final preparation may be adversely affected and should be discarded. Final preparation should appear clear to slightly opalescent and free of particulate matter and discoloration. {01} {10}
Note: Caution—Radioactive material.
Revised: 05/18/1995
References
1. CardioTec package insert (Squibb—US), Rev 12/90.
1. Squibb presentation at FDA on 11/17/90.
1. Personal communication, Canada Squibb Diagnostics 8/91.
1. Reviewers' comments on Technetium Tc 99m Sestamibi monograph.
1. Radiopharmaceuticals Advisory Panel meeting, 05/08/91.
1. Berman DS. Introduction—Technetium 99m myocardial perfusion imaging agents and their relation to thallium-201. Am J Cardiol 1990; 66(13): 1E-4E.
1. Meerdink DJ, Leppo JA. Experimental studies of the physiologic properties of technetium-99m agents: myocardial transport of perfusion imaging agents. Am J Cardiol 1990; 66(13): 9E-15E.
1. Berman DS, Kiat H, Van Train KF, et al. Comparison of SPECT using technetium-99m agents and thallium-201 and PET for the assessment of myocardial perfusion and viability. Am J Cardiol 1990; 66(13): 72E-79E.
1. Stewart RE, Chiao PC, Roger WL, et al. Assessment of myocardial blood flow by SPECT based on clearance kinetics of the new technetium labeled flow tracer SQ30217 [abstract]. Circulation 1989; 80: 618.
1. Johnson LL, Seldin DW. Clinical experience with technetium-99m teboroxime, a neutral, lipophilic myocardial perfusion imaging agent. Am J Cardiol 1990; 66: 63E-67E.
1. McSherry BA. Technetium-99m-Teboroxime: a new agent for myocardial perfusion imaging. J Nucl Med Technol 1991; 19(1): 22-6.
1. Seldin DW, Johnson LL, Blood DK, et al. Myocardial perfusion imaging with technetium-99m SQ30217: comparison with thallium-201 and coronary anatomy. J Nucl Med 1989: 30(3): 312-9.
1. Stewart RE, Schwaiger M, Hutchins GD, et al. Myocardial clearance kinetics of technetium-99m-SQ30217: a marker of regional myocardial blood flow. J Nucl Med 1990; 31(7): 1183-90.
1. Li Q-S, Solot G, Frank TL, et al. Tomographic myocardial perfusion imaging with technetium-99m-teboroxime at rest and after dipyridamole. J Nucl Med 1991; 32(10): 1968-76.
1. Hendel RC, McSherry B, Karimeddini M, et al. Diagnostic value of a new myocardial perfusion agent, teboroxime (SQ30217), utilizing a rapid planar imaging protocol: preliminary results. J Am Coll Cardiol 1990; 16(6): 855-61.
1. Marshall RC, Leidholdt EM Jr, Zhang D-Y, et al. The effect of flow on technetium-99m-teboroxime (SQ30217) and thallium-201 extraction and retention in rabbit heart. J Nucl Med 1991; 32(10): 1979-88.
1. Reviewer's comment, 09/91.
1. Reviewers' responses to Ballot of 5/11/94.
1. Stewart RE, Heyl B, O'Rourke RA, et al. Demonstration of differential post-stenotic myocardial technetium-99m-teboroxime clearance kinetics after experimental ischemia and hyperemic stress. J Nucl Med 1991; 32(10): 2000-8.
1. Iskandrian AS, Heo J, Nguyen T, et al. Myocardial imaging with Tc 99m teboroxime: technique and initial results. Am Heart J 1991; 121(3): 889-94.
1. Fleming RM, Kirkeeide RL, Taegtmeyer H, et al. Comparison of technetium-99m teboroxime tomography with automated quantitative coronary arteriography and thallium-201 tomographic imaging. J Am Coll Cardiol 1991; 17: 1297-302.
1. Narra RK, Feld T, Nunn AD. Absorbed radiation dose to humans from technetium-99m-teboroxime. J Nucl Med 1992; 33(1): 88-93.
1. Rumsey WL, Rosenpire KC, Nunn AD. Myocardial extraction of teboroxime: effects of teboroxime interaction with blood. J Nucl Med 1992; 33(1): 94-101.
1. Labonté C, Taillefer T, Lambert R, et al. Comparison between technetium-99m-teboroxime and thallium-201 dipyridamole planar myocardial perfusion imaging in detection of coronary artery disease. Am J Cardiol 1992; 69: 90-6.
1. Dahlberg ST, Weinstein H, Hendel RC, et al. Planar myocardial perfusion imaging with technetium-99m-teboroxime: comparison by vascular territory with thallium-201 and coronary angiography. J Nucl Med 1992; 33(10): 1783-88.
1. Williams KA, Taillon LA, Draho JM, et al. First-pass radionuclide angiographic studies of left ventricular function with technetium-99m-teboroxime, technetium-99m-sestamibi and technetium-99m-DTPA. J Nucl Med 1993; 34(3): 394-9.
1. Chua T, Kiat H, Germano G, et al. Rapid back to back adenosine stress/rest technetium-99m teboroxime myocardial perfusion SPECT using a triple-detector camera. J Nucl Med 1993; 34: 1485-93.
1. Chua T, Kiat H, Germano G, et al. Technetium-99m teboroxime regional myocardial washout in subjects with and without coronary artery disease. Am J Cardiol 1993; 72: 728-34.
1. Henzlova MJ, Machac J. Clinical utility of technetium-99m-teboroxime myocardial washout imaging. J Nucl Med 1994; 35: 575-9.
1. Johnson LL. Myocardial perfusion imaging with technetium-99m-teboroxime. J Nucl Med 1994; 35(4): 689-92.
1. Bisi G, Sciagra R, Santoro GM, et al. Sublingual isosorbide dinitrate to improve technetium-99m-teboroxime perfusion defect reversibility. J Nucl Med 1994; 35(8): 1274-8.
1. CardioTec package insert (Squibb—US), Rev 1/91.
1. Hockings B, Saltissi S, Croft DN, et al. Effect of beta adrenergic blockade of thallium-201 myocardial perfusion images. Br Heart J 1983; 49: 83-9.
1. Ponto JA, Holmes KA. Discontinuation of beta blockers before exercise radionuclide ventriculograms. J Nucl Med 1982; 23: 456-7.
1. Osbakken MD, Okada RD, Boucher CA, et al. The effect of Inderal, exercise level, and subcritical disease on the specificity of exercise thallium-201 imaging. J Nucl Med 1981; 22: 41.
1. Wolf R, Pretschner P, Engel HJ, et al. Effect of isosorbide dinitrate on 201-thallium myocardial imaging in coronary heart disease. Am J Cardiol 1979; 43: 432.
1. Reviewer's comment, 10/18/94.
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Fernanda Dias
Fernanda Dias
Associate Professor
Plant Protein Innovation Center (PPIC)
Dr. Fernanda Dias is an Assistant Professor of Analytical and Food Chemistry at the Department of Food Science and Nutrition, University of Minnesota. Dr. Dias obtained her Ph.D. in Food Science and postdoctoral training in Analytical Chemistry from the University of Campinas, Brazil. She also was a postdoctoral scholar in Food Science at the University of California, Davis (UC-Davis). Her research focuses on the use of lipidomic approaches to investigate the chemical transformations of foods as a function of lipid oxidation and the effects of processing and storage on markers of oil quality. Her research seeks to shed new light on how processing and storage affect the formation of oxidized lipid products and the formation of off-flavor in foods. The overall goal of her research is the use of analytical techniques and chemometrics tools to guide the development of environmentally friendly strategies to produce the next generation of health-promoting food ingredients.
Presentation Description
Due to the increasing world population and consumer desire for sustainable and nutritious protein sources, the food industry is currently experiencing tremendous pressure to develop innovative, sensorially acceptable, health-promoting plant-based products. However, increasing plant protein utilization is challenged by its intrinsic off-flavor that limits consumer acceptance. Since sensory perception plays a major role in consumer acceptance and eating habits, the development of new process strategies to remove and or reduce off-flavor in plant protein products is imperative to enhance its consumption and use. In this presentation, we will delve into the intricacies of flavor and off-flavor development in plant proteins, while also exploring effective strategies to address and mitigate these challenges.
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Heart disease this occurs due to changes in the large blood vessels leading to coronary, cerebral, and peripheral artery diseases, atherosclerosis, dyslipidemia etc.
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A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
MIE SCATTERING
DOI: 10.1615/AtoZ.m.mie_scattering
The Mie theory is a theory of absorption and scattering of plane electromagnetic waves by uniform isotropic particles of the simplest form (sphere, infinite cylinder) which are in a uniform, isotropic dielectric infinite medium. Though the initial assumptions of the Mie theory are idealized its results are widely used when solving problems of radiation heat transfer in light scattering media.
The basic aim of the theory is the calculation of efficiency coefficients (factors) for absorption (Qa), scattering (Qs) and extinction (Qe), The ratio of σi, the cross-section for the appropriate process, to the particle protected area,
defines the efficiency coefficients (factors) Qi, where r is the particle radius. The cross section σi is the ratio of the energy flux absorbed, scattered or (in sum) extinguished by a particle to the incident energy flux density (i.e., to the energy of undisturbed electromagnetic waves per unit area oriented normally to the wave front). The cross section is of area dimension while the efficiency coefficients factors are dimensionless.
According to the definition of extinction
(1)
The mathematics of the Mie theory for application to interaction with a spherical object can be divided into the following steps:
1. Introduction of the spherical coordinate system with the particle center as an origin.
2. Plane electromagnetic wave expansion in vector spherical functions.
3. Expansions of a spherical electromagnetic field and field inside the particle in spherical vector functions.
4. Determination of the coefficients of function expansions into series in vector functions: the coefficients are obtained for the field inside a particle and for the scattering field being solved.
5. The coefficients of scattering Qs and attenuation efficiencies Qe, are calculated by integrating the Pointing vector (expressed in terms of the electric and magnetic field expansions) with respect to angle and space variables.
In Bohren and Huffman (1983), Deirmendjian (1969) and Van de Hulst (1957) the detailed procedure is given to obtain the resulting relations of the Mie theory. The relations for scattering and extinction are of the form
(2)
(3)
where x = 2πr/λ is the diffraction parameter, Re is the real part of the sum of the complex numbers:
(4)
(5)
aj, bj are the expansion coefficients (the Mie coefficients) expressed in terrns of the Riccatty-Bessel functions Ψj(t) and ξi(t) which are expressed in terms of the Bessel functions of noninteger order
(6)
(7)
the stroke in Eqs. (4) and (5) means the differentiation with respect to an argument, ml = n1,λ + in2,λ is the complex refractive index of a particle material in the surrounding medium, n1,λ is the refractive index, n2,λ is the absorption index associated with the spectral absorption coefficient by the relative κλ = 4πn1,λ/λ.
The coefficient of absorption efficiency is determined after finding Qe and Qs with (1) taken into account. The dependence of Qe on x for water drops is given in Figure 1. For particle radii commensurable with a wave length (r = 1 μm) the typical spectral peculiarities are manifested, namely, the interference structure (large scale oscillations), ripple (irregular fine structure), and the weak spectral dependence region.
Extinction efficiency (Qe) as a function of diffraction parameter x (= 2πr/λ).
Figure 1. Extinction efficiency (Qe) as a function of diffraction parameter x (= 2πr/λ).
The Mie series (2), (3) are poorly converging series, especially for diffraction parameter x > 20. Numerous investigations are devoted to this problem which resulted in effective computational algorithms using formulas of direct and inverse recursion (the expression of the series subsequent terms in terms of the preceding ones) as well as computational programs [Bohren and Huffman (1983)].
Since the problem is azimuthally symmetrical the phase function pgl, according to Mie theory depends on the latitude angle θ between the scattering direction and that of undisturbed wave front propagation. The averaged cosine of a scattering angle
(where μ = cos θ) characterized the elongation degree of the phase function and is determined using the Mie coefficient
(9)
Here * means the complex conjugate quantity.
For small values of diffraction parameter, x << 1, one can retain just the first summands of the Mie series which corresponds to the Rayleigh law for scattering by particles the size of which are essentially less than the radiation wavelength. For large x ≥ 20 the efficiency coefficients are found from geometrical optics. The intermediate region for the diffraction parameter variation is called the "Mie scattering region."
The polarization characteristics of scattered radiation are rarely taken into account in the radiation heat transfer theory. However, if necessary they can be computed according to the Mie theory [Bohren and Huffman (1983)].
Volume spectral absorption coefficients involved in the radiation transfer equation are determined by formulas
(10)
where N0 is the total number of particles in unit volume, N(r) is the particle distribution (along the radius) function. For a monodisperse system of particles (of radius r0):
REFERENCES
Bohren, C, F. and Huffman, D. R. (1983) Absorption and Scattering of Light by Small Particles. A Wiley Interscience Publication, John Wiley & Sons, Inc.
Deirmendjian, D. (1969) Electromagnetic Scattering on Spherical Polydispersions, Elsevier, New York.
Van de Hulst, H. C. (1957) Light Scattering by Small Particles, Wiley, New York.
References
1. Bohren, C, F. and Huffman, D. R. (1983) Absorption and Scattering of Light by Small Particles. A Wiley Interscience Publication, John Wiley & Sons, Inc.
2. Deirmendjian, D. (1969) Electromagnetic Scattering on Spherical Polydispersions, Elsevier, New York.
3. Van de Hulst, H. C. (1957) Light Scattering by Small Particles, Wiley, New York.
Number of views: 62472 Article added: 2 February 2011 Article last modified: 14 February 2011 © Copyright 2010-2020 Back to top
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MK Microbio
Immunology (PREMATRIC)
QuestionAnswer
Immune System Function 1. Provide surveillance and defense against foreign substances. 2. Help maintain fluid balance.
Lymphatic System a network of vessels and organs where the cells of the immune system reside. -fluid balance -immune cell development -sites of interaction btw immune cells and foreign substances
Lymphatic vessels collect fluid and lymphocytes from tissues and return them to the blood. (cells can enter directly thru afferent lymphatic vessels, or migrate thru cardiovascular system).
Immune tissues and organs 1. Primary (development) 2. Secondary (trapping and activation) -diffuse lymphatic tissue -lymphatic nodules -lymph nodes -spleen (T-cells: from Thymus; B-cells: from red Bone marrow)
3 Step response to microbial encounter 1. barriers: physical, chemical, biological 2. innate immunity (0-96 hours) 3. adaptive immunity ( >96 hours )
Innate Immunity -phagocytosis -complement (small proteins that help the ability of antibodies & phagocytic cells; can be recruited by adaptive immune system.) -inflammation -cytokine release -NK (Natural killer cells) cell killing
Barriers to Infection Protection at external and internal body surfaces
Respiratory Tract Barriers -nose hairs -mucous -cilia -microcidal molecules
Gastrointestinal Tract Barriers -pH -Mucus -Microcidal molecules (antiseptic) -commensal microbes (live on skin, protection from infection)
Skin Barriers -RNases, DNases -Microcidal molecules -fatty acids -commensal microbes (secrete antimicrobial agent) (slightly acidic, cells slough off)
Urogenital Tract Barriers -pH -Mucous -Microcidal molecules -Fluid pressure
The Innate Immune System (4 main properties) 1. immediate 2. non-specific 3. not enhanced upon repeat exposure 4. helps induce adaptive response
Innate Immunity - Phagocytosis cellular process of engulfing solid particles by the cell membrane.
Innate immunity - Macrophage fuctions: 1. phagocytosis 2. cytokine secretion (activate inflammatory system) 3. antigen presentation
Innate immunity - Neutrophil 1. phagocytosis 2. granular release of antibacterial compounds
4 hallmarks of Inflammation 1. rubor (redness) 2. calor (heat) 3. dolor (pain) 4. tumor (swelling)
Inflammation -increased blood flow: to dilate potentially toxic agents -increased capillary permeability: to help transfer larger molecules across endothelium -increased migration of cells into tissues: to destroy bacteria, remove debris, restore norm tissue structu
Purpose of inflammation sequential recruitment of cells (bringing more immune cells and blood into the area of pathogen so they can eliminate the infection) 1. neutrophils - principle inflammatory cell 2. monocytes, macrophages 3. lymphocytes
2 phases of inflammation 1. acute (0-72 hours) 2. chronic (ex: autoimmune diseases, arthritis)
Adaptive (acquired) Immunity -requires several days to develop -response is SPECIFIC - recognizes features unique to each microbe -carried out by B-lymphocytes (antibodies), T-lymphocytes (cytokines), and APC's (antigen presenting cells). -provides long-lasting immunity
The Humoral Immune Response (HIR) adaptive immunity - mediated by secreted antibodies produced in the cells of the B lymphocyte lineage (B cells)
Cell-mediated immunity adaptive immune response that involves the activation of macrophages, natural killer cells (NK), antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen. (T cells)
Clonal selection hyphothesis (4 tenants of adaptive immunity) (Tenant #1) 1. each lymphocyte bears a single type of receptor with a unique specificity.
Clonal selection hyphothesis (4 tenants of adaptive immunity) (Tenant #2) 2. interaction between a foreign molecule & lymphocyte receptor capable of binding that mol with high affinity leads to lymphocyte activation.
Clonal selection hyphothesis (4 tenants of adaptive immunity) (Tenant #3) 3. the differentiated effector cells derived from an activated lymphocyte will bear receptors of identical specificity to those of the parental cell from which that lymphocyte was derived (memory)
Clonal selection hyphothesis (4 tenants of adaptive immunity) (Tenant #4) 4. lymphocytes bearing receptors specific for ubiquitious self molecules are deleted at an early stage in lymphoid cell development and are therefore absent from the repertoire of mature lymphocytes (recognizes self vs. non-self)
Cytotoxic T-cells (CD8+) -Each T-cell is specific for a unique antigen fragment -T-cells recognize antigen via their T-cell receptor (TCR) -once activated, go out into body and find any other of the same cells that activated them, and destroys them.
CD8+ T-cell activation CD8+ T-cells become activated when their TCR interacts w/ antigen/MHC I (major histocompatibility structures: secrete antigens) -activated CD8+ T-cells directly kill target cells
T-cell receptors (TCR) -has to recognize an antigen that is associated with MHCs (either I or II). -they are specific receptors (because they are leukocytes). -Structure is same for both CD8+ & CD4+ T-cells.
Rule of 8 CD8+ --> MHC I (8*1=8) CD4+ --> MHC II (4*2=8)
Helper T-cells (CD4+) -become activated when their TCR interacts with antigen/MHC II -MHC II is expressed on a subset of cells known as Antigen Presenting Cells (APC's)
CD4+ cell activation activated CD4+ cells secrete cytokines -help activate CD8+ cells -help activate B-cells -activate macrophages and NK cells
Antigen Presenting Cells (APC's) is a cell that displays foreign antigen complexes with major histocompatibility complex (MHC) on their surfaces. T-cells may recognize these complexes using their T-cell receptors (TCRs). These cells process antigens and present them to T-cells.
Three types of APC's 1. Macrophages 2. Dendritic cells 3. B-cells
T-cell receptor (TCR) structure -monovalent -interchain disulfide bonds -intrachain disulfide bonds -amino-terminal variable and c-terminal constant domains -carbohydrate attachment (alpha is light, beta is heavy)
TCR variable domains - V-region (variable region) - Hypervariable: site of contact (3 regions that contact the antigen; 3 from alpha, 3 from beta) -CDR (complementary determining region): determines specificity
Antigen Binding site is formed by the combination of CDRs from the alpha and beta chains
Complementary determining region(CDRs) determine specificity for specific antigens. The CDRs are the most variable part of the molecule, and contribute to the diversity of these molecules, allowing the antibody and the T cell receptor to recognize a vast repertoire of antigens.
How does the TCR recognize an antigen? -Helper T-cells (CD4): antigen binds with MHC II complex on APC. -Cytotoxic T-cells (CD8): antigen binds with MHC I complex on target cell. (TCR binding with antigen/MHC thru non-covalent interactions)
B-Cells -recognize native antigen via their B-cell receptor --> antibody (antibody can recognize free-floating, native antigen - doesn't need to be processed)
Antigen a substance/molecule that, when introduced into the body, triggers the production of an antibody by the immune system, which will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader.
B-cell activation activated when their antibody binds antigen AND they receive interactions/signals from CD4+ T-cells
Antibody aka: immunoglobulin: large, Y-shaped protein used by immune system to identify and neutralize foreign objects (such as bacteria/viruses) by recognizing it's antigen. Antibodies are produced by plasma cells.
Antibody structure -2 heavy chains (which are identical to each other) -2 light chains (which are also identical to each other) -hinge region -domains
Antibody function -bind foreign antigen -initiate its destruction
Antibody Isotypes -same structure (2 light/2heavy chains) (GAMED) 1. IgM 2. IgD 3. IgG 4. IgA 5. IgE (all have same capacity to bind the same antigen, but the heavy chain allows them to perform to specific functions)
Created by: Kanarema
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Equilibrium of Concurrent Forces
Concurrent Forces
Equilibrium of a body is a state in which all the forces acting on the body are balanced (cancelled out), and the net force acting on the body is zero. The state of equilibrium is a very important concept to learn in physics. If the net resultant force acting on a body is zero, it means that the net acceleration of the body is also zero (from the second law of motion).
Types of equilibrium of concurrent forces:
Generally, there are two types of equilibrium:
• 1) Static equilibrium: This is the type of equilibrium in which the resultant of all the forces acting on the body is zero, i.e. the net acceleration of the body is zero, and the velocity of the body is also zero. It means that the body is at rest. So if a body is at rest and the net acceleration of it is zero, it means the body is in static equilibrium.
Suppose a block is resting on a floor and two forces of 5 N each are acting on it from either side. The forces would cancel each other out and hence the net force on the block would be zero. Since the block is at rest, it will be in static equilibrium.
• 2) Dynamic equilibrium: This is the type of equilibrium in which the resultant of all the forces acting on the body is zero, i.e. the net acceleration of the body is zero, but the velocity of the body is not zero. It means that the body is moving with a constant velocity. So if the net force acting on the body is zero, and it is still moving with some constant velocity, the body is said to be in dynamic equilibrium.
A block attached to a spring under the influence of Simple Harmonic Motion (S.H.M.) is a common example of dynamic equilibrium. At the mean position, the net force acting on the block is zero but the velocity of the block is maximum, which means that the block is in dynamic equilibrium at that point.
Stay tuned with BYJU’S for more such interesting articles. Also, register to “BYJU’S – The Learning App” for loads of interactive, engaging Physics-related videos and an unlimited academic assist.
Frequently Asked Questions – FAQs
Q1
What is static equilibrium?
This is the type of equilibrium in which the resultant of all the forces acting on the body is zero, i.e. the net acceleration of the body is zero, and the velocity of the body is also zero. It means that the body is at rest. So if a body is at rest and the net acceleration of it is zero, it means the body is in static equilibrium.
Q2
What is dynamic equilibrium?
This is the type of equilibrium in which the resultant of all the forces acting on the body is zero, i.e. the net acceleration of the body is zero, but the velocity of the body is not zero. It means that the body is moving with a constant velocity. So if the net force acting on the body is zero, and it is still moving with some constant velocity, the body is said to be in dynamic equilibrium.
Q3
Define equilibrium.
Equilibrium is a state of the body where neither the internal energy nor the motion of the body changes with respect to time.
Q4
What are the types of force?
Force is a physical cause that can change the state of motion or the dimensions of an object. There are two types of forces based on their applications:
Contact Force
Non-Contact Force
Q5
Define the line of action of a force.
The line along which a force is acting on an object is called the line of action of the force. The point where the force is acting on an object is called the point of application of the force.
Test your knowledge on Concurrent forces
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Examples - Amazon Redshift
AWS 文档中描述的 AWS 服务或功能可能因区域而异。要查看适用于中国区域的差异，请参阅中国的 AWS 服务入门
本文属于机器翻译版本。若本译文内容与英语原文存在差异，则一律以英文原文为准。
Examples
以下示例从 GUESTS 用户组撤消对 SALES 表的 INSERT 权限。此命令使 GUESTS 的成员无法通过使用 INSERT 命令将数据加载到 SALES 表中。
revoke insert on table sales from group guests;
以下示例从用户 撤消对 QA_TICKIT 架构中所有表的 SELECT 权限。fred.
revoke select on all tables in schema qa_tickit from fred;
以下示例撤消用户 从视图中选择的权限。bobr.
revoke select on table eventview from bobr;
以下示例从所有用户撤消在 TICKIT 数据库中创建临时表的权限。
revoke temporary on database tickit from public;
以下示例从用户 cust_name 撤消对 cust_phone 表的 cust_profileuser1. 列的 SELECT 权限。
revoke select(cust_name, cust_phone) on cust_profile from user1;
以下示例从 cust_name 组中撤消对 cust_phonecust_contact_preference 列的 SELECT 权限，并撤消对 cust_profile 表的 sales_group 列的 UPDATE 权限。
revoke select(cust_name, cust_phone), update(cust_contact_preference) on cust_profile from group sales_group;
下面的示例演示如何使用 ALL 关键字从 cust_profile 组撤消对 sales_admin 表的三列的 SELECT 和 UPDATE 权限。
revoke ALL(cust_name, cust_phone,cust_contact_preference) on cust_profile from group sales_admin;
以下示例从 cust_name 用户撤消对 cust_profile_vw 视图的 user2 列的 SELECT 权限。
revoke select(cust_name) on cust_profile_vw from user2;
撤消数据共享的 USAGE 权限的示例
这是 Amazon Redshift 数据共享功能的预发布文档，目前为预览版。文档和功能均可能随时更改。我们建议您只在测试集群中使用此功能，而不要在生产环境中使用。有关预览版条款和条件，请参阅 AWS 服务条款中的 Beta 服务参与。将有关此功能的反馈发送至 redshift-datasharing@amazon.com。
以下示例撤消对 Marketing 命名空间SalesShare的数据共享的访问权限。
REVOKE USAGE ON DATASHARE SalesShare FROM NAMESPACE 'f5a0b31c-f2c7-45d6-ba3e-0d53ad027e8b';
以下示例将 上的 USAGE 权限撤销Sales_db给 Bob。
REVOKE USAGE ON DATABASE Sales_db FROM Bob;
以下示例 REVOKE USAGE 对 Sales_schema 的 权限Analyst_group
REVOKE USAGE ON SCHEMA Sales_schema FROM GROUP Analyst_group;
撤消 SUSEROLE 权限的示例
以下是撤消 ASSUMERROLE 权限的示例。
允许使用 SUSEROLE 权限
超级用户必须对集群运行以下语句一次，以便为用户和组启用 ASSUSEROLE 权限：
revoke assumerole on all from public for all;
从用户撤消 ASSUMEROLE 权限
以下语句撤消用户 reg_user1 针对所有 操作的所有角色的 ASSUMEROLE 权限。
revoke assumerole on all from reg_user1 for all;
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PDA
View Full Version : Preferred Web browser for linux
25-11-2001, 07:48 PM
Hi,
Is it possible to set a particular web browser as the default under linux? For example I have a link to this site on my desktop, but it opens under konqueror, which doesn't display it properly. I tried opening the URL with 'open with', and set it to remember to use this program with this file, but it used konqueror again the next time I tried it. I don't seem to be able to uninstall konqueror, and I want to use mozilla instead.
Thx in advance:)
26-11-2001, 02:50 PM
When you logout of KDE, does it have a box like 'save current setup' to click on in the 'are you sure' panel? That's what Gnome has. I ran into exactly that problem last night too: I was wanting to use the Adobe reader rather than xpdf for PDF files. Linux people seem to let you set up things for one session, without forcing you to have it that way forever. If you want to make changes permanent, you're expected to tell it that.
26-11-2001, 05:14 PM
Just come across a libarary book with a picture of a KDE control panel window: If you used the 'Default' button, rather than the 'OK' button, it would have set its default; not made your choice the default. The 'Apply' button would do it for now, but not save the setting. (Gnome has 'Revert', 'Try', and 'OK').
Keep at it Erin, it gets easier all the time.
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Maximizing Muscle Gains with Hamstring Training
November 12, 2023 3 min read
Maximizing Muscle Gains with Hamstring Training
Introduction to Hamstring Training
The hamstring muscles are one of the most important muscle groups for athletes and fitness enthusiasts alike. They are responsible for providing stability and power to movements such as running, jumping, and walking. Strong hamstrings also help improve balance and posture. Training your hamstrings is essential for optimal athletic performance and for reducing the risk of injury.
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Hamstring training can be intimidating for beginners, especially if they don’t understand where this group of muscles is located or what kind of exercises can effectively train them. To maximize muscle gains with hamstring training, it’s important to understand the anatomy of the hamstrings, which exercises target the hamstrings, and how to properly perform these exercises.
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Anatomy of the Hamstrings
The hamstrings are a group of three muscles located at the back of the upper leg. They are the biceps femoris, semitendinosus, and semimembranosus. These muscles are responsible for bending the knees and extending the hip when in motion. The hamstrings also play an important role in stabilizing the knee joint.
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When it comes to hamstring training, it’s important to understand the different parts of the hamstring and which exercises target each part. The biceps femoris is the outermost muscle and is responsible for knee flexion. It is targeted by exercises such as Romanian deadlifts, lying leg curls, and single-leg Romanian deadlifts. The semitendinosus is the middle muscle and is responsible for knee flexion and hip extension. Exercises such as glute bridges, hip thrusts, and reverse lunges target the semitendinosus.
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The semimembranosus is the innermost muscle and is responsible for knee flexion and hip extension. Exercises such as straight-leg deadlifts, kettlebell swings, and split squats target the semimembranosus.
Proper Form for Hamstring Exercises
Proper form is essential for hamstring training. When performing hamstring exercises, it’s important to keep your spine neutral and avoid excessive arching of the lower back. You should also remember to keep your core engaged and your chest up throughout the exercise.
When performing exercises such as Romanian deadlifts, it’s important to keep your shoulders back and down and your arms straight. During the eccentric portion, you should focus on pushing your hips back and keeping your back flat. During the concentric portion, you should focus on driving your hips forward and squeezing your glutes at the top of the movement.
For exercises such as glute bridges and hip thrusts, it’s important to keep your core tight and your shoulders pressed into the floor. You should also focus on driving through your heels and squeezing your glutes at the top of the movement.
For exercises such as split squats, it’s important to keep your chest up and your core engaged. You should also focus on dropping your back knee towards the floor and driving through your front heel to stand up.
Tips for Maximizing Muscle Gains with Hamstring Training
Once you understand the anatomy of the hamstrings and how to properly perform hamstring exercises, there are several tips you can follow to maximize muscle gains with hamstring training.
First, it’s important to incorporate a variety of exercises into your routine. This will ensure that all parts of the hamstrings are being targeted and challenged. Second, make sure to use an appropriate weight. Too light of a weight won’t challenge the muscles enough, while too heavy of a weight can lead to improper form and possible injury. Third, focus on the eccentric phase of the exercise. The eccentric phase is when the muscle is lengthening under tension, and focusing on this phase can lead to greater gains in strength and size.
Fourth, make sure to rest between sets. Rest allows your muscles to recover and rebuild, so it’s important to give yourself enough time to rest before moving onto the next set. Lastly, it’s important to pay attention to your nutrition. Eating a balanced diet and getting enough protein will ensure that your muscles have the necessary nutrients to repair and grow.
Hamstring training is an essential component of any fitness program. By understanding the anatomy of the hamstrings, which exercises target the hamstrings, and how to properly perform these exercises, you can maximize your muscle gains and reduce the risk of injury. Incorporating a variety of exercises, using an appropriate weight, focusing on the eccentric phase, resting between sets, and paying attention to nutrition are all key elements to optimizing your hamstring training.
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configure
Created Diff never expires
#! /bin/sh
#! /bin/sh
# Guess values for system-dependent variables and create Makefiles.
# Guess values for system-dependent variables and create Makefiles.
# Generated by GNU Autoconf 2.69 for Bitcoin Core 21.99.0.
# Generated by GNU Autoconf 2.69 for Bitcoin Core 21.99.0.
#
#
# Report bugs to <https://github.com/bitcoin/bitcoin/issues>.
# Report bugs to <https://github.com/bitcoin/bitcoin/issues>.
#
#
#
#
# Copyright (C) 1992-1996, 1998-2012 Free Software Foundation, Inc.
# Copyright (C) 1992-1996, 1998-2012 Free Software Foundation, Inc.
#
#
#
#
# This configure script is free software; the Free Software Foundation
# This configure script is free software; the Free Software Foundation
# gives unlimited permission to copy, distribute and modify it.
# gives unlimited permission to copy, distribute and modify it.
## -------------------- ##
## -------------------- ##
## M4sh Initialization. ##
## M4sh Initialization. ##
## -------------------- ##
## -------------------- ##
# Be more Bourne compatible
# Be more Bourne compatible
DUALCASE=1; export DUALCASE # for MKS sh
DUALCASE=1; export DUALCASE # for MKS sh
if test -n "${ZSH_VERSION+set}" && (emulate sh) >/dev/null 2>&1; then :
if test -n "${ZSH_VERSION+set}" && (emulate sh) >/dev/null 2>&1; then :
emulate sh
emulate sh
NULLCMD=:
NULLCMD=:
# Pre-4.2 versions of Zsh do word splitting on ${1+"$@"}, which
# Pre-4.2 versions of Zsh do word splitting on ${1+"$@"}, which
# is contrary to our usage. Disable this feature.
# is contrary to our usage. Disable this feature.
alias -g '${1+"$@"}'='"$@"'
alias -g '${1+"$@"}'='"$@"'
setopt NO_GLOB_SUBST
setopt NO_GLOB_SUBST
else
else
case `(set -o) 2>/dev/null` in #(
case `(set -o) 2>/dev/null` in #(
*posix*) :
*posix*) :
set -o posix ;; #(
set -o posix ;; #(
*) :
*) :
;;
;;
esac
esac
fi
fi
as_nl='
as_nl='
'
'
export as_nl
export as_nl
# Printing a long string crashes Solaris 7 /usr/bin/printf.
# Printing a long string crashes Solaris 7 /usr/bin/printf.
as_echo='\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\'
as_echo='\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\'
as_echo=$as_echo$as_echo$as_echo$as_echo$as_echo
as_echo=$as_echo$as_echo$as_echo$as_echo$as_echo
as_echo=$as_echo$as_echo$as_echo$as_echo$as_echo$as_echo
as_echo=$as_echo$as_echo$as_echo$as_echo$as_echo$as_echo
# Prefer a ksh shell builtin over an external printf program on Solaris,
# Prefer a ksh shell builtin over an external printf program on Solaris,
# but without wasting forks for bash or zsh.
# but without wasting forks for bash or zsh.
if test -z "$BASH_VERSION$ZSH_VERSION" \
if test -z "$BASH_VERSION$ZSH_VERSION" \
&& (test "X`print -r -- $as_echo`" = "X$as_echo") 2>/dev/null; then
&& (test "X`print -r -- $as_echo`" = "X$as_echo") 2>/dev/null; then
as_echo='print -r --'
as_echo='print -r --'
as_echo_n='print -rn --'
as_echo_n='print -rn --'
elif (test "X`printf %s $as_echo`" = "X$as_echo") 2>/dev/null; then
elif (test "X`printf %s $as_echo`" = "X$as_echo") 2>/dev/null; then
as_echo='printf %s\n'
as_echo='printf %s\n'
as_echo_n='printf %s'
as_echo_n='printf %s'
else
else
if test "X`(/usr/ucb/echo -n -n $as_echo) 2>/dev/null`" = "X-n $as_echo"; then
if test "X`(/usr/ucb/echo -n -n $as_echo) 2>/dev/null`" = "X-n $as_echo"; then
as_echo_body='eval /usr/ucb/echo -n "$1$as_nl"'
as_echo_body='eval /usr/ucb/echo -n "$1$as_nl"'
as_echo_n='/usr/ucb/echo -n'
as_echo_n='/usr/ucb/echo -n'
else
else
as_echo_body='eval expr "X$1" : "X\\(.*\\)"'
as_echo_body='eval expr "X$1" : "X\\(.*\\)"'
as_echo_n_body='eval
as_echo_n_body='eval
arg=$1;
arg=$1;
case $arg in #(
case $arg in #(
*"$as_nl"*)
*"$as_nl"*)
expr "X$arg" : "X\\(.*\\)$as_nl";
expr "X$arg" : "X\\(.*\\)$as_nl";
arg=`expr "X$arg" : ".*$as_nl\\(.*\\)"`;;
arg=`expr "X$arg" : ".*$as_nl\\(.*\\)"`;;
esac;
esac;
expr "X$arg" : "X\\(.*\\)" | tr -d "$as_nl"
expr "X$arg" : "X\\(.*\\)" | tr -d "$as_nl"
'
'
export as_echo_n_body
export as_echo_n_body
as_echo_n='sh -c $as_echo_n_body as_echo'
as_echo_n='sh -c $as_echo_n_body as_echo'
fi
fi
export as_echo_body
export as_echo_body
as_echo='sh -c $as_echo_body as_echo'
as_echo='sh -c $as_echo_body as_echo'
fi
fi
# The user is always right.
# The user is always right.
if test "${PATH_SEPARATOR+set}" != set; then
if test "${PATH_SEPARATOR+set}" != set; then
PATH_SEPARATOR=:
PATH_SEPARATOR=:
(PATH='/bin;/bin'; FPATH=$PATH; sh -c :) >/dev/null 2>&1 && {
(PATH='/bin;/bin'; FPATH=$PATH; sh -c :) >/dev/null 2>&1 && {
(PATH='/bin:/bin'; FPATH=$PATH; sh -c :) >/dev/null 2>&1 ||
(PATH='/bin:/bin'; FPATH=$PATH; sh -c :) >/dev/null 2>&1 ||
PATH_SEPARATOR=';'
PATH_SEPARATOR=';'
}
}
fi
fi
# IFS
# IFS
# We need space, tab and new line, in precisely that order. Quoting is
# We need space, tab and new line, in precisely that order. Quoting is
# there to prevent editors from complaining about space-tab.
# there to prevent editors from complaining about space-tab.
# (If _AS_PATH_WALK were called with IFS unset, it would disable word
# (If _AS_PATH_WALK were called with IFS unset, it would disable word
# splitting by setting IFS to empty value.)
# splitting by setting IFS to empty value.)
IFS=" "" $as_nl"
IFS=" "" $as_nl"
# Find who we are. Look in the path if we contain no directory separator.
# Find who we are. Look in the path if we contain no directory separator.
as_myself=
as_myself=
case $0 in #((
case $0 in #((
*[\\/]* ) as_myself=$0 ;;
*[\\/]* ) as_myself=$0 ;;
*) as_save_IFS=$IFS; IFS=$PATH_SEPARATOR
*) as_save_IFS=$IFS; IFS=$PATH_SEPARATOR
for as_dir in $PATH
for as_dir in $PATH
do
do
IFS=$as_save_IFS
IFS=$as_save_IFS
test -z "$as_dir" && as_dir=.
test -z "$as_dir" && as_dir=.
test -r "$as_dir/$0" && as_myself=$as_dir/$0 && break
test -r "$as_dir/$0" && as_myself=$as_dir/$0 && break
done
done
IFS=$as_save_IFS
IFS=$as_save_IFS
;;
;;
esac
esac
# We did not find ourselves, most probably we were run as `sh COMMAND'
# We did not find ourselves, most probably we were run as `sh COMMAND'
# in which case we are not to be found in the path.
# in which case we are not to be found in the path.
if test "x$as_myself" = x; then
if test "x$as_myself" = x; then
as_myself=$0
as_myself=$0
fi
fi
if test ! -f "$as_myself"; then
if test ! -f "$as_myself"; then
$as_echo "$as_myself: error: cannot find myself; rerun with an absolute file name" >&2
$as_echo "$as_myself: error: cannot find myself; rerun with an absolute file name" >&2
exit 1
exit 1
fi
fi
# Unset variables that we do not need and which cause bugs (e.g. in
# Unset variables that we do not need and which cause bugs (e.g. in
# pre-3.0 UWIN ksh). But do not cause bugs in bash 2.01; the "|| exit 1"
# pre-3.0 UWIN ksh). But do not cause bugs in bash 2.01; the "|| exit 1"
# suppresses any "Segmentation fault" message there. '((' could
# suppresses any "Segmentation fault" message there. '((' could
# trigger a bug in pdksh 5.2.14.
# trigger a bug in pdksh 5.2.14.
for as_var in BASH_ENV ENV MAIL MAILPATH
for as_var in BASH_ENV ENV MAIL MAILPATH
do eval test x\${$as_var+set} = xset \
do eval test x\${$as_var+set} = xset \
&& ( (unset $as_var) || exit 1) >/dev/null 2>&1 && unset $as_var || :
&& ( (unset $as_var) || exit 1) >/dev/null 2>&1 && unset $as_var || :
done
done
PS1='$ '
PS1='$ '
PS2='> '
PS2='> '
PS4='+ '
PS4='+ '
# NLS nuisances.
# NLS nuisances.
LC_ALL=C
LC_ALL=C
export LC_ALL
export LC_ALL
LANGUAGE=C
LANGUAGE=C
export LANGUAGE
export LANGUAGE
# CDPATH.
# CDPATH.
(unset CDPATH) >/dev/null 2>&1 && unset CDPATH
(unset CDPATH) >/dev/null 2>&1 && unset CDPATH
# Use a proper internal environment variable to ensure we don't fall
# Use a proper internal environment variable to ensure we don't fall
# into an infinite loop, continuously re-executing ourselves.
# into an infinite loop, continuously re-executing ourselves.
if test x"${_as_can_reexec}" != xno && test "x$CONFIG_SHELL" != x; then
if test x"${_as_can_reexec}" != xno && test "x$CONFIG_SHELL" != x; then
_as_can_reexec=no; export _as_can_reexec;
_as_can_reexec=no; export _as_can_reexec;
# We cannot yet assume a decent shell, so we have to provide a
# We cannot yet assume a decent shell, so we have to provide a
# neutralization value for shells without unset; and this also
# neutralization value for shells without unset; and this also
# works around shells that cannot unset nonexistent variables.
# works around shells that cannot unset nonexistent variables.
# Preserve -v and -x to the replacement shell.
# Preserve -v and -x to the replacement shell.
BASH_ENV=/dev/null
BASH_ENV=/dev/null
ENV=/dev/null
ENV=/dev/null
(unset BASH_ENV) >/dev/null 2>&1 && unset BASH_ENV ENV
(unset BASH_ENV) >/dev/null 2>&1 && unset BASH_ENV ENV
case $- in # ((((
case $- in # ((((
*v*x* | *x*v* ) as_opts=-vx ;;
*v*x* | *x*v* ) as_opts=-vx ;;
*v* ) as_opts=-v ;;
*v* ) as_opts=-v ;;
*x* ) as_opts=-x ;;
*x* ) as_opts=-x ;;
* ) as_opts= ;;
* ) as_opts= ;;
esac
esac
exec $CONFIG_SHELL $as_opts "$as_myself" ${1+"$@"}
exec $CONFIG_SHELL $as_opts "$as_myself" ${1+"$@"}
# Admittedly, this is quite paranoid, since all the known shells bail
# Admittedly, this is quite paranoid, since all the known shells bail
# out after a failed `exec'.
# out after a failed `exec'.
$as_echo "$0: could not re-execute with $CONFIG_SHELL" >&2
$as_echo "$0: could not re-execute with $CONFIG_SHELL" >&2
as_fn_exit 255
as_fn_exit 255
fi
fi
# We don't want this to propagate to other subprocesses.
# We don't want this to propagate to other subprocesses.
{ _as_can_reexec=; unset _as_can_reexec;}
{ _as_can_reexec=; unset _as_can_reexec;}
if test "x$CONFIG_SHELL" = x; then
if test "x$CONFIG_SHELL" = x; then
as_bourne_compatible="if test -n \"\${ZSH_VERSION+set}\" && (emulate sh) >/dev/null 2>&1; then :
as_bourne_compatible="if test -n \"\${ZSH_VERSION+set}\" && (emulate sh) >/dev/null 2>&1; then :
emulate sh
emulate sh
NULLCMD=:
NULLCMD=:
# Pre-4.2 versions of Zsh do word splitting on \${1+\"\$@\"}, which
# Pre-4.2 versions of Zsh do word splitting on \${1+\"\$@\"}, which
# is contrary to our usage. Disable this feature.
# is contrary to our usage. Disable this feature.
alias -g '\${1+\"\$@\"}'='\"\$@\"'
alias -g '\${1+\"\$@\"}'='\"\$@\"'
setopt NO_GLOB_SUBST
setopt NO_GLOB_SUBST
else
else
case \`(set -o) 2>/dev/null\` in #(
case \`(set -o) 2>/dev/null\` in #(
*posix*) :
*posix*) :
set -o posix ;; #(
set -o posix ;; #(
*) :
*) :
;;
;;
esac
esac
fi
fi
"
"
as_required="as_fn_return () { (exit \$1); }
as_required="as_fn_return () { (exit \$1); }
as_fn_success () { as_fn_return 0; }
as_fn_success () { as_fn_return 0; }
as_fn_failure () { as_fn_return 1; }
as_fn_failure () { as_fn_return 1; }
as_fn_ret_success () { return 0; }
as_fn_ret_success () { return 0; }
as_fn_ret_failure () { return 1; }
as_fn_ret_failure () { return 1; }
exitcode=0
exitcode=0
as_fn_success || { exitcode=1; echo as_fn_success failed.; }
as_fn_success || { exitcode=1; echo as_fn_success failed.; }
as_fn_failure && { exitcode=1; echo as_fn_failure succeeded.; }
as_fn_failure && { exitcode=1; echo as_fn_failure succeeded.; }
as_fn_ret_success || { exitcode=1; echo as_fn_ret_success failed.; }
as_fn_ret_success || { exitcode=1; echo as_fn_ret_success failed.; }
as_fn_ret_failure && { exitcode=1; echo as_fn_ret_failure succeeded.; }
as_fn_ret_failure && { exitcode=1; echo as_fn_ret_failure succeeded.; }
if ( set x; as_fn_ret_success y && test x = \"\$1\" ); then :
if ( set x; as_fn_ret_success y && test x = \"\$1\" ); then :
else
else
exitcode=1; echo positional parameters were not saved.
exitcode=1; echo positional parameters were not saved.
fi
fi
test x\$exitcode = x0 || exit 1
test x\$exitcode = x0 || exit 1
test -x / || exit 1"
test -x / || exit 1"
as_suggested=" as_lineno_1=";as_suggested=$as_suggested$LINENO;as_suggested=$as_suggested" as_lineno_1a=\$LINENO
as_suggested=" as_lineno_1=";as_suggested=$as_suggested$LINENO;as_suggested=$as_suggested" as_lineno_1a=\$LINENO
as_lineno_2=";as_suggested=$as_suggested$LINENO;as_suggested=$as_suggested" as_lineno_2a=\$LINENO
as_lineno_2=";as_suggested=$as_suggested$LINENO;as_suggested=$as_suggested" as_lineno_2a=\$LINENO
eval 'test \"x\$as_lineno_1'\$as_run'\" != \"x\$as_lineno_2'\$as_run'\" &&
eval 'test \"x\$as_lineno_1'\$as_run'\" != \"x\$as_lineno_2'\$as_run'\" &&
test \"x\`expr \$as_lineno_1'\$as_run' + 1\`\" = \"x\$as_lineno_2'\$as_run'\"' || exit 1
test \"x\`expr \$as_lineno_1'\$as_run' + 1\`\" = \"x\$as_lineno_2'\$as_run'\"' || exit 1
test -n \"\${ZSH_VERSION+set}\${BASH_VERSION+set}\" || (
test -n \"\${ZSH_VERSION+set}\${BASH_VERSION+set}\" || (
ECHO='\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\'
ECHO='\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\'
ECHO=\$ECHO\$ECHO\$ECHO\$ECHO\$ECHO
ECHO=\$ECHO\$ECHO\$ECHO\$ECHO\$ECHO
ECHO=\$ECHO\$ECHO\$ECHO\$ECHO\$ECHO\$ECHO
ECHO=\$ECHO\$ECHO\$ECHO\$ECHO\$ECHO\$ECHO
PATH=/empty FPATH=/empty; export PATH FPATH
PATH=/empty FPATH=/empty; export PATH FPATH
test \"X\`printf %s \$ECHO\`\" = \"X\$ECHO\" \\
test \"X\`printf %s \$ECHO\`\" = \"X\$ECHO\" \\
|| test \"X\`print -r -- \$ECHO\`\" = \"X\$ECHO\" ) || exit 1
|| test \"X\`print -r -- \$ECHO\`\" = \"X\$ECHO\" ) || exit 1
test \$(( 1 + 1 )) = 2 || exit 1"
test \$(( 1 + 1 )) = 2 || exit 1"
if (eval "$as_required") 2>/dev/null; then :
if (eval "$as_required") 2>/dev/null; then :
as_have_required=yes
as_have_required=yes
else
else
as_have_required=no
as_have_required=no
fi
fi
if test x$as_have_required = xyes && (eval "$as_suggested") 2>/dev/null; then :
if test x$as_have_required = xyes && (eval "$as_suggested") 2>/dev/null; then :
else
else
as_save_IFS=$IFS; IFS=$PATH_SEPARATOR
as_save_IFS=$IFS; IFS=$PATH_SEPARATOR
as_found=false
as_found=false
for as_dir in /bin$PATH_SEPARATOR/usr/bin$PATH_SEPARATOR$PATH
for as_dir in /bin$PATH_SEPARATOR/usr/bin$PATH_SEPARATOR$PATH
do
do
IFS=$as_save_IFS
IFS=$as_save_IFS
test -z "$as_dir" && as_dir=.
test -z "$as_dir" && as_dir=.
as_found=:
as_found=:
case $as_dir in #(
case $as_dir in #(
/*)
/*)
for as_base in sh bash ksh sh5; do
for as_base in sh bash ksh sh5; do
# Try only shells that exist, to save several forks.
# Try only shells that exist, to save several forks.
as_shell=$as_dir/$as_base
as_shell=$as_dir/$as_base
if { test -f "$as_shell" || test -f "$as_shell.exe"; } &&
if { test -f "$as_shell" || test -f "$as_shell.exe"; } &&
{ $as_echo "$as_bourne_compatible""$as_required" | as_run=a "$as_shell"; } 2>/dev/null; then :
{ $as_echo "$as_bourne_compatible""$as_required" | as_run=a "$as_shell"; } 2>/dev/null; then :
CONFIG_SHELL=$as_shell as_have_required=yes
CONFIG_SHELL=$as_shell as_have_required=yes
if { $as_echo "$as_bourne_compatible""$as_suggested" | as_run=a "$as_shell"; } 2>/dev/null; then :
if { $as_echo "$as_bourne_compatible""$as_suggested" | as_run=a "$as_shell"; } 2>/dev/null; then :
break 2
break 2
fi
fi
fi
fi
done;;
done;;
esac
esac
as_found=false
as_found=false
done
done
$as_found || { if { test -f "$SHELL" || test -f "$SHELL.exe"; } &&
$as_found || { if { test -f "$SHELL" || test -f "$SHELL.exe"; } &&
{ $as_echo "$as_bourne_compatible""$as_required" | as_run=a "$SHELL"; } 2>/dev/null; then :
{ $as_echo "$as_bourne_compatible""$as_required" | as_run=a "$SHELL"; } 2>/dev/null; then :
CONFIG_SHELL=$SHELL as_have_required=yes
CONFIG_SHELL=$SHELL as_have_required=yes
fi; }
fi; }
IFS=$as_save_IFS
IFS=$as_save_IFS
if test "x$CONFIG_SHELL" != x; then :
if test "x$CONFIG_SHELL" != x; then :
export CONFIG_SHELL
export CONFIG_SHELL
# We cannot yet assume a decent shell, so we have to provide a
# We cannot yet assume a decent shell, so we have to provide a
# neutralization value for shells without unset; and this also
# neutralization value for shells without unset; and this also
# works around shells that cannot unset nonexistent variables.
# works around shells that cannot unset nonexistent variables.
# Preserve -v and -x to the replacement shell.
# Preserve -v and -x to the replacement shell.
BASH_ENV=/dev/null
BASH_ENV=/dev/null
ENV=/dev/null
ENV=/dev/null
(unset BASH_ENV) >/dev/null 2>&1 && unset BASH_ENV ENV
(unset BASH_ENV) >/dev/null 2>&1 && unset BASH_ENV ENV
case $- in # ((((
case $- in # ((((
*v*x* | *x*v* ) as_opts=-vx ;;
*v*x* | *x*v* ) as_opts=-vx ;;
*v* ) as_opts=-v ;;
*v* ) as_opts=-v ;;
*x* ) as_opts=-x ;;
*x* ) as_opts=-x ;;
* ) as_opts= ;;
* ) as_opts= ;;
esac
esac
exec $CONFIG_SHELL $as_opts "$as_myself" ${1+"$@"}
exec $CONFIG_SHELL $as_opts "$as_myself" ${1+"$@"}
# Admittedly, this is quite paranoid, since all the known shells bail
# Admittedly, this is quite paranoid, since all the known shells bail
# out after a failed `exec'.
# out after a failed `exec'.
$as_echo "$0: could not re-execute with $CONFIG_SHELL" >&2
$as_echo "$0: could not re-execute with $CONFIG_SHELL" >&2
exit 255
exit 255
fi
fi
if test x$as_have_required = xno; then :
if test x$as_have_required = xno; then :
$as_echo "$0: This script requires a shell more modern than all"
$as_echo "$0: This script requires a shell more modern than all"
$as_echo "$0: the shells that I found on your system."
$as_echo "$0: the shells that I found on your system."
if test x${ZSH_VERSION+set} = xset ; then
if test x${ZSH_VERSION+set} = xset ; then
$as_echo "$0: In particular, zsh $ZSH_VERSION has bugs and should"
$as_echo "$0: In particular, zsh $ZSH_VERSION has bugs and should"
$as_echo "$0: be upgraded to zsh 4.3.4 or later."
$as_echo "$0: be upgraded to zsh 4.3.4 or later."
else
else
$as_echo "$0: Please tell bug-autoconf@gnu.org and
$as_echo "$0: Please tell bug-autoconf@gnu.org and
$0: https://github.com/bitcoin/bitcoin/issues about your
$0: https://github.com/bitcoin/bitcoin/issues about your
$0: system, including any error possibly output before this
$0: system, including any error possibly output before this
$0: message. Then install a modern shell, or manually run
$0: message. Then install a modern shell, or manually run
$0: the script under such a shell if you do have one."
$0: the script under such a shell if you do have one."
fi
fi
exit 1
exit 1
fi
fi
fi
fi
fi
fi
SHELL=${CONFIG_SHELL-/bin/sh}
SHELL=${CONFIG_SHELL-/bin/sh}
export SHELL
export SHELL
# Unset more variables known to interfere with behavior of common tools.
# Unset more variables known to interfere with behavior of common tools.
CLICOLOR_FORCE= GREP_OPTIONS=
CLICOLOR_FORCE= GREP_OPTIONS=
unset CLICOLOR_FORCE GREP_OPTIONS
unset CLICOLOR_FORCE GREP_OPTIONS
## --------------------- ##
## --------------------- ##
## M4sh Shell Functions. ##
## M4sh Shell Functions. ##
## --------------------- ##
## --------------------- ##
# as_fn_unset VAR
# as_fn_unset VAR
# ---------------
# ---------------
# Portably unset VAR.
# Portably unset VAR.
as_fn_unset ()
as_fn_unset ()
{
{
{ eval $1=; unset $1;}
{ eval $1=; unset $1;}
}
}
as_unset=as_fn_unset
as_unset=as_fn_unset
# as_fn_set_status STATUS
# as_fn_set_status STATUS
# -----------------------
# -----------------------
# Set $? to STATUS, without forking.
# Set $? to STATUS, without forking.
as_fn_set_status ()
as_fn_set_status ()
{
{
return $1
return $1
} # as_fn_set_status
} # as_fn_set_status
# as_fn_exit STATUS
# as_fn_exit STATUS
# -----------------
# -----------------
# Exit the shell with STATUS, even in a "trap 0" or "set -e" context.
# Exit the shell with STATUS, even in a "trap 0" or "set -e" context.
as_fn_exit ()
as_fn_exit ()
{
{
set +e
set +e
as_fn_set_status $1
as_fn_set_status $1
exit $1
exit $1
} # as_fn_exit
} # as_fn_exit
# as_fn_mkdir_p
# as_fn_mkdir_p
# -------------
# -------------
# Create "$as_dir" as a directory, including parents if necessary.
# Create "$as_dir" as a directory, including parents if necessary.
as_fn_mkdir_p ()
as_fn_mkdir_p ()
{
{
case $as_dir in #(
case $as_dir in #(
-*) as_dir=./$as_dir;;
-*) as_dir=./$as_dir;;
esac
esac
test -d "$as_dir" || eval $as_mkdir_p || {
test -d "$as_dir" || eval $as_mkdir_p || {
as_dirs=
as_dirs=
while :; do
while :; do
case $as_dir in #(
case $as_dir in #(
*\'*) as_qdir=`$as_echo "$as_dir" | sed "s/'/'\\\\\\\\''/g"`;; #'(
*\'*) as_qdir=`$as_echo "$as_dir" | sed "s/'/'\\\\\\\\''/g"`;; #'(
*) as_qdir=$as_dir;;
*) as_qdir=$as_dir;;
esac
esac
as_dirs="'$as_qdir' $as_dirs"
as_dirs="'$as_qdir' $as_dirs"
as_dir=`$as_dirname -- "$as_dir" ||
as_dir=`$as_dirname -- "$as_dir" ||
$as_expr X"$as_dir" : 'X\(.*[^/]\)//*[^/][^/]*/*$' \| \
$as_expr X"$as_dir" : 'X\(.*[^/]\)//*[^/][^/]*/*$' \| \
X"$as_dir" : 'X\(//\)[^/]' \| \
X"$as_dir" : 'X\(//\)[^/]' \| \
X"$as_dir" : 'X\(//\)$' \| \
X"$as_dir" : 'X\(//\)$' \| \
X"$as_dir" : 'X\(/\)' \| . 2>/dev/null ||
X"$as_dir" : 'X\(/\)' \| . 2>/dev/null ||
$as_echo X"$as_dir" |
$as_echo X"$as_dir" |
sed '/^X\(.*[^/]\)\/\/*[^/][^/]*\/*$/{
sed '/^X\(.*[^/]\)\/\/*[^/][^/]*\/*$/{
s//\1/
s//\1/
q
q
}
}
/^X\(\/\/\)[^/].*/{
/^X\(\/\/\)[^/].*/{
s//\1/
s//\1/
q
q
}
}
/^X\(\/\/\)$/{
/^X\(\/\/\)$/{
s//\1/
s//\1/
q
q
}
}
/^X\(\/\).*/{
/^X\(\/\).*/{
s//\1/
s//\1/
q
q
}
}
s/.*/./; q'`
s/.*/./; q'`
test -d "$as_dir" && break
test -d "$as_dir" && break
done
done
test -z "$as_dirs" || eval "mkdir $as_dirs"
test -z "$as_dirs" || eval "mkdir $as_dirs"
} || test -d "$as_dir" || as_fn_error $? "cannot create directory $as_dir"
} || test -d "$as_dir" || as_fn_error $? "cannot create directory $as_dir"
} # as_fn_mkdir_p
} # as_fn_mkdir_p
# as_fn_executable_p FILE
# as_fn_executable_p FILE
# -----------------------
# -----------------------
# Test if FILE is an executable regular file.
# Test if FILE is an executable regular file.
as_fn_executable_p ()
as_fn_executable_p ()
{
{
test -f "$1" && test -x "$1"
test -f "$1" && test -x "$1"
} # as_fn_executable_p
} # as_fn_executable_p
# as_fn_append VAR VALUE
# as_fn_append VAR VALUE
# ----------------------
# ----------------------
# Append the text in VALUE to the end of the definition contained in VAR. Take
# Append the text in VALUE to the end of the definition contained in VAR. Take
# advantage of any shell optimizations that allow amortized linear growth over
# advantage of any shell optimizations that allow amortized linear growth over
# repeated appends, instead of the typical quadratic growth present in naive
# repeated appends, instead of the typical quadratic growth present in naive
# implementations.
# implementations.
if (eval "as_var=1; as_var+=2; test x\$as_var = x12") 2>/dev/null; then :
if (eval "as_var=1; as_var+=2; test x\$as_var = x12") 2>/dev/null; then :
eval 'as_fn_append ()
eval 'as_fn_append ()
{
{
eval $1+=\$2
eval $1+=\$2
}'
}'
else
else
as_fn_append ()
as_fn_append ()
{
{
eval $1=\$$1\$2
eval $1=\$$1\$2
}
}
fi # as_fn_append
fi # as_fn_append
# as_fn_arith ARG...
# as_fn_arith ARG...
# ------------------
# ------------------
# Perform arithmetic evaluation on the ARGs, and store the result in the
# Perform arithmetic evaluation on the ARGs, and store the result in the
# global $as_val. Take advantage of shells that can avoid forks. The arguments
# global $as_val. Take advantage of shells that can avoid forks. The arguments
# must be portable across $(()) and expr.
# must be portable across $(()) and expr.
if (eval "test \$(( 1 + 1 )) = 2") 2>/dev/null; then :
if (eval "test \$(( 1 + 1 )) = 2") 2>/dev/null; then :
eval 'as_fn_arith ()
eval 'as_fn_arith ()
{
{
as_val=$(( $* ))
as_val=$(( $* ))
}'
}'
else
else
as_fn_arith ()
as_fn_arith ()
{
{
as_val=`expr "$@" || test $? -eq 1`
as_val=`expr "$@" || test $? -eq 1`
}
}
fi # as_fn_arith
fi # as_fn_arith
# as_fn_error STATUS ERROR [LINENO LOG_FD]
# as_fn_error STATUS ERROR [LINENO LOG_FD]
# ----------------------------------------
# ----------------------------------------
# Output "`basename $0`: error: ERROR" to stderr. If LINENO and LOG_FD are
# Output "`basename $0`: error: ERROR" to stderr. If LINENO and LOG_FD are
# provided, also output the error to LOG_FD, referencing LINENO. Then exit the
# provided, also output the error to LOG_FD, referencing LINENO. Then exit the
# script with STATUS, using 1 if that was 0.
# script with STATUS, using 1 if that was 0.
as_fn_error ()
as_fn_error ()
{
{
as_status=$1; test $as_status -eq 0 && as_status=1
as_status=$1; test $as_status -eq 0 && as_status=1
if test "$4"; then
if test "$4"; then
as_lineno=${as_lineno-"$3"} as_lineno_stack=as_lineno_stack=$as_lineno_stack
as_lineno=${as_lineno-"$3"} as_lineno_stack=as_lineno_stack=$as_lineno_stack
$as_echo "$as_me:${as_lineno-$LINENO}: error: $2" >&$4
$as_echo "$as_me:${as_lineno-$LINENO}: error: $2" >&$4
fi
fi
$as_echo "$as_me: error: $2" >&2
$as_echo "$as_me: error: $2" >&2
as_fn_exit $as_status
as_fn_exit $as_status
} # as_fn_error
} # as_fn_error
if expr a : '\(a\)' >/dev/null 2>&1 &&
if expr a : '\(a\)' >/dev/null 2>&1 &&
test "X`expr 00001 : '.*\(...\)'`" = X001; then
test "X`expr 00001 : '.*\(...\)'`" = X001; then
as_expr=expr
as_expr=expr
else
else
as_expr=false
as_expr=false
fi
fi
if (basename -- /) >/dev/null 2>&1 && test "X`basename -- / 2>&1`" = "X/"; then
if (basename -- /) >/dev/null 2>&1 && test "X`basename -- / 2>&1`" = "X/"; then
as_basename=basename
as_basename=basename
else
else
as_basename=false
as_basename=false
fi
fi
if (as_dir=`dirname -- /` && test "X$as_dir" = X/) >/dev/null 2>&1; then
if (as_dir=`dirname -- /` && test "X$as_dir" = X/) >/dev/null 2>&1; then
as_dirname=dirname
as_dirname=dirname
else
else
as_dirname=false
as_dirname=false
fi
fi
as_me=`$as_basename -- "$0" ||
as_me=`$as_basename -- "$0" ||
$as_expr X/"$0" : '.*/\([^/][^/]*\)/*$' \| \
$as_expr X/"$0" : '.*/\([^/][^/]*\)/*$' \| \
X"$0" : 'X\(//\)$' \| \
X"$0" : 'X\(//\)$' \| \
X"$0" : 'X\(/\)' \| . 2>/dev/null ||
X"$0" : 'X\(/\)' \| . 2>/dev/null ||
$as_echo X/"$0" |
$as_echo X/"$0" |
sed '/^.*\/\([^/][^/]*\)\/*$/{
sed '/^.*\/\([^/][^/]*\)\/*$/{
s//\1/
s//\1/
q
q
}
}
/^X\/\(\/\/\)$/{
/^X\/\(\/\/\)$/{
s//\1/
s//\1/
q
q
}
}
/^X\/\(\/\).*/{
/^X\/\(\/\).*/{
s//\1/
s//\1/
q
q
}
}
s/.*/./; q'`
s/.*/./; q'`
# Avoid depending upon Character Ranges.
# Avoid depending upon Character Ranges.
as_cr_letters='abcdefghijklmnopqrstuvwxyz'
as_cr_letters='abcdefghijklmnopqrstuvwxyz'
as_cr_LETTERS='ABCDEFGHIJKLMNOPQRSTUVWXYZ'
as_cr_LETTERS='ABCDEFGHIJKLMNOPQRSTUVWXYZ'
as_cr_Letters=$as_cr_letters$as_cr_LETTERS
as_cr_Letters=$as_cr_letters$as_cr_LETTERS
as_cr_digits='0123456789'
as_cr_digits='0123456789'
as_cr_alnum=$as_cr_Letters$as_cr_digits
as_cr_alnum=$as_cr_Letters$as_cr_digits
as_lineno_1=$LINENO as_lineno_1a=$LINENO
as_lineno_1=$LINENO as_lineno_1a=$LINENO
as_lineno_2=$LINENO as_lineno_2a=$LINENO
as_lineno_2=$LINENO as_lineno_2a=$LINENO
eval 'test "x$as_lineno_1'$as_run'" != "x$as_lineno_2'$as_run'" &&
eval 'test "x$as_lineno_1'$as_run'" != "x$as_lineno_2'$as_run'" &&
test "x`expr $as_lineno_1'$as_run' + 1`" = "x$as_lineno_2'$as_run'"' || {
test "x`expr $as_lineno_1'$as_run' + 1`" = "x$as_lineno_2'$as_run'"' || {
# Blame Lee E. McMahon (1931-1989) for sed's syntax. :-)
# Blame Lee E. McMahon (1931-1989) for sed's syntax. :-)
sed -n '
sed -n '
p
p
/[$]LINENO/=
/[$]LINENO/=
' <$as_myself |
' <$as_myself |
sed '
sed '
s/[$]LINENO.*/&-/
s/[$]LINENO.*/&-/
t lineno
t lineno
b
b
:lineno
:lineno
N
N
:loop
:loop
s/[$]LINENO\([^'$as_cr_alnum'_].*\n\)\(.*\)/\2\1\2/
s/[$]LINENO\([^'$as_cr_alnum'_].*\n\)\(.*\)/\2\1\2/
t loop
t loop
s/-\n.*//
s/-\n.*//
' >$as_me.lineno &&
' >$as_me.lineno &&
chmod +x "$as_me.lineno" ||
chmod +x "$as_me.lineno" ||
{ $as_echo "$as_me: error: cannot create $as_me.lineno; rerun with a POSIX shell" >&2; as_fn_exit 1; }
{ $as_echo "$as_me: error: cannot create $as_me.lineno; rerun with a POSIX shell" >&2; as_fn_exit 1; }
# If we had to re-execute with $CONFIG_SHELL, we're ensured to have
# If we had to re-execute with $CONFIG_SHELL, we're ensured to have
# already done that, so ensure we don't try to do so again and fall
# already done that, so ensure we don't try to do so again and fall
# in an infinite loop. This has already happened in practice.
# in an infinite loop. This has already happened in practice.
_as_can_reexec=no; export _as_can_reexec
_as_can_reexec=no; export _as_can_reexec
# Don't try to exec as it changes $[0], causing all sort of problems
# Don't try to exec as it changes $[0], causing all sort of problems
# (the dirname of $[0] is not the place where we might find the
# (the dirname of $[0] is not the place where we might find the
# original and so on. Autoconf is especially sensitive to this).
# original and so on. Autoconf is especially sensitive to this).
. "./$as_me.lineno"
. "./$as_me.lineno"
# Exit status is that of the last command.
# Exit status is that of the last command.
exit
exit
}
}
ECHO_C= ECHO_N= ECHO_T=
ECHO_C= ECHO_N= ECHO_T=
case `echo -n x` in #(((((
case `echo -n x` in #(((((
-n*)
-n*)
case `echo 'xy\c'` in
case `echo 'xy\c'` in
*c*) ECHO_T=' ';; # ECHO_T is single tab character.
*c*) ECHO_T=' ';; # ECHO_T is single tab character.
xy) ECHO_C='\c';;
xy) ECHO_C='\c';;
*) echo `echo ksh88 bug on AIX 6.1` > /dev/null
*) echo `echo ksh88 bug on AIX 6.1` > /dev/null
ECHO_T=' ';;
ECHO_T=' ';;
esac;;
esac;;
*)
*)
ECHO_N='-n';;
ECHO_N='-n';;
esac
esac
rm -f conf$$ conf$$.exe conf$$.file
rm -f conf$$ conf$$.exe conf$$.file
if test -d conf$$.dir; then
if test -d conf$$.dir; then
rm -f conf$$.dir/conf$$.file
rm -f conf$$.dir/conf$$.file
else
else
rm -f conf$$.dir
rm -f conf$$.dir
mkdir conf$$.dir 2>/dev/null
mkdir conf$$.dir 2>/dev/null
fi
fi
if (echo >conf$$.file) 2>/dev/null; then
if (echo >conf$$.file) 2>/dev/null; then
if ln -s conf$$.file conf$$ 2>/dev/null; then
if ln -s conf$$.file conf$$ 2>/dev/null; then
as_ln_s='ln -s'
as_ln_s='ln -s'
# ... but there are two gotchas:
# ... but there are two gotchas:
# 1) On MSYS, both `ln -s file dir' and `ln file dir' fail.
# 1) On MSYS, both `ln -s file dir' and `ln file dir' fail.
# 2) DJGPP < 2.04 has no symlinks; `ln -s' creates a wrapper executable.
# 2) DJGPP < 2.04 has no symlinks; `ln -s' creates a wrapper executable.
# In both cases, we have to default to `cp -pR'.
# In both cases, we have to default to `cp -pR'.
ln -s conf$$.file conf$$.dir 2>/dev/null && test ! -f conf$$.exe ||
ln -s conf$$.file conf$$.dir 2>/dev/null && test ! -f conf$$.exe ||
as_ln_s='cp -pR'
as_ln_s='cp -pR'
elif ln conf$$.file conf$$ 2>/dev/null; then
elif ln conf$$.file conf$$ 2>/dev/null; then
as_ln_s=ln
as_ln_s=ln
else
else
as_ln_s='cp -pR'
as_ln_s='cp -pR'
fi
fi
else
else
as_ln_s='cp -pR'
as_ln_s='cp -pR'
fi
fi
rm -f conf$$ conf$$.exe conf$$.dir/conf$$.file conf$$.file
rm -f conf$$ conf$$.exe conf$$.dir/conf$$.file conf$$.file
rmdir conf$$.dir 2>/dev/null
rmdir conf$$.dir 2>/dev/null
if mkdir -p . 2>/dev/null; then
if mkdir -p . 2>/dev/null; then
as_mkdir_p='mkdir -p "$as_dir"'
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|
US4117257A - Temperature sensor holding device - Google Patents
Temperature sensor holding device Download PDF
Info
Publication number
US4117257A
US4117257A US05/686,746 US68674676A US4117257A US 4117257 A US4117257 A US 4117257A US 68674676 A US68674676 A US 68674676A US 4117257 A US4117257 A US 4117257A
Authority
US
United States
Prior art keywords
spacer
plate
temperature sensor
conductor
cover
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
US05/686,746
Inventor
Harry L. Thomas
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
GTE Sylvania Inc
Original Assignee
GTE Sylvania Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by GTE Sylvania Inc filed Critical GTE Sylvania Inc
Priority to US05/686,746 priority Critical patent/US4117257A/en
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Publication of US4117257A publication Critical patent/US4117257A/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current
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• HELECTRICITY
• H01BASIC ELECTRIC ELEMENTS
• H01LSEMICONDUCTOR DEVICES; ELECTRIC SOLID STATE DEVICES NOT OTHERWISE PROVIDED FOR
• H01L23/00Details of semiconductor or other solid state devices
• H01L23/34Arrangements for cooling, heating, ventilating or temperature compensation ; Temperature sensing arrangements
• GPHYSICS
• G01MEASURING; TESTING
• G01KMEASURING TEMPERATURE; MEASURING QUANTITY OF HEAT; THERMALLY-SENSITIVE ELEMENTS NOT OTHERWISE PROVIDED FOR
• G01K1/00Details of thermometers not specially adapted for particular types of thermometer
• G01K1/14Supports; Fastening devices; Mounting thermometers in particular locations
• HELECTRICITY
• H01BASIC ELECTRIC ELEMENTS
• H01LSEMICONDUCTOR DEVICES; ELECTRIC SOLID STATE DEVICES NOT OTHERWISE PROVIDED FOR
• H01L23/00Details of semiconductor or other solid state devices
• H01L23/34Arrangements for cooling, heating, ventilating or temperature compensation ; Temperature sensing arrangements
• H01L23/40Mountings or securing means for detachable cooling or heating arrangements ; fixed by friction, plugs or springs
• H01L23/4006Mountings or securing means for detachable cooling or heating arrangements ; fixed by friction, plugs or springs with bolts or screws
• HELECTRICITY
• H01BASIC ELECTRIC ELEMENTS
• H01LSEMICONDUCTOR DEVICES; ELECTRIC SOLID STATE DEVICES NOT OTHERWISE PROVIDED FOR
• H01L23/00Details of semiconductor or other solid state devices
• H01L23/34Arrangements for cooling, heating, ventilating or temperature compensation ; Temperature sensing arrangements
• H01L23/40Mountings or securing means for detachable cooling or heating arrangements ; fixed by friction, plugs or springs
• H01L23/4006Mountings or securing means for detachable cooling or heating arrangements ; fixed by friction, plugs or springs with bolts or screws
• H01L2023/4075Mechanical elements
• H01L2023/4087Mounting accessories, interposers, clamping or screwing parts
• HELECTRICITY
• H01BASIC ELECTRIC ELEMENTS
• H01LSEMICONDUCTOR DEVICES; ELECTRIC SOLID STATE DEVICES NOT OTHERWISE PROVIDED FOR
• H01L2924/00Indexing scheme for arrangements or methods for connecting or disconnecting semiconductor or solid-state bodies as covered by H01L24/00
• H01L2924/0001Technical content checked by a classifier
• H01L2924/0002Not covered by any one of groups H01L24/00, H01L24/00 and H01L2224/00
Abstract
A temperature sensor holding device for electronic apparatus includes a plate member having an aperture for receiving a heat generating semi-conductor and formed for attachment to a heat sink, a spacer member fastened to the plate member and formed to telescope over the heat generating semi-conductor, and a cover member formed for attachment to the spacer and plate members and having a cut out portion on the inner surface thereof for receiving a temperature sensor device.
Description
BACKGROUND OF THE INVENTION
In electronic apparatus having amplifier stages with relatively large power output capabilities, such as audio amplifier for example, a commonly encountered problem is a thermal run away condition of the amplifier device. Frequently, the idle current of the device is sufficient to cause this thermal run away condition which destroys the device.
One approach to solving the thermal run away problem is the use of a semi-conductor to sense a temperature change in the output device. Upon sensing the temperature change, the temperature sensor semi-conductor feeds back a signal which automatically controls the idle current of the output device and inhibits any tendency toward the run away condition.
In the prior art, a well-known technique for inhibiting thermal run away in an assembled power amplifier and temperature sensitive semi-conductor device, was to affix the power amplifier to the heat sink with a mica insulator between the heat sink and the amplifier. Also, the temperature sensitive device was affixed to the heat sink by a mounting bracket. Thus, the thermal path from the output device to the temperature sensitive device included (a) the case of the output device, (b) a mica insulator, (c) the heat sink, (d) through a portion of the heat sink, (e) a sensor device mounting bracket, and (f) the temperature sensitive device.
Obviously, such an extended thermal path includes numerous variables and the variables are different for each configuration. As a result, the response of the temperature sensitive device is different for each configuration and the time lag of the correction circuit may be of a length sufficient to cause failure of the power amplifier before the temperature sensitive device has had time to effect the correction.
OBJECTS AND SUMMARY OF THE INVENTION
An object of the present invention is to enhance the temperature sensing capabilities of electronic apparatus. Another object of the invention is to provide an improved capability for mounting a heat generating semi-conductor and temperature sensor device. Still another object of the invention is to provide an improved thermal path between a heat generating semi-conductor and a temperature sensor device.
These and other objects, advantages and capabilities are achieved in one aspect of the invention by a temperature sensor holding device having an apertured plate member affixed to an aperture spacer member telescoped over a heat generating semi-conductor attaching with the plate and spacer members and semi-conductor attached to a heat sink and a cover member having an inner surface cut out for a temperature sensitive device aligned with the aperture for receiving the heat generating semi-conductor and formed for attachment to the spacer and plate members.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an exploded isometric illustration of a preferred embodiment of the invention;
FIG. 2 is a sectional view of the embodiment of FIG. 1 taken along the line 2--2; and
FIG. 3 is a top elevational view of the embodiment of FIG. 1.
PREFERRED EMBODIMENT OF THE INVENTION
For a better understanding of the present invention, together with other and further objects, advantages and capabilities thereof, reference is made to the following disclosure and appended claims in conjunction with the accompanying drawings.
Referring to FIG. 1 of the drawings, a temperature sensor holding device includes a plate member 5, a spacer member 7, and a cover member 9. The plate, spacer, and cover members 5, 7, and 9 all have a common axis and formed for cooperative coupling therebetween.
The plate member 5 is of a substantially rectangular shape and preferably fabricated of an electrical current and thermal conductive metal with a central aperture 11 formed to receive a heat generating semi-conductor device (not shown). A pair of diametrically opposed slots 13 intersect the central aperture 11 and provide passageway for a holding means for the semi-conductor device and the plate member 5 as will be further explained hereinafter. Also, the plate member 5 includes first and second pairs of diametrically opposed holes 15 and 17 formed to receive a fastening means.
The spacer member 7 is substantially rectangular-shaped and of an electrical insulating material such as a molded plastic for example. The spacer member 7 has a central aperture 19 formed for alignment with the central aperture 11 of the plate member 5 and formed to telescope over a heat generating device (not shown) disposed in the central aperture 11. A pair of diametrically opposed openings 21 intersect the central aperture 19 and are aligned with the opposed slots 13 of the plate member 5. These opposed openings 21 are formed to receive a means for fastening the plate member 5 and a semi-conductor device (not shown) to a heat sink. A pair of counter sunk, diametrically opposed holes 23 are aligned with the first pair of holes 15 of the plate member 5 and formed to receive a first fastening means such as a pair of rivets 25. Moreover, the spacer member 7 includes a pair of opposed screw holes 27 aligned with the diametrically opposed holes 17 of the plate member 5.
The cover member 9 is also substantially rectangular-shaped with a pair of openings 29 aligned with the openings 21 of the spacer member 7 and the slots 13 of the plate member 5. The cover member 9 includes an inner surface cut out portion 31 formed to receive a temperature sensor device (not shown). The cut out portion 31 extends outwardly to the perimeter of the cover member 9 and forms a gap 33 intermediate to the spacer and cover members 7 and 9 respectively. A pair of screw holes 35 are aligned with the screw holes 27 of the spacer member 7 and the screw holes 17 of the plate member 5. A second holding means in the form of a pair of screws 37 are provided for cooperation with the screw holes 35, 27, and 17.
As to utilization of the above-described temperature sensor holding device, the plate and spacer members 5 and 7 are affixed to one another by the first fastening means 25. In this instance the fastening means 25 is in the form of rivets although other well-known fasteners are appropriate. As can be seen in FIG. 2, the central aperture 11 of the plate member 5 is aligned with the central aperture 19 of the spacer member 7 and both are aligned with the cut out portion 31 of the cover member 9. Also, the slots 13 of the plate member and the openings 21 of the spacer member 7 are aligned to receive a common fastener.
In assembling the above-described apparatus, an insulator material such as mica is placed in contact with a heat sink and a heat-generating semi-conductor device having a pair of diametrically opposed apertured ear members is placed in contact with the mica. Then, the attached plate and spacer members 5 and 7 are telescoped over the heat-generating semi-conductor device, and a pair of screws (not shown) attach the plate member 5, spacer member 7, and heat-generating semi-conductor device to the heat sink via the openings 21 of the spacer member 7, the slots 13 of the plate member 5 and the apertured ear members of the heat generating semi-conductor device (not shown). Thus, the heat generating semi-conductor device, the plate member 5, and the spacer member 7 are all easily detached from a heat sink by removel of the screws (not shown).
Thereafter, the cover member 9 of FIG. 3 is affixed to the spacer member 7 and plate member 5 by the second fastening means in the form of a pair of screws 37. These screws 37 pass through the screw holes 35 of the cover member 9, the screw holes 27 of the spacer member 7, and the holes 17 of the plate member 5. Also, the openings 29 of the cover member 9 permit access to the screws (not shown) passing through the openings 21 of the spacer member 7, the slots 13 of the plate member 5, and the apertured ear members of a heat generating semi-conductor (not shown).
In this manner, a temperature sensor device (not shown) disposed within the cut out portion 31 of the cover member 9 is brought into intimate contact with the heat generating semi-conductor device (not shown) disposed within the apertures 19 and 11 of the spacer and plate members 7 and 5. Also, the gap 33 intermediate to the cover and spacer members 9 and 7 provides strain relief of leads normally extending outwardly from a temperature sensor device disposed within the cut out portion 31 of the cover member 9. The cover member surrounds the heat sensor device and tends to provide thermal insulation for the heat generating semi-conductor and heat sensor devices from ambient temperature conditions of associated electronic apparatus.
Thus, there has been provided a unique temperature sensor holding device having numerous advantages over other known devices. The holding device is easily attachable to and detachable from a heat sink by fastening means normally employed to fasten a heat generating semi-conductor device. Also, a temperature sensor device is readily placed in intimate contact with, replaced, or removed from the vicinity of the heat generating semi-conductor device by a simple fastening or unfastening of the cover member.
Further, the holding device provides thermal shielding of the heat generating semi-conductor and temperature sensor device from ambient thermal conditions while providing intimate contact therebetween and to a heat sink. Moreover, the abovementioned shortened thermal path between the heat generating semi-conductor and temperature sensor device has provided a greatly reduced delay in circuit operation whereby failure of the heat generating semi-conductor due to slow circuit reaction is reduced.
While there has been shown and described what is at present considered a preferred embodiment of the invention, it will be obvious to those skilled in the art that various changes and modifications may be made therein without departing from the invention as defined by the appended claims.
Claims (7)
What is claimed is:
1. In electronic apparatus, a temperature sensor holding device comprising:
plate member means having an aperture therein for receiving a heat generating semi-conductor and formed for attachment to a heat sink;
spacer member means having an aperture aligned with said aperture of said plate member means and formed to telescope over said heat generating semi-conductor;
a first holding means connecting said plate and spacer member means;
cover member means formed for attachment to said plate and spacer member means, said cover member means having a cut out portion on the inner surface thereof aligned with said aperture of said spacer member means and formed to receive a temperature sensor device; and
a second holding means connecting said cover member means to said spacer and plate member means.
2. The temperature sensor holding device of claim 1 wherein said plate member and spacer member means each include a pair of diametrically opposed holes to provide overlaying of said plate member means by said heat generating semi-conductor and attachment of said plate member means and said heat generating semi-conductor to said heat sink.
3. The temperature sensor holding device of claim 1 wherein said cover member means includes a gap extending outwardly from said cut out portion to the ends of said cover and spacer member means whereby strain relief of leads extending from a temperature sensor device may be provided.
4. A temperature sensor holding device for an electronic apparatus comprising:
a plate member having a central aperture formed to telescope over a heat generating semi-conductor device;
a spacer member attached to the plate member, the spacer member having a central aperture formed to telescope over a heat generating semi-conductor device and having a pair of diametrically opposed openings intersecting its central aperture and aligned with a pair of diametrically opposed slots intersecting the central aperture of the plate member;
fastening means affixing the spacer and plate member to each other and for affixing those members to a heat generating semi-conductor device and to a heat sink; and
a cover member of electrical insulating material having a cut out portion on the inner surface thereof for receiving a temperature sensor device and for alignment with a heat generating semi-conductor device, the cover member attached to the spacer and plate members so that intimate contact may be effected between the heat generating semi-conductor device and the temperature sensor device.
5. The temperature sensor holding device of claim 4 including a gap intermediate to said spacer and cover members and extending outwardly from said cut out portion on the inner surface of said cover member to the outer edge of said spacer and cover members.
6. The temperature sensor holding device of claim 4 including a first holding means affixing said spacer member to said plate member and a second holding means affixing said cover member to said spacer and plate members.
7. The temperature sensor holding device of claim 6 wherein said first and second holding means are each in the form of a pair of spaced screw members.
US05/686,746 1976-05-17 1976-05-17 Temperature sensor holding device Expired - Lifetime US4117257A (en)
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Cited By (9)
* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5019940A (en) * 1987-02-24 1991-05-28 Thermalloy Incorporated Mounting apparatus for electronic device packages
FR2694083A1 (en) * 1992-07-27 1994-01-28 Peugeot Temperature sensor housing - consists of hinged lid provided with male studs for snapping into lower block and cooperating with female part in block for locating sensor, and self-adhesive base
US6447332B1 (en) * 1999-07-05 2002-09-10 Israel Aircraft Industries Ltd. Adapter for use in EGT measurement of a jet engine
US6477047B1 (en) * 2000-11-30 2002-11-05 Advanced Micro Devices, Inc. Temperature sensor mounting for accurate measurement and durability
US20040185712A1 (en) * 2003-03-18 2004-09-23 Delta Electronics, Inc. Structure of power line fixing module in electronic apparatus
US20070248142A1 (en) * 2006-03-29 2007-10-25 Harris Corporation Flexible circuit temperature sensor assembly for flanged mounted electronic devices
US10488062B2 (en) 2016-07-22 2019-11-26 Ademco Inc. Geofence plus schedule for a building controller
US10534331B2 (en) 2013-12-11 2020-01-14 Ademco Inc. Building automation system with geo-fencing
US10768589B2 (en) 2019-12-27 2020-09-08 Ademco Inc. Building automation system with geo-fencing
Citations (6)
* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2487900A (en) * 1946-10-23 1949-11-15 Julius U Sopher Protecting guard for attachment to wall receptacles
US2524250A (en) * 1946-08-03 1950-10-03 Elwin A Andrus Electrical outlet safety accessory
US2916733A (en) * 1957-07-26 1959-12-08 Hirsch Wilbert Cover for electric wiring and outlet
US3252611A (en) * 1964-06-17 1966-05-24 Slater Electric Inc Weatherproof electrical outlet box cover
US3859570A (en) * 1973-02-20 1975-01-07 Bose Corp Power transistor mounting
US3901080A (en) * 1972-06-02 1975-08-26 William Dwight Hilborn Temperature measuring device
Patent Citations (6)
* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2524250A (en) * 1946-08-03 1950-10-03 Elwin A Andrus Electrical outlet safety accessory
US2487900A (en) * 1946-10-23 1949-11-15 Julius U Sopher Protecting guard for attachment to wall receptacles
US2916733A (en) * 1957-07-26 1959-12-08 Hirsch Wilbert Cover for electric wiring and outlet
US3252611A (en) * 1964-06-17 1966-05-24 Slater Electric Inc Weatherproof electrical outlet box cover
US3901080A (en) * 1972-06-02 1975-08-26 William Dwight Hilborn Temperature measuring device
US3859570A (en) * 1973-02-20 1975-01-07 Bose Corp Power transistor mounting
Cited By (13)
* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5019940A (en) * 1987-02-24 1991-05-28 Thermalloy Incorporated Mounting apparatus for electronic device packages
FR2694083A1 (en) * 1992-07-27 1994-01-28 Peugeot Temperature sensor housing - consists of hinged lid provided with male studs for snapping into lower block and cooperating with female part in block for locating sensor, and self-adhesive base
US6447332B1 (en) * 1999-07-05 2002-09-10 Israel Aircraft Industries Ltd. Adapter for use in EGT measurement of a jet engine
US6477047B1 (en) * 2000-11-30 2002-11-05 Advanced Micro Devices, Inc. Temperature sensor mounting for accurate measurement and durability
US20040185712A1 (en) * 2003-03-18 2004-09-23 Delta Electronics, Inc. Structure of power line fixing module in electronic apparatus
US6921281B2 (en) * 2003-03-18 2005-07-26 Delta Electronics, Inc. Structure of power line fixing module in electronic apparatus
US7416332B2 (en) * 2006-03-29 2008-08-26 Harris Corporation Flexible circuit temperature sensor assembly for flanged mounted electronic devices
US20070248142A1 (en) * 2006-03-29 2007-10-25 Harris Corporation Flexible circuit temperature sensor assembly for flanged mounted electronic devices
US10534331B2 (en) 2013-12-11 2020-01-14 Ademco Inc. Building automation system with geo-fencing
US10591877B2 (en) 2013-12-11 2020-03-17 Ademco Inc. Building automation remote control device with an in-application tour
US10649418B2 (en) 2013-12-11 2020-05-12 Ademco Inc. Building automation controller with configurable audio/visual cues
US10488062B2 (en) 2016-07-22 2019-11-26 Ademco Inc. Geofence plus schedule for a building controller
US10768589B2 (en) 2019-12-27 2020-09-08 Ademco Inc. Building automation system with geo-fencing
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0
estoy practicando y le he estado dando vueltas a esto.
En Angular intento consumir datos de http://api.openweathermap.org, tengo mis servicios que se conectan con los datos, estos los puedo ver por consola. Tengo los servicios cargados en un componente básico, hice una función que hará la llamada al servicio mencionado anteriormente, dentro de esta función hay una suscribe, el punto es que dentro del suscribe puedo ver los datos por consola, pero cuando intento guardar los datos fuera de esta función en una variable global que ya había creado no lo guarda, intenté colocarle un return dentro del suscribe pero tampoco me deja sacar el arreglo para procesarlo fuera del suscribe, cuando hago un console log de este ultimo array me devuelve undefined Estoy confundido, alguien puede orientarme? Dejo un pedazo del código: *** Ya todo esta importado y conectado con los servicios correspondientes.
export class UnoComponent implements OnInit {
AllDataObj = {};
AllData_Arr = {};
constructor(private dataApi: DataAppService) { }
ngOnInit():void {
console.log(this.GetAllData());
}
GetAllData(){
this.dataApi.getAllData().subscribe((data) =>
{
this.AllDataObj = (data);
this.AllData_Arr= JSON.stringify(this.AllDataObj);
return this.AllData_Arr;
});
}
• Estas difiniendo mal el tipo de dato de tus variables cambia {} por [] ya que lo que recibes es un array – FRANCISCO J. BLANCO el 15 ago. 19 a las 15:13
0
Es un error común al trabajar con observables. El procesamiento de los datos debe hacerse en la función callback del subscribe. Te explico un poco, la función subscribe() crea una subscripción al objeto que está emitiendo datos, pero como no se sabe en qué momento se emitirá un dato por eso se le pasa al subscribe() una función callback, esa función será llamada cada vez que se produzca un dato y se le pasará como parámetro, en este caso llamado data, el valor producido. Por eso dentro de esa función debe colocarse la lógica para procesar los datos recibidos. Y si inmediatamente luego de llamar a subscribe(); haces un console.log(variable); el resultado será undefined porque todavía no se han producido datos para guardar en esa variable.
GetAllData(){
this.dataApi.getAllData().subscribe((data) =>
{
this.AllDataObj = (data);
this.AllData_Arr= JSON.stringify(this.AllDataObj);
//aquí se procesan los datos recibidos.
});
console.log(this.AllDataObj) // undefined porque todavía no se ha producido un valor
}
0
Lo que veo es que estas definiendo tus variables para un tipo Object y no para un array modifica tu código de la siguiente forma:
export class UnoComponent implements OnInit {
AllDataObj: any;
AllData_Arr = [];
constructor(private dataApi: DataAppService) { }
ngOnInit(){
this.GetAllData();
}
GetAllData() {
this.dataApi.getAllData().subscribe(
result => {
this.AllDataObj = result;
this.AllData_Arr= JSON.stringify(this.AllDataObj);
console.log(this.AllData_Arr)
});
}
• Hola Francisco, gracias por responder. Tengo una pregunta adicional, tomando en consideración los comentarios de todos analicé la situación y replantié el ejemplo: private getPosts() { this.wp.getAll(5) .subscribe( data => { this.feed = data; this.allDataArr = JSON.stringify(this.feed); // console.log(this.allDataArr); <-- aqui puedo ver por consola. }); Cómo hago para los datos de allDataArr de la función getPost(), por consola puyedo verlos, sin embargo, los console.log fuera de esta función devuelven undefined y los retornos dentro de suscribe no work – Josueth Acevedo el 16 ago. 19 a las 13:51
• Muestrame como tienes definido this.allDataArr ? – FRANCISCO J. BLANCO el 16 ago. 19 a las 13:54
• Hola Francisco, buscando en internet, encontré una alternativa similar a lo que estoy haciendo. Para resolverlo el profesional insertó dentro del result una función para que manejara la asignación del resultado de forma externa, en mi caso funcinó esto: result=> this.construyeURLJson(result) pero ahora me quedan más dudas respecto al funcionamiento de esta función, Acaso es una rutina encapsulada? solo es válida la data mientras se ejecuta esa línea? necesita de un elemento asincrono o una promesa? seguiré investigando y probando. Gracias por sus comentarios. – Josueth Acevedo el 17 ago. 19 a las 15:17
0
Este error se debe al tipo de dato que devuelve tu funcion getAllData(), para solucionar esto ve a tu DataAppService en el metodo getAllData() añade o cambia el tipo de dato de retorno a ":any" de la siguiente manera:
getAllData():any{
//return http. etc,etc
}
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Even for an Essential Nutrient, Vitamin D Overdose May Be Too Much of a Good Thing
It's always possible to get too much of a good thing. Vitamin D overdose is rare, but in susceptible individuals, the consequences can be severe.
Vitamin D Overdose at the Supermarket
Hans was a health-conscious shopper who had one notably unhealthy habit. He loved greasy, grilled hamburgers cooked on his backyard barbecue. One Saturday Hans walked into his neighborhood butcher shop and found that hamburger meat was on special, going for less than half price. But the hamburger looked rosy red and smelled fine.
Hans fired up the grill and gathered his family for their weekly greasy treat. The meat tasted fine and there were no ill effects until the next day when they all went for a hike in the woods. Even on a cloudy day and even while walking in dense woods, Hans and his family soon developed severe sunburn, so sunburn they had to go to the ER.
Taking Too Much Vitamin D Is More Common than You May Think
Too Much Vitamin Consumption
It turned out that the cause of the super-sensitivity to sunlight experienced by Hans, his wife, and their children was caused by an extreme overdose of vitamin D. Before the practice was banned, many butchers added vitamin D to ground meat to keep it from getting a green tint as it sat in the counter. Hans and his family had consumed the equivalent of nearly ten million units of vitamin D in just one meal, changing the physiology of their body in major ways. Fortunately, they were treated before the effects became permanent.
As a result of this and many similar case histories, the European Union severely regulates the use of vitamin D in food and supplements. The argument can be made that the EU comes down to hard on vitamin D dosages, but hypervitaminosis D, or vitamin D overdose, is more common than you might think.
What Are the Symptoms of Vitamin D Overdose?
Only the most extreme overdoses of vitamin D produce dramatic symptoms requiring emergency treatment. Usually hypervitaminosis causes symptoms that are more subtle and that occur over a period of weeks or months. Typical symptoms of too much vitamin D include:
Vitamin D itself usually does not cause drastic changes in health, but when vitamin D shifts calcium balance, then hypercalcemia, or the accumulation of calcium in the bloodstream, can. High calcium levels can cause groans, moans, stones, and psychiatric overtones manifesting themselves as abdominal pain, depression, bone pains, and confusion. A combination of too much vitamin D and too much calcium is especially problematic.
Does vitamin D cause constipation? It's actually calcium that causes constipation when you consume too much vitamin D, and fiber can both ease constipation and slow down the absorption of calcium.
How Much Vitamin D Is Too Much?
The symptoms of vitamin D overload usually kick in at about 100,000 IU per day, so most experts advise taking no more than 10% as much, or 10,000 IU per day. (A dose of 10,000 IU per day is equivalent to 1250 micrograms per day.) If you have active cancer, you should not take vitamin D except under the supervision of a physician. If you are pregnant, be sure that you also take vitamin K or eat several servings of green leafy vegetables to get your K, every week. If you have actually been poisoned by vitamin D, then stopping all vitamin D supplementation, consuming vitamin K, and avoiding calcium usually corrects symptoms in about a month.
Selected Reference:
Lips, P (2007). "Vitamin D status and nutrition in Europe and Asia". The Journal of steroid biochemistry and molecular biology 103 (3-5): 620–5.
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Simple Encryption for Beginners: Just the Basics
Computer jargon and the technologies they describe can be very complicated. There’s nothing wrong with that and, for the people who develop and make this stuff, the complexities are part of the thrill.
Even as an enthusiast user, most of the low-level mathematical details of how high-technology works are completely beyond me.
If you aren’t an enthusiast of computer technology, then do you really need to know and understand all of the details? The answer is of course no. In fact, if a technology needs specialized knowledge to use it, then it’s not ready for prime time.
The same is true for computer encryption. While the technical details of encryption can be mystifying, actually using it as a consumer isn’t that hard at all. You do need some foundational knowledge about how encryption works in general to make good decisions. When it comes to your own security, the ultimate responsibility falls on you. So being informed is essential.
Encryption: Explain it to me Like I’m 5
Say you wanted to send someone a letter, but the content of the message is pretty sensitive. It has a big secret that ONLY the person who is meant to read should ever see. If someone else got their hands on it, you’d be in more trouble than you imagine. Let’s just say that you are very motivated to keep the message out of the wrong hands.
So how would you do it? Would you hire armed guards? Put it in a very strong lockbox? What about putting a code on it and if the wrong PIN is put in, the message self-destructs?
These are all pretty serious solutions, but even then there’s no guarantee that someone won’t get around it. So why not just write the message in a form that ONLY the person on the other end knows how to read? Almost like a secret language between the two of you.
That’s a good analogy if what “encryption” is. It’s a way of manipulating your message so that no one else understands it. The other person knows how you manipulated it and can reverse the process when they get your message. So it doesn’t matter if someone else has a copy of the information. It won’t make any sense.
That’s encryption in a nutshell.
OK, But How?
That’s a good question. It’s one thing to say we “manipulate” the message to make it unreadable, but what does the actual process look like?
First, let’s introduce some terms. You already know that the act of scrambling the message is called encryption. Encryption is the practical part of a field known as cryptography. The method we use to manipulate the message to scramble it is called a “cipher”.
All cryptography is based on the art of creating ciphers. The cipher is the bit you have to share with the other person who is going to receive the message. You use the instructions built into the cipher to mix up the message. Then the person on the other end uses the cipher to un-mix the whole thing.
What does a cipher actually look like? The simplest example is the substitution cipher. This is one you don’t need a computer for but has actually been of practical use in history. Good enough for army generals and such. What you do is you take a letter in the message and then you substitute it for something else. It could be another letter in the alphabet, some symbols you made up.
It’s all About Keys These Days
PIle of Keys
The ciphers we use on computers these days are conceptually the same as other cipher types. The key difference is that knowing how the cipher works isn’t enough to reverse its effects. How can this be? It’s thanks to the inclusion of randomness. As you probably already know, randomness is patternless by definition. If you choose 100 numbers at random then there is nothing connecting them to one another.
The ciphers we use for computers leave a little gap in them that has to be filled with a random sequence of symbols. These then form an integral part of how the cipher scrambles up the information. This means that simply knowing how the cipher works, in general, won’t help you decode a specific message.
As a part of the cipher’s functionality, there’s a unique string of symbols known as the encryption key. You need both this key and the cipher in order to make sense of the message again. The ciphers are so complicated that only a computer has any hope of applying them. Which means the only way forward is to guess the key. Except, there’s one little problem with that…
The Keys are Impossible to Guess
Encryption
Well, not technically impossible, but so hard that it might as well be impossible. Remember that the keys are randomized, which means there is no way to predict or derive the key from anything else.
That means to break the encryption you’ll have to guess. How long will that take? OK, let’s do a quick example to give you an idea. Let’s say you wanted to steal a bicycle. I don’t know why you just want one desperately.
The bicycle has a padlock with a four-digit combination. Each digit can be anything from 0-9. Since there are four digits, it means the number that will unlock the bike is between 0000 and 9999. That’s 10 000 possible numbers. If you had to guess every possible number and you could do one number per second, it would take you almost three hours to go through all of them. Of course, you’ll probably hit the correct number sooner than that. There’s a 50% chance it will be in the first half of possible numbers. That’s “only” about an hour and a half. Still, you’d probably be caught long before you actually found the answer.
Now imagine we add just one digit to this lock. Then we can go from 00000-99999. Now we have ten times as many possible combinations and it would now take ten times as long. With each additional digit in the code, the difficulty of guessing it goes up by a factor of ten.
The same is true of encryption keys, but the numbers are far, far more insane. The typical encryption key is 128 or 256 digits long. Moreover, each digit isn’t just between 0-9. Instead, it has the whole alphanumeric set available. That includes all the numbers and both cases of the alphabet. The total number of guesses is in the trillions, which means there simply isn’t enough time or energy in the universe to ever guess the right answer.
Everyone Has a Type – of Cryptography
There are many ways to approach encryption. You already know that today’s encryption centers around keys, but not all key-based encryption is the same. There are three main encryption types you should know about as an internet user.
The most basic type is symmetric encryption. That’s just a fancy way to say that the key you use to encrypt, also decrypts. That means if anyone ever got their hands on the key, you’re in trouble. WiFi networks use this setup. Your WiFi password is the key in this case. That’s why you should use a VPN with public WiFi. Everyone has the key, so they can spy on you if they want to.
To solve the issue of getting keys to people without giving them decryption access, we invented asymmetric encryption. Now there are two of these keys. Each one can only do a single job: encrypt or decrypt.
So you can safely make one public. Anyone who wants to send you a message can use your public key. Only you can decipher it with your private key. To send info back the other way, you use the other person’s public key.
Finally, there’s hashing, which is not exactly data encryption, but it’s related. When you hash a piece of data you get a unique signature. If just one bit was different in the data, the hash looks completely different. The actual data is not in the hash itself. Hashes are used to verify if data has been altered. We also use them for passwords. A provider like Facebook doesn’t have your actual password on file. Just the hash of it. When you type in a password, it gets hashed again. If both hashes match exactly, you are given access.
What Cryptography Does for Us
It’s not hard to find an example of cryptography helping you out in your daily life. For example, you’re probably connected to a WiFi network right now or will be at some point today. The WiFi passcode is actually an encryption key, albeit a rather simple and short one. Based on what you read above, you might have figured out that it’s an example of symmetric encryption.
That’s not the only place by a long shot. Here are some common use cases where encryption makes your life better.
Disk and Device Encryption
Hard Drive Internals
The information on our computer drives and smartphones are likely to contain some very sensitive and a need to protect are obviously there.
Encryption can help in a big way. There are plenty of full disk encryption programs out there to turn your Windows, Mac or Linux PC into a data fortress.
The same goes for Android and iOS phones and tablet. These days they come with full disk encryption activated by default. With disk encryption in place, it doesn’t matter if someone gets physical access to your data. Without a decryption key, they have zero chance of getting to your information.
Internet Encryption
Ethernet Cables
If you use WiFi, the router encrypts the signal between itself and your device. If you visit a website that has HTTPS protection, all the information about you and their server is protected. That’s very useful if you don’t want banking details or other private info being intercepted on the way to or from a web server.
Then there’s VPN protection. A VPN or virtual private network encrypts every single bit of data that left or enters your network port. This means that your internet provider and your government can’t spy on what you are doing. The site you are connecting to doesn’t know who or where you are either. It’s a strong form of protection that’s within everyone’s reach. We like ExpressVPN in particular. So that might be a good place to start.
Encryption: Hard to Crack, Easy to Understand
These are all the basic facts needed to understand encryption and its role in our daily digital lives. Thanks to encryption we all get to live and work in relative safety. By integrating encryption into your daily life, you can effectively combat a world which wants to strip you of your privacy. I don’t know about you, but that doesn’t sound like a good deal!
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Delta 9-Thc is a new and exciting cannabinoid that is quickly gaining popularity in the cannabis industry. Delta 9-thc is a delta-9 THC cannabinoid, which is different than other cannabinoids found in cannabis. Delta 9-thc has been shown to have a wide range of benefits, including reducing anxiety, improving mood, and reducing pain.
What is Delta-9 THC?
Delta 9-thc is a new and exciting cannabinoid that is quickly gaining popularity in the cannabis industry. Delta 9-thc is a delta-9 THC cannabinoid, which is different than other cannabinoids found in cannabis. Delta 9-thc has been shown to have a wide range of benefits, including reducing anxiety, improving mood, and reducing pain.
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The benefits of delta 9-thc are still being studied, but are thought to include reducing anxiety, improving mood, and reducing pain.
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What is the Dose of Delta-9 THC?
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Delta 9-thc is currently legal in all 50 states. There has been some debate over the past few years as to whether or not delta 9-thc should be classified as a Schedule I drug, which would make it more difficult to access and study. However, the Drug Enforcement Administration has not made any decisions on its classification yet.
Which Delta-9 THC Product is right more me?
Delta-9 THC products come in a variety of different concentrations, from very low to extremely high. For many people, the ideal product will fall somewhere in the middle; it should provide a noticeable psychoactive effect but not be too strong or overpowering.
When choosing a delta-9 THC product, it is important to consider your specific needs and preferences. Some people prefer products with low concentrations of THC, while others enjoy products that are high in THC content. It is also important to consider how you will use the delta-9 THC product.
If you plan on using it recreationally, then you will want to choose a product with high concentrations of THC. If you are using it for medical purposes, then you will want to choose a product with lower concentrations of THC.
What’s The Difference between Delta-9 THC & Delta-8 THC?
Delta-9 THC is the purest form of THC available, while delta-8 THC is a derivative of delta-9 THC. Delta-8 THC is often more potent than delta-9 THC, and it is often used in medical applications.
Conclusion
Delta 9-thc is a new and exciting cannabinoid that is quickly gaining popularity in the cannabis industry. Delta 9-thc is a delta-9 THC cannabinoid, which is different than other cannabinoids found in cannabis. Delta 9-thc has been shown to have a wide range of benefits, including reducing anxiety, improving mood, and reducing pain. Be sure to speak with a doctor or pharmacist about the correct dose for you before using delta 9-thc.
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Ffmpeg Filter Threads
In fact, FFmpeg allows custom conversion and other operations defined under-filter_complex flag, a more elegant way. Use FF_THREAD_SLICE threading mode in FFmpeg for MediaSource streams. And when i use ffmpeg directly in command line coding from file to file using parameter -threads 0 or -threads 2 it works nice. ffmpeg -i video. vob Someone recently found that the Windows XP Pro's QoS policy was throttling his pyTivo transfers quite a bit and posted instructions to workaround it here:. FFmpeg is a free, open-source software and it's the Swiss Army knife of video- and audio-related processing. (ex: C:\ffmpeg) 5. Open multi-thread, the avcodec_encode_video2 function execution time is 2% before. 0 ffmpeg libavformat version. The default is the number of available CPUs. This package is known to build and work properly using an LFS-9. mp4 -i logo. This is true for all filters syntax in windows ffmpeg with full paths eg. This option is only available when FFmpeg has been compiled with "--enable-opencl". Wow! Is it really. I can dump images from video but how to reverse all images and make video. 转换命令： FFmpeg -i IN -map 0 -r 25 -threads 4 -y Out 本机测试机环境： win7 旗舰版 +Intel(R) Core （ TM ） i5-2400 CPU @3. User testing is not going to teach us much. The reason i ask is that before, on linux, i used this with a program called Ps3mediaserver. The two cores are used about equally but when i use ffserver only one core i uses as most, the second one is not on much load (about 2-5%) Josh Joy pisze:. -filter_threads number of non-complex filter threads -filter_complex_threads number of threads for -filter_complex -stats print progress report during encoding. post314-g78a3d57 | about patchwork patch tracking system | version v2. Previous behavior can be restored with the -noaccurate_seek option. FFmpeg may delay frames in FF_THREAD_FRAME mode, which affects MediaSource streams. _____ In Mike Kavanagh's code: -filter_complex "concat=n=3:v=1:a=0 [a] [v]" a=0 should be a=1 It's the number of output streams, not a stream index. FFMpeg usually fires as many threads as possible for the codec but limited to the amount of cores in the processor. See this link that from i am use to library in my gradle. It will not hurt anything being there. You'll find everything what you need with this package. Press question mark to learn the rest of the keyboard shortcuts. '-filter_threads nb_threads' Defines how many threads are used to process a filter pipeline. 3), kernel 4. HD videos. You can find all the libvmaf options here. To see what filters are available with your build see ffmpeg -filters. There are several threads regarding this "issue" that the amix filter changes the volume of the input files. ffmpeg -loglevel debug -threads:v 2 -threads:a 8 -filter_threads 2 \ -thread_queue_size 512 -f x11grab -s 1920x1080 -framerate 60 -i :0. I'm trying to use the subtitle filter to burn in the subtitles while encoding. mkv Note that in the above example the shortest option for overlay filter is used to end the output video at the length of the shortest input file, which in this case is input. BUG=338529. A53 CC bitstream is stored as uint8_t in AVFrameSideData. These instructions are for Ubuntu Karmic Koala 9. FFmpeg filtering is a wide topic because there are hundreds of filters and thousands of combinations. mkv -vcodec mpeg2video -b 12Mi -maxrate 30000k -bufsize 12Mi -ab 448k -ar 48000 -acodec ac3 -copyts -threads 2 -drc_scale 0. How many encoding threads should be used. Current ffmpeg has two filters that can be directly used for normalization – although they are already quite advanced, so they do not simply apply gain to reach a peak level. I’ve been testing the various deinterlacing filters in FFMPEG, and no matter what I try, NNEDI fails to initialize. 247 probe in dash demuxer. Using ffmpeg to fade and cross fade audio and video ffmpeg can be used to fade and cross fade audio and video in a single clip, or between 2 or more clips which is handy if you dont wont to open a video editor Combine audio and video files into a new file Sometimes you need to extract the. It was: ffmpeg -f alsa -ac 2 -i pulse -f x11grab -r 30 -s 1280x1024 -i :0. This package is known to build and work properly using an LFS-9. libvmaf – Identify the filter "model_path=vmaf_v0. It supports the most obscure ancient formats up to the cutting edge. FFmpeg's curve filter is normalized 0-1. As first step you will need to install FFMpeg on your development machine. To enter full paths, for every colon , you need to enter a preceding backslash. As we know ffmpeg is provided for Windows operating systems too. -lavfi filtergraph (global). If you have a program that works with video, there is probably a copy of FFMPEG on your computer. gif -filter_complex overlay=shortest=1 out. mp4-vcodec copy -acodec copy -scodec copy outputfile. mp4 -vf crop=h=in_h/2:y=0 -c:a copy output. DNxHR is for resolutions bigger than 1080p such as 2K, 4K, and 8K. Note: avconv and ffmpeg are not entirely drop-in replacements. FFmpeg can also convert from any sample rate to any other, and resize video on the fly with a high quality polyphase filter. mp4 -pix_fmt yuv420p -deinterlace -vf "scale=640:360" -vsync 1 -vcodec libx264 -r 29. FFMPEG via commandline What is the difference between WingsVIOSO and WingsRX? How do I set up a camera based calibration for a stacked projection with WINGS VIOSO?. It works fine, but with these other lines I can convert a video to x264 with a much better quality (thanks, in part, to a sharpen filter): ffmpeg -i "test. i was wondering if anyone has tried compiling the experimental multithreaded version of ffmpeg on freebsd 7. C# Thread 관련 API 중 왠만하면 절대 사용하면 안되는 함수 Thread. The FFmpeg filters you choose now may be changed in future releases and patches. This will make a Matroska container with a VP9 video stream and a Vorbis audio stream, essentially the same as the WebM we made earlier. Tacomas (1995-2004)' started by austinsdad99, You can use either the D1 or D3, both have the same threads, D3 is a. How to detect ffmpeg lib in xamarin? Sorry my bad English language Thanks for advice. That said, this is a new video filter that may. It can also convert between arbitrary sample rates and resize video on the fly with a high quality polyphase filter. I used ffmpeg to record my desktop/games on Ubuntu. FFmpeg includes libavcodec audio/video codec library in it. ffmpeg is a very fast video and audio converter that can also grab from a live audio/video source. 0 Comments. mkv -filter_complex_threads nb_threads (global) Defines how many threads are used to process a filter_complex graph. MidwayUSA is a privately held American retailer of various hunting and outdoor-related products. FFmpeg should automatically choose the number of CPU threads available. > In all cases the x264 gets the correct interlaced params - media info shows > "interlaced=tff" in the 'Encoding settings', but the 'idet' test remains > the same. The main reason is, that the libraries, which ffmpeg uses provide more encoding options (like x264) which can improve quality, or are necessary for professional encoders, and the ffmpeg command line options are very limited (the C/C++ interface has the same limitations). When I run 'top' this process is consuming almost 500% of my CPU (according to. Its a real shame ffplay isnt installed with ffmpeg as its very useful for testing audio and video filters If building ffmpeg with poudriere is the only option to enable ffplay, then i will do a full write up of the steps involved. mkv Note that in the above example the shortest option for overlay filter is used to end the output video at the length of the shortest input file, which in this case is input. Toyota oil filter. Use the option "-filters" to show all the available filters (including also sources and sinks). Have a fun in development. Press question mark to learn the rest of the keyboard shortcuts. FFmpeg also has a -threads option that limits the number of threads used (CPU cores). How to avoid recording over the previous recordings. I don't know how much processing power is needed to run this filter in real-time, but the re-encoding of an 1080p video results in about 25fps on my machine. When FFmpeg is configured with "--enable-opencl", the options for the global OpenCL context are set via -opencl_options. However there seems to be no way in R2 to do things like append custom FFmpeg vf parameters for custom filtergraphs, do stream selection or apply bitstream filters. I am using a shared hosting with ffmpeg enabled (version 2. 3 %: 248 / 374: 43. 1 -c:v libx264 -g 24 -bf 3 -b_strategy 2 -coder 1 -r 25000/1000. mp4 -filter:v "crop=out_w:out_h:x:y" output. You can apply filters on FFMpeg\Media\Audio with the FFMpeg\Media\Audio::addFilter method. Foreword: just like everything else in FFmpeg, libavfilter is monolithic, which. FFmpeg Basics by Frantisek Korbel, describes various FFmpeg features and common tasks. I use the ffmpeg at mobile browser. File filter Filter file types. ffmpeg -i -vcodec dnxhd however, this does not work, and the examples I have seen on converting into dnxhd with ffmpeg I do not understand, they seemed each time having some different tags without explaining why to use them. 39 (libva 1. Turn Off Multi-Threading. All builds require at least Windows 7 or Mac OS X 10. This package is known to build and work properly using an LFS-7. mkv Note that in the above example the shortest option for overlay filter is used to end the output video at the length of the shortest input file, which in this case is input. - add a FATE test, generally by adding an entry in: tests/fate/filter-video. Like • Show 0 Likes 0. Cuts the audio at a desired point. mp4" -an -pass 1 -vcodec libx264 -r 30 -preset slow -s 640x360 -b:v 750k -bt:v 850k -vf unsharp=5:5:1. I have been trying to utilize the amf-amdgpu-pro package from driver 19. Joining videos in Xabe. When you use it with pscrn=none it produces essentially perfect results. 5 will reduce signal level by half (2 multiplied by 0. FFmpeg is an audio/video conversion tool. FFmpeg is a robust open-source framework designed for command-line-based processing of video and audio files, and widely used for format transcoding, basic editing (trimming and concatenation), video scaling, video post-production effects, and standards compliance. (ex: C:\ffmpeg) 5. It works fine, but with these other lines I can convert a video to x264 with a much better quality (thanks, in part, to a sharpen filter): ffmpeg -i "test. I've just been using an older version of ffmpeg because it doesn't have this problem. what is "default is 1" in the first 3 options?) of FFmpeg alimiter filter? gain is simple multiplier - 1 mean no modification of audio (2 multiplied by 1 stay 2) - 0. -opencl_bench This option is used to benchmark all available OpenCL devices and print the results. That’s why the script is so useful because it looks at the file to begin with to determine what is needed and will perform the “fastest” method. 5 will be 1), gain 2 will "amplify. This will rotate the video 180° counter-clockwise. I'm currently stuck, because certain ffmpeg commands only seem to work properly in newer versions of ffmpeg. FFmpeg can use a Video4Linux compatible video source and any Open Sound System audio source. The CIAO package includes the dmextract tool to calculate the lightcurve of a dataset (or region within a dataset), and the dmgti tool to create a GTI file given a table and a set of limits. Below are examples showcasing Subscribe logo in different locations. 263, which is a less CPU. 0L's injectors clean as a whistle. 대신 모든 쓰레드의 종료는 Thread. Audio options:-ab bitrate audio bitrate (please use -b:a)-ac channels set number of audio channels-acodec codec force audio codec ('copy' to copy stream)-af filter_graph set audio filters-aframes number set the number of audio frames. It runs on Linux, Windows, Mac Os X, iOS, Android OS, and others. Note: avconv and ffmpeg are not entirely drop-in replacements. It is the same syntax supported by the C printf function, but only formats accepting a normal integer are suitable. mp4 example of big buck bunny cropped, converted to grayscale and padded then overlayed onto of Night of the living dead to mix the footage together. If you re-read my first post you will see that you now have the '-ac 2' parameter after the '-i hw:1,0' parameter so it forces 2 channels on the output. i am use to FFmpeg library in android for reverse video. Basically it looks like ffmpeg+h264_vaapi emits packets very rarely, only a couple per second. ffmpeg distinguishes between two types of filtergraphs: simple and complex. mkv But now on openSUSE I have absolutely no ideia how to get it to work. Nightly git builds are licensed as GPL 3. The number of actual threads used by FFmpeg do not line up with the number I pass using the -threads argument. As first step you will need to install FFMpeg on your development machine. Nor has this filter been tested with anyone who has photosensitive epilepsy. avi -vcodec mjpeg -q:v 0 -f avi -acodec libmp3lame -vf scale=1280x720:dst_format=rgb8 - | ffmpeg -i - -lavfi "[0:v]format=gbrp12le,scale=1280x721:dst_format=gbrp12be,scale=src_format=gbrp12le,scale=1280x720,setsar=1/1[out]" -map "[out. Tried to reply from Nabble, but it said my message didn't go through to the mailing list. mp3" -i "audio_2. pkl - path to VMAF model (this is the default model):log_path=VMAF. [FFmpeg-user] Multiple FFMpeg-Cuda-HLS-Transcoding Instances -> Deadlock Behavior Marco Kittel Mon, 04 May 2020 01:23:23 -0700 Hello, i'm having a hard time rendering multiple hls instances with nvidia gear. Overview Synopsis: It may be necessary to filter your data to remove periods of anomalous background levels, such as the flares seen in ACIS observations. Use the option "-filters" to show all the available filters (including also sources and sinks). mp2, via Windows. mkv There were 3 parts, as my camera splits into 2 GB files, after they were sped up, avidemux was used to combine them. FFmpeg is the leading multimedia framework, able to decode, encode, transcode, mux, demux, stream, filter and play pretty much anything that humans and machines have created. But, I fixed this by upgrading tovid to 0. Finally, the image is scaled using scale_npp and encoded on the GPU. But you can use several threads with proper locking, you. /ffmpeg -formats command to list all supported formats. You can get a lot of information about how to encode with FFmpeg all over the web including FFmpeg/libav's web site. "-threads:1 4" would set the thread count for the second stream to 4. Welcome to LinuxQuestions. And, is there a way to deactivate it? Because it also makes opendml files even with. So the default may still be optimal in the sense of "as good as this ffmpeg. Hello there, I'm trying to get the Vulkan H/W filters, specifically scale_vulkan working with NVIDIA GPUs, but to no avail. SPEED UP OR SLOW DOWN THE VIDEO. For example, this command: ffmpeg -y -i "audio_1. I'm currently stuck, because certain ffmpeg commands only seem to work properly in newer versions of ffmpeg. oil pumps 101 and oil filter. OS X Users: The homebrew version of ffmpeg doesn't include webm support by default, try brew install ffmpeg --with-libvpx. /ffmpeg -i input. 30 in Ubuntu 18. FFmpeg中已经支持libvmaf作为filter进行处理，但需要单独进行配置 安装 在Linux下只需下载vmaf源码直接make install，然后使用配置. Is it because > the rest of ffmpeg is multi-threaded, and that's why it's at 500 percent? > Please forgive me if I don't undersdtan the internal architecture of > ffmpeg. REM without opencl ". You can build your own filters and some are bundled in PHP-FFMpeg - they are accessible through the FFMpeg\Media\Audio::filters method. One filter graph must be handled from a single thread at a time. Also see the ffmpeg filters (FFMpeg Video Filters) for padding/cropping methods. 2的overlay必须是complex filter，调试这个命令： ffmpeg -re -i ~/test_22m. Processing callbacks on correct thread 5. Some options can be changed during the operation of the filter using a command. You can apply filters on FFMpeg\Media\Audio with the FFMpeg\Media\Audio::addFilter method. r/ffmpeg: FFmpeg is the leading multimedia framework, able to decode, encode, transcode, mux, demux, stream, filter and play pretty much anything … Press J to jump to the feed. Description ffmpeg is a very fast video and audio converter that can also grab from a live audio/video source. Code: Cropdetect C:\FFMPEG64\bin\ffmpeg. ffmpeg -i capture. You have to apply a patch before building ffmpeg in order to access that functionality. DNxHR example. added simple image watermarking example with FFMpeg filter graph (DemoWebForms) 2014 Aug 04: v. Debug, Improvements, Optimization FFmpeg is a 17 years of Video Processing experience. bat files and ffmpeg. The main reason is, that the libraries, which ffmpeg uses provide more encoding options (like x264) which can improve quality, or are necessary for professional encoders, and the ffmpeg command line options are very limited (the C/C++ interface has the same limitations). Open the 'Project Settings' dialog box and in the C++ tab, choose the 'Preprocessor' option. You can get a lot of information about how to encode with FFmpeg all over the web including FFmpeg/libav's web site. DNxHR is for resolutions bigger than 1080p such as 2K, 4K, and 8K. ffmpeg -i input_0001. FFMPEG threads option Add an option to specify the amount of encoding threads for FFMPEG Mikk36 Feb 25, 2015. This may slow down video decoding for streams that were encoded without slicing, as in that case decoding will be happening on a single thread. 0625 , so on a [0,1] interval scale, x=0, y=0 is remapped to x=0, y=0. The default is the number of available CPUs. This wiki page is for user contributed examples and tips, and contributions to this page are encouraged. exe" -threads 0 -threads 0 -i ". Today we want to make a simple script that allows you to record the screen with your voice from the mic avoding to overwrite what you. This package is known to build and work properly using an LFS-8. I only want to change the h264 level to 4. fedulova on Nov 5, 2019 Latest reply on Nov 5, 2019 by techsupp. Documentation. ffmpeg installation in solaris 10 807557 Jul 15, 2009 11:34 AM Hello, SunOS MixemSun 5. FFmpeg is the leading multimedia framework, able to decode, encode, transcode, mux, demux, stream, filter and play pretty much anything that humans and machines have created. 100000:first_pts=0" -f mp4 -y. 1 将输入的1920x1080缩小到960x540输出:. When the input packets aren't dequeued fast enough and the queue is full, ffmpeg can't deposit new packets from the input into the queue so it has to wait and the warning is printed. x, but keeps saying “ffmpeg is already the newest version (7:4. FFmpeg and its photosensitivity filter are not making any medical claims. avi -sameq -vcodec libx264 -nr 1000 -pass 1 -passlogfile passlog -acodec libvo_aacenc outvideo. FFMPEG via commandline What is the difference between WingsVIOSO and WingsRX? How do I set up a camera based calibration for a stacked projection with WINGS VIOSO?. mkv -vf scale=720:412,fifo,pad=720:576:0:82:0x000000 -y -target pal-dvd -sn -acodec copy -g 12 -t 60. mkv Note that in the above example the shortest option for overlay filter is used to end the output video at the length of the shortest input file, which in this case is input. 10 Generic_120012-14 i86pc i386 i86pc I am trying to install ffmpeg in solaris 10 but no luck, Not able to install. This option is only available when FFmpeg has been compiled with "--enable-opencl". The FFmpeg code itself has not stopped being XP/Vista compatible, but the inclusion by Zeranoe of some external libs that are either themselves by default not compatible or have become incompatible at some stage of their development is what broke recent Zeranoe builds on XP/Vista. No one was streaming anything and nothing seems to be transcoding but Process Explorer shows this command line that was launched by Mezzmo. -threads:1 4 would set the thread count for the second stream to 4. r/ffmpeg: FFmpeg is the leading multimedia framework, able to decode, encode, transcode, mux, demux, stream, filter and play pretty much anything … Press J to jump to the feed. filter_graph is a description of the filter graph to apply to the input video. exe" -threads 0 -threads 0 -i ". Greetings all, The Problem is solved. Can anyone please explain the options, especially the first 3, and the settings ( e. ImageMagick utilizes multiple computational threads to increase performance and can read, process, or write mega-, giga-, or tera-pixel image sizes. 0: - Common Encryption (CENC) MP4 encoding and decoding support - DXV decoding - extrastereo filter - ocr filter - alimiter filter - stereowiden filter - stereotools filter - rubberband filter - tremolo. Finally, the image is scaled using scale_npp and encoded on the GPU. 137 --disable-w32threads disable Win32 threads 415 --sws-max-filter-size=N the max filter size 534 [email protected] avi The syntax "foo-%03d. 0625 , so on a [0,1] interval scale, x=0, y=0 is remapped to x=0, y=0. I want to filter all values longer than 30 characters. We could commit this with thread count set to 2 and the audaspace changes left out, for the purpose of getting the small speedup. In this example, the "hold" knot is at x=1, y=1 16/256 code values = 0. Use the option "-filters" to show all the available filters (including also sources and sinks). Affects: Encoding, Video. You can build your own filters and some are bundled in PHP-FFMpeg - they are accessible through the FFMpeg\Media\Audio::filters method. Using ffmpeg to fade and cross fade audio and video ffmpeg can be used to fade and cross fade audio and video in a single clip, or between 2 or more clips which is handy if you dont wont to open a video editor Combine audio and video files into a new file Sometimes you need to extract the. APACHE2_MODULES='authn_core authz_core socache_shmcb unixd actions alias auth_basic authn_alias authn_anon authn_dbm authn_default authn_file authz_dbm authz_default authz_groupfile authz_host authz_owner authz_user autoindex cache cgi cgid dav dav_fs dav_lock deflate dir disk_cache env expires ext_filter file_cache filter headers include info log_config logio mem_cache mime mime_magic. Looking through the manual for avconv, it seems as though I need to use the concat protocol, but I can't get it working. ‘stream_type[:stream_index]’ stream_type is one of following: ’v’ for video, ’a’ for audio, ’s’ for subtitle, ’d’ for data, and ’t’ for attachments. It was only a problem of the correct hyphens around the object '0:a' should be '0:a' ffmpeg -y -threads 16 -i video. Can anyone please explain the options, especially the first 3, and the settings ( e. 5 * 6 * FFmpeg is free software; you can redistribute it and/or: 7 * modify it under the terms of the GNU Lesser General Public: 8 * License as published by the Free Software Foundation; either: 9 * version 2. mp4 -filter:v "crop=out_w:out_h:x:y" output. It only accepts audio filters. Once upon time we had to deal with that feature. Basically it looks like ffmpeg+h264_vaapi emits packets very rarely, only a couple per second. The recommended value is the total number of CPU cores minus one or two. The other answers are general RAM and CPU answer and are not related to FFMPEG at all. In FFmpeg, the way to place your logo picture is to use the -filter_complex parameter and defining the position by setting the overlay coordinate. mp4 as the GIF in this example loops infinitely. A lot of other programs use it to edit, stream or convert video and audio. 263, which is a less CPU. An experimental streaming server for live broadcasts is also included. -filter_threads nb_threads. You can find all the libvmaf options here. Use FF_THREAD_SLICE threading mode in FFmpeg for MediaSource streams. X:XXX" -filter_complex "yadif=0:-1:0,scale=1280:720" -c:v libx265 -vb 1050000 -maxrate 1050000 -bufsize 1050000 -tune zerolatency -preset veryfast -r 25 -x265-params "keyint=25:no-scenecut" -acodec libfdk_aac -ab 96000 -strict experimental -f rtsp -muxdelay 0. 5 will be 1), gain 2 will "amplify. Don't hesitate to contact our team for development services when you need to extend this product functionality. I use the ffmpeg at mobile browser. ffmpeg [global_options] {[input_file_options] -i input_url} {[output_file_options] output_url} 2 Description. Looking through the manual for avconv, it seems as though I need to use the concat protocol, but I can't get it working. exe -i sample3. FFmpeg wird unter Linux und anderen unixähnlichen Systemen (Unixoiden) entwickelt und wurde auch auf andere Betriebssysteme und Plattformen portiert. Hello there, I'm trying to get the Vulkan H/W filters, specifically scale_vulkan working with NVIDIA GPUs, but to no avail. UNCLASSIFIED TIPS * share the current directory tree (via http) at http://$HOSTNAME:8000/ >> python -m SimpleHTTPServer * Copy ssh keys to [email protected] to enable. 970 -threads 0 -b:v: 1024k -bufsize 1216k -maxrate 1280k -preset medium -profile:v main -tune film -g 60 -x264opts no-scenecut -acodec aac -b:a 192k -ac 2 -ar 44100 -af "aresample=async=1:min_hard_comp=0. You can apply filters on FFMpeg\Media\Video with the FFMpeg\Media\Video::addFilter method. 8 then it works. You can build your own filters and some are bundled in PHP-FFMpeg - they are accessible through the FFMpeg\Media\Audio::filters method. png -filter_complex "[1:v]scale=100:-1[logo];[0:v]scale=720:576[vid];[vid][logo]overlay=590:40[out]" -map '[out]' -map '0:a' -preset slower -profile:v main -level 3. 2015 edit: on a 12-core CPU, some ffmpeg commands have Linux top showing at most 200% cpu (only 2 cores), no matter what number is given to -threads. When testing the impact of these filters, Danil found the CPU usage of a system with Intel Core i5 and Radeon HD 8750M graphics dropped from an average of 68% down to 28%. Discussion Starter. Summary of the bug: When using FFmpeg to encode two seperate video outputs from a single video source, performance drops significantly when using the "unsharp" video filter on BOTH outputs. 0 -threads 0 "test. 04, and am trying to upgrade FFmpeg to 4. FFmpeg was written by Fabrice Bellard (creator of QEMU and BPG). mkv 6 of 11. Here they are: loudnorm: loudness normalization according to EBU R128. FFmpeg utility supports almost all major audio and video formats, if you want to check the ffmpeg supported available formats you can use. Now I used a data validator to filter the string lenghts that are above 30. mp4-vcodec copy -acodec copy -scodec copy outputfile. ffmpeg -i input. I try also the fifo filter for both inputs, but after some time the message comes again. A lot of other programs use it to edit, stream or convert video and audio. Several chained filters form a filter graph. If stream_index is given, then it matches stream number stream_index of this type. FFmpeg can also convert from any sample rate to any other, and resize video on the fly with a high quality polyphase filter. 5 -filter:v yadif -f image2pipe -vcodec ppm - | ffmpeg -r 29. The default is the number of available CPUs. mp4 -c:v vp9 -c:a libvorbis output. Thus, the head post often has BSPP threads closest to the casting, then 1. / filters / ffmpeg_demuxer. Before encoding, ffmpeg can process raw audio and video frames using filters from the libavfilter library. 2 doesn't seem to do what I want and 4. FFmpeg is the leading multimedia framework to decode, encode, transcode, mux, demux, stream, filter and play. FFmpeg documentation also suggests that in our use case, it may make more sense to launch multiple FFmpeg instances in parallel. 4 * This file is part of FFmpeg. After multi-thread is turned on, avcodec_encode_video2 is non-blocking, and blocking get result every few calls. /ffmpeg -i input. FFmpeg Basics by Frantisek Korbel, describes various FFmpeg features and common tasks. Vorbis is a free and open source, lossy audio codec project headed by the Xiph. FFmpeg is a free, open-source software and it's the Swiss Army knife of video- and audio-related processing. 0 -acodec flac -vcodec libx264 -preset ultrafast -crf 0 -threads 0 output. These codecs and filters show very high performance and they are much faster in comparison with CPU-based versions. Open the 'Project Settings' dialog box and in the C++ tab, choose the 'Preprocessor' option. Looking through the manual for avconv, it seems as though I need to use the concat protocol, but I can't get it working. The name of the command is the name of the option and the argument is. unable to create FFMpeg filters via c++ application I am trying to follow ffmpeg filter_audio. I understand that setting "threads 0" allows ffmpeg (or the codec - in this case libx264) to optimise. It only accepts audio filters. input, video, filters, audio, output), failing to do so may cause parameters being skipped or will prevent FFmpeg from executing. If you are new to this tool, here are some handy commands. I don't know how much processing power is needed to run this filter in real-time, but the re-encoding of an 1080p video results in about 25fps on my machine. mkv Note that in the above example the shortest option for overlay filter is used to end the output video at the length of the shortest input file, which in this case is input. It includes libavcodec, the leading open source codec library. filter_graph is a description of the filter graph to apply to the input video. ffmpeg -i input. Rule of thumb is anything intended is for television is interlace, any other delivery format is most likely progressive. 2-1build1~18. Crashes in hardware encoders usually come from unsatisfactory cooling, stability issues, bad CPU overclocking, memory corruption, gpu overclocking, and many other reasons. I am using ffmpeg in the cloud (Amazon EC2 specifically) and am wondering about the optimisation of threads when running multiple independent ffmpeg processes on the same "machine". Is it because > the rest of ffmpeg is multi-threaded, and that's why it's at 500 percent? > Please forgive me if I don't undersdtan the internal architecture of > ffmpeg. You can add filters when transcoding: ffmpeg -i inputfile. jinja2 (1). From the back trace, we can see that ffmpeg frees a filter array firstly: #0 av_free (ptr=0x32bb920) at libavutil/mem. Does filter graph support multi-thread? or > it can only be called in single thread, and I must make multi-thread > program based on filter graph functions in ffmpeg? Your question is unclear. Naturally these are a bit noisy and I read that ffmpeg can do noise reduction in two pass mode. johni6020 · Registered. I wrote a small script to scan my archive using threads to process files in parallel and posted the results in the other thread. mp4" -an -pass 1 -vcodec libx264 -r 30 -preset slow -s 640x360 -b:v 750k -bt:v 850k -vf unsharp=5:5:1. ffmpeg -loglevel debug -y -hwaccel cuvid -init_hw_device opencl:0. To enable compilation of this filter you need to configure FFmpeg with "--enable-libflite". 39 (libva 1. If the filter clogs or even if it simply impedes airflow, bypass air will be pulled in underneath the filter directly from the cabin. ffmpeg-php is an extension for PHP that adds an easy to use, object-oriented API for accessing and retrieving information from video and audio files. mp4 is the output file. If stream_index is given, then it matches stream number stream_index of this type. png 10 pixels from the top and 10 pixels from the left. > I made a benchmark between the x264 with -threads 0 option and the flv > codec with the command I specified in my first message, but the flv > codec is faster than the x264 one. ffmpeg -i input. mkv -vcodec copy -acodec copy -vbsf h264_changesps=level=41 abmmuss. User testing is not going to teach us much. Join multiple. Hi I've been searching for some time (both web at large and the ffmpeg-users list) for more information on this. Greetings all, The Problem is solved. FFMPEG crop + pad = off by one error? So what I wanted to do is do a picture-in-picture with a border. The authoritative ImageMagick web site is https://imagemagick. Step 3 You will need to cut the filter material to size and wrap the material around the pipe and the bucket, and secure it with zip ties. You can place more control points if you wanted to. Use FF_THREAD_SLICE threading mode in FFmpeg for MediaSource streams. In libavfilter, it is possible for filters to have multiple inputs and multiple outputs. If the filter clogs or even if it simply impedes airflow, bypass air will be pulled in underneath the filter directly from the cabin. If you are new to this tool, here are some handy commands. ffmpeg -i "%~1" -c:v mpeg2video -intra -q:v 1 -qmin 1 -pix_fmt yuv422p -r 25 -filter:v "setpts=1/20*PTS" -an -y -threads 8 "%~1. This will make a Matroska container with a VP9 video stream and a Vorbis audio stream, essentially the same as the WebM we made earlier. FFmpeg's curve filter is normalized 0-1. FFplay is a very simple and portable media player using the FFmpeg libraries and the SDL library. switch (config. 2 amd64 I notice it's not in ports but the ffmpeg-mt site says it should work on freebsd. [FFmpeg-devel,v5,21/22] h264_metadata_bsf: Refactor the filter function into smaller parts [FFmpeg-devel,v5,01/22] cbs: Mention all codecs in unit type comment - 1 -. gif -filter_complex overlay=shortest=1 out. ‘stream_type[:stream_index]’ stream_type is one of following: ’v’ for video, ’a’ for audio, ’s’ for subtitle, ’d’ for data, and ’t’ for attachments. 264 Long GOP o MPEG-2 I-frame only in Highest Quality o MPEG-2 Long GOP * Muxing and Wrapping : o D10 into QuickTime ( for Final Cut Pro import ) o MPEG-2 Program Stream * Demuxing and. post314-g78a3d57 | about patchwork. \sample6-2mins. FFmpeg can also convert from any sample rate to any other, and resize video on the fly with a high quality polyphase filter. This will allow you to use larger holes for better air flow while keeping the carbon from falling through. The default is the number of available CPUs. png -q:v 1 -filter_complex " [1:v]scale=1920:1080 [ovrl], [0:v][ovrl] overlay=0:0" -threads 2 -an -vcodec libx264 -b:v 6500k -minrate 6500k -maxrate 6500k -bufsize 1835k firstImageWithFooter. Joined Nov 20, 2009 · 1,389 Posts. mp4" -acodec libmp3lame -ar 44100 -ab. Oil Mist Filter, 3/8 BSP Male Threads G1099-80039. Default value is 0. Drawtext filter, based on the original FFmpeg vhook/drawtext. Now I used a data validator to filter the string lenghts that are above 30. Its a real shame ffplay isnt installed with ffmpeg as its very useful for testing audio and video filters If building ffmpeg with poudriere is the only option to enable ffplay, then i will do a full write up of the steps involved. ffmpeg -i input. 39 (libva 1. mp4 -i logo. Use 'list' as parameter to show all the supported pixel formats. Thus, the head post often has BSPP threads closest to the casting, then 1. If you are new to this tool, here are some handy commands. It can be used to do an unbelievable range of things and it's being utilized by virtually anyone who's doing any form of video processing. See the ffmpeg-filters manual for more information about the filtergraph syntax. - FFmpeg Forum. FFmpeg is a free and open-source project consisting of a vast software suite of libraries and programs for handling video, audio, and other multimedia files and streams. ffmpeg -i ~/Input. Otherwise, it matches all streams of this type. Join multiple. The default is the number of available CPUs. Other (non ffmpeg) YUV to RGB as input is ok (so filter doesn't cause the brightness difference) Unfortunately no other way in ffmpeg currently for RGB<=>YUV except through swscale. These codecs and filters show very high performance and they are much faster in comparison with CPU-based versions. I'm currently stuck, because certain ffmpeg commands only seem to work properly in newer versions of ffmpeg. No matter if they were designed by some standards committee, the community or a corporation. FFmpeg Basics by Frantisek Korbel, describes various FFmpeg features and common tasks. In order to make any ffmpeg commands work, I need to add -threads 1 into the command. I, somehow, managed to come up with a command that actually recorded everything. Other Options. This package is known to build and work properly using an LFS-9. Filters are chainable. \sample6-2mins. -vf filter_graph set video filters-vframes number set the number of video frames to output-vn disable video. Porting that filter to ffmpeg would be a bit awkward. I don't know what the '17 or newer cabin air filter covers look like, but on earlier models they have a bypass flap. The book had (for me) not one but several simple-yet-profound ideas that were forever inserted into the foreground of how I make sense of the world. 1 executables on Windows from the official ffmpeg site and 3. Once upon time we had to deal with that feature. mp3" -threads 1 -filter_complex "[0:a][1:a]amerge=inputs=2[a]" -map [a] -c:a libfdk_aac "test5. Open the 'Project Settings' dialog box and in the C++ tab, choose the 'Preprocessor' option. sav0)” Ubuntu 18. 12 on AMD Radeon R9 Fury X: there are weird issues with the video it produces. Now I used a data validator to filter the string lenghts that are above 30. Overlay frame numbers on YUV If you are on Windows, use ShowFrameNumber() option available in Avisynth. The CIAO package includes the dmextract tool to calculate the lightcurve of a dataset (or region within a dataset), and the dmgti tool to create a GTI file given a table and a set of limits. New feature to filter files by extension, size, bitrate, video or audio codec, frame rate, frame size, metadata, custom strings. To enable compilation of this filter you need to configure FFmpeg with "--enable-libflite". You can build your own filters and some are bundled in PHP-FFMpeg - they are accessible through the FFMpeg\Media\Video::filters method. input, video, filters, audio, output), failing to do so may cause parameters being skipped or will prevent FFmpeg from executing. Transcoding Videos for Web Streaming with FFmpeg using Laravel Queues I’ve been working on a project where we were using AWS elastic transcoder for media conversion. mkv I mean only ffmpeg's own instruments, without multiple processes and other OS features. 2的overlay必须是complex filter，调试这个命令： ffmpeg -re -i ~/test_22m. FILTERING INTRODUCTION Filtering in FFmpeg is enabled through the libavfilter library. png 10 pixels from the top and 10 pixels from the left. dpx -framerate 59. ffmpeg -i input. ffmpeg -i IN. Before encoding, ffmpeg can process raw audio and video frames using filters from the libavfilter library. Below is the phpinfo php --info | grep ffmpeg ffmpeg ffmpeg-php version => 0. I have not however been able to confirm that in the ffmpeg documentation. X:XXX" -filter_complex "yadif=0:-1:0,scale=1280:720" -c:v libx265 -vb 1050000 -maxrate 1050000 -bufsize 1050000 -tune zerolatency -preset veryfast -r 25 -x265-params "keyint=25:no-scenecut" -acodec libfdk_aac -ab 96000 -strict experimental -f rtsp -muxdelay 0. I found some web pages that discussed FFMPEG commands to take a Front & Rear video file and combine into a single file with a PIP rear view (similar to how the Blackvue Viewer app looks). FFmpeg can also convert from any sample rate to any other, and resize video on the fly with a high quality polyphase filter. -threads:1 4 would set the thread count for the second stream to 4. You can apply filters on FFMpeg\Media\Audio with the FFMpeg\Media\Audio::addFilter method. FFmpeg is a robust open-source framework designed for command-line-based processing of video and audio files, and widely used for format transcoding, basic editing (trimming and concatenation), video scaling, video post-production effects, and standards compliance. Now I used a data validator to filter the string lenghts that are above 30. You can get a lot of information about how to encode with FFmpeg all over the web including FFmpeg/libav's web site. Greetings all, The Problem is solved. -lavfi filtergraph (global). brands of gasoline contain adequate amounts of fuel injector cleaners to keep the 4. Also, virtually all of today's major U. Use FF_THREAD_SLICE threading mode in FFmpeg for MediaSource streams. 是不是想查看ffmpeg有多少filter？用下面的命令。. Press question mark to learn the rest of the keyboard shortcuts. You'll find everything what you need with this package. The default is the number of available CPUs. I have a Logitech C922 webcam and I'm recording using ffmpeg with this settings: ffmpeg -thread_queue_size 1024 -f alsa -r 16000 -i hw:1,0 -f video4linux2 -thread_queue_size 512 -s 1920x1080 -i /dev/. 2 amd64 I notice it's not in ports but the ffmpeg-mt site says it should work on freebsd. This package is known to build and work properly using an LFS-9. such as codecs, video and audio streams, filters or metadata. The name of the command is the name of the option and the argument is. FFmpeg is a cross platform, free, open source media encoder/decoder toolkit. pkl – path to VMAF model (this is the default model):log_path=VMAF. One filter graph must be handled from a single >thread at a time. mp4 -filter:v "crop=1440:1080:240:0,hue=s=0,pad=1920:ih:(ow-iw)/2" outfile. However now I need to update due to an updated library in the newer versions. In this tutorial we will look most wanted and useful features like convert, resize,… of ffmpeg. mpg" -threads 0 -an -threads 0 -map_metadata -1 -sws_flags lanczos+accurate_rnd+full_chroma_int+full_chroma_inp -filter:v yadif=0:0:0,unsharp=opencl=0:luma_msize_x. Xaymar submitted a new resource: FFmpeg Encoders for OBS Studio - Get all the power of FFmpeg without using a custom output! This plugin adds all FFmpeg encoders to the normal OBS Studio recording and streaming options, as long as the OBS Studio bundled FFmpeg version was built with them. It's all worked fine up until the point I needed to user filter_complex. 354 to try and let the main thread(s) clean up and gracefully terminate 355 (we have at most 5 seconds, but should be done far before that). For example, this command: ffmpeg -y -i "audio_1. mp4 -c:v vp9 -c:a libvorbis output. 39 (libva 1. mp4 as the GIF in this example loops infinitely. 50-16 threads further down. However, I am keeping the libraries freetype, fontconfig, and fribidi, because they allow full use of the drawtext filter, which is handy if you want to put timestamps or any other text on the video. This version uses the new pad filter of ffmpeg. texi +++ b/doc/filters. NNEDI requires the use of a binary filter file for the "weights", which FFMPEG provides a link to here:. -lavfi filtergraph (global) Define a complex filtergraph, i. Is it because > the rest of ffmpeg is multi-threaded, and that's why it's at 500 percent? > Please forgive me if I don't undersdtan the internal architecture of > ffmpeg. Step 3 You will need to cut the filter material to size and wrap the material around the pipe and the bucket, and secure it with zip ties. 2: upgrade FFMpeg to version built on Jul 28 2014. I try also the fifo filter for both inputs, but after some time the message comes again. You can remux streams (put them in a different container) without transcoding them: ffmpeg -i inputfile. You should not use ffmpeg-based tools for the encoding of video content. Summary of the bug: When using FFmpeg to encode two seperate video outputs from a single video source, performance drops significantly when using the "unsharp" video filter on BOTH outputs. An HDCD filter was added in FFmpeg 3. pkl - path to VMAF model (this is the default model):log_path=VMAF. FFmpeg's curve filter is normalized 0-1. ffmpeg -i -vcodec dnxhd however, this does not work, and the examples I have seen on converting into dnxhd with ffmpeg I do not understand, they seemed each time having some different tags without explaining why to use them. 263, which is a less CPU. I use the ffmpeg at mobile browser. m2v -i footer. \ffmpeg_x64_opencl. The command ffmpeg -codecs will print every codec FFmpeg knows about. FFmpeg is an excellent tool for converting videos into animated GIFs and the quality isn't bad either. FFmpeg and its photosensitivity filter are not making any medical claims. This tutorial will help you to install FFmpeg on Ubuntu Ubuntu 18. FFmpeg is an audio/video conversion tool. " From looking through the source the call that is failing is to InitVulkan it appears to be passed Null by ffmpeg based on the documentation this should. FILTERING INTRODUCTION Filtering in FFmpeg is enabled through the libavfilter library. This option is only available when FFmpeg has been compiled with "--enable-opencl". c:209 #1 0x000000000162a759 in initFilter (outFilter=0x32ae7f8, filterPos=0x32ae818, outFilterSize=0x32ae82c, xInc=65536, srcW=45, dstW=45, filterAlign=1, one=4096, flags=8196, cpu_flags=1037275, srcFilter=0x0, dstFilter=0x0. You can remux streams (put them in a different container) without transcoding them: ffmpeg -i inputfile. mp4 as the GIF in this example loops infinitely. c [code] Video fade filter based heavily on vf_negate. Xaymar submitted a new resource: FFmpeg Encoders for OBS Studio - Get all the power of FFmpeg without using a custom output! This plugin adds all FFmpeg encoders to the normal OBS Studio recording and streaming options, as long as the OBS Studio bundled FFmpeg version was built with them. You would rarely change this unless you want to force FFMpeg use less threads, thus leaving free processor cores for other work 'n fun. 2 and ffmpeg 4. FFmpeg wird unter Linux und anderen unixähnlichen Systemen (Unixoiden) entwickelt und wurde auch auf andere Betriebssysteme und Plattformen portiert. -vf filter_graph set video filters-vframes number set the number of video frames to output-vn disable video. VMAF filter is a very important video quality metric today. c by Bobby Bingham. For people having syntax issues - For Windoze, the issue with ffmpeg and filters is escape characters. When multiple -i inputs are provided, FFmpeg reads each input in a separate thread and buffers packets till requested from further down the pipeline. Below is the phpinfo php --info | grep ffmpeg ffmpeg ffmpeg-php version => 0. Can anyone please explain the options, especially the first 3, and the settings ( e. 5 will reduce signal level by half (2 multiplied by 0. mkv 6 of 11. 0 Comments. jinja2 (1). Join multiple. By the way, thanks for trying to help me but I never used threads option before and FFmpeg Filters Documentation does not list any threads option for filters used so I googled your threads=1 recommendation. 6-1ubuntu2_amd64 NAME ffmpeg - ffmpeg video converter SYNOPSIS ffmpeg [global_options] {[input_file_options] -i input_file} {[output_file_options] output_file} DESCRIPTION ffmpeg is a very fast video and audio converter that can also grab from a live audio/video source. ffmpeg -loglevel debug -threads:v 2 -threads:a 8 -filter_threads 2 \ -thread_queue_size 512 -f x11grab -s 1920x1080 -framerate 60 -i :0. FFmpeg utility supports almost all major audio and video formats, if you want to check the ffmpeg supported available formats you can use. Questions tagged [ffmpeg] Ask Question `ffmpeg` is a free software project aimed at producing tools (libraries and programs) for handling multimedia data. Video encoding, decoding and transcoding. FFmpeg can also convert from any sample rate to any other, and resize video on the fly with a high quality polyphase filter. FFmpeg's curve filter is normalized 0-1. You can add filters when transcoding: ffmpeg -i inputfile. 970 -threads 0 -b:v: 1024k -bufsize 1216k -maxrate 1280k -preset medium -profile:v main -tune film -g 60 -x264opts no-scenecut -acodec aac -b:a 192k -ac 2 -ar 44100 -af "aresample=async=1:min_hard_comp=0. mkv files into one using avconv or ffmpeg Hi all, I'm looking to join lots of small video segments into one big one. exe -y -i %* -vf cropdetect -threads 0. Joining videos in Xabe. FFmpeg can also convert from any sample rate to any other, and resize video on the fly with a high quality polyphase filter. Thread message queue blocking: when pipe and use filter complex Hello, when I use pipe to ffmpeg in combination with *filter_complex overlay, *I always get the message: Thread message queue blocking; consider raising the thread_queue_size option (current value: 256) It doesn't matter how big I raise the thread_queue_size, the message comes son. mkv") will report "AMF failed to initialise on the given Vulkan device: 1. 10 Generic_120012-14 i86pc i386 i86pc I am trying to install ffmpeg in solaris 10 but no luck, Not able to install. 354 to try and let the main thread(s) clean up and gracefully terminate 355 (we have at most 5 seconds, but should be done far before that). 2 Filtering Introduction. No matter if they were designed by some standards committee, the community or a corporation. mp4 -ignore_loop 0 -i input. 1 -rc:v vbr_hq -cq:v \ 19 -b:v 17500k \ -maxrate:v 22000k ~/Desktop/sdr. The main reason is, that the libraries, which ffmpeg uses provide more encoding options (like x264) which can improve quality, or are necessary for professional encoders, and the ffmpeg command line options are very limited (the C/C++ interface has the same limitations). Below are examples showcasing Subscribe logo in different locations. Before encoding, ffmpeg can process raw audio and video frames using filters from the libavfilter library. I have a dual GPU system with a rx vega 56 and a rx 480. 8 -y -i "D:\MCEBuddy\MCEBuddy 2. The output of this command will change depending on the version of FFmpeg you have. mp4-vf "filter1,filter2" outputfile. See the ffmpeg-filters manual for more information about the filtergraph syntax. ffmpeg is a very fast video and audio converter that can also grab from a live audio/video source. FFMPEG crop + pad = off by one error? So what I wanted to do is do a picture-in-picture with a border. 1 of the License, or (at your option) any later version. [FFmpeg-devel,V1,1/4] lavf/flvdec: set AVFMT_TS_DISCONT flag on FLV demuxer [FFmpeg-devel,V1,1/4] lavf/flvdec: set AVFMT_TS_DISCONT flag on FLV demuxer - - - ---1: 2020-03-30: Jun Zhao: New [FFmpeg-devel,V1,1/3] lavf/dashenc: add 3GPP TS26. Wow! Is it really. ffmpeg_filter. Each pipeline will produce a thread pool with this many threads available for parallel processing. filter_graph is a description of the filter graph to apply to the input video. (3) enable custom filter options on ffmpeg input: case use: -filter_complex on audio and video One would need to pass options to ffmpeg here: ffmpeg -i INPUT [HERE] -c:v [video codec options] -c:a [audio options] -f muxer [ muxer options] OUTPUT. Hello, when I use pipe to ffmpeg in combination with *filter_complex overlay, *I always get the message: Thread message queue blocking; consider raising the thread_queue_size option (current value: 256) It doesn't matter how big I raise the thread_queue_size, the message comes son or later. This document is a tutorial/initiation for writing simple filters in: libavfilter. FFmpeg and its photosensitivity filter are not making any medical claims. 0 %: 156 / 156: libavcodec/cbrt_tablegen. mkv There were 3 parts, as my camera splits into 2 GB files, after they were sped up, avidemux was used to combine them. 1 executables on Windows from the official ffmpeg site and 3. unable to create FFMpeg filters via c++ application I am trying to follow ffmpeg filter_audio. It can be used to do an unbelievable range of things and it's being utilized by virtually anyone who's doing any form of video processing. 4 Stream selection By default, ffmpeg includes only one stream of each type (video, audio, subtitle) present in the input. Using threads=1 option improves output a little but doesn't fix the issue. All builds require at least Windows 7 or Mac OS X 10. Has anyone fooled around with FFMPEG and its audio filters as guitar effects? FFMPEG is a GNU [like freeware] program that does all sorts of things with audio and video. ffmpeg-php is an extension for PHP that adds an easy to use, object-oriented API for accessing and retrieving information from video and audio files. gif -filter_complex overlay=shortest=1 out. 2019-05-15 09:39. --list-bsfs show all available bitstream filters--list-indevs show all available input devices--list-outdevs show all available output devices--list-filters show all available filters. mpg -s 1280x720 -acodec copy -sameq -swsflags lanczos -f mpegts -vcodec libx264 -threads 0 out. Basically it looks like ffmpeg+h264_vaapi emits packets very rarely, only a couple per second. It can be used to do an unbelievable range of things and it's being utilized by virtually anyone who's doing any form of video processing. 0625 This behaves correctly as the output_low or output_black for a levels filter, or a "lift" in resolve. FFmpeg integration with NVIDIA GPU. You can see the output file failure_with_threads_1. I use the ffmpeg at mobile browser. All you have to do is execute a single line command. - Compression Techniques Forum. FFMpeg allows to crop a given media file in any dimension of our choice. The CIAO package includes the dmextract tool to calculate the lightcurve of a dataset (or region within a dataset), and the dmgti tool to create a GTI file given a table and a set of limits. ffmpeg -f image2 -i foo-%03d. This tutorial will help you to install FFmpeg on Ubuntu Ubuntu 18. exe" -threads 0 -threads 0 -i ". See ffmpeg -filters to view which filters have timeline support. Give input width as twice the actual width and crop appropriately. This may slow down video decoding for streams that were encoded without slicing, as in that case decoding will be happening on a single thread. mp4 Cut a piece out of a video. Drawtext filter, based on the original FFmpeg vhook/drawtext. \ffmpeg_x64_opencl. The TJ's fuel filter is, as described above, mounted on the fuel pump and regulator assembly. 04 using the latest branch of FFmpeg to do an h264_amf encode with varying success. See the ffmpeg-filters manual for more information about the filtergraph syntax. olhygqon6n751, clp5qgseh2d, jwlkhq4xgb8gc99, fpzapwpscpf3kd, pr9gzqf0wnsfe, 1j2gyksjadru, rtpke546275a7, fs9n20s4532j, rhv6428k0eyek61, 8qgscofg3ik2, uqg6x47r2jc8k, ese5wqfm1zf, wvmxmrf6tvcb6u, 8gggm6mihnok7h, gi2cd3rndcg, vvom0710n4, vod4wy8tqxxrsz, 2mzln0czvozjjnj, n45n7an1dizm31, uzxlnfrkllee, sk0psuins1093j8, jg9wpxmzphcpq9, 3426h1jdd6vii91, sjc8hkldz1o, 7noojwlhlbyka, 0q763hefps6u
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href=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u0022download-ppt last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/75549\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-3\u0022\u003E\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003EAbstract\u003C\/h2\u003E\u003Cp id=\u0022p-1\u0022\u003EQuantitative assessment of drug-drug interactions (DDIs) via organic anion transporting polypeptide (OATP) 1B1 is one of the key issues in drug development. Although OATP1B1 inhibition exhibits unique characteristics, including preincubation dependence for some inhibitors, a limited approach has been attempted based on the static model that considers such preincubation dependence in the prediction of DDIs via OATP1B1. The present study aimed to establish the prediction of DDIs via OATP1B1 using preincubation-dependent inhibitors based on the static model and incorporating both inactivation and recovery of OATP1B1 activity. Cyclosporine A was selected as a preincubation-dependent inhibitor, as well as five substrates that include probes and pharmaceuticals. The inhibition ratio (R value) calculated on the basis of a conventional static model, considering inhibition of OATP1B1 and contribution ratio of OATP1B1 to the overall hepatic uptake, was much lower than the reported AUC ratio, even when IC\u003Csub\u003E50\u003C\/sub\u003E values were estimated after preincubation conditions. Conversely, the R value that was estimated by considering inactivation and recovery parameters was closer to the AUC ratio. The R value that was calculated assuming the complete contribution of OATP1B1 was much higher than the AUC ratio, avoiding false-negative prediction. The R value estimated by considering inactivation and recovery for another combination of a preincubation-dependent inhibitor, asunaprevir, and substrate drug, rosuvastatin, was also closer to the AUC ratio. Thus, R values calculated based on such OATP1B1 kinetics would be potential alternative indexes for the quantitative prediction of OATP1B1-mediated DDIs using preincubation-dependent inhibitors, although this prediction is affected by estimation of the contribution ratio of substrates.\u003C\/p\u003E\u003Cdiv id=\u0022sec-1\u0022 class=\u0022subsection\u0022\u003E\u003Cp id=\u0022p-2\u0022\u003E\u003Cstrong\u003ESIGNIFICANCE STATEMENT\u003C\/strong\u003E Static model\u2013based quantitative prediction of organic anion transporting polypeptide 1B1\u2013mediated drug-drug interactions induced by preincubation-dependent inhibitors was newly proposed to avoid false-negative prediction.\u003C\/p\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022section intro\u0022 id=\u0022sec-2\u0022\u003E\u003Ch2 class=\u0022\u0022\u003EIntroduction\u003C\/h2\u003E\u003Cp id=\u0022p-4\u0022\u003EIn the pharmaceutical industry, drug-drug interactions (DDIs) are a major concern during drug development. DDIs alter systemic exposure of the victim drug, resulting in unwanted clinical outcomes, such as severe side effects and a decrease in therapeutic efficacy. Therefore, it is important to evaluate potential DDIs for new chemical entities (NCEs). During the early drug developmental stage, this evaluation is often performed based on the so-called static model, which principally incorporates inhibition potential to target enzymes of NCEs designated as IC\u003Csub\u003E50\u003C\/sub\u003E values and the maximum unbound NCE concentration plausibly exposed to humans. This approach could be valuable to avoid false-negative predictions of DDIs induced by competitive inhibition of drug-metabolizing enzymes and transporters. However, its application to the perpetrator drugs, which may potentially exhibit time-dependent enzyme inhibition, should be carefully examined.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EOrganic anion transporting polypeptide (OATP) 1B1 is expressed on sinusoidal membranes in the liver (\u003Ca id=\u0022xref-ref-11-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-11\u0022\u003EKalliokoski and Niemi, 2009\u003C\/a\u003E). OATP1B1 plays an important role in the hepatic uptake of endogenous and many therapeutic agents, determining their elimination rate from the liver ((\u003Ca id=\u0022xref-ref-13-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-13\u0022\u003EMaeda, 2015\u003C\/a\u003E)). Inhibition and\/or reduction of OATP1B1 activity can reduce the uptake of drugs by hepatocytes, thereby increasing the drug concentration in the systemic circulation. In clinical settings, the plasma concentration of OATP substrates is altered by coadministration with its inhibitor drugs (\u003Ca id=\u0022xref-ref-24-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-24\u0022\u003EYoshida et al., 2012\u003C\/a\u003E). Therefore, the prediction of OATP1B1-mediated DDIs is a key issue for patient safety in drug development.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003ETo evaluate OATP1B1-mediated DDIs induced by competitive inhibition, the inhibition ratios (R values) have been estimated based on the IC\u003Csub\u003E50\u003C\/sub\u003E values and theoretically maximum unbound concentration of perpetrators in the inlet of the liver (I\u003Csub\u003Eu,inlet,max\u003C\/sub\u003E). Nevertheless, false-negative predictions for DDIs cannot be avoided via this transporter, even when using such a conservative method (\u003Ca id=\u0022xref-ref-22-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-22\u0022\u003EVaidyanathan et al., 2016\u003C\/a\u003E). Although exact reasons for such a discrepancy remain unknown, unique features of OATP1B1, such as preincubation-dependent, long-lasting, and substrate-dependent inhibition, have been previously reported (\u003Ca id=\u0022xref-ref-10-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-10\u0022\u003EIzumi et al., 2015\u003C\/a\u003E; \u003Ca id=\u0022xref-ref-16-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-16\u0022\u003EShitara and Sugiyama, 2017\u003C\/a\u003E), and these may be relevant to the obstacles in predicting DDIs based on in vitro studies. Previously, cyclosporine A (CsA), human immunodeficiency virus protease inhibitors, direct-acting antihepatitis C virus (HCV) agents, and tyrosine kinase inhibitors (TKIs) have exhibited the preincubation-dependent inhibition of OATP1B1 (\u003Ca id=\u0022xref-ref-17-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-17\u0022\u003EShitara et al., 2013\u003C\/a\u003E; \u003Ca id=\u0022xref-ref-6-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-6\u0022\u003EFurihata et al., 2014\u003C\/a\u003E; \u003Ca id=\u0022xref-ref-15-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-15\u0022\u003EPahwa et al., 2017\u003C\/a\u003E; \u003Ca id=\u0022xref-ref-21-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-21\u0022\u003ETaguchi at al., 2019\u003C\/a\u003E). Furthermore, CsA, HCV agents, and pazopanib have also been reported as long- or short-lasting inhibitors (\u003Ca id=\u0022xref-ref-17-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-17\u0022\u003EShitara et al., 2013\u003C\/a\u003E; \u003Ca id=\u0022xref-ref-6-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-6\u0022\u003EFurihata et al., 2014\u003C\/a\u003E; \u003Ca id=\u0022xref-ref-21-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-21\u0022\u003ETaguchi at al., 2019\u003C\/a\u003E). Although the so-called dynamic model has been recently proposed for the long-lasting inhibition of OATP1B1 by CsA (\u003Ca id=\u0022xref-ref-16-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-16\u0022\u003EShitara and Sugiyama 2017\u003C\/a\u003E), a direct inhibition\u2013based conventional static model is recommended to be considered in the prediction of DDIs via OATP1B1. Moreover, a systematic assessment of the interaction between CsA and the OATP substrate pravastatin has been performed in rats, revealing that this interaction appears to be long-lasting and can be described by the static model with the apparent IC\u003Csub\u003E50\u003C\/sub\u003E value for unbound CsA more than 1000 times lower than that experimentally measured in vitro in isolated rat hepatocytes ((\u003Ca id=\u0022xref-ref-20-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-20\u0022\u003ETaguchi et al., 2016\u003C\/a\u003E)). Thus, the prediction based on a simple static model incorporating direct inhibition alone is not applicable for DDIs mediated by OATP1B1 inhibition by preincubation-dependent inhibitors.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EIn the present study, we attempted to investigate another approach for the prediction of OATP1B1-mediated DDIs with preincubation-dependent inhibitors. Physiologically based pharmacokinetic model analysis is useful for the quantitative prediction of DDIs, although it is sometimes complex and takes more time compared with the static model\u2013based analysis. Therefore, we focused on the static model\u2013based approach. We proposed R values that consider not only IC\u003Csub\u003E50\u003C\/sub\u003E and I\u003Csub\u003Eu,inlet,max\u003C\/sub\u003E values but also the inactivation and recovery kinetics of OATP1B1 activity and contribution ratio of OATP1B1 to the overall hepatic uptake of the victim drugs. As a perpetrator drug, cyclosporine A was first selected because abundant in vitro information is available that demonstrates its long-lasting inhibition, as well as clinical data regarding DDIs via OATP1B1 induced by this drug. In the present study, the original concept of the prediction strategy was deduced from the kinetic analysis of time-dependent inhibition of the metabolic enzyme; to the best of our knowledge, there has been no report on its application to OATP1B1. Here, typical OATP1B1 substrates were used as victim drugs to validate the approach because substrate-dependent OATP1B1 inhibition has been reported (\u003Ca id=\u0022xref-ref-10-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-10\u0022\u003EIzumi et al., 2015\u003C\/a\u003E). Furthermore, the inhibition potential of other preincubation-dependent inhibitor drugs of OATP1B1, such as anti-HCV agents and TKIs, was also examined.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv class=\u0022section materials-methods\u0022 id=\u0022sec-3\u0022\u003E\u003Ch2 class=\u0022\u0022\u003EMaterials and Methods\u003C\/h2\u003E\u003Cdiv id=\u0022sec-4\u0022 class=\u0022subsection\u0022\u003E\u003Cdiv id=\u0022sec-5\u0022 class=\u0022subsection\u0022\u003E\u003Ch4\u003EMaterials.\u003C\/h4\u003E\u003Cp id=\u0022p-8\u0022\u003ECsA and atorvastatin calcium trihydrate were purchased from FUJIFILM Wako Pure Chemical (Tokyo, Japan). Asunaprevir was procured from Santa Cruz Biotechnology (Dallas, TX), nilotinib was from ChemScene, LLC (Monmouth Junction, NJ), regorafenib was from Toronto Research Chemicals (North York, ON), pazopanib was from Synkinase Pvt Ltd (Victoria, Australia), pitavastatin calcium was from Avachem Scientific (San Antonio, TX), and rosuvastatin calcium was from AK Scientific (Union City, CA). [\u003Csup\u003E3\u003C\/sup\u003EH]Estrone 3-sulfate (E\u003Csub\u003E1\u003C\/sub\u003ES) and [\u003Csup\u003E3\u003C\/sup\u003EH]estradiol-17\u003Cem\u003E\u03b2\u003C\/em\u003E-glucuronide (E\u003Csub\u003E2\u003C\/sub\u003EG) were obtained from PerkinElmer (Waltham, MA). All other reagents were of analytical grade.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-6\u0022 class=\u0022subsection\u0022\u003E\u003Ch4\u003ECell Culture.\u003C\/h4\u003E\u003Cp id=\u0022p-9\u0022\u003EHEK293 cells stably expressing OATP1B1 (HEK293\/OATP1B1 cells) and the vector alone (HEK293\/mock) were constructed as previously described ((\u003Ca id=\u0022xref-ref-5-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-5\u0022\u003EFujita et al., 2014\u003C\/a\u003E)). HEK293\/OATP1B1 cells were routinely grown in culture medium consisting of Dulbecco\u2019s modified Eagle\u2019s medium (high glucose) without \u003Cspan class=\u0022sc\u0022\u003El\u003C\/span\u003E-glutamine and phenol red (FUJIFILM Wako Pure Chemical) and containing 10% fetal bovine serum, penicillin, streptomycin, and 1 mg\/ml G418 in a humidified incubator at 37\u00b0C and 5% CO\u003Csub\u003E2\u003C\/sub\u003E. For the transport studies, HEK293\/OATP1B1 and HEK293\/mock cells were seeded in 24-well plates (Becton Dickinson, Franklin Lakes, NJ) coated with poly-\u003Cspan class=\u0022sc\u0022\u003Ed\u003C\/span\u003E-lysine (R\u0026amp;D Systems, Minneapolis, MN) at a density of 1.0 \u00d7 10\u003Csup\u003E5\u003C\/sup\u003E cells per well and cultured in the culture medium. After 2 days, 5 \u03bcl of 500 mM sodium butyrate was added to the medium for the induction of OATP1B1 expression to obtain a final concentration of 5 mM. The following preincubation-dependent inhibition, inactivation, and recovery studies were started 1 day after the addition of butylate.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-7\u0022 class=\u0022subsection\u0022\u003E\u003Ch4\u003EPreincubation-Dependent Inhibition Study.\u003C\/h4\u003E\u003Cp id=\u0022p-10\u0022\u003EThe cells were washed twice with the transport buffer (125 mM NaCl, 4.8 mM KCl, 1.2 mM CaCl\u003Csub\u003E2\u003C\/sub\u003E, 1.2 mM KH\u003Csub\u003E2\u003C\/sub\u003EPO\u003Csub\u003E4\u003C\/sub\u003E, 1.2 mM MgSO\u003Csub\u003E4\u003C\/sub\u003E, 35 mM HEPES, and 5.6 mM \u003Cspan class=\u0022sc\u0022\u003Ed\u003C\/span\u003E-glucose, pH 7.4) prewarmed at 37\u00b0C and pretreated for 5 minutes with the transport buffer without substrates or inhibitors. The medium was then replaced with the transport buffer containing the vehicle alone (1% dimethyl sulfoxide) or inhibitors at various concentrations, and cells were further preincubated for the designated period at 37\u00b0C. After preincubation, the transport buffer containing the vehicle alone or inhibitors was removed, and the reaction was then started by applying prewarmed fresh transport buffer containing each OATP1B1 substrate and inhibitor to the cells. At 0.5 minutes ([\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E1\u003C\/sub\u003ES and [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E2\u003C\/sub\u003EG) or 1 minute (atorvastatin, pitavastatin, and rosuvastatin), the reaction solution was removed by aspiration, and cells were washed twice with ice-cold transport buffer.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-8\u0022 class=\u0022subsection\u0022\u003E\u003Ch4\u003EInactivation Study for OATP1B1 Activity.\u003C\/h4\u003E\u003Cp id=\u0022p-11\u0022\u003EThe cells were washed twice with the prewarmed transport buffer at 37\u00b0C. After pretreatment for 5 minutes with the transporter buffer alone, HEK293\/OATP1B1 cells were preincubated with the transport buffer containing the vehicle control (1% dimethyl sulfoxide) or inhibitors at the designated concentrations (CsA, 0.05\u20130.5 \u03bcM; asunaprevir, 0.05\u20131 \u03bcM; nilotinib, 0.2\u20135 \u03bcM; regorafenib, 1\u201310 \u03bcM; pazopanib, 0.1\u20132 \u03bcM) for the designated period (CsA, 20 seconds to 3 minutes; asunaprevir, 1\u20135 minutes; nilotinib, 1\u20135 minutes; regorafenib, 5\u201330 minutes; pazopanib, 0.5\u20132 minutes) at 37\u00b0C. This period was designed to be appropriate for chasing OATP1B1 inactivation by each compound. After preincubation, the cells were washed once with the prewarmed transport buffer without inhibitors to minimize the effect of inhibitors remaining in the reaction solution; the prewarmed transport buffer containing OATP1B1 substrates without inhibitors was then immediately applied. At 0.5 or 1 minute, the reaction solution was removed by aspiration, and cells were washed twice with ice-cold transport buffer.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-9\u0022 class=\u0022subsection\u0022\u003E\u003Ch4\u003ERecovery Study for OATP1B1 Activity.\u003C\/h4\u003E\u003Cp id=\u0022p-12\u0022\u003EThe medium was replaced with fresh culture medium containing the inhibitors, followed by preincubation with the inhibitors for 30 (CsA) or 60 (asunaprevir, nilotinib, regorafenib, and pazopanib) minutes. Next, the medium was again replaced with the culture medium without inhibitors, and the cells were cultured for the designated period (0\u20132 hours for CsA and 0\u201315 minutes for asunaprevir, nilotinib, regorafenib, and pazopanib) to recover OATP1B1 activity. This period was designed to be appropriate for chasing recovery of OATP1B1 activity after preincubation with each compound. Notably, the culture medium, not the transport buffer, was used in the preincubation and recovery phase because of the prolonged incubation period (\u223c2.5 hours). Then, the cells were washed once with the prewarmed transport buffer, and the uptake study was immediately started by replacing the medium with the transport buffer containing each OATP1B1 substrate alone. At 0.5 or 1 minute, cells were washed twice with the ice-cold transport buffer.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-10\u0022 class=\u0022subsection\u0022\u003E\u003Ch4\u003EDetermination of Cell-Associated Radioactivity.\u003C\/h4\u003E\u003Cp id=\u0022p-13\u0022\u003EThe cells were solubilized with 0.2 ml of 0.2 N NaOH overnight, followed by neutralization with HCl. Cell lysates and the reaction solution were then mixed with a scintillation fluid, and radioactivity was measured with a liquid scintillation analyzer (Tricarb 4910TR; PerkinElmer). The cellular protein content was determined according to the Bradford method using a protein assay kit (Bio-Rad Laboratories, Hercules, CA), with bovine serum albumin as the standard.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-11\u0022 class=\u0022subsection\u0022\u003E\u003Ch4\u003EEstimation of the Unbound Fraction in Plasma.\u003C\/h4\u003E\u003Cp id=\u0022p-14\u0022\u003EHuman plasma was obtained from eight volunteers in accordance with the Declaration of Helsinki and approval from the Kaken Research Ethics Committee, and a mixture of their plasma was used. The unbound fraction (f\u003Csub\u003Eu,p\u003C\/sub\u003E) of CsA in human plasma was determined by the equilibrium dialysis method. Dialysis membranes (pore diameter of 5 nm, 14,000-Da molecular mass cutoff) were soaked for 1 hour in distilled water and set to the equilibrium dialysis device (Sekisui medical, Tokyo, Japan). A 750-\u03bcl aliquot of the plasma and buffer samples was placed in the opposing reservoirs separated by a dialysis membrane and dialyzed at 37\u00b0C for 20 hours. The concentrations of CsA in the dialysates were determined using liquid chromatography\u2013mass spectrometry.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-12\u0022 class=\u0022subsection\u0022\u003E\u003Ch4\u003ELiquid Chromatography\u2013Tandem Mass Spectrometry Analysis.\u003C\/h4\u003E\u003Cp id=\u0022p-15\u0022\u003ETo analyze the cell-associated amount of the unlabeled compound (atorvastatin, pitavastatin, and rosuvastatin), the cells were recovered by cell scraper and disrupted in distilled water with a sonicator. The pretreatment of this sample and dialysates obtained in equilibrium dialysis was performed as described previously ((\u003Ca id=\u0022xref-ref-25-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-25\u0022\u003EYoshimatsu et al., 2016\u003C\/a\u003E)). Quantification of CsA, atorvastatin, pitavastatin, and rosuvastatin was performed using TSQ QUANTUM Vantage mass spectrometer (ThermoFisher Scientific) coupled to a liquid chromatography system (NANOAPACE NASCA2 5200) (Shiseido, Tokyo, Japan). Liquid chromatography conditions for CsA were as follows: Capcell Pak C18 (3-\u00b5m particle size, 1.5 mm inner diameter \u00d7 35 mm; Shiseido); column temperature, 40\u00b0C; step-gradient elution [0\u20130.6 minutes, 85% A\/15% B; 0.6\u20132.8 minutes, 5% A\/95% B; 2.8\u20134.6 minutes, 0% A\/100% B; 4.6\u20137.5 minutes, 85% A\/15% B (A, 1 mM ammonium acetate; B, acetonitrile)]; flow rate (0\u20133.7 minutes, 0.4 ml\/min; 3.7\u20134.6 minutes, 0.6 ml\/min; 4.6\u20137.5 minutes, 0.4 ml\/min), and injection volume, 10 \u00b5l. Liquid chromatography conditions for atorvastatin, pitavastatin, and fluvastatin were as follows: YMC-Triart C18 (5-\u00b5m particle size, 2.0 mm inner diameter \u00d7 50 mm; YMC, Kyoto); column temperature, 40\u00b0C; step-gradient elution [0\u20130.6 minutes, 85% A\/15% B; 0.6\u20132.8 minutes, 5% A\/95% B; 2.8\u20134.6 minutes, 0% A\/100% B; 4.6\u20137.5 minutes, 85% A\/15% B (A, 0.1% formic acid; B, methanol)]; flow rate (0\u20133.7 minutes, 0.4 ml\/min; 3.7\u20134.6 minutes, 0.6 ml\/min; 4.6\u20137.5 minutes, 0.4 ml\/min), and injection volume, 10 \u00b5l. The parameters for the mass spectrometer were as follows: electrospray ionization; spray voltage, 3500 V; capillary temperature, 330\u00b0C; multiple reaction monitoring method with transitions of \u003Cem\u003Em\/z\u003C\/em\u003E 1202.9 \u2192 425.3 for CsA, \u003Cem\u003Em\/z\u003C\/em\u003E 422.3 \u2192 274.1 for pitavastatin, and \u003Cem\u003Em\/z\u003C\/em\u003E 531.2 \u2192 243.9 for ketoconazole (internal standard) in the positive ion mode and \u003Cem\u003Em\/z\u003C\/em\u003E 557.3 \u2192 278.2 for atorvastatin and \u003Cem\u003Em\/z\u003C\/em\u003E 480.2 \u2192 418.2 for rosuvastatin in the negative ion mode. Validation of the bioanalytical methods is shown in \u003Ca href=\u0022http:\/\/dmd.aspetjournals.org\/lookup\/suppl\/doi:10.1124\/dmd.120.000020\/-\/DC1\u0022\u003ESupplemental Table 1\u003C\/a\u003E.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-13\u0022 class=\u0022subsection\u0022\u003E\u003Ch4\u003EData Analysis.\u003C\/h4\u003E\u003Cp id=\u0022p-16\u0022\u003EOATP1B1-mediated uptake was calculated by subtraction of the uptake observed in HEK293\/mock cells from that in HEK293\/OATP1B1 cells. Concentration-dependent inhibition of uptake was fitted to the following equation to estimate the IC\u003Csub\u003E50\u003C\/sub\u003E values:\u003Cspan class=\u0022disp-formula\u0022 id=\u0022disp-formula-1\u0022\u003E\u003Cspan class=\u0022highwire-responsive-lazyload\u0022\u003E\u003Cimg src=\u0022data:image\/gif;base64,R0lGODlhAQABAIAAAAAAAP\/\/\/yH5BAEAAAAALAAAAAABAAEAAAIBRAA7\u0022 class=\u0022highwire-embed lazyload\u0022 alt=\u0022Embedded Image\u0022 data-src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/graphic-2.gif\u0022\/\u003E\u003Cnoscript\u003E\u003Cimg class=\u0022highwire-embed\u0022 alt=\u0022Embedded Image\u0022 src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/graphic-2.gif\u0022\/\u003E\u003C\/noscript\u003E\u003C\/span\u003E\u003Cspan class=\u0022disp-formula-label\u0022\u003E(1)\u003C\/span\u003E\u003C\/span\u003Ewhere V\u003Csub\u003Econtrol\u003C\/sub\u003E and V\u003Csub\u003Einhibitor\u003C\/sub\u003E are the uptake of the substrate in the absence and presence of inhibitor, respectively, I is the inhibitor concentration, and \u003Cem\u003E\u03b3\u003C\/em\u003E is Hill\u2019s coefficient.\u003C\/p\u003E\u003Cp id=\u0022p-17\u0022\u003EIn the inactivation study, the natural logarithm of percent remaining activity was plotted against the preincubation period for each inhibitor concentration. The slope from the linear regression analysis presented the apparent first-order inactivation rate constant (k\u003Csub\u003Eobs,app\u003C\/sub\u003E) for each concentration. Then, k\u003Csub\u003Eobs,app\u003C\/sub\u003E and I were fitted to the following equation to estimate the k\u003Csub\u003Einact\u003C\/sub\u003E and K\u003Csub\u003EI\u003C\/sub\u003E values:\u003Cspan class=\u0022disp-formula\u0022 id=\u0022disp-formula-2\u0022\u003E\u003Cspan class=\u0022highwire-responsive-lazyload\u0022\u003E\u003Cimg src=\u0022data:image\/gif;base64,R0lGODlhAQABAIAAAAAAAP\/\/\/yH5BAEAAAAALAAAAAABAAEAAAIBRAA7\u0022 class=\u0022highwire-embed lazyload\u0022 alt=\u0022Embedded Image\u0022 data-src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/graphic-3.gif\u0022\/\u003E\u003Cnoscript\u003E\u003Cimg class=\u0022highwire-embed\u0022 alt=\u0022Embedded Image\u0022 src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/graphic-3.gif\u0022\/\u003E\u003C\/noscript\u003E\u003C\/span\u003E\u003Cspan class=\u0022disp-formula-label\u0022\u003E(2)\u003C\/span\u003E\u003C\/span\u003Ewhere k\u003Csub\u003Einact\u003C\/sub\u003E is the maximal inactivation rate constant, and K\u003Csub\u003EI\u003C\/sub\u003E is the inhibitor concentration causing half-maximal inactivation. The damping Gauss-Newton method algorithm was used with a MULTI program to perform nonlinear least-squares data fitting ((\u003Ca id=\u0022xref-ref-23-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-23\u0022\u003EYamaoka et al., 1981\u003C\/a\u003E)).\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-14\u0022 class=\u0022subsection\u0022\u003E\u003Ch4\u003EEstimation of R Values.\u003C\/h4\u003E\u003Cp id=\u0022p-18\u0022\u003EThe inhibitory potential of a perpetrator drug on OATP1B1 activity was first calculated by estimating the R\u003Csub\u003E0\u003C\/sub\u003E value as follows:\u003Cspan class=\u0022disp-formula\u0022 id=\u0022disp-formula-3\u0022\u003E\u003Cspan class=\u0022highwire-responsive-lazyload\u0022\u003E\u003Cimg src=\u0022data:image\/gif;base64,R0lGODlhAQABAIAAAAAAAP\/\/\/yH5BAEAAAAALAAAAAABAAEAAAIBRAA7\u0022 class=\u0022highwire-embed lazyload\u0022 alt=\u0022Embedded Image\u0022 data-src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/graphic-4.gif\u0022\/\u003E\u003Cnoscript\u003E\u003Cimg class=\u0022highwire-embed\u0022 alt=\u0022Embedded Image\u0022 src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/graphic-4.gif\u0022\/\u003E\u003C\/noscript\u003E\u003C\/span\u003E\u003Cspan class=\u0022disp-formula-label\u0022\u003E(3)\u003C\/span\u003E\u003C\/span\u003E\u003Cspan class=\u0022disp-formula\u0022 id=\u0022disp-formula-4\u0022\u003E\u003Cspan class=\u0022highwire-responsive-lazyload\u0022\u003E\u003Cimg src=\u0022data:image\/gif;base64,R0lGODlhAQABAIAAAAAAAP\/\/\/yH5BAEAAAAALAAAAAABAAEAAAIBRAA7\u0022 class=\u0022highwire-embed lazyload\u0022 alt=\u0022Embedded Image\u0022 data-src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/graphic-5.gif\u0022\/\u003E\u003Cnoscript\u003E\u003Cimg class=\u0022highwire-embed\u0022 alt=\u0022Embedded Image\u0022 src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/graphic-5.gif\u0022\/\u003E\u003C\/noscript\u003E\u003C\/span\u003E\u003Cspan class=\u0022disp-formula-label\u0022\u003E(4)\u003C\/span\u003E\u003C\/span\u003Ewhere f represents the contribution ratio of OATP1B1-mediated uptake to overall hepatic uptake of victim drug. K\u003Csub\u003Ei\u003C\/sub\u003E represents the inhibition constant and was assumed to be equal to IC\u003Csub\u003E50\u003C\/sub\u003E values because the concentration of the substrate was much lower than the relevant K\u003Csub\u003Em\u003C\/sub\u003E value (see \u003Ca href=\u0022http:\/\/dmd.aspetjournals.org\/lookup\/suppl\/doi:10.1124\/dmd.120.000020\/-\/DC1\u0022\u003ESupplemental Table 2\u003C\/a\u003E). These IC\u003Csub\u003E50\u003C\/sub\u003E values were estimated without preincubation. I\u003Csub\u003Eu,inlet,max\u003C\/sub\u003E was calculated using the following equation (\u003Ca id=\u0022xref-ref-7-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-7\u0022\u003EIto et al., 1998\u003C\/a\u003E):\u003Cspan class=\u0022disp-formula\u0022 id=\u0022disp-formula-5\u0022\u003E\u003Cspan class=\u0022highwire-responsive-lazyload\u0022\u003E\u003Cimg src=\u0022data:image\/gif;base64,R0lGODlhAQABAIAAAAAAAP\/\/\/yH5BAEAAAAALAAAAAABAAEAAAIBRAA7\u0022 class=\u0022highwire-embed lazyload\u0022 alt=\u0022Embedded Image\u0022 data-src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/graphic-6.gif\u0022\/\u003E\u003Cnoscript\u003E\u003Cimg class=\u0022highwire-embed\u0022 alt=\u0022Embedded Image\u0022 src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/graphic-6.gif\u0022\/\u003E\u003C\/noscript\u003E\u003C\/span\u003E\u003Cspan class=\u0022disp-formula-label\u0022\u003E(5)\u003C\/span\u003E\u003C\/span\u003Ewhere I\u003Csub\u003Emax\u003C\/sub\u003E is the maximum systemic plasma concentration, k\u003Csub\u003Ea\u003C\/sub\u003E is the absorption rate constant, F\u003Csub\u003Ea\u003C\/sub\u003EF\u003Csub\u003Eg\u003C\/sub\u003E is the fraction of the dose that is absorbed, Dose is the dose of the perpetrator, Q\u003Csub\u003Eh\u003C\/sub\u003E is hepatic blood flow, and R\u003Csub\u003EB\u003C\/sub\u003E is the blood-to-plasma concentration ratio. Thus, the estimation of R\u003Csub\u003E0\u003C\/sub\u003E values was based on the static model considering maximum competitive\/noncompetitive inhibition potential without preincubation.\u003C\/p\u003E\u003Cp id=\u0022p-19\u0022\u003ETo predict the OATP1B1-mediated DDIs by preincubation-dependent inhibitors, the IC\u003Csub\u003E50\u003C\/sub\u003E values experimentally estimated after preincubation with the inhibitor were used to estimate the R values based on \u003Ca id=\u0022xref-disp-formula-3-1\u0022 class=\u0022xref-disp-formula\u0022 href=\u0022#disp-formula-3\u0022\u003Eeqs. 3\u003C\/a\u003E and \u003Ca id=\u0022xref-disp-formula-4-1\u0022 class=\u0022xref-disp-formula\u0022 href=\u0022#disp-formula-4\u0022\u003E4\u003C\/a\u003E. These R values were designated as R\u003Csub\u003E1\u003C\/sub\u003E and R\u003Csub\u003E1\u003C\/sub\u003E\u2032 values. Then, the following R\u003Csub\u003E2\u003C\/sub\u003E and R\u003Csub\u003E3\u003C\/sub\u003E values were also proposed in the present study:\u003Cspan class=\u0022disp-formula\u0022 id=\u0022disp-formula-6\u0022\u003E\u003Cspan class=\u0022highwire-responsive-lazyload\u0022\u003E\u003Cimg src=\u0022data:image\/gif;base64,R0lGODlhAQABAIAAAAAAAP\/\/\/yH5BAEAAAAALAAAAAABAAEAAAIBRAA7\u0022 class=\u0022highwire-embed lazyload\u0022 alt=\u0022Embedded Image\u0022 data-src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/graphic-7.gif\u0022\/\u003E\u003Cnoscript\u003E\u003Cimg class=\u0022highwire-embed\u0022 alt=\u0022Embedded Image\u0022 src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/graphic-7.gif\u0022\/\u003E\u003C\/noscript\u003E\u003C\/span\u003E\u003Cspan class=\u0022disp-formula-label\u0022\u003E(6)\u003C\/span\u003E\u003C\/span\u003E\u003Cspan class=\u0022disp-formula\u0022 id=\u0022disp-formula-7\u0022\u003E\u003Cspan class=\u0022highwire-responsive-lazyload\u0022\u003E\u003Cimg src=\u0022data:image\/gif;base64,R0lGODlhAQABAIAAAAAAAP\/\/\/yH5BAEAAAAALAAAAAABAAEAAAIBRAA7\u0022 class=\u0022highwire-embed lazyload\u0022 alt=\u0022Embedded Image\u0022 data-src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/graphic-8.gif\u0022\/\u003E\u003Cnoscript\u003E\u003Cimg class=\u0022highwire-embed\u0022 alt=\u0022Embedded Image\u0022 src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/graphic-8.gif\u0022\/\u003E\u003C\/noscript\u003E\u003C\/span\u003E\u003Cspan class=\u0022disp-formula-label\u0022\u003E(7)\u003C\/span\u003E\u003C\/span\u003E\u003Cspan class=\u0022disp-formula\u0022 id=\u0022disp-formula-8\u0022\u003E\u003Cspan class=\u0022highwire-responsive-lazyload\u0022\u003E\u003Cimg src=\u0022data:image\/gif;base64,R0lGODlhAQABAIAAAAAAAP\/\/\/yH5BAEAAAAALAAAAAABAAEAAAIBRAA7\u0022 class=\u0022highwire-embed lazyload\u0022 alt=\u0022Embedded Image\u0022 data-src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/graphic-9.gif\u0022\/\u003E\u003Cnoscript\u003E\u003Cimg class=\u0022highwire-embed\u0022 alt=\u0022Embedded Image\u0022 src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/graphic-9.gif\u0022\/\u003E\u003C\/noscript\u003E\u003C\/span\u003E\u003Cspan class=\u0022disp-formula-label\u0022\u003E(8)\u003C\/span\u003E\u003C\/span\u003Ewhere k\u003Csub\u003Eobs\u003C\/sub\u003E is the inactivation rate constant, and k\u003Csub\u003Erecovery\u003C\/sub\u003E is apparent first-order recovery rate constant. Estimation of the R\u003Csub\u003E2\u003C\/sub\u003E value considered inactivation and recovery of OATP1B1 activity and was based on kinetic analysis of time-dependent inhibition (\u003Ca id=\u0022xref-ref-14-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-14\u0022\u003EMayhew et al., 2000\u003C\/a\u003E):\u003Cspan class=\u0022disp-formula\u0022 id=\u0022disp-formula-9\u0022\u003E\u003Cspan class=\u0022highwire-responsive-lazyload\u0022\u003E\u003Cimg src=\u0022data:image\/gif;base64,R0lGODlhAQABAIAAAAAAAP\/\/\/yH5BAEAAAAALAAAAAABAAEAAAIBRAA7\u0022 class=\u0022highwire-embed lazyload\u0022 alt=\u0022Embedded Image\u0022 data-src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/graphic-10.gif\u0022\/\u003E\u003Cnoscript\u003E\u003Cimg class=\u0022highwire-embed\u0022 alt=\u0022Embedded Image\u0022 src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/graphic-10.gif\u0022\/\u003E\u003C\/noscript\u003E\u003C\/span\u003E\u003Cspan class=\u0022disp-formula-label\u0022\u003E(9)\u003C\/span\u003E\u003C\/span\u003E\u003Cspan class=\u0022disp-formula\u0022 id=\u0022disp-formula-10\u0022\u003E\u003Cspan class=\u0022highwire-responsive-lazyload\u0022\u003E\u003Cimg src=\u0022data:image\/gif;base64,R0lGODlhAQABAIAAAAAAAP\/\/\/yH5BAEAAAAALAAAAAABAAEAAAIBRAA7\u0022 class=\u0022highwire-embed lazyload\u0022 alt=\u0022Embedded Image\u0022 data-src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/graphic-11.gif\u0022\/\u003E\u003Cnoscript\u003E\u003Cimg class=\u0022highwire-embed\u0022 alt=\u0022Embedded Image\u0022 src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/graphic-11.gif\u0022\/\u003E\u003C\/noscript\u003E\u003C\/span\u003E\u003Cspan class=\u0022disp-formula-label\u0022\u003E(10)\u003C\/span\u003E\u003C\/span\u003E\u003Cspan class=\u0022disp-formula\u0022 id=\u0022disp-formula-11\u0022\u003E\u003Cspan class=\u0022highwire-responsive-lazyload\u0022\u003E\u003Cimg src=\u0022data:image\/gif;base64,R0lGODlhAQABAIAAAAAAAP\/\/\/yH5BAEAAAAALAAAAAABAAEAAAIBRAA7\u0022 class=\u0022highwire-embed lazyload\u0022 alt=\u0022Embedded Image\u0022 data-src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/graphic-12.gif\u0022\/\u003E\u003Cnoscript\u003E\u003Cimg class=\u0022highwire-embed\u0022 alt=\u0022Embedded Image\u0022 src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/graphic-12.gif\u0022\/\u003E\u003C\/noscript\u003E\u003C\/span\u003E\u003Cspan class=\u0022disp-formula-label\u0022\u003E(11)\u003C\/span\u003E\u003C\/span\u003Ewhere A\u003Csub\u003Eh\u003C\/sub\u003E and B\u003Csub\u003Eh\u003C\/sub\u003E denote direct (competitive or noncompetitive) inhibition and preincubation-dependent inactivation, respectively, and IC\u003Csub\u003E50,pre(-)\u003C\/sub\u003E is IC\u003Csub\u003E50\u003C\/sub\u003E estimated without preincubation with perpetrators. Thus, R\u003Csub\u003E3\u003C\/sub\u003E includes both direct and preincubation-dependent inhibition (\u003Ca id=\u0022xref-ref-4-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-4\u0022\u003EFahmi et al., 2009\u003C\/a\u003E). The R\u003Csub\u003E1\u003C\/sub\u003E\u2032, R\u003Csub\u003E2\u003C\/sub\u003E\u2032, and R\u003Csub\u003E3\u003C\/sub\u003E\u2032 values were thus R\u003Csub\u003E1\u003C\/sub\u003E, R\u003Csub\u003E2\u003C\/sub\u003E, and R\u003Csub\u003E3\u003C\/sub\u003E values when the f value was assumed to be unity (OATP1B1 solely contributes to hepatic uptake of victim drug) where\u003Cspan class=\u0022disp-formula\u0022 id=\u0022disp-formula-12\u0022\u003E\u003Cspan class=\u0022highwire-responsive-lazyload\u0022\u003E\u003Cimg src=\u0022data:image\/gif;base64,R0lGODlhAQABAIAAAAAAAP\/\/\/yH5BAEAAAAALAAAAAABAAEAAAIBRAA7\u0022 class=\u0022highwire-embed lazyload\u0022 alt=\u0022Embedded Image\u0022 data-src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/graphic-13.gif\u0022\/\u003E\u003Cnoscript\u003E\u003Cimg class=\u0022highwire-embed\u0022 alt=\u0022Embedded Image\u0022 src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/graphic-13.gif\u0022\/\u003E\u003C\/noscript\u003E\u003C\/span\u003E\u003Cspan class=\u0022disp-formula-label\u0022\u003E(12)\u003C\/span\u003E\u003C\/span\u003EThe R values, means, and S.E. values were calculated using Microsoft Excel 2013.\u003C\/p\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022section results\u0022 id=\u0022sec-15\u0022\u003E\u003Ch2 class=\u0022\u0022\u003EResults\u003C\/h2\u003E\u003Cdiv id=\u0022sec-16\u0022 class=\u0022subsection\u0022\u003E\u003Cdiv id=\u0022sec-17\u0022 class=\u0022subsection\u0022\u003E\u003Ch4\u003EPreincubation-Dependent Inhibition by CsA of OATP1B1-Mediated Uptake of Various Substrates.\u003C\/h4\u003E\u003Cp id=\u0022p-20\u0022\u003EThe preincubation period with CsA was first fixed as 30 minutes because in our previous studies, this period was sufficient to investigate potential preincubation-dependent OATP1B1 inhibition by this compound using [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E1\u003C\/sub\u003ES as an OATP1B1 substrate (\u003Ca id=\u0022xref-ref-21-3\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-21\u0022\u003ETaguchi et al., 2019\u003C\/a\u003E). The OATP1B1-mediated uptake of five substrates was examined and was reduced after preincubation with CsA for 30 minutes when compared with the no-preincubation condition (\u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFig. 1\u003C\/a\u003E). The IC\u003Csub\u003E50\u003C\/sub\u003E values of CsA after 30 minutes of preincubation were 4.7- to 11-fold lower than those without preincubation and were comparable among the five substrates examined (0.02\u20130.05 \u00b5M, \u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). The IC\u003Csub\u003E50\u003C\/sub\u003E values and fold change were comparable with the previously reported values for CsA after preincubation for 1 hour (0.01\u20130.07 \u03bcM and 4.5- to 9.6-fold, respectively) when E\u003Csub\u003E1\u003C\/sub\u003ES, E\u003Csub\u003E2\u003C\/sub\u003EG, atorvastatin, and pitavastatin were used as substrates (\u003Ca id=\u0022xref-ref-10-3\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-10\u0022\u003EIzumi et al., 2015\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022F2\u0022 class=\u0022fig pos-float odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Inhibition of OATP1B1-mediated uptake of [3H]E1S (A), [3H]E2G (B), atorvastatin (C), pitavastatin (D), and rosuvastatin (E) after preincubation with CsA. The cells were washed with transport buffer prewarmed at 37\u0026#xB0;C and were then pretreated for 5 minutes with the transport buffer without substrates or inhibitors. The medium was then replaced with the transport buffer containing inhibitors at the various concentrations of CsA, and cells were further preincubated for 0 or 30 minutes at 37\u0026#xB0;C. After the preincubation, the transport buffer containing inhibitors was removed, and the reaction was then started by applying prewarmed fresh transport buffer containing [3H]E1S, [3H]E2G, atorvastatin (0.3 \u0026#x3BC;M), pitavastatin (0.5 \u0026#x3BC;M), or rosuvastatin (3 \u0026#x3BC;M) and the inhibitors to the cells. At 0.5 minutes ([3H]E1S and [3H]E2G) or 1 minute (atorvastatin, pitavastatin, and rosuvastatin), the reaction solution was removed by aspiration, and cells were washed with ice-cold transport buffer. The OATP1B1-mediated uptake was obtained by subtracting the uptake in HEK293\/mock cells from that in HEK293\/OATP1B1 cells. Data are shown as percentage mean uptake volume values \u0026#xB1; S.E. of three to six wells in one to two independent experiments compared with those of the control.\u0022 class=\u0022highwire-fragment fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-852486403\u0022 data-figure-caption=\u0022\u0026lt;div class=\u0026quot;highwire-markup\u0026quot;\u0026gt;\u0026lt;div xmlns=\u0026quot;http:\/\/www.w3.org\/1999\/xhtml\u0026quot;\u0026gt;Inhibition of OATP1B1-mediated uptake of [\u0026lt;sup\u0026gt;3\u0026lt;\/sup\u0026gt;H]E\u0026lt;sub\u0026gt;1\u0026lt;\/sub\u0026gt;S (A), [\u0026lt;sup\u0026gt;3\u0026lt;\/sup\u0026gt;H]E\u0026lt;sub\u0026gt;2\u0026lt;\/sub\u0026gt;G (B), atorvastatin (C), pitavastatin (D), and rosuvastatin (E) after preincubation with CsA. The cells were washed with transport buffer prewarmed at 37\u0026#xB0;C and were then pretreated for 5 minutes with the transport buffer without substrates or inhibitors. The medium was then replaced with the transport buffer containing inhibitors at the various concentrations of CsA, and cells were further preincubated for 0 or 30 minutes at 37\u0026#xB0;C. After the preincubation, the transport buffer containing inhibitors was removed, and the reaction was then started by applying prewarmed fresh transport buffer containing [\u0026lt;sup\u0026gt;3\u0026lt;\/sup\u0026gt;H]E\u0026lt;sub\u0026gt;1\u0026lt;\/sub\u0026gt;S, [\u0026lt;sup\u0026gt;3\u0026lt;\/sup\u0026gt;H]E\u0026lt;sub\u0026gt;2\u0026lt;\/sub\u0026gt;G, atorvastatin (0.3 \u0026#x3BC;M), pitavastatin (0.5 \u0026#x3BC;M), or rosuvastatin (3 \u0026#x3BC;M) and the inhibitors to the cells. At 0.5 minutes ([\u0026lt;sup\u0026gt;3\u0026lt;\/sup\u0026gt;H]E\u0026lt;sub\u0026gt;1\u0026lt;\/sub\u0026gt;S and [\u0026lt;sup\u0026gt;3\u0026lt;\/sup\u0026gt;H]E\u0026lt;sub\u0026gt;2\u0026lt;\/sub\u0026gt;G) or 1 minute (atorvastatin, pitavastatin, and rosuvastatin), the reaction solution was removed by aspiration, and cells were washed with ice-cold transport buffer. The OATP1B1-mediated uptake was obtained by subtracting the uptake in HEK293\/mock cells from that in HEK293\/OATP1B1 cells. Data are shown as percentage mean uptake volume values \u0026#xB1; S.E. of three to six wells in one to two independent experiments compared with those of the control.\u0026lt;\/div\u0026gt;\u0026lt;\/div\u0026gt;\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cspan class=\u0022hw-responsive-img\u0022\u003E\u003Cimg class=\u0022highwire-fragment fragment-image lazyload\u0022 alt=\u0022Fig. 1.\u0022 src=\u0022data:image\/gif;base64,R0lGODlhAQABAIAAAAAAAP\/\/\/yH5BAEAAAAALAAAAAABAAEAAAIBRAA7\u0022 data-src=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F2.medium.gif\u0022 width=\u0022440\u0022 height=\u0022296\u0022\/\u003E\u003Cnoscript\u003E\u003Cimg class=\u0022highwire-fragment fragment-image\u0022 alt=\u0022Fig. 1.\u0022 src=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F2.medium.gif\u0022 width=\u0022440\u0022 height=\u0022296\u0022\/\u003E\u003C\/noscript\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u0022download-fig first\u0022\u003E\u003Ca href=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Fig. 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u0022new-tab\u0022\u003E\u003Ca href=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F2.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u0022download-ppt last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/75553\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFig. 1.\u003C\/span\u003E \u003Cp id=\u0022p-21\u0022 class=\u0022first-child\u0022\u003EInhibition of OATP1B1-mediated uptake of [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E1\u003C\/sub\u003ES (A), [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E2\u003C\/sub\u003EG (B), atorvastatin (C), pitavastatin (D), and rosuvastatin (E) after preincubation with CsA. The cells were washed with transport buffer prewarmed at 37\u00b0C and were then pretreated for 5 minutes with the transport buffer without substrates or inhibitors. The medium was then replaced with the transport buffer containing inhibitors at the various concentrations of CsA, and cells were further preincubated for 0 or 30 minutes at 37\u00b0C. After the preincubation, the transport buffer containing inhibitors was removed, and the reaction was then started by applying prewarmed fresh transport buffer containing [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E1\u003C\/sub\u003ES, [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E2\u003C\/sub\u003EG, atorvastatin (0.3 \u03bcM), pitavastatin (0.5 \u03bcM), or rosuvastatin (3 \u03bcM) and the inhibitors to the cells. At 0.5 minutes ([\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E1\u003C\/sub\u003ES and [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E2\u003C\/sub\u003EG) or 1 minute (atorvastatin, pitavastatin, and rosuvastatin), the reaction solution was removed by aspiration, and cells were washed with ice-cold transport buffer. The OATP1B1-mediated uptake was obtained by subtracting the uptake in HEK293\/mock cells from that in HEK293\/OATP1B1 cells. Data are shown as percentage mean uptake volume values \u00b1 S.E. of three to six wells in one to two independent experiments compared with those of the control.\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline table-callout-links\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u0022view-inline first\u0022\u003E\u003Ca href=\u0022##\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/75547\/expansion?postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u0022view-popup last\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/75547\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETABLE 1\u003C\/span\u003E \u003Cp id=\u0022p-22\u0022 class=\u0022first-child\u0022\u003EKinetic parameters for inhibition, inactivation, and recovery of OATP1B1 activity and estimation of DDI potential of CsA\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-18\u0022 class=\u0022subsection\u0022\u003E\u003Ch4\u003EInactivation Profile of OATP1B1 Activity by Preincubation with CsA.\u003C\/h4\u003E\u003Cp id=\u0022p-32\u0022\u003ENext, OATP1B1 activity remaining after preincubation with CsA was assessed using the uptake study of each OATP1B1 substrate. OATP1B1 activity assessed as the uptake of all the five substrates examined was reduced by preincubation with CsA in a concentration-dependent manner (\u003Ca id=\u0022xref-fig-3-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F3\u0022\u003EFig. 2\u003C\/a\u003E). In the case of uptake of [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E1\u003C\/sub\u003ES, [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E2\u003C\/sub\u003EG, pitavastatin, and rosuvastatin, the OATP1B1 activity rapidly declined during preincubation with CsA for 20 seconds and did not linearly decline up to 1 minute (\u003Ca id=\u0022xref-fig-3-2\u0022 class=\u0022xref-fig\u0022 href=\u0022#F3\u0022\u003EFig. 2, A, B, D, and E\u003C\/a\u003E). Conversely, the OATP1B1 activity assessed as the uptake of atorvastatin almost linearly declined with up to 3 minutes of the preincubation, at least at lower concentrations of CsA (\u003Ca id=\u0022xref-fig-3-3\u0022 class=\u0022xref-fig\u0022 href=\u0022#F3\u0022\u003EFig. 2C\u003C\/a\u003E). Based on these kinetics of OATP1B1 activity inactivation, the k\u003Csub\u003Eobs,app\u003C\/sub\u003E values were then estimated from the slope of the remaining OATP1B1 activity (\u003Ca id=\u0022xref-fig-3-4\u0022 class=\u0022xref-fig\u0022 href=\u0022#F3\u0022\u003EFig. 2\u003C\/a\u003E). Because of difficulty in preincubating for a period shorter than 20 seconds, the k\u003Csub\u003Eobs,app\u003C\/sub\u003E was calculated from the slope of the remaining OATP1B1 activity at 0 and 20 seconds for the uptake of [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E1\u003C\/sub\u003ES, [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E2\u003C\/sub\u003EG, pitavastatin, and rosuvastatin. The k\u003Csub\u003Eobs,app\u003C\/sub\u003E for atorvastatin uptake was calculated as the slope from the linear regression analysis until 3 minutes. The observed k\u003Csub\u003Eobs,app\u003C\/sub\u003E values were plotted versus the concentration of CsA preincubated (\u003Ca id=\u0022xref-fig-4-2\u0022 class=\u0022xref-fig\u0022 href=\u0022#F4\u0022\u003EFig. 3\u003C\/a\u003E), and both k\u003Csub\u003Einact\u003C\/sub\u003E and K\u003Csub\u003EI\u003C\/sub\u003E values were calculated based on \u003Ca id=\u0022xref-disp-formula-2-2\u0022 class=\u0022xref-disp-formula\u0022 href=\u0022#disp-formula-2\u0022\u003Eeq. 2\u003C\/a\u003E (\u003Ca id=\u0022xref-table-wrap-1-2\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022F3\u0022 class=\u0022fig pos-float odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F3.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Inactivation of OATP1B1-mediated uptake of [3H]E1S (A), [3H]E2G (B), atorvastatin (C), pitavastatin (D), and rosuvastatin (E) after preincubation with CsA. HEK293\/OATP1B1 cells were preincubated with CsA at 0 (\u0026#x3007;, black), 0.02 (\u0026#x25B3;, blue), 0.05 (\u0026#x25A1;, green), 0.1 (\u0026#x25CF;, orange), 0.2 (\u0026#x25B2;, red), and 0.5 \u0026#x3BC;M (\u0026#x25A0;, purple) for [3H]E1S and [3H]E2G and 0 (\u0026#x3007;, black), 0.005 (\u0026#x25B3;, blue), 0.01(\u0026#x25A1;, green), 0.02 (\u0026#x25CF;, orange), 0.05 (\u0026#x25B2;, red), and 0.1 \u0026#x3BC;M (\u0026#x25A0;, purple) for atorvastatin, pitavastatin, and rosuvastatin for the designated periods. After preincubation, the cells were washed once with prewarmed transport buffer and incubated with each substrate. At 0.5 ([3H]E1S and [3H]E2G) or 1 minute (atorvastatin, pitavastatin, and rosuvastatin), the reaction solution was aspirated, and the cells were washed twice with ice-cold transport buffer, followed by determination of their uptake. Uptake values are represented as the percentage of the activity obtained in the vehicle control samples and are plotted vs. the preincubation period. Each symbol represents the mean \u0026#xB1; S.E. of three wells in a single experiment.\u0022 class=\u0022highwire-fragment fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-852486403\u0022 data-figure-caption=\u0022\u0026lt;div class=\u0026quot;highwire-markup\u0026quot;\u0026gt;\u0026lt;div xmlns=\u0026quot;http:\/\/www.w3.org\/1999\/xhtml\u0026quot;\u0026gt;Inactivation of OATP1B1-mediated uptake of [\u0026lt;sup\u0026gt;3\u0026lt;\/sup\u0026gt;H]E\u0026lt;sub\u0026gt;1\u0026lt;\/sub\u0026gt;S (A), [\u0026lt;sup\u0026gt;3\u0026lt;\/sup\u0026gt;H]E\u0026lt;sub\u0026gt;2\u0026lt;\/sub\u0026gt;G (B), atorvastatin (C), pitavastatin (D), and rosuvastatin (E) after preincubation with CsA. HEK293\/OATP1B1 cells were preincubated with CsA at 0 (\u0026#x3007;, black), 0.02 (\u0026#x25B3;, blue), 0.05 (\u0026#x25A1;, green), 0.1 (\u0026#x25CF;, orange), 0.2 (\u0026#x25B2;, red), and 0.5 \u0026#x3BC;M (\u0026#x25A0;, purple) for [\u0026lt;sup\u0026gt;3\u0026lt;\/sup\u0026gt;H]E\u0026lt;sub\u0026gt;1\u0026lt;\/sub\u0026gt;S and [\u0026lt;sup\u0026gt;3\u0026lt;\/sup\u0026gt;H]E\u0026lt;sub\u0026gt;2\u0026lt;\/sub\u0026gt;G and 0 (\u0026#x3007;, black), 0.005 (\u0026#x25B3;, blue), 0.01(\u0026#x25A1;, green), 0.02 (\u0026#x25CF;, orange), 0.05 (\u0026#x25B2;, red), and 0.1 \u0026#x3BC;M (\u0026#x25A0;, purple) for atorvastatin, pitavastatin, and rosuvastatin for the designated periods. After preincubation, the cells were washed once with prewarmed transport buffer and incubated with each substrate. At 0.5 ([\u0026lt;sup\u0026gt;3\u0026lt;\/sup\u0026gt;H]E\u0026lt;sub\u0026gt;1\u0026lt;\/sub\u0026gt;S and [\u0026lt;sup\u0026gt;3\u0026lt;\/sup\u0026gt;H]E\u0026lt;sub\u0026gt;2\u0026lt;\/sub\u0026gt;G) or 1 minute (atorvastatin, pitavastatin, and rosuvastatin), the reaction solution was aspirated, and the cells were washed twice with ice-cold transport buffer, followed by determination of their uptake. Uptake values are represented as the percentage of the activity obtained in the vehicle control samples and are plotted vs. the preincubation period. Each symbol represents the mean \u0026#xB1; S.E. of three wells in a single experiment.\u0026lt;\/div\u0026gt;\u0026lt;\/div\u0026gt;\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cspan class=\u0022hw-responsive-img\u0022\u003E\u003Cimg class=\u0022highwire-fragment fragment-image lazyload\u0022 alt=\u0022Fig. 2.\u0022 src=\u0022data:image\/gif;base64,R0lGODlhAQABAIAAAAAAAP\/\/\/yH5BAEAAAAALAAAAAABAAEAAAIBRAA7\u0022 data-src=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F3.medium.gif\u0022 width=\u0022440\u0022 height=\u0022278\u0022\/\u003E\u003Cnoscript\u003E\u003Cimg class=\u0022highwire-fragment fragment-image\u0022 alt=\u0022Fig. 2.\u0022 src=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F3.medium.gif\u0022 width=\u0022440\u0022 height=\u0022278\u0022\/\u003E\u003C\/noscript\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u0022download-fig first\u0022\u003E\u003Ca href=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F3.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Fig. 2.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u0022new-tab\u0022\u003E\u003Ca href=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F3.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u0022download-ppt last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/75559\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFig. 2.\u003C\/span\u003E \u003Cp id=\u0022p-33\u0022 class=\u0022first-child\u0022\u003EInactivation of OATP1B1-mediated uptake of [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E1\u003C\/sub\u003ES (A), [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E2\u003C\/sub\u003EG (B), atorvastatin (C), pitavastatin (D), and rosuvastatin (E) after preincubation with CsA. HEK293\/OATP1B1 cells were preincubated with CsA at 0 (\u3007, black), 0.02 (\u25b3, blue), 0.05 (\u25a1, green), 0.1 (\u25cf, orange), 0.2 (\u25b2, red), and 0.5 \u03bcM (\u25a0, purple) for [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E1\u003C\/sub\u003ES and [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E2\u003C\/sub\u003EG and 0 (\u3007, black), 0.005 (\u25b3, blue), 0.01(\u25a1, green), 0.02 (\u25cf, orange), 0.05 (\u25b2, red), and 0.1 \u03bcM (\u25a0, purple) for atorvastatin, pitavastatin, and rosuvastatin for the designated periods. After preincubation, the cells were washed once with prewarmed transport buffer and incubated with each substrate. At 0.5 ([\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E1\u003C\/sub\u003ES and [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E2\u003C\/sub\u003EG) or 1 minute (atorvastatin, pitavastatin, and rosuvastatin), the reaction solution was aspirated, and the cells were washed twice with ice-cold transport buffer, followed by determination of their uptake. Uptake values are represented as the percentage of the activity obtained in the vehicle control samples and are plotted vs. the preincubation period. Each symbol represents the mean \u00b1 S.E. of three wells in a single experiment.\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv id=\u0022F4\u0022 class=\u0022fig pos-float odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F4.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Observed kobs,app values of OATP1B1-mediated uptake of [3H]E1S (A), [3H]E2G (B), atorvastatin (C), pitavastatin (D), and rosuvastatin (E) vs. CsA concentration. The kobs,app values were determined as the negative slopes of the natural logarithm (0\u0026#x2013;20 seconds for [3H]E1S, [3H]E2G, pitavastatin, and rosuvastatin; 0\u0026#x2013;3 minutes for atorvastatin) shown in Fig. 2. Solid lines represent the fitting curves of the observed kobs,app vs. CsA concentration by nonlinear regression analysis based on eq. 2. Each symbol represents the mean \u0026#xB1; S.E. of three wells in a single experiment.\u0022 class=\u0022highwire-fragment fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-852486403\u0022 data-figure-caption=\u0022\u0026lt;div class=\u0026quot;highwire-markup\u0026quot;\u0026gt;\u0026lt;div xmlns=\u0026quot;http:\/\/www.w3.org\/1999\/xhtml\u0026quot;\u0026gt;Observed k\u0026lt;sub\u0026gt;obs,app\u0026lt;\/sub\u0026gt; values of OATP1B1-mediated uptake of [\u0026lt;sup\u0026gt;3\u0026lt;\/sup\u0026gt;H]E\u0026lt;sub\u0026gt;1\u0026lt;\/sub\u0026gt;S (A), [\u0026lt;sup\u0026gt;3\u0026lt;\/sup\u0026gt;H]E\u0026lt;sub\u0026gt;2\u0026lt;\/sub\u0026gt;G (B), atorvastatin (C), pitavastatin (D), and rosuvastatin (E) vs. CsA concentration. The k\u0026lt;sub\u0026gt;obs,app\u0026lt;\/sub\u0026gt; values were determined as the negative slopes of the natural logarithm (0\u0026#x2013;20 seconds for [\u0026lt;sup\u0026gt;3\u0026lt;\/sup\u0026gt;H]E\u0026lt;sub\u0026gt;1\u0026lt;\/sub\u0026gt;S, [\u0026lt;sup\u0026gt;3\u0026lt;\/sup\u0026gt;H]E\u0026lt;sub\u0026gt;2\u0026lt;\/sub\u0026gt;G, pitavastatin, and rosuvastatin; 0\u0026#x2013;3 minutes for atorvastatin) shown in Fig. 2. Solid lines represent the fitting curves of the observed k\u0026lt;sub\u0026gt;obs,app\u0026lt;\/sub\u0026gt; vs. CsA concentration by nonlinear regression analysis based on eq. 2. Each symbol represents the mean \u0026#xB1; S.E. of three wells in a single experiment.\u0026lt;\/div\u0026gt;\u0026lt;\/div\u0026gt;\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cspan class=\u0022hw-responsive-img\u0022\u003E\u003Cimg class=\u0022highwire-fragment fragment-image lazyload\u0022 alt=\u0022Fig. 3.\u0022 src=\u0022data:image\/gif;base64,R0lGODlhAQABAIAAAAAAAP\/\/\/yH5BAEAAAAALAAAAAABAAEAAAIBRAA7\u0022 data-src=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F4.medium.gif\u0022 width=\u0022440\u0022 height=\u0022265\u0022\/\u003E\u003Cnoscript\u003E\u003Cimg class=\u0022highwire-fragment fragment-image\u0022 alt=\u0022Fig. 3.\u0022 src=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F4.medium.gif\u0022 width=\u0022440\u0022 height=\u0022265\u0022\/\u003E\u003C\/noscript\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u0022download-fig first\u0022\u003E\u003Ca href=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F4.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Fig. 3.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u0022new-tab\u0022\u003E\u003Ca href=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F4.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u0022download-ppt last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/75554\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFig. 3.\u003C\/span\u003E \u003Cp id=\u0022p-34\u0022 class=\u0022first-child\u0022\u003EObserved k\u003Csub\u003Eobs,app\u003C\/sub\u003E values of OATP1B1-mediated uptake of [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E1\u003C\/sub\u003ES (A), [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E2\u003C\/sub\u003EG (B), atorvastatin (C), pitavastatin (D), and rosuvastatin (E) vs. CsA concentration. The k\u003Csub\u003Eobs,app\u003C\/sub\u003E values were determined as the negative slopes of the natural logarithm (0\u201320 seconds for [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E1\u003C\/sub\u003ES, [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E2\u003C\/sub\u003EG, pitavastatin, and rosuvastatin; 0\u20133 minutes for atorvastatin) shown in \u003Ca id=\u0022xref-fig-3-5\u0022 class=\u0022xref-fig\u0022 href=\u0022#F3\u0022\u003EFig. 2\u003C\/a\u003E. Solid lines represent the fitting curves of the observed k\u003Csub\u003Eobs,app\u003C\/sub\u003E vs. CsA concentration by nonlinear regression analysis based on \u003Ca id=\u0022xref-disp-formula-2-3\u0022 class=\u0022xref-disp-formula\u0022 href=\u0022#disp-formula-2\u0022\u003Eeq. 2\u003C\/a\u003E. Each symbol represents the mean \u00b1 S.E. of three wells in a single experiment.\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-19\u0022 class=\u0022subsection\u0022\u003E\u003Ch4\u003ERecovery of OATP1B1 Activity after Preincubation with CsA.\u003C\/h4\u003E\u003Cp id=\u0022p-35\u0022\u003EAfter preincubation with CsA for 30 minutes, HEK293\/OATP1B1 cells were washed and cultured for the designated period without CsA or substrates, and the uptake of OATP1B1 substrates was then examined in the absence of the inhibitor. Immediately after preincubation with 0.3 \u03bcM CsA, OATP1B1-mediated uptake of [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E1\u003C\/sub\u003ES, [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E2\u003C\/sub\u003EG, atorvastatin, pitavastatin, and rosuvastatin was reduced to 26%, 29%, 18%, 36%, and 57% of the control, respectively (\u003Ca id=\u0022xref-fig-5-2\u0022 class=\u0022xref-fig\u0022 href=\u0022#F5\u0022\u003EFig. 4\u003C\/a\u003E). The reduced OATP1B1 activity was recovered in a culture period\u2013dependent manner (\u003Ca id=\u0022xref-fig-5-3\u0022 class=\u0022xref-fig\u0022 href=\u0022#F5\u0022\u003EFig. 4\u003C\/a\u003E), and the k\u003Csub\u003Erecovery\u003C\/sub\u003E value was calculated using linear regression analysis (\u003Ca id=\u0022xref-table-wrap-1-3\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022F5\u0022 class=\u0022fig pos-float odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F5.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Recovery of OATP1B1 activity after preincubation with CsA. HEK293\/OATP1B1 cells were preincubated with culture medium containing CsA (0.3 \u0026#x3BC;M) for 30 minutes. The medium was replaced with fresh culture medium and further incubated in the absence of CsA for the designated periods. The cells were then washed with prewarmed transport buffer once, and the transport buffer, including [3H]E1S (\u0026#x3007;), [3H]E2G (\u0026#x25B3;), atorvastatin (\u0026#x25CF;), pitavastatin (\u0026#x25B2;), and rosuvastatin (\u0026#x25A0;), was added, followed by determination of their uptake. Data are normalized with the control value obtained without the inhibitor and are shown as means \u0026#xB1; S.E. of three wells in a single experiment.\u0022 class=\u0022highwire-fragment fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-852486403\u0022 data-figure-caption=\u0022\u0026lt;div class=\u0026quot;highwire-markup\u0026quot;\u0026gt;\u0026lt;div xmlns=\u0026quot;http:\/\/www.w3.org\/1999\/xhtml\u0026quot;\u0026gt;Recovery of OATP1B1 activity after preincubation with CsA. HEK293\/OATP1B1 cells were preincubated with culture medium containing CsA (0.3 \u0026#x3BC;M) for 30 minutes. The medium was replaced with fresh culture medium and further incubated in the absence of CsA for the designated periods. The cells were then washed with prewarmed transport buffer once, and the transport buffer, including [\u0026lt;sup\u0026gt;3\u0026lt;\/sup\u0026gt;H]E\u0026lt;sub\u0026gt;1\u0026lt;\/sub\u0026gt;S (\u0026#x3007;), [\u0026lt;sup\u0026gt;3\u0026lt;\/sup\u0026gt;H]E\u0026lt;sub\u0026gt;2\u0026lt;\/sub\u0026gt;G (\u0026#x25B3;), atorvastatin (\u0026#x25CF;), pitavastatin (\u0026#x25B2;), and rosuvastatin (\u0026#x25A0;), was added, followed by determination of their uptake. Data are normalized with the control value obtained without the inhibitor and are shown as means \u0026#xB1; S.E. of three wells in a single experiment.\u0026lt;\/div\u0026gt;\u0026lt;\/div\u0026gt;\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cspan class=\u0022hw-responsive-img\u0022\u003E\u003Cimg class=\u0022highwire-fragment fragment-image lazyload\u0022 alt=\u0022Fig. 4.\u0022 src=\u0022data:image\/gif;base64,R0lGODlhAQABAIAAAAAAAP\/\/\/yH5BAEAAAAALAAAAAABAAEAAAIBRAA7\u0022 data-src=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F5.medium.gif\u0022 width=\u0022440\u0022 height=\u0022271\u0022\/\u003E\u003Cnoscript\u003E\u003Cimg class=\u0022highwire-fragment fragment-image\u0022 alt=\u0022Fig. 4.\u0022 src=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F5.medium.gif\u0022 width=\u0022440\u0022 height=\u0022271\u0022\/\u003E\u003C\/noscript\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u0022download-fig first\u0022\u003E\u003Ca href=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F5.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Fig. 4.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u0022new-tab\u0022\u003E\u003Ca href=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F5.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u0022download-ppt last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/75557\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFig. 4.\u003C\/span\u003E \u003Cp id=\u0022p-36\u0022 class=\u0022first-child\u0022\u003ERecovery of OATP1B1 activity after preincubation with CsA. HEK293\/OATP1B1 cells were preincubated with culture medium containing CsA (0.3 \u03bcM) for 30 minutes. The medium was replaced with fresh culture medium and further incubated in the absence of CsA for the designated periods. The cells were then washed with prewarmed transport buffer once, and the transport buffer, including [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E1\u003C\/sub\u003ES (\u3007), [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E2\u003C\/sub\u003EG (\u25b3), atorvastatin (\u25cf), pitavastatin (\u25b2), and rosuvastatin (\u25a0), was added, followed by determination of their uptake. Data are normalized with the control value obtained without the inhibitor and are shown as means \u00b1 S.E. of three wells in a single experiment.\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-20\u0022 class=\u0022subsection\u0022\u003E\u003Ch4\u003EAssessment of OATP1B1-Mediated DDI Potential with CsA Based on the Static Model Incorporating Inactivation and Recovery of OATP1B1 Activity.\u003C\/h4\u003E\u003Cp id=\u0022p-37\u0022\u003EStatic model\u2013based assessment of OATP1B1-mediated DDI potential was next performed for three OATP1B1 substrates, for which the AUC ratio with or without the coadministration of CsA was clinically reported. First, the f\u003Csub\u003Eu,p\u003C\/sub\u003E value (0.0107) of CsA was evaluated by equilibrium dialysis in-house, whereas the I\u003Csub\u003Eu,inlet,max\u003C\/sub\u003E value of CsA was calculated by \u003Ca id=\u0022xref-disp-formula-5-2\u0022 class=\u0022xref-disp-formula\u0022 href=\u0022#disp-formula-5\u0022\u003Eeq. 5\u003C\/a\u003E using pharmacokinetic parameters summarized in \u003Ca href=\u0022http:\/\/dmd.aspetjournals.org\/lookup\/suppl\/doi:10.1124\/dmd.120.000020\/-\/DCSupplemental\u0022\u003ESupplemental Table 3\u003C\/a\u003E (\u003Ca id=\u0022xref-table-wrap-1-4\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). Contribution ratio (f value) of OATP1B1-mediated uptake to overall uptake of the three OATP1B1 substrates in human hepatocytes was estimated as the average of previously reported values (\u003Ca id=\u0022xref-ref-12-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-12\u0022\u003EKunze et al., 2014\u003C\/a\u003E; \u003Ca id=\u0022xref-ref-9-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-9\u0022\u003EIzumi et al., 2018\u003C\/a\u003E; \u003Ca id=\u0022xref-ref-26-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-26\u0022\u003EZhang et al., 2019\u003C\/a\u003E) (\u003Ca id=\u0022xref-table-wrap-1-5\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). The R\u003Csub\u003E0\u003C\/sub\u003E values of CsA without consideration of the preincubation effect were first calculated by \u003Ca id=\u0022xref-disp-formula-3-2\u0022 class=\u0022xref-disp-formula\u0022 href=\u0022#disp-formula-3\u0022\u003Eeq. 3\u003C\/a\u003E for the five OATP1B1 substrates and were close to unity (\u003Ca id=\u0022xref-table-wrap-1-6\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E), suggesting that direct inhibition of OATP1B1 by CsA does not present a clinical impact. Then, R\u003Csub\u003E1\u003C\/sub\u003E values were next calculated using IC\u003Csub\u003E50\u003C\/sub\u003E values estimated after 30 minutes of preincubation with CsA and were higher than R\u003Csub\u003E0\u003C\/sub\u003E values (\u003Ca id=\u0022xref-table-wrap-1-7\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). However, the R\u003Csub\u003E1\u003C\/sub\u003E values calculated for the three OATP1B1 substrate drugs remained considerably lower than the observed AUC ratio (\u003Ca id=\u0022xref-table-wrap-1-8\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). In contrast, the R\u003Csub\u003E2\u003C\/sub\u003E and R\u003Csub\u003E3\u003C\/sub\u003E values calculated by \u003Ca id=\u0022xref-disp-formula-6-1\u0022 class=\u0022xref-disp-formula\u0022 href=\u0022#disp-formula-6\u0022\u003Eeqs. 6\u003C\/a\u003E and \u003Ca id=\u0022xref-disp-formula-9-1\u0022 class=\u0022xref-disp-formula\u0022 href=\u0022#disp-formula-9\u0022\u003E9\u003C\/a\u003E, respectively, were higher than the R\u003Csub\u003E1\u003C\/sub\u003E values and closer to the observed AUC ratio (\u003Ca id=\u0022xref-table-wrap-1-9\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). To estimate the maximum potential of OATP1B1-mediated DDI, the R\u2032 values were also estimated when OATP1B1 alone was assumed to contribute to the overall hepatic uptake of each substrate (the f value was considered to be unity). Thus, The R\u003Csub\u003E1\u003C\/sub\u003E\u2032 values estimated were comparable with the R\u003Csub\u003E1\u003C\/sub\u003E values and lower than the AUC ratios. On the other hand, R\u003Csub\u003E2\u003C\/sub\u003E\u2032 and R\u003Csub\u003E3\u003C\/sub\u003E\u2032 values were markedly higher than the R\u003Csub\u003E2\u003C\/sub\u003E and R\u003Csub\u003E3\u003C\/sub\u003E values and the AUC ratio clinically reported (\u003Ca id=\u0022xref-table-wrap-1-10\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E).\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-21\u0022 class=\u0022subsection\u0022\u003E\u003Ch4\u003EEstimation of OATP1B1-Mediated DDI Potential by Preincubation-Dependent Inhibitors Other than CsA.\u003C\/h4\u003E\u003Cp id=\u0022p-38\u0022\u003EIt was previously reported that the inhibition of OATP1B1 by compounds other than CsA, including simeprevir, asunaprevir, and ritonavir, was increased by preincubation with the respective compounds (\u003Ca id=\u0022xref-ref-17-3\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-17\u0022\u003EShitara et al., 2013\u003C\/a\u003E; \u003Ca id=\u0022xref-ref-6-3\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-6\u0022\u003EFurihata et al., 2014\u003C\/a\u003E), although the enhanced OATP1B1 inhibition was not remarkable when compared with CsA. Furthermore, many TKIs strongly inhibit OATP1B1 after preincubation for 15 minutes ((\u003Ca id=\u0022xref-ref-19-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-19\u0022\u003ESprowl et al., 2016\u003C\/a\u003E)), with details regarding the effects of such preincubation on their inhibitory potential not presented in the report. To investigate the potential preincubation-dependent OATP1B1 inhibition by these compounds, inhibition studies were conducted with or without preincubation with the compounds in the present study. Preincubation for 30 minutes with all investigated inhibitors reduced the OATP1B1-mediated uptake of [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E1\u003C\/sub\u003ES when compared with that observed without preincubation (\u003Ca id=\u0022xref-fig-6-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F6\u0022\u003EFig. 5\u003C\/a\u003E). Among the inhibitors, asunaprevir, regorafenib, nilotinib, and pazopanib were selected for further evaluation of their potential for OATP1B1-mediated DDI. Inhibition, inactivation, and recovery after preincubation with these compounds were then examined with CsA (\u003Ca href=\u0022http:\/\/dmd.aspetjournals.org\/lookup\/suppl\/doi:10.1124\/dmd.120.000020\/-\/DC1\u0022\u003ESupplemental Figs. 1\u003C\/a\u003E\u2013\u003Ca href=\u0022http:\/\/dmd.aspetjournals.org\/lookup\/suppl\/doi:10.1124\/dmd.120.000020\/-\/DC1\u0022\u003E3\u003C\/a\u003E). In the case of asunaprevir, OATP1B1-mediated uptake was decreased in a concentration-dependent manner with and without preincubation, the inhibition being more potent after preincubation for longer than 30 minutes (\u003Ca href=\u0022http:\/\/dmd.aspetjournals.org\/lookup\/suppl\/doi:10.1124\/dmd.120.000020\/-\/DC1\u0022\u003ESupplemental Fig. 1\u003C\/a\u003E). In contrast, the inhibition of OATP1B1-mediated uptake by regorafenib and nilotinib without preincubation was only minimal (25% and 17% of control, respectively), even at 10 \u03bcM (\u003Ca href=\u0022http:\/\/dmd.aspetjournals.org\/lookup\/suppl\/doi:10.1124\/dmd.120.000020\/-\/DC1\u0022\u003ESupplemental Fig. 1\u003C\/a\u003E), whereas inhibition was evident when the cells were preincubated with these compounds (\u003Ca href=\u0022http:\/\/dmd.aspetjournals.org\/lookup\/suppl\/doi:10.1124\/dmd.120.000020\/-\/DC1\u0022\u003ESupplemental Fig. 1\u003C\/a\u003E). The IC\u003Csub\u003E50\u003C\/sub\u003E values of regorafenib and nilotinib can be estimated only with preincubation longer than 30 minutes and 1 minute, respectively (\u003Ca href=\u0022http:\/\/dmd.aspetjournals.org\/lookup\/suppl\/doi:10.1124\/dmd.120.000020\/-\/DC1\u0022\u003ESupplemental Table 4\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022F6\u0022 class=\u0022fig pos-float odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F6.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Screening of preincubation-dependent OATP1B1 inhibitors. HEK293\/OATP1B1 and HEK293\/mock cells were first preincubated with each compound at 1 \u0026#xB5;M for 30 minutes (closed column) or subjected to no preincubation (open column). Cells were then incubated with [3H]E1S and each compound for 0.5 minutes, followed by determination of OATP1B1-mediated uptake. Data are shown as the percentages of OATP1B1-mediated uptake obtained in the vehicle control samples of three wells in a single experiment.\u0022 class=\u0022highwire-fragment fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-852486403\u0022 data-figure-caption=\u0022\u0026lt;div class=\u0026quot;highwire-markup\u0026quot;\u0026gt;\u0026lt;div xmlns=\u0026quot;http:\/\/www.w3.org\/1999\/xhtml\u0026quot;\u0026gt;Screening of preincubation-dependent OATP1B1 inhibitors. HEK293\/OATP1B1 and HEK293\/mock cells were first preincubated with each compound at 1 \u0026#xB5;M for 30 minutes (closed column) or subjected to no preincubation (open column). Cells were then incubated with [\u0026lt;sup\u0026gt;3\u0026lt;\/sup\u0026gt;H]E\u0026lt;sub\u0026gt;1\u0026lt;\/sub\u0026gt;S and each compound for 0.5 minutes, followed by determination of OATP1B1-mediated uptake. Data are shown as the percentages of OATP1B1-mediated uptake obtained in the vehicle control samples of three wells in a single experiment.\u0026lt;\/div\u0026gt;\u0026lt;\/div\u0026gt;\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cspan class=\u0022hw-responsive-img\u0022\u003E\u003Cimg class=\u0022highwire-fragment fragment-image lazyload\u0022 alt=\u0022Fig. 5.\u0022 src=\u0022data:image\/gif;base64,R0lGODlhAQABAIAAAAAAAP\/\/\/yH5BAEAAAAALAAAAAABAAEAAAIBRAA7\u0022 data-src=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F6.medium.gif\u0022 width=\u0022440\u0022 height=\u0022319\u0022\/\u003E\u003Cnoscript\u003E\u003Cimg class=\u0022highwire-fragment fragment-image\u0022 alt=\u0022Fig. 5.\u0022 src=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F6.medium.gif\u0022 width=\u0022440\u0022 height=\u0022319\u0022\/\u003E\u003C\/noscript\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u0022download-fig first\u0022\u003E\u003Ca href=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F6.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Fig. 5.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u0022new-tab\u0022\u003E\u003Ca href=\u0022https:\/\/dmd.aspetjournals.org\/content\/dmd\/48\/9\/750\/F6.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u0022download-ppt last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/75578\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFig. 5.\u003C\/span\u003E \u003Cp id=\u0022p-39\u0022 class=\u0022first-child\u0022\u003EScreening of preincubation-dependent OATP1B1 inhibitors. HEK293\/OATP1B1 and HEK293\/mock cells were first preincubated with each compound at 1 \u00b5M for 30 minutes (closed column) or subjected to no preincubation (open column). Cells were then incubated with [\u003Csup\u003E3\u003C\/sup\u003EH]E\u003Csub\u003E1\u003C\/sub\u003ES and each compound for 0.5 minutes, followed by determination of OATP1B1-mediated uptake. Data are shown as the percentages of OATP1B1-mediated uptake obtained in the vehicle control samples of three wells in a single experiment.\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-40\u0022\u003EThe pharmacokinetic parameters of these inhibitors obtained from the literature (\u003Ca href=\u0022http:\/\/dmd.aspetjournals.org\/lookup\/suppl\/doi:10.1124\/dmd.120.000020\/-\/DC1\u0022\u003ESupplemental Table 3\u003C\/a\u003E) were used to estimate the R values based on inactivation and recovery kinetics of OATP1B1 activity examined in the present study. The R\u003Csub\u003E0\u003C\/sub\u003E\u2032 values were close to unity, whereas the R\u003Csub\u003E1\u003C\/sub\u003E\u2032, R\u003Csub\u003E2\u003C\/sub\u003E\u2032, and R\u003Csub\u003E3\u003C\/sub\u003E\u2032 values of regorafenib and nilotinib were at most 1.2\u20131.3. The R\u003Csub\u003E2\u003C\/sub\u003E\u2032 and R\u003Csub\u003E3\u003C\/sub\u003E\u2032 values of pazopanib were approximately 2 (\u003Ca id=\u0022xref-table-wrap-2-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T2\u0022\u003ETable 2\u003C\/a\u003E). In the case of asunaprevir, a clinical DDI study with rosuvastatin was previously conducted, and the R value was calculated using the contribution ratio of OATP1B1 to overall hepatic uptake for rosuvastatin (\u003Ca id=\u0022xref-table-wrap-1-11\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). In this combination, the R\u003Csub\u003E0\u003C\/sub\u003E and R\u003Csub\u003E1\u003C\/sub\u003E values were lower, but the R\u003Csub\u003E2\u003C\/sub\u003E and R\u003Csub\u003E3\u003C\/sub\u003E values were close to the observed AUC ratio (\u003Ca id=\u0022xref-table-wrap-2-2\u0022 class=\u0022xref-table\u0022 href=\u0022#T2\u0022\u003ETable 2\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022T2\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline table-callout-links\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u0022view-inline first\u0022\u003E\u003Ca href=\u0022##\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/75550\/expansion?postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u0022view-popup last\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/75550\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETABLE 2\u003C\/span\u003E \u003Cp id=\u0022p-41\u0022 class=\u0022first-child\u0022\u003EKinetic parameters for inhibition, inactivation, and recovery of OATP1B1 activity and estimation of DDIs potential of preincubation-dependent inhibitors\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022section discussion\u0022 id=\u0022sec-22\u0022\u003E\u003Ch2 class=\u0022\u0022\u003EDiscussion\u003C\/h2\u003E\u003Cp id=\u0022p-56\u0022\u003EThe avoidance of false-negative predictions in the case of DDIs via OATP1B1 is one of the most critical standpoints in patient safety during drug development. Inhibition of OATP1B1 by several drugs exhibits preincubation dependence, which could potentially lead to the false-negative prediction of their DDI potential. Here, we attempted to construct a static model for the prediction of OATP1B1-mediated DDIs induced by preincubation-dependent inhibitors by considering not only IC\u003Csub\u003E50\u003C\/sub\u003E values and I\u003Csub\u003Eu,inlet,max\u003C\/sub\u003E of perpetrators but also the inactivation and recovery kinetics of OATP1B1 activity. The rationale of this proposal could be explained by the R\u003Csub\u003E1\u003C\/sub\u003E values of CsA and asunaprevir calculated using IC\u003Csub\u003E50\u003C\/sub\u003E values estimated after preincubation being lower than the observed AUC ratios (\u003Ca id=\u0022xref-table-wrap-1-12\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETables 1\u003C\/a\u003E and \u003Ca id=\u0022xref-table-wrap-2-3\u0022 class=\u0022xref-table\u0022 href=\u0022#T2\u0022\u003E2\u003C\/a\u003E), indicating that the false-negative prediction of DDI potential cannot be avoided, even when we performed preincubation using in vitro transport studies to estimate the IC\u003Csub\u003E50\u003C\/sub\u003E values.\u003C\/p\u003E\u003Cp id=\u0022p-57\u0022\u003ECsA is a preincubation-dependent OATP1B1 inhibitor with abundant clinical DDI information. Therefore, the inhibition, inactivation, and recovery studies using CsA as a typical inhibitor were first conducted to validate the approach in the present study. The R\u003Csub\u003E1\u003C\/sub\u003E values of CsA for the three OATP1B1 substrates were much lower than the observed AUC ratios, whereas the R\u003Csub\u003E2\u003C\/sub\u003E and R\u003Csub\u003E3\u003C\/sub\u003E values for the three OATP1B1 substrates were closer to the observed AUC ratios (\u003Ca id=\u0022xref-table-wrap-1-13\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). A similar tendency was also observed for the R\u003Csub\u003E1\u003C\/sub\u003E, R\u003Csub\u003E2\u003C\/sub\u003E, and R\u003Csub\u003E3\u003C\/sub\u003E values for another combination of DDI (asunaprevir versus rosuvastatin, \u003Ca id=\u0022xref-table-wrap-2-4\u0022 class=\u0022xref-table\u0022 href=\u0022#T2\u0022\u003ETable 2\u003C\/a\u003E), suggesting that the R\u003Csub\u003E2\u003C\/sub\u003E and R\u003Csub\u003E3\u003C\/sub\u003E values were better indexes for the quantitative prediction of OATP1B1-mediated DDI. Since the R\u003Csub\u003E2\u003C\/sub\u003E and R\u003Csub\u003E3\u003C\/sub\u003E values consider inactivation and recovery kinetics of OATP1B1 activity during preincubation with the inhibitors, these results suggest the utility of the static model incorporating such OATP1B1 kinetics for predicting DDIs induced by preincubation-dependent inhibitors. It should be noted, however, that precise estimation of the inactivation and recovery kinetics with a sufficient amount of data would be critical for the DDI\u2019s prediction in this strategy.\u003C\/p\u003E\u003Cp id=\u0022p-58\u0022\u003EHowever, the R\u003Csub\u003E2\u003C\/sub\u003E and R\u003Csub\u003E3\u003C\/sub\u003E values for CsA and the three OATP1B1 substrates were lower than the observed AUC ratio (\u003Ca id=\u0022xref-table-wrap-1-14\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E), demonstrating the underprediction of DDIs. The static model proposed in the present study only considered OATP1B1-mediated DDI, whereas clinical DDIs with CsA may involve inhibition of not only OATP1B1 but also other metabolizing enzymes and\/or transporters. Then, one of the possible reasons could be the inhibition by CsA of other metabolic pathways and\/or transporters rather than OATP1B1. Actually, CsA is an inhibitor of OATP1B3, breast cancer resistance protein, and CYP3A4 (\u003Ca id=\u0022xref-ref-2-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-2\u0022\u003EDuan et al., 2017\u003C\/a\u003E). Another possible reason for the lower R\u003Csub\u003E2\u003C\/sub\u003E and R\u003Csub\u003E3\u003C\/sub\u003E values when compared with the AUC ratio would be the estimation of the f value. The estimation of the R values (R\u003Csub\u003E1\u003C\/sub\u003E, R\u003Csub\u003E2\u003C\/sub\u003E, and R\u003Csub\u003E3\u003C\/sub\u003E) is affected by the f values (\u003Ca id=\u0022xref-disp-formula-3-3\u0022 class=\u0022xref-disp-formula\u0022 href=\u0022#disp-formula-3\u0022\u003Eeqs. 3\u003C\/a\u003E, \u003Ca id=\u0022xref-disp-formula-6-2\u0022 class=\u0022xref-disp-formula\u0022 href=\u0022#disp-formula-6\u0022\u003E6\u003C\/a\u003E, and \u003Ca id=\u0022xref-disp-formula-9-2\u0022 class=\u0022xref-disp-formula\u0022 href=\u0022#disp-formula-9\u0022\u003E9\u003C\/a\u003E), and the f values used in the present study represented the average of reported values and may exhibit experimental\/interindividual variability, which may affect the accuracy of the R values. From this perspective, other types of R values (R\u003Csub\u003E1\u003C\/sub\u003E\u2032, R\u003Csub\u003E2\u003C\/sub\u003E\u2032, and R\u003Csub\u003E3\u003C\/sub\u003E\u2032) were also estimated by assuming an f value of unity in the present study. These R values may be valid to avoid false-negative DDI predictions since OATP1B1 alone was assumed to be involved in the hepatic uptake of each substrate. R\u003Csub\u003E2\u003C\/sub\u003E\u2032 and R\u003Csub\u003E3\u003C\/sub\u003E\u2032 values were higher than the observed AUC ratio (\u003Ca id=\u0022xref-table-wrap-1-15\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETables 1\u003C\/a\u003E and \u003Ca id=\u0022xref-table-wrap-2-5\u0022 class=\u0022xref-table\u0022 href=\u0022#T2\u0022\u003E2\u003C\/a\u003E), showing overestimation but no false-negative DDI predictions. This would be beneficial in terms of the maximum DDI potential via OATP1B1 through the inhibitor compounds examined. Therefore, the present strategy using the R\u003Csub\u003E2\u003C\/sub\u003E\u2032\/R\u003Csub\u003E3\u003C\/sub\u003E\u2032 values may be valuable when the maximum DDI potential for candidate compounds is estimated in the preclinical stage of drug development. However, it should be noted that the difference between the R\u003Csub\u003E2\u003C\/sub\u003E\u2032\/R\u003Csub\u003E3\u003C\/sub\u003E\u2032 values and the observed AUC ratio was substantial, especially for the combination of CsA versus pitavastatin and rosuvastatin (\u003Ca id=\u0022xref-table-wrap-1-16\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). Higher k\u003Csub\u003Einact\u003C\/sub\u003E and lower k\u003Csub\u003Erecovery\u003C\/sub\u003E values were observed for these two substrates (\u003Ca id=\u0022xref-table-wrap-1-17\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E), indicating larger inactivation with slower recovery of OATP1B1 activity. Thus, the precise estimation of DDI potential for the inhibitors showing such a remarkable effect on the turnover of OATP1B1 activity could be hindered by the estimation of the f values.\u003C\/p\u003E\u003Cp id=\u0022p-59\u0022\u003EThe approach proposed in the present study has mainly focused on avoidance of false-negative prediction, but it should be noted that this may concomitantly increase the false-positive rate. Therefore, avoidance of false-negative prediction of DDIs should also be achieved by building the necessary margins and\/or simulating the worst-case scenarios by construction of a dynamic model, such as a physiologically based pharmacokinetic model.\u003C\/p\u003E\u003Cp id=\u0022p-60\u0022\u003EIn the present study, various inhibitors other than CsA were found to exhibit the preincubation-dependent inhibition of OATP1B1 (\u003Ca id=\u0022xref-fig-6-2\u0022 class=\u0022xref-fig\u0022 href=\u0022#F6\u0022\u003EFig. 5\u003C\/a\u003E). Therefore, the kinetics of inactivation and recovery of OATP1B1 activity was also examined for some of these inhibitors. Notably, the inhibition of OATP1B1 by regorafenib and nilotinib was apparent only when the HEK293\/OATP1B1 cells were preincubated with these compounds (\u003Ca href=\u0022http:\/\/dmd.aspetjournals.org\/lookup\/suppl\/doi:10.1124\/dmd.120.000020\/-\/DC1\u0022\u003ESupplemental Fig. 1\u003C\/a\u003E), indicating the importance of the preincubation step in the estimation of the maximum inhibition potential for specific types of OATP1B1 inhibitors. However, the R\u2032 values for these two compounds were at most 1.2\u20131.3 (\u003Ca id=\u0022xref-table-wrap-2-6\u0022 class=\u0022xref-table\u0022 href=\u0022#T2\u0022\u003ETable 2\u003C\/a\u003E), suggesting their limited OATP1B1-mediated DDI potential even when inactivation and recovery kinetics were considered. On the other hand, pazopanib exhibited larger R\u003Csub\u003E2\u003C\/sub\u003E and R\u003Csub\u003E3\u003C\/sub\u003E values because of its higher k\u003Csub\u003Eobs\u003C\/sub\u003E value (\u003Ca id=\u0022xref-table-wrap-2-7\u0022 class=\u0022xref-table\u0022 href=\u0022#T2\u0022\u003ETable 2\u003C\/a\u003E). Although coadministration of pazopanib was reported to increase the AUC of the OATP1B1 substrate SN-38 (\u003Ca id=\u0022xref-ref-1-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-1\u0022\u003EBennouna et al., 2015\u003C\/a\u003E), this interaction was proposed to be accounted for primarily through the inhibition of glucuronidation of SN-38 by pazopanib (\u003Ca id=\u0022xref-ref-8-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-8\u0022\u003EIwase et al., 2019\u003C\/a\u003E). Regarding asunaprevir, \u003Ca id=\u0022xref-ref-3-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-3\u0022\u003EEley et al. (2015)\u003C\/a\u003E have proposed that this compound is a weak OATP inhibitor, showing a 1.41-fold increase in the AUC of rosuvastatin, which seemed comparable with the R\u003Csub\u003E2\u003C\/sub\u003E and R\u003Csub\u003E3\u003C\/sub\u003E values estimated in the present study (\u003Ca id=\u0022xref-table-wrap-2-8\u0022 class=\u0022xref-table\u0022 href=\u0022#T2\u0022\u003ETable 2\u003C\/a\u003E).\u003C\/p\u003E\u003Cp id=\u0022p-61\u0022\u003E\u003Ca id=\u0022xref-ref-10-4\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-10\u0022\u003EIzumi et al. (2015)\u003C\/a\u003E have reported that, after 1 hour of preincubation, the IC\u003Csub\u003E50\u003C\/sub\u003E values of CsA reported approximately a 6-fold difference among the five OATP1B1 substrates examined (\u003Ca id=\u0022xref-ref-10-5\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-10\u0022\u003EIzumi et al., 2015\u003C\/a\u003E). In the present study, the kinetics of inactivation and recovery of OATP1B1 activity induced by CsA was further evaluated for several OATP1B1 substrates and was found to also be substrate-dependent (\u003Ca id=\u0022xref-fig-3-6\u0022 class=\u0022xref-fig\u0022 href=\u0022#F3\u0022\u003EFigs. 2\u003C\/a\u003E\u003Ca id=\u0022xref-fig-4-3\u0022 class=\u0022xref-up-link\u0022 href=\u0022#F4\u0022\u003E\u003Cspan\u003E\u21d1\u003C\/span\u003E\u003C\/a\u003E\u2013\u003Ca id=\u0022xref-fig-5-4\u0022 class=\u0022xref-fig\u0022 href=\u0022#F5\u0022\u003E4\u003C\/a\u003E). Both k\u003Csub\u003Einact\u003C\/sub\u003E and k\u003Csub\u003Erecovery\u003C\/sub\u003E values of CsA were found to exhibit a three-to-seven-times difference among the substrates (\u003Ca id=\u0022xref-table-wrap-1-18\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). Therefore, to predict the DDI potential based on the static model proposed in the present study, selection of the OATP1B1 substrates for the in vitro studies could be critical, and it would be preferable to select substrates that will concomitantly be used in clinical situations with the inhibitors examined. Additionally, E\u003Csub\u003E2\u003C\/sub\u003EG exhibited higher values of R\u003Csub\u003E2\u003C\/sub\u003E and R\u003Csub\u003E3\u003C\/sub\u003E when compared with E\u003Csub\u003E1\u003C\/sub\u003ES (\u003Ca id=\u0022xref-table-wrap-1-19\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E), suggesting that E\u003Csub\u003E2\u003C\/sub\u003EG would be a superior substrate to avoid false-negative predictions among these two OATP1B1 substrates, although it should be noted that selection of the most-sensitive substrate, like E\u003Csub\u003E2\u003C\/sub\u003EG, may increase the false-positive rate. The expression level of OATP1B1 was not affected by incubation with CsA, with no obvious change observed in its subcellular localization (\u003Ca id=\u0022xref-ref-18-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-18\u0022\u003EShitara et al., 2012\u003C\/a\u003E), whereas the combination of \u003Cem\u003Ecis\u003C\/em\u003E- and \u003Cem\u003Etrans\u003C\/em\u003E-inhibition of OATP1B1 by CsA has been proposed to explain such preincubation-dependent inhibition (\u003Ca id=\u0022xref-ref-16-3\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-16\u0022\u003EShitara and Sugiyama 2017\u003C\/a\u003E).\u003C\/p\u003E\u003Cp id=\u0022p-62\u0022\u003EIn the present study, IC\u003Csub\u003E50\u003C\/sub\u003E values, but not inhibition constant (K\u003Csub\u003Ei\u003C\/sub\u003E), were estimated for calculating the R values. Here, the IC\u003Csub\u003E50\u003C\/sub\u003E values were assumed to be equal to K\u003Csub\u003Ei\u003C\/sub\u003E values, as the substrate concentration used was much lower than the K\u003Csub\u003Em\u003C\/sub\u003E values. This assumption is true in the case of competitive or noncompetitive inhibition, whereas CsA exhibits preincubation-dependent inhibition, and therefore, the IC\u003Csub\u003E50\u003C\/sub\u003E values may not be equal to the K\u003Csub\u003Ei\u003C\/sub\u003E values even when the initial phase of substrate uptake was examined. Furthermore, inactivation of OATP1B1 activity induced by CsA was rapid (\u003Ca id=\u0022xref-fig-3-7\u0022 class=\u0022xref-fig\u0022 href=\u0022#F3\u0022\u003EFig. 2\u003C\/a\u003E), and this may hinder the accurate estimation of k\u003Csub\u003Einact\u003C\/sub\u003E, especially at higher inhibitor concentrations. Thus, the static model proposed in the present study should be further validated and improved by focusing on other combinations of preincubation-dependent inhibitors and substrates.\u003C\/p\u003E\u003Cp id=\u0022p-63\u0022\u003EIn conclusion, the static model incorporating both inactivation and recovery kinetics of OATP1B1 activity has been proposed to predict OATP1B1-mediated DDI potential for preincubation-dependent inhibitors. This approach would be beneficial for the quantitative prediction of DDIs when compared with the current basic model approach and to avoid false-negative predictions of the DDIs. However, the limitation of this approach regarding the precise estimation of DDI potential should be considered, especially in potent preincubation-dependent inhibition cases.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv class=\u0022section ack\u0022 id=\u0022ack-1\u0022\u003E\u003Ch2 class=\u0022\u0022\u003EAcknowledgments\u003C\/h2\u003E\u003Cp id=\u0022p-80\u0022\u003EWe would like to thank Masahiro Satsukawa (Kaken Pharmaceutical Co., Ltd.) for valuable discussions. We would also like to thank Yoshiyuki Sakai for performing the uptake experiments.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv class=\u0022section notes\u0022 id=\u0022notes-1\u0022\u003E\u003Ch2 class=\u0022\u0022\u003EAuthorship Contributions\u003C\/h2\u003E\u003Cp id=\u0022p-81\u0022\u003E\u003Cem\u003EParticipated in research design:\u003C\/em\u003E Taguchi, Masuo, Futatsugi, Kato.\u003C\/p\u003E\u003Cp id=\u0022p-82\u0022\u003E\u003Cem\u003EConducted experiments:\u003C\/em\u003E Taguchi.\u003C\/p\u003E\u003Cp id=\u0022p-83\u0022\u003E\u003Cem\u003EPerformed data analysis:\u003C\/em\u003E Taguchi.\u003C\/p\u003E\u003Cp id=\u0022p-84\u0022\u003E\u003Cem\u003EWrote or contributed to the writing of the manuscript:\u003C\/em\u003E Taguchi, Masuo, Futatsugi, Kato.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv class=\u0022section fn-group\u0022 id=\u0022fn-group-1\u0022\u003E\u003Ch2\u003EFootnotes\u003C\/h2\u003E\u003Cul\u003E\u003Cul class=\u0022history-list\u0022\u003E\u003Cli xmlns:hwp=\u0022http:\/\/schema.highwire.org\/Journal\u0022 class=\u0022received\u0022 hwp:start=\u00222020-03-18\u0022\u003E\u003Cspan class=\u0022received-label\u0022\u003EReceived \u003C\/span\u003EMarch 18, 2020.\u003C\/li\u003E\u003Cli xmlns:hwp=\u0022http:\/\/schema.highwire.org\/Journal\u0022 class=\u0022accepted\u0022 hwp:start=\u00222020-06-23\u0022\u003E\u003Cspan class=\u0022accepted-label\u0022\u003EAccepted \u003C\/span\u003EJune 23, 2020.\u003C\/li\u003E\u003C\/ul\u003E\u003Cli class=\u0022fn-supported-by\u0022 id=\u0022fn-24\u0022\u003E\u003Cp id=\u0022p-77\u0022\u003EThis work was financed by Kaken Pharmaceutical Co., Ltd.\u003C\/p\u003E\u003C\/li\u003E\u003Cli class=\u0022fn-other\u0022 id=\u0022fn-25\u0022\u003E\u003Cp id=\u0022p-78\u0022\u003E\u003Ca href=\u0022https:\/\/doi.org\/10.1124\/dmd.120.000020\u0022\u003Ehttps:\/\/doi.org\/10.1124\/dmd.120.000020\u003C\/a\u003E.\u003C\/p\u003E\u003C\/li\u003E\u003Cli class=\u0022fn-supplementary-material\u0022 id=\u0022fn-26\u0022\u003E\u003Cp id=\u0022p-79\u0022\u003E\u003Ca class=\u0022rev-xref\u0022 href=\u0022#xref-fn-26-1\u0022\u003E\u21b5\u003C\/a\u003E\u003Cspan class=\u0022highwire-responsive-lazyload\u0022\u003E\u003Cimg src=\u0022data:image\/gif;base64,R0lGODlhAQABAIAAAAAAAP\/\/\/yH5BAEAAAAALAAAAAABAAEAAAIBRAA7\u0022 class=\u0022highwire-embed lazyload\u0022 alt=\u0022Embedded Image\u0022 data-src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/inline-graphic-2.gif\u0022\/\u003E\u003Cnoscript\u003E\u003Cimg class=\u0022highwire-embed\u0022 alt=\u0022Embedded Image\u0022 src=\u0022https:\/\/dmd.aspetjournals.org\/sites\/default\/files\/highwire\/dmd\/48\/9\/750\/embed\/inline-graphic-2.gif\u0022\/\u003E\u003C\/noscript\u003E\u003C\/span\u003EThis article has supplemental material available at \u003Ca href=\u0022http:\/\/dmd.aspetjournals.org\u0022\u003Edmd.aspetjournals.org\u003C\/a\u003E.\u003C\/p\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022section glossary\u0022 id=\u0022glossary-1\u0022\u003E\u003Ch2 class=\u0022\u0022\u003EAbbreviations\u003C\/h2\u003E\u003Cdl id=\u0022def-list-1\u0022\u003E\u003Cdt id=\u0022def-item-1\u0022\u003EAUC\u003Cspan class=\u0022def-item-dt-sep\u0022\u003E\u003C\/span\u003E\u003C\/dt\u003E\u003Cdd\u003Earea under the curve\u003Cspan class=\u0022def-item-dd-sep\u0022\u003E\u003C\/span\u003E\u003C\/dd\u003E\u003Cdt id=\u0022def-item-2\u0022\u003ECsA\u003Cspan class=\u0022def-item-dt-sep\u0022\u003E\u003C\/span\u003E\u003C\/dt\u003E\u003Cdd\u003Ecyclosporine A\u003Cspan class=\u0022def-item-dd-sep\u0022\u003E\u003C\/span\u003E\u003C\/dd\u003E\u003Cdt id=\u0022def-item-3\u0022\u003EDDI\u003Cspan class=\u0022def-item-dt-sep\u0022\u003E\u003C\/span\u003E\u003C\/dt\u003E\u003Cdd\u003Edrug-drug interaction\u003Cspan class=\u0022def-item-dd-sep\u0022\u003E\u003C\/span\u003E\u003C\/dd\u003E\u003Cdt id=\u0022def-item-4\u0022\u003EE\u003Csub\u003E2\u003C\/sub\u003EG\u003Cspan class=\u0022def-item-dt-sep\u0022\u003E\u003C\/span\u003E\u003C\/dt\u003E\u003Cdd\u003Eestradiol-17\u003Cem\u003E\u03b2\u003C\/em\u003E-glucuronide\u003Cspan class=\u0022def-item-dd-sep\u0022\u003E\u003C\/span\u003E\u003C\/dd\u003E\u003Cdt id=\u0022def-item-5\u0022\u003EE\u003Csub\u003E1\u003C\/sub\u003ES\u003Cspan class=\u0022def-item-dt-sep\u0022\u003E\u003C\/span\u003E\u003C\/dt\u003E\u003Cdd\u003Eestrone 3-sulfate\u003Cspan class=\u0022def-item-dd-sep\u0022\u003E\u003C\/span\u003E\u003C\/dd\u003E\u003Cdt id=\u0022def-item-6\u0022\u003Ef\u003Csub\u003Eu,p\u003C\/sub\u003E\u003Cspan class=\u0022def-item-dt-sep\u0022\u003E\u003C\/span\u003E\u003C\/dt\u003E\u003Cdd\u003Eunbound fraction in plasma\u003Cspan class=\u0022def-item-dd-sep\u0022\u003E\u003C\/span\u003E\u003C\/dd\u003E\u003Cdt id=\u0022def-item-7\u0022\u003EHCV\u003Cspan class=\u0022def-item-dt-sep\u0022\u003E\u003C\/span\u003E\u003C\/dt\u003E\u003Cdd\u003Ehepatitis C virus\u003Cspan class=\u0022def-item-dd-sep\u0022\u003E\u003C\/span\u003E\u003C\/dd\u003E\u003Cdt id=\u0022def-item-8\u0022\u003EHEK\u003Cspan class=\u0022def-item-dt-sep\u0022\u003E\u003C\/span\u003E\u003C\/dt\u003E\u003Cdd\u003Ehuman embryonic kidney\u003Cspan class=\u0022def-item-dd-sep\u0022\u003E\u003C\/span\u003E\u003C\/dd\u003E\u003Cdt id=\u0022def-item-9\u0022\u003EI\u003Csub\u003Eu,inlet,max\u003C\/sub\u003E\u003Cspan class=\u0022def-item-dt-sep\u0022\u003E\u003C\/span\u003E\u003C\/dt\u003E\u003Cdd\u003Emaximum unbound concentration of perpetrators in the inlet of the liver\u003Cspan class=\u0022def-item-dd-sep\u0022\u003E\u003C\/span\u003E\u003C\/dd\u003E\u003Cdt id=\u0022def-item-10\u0022\u003ENCE\u003Cspan class=\u0022def-item-dt-sep\u0022\u003E\u003C\/span\u003E\u003C\/dt\u003E\u003Cdd\u003Enew chemical entity\u003Cspan class=\u0022def-item-dd-sep\u0022\u003E\u003C\/span\u003E\u003C\/dd\u003E\u003Cdt id=\u0022def-item-11\u0022\u003EOATP\u003Cspan class=\u0022def-item-dt-sep\u0022\u003E\u003C\/span\u003E\u003C\/dt\u003E\u003Cdd\u003Eorganic anion transporting polypeptide\u003Cspan class=\u0022def-item-dd-sep\u0022\u003E\u003C\/span\u003E\u003C\/dd\u003E\u003Cdt id=\u0022def-item-12\u0022\u003ER value\u003Cspan class=\u0022def-item-dt-sep\u0022\u003E\u003C\/span\u003E\u003C\/dt\u003E\u003Cdd\u003Einhibition ratio\u003Cspan class=\u0022def-item-dd-sep\u0022\u003E\u003C\/span\u003E\u003C\/dd\u003E\u003Cdt id=\u0022def-item-13\u0022\u003ETKI\u003Cspan class=\u0022def-item-dt-sep\u0022\u003E\u003C\/span\u003E\u003C\/dt\u003E\u003Cdd\u003Etyrosine kinase inhibitor\u003C\/dd\u003E\u003C\/dl\u003E\u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003ECopyright \u00a9 2020 by The American Society for Pharmacology and Experimental Therapeutics\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section ref-list\u0022 id=\u0022ref-list-1\u0022\u003E\u003Ch2 class=\u0022\u0022\u003EReferences\u003C\/h2\u003E\u003Col class=\u0022cit-list ref-use-labels\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-1-2\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-1\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-48.9.750.1\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EBennouna\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EJ\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EDeslandres\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EM\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ESenellart\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EH\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003Ede Labareyre\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EC\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ERuiz-Soto\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ER\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EWixon\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EC\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EBotbyl\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EJ\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ESuttle\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EAB\u003C\/span\u003E\u003C\/span\u003E, and \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EDelord\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EJP\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E (\u003Cspan class=\u0022cit-pub-date\u0022\u003E2015\u003C\/span\u003E) \u003Cspan class=\u0022cit-article-title\u0022\u003EA phase I open-label study of the safety, tolerability, and pharmacokinetics of pazopanib in combination with irinotecan and cetuximab for relapsed or refractory metastatic colorectal cancer\u003C\/span\u003E. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EInvest New Drugs\u003C\/abbr\u003E \u003Cspan class=\u0022cit-vol\u0022\u003E33\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E138\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E147\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DInvest%2BNew%2BDrugs%26rft.volume%253D33%26rft.spage%253D138%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-2-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-2\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-48.9.750.2\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EDuan\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EP\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhao\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EP\u003C\/span\u003E\u003C\/span\u003E, and \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EL\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E (\u003Cspan class=\u0022cit-pub-date\u0022\u003E2017\u003C\/span\u003E) \u003Cspan class=\u0022cit-article-title\u0022\u003EPhysiologically based pharmacokinetic (PBPK) modeling of pitavastatin and atorvastatin to predict drug-drug interactions (DDIs)\u003C\/span\u003E. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EEur J Drug Metab Pharmacokinet\u003C\/abbr\u003E \u003Cspan class=\u0022cit-vol\u0022\u003E42\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E689\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E705\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DEur%2BJ%2BDrug%2BMetab%2BPharmacokinet%26rft.volume%253D42%26rft.spage%253D689%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-3-2\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-3\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-48.9.750.3\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EEley\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ET\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EHan\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EYH\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EHuang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ESP\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EHe\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EB\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ELi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EW\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EBedford\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EW\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EStonier\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EM\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EGardiner\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ED\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ESims\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EK\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ERodrigues\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EAD\u003C\/span\u003E\u003C\/span\u003E, \u003Cspan class=\u0022cit-etal\u0022\u003Eet al.\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E (\u003Cspan class=\u0022cit-pub-date\u0022\u003E2015\u003C\/span\u003E) \u003Cspan class=\u0022cit-article-title\u0022\u003EOrganic anion transporting polypeptide-mediated transport of, and inhibition by, asunaprevir, an inhibitor of hepatitis C virus NS3 protease\u003C\/span\u003E. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EClin Pharmacol Ther\u003C\/abbr\u003E \u003Cspan class=\u0022cit-vol\u0022\u003E97\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E159\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E166\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DClin%2BPharmacol%2BTher%26rft.volume%253D97%26rft.spage%253D159%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-4-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-4\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-48.9.750.4\u0022 data-doi=\u002210.1124\/dmd.108.026252\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EFahmi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EOA\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EHurst\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ES\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EPlowchalk\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ED\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ECook\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EJ\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EGuo\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EF\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EYoudim\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EK\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EDickins\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EM\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EPhipps\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EA\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EDarekar\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EA\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EHyland\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ER\u003C\/span\u003E\u003C\/span\u003E, \u003Cspan class=\u0022cit-etal\u0022\u003Eet al.\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E (\u003Cspan class=\u0022cit-pub-date\u0022\u003E2009\u003C\/span\u003E) \u003Cspan class=\u0022cit-article-title\u0022\u003EComparison of different algorithms for predicting clinical drug-drug interactions, based on the use of CYP3A4 in vitro data: predictions of compounds as precipitants of interaction\u003C\/span\u003E. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EDrug Metab Dispos\u003C\/abbr\u003E \u003Cspan class=\u0022cit-vol\u0022\u003E37\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E1658\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E1666\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DDrug%2BMetab%2BDispos%26rft_id%253Dinfo%253Adoi%252F10.1124%252Fdmd.108.026252%26rft_id%253Dinfo%253Apmid%252F19406954%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/ijlink\/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiZG1kIjtzOjU6InJlc2lkIjtzOjk6IjM3LzgvMTY1OCI7czo0OiJhdG9tIjtzOjE4OiIvZG1kLzQ4LzkvNzUwLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-ijlink\u0022\u003E\u003Cspan\u003E\u003Cspan class=\u0022cit-reflinks-abstract\u0022\u003EAbstract\u003C\/span\u003E\u003Cspan class=\u0022cit-sep cit-reflinks-variant-name-sep\u0022\u003E\/\u003C\/span\u003E\u003Cspan class=\u0022cit-reflinks-full-text\u0022\u003E\u003Cspan class=\u0022free-full-text\u0022\u003EFREE \u003C\/span\u003EFull Text\u003C\/span\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-5-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-5\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-48.9.750.5\u0022 data-doi=\u002210.1007\/s11095-013-1153-x\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EFujita\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EK\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ESugiura\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ET\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EOkumura\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EH\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EUmeda\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ES\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ENakamichi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EN\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EWatanabe\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ESuzuki\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EH\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ESunakawa\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EShimada\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EK\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EKawara\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EK\u003C\/span\u003E\u003C\/span\u003E, \u003Cspan class=\u0022cit-etal\u0022\u003Eet al.\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E (\u003Cspan class=\u0022cit-pub-date\u0022\u003E2014\u003C\/span\u003E) \u003Cspan class=\u0022cit-article-title\u0022\u003EDirect inhibition and down-regulation by uremic plasma components of hepatic uptake transporter for SN-38, an active metabolite of irinotecan, in humans\u003C\/span\u003E. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EPharm Res\u003C\/abbr\u003E \u003Cspan class=\u0022cit-vol\u0022\u003E31\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E204\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E215\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DPharm%2BRes%26rft.volume%253D31%26rft.spage%253D204%26rft_id%253Dinfo%253Adoi%252F10.1007%252Fs11095-013-1153-x%26rft_id%253Dinfo%253Apmid%252F23921491%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1007\/s11095-013-1153-x\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=23921491\u0026amp;link_type=MED\u0026amp;atom=%2Fdmd%2F48%2F9%2F750.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-6-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-6\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-48.9.750.6\u0022 data-doi=\u002210.1128\/AAC.02724-14\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EFurihata\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ET\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EMatsumoto\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ES\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EFu\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EZ\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ETsubota\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EA\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ESun\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EMatsumoto\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ES\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EKobayashi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EK\u003C\/span\u003E\u003C\/span\u003E, and \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EChiba\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EK\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E (\u003Cspan class=\u0022cit-pub-date\u0022\u003E2014\u003C\/span\u003E) \u003Cspan class=\u0022cit-article-title\u0022\u003EDifferent interaction profiles of direct-acting anti-hepatitis C virus agents with human organic anion transporting polypeptides\u003C\/span\u003E. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EAntimicrob Agents Chemother\u003C\/abbr\u003E \u003Cspan class=\u0022cit-vol\u0022\u003E58\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E4555\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E4564\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DAntimicrob%2BAgents%2BChemother%26rft_id%253Dinfo%253Adoi%252F10.1128%252FAAC.02724-14%26rft_id%253Dinfo%253Apmid%252F24867984%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/ijlink\/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiYWFjIjtzOjU6InJlc2lkIjtzOjk6IjU4LzgvNDU1NSI7czo0OiJhdG9tIjtzOjE4OiIvZG1kLzQ4LzkvNzUwLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-ijlink\u0022\u003E\u003Cspan\u003E\u003Cspan class=\u0022cit-reflinks-abstract\u0022\u003EAbstract\u003C\/span\u003E\u003Cspan class=\u0022cit-sep cit-reflinks-variant-name-sep\u0022\u003E\/\u003C\/span\u003E\u003Cspan class=\u0022cit-reflinks-full-text\u0022\u003E\u003Cspan class=\u0022free-full-text\u0022\u003EFREE \u003C\/span\u003EFull Text\u003C\/span\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-7-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-7\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-48.9.750.7\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EIto\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EK\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EIwatsubo\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ET\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EKanamitsu\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ES\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EUeda\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EK\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ESuzuki\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EH\u003C\/span\u003E\u003C\/span\u003E, and \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ESugiyama\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E (\u003Cspan class=\u0022cit-pub-date\u0022\u003E1998\u003C\/span\u003E) \u003Cspan class=\u0022cit-article-title\u0022\u003EPrediction of pharmacokinetic alterations caused by drug-drug interactions: metabolic interaction in the liver\u003C\/span\u003E. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EPharmacol Rev\u003C\/abbr\u003E \u003Cspan class=\u0022cit-vol\u0022\u003E50\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E387\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E412\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DPharmacological%2BReviews%26rft.stitle%253DPharmacol.%2BRev.%26rft.aulast%253DIto%26rft.auinit1%253DK.%26rft.volume%253D50%26rft.issue%253D3%26rft.spage%253D387%26rft.epage%253D412%26rft.atitle%253DPrediction%2Bof%2BPharmacokinetic%2BAlterations%2BCaused%2Bby%2BDrug-Drug%2BInteractions%253A%2BMetabolic%2BInteraction%2Bin%2Bthe%2BLiver%26rft_id%253Dinfo%253Apmid%252F9755288%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/ijlink\/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6ODoicGhhcm1yZXYiO3M6NToicmVzaWQiO3M6ODoiNTAvMy8zODciO3M6NDoiYXRvbSI7czoxODoiL2RtZC80OC85Lzc1MC5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-ijlink\u0022\u003E\u003Cspan\u003E\u003Cspan class=\u0022cit-reflinks-abstract\u0022\u003EAbstract\u003C\/span\u003E\u003Cspan class=\u0022cit-sep cit-reflinks-variant-name-sep\u0022\u003E\/\u003C\/span\u003E\u003Cspan class=\u0022cit-reflinks-full-text\u0022\u003E\u003Cspan class=\u0022free-full-text\u0022\u003EFREE \u003C\/span\u003EFull Text\u003C\/span\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-8-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-8\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-48.9.750.8\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EIwase\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EM\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EFujita\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EKI\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ENishimura\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ESeba\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EN\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EMasuo\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EIshida\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EH\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EKato\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY\u003C\/span\u003E\u003C\/span\u003E, and \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EKiuchi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E (\u003Cspan class=\u0022cit-pub-date\u0022\u003E2019\u003C\/span\u003E) \u003Cspan class=\u0022cit-article-title\u0022\u003EPazopanib interacts with irinotecan by inhibiting UGT1A1-mediated glucuronidation, but not OATP1B1-mediated hepatic uptake, of an active metabolite SN-38\u003C\/span\u003E. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003ECancer Chemother Pharmacol\u003C\/abbr\u003E \u003Cspan class=\u0022cit-vol\u0022\u003E83\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E993\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E998\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DCancer%2BChemother%2BPharmacol%26rft.volume%253D83%26rft.spage%253D993%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-9-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-9\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-48.9.750.9\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EIzumi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ES\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ENozaki\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EKusuhara\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EH\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EHotta\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EK\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EMochizuki\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ET\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EKomori\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ET\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EMaeda\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EK\u003C\/span\u003E\u003C\/span\u003E, and \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ESugiyama\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E (\u003Cspan class=\u0022cit-pub-date\u0022\u003E2018\u003C\/span\u003E) \u003Cspan class=\u0022cit-article-title\u0022\u003ERelative activity factor (RAF)-based scaling of uptake clearance mediated by organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 in human hepatocytes\u003C\/span\u003E. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EMol Pharm\u003C\/abbr\u003E \u003Cspan class=\u0022cit-vol\u0022\u003E15\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E2277\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E2288\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DMol%2BPharm%26rft.volume%253D15%26rft.spage%253D2277%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-10-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-10\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-48.9.750.10\u0022 data-doi=\u002210.1124\/dmd.114.059105\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EIzumi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ES\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ENozaki\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EMaeda\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EK\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EKomori\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ET\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ETakenaka\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EO\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EKusuhara\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EH\u003C\/span\u003E\u003C\/span\u003E, and \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ESugiyama\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E (\u003Cspan class=\u0022cit-pub-date\u0022\u003E2015\u003C\/span\u003E) \u003Cspan class=\u0022cit-article-title\u0022\u003EInvestigation of the impact of substrate selection on in vitro organic anion transporting polypeptide 1B1 inhibition profiles for the prediction of drug-drug interactions\u003C\/span\u003E. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EDrug Metab Dispos\u003C\/abbr\u003E \u003Cspan class=\u0022cit-vol\u0022\u003E43\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E235\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E247\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DDrug%2BMetab%2BDispos%26rft_id%253Dinfo%253Adoi%252F10.1124%252Fdmd.114.059105%26rft_id%253Dinfo%253Apmid%252F25414411%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/ijlink\/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiZG1kIjtzOjU6InJlc2lkIjtzOjg6IjQzLzIvMjM1IjtzOjQ6ImF0b20iO3M6MTg6Ii9kbWQvNDgvOS83NTAuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-ijlink\u0022\u003E\u003Cspan\u003E\u003Cspan class=\u0022cit-reflinks-abstract\u0022\u003EAbstract\u003C\/span\u003E\u003Cspan class=\u0022cit-sep cit-reflinks-variant-name-sep\u0022\u003E\/\u003C\/span\u003E\u003Cspan class=\u0022cit-reflinks-full-text\u0022\u003E\u003Cspan class=\u0022free-full-text\u0022\u003EFREE \u003C\/span\u003EFull Text\u003C\/span\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-11-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-11\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-48.9.750.11\u0022 data-doi=\u002210.1111\/j.1476-5381.2009.00430.x\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EKalliokoski\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EA\u003C\/span\u003E\u003C\/span\u003E and \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ENiemi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EM\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E (\u003Cspan class=\u0022cit-pub-date\u0022\u003E2009\u003C\/span\u003E) \u003Cspan class=\u0022cit-article-title\u0022\u003EImpact of OATP transporters on pharmacokinetics\u003C\/span\u003E. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EBr J Pharmacol\u003C\/abbr\u003E \u003Cspan class=\u0022cit-vol\u0022\u003E158\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E693\u003C\/span\u003E\u2013\u003Cspan 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class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EKunze\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EA\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EHuwyler\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EJ\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ECamenisch\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EG\u003C\/span\u003E\u003C\/span\u003E, and \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EPoller\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EB\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E (\u003Cspan class=\u0022cit-pub-date\u0022\u003E2014\u003C\/span\u003E) \u003Cspan class=\u0022cit-article-title\u0022\u003EPrediction of organic anion-transporting polypeptide 1B1- and 1B3-mediated hepatic uptake of statins based on transporter protein expression and activity data\u003C\/span\u003E. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EDrug Metab Dispos\u003C\/abbr\u003E \u003Cspan class=\u0022cit-vol\u0022\u003E42\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E1514\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E1521\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca 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class=\u0022cit-reflinks-abstract\u0022\u003EAbstract\u003C\/span\u003E\u003Cspan class=\u0022cit-sep cit-reflinks-variant-name-sep\u0022\u003E\/\u003C\/span\u003E\u003Cspan class=\u0022cit-reflinks-full-text\u0022\u003E\u003Cspan class=\u0022free-full-text\u0022\u003EFREE \u003C\/span\u003EFull Text\u003C\/span\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-13-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-13\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-48.9.750.13\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EMaeda\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EK\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E (\u003Cspan class=\u0022cit-pub-date\u0022\u003E2015\u003C\/span\u003E) \u003Cspan class=\u0022cit-article-title\u0022\u003EOrganic anion transporting polypeptide (OATP)1B1 and OATP1B3 as important regulators of the pharmacokinetics of substrate drugs\u003C\/span\u003E. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EBiol Pharm Bull\u003C\/abbr\u003E \u003Cspan class=\u0022cit-vol\u0022\u003E38\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E155\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E168\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DBiol%2BPharm%2BBull%26rft.volume%253D38%26rft.spage%253D155%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-14-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-14\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-48.9.750.14\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EMayhew\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EBS\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EJones\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EDR\u003C\/span\u003E\u003C\/span\u003E, and \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EHall\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ESD\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E (\u003Cspan class=\u0022cit-pub-date\u0022\u003E2000\u003C\/span\u003E) \u003Cspan class=\u0022cit-article-title\u0022\u003EAn in vitro model for predicting in vivo inhibition of cytochrome P450 3A4 by metabolic intermediate complex formation\u003C\/span\u003E. 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href=\u0022{openurl}?query=rft.jtitle%253DDrug%2BMetabolism%2Band%2BDisposition%26rft.stitle%253DDrug%2BMetab.%2BDispos.%26rft.aulast%253DMayhew%26rft.auinit1%253DB.%2BS.%26rft.volume%253D28%26rft.issue%253D9%26rft.spage%253D1031%26rft.epage%253D1037%26rft.atitle%253DAn%2BIn%2BVitro%2BModel%2Bfor%2BPredicting%2BIn%2BVivo%2BInhibition%2Bof%2BCytochrome%2BP450%2B3A4%2Bby%2BMetabolic%2BIntermediate%2BComplex%2BFormation%26rft_id%253Dinfo%253Apmid%252F10950845%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca 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text\u0022 id=\u0022ref-15\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-48.9.750.15\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EPahwa\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ES\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EAlam\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EK\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ECrowe\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EA\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EFarasyn\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ET\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ENeuhoff\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ES\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EHatley\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EO\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EDing\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EK\u003C\/span\u003E\u003C\/span\u003E, and \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EYue\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EW\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E (\u003Cspan class=\u0022cit-pub-date\u0022\u003E2017\u003C\/span\u003E) \u003Cspan class=\u0022cit-article-title\u0022\u003EPretreatment with rifampicin and tyrosine kinase inhibitor dasatinib potentiates the inhibitory effects toward OATP1B1- and OATP1B3-mediated transport\u003C\/span\u003E. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EJ Pharm Sci\u003C\/abbr\u003E \u003Cspan class=\u0022cit-vol\u0022\u003E106\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E2123\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E2135\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DJ%2BPharm%2BSci%26rft.volume%253D106%26rft.spage%253D2123%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-16-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-16\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-48.9.750.16\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EShitara\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY\u003C\/span\u003E\u003C\/span\u003E and \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ESugiyama\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E (\u003Cspan class=\u0022cit-pub-date\u0022\u003E2017\u003C\/span\u003E) \u003Cspan class=\u0022cit-article-title\u0022\u003EPreincubation-dependent and long-lasting inhibition of organic anion transporting polypeptide (OATP) and its impact on drug-drug interactions\u003C\/span\u003E. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EPharmacol Ther\u003C\/abbr\u003E \u003Cspan class=\u0022cit-vol\u0022\u003E177\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E67\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E80\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DPharmacol%2BTher%26rft.volume%253D177%26rft.spage%253D67%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-17-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-17\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-48.9.750.17\u0022 data-doi=\u002210.1002\/jps.23477\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EShitara\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ETakeuchi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EK\u003C\/span\u003E\u003C\/span\u003E, and \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EHorie\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ET\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E (\u003Cspan class=\u0022cit-pub-date\u0022\u003E2013\u003C\/span\u003E) \u003Cspan class=\u0022cit-article-title\u0022\u003ELong-lasting inhibitory effects of saquinavir and ritonavir on OATP1B1-mediated uptake\u003C\/span\u003E. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EJ Pharm Sci\u003C\/abbr\u003E \u003Cspan class=\u0022cit-vol\u0022\u003E102\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E3427\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E3435\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DJ%2BPharm%2BSci%26rft.volume%253D102%26rft.spage%253D3427%26rft_id%253Dinfo%253Adoi%252F10.1002%252Fjps.23477%26rft_id%253Dinfo%253Apmid%252F23440887%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1002\/jps.23477\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=23440887\u0026amp;link_type=MED\u0026amp;atom=%2Fdmd%2F48%2F9%2F750.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-18-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-18\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-48.9.750.18\u0022 data-doi=\u002210.2133\/dmpk.DMPK-11-RG-096\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EShitara\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ETakeuchi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EK\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ENagamatsu\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EWada\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ES\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ESugiyama\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY\u003C\/span\u003E\u003C\/span\u003E, and \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EHorie\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ET\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E (\u003Cspan class=\u0022cit-pub-date\u0022\u003E2012\u003C\/span\u003E) \u003Cspan class=\u0022cit-article-title\u0022\u003ELong-lasting inhibitory effects of cyclosporin A, but not tacrolimus, on OATP1B1- and OATP1B3-mediated uptake\u003C\/span\u003E. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EDrug Metab Pharmacokinet\u003C\/abbr\u003E \u003Cspan class=\u0022cit-vol\u0022\u003E27\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E368\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E378\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DDrug%2BMetab%2BPharmacokinet%26rft.volume%253D27%26rft.spage%253D368%26rft_id%253Dinfo%253Adoi%252F10.2133%252Fdmpk.DMPK-11-RG-096%26rft_id%253Dinfo%253Apmid%252F22240838%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.2133\/dmpk.DMPK-11-RG-096\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=22240838\u0026amp;link_type=MED\u0026amp;atom=%2Fdmd%2F48%2F9%2F750.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-19-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-19\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-48.9.750.19\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ESprowl\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EJA\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EOng\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ESS\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EGibson\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EAA\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EHu\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ES\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EDu\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EG\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ELin\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EW\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ELi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EL\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EBharill\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ES\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ENess\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ERA\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EStecula\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EA\u003C\/span\u003E\u003C\/span\u003E, \u003Cspan class=\u0022cit-etal\u0022\u003Eet al.\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E (\u003Cspan class=\u0022cit-pub-date\u0022\u003E2016\u003C\/span\u003E) \u003Cspan class=\u0022cit-article-title\u0022\u003EA phosphotyrosine switch regulates organic cation transporters\u003C\/span\u003E. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003ENat Commun\u003C\/abbr\u003E \u003Cspan class=\u0022cit-vol\u0022\u003E7\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E10880\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DNat%2BCommun%26rft.volume%253D7%26rft.spage%253D10880%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-20-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-20\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-48.9.750.20\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ETaguchi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ET\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EMasuo\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EKogi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ET\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ENakamichi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EN\u003C\/span\u003E\u003C\/span\u003E, and \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EKato\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E (\u003Cspan class=\u0022cit-pub-date\u0022\u003E2016\u003C\/span\u003E) \u003Cspan class=\u0022cit-article-title\u0022\u003ECharacterization of Long-Lasting Oatp Inhibition by Typical Inhibitor Cyclosporine A and In Vitro-In Vivo Discrepancy in Its Drug Interaction Potential in Rats\u003C\/span\u003E. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EJ Pharm Sci\u003C\/abbr\u003E \u003Cspan class=\u0022cit-vol\u0022\u003E105\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E2231\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E2239\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DJ%2BPharm%2BSci%26rft.volume%253D105%26rft.spage%253D2231%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-21-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-21\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-48.9.750.21\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ETaguchi\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ET\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EMasuo\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ESakai\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY\u003C\/span\u003E\u003C\/span\u003E, and \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EKato\u003C\/span\u003E 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href=\u0022{openurl}?query=rft.jtitle%253DDrug%2BMetab%2BPharmacokinet%26rft.volume%253D34%26rft.spage%253D372%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-22-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-22\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-48.9.750.22\u0022 data-doi=\u002210.1002\/jcph.723\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EVaidyanathan\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EJ\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EYoshida\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EK\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EArya\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EV\u003C\/span\u003E\u003C\/span\u003E, and \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EZhang\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EL\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E (\u003Cspan class=\u0022cit-pub-date\u0022\u003E2016\u003C\/span\u003E) \u003Cspan class=\u0022cit-article-title\u0022\u003EComparing various in vitro prediction criteria to assess the potential of a new molecular entity to inhibit organic anion transporting polypeptide 1B1\u003C\/span\u003E. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EJ Clin Pharmacol\u003C\/abbr\u003E \u003Cspan class=\u0022cit-vol\u0022\u003E56\u003C\/span\u003E (\u003Cspan class=\u0022cit-supplement\u0022\u003ESuppl 7\u003C\/span\u003E):\u003Cspan class=\u0022cit-fpage\u0022\u003ES59\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003ES72\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DJ%2BClin%2BPharmacol%26rft.volume%253D56%26rft.spage%253DS59%26rft_id%253Dinfo%253Adoi%252F10.1002%252Fjcph.723%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1002\/jcph.723\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-23-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-23\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-48.9.750.23\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EYamaoka\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EK\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ETanigawara\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ENakagawa\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ET\u003C\/span\u003E\u003C\/span\u003E, and \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EUno\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003ET\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E (\u003Cspan class=\u0022cit-pub-date\u0022\u003E1981\u003C\/span\u003E) \u003Cspan class=\u0022cit-article-title\u0022\u003EA pharmacokinetic analysis program (multi) for microcomputer\u003C\/span\u003E. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EJ Pharmacobiodyn Actions\u003C\/abbr\u003E \u003Cspan class=\u0022cit-vol\u0022\u003E4\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E879\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E885\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DJ%2BPharmacobiodyn%2BActions%26rft.volume%253D4%26rft.spage%253D879%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-24-1\u0022 title=\u0022View reference in text\u0022 id=\u0022ref-24\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-48.9.750.24\u0022 data-doi=\u002210.1038\/clpt.2011.351\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EYoshida\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EK\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EMaeda\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EK\u003C\/span\u003E\u003C\/span\u003E, and \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003ESugiyama\u003C\/span\u003E \u003Cspan class=\u0022cit-name-given-names\u0022\u003EY\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E (\u003Cspan class=\u0022cit-pub-date\u0022\u003E2012\u003C\/span\u003E) \u003Cspan class=\u0022cit-article-title\u0022\u003ETransporter-mediated drug--drug interactions involving OATP substrates: predictions based on in vitro inhibition studies\u003C\/span\u003E. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EClin Pharmacol Ther\u003C\/abbr\u003E \u003Cspan class=\u0022cit-vol\u0022\u003E91\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E1053\u003C\/span\u003E\u2013\u003Cspan class=\u0022cit-lpage\u0022\u003E1064\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DClinical%2Bpharmacology%2Band%2Btherapeutics%26rft.stitle%253DClin%2BPharmacol%2BTher%26rft.aulast%253DYoshida%26rft.auinit1%253DK.%26rft.volume%253D91%26rft.issue%253D6%26rft.spage%253D1053%26rft.epage%253D1064%26rft.atitle%253DTransporter-mediated%2Bdrug--drug%2Binteractions%2Binvolving%2BOATP%2Bsubstrates%253A%2Bpredictions%2Bbased%2Bon%2Bin%2Bvitro%2Binhibition%2Bstudies.%26rft_id%253Dinfo%253Adoi%252F10.1038%252Fclpt.2011.351%26rft_id%253Dinfo%253Apmid%252F22534868%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1038\/clpt.2011.351\u0026amp;link_type=DOI\u0022 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Every person suffers from acid reflux at some point of time in their lives. However, how long this will last is something that everyone wonders. The longer it lasts, the more difficult it will be to cope with the symptoms like heartburn, sore throat, hoarseness in voice and swallowing problems. Sometimes, it can even lead to breathing troubles.
How Long Does Acid Reflux Last?
How Long Does Acid Reflux Last?
To answer this question simply, it needs to be stated that there is no particular time that can be pre-determined as to how long acid reflux problems will last. While elaborating this, it can be said that as soon as the acidity reduces or the stomach acids stop irritating the esophagus, larynx and pharynx, the problem will subside.
Since the mechanism of acid reflux is the irritation of throat and esophagus tissue due to the acidic nature of the stomach juices, consuming antacids can work fast in reducing, as well as treating the condition. The antacids reduce the pH value of these stomach acids that move up towards the esophagus and throat in case of acid reflux or gastro-esophageal reflux disease (GERD). Thus, it loses its acidity and become neutralized.
Hence, it can be said that as soon as you feel that you have got an acid reflux and you take an antacid, your problem will gradually subside. However, on an average, the condition lasts for about 2 hours in most cases. It can last for a longer period if spicy foods, fatty foods, carbonated drinks, alcohol and citrus foods and drinks are consumed during an acid reflux. Even going to bed or staying in a lying position before or within 2 to 3 hours of eating or without treating the condition will contribute in lasting the condition longer.
What are the Effects of Acid Reflux?
Many people consider acid reflux to be a very light problem that will subside on its own. However, it is "not OKAY" to have acid reflux or GERD frequently. Frequent, Acid Refluxes only indicate that there are other complications that are going on in the inside of your body. On the other hand, leaving GERD untreated or to be treated on its own will have their long-lasting and more complicated effects. These include –
• Esophageal Ulcers: One of the effects of acid reflux is esophageal ulcer. If acid reflux or GERD is frequent and long lasting, it can lead to esophageal ulcers. In fact, the most common cause of esophageal ulcers is GERD or Acid Reflux. As the stomach acids will continuously irritate the tissue of the esophagus, it may sore the area and sometimes, the sores become ulcers.
• Esophagitis or Painful Swallowing: As the acids from the stomach continuously irritate the esophagus, it inflames the esophagus. Hence, swallowing becomes a problem. This esophageal inflammation is called esophagitis.
• Acid Reflux Leading to Esophageal Stricture: The lining of the esophagus can be scarred due to the continuous damage caused by the stomach acids. As the scar tissue builds up in the esophagus, it narrows down the space of the esophagus. These narrowed down spots are called strictures and when strictures occur in the oesophagus, it makes it difficult to swallow the food and drinks. Dehydration and weight loss come as a consequence of the esophageal stricture.
• Barrett's Esophagus as an Effect of Acid Reflux: This is quite a serious effect of untreated or chronic acid reflux. Amongst all the GERD or acid reflux sufferers, about 5 to 10% people are found to encounter a pre-cancerous cell change due to the stomach acid exposure. If not treated on time, this can lead to esophageal cancer. However, the doctor can remove the abnormal cells quite in advance; preventing them from leading to cancer and only about 1% people with Barrett's esophagus get esophageal cancer. To prevent, early diagnosis of the condition is a must. Since there are no obvious signs and symptoms that indicate Barrett's esophagus or differentiate the condition from other acid reflux symptoms, if you have frequent GERD, seeing a doctor without delay is a wise decision.
• Esophageal Cancer: As already stated, with chronic GERD and Barrett's esophagus, the chances of getting esophageal cancer become high. The problem with this condition is that symptoms of esophageal cancer such as chest pain and swallowing troubles will occur only at the later stage of the disease. At that stage, it becomes quite difficult to treat the condition. Hence, seeing a doctor and undergoing endoscopy regularly, in case you have chronic GERD and Barrett's oesophagus is a good idea.
• Dysphagia: Since the esophagus gets narrowed down due to the stricture, one will feel that something is stuck at the back of the throat. This symptom is called dysphagia. It is a very uncomfortable effect of acid reflux that disturbs the regular diet.
• Weight Loss as an Effect of Acid Reflux: As the esophageal stricture narrows down the esophagus and disturbs the diet, proper eating habits are disrupted. Consequently, one loses weight. However, this is not the case for everyone. It is a condition that mostly affects those, who have frequent GERD leading to esophagitis and esophageal stricture.
• Sore Throat and Hoarseness: One of the most common and significant effects of acid reflux are hoarseness in throat or sore throat. The stomach acids that come up to the larynx, irritates the throat tissues and hoarseness and sore throat are obvious consequences.
• Acid Reflux Causing Heartburn: As the stomach acids move up to the esophagus, there is a burning sensation felt in your chest. However, there is a tricky factor associated with GERD and heartburn and that is, with esophageal strictures, the heartburn may decrease. This is because the narrowing of esophagus prevents the stomach acids from moving up. However the decrease in heartburn should not be mistaken as the GERD being treated. In fact, with ignorance this can lead to other difficulties.
• Tooth Decay: Many acid reflux or GERD sufferers are found to have tooth decay. The reason behind this can be the stomach acids that move upwards and reach the mouth. As the teeth enamel is exposed to these stomach acids, they undergo decay. This can lead to bad breath and even the saliva production of the mouth is often increased.
• Esophageal Spasms: Often mistaken to be heart attacks, esophageal spasms can be encountered by many. It is associated with chest pain and is quite unpleasant effect of acid reflux.
• Breathing Problems: Research studies have proven that GERD has a strong association with breathing problems or asthma. About 30 to 80% asthma patients are found to be suffering from GERD. Though the exact cause of this is not clear, it is widely believed that the stomach acids get into the airways and causes the breathing problems. Though these are the serious effects of Acid Reflux, there are other common effects such as bloating, nausea and hiccups that should not be ignored. If any of these symptoms are felt, treatment without a delay is a must, so that the critical complications can be avoided.
Also Read:
Written, Edited or Reviewed By:
, MD, FFARCSI
Last Modified On: June 6, 2017
Pain Assist Inc.
Pramod Kerkar
Note: Information provided is not a substitute for physician, hospital or any form of medical care. Examination and Investigation is necessary for correct diagnosis.
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wikiHow to Increase Amniotic Fluid
Three Methods:Increasing Amniotic Fluid with MedicineIncreasing Amniotic Fluid with Home ManagementUnderstanding OligohydramniosCommunity Q&A
When you become pregnant, your uterus will form an amniotic sac that will produce amniotic fluid. This fluid acts as protection for your baby while he or she is in your uterus. Oligohydramnios is a condition that can develop where your amniotic fluid levels decrease. This can cause problems for your pregnancy, so it is very important that you bring your fluid levels back up through both medical and at-home intervention.
1
Increasing Amniotic Fluid with Medicine
1. 1
Understand that treatment is based on how far along you are in your pregnancy. The recommendations your doctor will have for treatment will be based on how far along in your pregnancy you are. Generally, your doctor will recommend one of the treatments listed in this section, as well as rehydration at home, which is outlined in the second section of this article.[1]
• If you are not yet in full term, your doctor will monitor you and your levels very closely. Tests such as non-stress and contraction stress tests may be done to monitor your baby’s activity. Your doctor may also suggest one of the following medical treatments listed in this method.
• If you are close to full term, your doctor may recommend that you deliver your baby via cesarean section as low amniotic fluid levels right before pregnancy can be dangerous for both you and your baby.
2. 2
Get an injection of amniotic fluid. In this process, your doctor will inject the leaking amniotic fluids back into the amniotic sac with a needle. This will help your condition because it will increase the amount of amniotic fluid in your uterus. This procedure is a lot like amniocentesis (a way to check your amniotic fluid levels), except that instead of withdrawing the amniotic fluid, the doctor injects the leaking amniotic fluids back into the amniotic sac with a needle. [2]
• This procedure is often used as a short term fix because amniotic fluid levels tend to drop again after a couple of weeks. However, doctors choose to use this method because it helps them to find the problem that is causing your amniotic fluid levels to be low.
3. 3
Get fluid intravenously. Some pregnant women are admitted to the hospital for additional intravenous fluid therapy if natural means of rehydration (like drinking lots of water) are not able to increase the amount of amniotic fluid. If you have tried rehydrating at home with no changes in amniotic fluid levels, you will most likely have to get an IV to stay hydrated.[3]
• Once your amniotic fluid levels are back to normal, you will most likely be discharged.
• Keep in mind that sometimes IV therapy will continue until you are ready to give birth if you are having troubles staying hydrated.
4. 4
Use a catheter to increase fluid levels. Amnioinfusion is when Lactated Ringer’s Solution or a regular saline solution is infused into the amniotic fluid sac by a catheter. Doing this increases the amniotic fluid levels around your baby and provides extra padding for your baby and the umbilical cord.[4]
• The amount of saline injected will depend on how low your amniotic fluid levels are.
5. 5
Talk to your doctor about having a shunt placed in your body. Shunts are used to move body fluid from one place in your body to another. In this case, a shunt diverts fetal urine into your amniotic fluid cavity if the reason you have low amniotic fluid levels is because of fetal obstructive uropathy (kidney problems that decrease amniotic fluid).[5]
2
Increasing Amniotic Fluid with Home Management
1. 1
Drink at least 8 to 10 glasses of water each day. One of the simplest ways to increase your amniotic fluid is to make sure that you are always hydrated. When you increase the amount of water you have in your body, your amniotic fluid levels will also rise.[6]
• Drink water throughout the day and try to drink at least 8 to 10 glasses at a minimum.
2. 2
Eat fruits that have water contents. A great way to stay hydrated while also getting good nutrients is to eat fruits and vegetables that have high water concentrations. As stated above, when you increase the amount of hydration your body gets, you will also increase the amount of amniotic fluid you have. Good fruits and vegetables to eat when needing hydration include[7]:
• Vegetables like: Cucumber (96.7% water), iceberg lettuce (95.6%), celery (95.4%), radishes (95.3%), green peppers (93.9%), cauliflower (92.1%), spinach (91.4%), broccoli (90.7%), and baby carrots (90.4%).
• Fruits like: Watermelon (91.5%), tomatoes (94.5%), star fruit (91.4%), strawberries (91.0%), grapefruit (90.5%), and cantaloupe (90.2%).
3. 3
Avoid herbal supplements that can dehydrate you. Some herbal supplements can act as diuretics that make you have to urinate more. The more you go to the bathroom, the likelier you are to become dehydrated. It is very important that you stay hydrated when you are concerned about your levels of amniotic fluid. Herbal supplements to stay away from include:
• Dandelion extract, celery seed, watercress, and parsley.[8]
4. 4
Stay away from alcohol. If you are pregnant, you should not drink alcohol at all because it is not good for your baby’s health. Alcohol can also dehydrate you and cause your amniotic fluid levels to shrink.
5. 5
Do light exercise regularly if your doctor has not asked you to get bed rest. You should try to get at least 30 to 45 minutes of non-weight bearing exercise every day. Exercises promote an increased blood flow to the different areas in your body. If there is an increased blood circulating in the uterus and placenta, there is also an increase in the amniotic fluid index and fetal urine production rate (the amount your baby urinates). As your baby passes more urine in the amniotic sac, the volume of the amniotic fluid increases. Exercises you should consider doing include:
• Swimming or water aerobics. These are the best exercises to do when you are pregnant because it takes all the weight of your baby off of you.
• Walking and light hiking.
6. 6
Lie on your left side when you relax. If your doctor has asked you to stay in bed (what is referred to as complete bed rest) you should lay on your left side when you can. When you lie on your left side, your blood flows more smoothly through the uterine blood vessels and allows your baby’s blood flow to also move at a regular rate. This may cause the amniotic fluid index to rise.
7. 7
Talk to your doctor about changing your prescription if you are taking Angiotensin Converting Enzyme Inhibitors (ACE). ACE inhibitors are medications that help to lower your high blood pressure by stopping your body’s conversion of Angiotensin I to Angiotensin II. While it is normally good to take these medications, you should not take them while you are pregnant because they can lower the amount of amniotic fluid that your body creates.[9]
3
Understanding Oligohydramnios
1. 1
Understand what amniotic fluid’s purpose is. The most important thing that amniotic fluid does is keep your baby safe while he or she is in the womb. It does this by cushioning your baby. It also has other functions, which include:
• Keeping the baby warm.
• Acting as a lubricant. Sometimes, some babies are born with webbed fingers and toes due to insufficient amount of amniotic fluid.
• Promoting proper lung and kidney development.
• Helping the baby move freely, which in turn lets him/her exercise the limbs and become strong.
2. 2
Be aware of the symptoms of oligohydramnios. Oligohydramnios is the condition that occurs when your amniotic fluid gets very low (specifically below 300 ml). If you are concerned that you might have developed this condition, you should always talk to your doctor. If you are concerned you might develop the condition in the future, it is helpful to know what to look for. Symptoms include:
• Leakage of amniotic fluid.
• Your abdomen is smaller than you think it should be given your gestational period (how long you have been pregnant).
• Feeling like your baby is moving around less.
• Smaller than expected urine amounts when you go to the bathroom.
• Visible lack of amniotic fluid when you get an ultrasound.
3. 3
Be aware of the risk factors that could lead you to having low amounts of amniotic fluid. There are some conditions or factors that can predispose you to having troubles with your amniotic fluid amounts. Some of the more common reasons include:
• If your baby is small for his or her gestational age.
• If you have high blood pressure while you are pregnant (a condition called pre-eclampsia).
• If your placenta partially or completely peels away from your uterine wall even before the onset of delivery. This condition is known as abruptio placenta.
• If you are having identical twins. If identical twins share a placenta, sometimes their amniotic fluid levels become out of balance. This happens when one twin gets more blood via the placenta than the other.
• If you have certain medical conditions like lupus.
• If you are in post-term pregnancy. If your pregnancy has gone over 42 weeks, you have a higher risk of low levels of amniotic fluid due to declining placental function – amniotic fluid starts to decrease by the 38th week of pregnancy.
4. 4
Understand that low levels of amniotic fluid can generally only be diagnosed by ultrasound. The actual volume of amniotic fluid cannot be safely measured directly so the condition is diagnosed by using ultrasounds that check the amniotic fluid index (AFI).[10]
• A normal AFI range is between 5 and 25 cm.
Community Q&A
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Add New Question
• How can I increase the liquid level in 38 weeks of pregnancy for normal delivery?
wikiHow Contributor
Drink 2 liters of water per day and consume plenty of fruits to stay hydrated.
• My amniotic fluid is 7 cm, is this normal or not?
wikiHow Contributor
It depends on the number of weeks you are pregnant. If you are close to your delivery, your water levels should be at least 10 cm or more, but this is nothing to worry about. Drink 1.5-2 liters of water daily, eat fruits such as watermelon, pears, apples, and strawberries, Drink at least a glass or two of milk per day and a glass of juice or coconut water per day. The main idea is to keep yourself hydrated as much as possible. Sleeping on your left side also helps to increase your water levels.
• I'm 34 weeks pregnant and my fluid level is 8. Is that okay?
wikiHow Contributor
It is likely not sufficient. Drink plenty of water, eat fruits that have a high water content and consult your doctor.
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Tips
• Make drinking water more enjoyable by adding splashes of fruit juice to it to give it some flavor.
Warnings
• If you are at all concerned that you may have low levels of amniotic fluid, talk to your doctor right away.
Sources and Citations
1. Outline in obstetrics. A textbook and reviewer for nurses and midwives by Maria Loreto J. Evangelista – Sia. 2008 Edition
2. William’s Obstetrics Twenty-Second Ed. Cunningham, F. Gary, et al, Ch. 21.
3. Copel, J., D’Alton, M., et al (n.d.). Obstetric Imaging 1st Edition.
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Categories: Pregnancy
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Español: aumentar el líquido amniótico, Português: Aumentar Seu Líquido Amniótico, Deutsch: Die Fruchtwassermenge erhöhen, Italiano: Aumentare il Liquido Amniotico, Русский: увеличить амниотическую жидкость, Français: augmenter la quantité de liquide amniotique, Bahasa Indonesia: Meningkatkan Volume Cairan Ketuban, Nederlands: Meer vruchtwater aanmaken, 中文: 增加羊水, Čeština: Jak zvýšit množství plodové vody, العربية: الزيادة من السائل الأمينوسي
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Fatty Liver and Dementia
Fatty Liver and Dementia
Fatty Liver and Dementia
Introduction
Fatty Liver can be caused by alcohol use, but it can also happen in people who don’t drink or use very little alcohol.
Called “NAFLD” (Non-Alcoholic Fatty Liver Disease”), it affects 25 to 30 percent of people in the US and Europe.
Recent studies link NAFLD with cognitive impairment and dementia. This can occur even with no other symptoms.
You may or may not develop symptoms from NAFLD. The most common symptoms are feeling tired or discomfort or pain in the upper right side of your abdomen.
However, your only symptom may be a loss of short-term memory and slowed-down thinking. Studies are showing that NAFLD may also cause Alzheimer’s Disease.
If you’re wondering what has happened to your previously sharp mind, this is a possible answer.
NAFLD should not be ignored in any case, as it can lead to cirrhosis, a severe and potentially fatal disease.
Fatty Liver Chart
What Causes Fatty Liver?
Eating sugar, refined carbs (bread, cakes, rice, pasta, potatoes), and bad fats (fried foods, chips) creates a risk for Fatty Liver.
• The same process that causes Type II diabetes also can cause Fatty Liver Disease. If you’re “Pre-diabetes” or a diabetic, you’re at risk.
• High levels of fat (especially triglycerides) in your blood.
• Overweight
What to do about Fatty Liver Disease
As with most chronic illnesses, NAFLD has different causes in each person. If you want to get the problem handled, you’ll need to be tested to determine the exact problem causing your body stress and preventing it from healing. Go HERE to get started on this process.
DIY NAFLD Improvement:
(See article below for more information):
1: Lose excess weight–losing between 7 and 10 percent of body weight can improve other symptoms of NAFLD, such as inflammation, fibrosis, and scarring
2: Research from 2017 suggests that the Mediterranean diet may help to reduce liver fat, even without weight loss.
3: Exercise: It’s important to stay active when you have NAFLD. A good goal to shoot for is at least 150 minutes of moderate-intensity exercise per week.
4: Avoid foods with added sugars-Dietary sugars such as fructose and sucrose have been linked to NAFLD development.
5: Take an omega-3 supplement–A peer review study suggests that taking an omega-3 supplement may reduce liver fat.
6: Avoid known liver irritants–Certain substances can put excess stress on your liver. They include alcohol and certain over-the-counter medications.
7: Consider taking vitamin E--Vitamin E is one antioxidant that may reduce inflammation caused by NAFLD. Must take all components of vitamin E. This would include Mixed Tocopherols and Tocotrienols
8: Consider Herbs--A 2018 paper identified certain herbs, supplements, and spices that have been used as alternative treatments for NAFLD. Compounds that have positive effects on liver health include turmeric, milk thistle, resveratrol, and green tea.
I hope this helps!
Dr. Melodie Billiot
How to avoid toxic fats that cause Fatty Liver
READ: Have Toxic Seed Oils Torched Your Body?
NAFLD and Dementia
Ronald Grisanti D.C., D.A.B.C.O., DACBN, MS, CFMP
A study from the journal Neurology revealed that nonalcoholic fatty liver disease (NAFLD) is independently associated with cognitive impairment.
Nonalcoholic fatty liver disease (NAFLD) is an umbrella term for various liver conditions affecting people who drink little to no alcohol. As the name implies, the main characteristic of NAFLD is too much fat stored in liver cells.
Dementia and NAFLD are two frequent conditions that share underlying risk factors mainly in the realm of metabolic disease.
The study from the journal, Neurology included 4,472 adults aged 20–59 years.
The participants underwent assessment of liver enzyme activity and hepatic steatosis by ultrasound. They underwent cognitive evaluation using the following computer-administered tests: the Simple Reaction Time Test (SRTT), the Symbol-Digit Substitution Test (SDST), and the Serial Digit Learning Test (SDLT).
Increased activity of the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) correlated with lower performance on the SDLT, while increased alanine aminotransferase was also correlated with lower performance in the SDST.
The current studies suggest that NAFLD patients incur cognitive dysfunction.
Although if left untreated, NAFLD can lead to much more serious conditions, including cirrhosis and liver failure. The good news is that fatty liver disease can be reversed—and even cured.
8 Steps to Effectively Treat Fatty Liver Disease
1: Lose excess weight–losing between 7 and 10 percent of body weight can improve other symptoms of NAFLD, such as inflammation, fibrosis, and scarring
2: Research from 2017 suggests that the Mediterranean diet may help to reduce liver fat, even without weight loss.
3: Exercise: It’s important to stay active when you have NAFLD. A good goal to shoot for is at least 150 minutes of moderate-intensity exercise per week.
4: Avoid foods with added sugars-Dietary sugars such as fructose and sucrose have been linked to NAFLD development.
5: Take an omega-3 supplement–A peer review study suggests that taking an omega-3 supplement may reduce liver fat.
6: Avoid known liver irritants–Certain substances can put excess stress on your liver. They include alcohol and certain over-the-counter medications.
7: Consider taking vitamin E--Vitamin E is one antioxidant that may reduce inflammation caused by NAFLD. Must take all components of vitamin E. This would include Mixed Tocopherols and Tocotrienols
8: Consider Herbs--A 2018 paper identified certain herbs, supplements, and spices that have been used as alternative treatments for NAFLD. Compounds shown to have positive effects on liver health include turmeric, milk thistle, resveratrol, and green tea.
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PHP Begriffserklärung und Definition
PHPDie Skriptsprache PHP (Hypertext Preprocessor) zeichnet sich durch eine an C angelehnte einfache Syntax, eine gute Datenbankanbindung und umfangreiche Funktionsbibliotheken aus. PHP ist durch den zahlreichen Einsatz bei dynamischen Webseiten und Webanwendungen weit verbreitet und beliebt.
Geschichte von PHP
PHP wurde 1995 veröffentlicht und hat insbesondere seit PHP 3 eine rasante Entwicklung erfahren. Mit PHP 4 waren Klassen nutzbar und mit PHP 5 wurde der Fokus noch mehr auf die objektorientierte Programmierung gerichtet. Mit Version 4 wurde auch die Sicherheit und das Sessionmanagement verbessert. PHP hatte inzwischen auch seinen Vorgänger Perl abgelöst, da PHP als einfacher für den Webbereich zu erlernen galt.
2004 wurde PHP 5 veröffentlicht. Objektorientierte Programmierung wurde effizienter, Überladungen wurden möglich, ebenso wie Reflections und Exceptions. Ab Version 5.3 kamen Namespaces, Traits, Generatoren, Late Static Bindings und eine bessere Speicheranforderung dazu.
Durch Datenkapselung, Exceptions, Konstruktoren und Destruktoren näherte Sich PHP immer mehr anderen Programmiersprachen an. So wurde z.B. nur noch auf Objekte referenziert, anstatt sie direkt zu nutzen wie in PHP 4.
PHP 6 war ursprünglich als nächste Version geplant. Man entschied sich jedoch die Versionen von 5.3 weiter zu entwickeln und Version 6 zurück zu stellen.
Verbreitung
PHP ist die am häufigsten verwendete Programmiersprache zum Erstellen von Webseiten und Webanwendungen. Die stetig wachsende Popularität liegt in den zahlreich genutzten PHP-Applikationen begründet. Dazu gehören u.a. phpBB (Foren- Software), MediaWiki (wird von Wikipedia verwendet), osCommerce (E-Commerce Software) und easyImage (Bildergalerie).
Durch die stetig steigenden Anforderungen des Internets und dessen Benutzer, sind Webseiten keine kleinen Projekte mehr. Um der Menge an Daten und Quellcode gewachsen zu sein, ist die Verwendung von Datenbanken wie MySQL und der Einsatz von Frameworks wie Zend Framework in der heutigen Webentwicklung praktisch ein Muss.
Funktionsweise
PHP ist eine serverseitige Skriptsprache. Das bedeutet, dass eine Anfrage vom Client (Webbrowser) an den Server geschickt wird, der Dateien mit der Endung .PHP an einen Interpreter weiterleitet und das Ergebnis, meistens in einem HTML Dokument eingebettet, zurück an den Browser schickt. Das HTML Dokument bleibt dabei unverändert.
Wie in HTML gibt einen Anfangs- und Endtag, die den Anfang und das Ende eines Befehls kennzeichnen. Alles zwischen wird von einem Interpreter Zeile für Zeile geparst. So ist es möglich innerhalb eines HTML Dokuments an unterschiedlichen Stellen PHP Code einzubetten. Aufgrund immer umfangreicher werdender Webseiten führt dies jedoch zu einem unübersichtlichen Quellcode. Um dem entgegen zu wirken, trennt man HTML von PHP Code. Dabei helfen inzwischen zu diesem Zweck weit verbreitete CMS (Content Management Systeme) wie Typo3 und Joomla. Der Einsatz von CMS ist inzwischen ebenfalls wie PHP bei den meisten Webhostern möglich.
Die PHP GTK Erweiterung bietet die Möglichkeit PHP Anwendungen mit einer grafischen Oberfläche zu versehen, ohne dass ein Webserver oder Browser verwendet werden muss. Dennoch wird PHP überwiegend auf Webservern genutzt.
Nachteile
Neben den Vorteilen wie eine einfache Syntax, der weiteren Annäherung an andere Sprachen mit objektorientierter Programmierung, gute Datenbankanbindung und steter Weiterentwicklung dank immer populärer werdenden Webanwendungen gibt es auch viele Kritiken. Dazu gehören vor allem die vielen Funktionen die in den Standardbibliotheken noch imperativ vorhanden sind. Ebenso Funktionen die das Gleiche bewirken, aber unterschiedlich benannt sind. Im Gegensatz zu Sprachen wie Java ist in PHP Threading nicht möglich und gilt in einigen Modulen auch als zu unsicher dafür. Da PHP wie Ruby, Python oder Perl eine Skriptsprache und keine Compilersprache ist, wird derselbe Quellcode bei jedem Aufruf immer wieder übersetzt und ausgeführt, anstatt den übersetzten Code immer wieder zu verwenden. Der größte Nachteil an PHP ist demnach die mangelhafte Performance. In einigen Projekten ist man bemüht PHP Bytecode Caches zu entwickeln, mit denen man bei eigener Installation eine bessere Performance erzielen kann. Ein weiterer Nachteil ist die schwache Typisierung, die zwar zum Konzept gehört, aber eine häufige Fehlerquelle insbesondere bei Vergleichen bietet. Die fehlende Variablendeklaration ist ebenfalls eine bekannte Fehlerquelle, zusammen mit der Tatsache, dass Variablennamen case sensitive sind. Unterscheiden sich zwei Variablen namentlich durch den ersten Buchstaben in der Klein und Großschreibung, kann das im Laufe des Skripts zu Fehlern führen. Zumindest diese Namensproblematik kann beim Einhalten der bekannten Konventionen eingeschränkt werden. Denn bleibt das Problem bestehen, dass eine Variable registriert wird, sobald sie das erste Mal zur Anwendung kommt.
Sicherheit
Mit einer falschen Webserver Konfiguration können im Zusammenhang mit globalen Variablen Sicherheitslücken entstehen. Eine sichere Methode ist die generelle Initialisierung einer Variable vor dem Gebrauch. Gefahren drohen jedoch nicht nur von falschen Server Konfigurationen und PHP Sicherheitslücken, sondern auch durch schlechte Programmierung. PHP bietet Funktionen, die es ermöglichen Daten zu überprüfen und zu filtern. Diese sollten in jedem Fall genutzt werden, um unerwünschten Code durch Cross-Site-Scripting und Injections zu verhindern.
Lizenz
PHP wurde anfangs unter der GNU General Public License (GPL) ausgegeben.
Seit PHP 4 wird es unter der PHP License vertrieben. Diese Lizenz erlaubt es Quelltexte frei zu verwenden und zu verändern. PHP kann weiterhin kostenlos von der Webseite heruntergeladen werden.
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You even have a little more courage than my brother.Lin Haoming didn t know about Pang Zheng s background before, but he didn Fastest Weight Loss Pill does chilli help you lose weight t expect Jia Kai to tell him directly.
Lin Zhen also felt the same way. In the past, she thought that even if Qiniang was beautiful, she was not inferior, but this moment of youthful beauty was something she couldn t compare to.If Fairy really rejects me, then we are not the only ones who will be divided Gan Yan threatened without concealment.
This kind of does chilli help you lose weight person is capable. If he can t be Boost Metabolism Pills how to slim down in 3 days used by me, does chilli help you lose weight why not let him deal with us Zhang Qifeng said without the slightest emotion.I know you only want revenge, but you also need to choose the best way to take revenge, and you also need to think about your own keto burn pills and organic apple cider vinegar future after revenge.
Lin Haoming ordered. Yes, I also have the same plan.
But now, it has become does chilli help you lose weight Dietary Supplements For Weight Loss a situation where there is me in you and you in me.A new type of tank for the Eighth Route Army Fukada Shaozuo asked suspiciously Is this what the Eighth Route Army wants to hide Then Sagara Zhenying added another order Inform the Tiger Type of the situation and let them prepare to best pill to lose weight meet them.
They even passed on false military orders to create the illusion that Mine Koga is still in Tokyo to stabilize the United Fleet Who knows The Eighth Route Army is becoming more and more unpredictable President Takachan said.Wang Xuexin s purpose of attacking Xinjing is secondly to divide the internal forces of Xinjing, and his main purpose is to force the devils to do it.
The aviation team had to be dispatched As soon as the air team was dispatched, it broke away from the cover of the air defense system and fought with the Devil Air Force in the airspace outside the city.Only the platoon leader is equipped, and a company only has two or three.
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One of the shortcomings was raised by Xu Huandong. After Xu Huandong reported the general process and results of does chilli help you lose weight Dietary Supplements For Weight Loss this battle, he added a sentence Commander, I think our army s torpedo planes are seriously insufficient, and this may cause problems in a formal battle with the enemy.The refraction of light by the glass on the gas mask is not easy to grasp, and it can even be said to be impossible to grasp, because every time you lie down or turn your head, the angle of the glass facing the envision medical weight loss light is different, which is a random value.
If the speed is not enough, they will almost only be passively beaten.My quick way of how to slim down in 3 days Whats Taint drawing this picture has inadvertently made a contribution What Gu Hefeng didn t know was that his actions doronjo.xsrv.jp does chilli help you lose weight startled the Eighth Route Army, including the aircraft carrier captain Yu Ping.
As the saying goes, Feng fat burner results Shui turns in turns, but Guo Wenyong did not expect this tactic to be learned today.This is how he reported Comrade Zong Gu, this is simply amazing It uses a smoothbore gun Just think, how much money this can save us Even other tanks do not need to be produced, we use T34 is likely to win this battle After sending the telegram, the General Counsel couldn t help but walked anxiously in front of the radio station, and then added a sentence to Lemon Lokoff Report at any time The transaction is Best Weight Loss Pills 2023 does chilli help you lose weight progressing The general counsel did not think that Lemon Lokoff was exaggerating, he knew very well what it meant if a gun could penetrate a 250mm steel plate at a distance of one kilometer and still have accuracy.
The flight time of the Feiyan fighter is more than twice that of the La 5.Later, the eagle sauce bombed it. Due to the height of the Best Weight Loss Pills 2023 does chilli help you lose weight bomber, does chilli help you lose weight we can only install 75MM anti tank guns on fighter jets to try to make up for the lack of height with range, and even if we do this, there is only one chance to attack the fighter jets go up at full speed and use the inertia to reach the highest point to hit the eagle.
So Okabe Naozaburo understood that the missile technology of the imperial army was not up to standard.Therefore, Wang Xuexin thinks that he should be content.
After changing T44, it becomes T54, which is our 59.This point. It is hard to imagine that the Eighth Route Army can even defeat BF109 with it I know Wang Xuexin replied with a smile I believe this time, the Supreme Deputy Commander will still be unhappy So, I hope our relationship can i still eat carbs and lose weight can ease some Of course, part of the reason for this is that the quality of the smoothbore guns at that time was not that good and its lifespan was only more than 100 rounds.
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The soldiers had good reasons What if the devils make small moves That s a gas bomb, just ignite a grenade and it s over We are here to ensure the safety of the gas bomb Only death The devils are the safest. The second layer of information blockade is stronger.Then someone even proposed a plan to increase the speed if the weight is reduced without changing the engine thrust and aerodynamic layout, the speed will naturally increase.
In addition, More importantly Note Each 25 ton inland gunboat can carry 20 fully armed soldiers.Because Wang Xuexin understands one thing the speed of anti ship missiles is only more than does chilli help you lose weight 300 kilometers, and it is easy for Devil fighters to intercept them.
The reason why Siping was chosen is mainly because after the Eighth Route Army and the stubborn army entered the Northeast in history, hundreds of thousands of troops were invested in Siping, a little known place, to fight repeatedly, and four major battles were fought successively.The problem was that no suitable materials could be found does chilli help you lose weight for making filaments, so the lifespan was short and the cost was high.
However Wang Xuexin replied Sun Erwei, you just bought a few anti ship missiles from us.Their quality is definitely not comparable to that of the tank soldiers of the Eighth Route Army.
It only takes about one minute from entering the range of your anti aircraft missiles to reaching the target You can make all reactions within one minute and will It shot down After approaching the target, it suddenly climbed to a certain height, and then dived towards the target.What Lemon Lokoff didn t know was that Wang Xuexin s request for T34 was actually out of ulterior motives Wang Xuexin s choice of T44 is not wrong, because he chose T44, in addition to confronting the Devil s Tiger Style , he also planned to develop it into 59, and he also planned to develop it into 59 first.
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What. But Wang Xuexin s expression is completely different in the eyes of Chen does chilli help you lose weight Songyong and others They are people who have experienced hunger, and at that time, a large number of people starved to death outside the base of the Eighth Route Army.This made Shinichi Takagi, who was in the city hall, feel unprecedented pressure.
Wouldn t the Boost Metabolism Pills how to slim down in 3 days best way to destroy the enemy be to lay defenses along the coast Doolittle shook his head It s just hearsay, General, but I weight loss surgery supplements nz think it s very credible This is not what the admiral wants to see, because it will cause heavy casualties to the Yingjiang soldiers.The time is wrong Toshihei Inoguchi replied, I thought the Eighth Route Army would wait until dawn before can i lose weight by running a mile a day leaving the port, but they actually left the port after it was dark Now, they know our location, but we don t know theirs.
However, there are wooden beams inside the brick structure that can block part of the force, so many devils were actually injured by smashing and then went through a long and long time inside.Without knowledge of naval warfare, is there still a shortage of staff officers with knowledge of naval warfare on warships What s more, does an aircraft carrier need a naval battle It is almost impossible to have a ship to ship situation I can t swim, and when I need to swim in the sea, the aircraft carrier will be bombed and sunk Now being reminded by Wang Xuexin like this, Xu Huandong felt enlightened Xu Huandong immediately understood Yes, regiment commander I have no objection and obey the command At this time, Yu Ping ran up to Wang Xuexin and reported to Wang Xuexin.
In the previous battles, especially the battle against Jinzhou, Fengtian does chilli help you lose weight s troops have already been consumed.But we can t blame them. This is a ship to ship battle.
Not to mention the turmoil happening one after another among the people, the puppet army is also constantly losing, and the intelligence of the puppet army are hydroxycut diet pills safe defecting and rebelling is one after another.cover. Although these shells were not very accurate when fired from the bumpy car, the devils had no fortifications or cover.
Because they all know that the Eighth Route Army has a piece of equipment that can destroy warships from a long distance, and the result of the HLD battle not long ago has already shocked the entire military circle.Isn t it from these three directions to reduce costs Either use cheaper materials, or reduce the process, or reduce the volume, that is, reduce the use of raw materials.
Let Halsey come back immediately The admiral ordered At least one fleet must be brought back Yes Doolittle hurriedly took the admiral s order to contact does chilli help you lose weight Halsey.Don t launch it, all radar soldiers are on high alert, especially the air defense system must be kept running for a long time.
Therefore, the camera imported from Yingjiang can be installed directly without modification, but an antenna needs to be added for wireless data transmission.The Musashi was originally Koga Mineichi s flagship.
But these things are trivial matters for CNC machine tools.The half track car is the boss, does chilli help you lose weight and it becomes the target of the devil does chilli help you lose weight s infantry artillery and grenades on the ground.
Then Chen Songyong pointed to the map and added The devil also specially chose terrain defenses that are easy to release poisonous gas, such as curved canyons, and for example It is a forest full of trees, and there are low windless areas Once poisonous gas bombs hit these places, the poisonous gas will stay in it for a long time and it is difficult to dissipate, which will does chilli help you lose weight bring great obstacles to our army s offensive Before the words finished, the researchers were does chilli help you lose weight Dietary Supplements For Weight Loss already cursing It s too hateful, the devil is simply insane Is there no one to care about the flagrant violation of the Geneva Conventions We should publicize this matter internationally, so that people all over the world know the devil s despicable deeds Most of the researchers are intellectuals, and many of them have been abroad, so they still have illusions about the so called international influence.
In addition, Wang Xuexin randomly selected a few platoon leaders with experience in infantry command and several soldiers from the guard company.It is said that half an hour is not bad, but other times Su Liguo would go in for several hours, and he would not come out to take a breath until his body couldn t take it anymore.
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14 December 2019
5 Components of Fitness at a Glance
We all know how important regular exercise is for our bodies. But did you know that there is more to fitness than just how much cardio and resistance training you can do? There are, in fact, five components of fitness that together form total physical fitness.
It is common to gauge fitness levels by how far we can run or how heavy we can lift, but in order to achieve true fitness, all five of these pillars need to be upheld.
What are the Five Components of Physical Fitness?
1. Cardiovascular endurance
2. Muscular strength
3. Muscular endurance
4. Flexibility
5. Body composition
Let's look at each of these five components of fitness in more detail.
Cardiovascular endurance refers to the ability of the heart and lungs to sustain the body during cardiovascular exercise. If your cardiovascular endurance is good, you will have the stamina needed to perform cardio exercise for prolonged periods of time. The Cooper 12-minute Run Test is a popular method of evaluation for cardiovascular endurance.
Muscular strength signifies the amount of force the muscles can produce in resistance exercises. As your muscular strength increases, you will be able to lift heavier weights, and bodyweight exercises such as pull-ups and press-ups will become easier. Press-ups are a common exercise used to test muscular strength.
Muscular endurance indicates the amount of time the muscles can work without becoming tired. If you have good muscular endurance, you will be able to workout for longer intervals. Sit-ups are often used to test muscular endurance levels.
Flexibility is about the ability of the muscle fibers to allow the joints their full range of motion. As your flexibility increases, you will be able to perform exercises and everyday tasks with greater comfort and ease. Your posture will improve, too. The sit-and-reach test is a great way to test flexibility as it requires the entire back of the body to stretch.
Body composition refers to the body's fat mass compared to muscle, organ, and bone mass. As you become fitter, your fat mass will decrease, and your lean muscle mass will increase. Standard tests for body composition include skinfold readings and bioelectrical impedance testing using a machine.
How Can the Five Components of Fitness Benefit Me?
Testing yourself on all of these five components of fitness gives you a genuine picture of your physical fitness. Having this information also gives you a baseline from which to work. Then, you can work on each of these areas and test yourself regularly to track your progress. Testing every month is ideal. You can also enlist the help of a friend or personal trainer to help you perform the tests and record the results.
It feels great to know that you are developing your total fitness, as opposed to being unbalanced in just one or two areas. Improving your total fitness will benefit your health, bring ease into your everyday activities, and help to prevent injury.
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Easy and several logistic regression data out-of products affecting bed quality
Easy and several logistic regression data out-of products affecting bed quality
However, age, sex, and you may staff member period weren’t discovered to be tall regarding several logistic regression investigation (Desk 4)
Good sleep quality was reported by 1152 (78.3%) participants, while 319 (21.7%) reported poor sleep quality. Poor sleep quality was experienced by 19.8% of participants with adequate serum vitamin D levels and by 26.2% of participants with serum vitamin D deficiency (P = .007). Poor sleep quality was more common in those younger than 30 years of age (26.3%) than in those 30 years of age or older (18.0%) (P < .001). Poor sleep quality was significantly more common (P = .006) in females (27.6%) than in males (20.2%). Unmarried participants were more likely to have poor sleep quality (26.2%) than married participants (17.6%) (P < .001). Participants with a high school education or less reported poor sleep quality more frequently (27.2%) than those with a bachelor's degree or higher (19.0%) (P < .001). Those who had worked for 5–9 years had the highest prevalence of poor sleep quality (24.5%), while those with a work tenure of 10 years or more had the lowest prevalence of poor sleep quality (18.5%) (P = .037). Those who reported high levels of occupational stress exhibited poor sleep quality more frequently (29.3%) than those with low levels of occupational stress (19.5%) (P < .001). Regular exercise, smoking habits, alcohol consumption habits, body mass index, and testing season were not associated with significant differences in sleep quality (Table 3).
Logistic regression analysis was used to identify variables with a effect on sleep quality. Simple logistic regression analysis showed an odds ratio (OR) of 1.43 (95% CI, 1.10–1.87) for having poor sleep quality in those with serum vitamin D deficiency. High risks of poor sleep quality were also found in other groups: those younger than 30 years of age (OR = 1.63; 95% CI, 1.27–2.09), females (OR = 1.50; 95% CI, 1.12–2.01), unmarried subjects (OR = 1.67; 95% CI, 1.30–2.14), those with a high school education or less (OR = 1.59; 95% CI, 1.23–2.06), and those with high occupational stress (OR = 1.55; 95% CI, 1.15–2.09). Employee tenure of 10 or more years was associated with a lower risk of poor sleep quality (OR = 0.74; 95% CI, 0.55–0.99) than those with <5 years of tenure. Variables in the simple logistic regression analysis were adjusted for in the multiple logistic regression analysis. The resulting OR was 1.36 (95% CI, 1.01–1.82) for poor sleep quality in the serum vitamin D deficiency group. Statistical significance was also found for being unmarried (OR = 1.47; 95% CI, 1.04–2.08), having a high school education or less (OR = 1.32; 95% CI, 1.03–1.77), and high occupational stress (OR = 1.85; 95% CI, 1.38–2.47).
Variations in the general PSQI score plus in for every items of the newest men seeking women sites review PSQI based on solution supplement D membership
The mean total PSQI score of all participants was 3.97 ± 2.26. Subjects in the serum vitamin D deficiency group showed a mean PSQI score of 4.25 ± 2.37, while those with serum vitamin D levels ?10 ng/mL averaged 3.85 ± 2.15 (P = .002). The mean scores for each PSQI component were as follows: subjective sleep quality was poorer in those with vitamin D deficiency (1.05 ± 0.63, vs. 0.96 ± 0.61 in the non-deficient group) (P = .020), sleep latency was poorer in those with vitamin D deficiency (0.84 ± 0.85, vs. 0.64 ± 0.75 in the non-deficient group) (P < .001), and the sleep duration score was poorer in those with vitamin D deficiency (1.10 ± 0.65, vs. 1.03 ± 0.62 in the non-deficient group) (P = .041). Significant differences in the mean score were not found for the remaining categories of habitual sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction (Table 5).
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91feeds is a news site. https://www.91feeds.com/group_yoga/ Yoga Fri, 22 Jan 2021 21:38:45 +0800 en-US daily 1 https://www.91feeds.com/ Benefits Of Yoga - Five Great Things Yoga Can Do For You https://www.91feeds.com/articles_zjdtea.html https://www.91feeds.com/articles_zjdtea.html#respond Mon, 27 May 2019 08:53:00 +0800 Below you'll find five great benefits of attending yoga classes.
Give it a go and see what yoga can do for you: 1.
Easy does it.
Yoga practice can help you achieve and then maintain a supple body, capable of easy, effortless movement.
If everyday physical tasks and movements feel easier then this in turn will make you feel more energetic.
2.
Gently does it! Many yoga styles use an extremely gentle approach, allowing participants to gain all the benefits of exercise without the risk of strain or injury.
Poses used in yoga can be easily adapted to an individual's specific needs.
They are also practiced with relaxed knees and elbows, reducing the risk of damage to these joints.
3.
Be prepared.
As well as being a great form of exercise in itself, yoga can also be used as part of a warm-up (or cool down) routine for other forms of exercise or sport.
Improved focus and raised energy levels can improve athletic performance.
Many top athletes use yoga in their training regimes.
4.
Deal with it.
Yoga practice can help you to cope better with life's stresses and strains.
Everybody functions better and deals with life more effectively if they feel relaxed and focused rather than stressed out and anxious.
Whether it's an important meeting at work, a job interview, family problems, financial problems or any other of the frequently stressful situations we can find ourselves in, they are easier to deal with and resolve if we can feel calmer and relaxed in ourselves.
The situation we're confronted with is the same but our ability to deal with it improves.
5.
Take it with you.
Yoga is adaptable and portable Yoga can be practiced anywhere - not just in yoga classes.
You don't need any special equipment with you apart from a mat.
Visiting friends for the weekend or in a hotel room anywhere in the world - yoga goes with you! So what are you waiting for? Check out the yoga classes in your area to find one that's right for you and start reaping the benefits of this fantastic universal exercise.
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Yoga and Children https://www.91feeds.com/articles_x7dwca.html https://www.91feeds.com/articles_x7dwca.html#respond Mon, 27 May 2019 08:50:00 +0800 Helping their bodies build muscle and retain flexibility as they grow can give them better health going into adulthood.
Yoga can also benefit a growing child's brain by allowing them to learn to control their stress and emotions.
Yoga and children is a great avenue for any child that needs help in any of these areas.
If you are planning to become a certified yoga instructor, consider getting your yoga for kids certification.
Working with yoga and children will give you the satisfaction of knowing you are impacting a child in a real way.
Teaching yoga to kids will be fun and interesting, and you will find it very rewarding.
Health and fitness is very important for children.
Many kids today are showing signs of health problems due to a lack of exercise.
A yoga and children program can combat and prevent these problems.
Yoga is a fun activity, making it a great choice for children who are not much into exercise.
The low impact nature of yoga gives kids the chance to get physical fitness in their routine without causing them any injury.
Children with disabilities will find yoga to be a fun and exciting activity.
And the parents can take comfort in the fact that they are helping their differently challenged child improve their motor skills and overall health.
Parents and children can both benefit from a class that allows kids and their parents to learn yoga together.
A yoga and children program is a great choice for your child.
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Yogic Insights - Making Time to Give Thanks https://www.91feeds.com/articles_61fpda.html https://www.91feeds.com/articles_61fpda.html#respond Mon, 27 May 2019 08:44:00 +0800 "? We have all heard plenty of creative excuses to avoid Yoga practice, meditation, and taking care of one's health.
Maybe you wish there was a way to get through to people who never seem to run out of excuses.
Unless someone wants to take care of him or herself, it does not matter what we do or say.
We can talk until we run out of air, and it will have no effect on the person who refuses to take action toward good health.
Yet, there is one matter for every Yoga teacher and practitioner to be thankful for.
Each of us should be thankful that we have received the "God given" intelligence to recognize that we have the power within to make changes for the best.
Through Yoga practice, we can see the value in giving thanks every day of our lives.
Many people claim to be so busy that they have no time for thanks, manners, or courtesy.
Some of us save it all up for the holidays.
What are holidays for? To some people, holidays were made to make up for an unthankful lifestyle.
When we study Karma Yoga, we must realize that thanks giving is part of daily life.
Why avoid giving thanks to God and your loved ones until the holidays? To take this a bit further: Why avoid courtesy to those we meet 364 days a year? Granted, charities realize that many people give monetary donations only once per year, so they gear themselves to go after the holiday donations.
With all this being said, some of us reserve kindness to avoid appearing weak.
It is a sad state of affairs, when one cannot thank another for an act of courtesy.
Yet, it must be asked: "What is the source of our lack of time to give thanks?" Are we really that busy? Yes, we are busy, but so were past generations, who worked physically at their jobs all year long.
The difference is making the time for daily tradition and rituals.
Each morning and evening, we should give thanks to those around us.
We should also give daily thanks to our creator for our chance to make a difference in this life.
After all, life is a gift and we should be extremely thankful for it.
© Copyright 2009 - Paul Jerard / Aura Publications ]]>
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Yoga Pose For Back Pain https://www.91feeds.com/articles_kyucba.html https://www.91feeds.com/articles_kyucba.html#respond Mon, 27 May 2019 08:43:00 +0800
Beginning with a pose called Salamba Sarvangasana, a supported shoulder stand in which the body rests on its shoulders with the legs extended straight above your head, exhale and begin to bend your body from the hip joints. Now slowly lower you legs above and behind your head until your toes touch the floor. When practicing this yoga pose for back pain be sure to keep your torso perpendicular to the floor and your legs fully straight and extended.
With your toes still touching the floor, lift your things and tailbone up towards the ceiling and pull your inner groins into the pelvis. Your hands can either be placed on the back of your torso for added support or allowed to stretch out flat behind you. Hold this yoga pose for back pain anywhere from one to five minutes.
When you are ready to exit the Halasana pose bring your hands back onto your torso, if they arent already there, and slowly lift your legs above your head into the previous Salamba Sarvangasana position. Remember to exhale slowly while lifting your legs. From here, you will end this yoga pose for back pain by rolling onto your back.
Since most beginners wont be able to comfortably practice this yoga pose for back pain, they can try a modified version of the Halasana by using a prop. Take a folding metal chair and place the back of it against a wall. Next take a supporting blanket and lay it down approximately a foot in front of the edge of the chairs seat. Now lie down on the support blanket with your head resting on the floor between the blanket and the chair.
From here simply roll up, exhaling as you go, and rest your feet on the seat of the chair. When youre ready, lift your legs into the Salamba Sarvangasana position and then move on to the Halasana yoga pose for back pain. Exit this pose by reversing it, remembering to exhale when raising the legs.
While this pose is not recommended for those with neck injury or pregnant women who have not previously practiced yoga, the Halasana is suitable for expectant mothers who are regular practitioners of yoga. If back pain is getting the better of you try finding relief with the Halasana yoga pose for back pain.]]>
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Guidelines For Effective Chakra Meditation https://www.91feeds.com/articles_wsieca.html https://www.91feeds.com/articles_wsieca.html#respond Mon, 27 May 2019 08:15:00 +0800
A regular 60 minute meditation session makes you positive and relaxes you and maybe even transforms your mind and soul. If you enjoy that, how about going a step forward and concentrating on your "chakras" and even balancing them? How do you think your health is positive? How do you think your mind is alert? How do you think mediation helps in sending positive signals to the brains? Well, this is all because of the Chakras in your body. Think of these Chakras as the life circles or the life centers. Each Chakra has a different purpose in the body (albeit invisible and not really touchable!). These are energy centers and have a definite reason to be there. Your body has overall 7 Chakras and each has tones of energy in it. It totally depends on us how we capitalize on this energy, how we make sure that it stays positive and full of life. It is easy to toxicate our energy and this will directly affect our health and maybe even emotional well being. That is the reason why Chakras need to be cleansed often and balanced out properly. Chakra Meditation does that!
• The first and most important step is to familiarize and know all the Chakras. How will you balance them out and make sure they are all cleansed if you do not know which all are the chakras, their significance and their location in the body!!
• Another important thing about this meditation is that things do not happen overnight and thus perseverance and patience are the key factors. Be at it for at least some time and only then will you be able to do it
• Make sure you learn it from an authentic source and a master! Do not rely on phony classes and people who think they can teach you to meditate overnight! Get a master or a great Guru for yourself
• Once you have learned it, make sure you practice it regularly. If you are doing Chakra meditation, the chances are that you are doing it to be more positive and to balance out the chakras. Chakras do not get balanced in one session and even if they do, they may get unbalanced in a few days. Thus, practicing it every few days or weeks is a great idea
• Meditation is an art - learn it and savor it - It will always add positivity back in your life!
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Yoga Exercises Are Very Beneficial For Good Health https://www.91feeds.com/articles_utg8ca.html https://www.91feeds.com/articles_utg8ca.html#respond Mon, 27 May 2019 08:13:00 +0800 It basically combines several different breathing exercises with meditation.
Yoga has been practiced for more than 5000 years.
What is unique about these yoga exercises is that they can be practiced by anyone, regardless of caste, creed, age, color or religion.
Yoga Exercises Act as an Alternative Medicine Yoga exercises are beneficial for calming and relaxing the nervous system as well as for balancing the mind, spirit and body.
It is believed that the constant and regimented practice of yoga can be an immense help in treating or curbing many medical ailments.
It is observed by medical practitioners all over the world, that people, who perform yoga daily have lower blood pressure, improved flexibility, better sleep, better concentration, better coordination and an improved digestion.
In fact, yoga has also been seen to reduce stress levels drastically.
It is surprising to learn that yoga is also used as a supplementary therapy for curing such diverse conditions as cancer, asthma, AIDS and diabetes.
The therapeutic qualities of yoga are not restricted to these ailments alone.
There are other areas where yoga has been found to be helpful and relieving.
Medical problems like acidity, anemia, arthritis, Alzheimer disease, allergies, skin problems, menopause, facial wrinkles, menstrual cramps, depression, hypertension, blood pressures, obesity, stress, insomnia and many others can all be treated by yoga.
Restorative yoga It is associated with the healing of various diseases.
Restorative yoga is practiced in a relaxed states via the use of supports in lieu of the muscular tension for maintaining the alignments of the pose.
Restorative yoga aids in relieving the chronic stress that effects us in a lot of different ways.
- Proper use provides an absolutely different atmosphere for complete relaxation.
- Every restorative sequence is basically designed to move the spine in every direction.
- If the restorative practice is well sequenced, it also incorporates the inverted poses that reverse the gravity effects.
It helps in enhancing the heart function to a great extent.
- It soothes and stimulates the organs of the body alternately.
Advantages of doing yoga exercises: 1.
It boosts the physical strength, flexibility and stamina.
2.
It enhances self control and concentration power.
3.
It helps in improving the blood circulation that makes the skin healthy and glowing.
4.
It inculcates the impulse control.
5.
It lowers the stress levels and relaxes the entire body.
6.
Immune system is enhanced to a great extent.
7.
It imparts a positive outlook towards life.
8.
It brings internal peace and harmony.
9.
The overall functioning of the organs is improved.
10.
There is intensification of mental clarity and pain tolerance.
Various poses of yoga and breathing Breathing is one of the most important parts of yoga exercises.
This is the way one inhales and exhales during various yoga poses.
Generally, yoga poses include standing poses, inversions, the restorative and relaxation poses, counter poses, twists, balancing poses, as well as forward and backward bends.
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Got Lower Back Pain? Try Yoga https://www.91feeds.com/articles_5vkffa.html https://www.91feeds.com/articles_5vkffa.html#respond Mon, 27 May 2019 08:09:00 +0800 I have friends who have been doing it for years for the sole purpose of relieving their chronic lower back pain.
Back pain is often caused by sitting for hours in the same position.
This practice can cause stress on the spine and the surrounding muscles that then result in pain and stiffness.
Discomfort might not be apparent until the damage has been done, and then it can take quite some time to improve flexibility.
Hot baths and massage might help a little for a short period of time, but they won't do much to strengthen the back for a longer term solution.
There was also a recent study that discovered regular participants experienced significantly less pain than those who performed stretching exercises or used a self-help book.
The yoga practitioners discovered how they could manage their pain.
There are many forms of yoga, but the styles that were reported to provide the best results when it comes to back pain are the Hatha, Iyenga and viniyoga types.
The ideal number of poses per day is between 5 and 11.
Add a guided meditation session and you should gain the benefits of less pain.
The sufferers in the study were able to strengthen their lower back muscles and also enjoyed some positive spiritual or mental spin-offs.
The study also gave hope for other body pain sufferers to be able to manage their pain.
If you are considering taking up yoga and you suffer from back pain, then it's important that speak to your medical practitioner before getting started.
It is also recommended that you speak to a yoga instructor regarding their experience when it comes to lower back pain and poses.
They could advise you on which poses will help you the most.
Why yoga helps back pain is attributed to being able to make the muscles stronger.
It also increases mobility and flexibility.
Oxygen is carried to the muscles and the meditative benefits can be superb.
People who regularly meditate report less pain anyway, so in combination with yoga it will be even better.
Even practicing a few simple poses can make a huge difference.
True health is also reputed to come from a flexible spine.
Those with one will age better and will be able to be more active in the later years.
Young people naturally have a spine that is flexible.
As people age, less exercise is performed and the spine and lower back can stiffen up.
Regular Yoga practice offers an opportunity to limber up the spine.
Even after a few weeks of practicing yoga, you can expect to enjoy a more elongated spine.
You should also experience greater energy that may have lied dormant for years.
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Improve Child Literacy With Yoga Stories https://www.91feeds.com/articles_h76cfa.html https://www.91feeds.com/articles_h76cfa.html#respond Mon, 27 May 2019 08:00:00 +0800 One life skill that is essential for success throughout life is literacy.
Literacy includes reading, writing, speaking, listening, and a general appreciation of language.
Children begin to work on literacy from the moment they are born, as they are introduced to the sounds of the language.
As they grow, their ideas of literacy expand to books, songs, poems, and rhymes.
The more children are exposed to rich language, creative stories, songs, and books, the more literate they become.
Elementary teachers often focus the entire academic year around literacy activities.
Yoga instructors can also help develop children's literacy through stories.
While the concept of storytelling is rather simple, the concepts and skills children learn from a good story are simply priceless.
Through stories, children learn valuable life lessons about virtues, feelings, emotions, conflicts, and resolutions.
In a Yoga class, they can learn important Yogic principles, including respect for others, positive thinking, releasing negativity, and using your body to help you through emotional issues.
Children learn the basic components of a story through storytelling.
They learn that stories have a beginning, middle, and end.
They learn about characters, setting, plot, and conflict.
These are all important literacy concepts.
Yoga stories ignite the imaginations of children, exposing them to a variety of ideas and concepts.
Stories show no discrimination, engaging kids with different backgrounds, prior knowledge, and learning levels.
Yoga teachers should use stories to help children learn and remember Yoga poses, and to teach important Yogic philosophies.
Yoga stories can be interactive, where the students act out the poses as the story unfolds.
Yoga instructors can also use props to add interest to the story, and to allow kids to use their imaginations, as they transform their bodies into various animals and objects.
The options, of learning through stories, are limitless.
Yoga instructors can use books, or make up their own stories.
They can allow the children to participate by adding bits and pieces to the story.
Children also love when a story is familiar and take pride in being able to retell stories in their own words.
Children can make valuable connections when they realize that stories are a part of many different venues in life, including school, home, and even Yoga class.
Share a story during your next Kids' Yoga class and you might be surprised how well the children respond.
© Copyright 2012 - Aura Wellness Center - Publications Division ]]>
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The Facts Of Meditation Simplified For You https://www.91feeds.com/articles_4ecqba.html https://www.91feeds.com/articles_4ecqba.html#respond Mon, 27 May 2019 08:00:00 +0800
Are you a negative individual? Do you find that you are generally thinking with the negative outcomes and not focusing on the positive? The sheer act of being unfavorable isn't healthy for our minds or our bodies, but by applying meditation you'll be able to aid to transform this negative way of pondering into a optimistic method of thinking, therefore obtaining a greater lifestyle and greater health. It might surprise you to understand that you simply possess the power to help yourself transform in to a beneficial being rather than a negative one. Feeling stressed out? Meditation will help you here too, though it's not the least complicated thing to try and do, depression could be overcome when you give mediation a try.
Meditation has been proven to be an efficient alternative in body and mind medicine. Physicians have actually prescribed it to individuals who suffer from high blood pressure. It is highly valuable when it comes to aiding patients with asthma and sleeping difficulties considering that it aids to minimize tension and stress. Heart patients benefit since it helps to enhance their workout performance and stamina. It helps to maintain you in total emotional, physical and mental balance.
Meditation is practiced for recovery in many cultures through the world. Religions also use meditation and it is a good value to supporting to alleviate discomfort and aids promote healing back since the ancient times.
Studies have shown that medication's recovery properties are powerful. During the state of meditation our bodies go into an elevated point of deep relaxation or rest and this allows the metabolic rate decrease.
Due to the fact the metabolic rate decreases, it allows to lower our heart rate and reduces the pressure on our heart; it lowers the amounts of specific stress hormones that are produced; lowers blood pressure; lowers cholesterol amounts and increases the flow of air into our lungs.
Transform on your own today in to a happier, far more positive person with the use of meditation. It delivers you with psychological and physical rewards so you only stand to gain from it.
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Learning or Practicing Yoga gives us inner peace and mental satisfaction https://www.91feeds.com/articles_sae2aa.html https://www.91feeds.com/articles_sae2aa.html#respond Mon, 27 May 2019 07:43:00 +0800
To overcome this stress and physical problems, people join various centers which provide physical and mental peace. They keep on paying lots of Dollars to get that satisfaction which is always hidden in themselves. These Yoga Instructors charge a lot from these people who are not happy and satisfied from their life. Somehow these Yoga Instructors live upto their satisfaction and provides them happiness which takes away their stress.
Yoga is a form of exercise which does not involve any machine or tools. It is done with the help of your body parts and actively involves your mind. Regular practice of Yoga helps you to stay healthy and mentally fit. In fact one should adapt to such necessities in life which would not only help you to avoid stress but would bring back smile on your face.
Whenever we speak about Yoga we cannot forget about Ashtanga Yoga & vinyasa yoga teacher training. These trainings are important and vital when you are looking to take this as a career option, otherwise regular yoga training classes would be quite enough to practice yoga and get immense benefits from it. There are several forms of yoga along with the multi-lingual diversity and social beliefs which adds to the value of yoga when we speak about the form of exercise around the world. But there are certain things and positions which do not change wherever you go. For Example steps involved in surya namaskar are the same wherever you go. Also Ashtanga & vinyasa yoga are the forms of yoga which connects your breath with the soul, you can feel light in the air, foot and your mind. Stress and tension is minimized when we practice such forms on a regular basis which gives us energy and strength to perform well in our day to day lives.
We have to understand that if we need to attain our goals then it is vital to stay physically and mentally healthy. We should be regular on morning or evening walks as it would give us fresh air and thoughts. And some exercise like yoga for aerobics would help us to stay healthy and in shape, this would be reflected to others when they would see you smiling always.
Yoga instructor training should be only taken when you feel that you are ready to teach and share your experience with others. Teaching is always a noble job where you spread education, awareness and take care of your student queries. Teaching as a profession also provides mental satisfaction because you are in constant touch of your subject and are regularly practicing it.
Yoga teaching is considered as one of the toughest job because you need to give your more than 100% in order to give your students 100%, you need to be knowledgeable enough to answer to your students queries which would help you to get higher experience levels in your domain.
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What Are The Signs of an Electrolyte Imbalance?
What Are The Signs of an Electrolyte Imbalance?
When you think about electrolytes, what is the first thought that typically comes to mind? For most, it is usually one of the many colorful and popular sports drinks that can be purchased just about anywhere these days. Many people have heard electrolytes are important, so they pay for these pricey drinks and gulp them down, believing they just got a healthy dose of vitamins and minerals.
However, what they're actually getting is an unhealthy dose of sugar - yikes!
What exactly are electrolytes?
Electrolytes may not make your body run, but they do help to make it run efficiently! Similar to a car battery, these crucial minerals found in your blood stimulate voltages that carry electrical impulses across your cells. This strong and powerful electrical energy keeps your organs working properly to help support a healthy body. In addition, electrolytes work to keep your body in balance. Balanced electrolyte levels are important for:
• Maintaining alkalinity of pH levels in the blood.
• Transmitting signals from muscles, nerves, and cells throughout the body.
• Regulating fluid levels in the human body.
• Contracting muscles, including the beating of your heart.
• Building new tissue and clotting blood.
With that in mind, it goes without saying that electrolytes are important! The main electrolytes and their functions are as follows:
• Sodium (Na+): an important mineral that regulates water and fluid in the body. It can be found in the bloodstream, with sodium levels being responsible for telling the kidneys how much water needs to be retained and how much should be excreted.
• Potassium (K+): found inside the cells and is critical for regulating water and fluid in the body. Proper potassium levels are also responsible for proper muscle function, including involuntary muscles like those surrounding the heart, which contracts rhythmically to keep it pumping.
• Chloride (Cl-): another vital electrolyte that is important for maintaining fluid balance in the cells is known as chloride. Like sodium, it's found outside the cells and helps to regulate the water going in and out of the cells. In addition, chloride also plays a large role in regulating the body's pH balance.
• Bicarbonate (HCO3-): also important in regulating the body's pH balance. Since it is alkaline, it helps neutralize excess acid in the digestive system and blood.
• Calcium (Ca++): notorious for its role in bone health. Proper calcium levels help to build strong bones and teeth and is important for repairing damaged muscle and bones. Calcium also is important for muscle contractions, including those of the heart and for nerve signaling.
• Phosphate (HPO4-): also plays a key factor in strengthening bones and teeth - just like calcium! It is also important in manufacturing proteins that the body uses to repair and grow cells.
• Magnesium (Mg++): arguably one of the most important minerals of them all. This super electrolyte is involved in over 300 chemical reactions in the body and is crucial for enzyme activity, cell function, muscle function, nerve signaling, regulating mood, and even sleep. Magnesium and calcium go hand in hand: without sufficient magnesium, your body can't absorb calcium.
What is an Electrolyte Imbalance?
All seven of these electrolytes work together in harmony to promote the body's central functions. However, the human body naturally loses these minerals through a variety of natural activities like breathing, perspiring, and urinating.
Here are some of the primary causes of an electrolyte imbalance:
• Excessive heat.
• Illness that causes fever, diarrhea or vomiting.
• Intense exercise or labor during hot weather.
• High fluid loss without sufficient fluid intake.
• Certain medications, including laxatives and diuretics.
• Medical conditions and respiratory ailments- renal dysfunction, diabetes, emphysema, etc
When levels of electrolytes aren't where they should be, you may experience uncomfortable symptoms, including dehydration - which is a condition where the body doesn't get enough fluids. When you don't have the right electrolyte balance in your body, you may experience some symptoms of electrolyte imbalance.
Some of the most common symptoms associated with low levels are:
• Irregular heartbeat
• Fast heartbeat
• Fatigue
• Lethargy
• Convulsions or seizures
• Nausea
• Vomiting
• Diarrhea or constipation
• Headaches
• Muscle cramps, spasms, and twitching
• Muscle weakness
• Changes in blood pressure
• Confusion
An electrolyte imbalance can be determined by simple blood tests. However, certain evidence like loss of elasticity in the skin, slow reflexes, irregular heart rhythm, or ECG changes can also point towards the imbalance. In general, to help normalize an electrolyte imbalance, certain treatments can be done, such as administration of IV fluids, IV medications, oral medications, and even supplements--your health care professional can guide you through which route is appropriate for your specific levels.
Maintaining Body Fluids & Preventing Electrolyte Disturbances
Okay, so we already know that electrolytes are important, especially when it comes to a well-functioning nervous system and kidney function, but how do you stay hydrated to prevent an imbalance from happening in the first place?
Great question! Here are a few tips to help you to stay hydrated:
Drink more water.
Most of us know the recommendation to drink eight, 8-ounce glasses of water per day. However, since everyone is different, individual fluid needs tend to vary. The Institute of Medicine has set a general recommendation suggesting that men should consume about 125 fluid ounces per day while women should aim for roughly 91 fluid ounces. The key is to really pay attention to how often you're urinating. If you use the restroom every two to four hours, chances are you are probably doing your part to stay hydrated by drinking a sufficient amount of H2O. If you are using the restroom a lot less, your body could likely benefit from a little more water! Chances are overhydration isn't something you'll need to worry about because most people are actually chronically dehydrated and they don't even know it!
Try Hydration Supplements
Another great way to keep your body hydrated is with hydration supplements. These supplements make it easy to get the vitamins and minerals your body needs to avoid an electrolyte imbalance. Look for supplements that are designed to be fast-acting and potent like Adapted Nutrition's Hi-Lyte Concentrate. It can easily be added into any liquid to create a powerful electrolyte drink to support your active and healthy lifestyle.
Eat More Fresh Fruits and Veggies
Last on the list, but definitely not least: eat more fresh fruits and veggies to help keep your body hydrated! Healthy fruits and vegetables like watermelon, cucumber, and celery contain over 80% water, making them a great choice when looking to boost your fluid and mineral intake.
In Conclusion
Electrolytes are important minerals that are necessary for your body to run properly. If you notice any of the signs that you could have an imbalance, it is important to do what you can to get your electrolytes back in check. Try drinking more h2O, taking an electrolyte supplement, and eating more fresh fruits and veggies to start!
Sources:
1. https://www.merckmanuals.com/home/hormonal-and-metabolic-disorders/electrolyte-balance/overview-of-electrolytes#:~:text=Electrolytes%20are%20minerals%20that%20carry,base%20balance%20and%20water%20balance.
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282244/
3. https://medlineplus.gov/fluidandelectrolytebalance.html
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Routing
From Wikipedia, the free encyclopedia
Jump to: navigation, search
Routing is the process of selecting a path for traffic in a network, or between or across multiple networks. Routing is performed for many types of networks, including circuit-switched networks, such as the public switched telephone network (PSTN), computer networks, such as the Internet.
In packet switching networks, routing is the higher-level decision making that directs network packets from their source toward their destination through intermediate network nodes by specific packet forwarding mechanisms. Packet forwarding is the transit of logically addressed network packets from one network interface to another. Intermediate nodes are typically network hardware devices such as routers, bridges, gateways, firewalls, or switches. General-purpose computers also forward packets and perform routing, although they have no specially optimized hardware for the task. The routing process usually directs forwarding on the basis of routing tables, which maintain a record of the routes to various network destinations. Thus, constructing routing tables, which are held in the router's memory, is very important for efficient routing. Most routing algorithms use only one network path at a time. Multipath routing techniques enable the use of multiple alternative paths.
Routing, in a narrower sense of the term, is often contrasted with bridging in its assumption that network addresses are structured and that similar addresses imply proximity within the network. Structured addresses allow a single routing table entry to represent the route to a group of devices. In large networks, structured addressing (routing, in the narrow sense) outperforms unstructured addressing (bridging). Routing has become the dominant form of addressing on the Internet. Bridging is still widely used within localized environments.
Delivery schemes[edit]
Routing schemes
Cast.svg
unicast
Unicast.svg
broadcast
Broadcast.svg
multicast
Multicast.svg
anycast
Anycast-BM.svg
geocast
Geocast.svg
Routing schemes differ in how they deliver messages:
• unicast delivers a message to a single specific node
• broadcast delivers a message to all nodes in the network
• multicast delivers a message to a group of nodes that have expressed interest in receiving the message
• anycast delivers a message to any one out of a group of nodes, typically the one nearest to the source
• geocast delivers a message to a geographic area
Unicast is the dominant form of message delivery on the Internet. This article focuses on unicast routing algorithms.
Topology distribution[edit]
In static routing (or non-dynamic routing), small networks may use manually configured routing tables. Larger networks have complex topologies that can change rapidly, making the manual construction of routing tables unfeasible. Nevertheless, most of the public switched telephone network (PSTN) uses pre-computed routing tables, with fallback routes if the most direct route becomes blocked (see routing in the PSTN).
Dynamic routing attempts to solve this problem by constructing routing tables automatically, based on information carried by routing protocols, allowing the network to act nearly autonomously in avoiding network failures and blockages. Dynamic routing dominates the Internet. Examples of dynamic-routing protocols and algorithms include Routing Information Protocol (RIP), Open Shortest Path First (OSPF) and Enhanced Interior Gateway Routing Protocol (EIGRP).
Distance vector algorithms[edit]
Distance vector algorithms use the Bellman–Ford algorithm. This approach assigns a cost number to each of the links between each node in the network. Nodes send information from point A to point B via the path that results in the lowest total cost (i.e. the sum of the costs of the links between the nodes used).
The algorithm operates in a very simple manner. When a node first starts, it only knows of its immediate neighbours, and the direct cost involved in reaching them. (This information — the list of destinations, the total cost to each, and the next hop to send data to get there — makes up the routing table, or distance table.) Each node, on a regular basis, sends to each neighbour node its own current assessment of the total cost to get to all the destinations it knows of. The neighbouring nodes examine this information and compare it to what they already 'know'; anything that represents an improvement on what they already have, they insert in their own routing table(s). Over time, all the nodes in the network discover the best next hop for all destinations, and the best total cost.
When one network node goes down, any nodes that used it as their next hop discard the entry, and create new routing-table information. These nodes convey the updated routing information to all adjacent nodes, which in turn repeat the process. Eventually all the nodes in the network receive the updates, and discover new paths to all the destinations they can still "reach".
Link-state algorithms[edit]
When applying link-state algorithms, a graphical map of the network is the fundamental data used for each node. To produce its map, each node floods the entire network with information about the other nodes it can connect to. Each node then independently assembles this information into a map. Using this map, each router independently determines the least-cost path from itself to every other node using a standard shortest paths algorithm such as Dijkstra's algorithm. The result is a tree graph rooted at the current node, such that the path through the tree from the root to any other node is the least-cost path to that node. This tree then serves to construct the routing table, which specifies the best next hop to get from the current node to any other node.
Optimized Link State Routing algorithm[edit]
A link-state routing algorithm optimized for mobile ad hoc networks is the optimized Link State Routing Protocol (OLSR).[1] OLSR is proactive; it uses Hello and Topology Control (TC) messages to discover and disseminate link state information through the mobile ad hoc network. Using Hello messages, each node discovers 2-hop neighbor information and elects a set of multipoint relays (MPRs). MPRs distinguish OLSR from other link state routing protocols.
Path vector protocol[edit]
Distance vector and link state routing are both intra-domain routing protocols. They are used inside an autonomous system, but not between autonomous systems. Both of these routing protocols become intractable in large networks and cannot be used in Inter-domain routing. Distance vector routing is subject to instability if there are more than a few hops in the domain. Link state routing needs huge amount of resources to calculate routing tables. It also creates heavy traffic due to flooding.
Path vector routing is used for inter-domain routing. It is similar to distance vector routing. Path vector routing assumes that one node (there can be many) in each autonomous system acts on behalf of the entire autonomous system. This node is called the speaker node. The speaker node creates a routing table and advertises it to neighboring speaker nodes in neighboring autonomous systems. The idea is the same as distance vector routing except that only speaker nodes in each autonomous system can communicate with each other. The speaker node advertises the path, not the metric, of the nodes in its autonomous system or other autonomous systems. Path vector routing is discussed in RFC 1322; the path vector routing algorithm is somewhat similar to the distance vector algorithm in the sense that each border router advertises the destinations it can reach to its neighboring router. However, instead of advertising networks in terms of a destination and the distance to that destination, networks are advertised as destination addresses and path descriptions to reach those destinations. A route is defined as a pairing between a destination and the attributes of the path to that destination, thus the name, path vector routing, where the routers receive a vector that contains paths to a set of destinations. The path, expressed in terms of the domains (or confederations) traversed so far, is carried in a special path attribute that records the sequence of routing domains through which the reachability information has passed.
Path selection[edit]
Path selection involves applying a routing metric to multiple routes to select (or predict) the best route.
In computer networking, the metric is computed by a routing algorithm, and can cover information such as bandwidth, network delay, hop count, path cost, load, MTU (maximum transmission unit), reliability, and communication cost (see e.g. this survey for a list of proposed routing metrics). The routing table stores only the best possible routes, while link-state or topological databases may store all other information as well.
In case of overlapping or equal routes, algorithms consider the following elements to decide which routes to install into the routing table (sorted by priority):
1. Prefix-Length: where longer subnet masks are preferred (independent of whether it is within a routing protocol or over different routing protocol)
2. Metric: where a lower metric/cost is preferred (only valid within one and the same routing protocol)
3. Administrative distance: where a route learned from a more reliable routing protocol is preferred (only valid between different routing protocols)
Because a routing metric is specific to a given routing protocol, multi-protocol routers must use some external heuristic to select between routes learned from different routing protocols. Cisco routers, for example, attribute a value known as the administrative distance to each route, where smaller administrative distances indicate routes learned from a supposedly more reliable protocol.
A local network administrator, in special cases, can set up host-specific routes to a particular device that provides more control over network usage, permits testing, and better overall security. This is useful for debugging network connections or routing tables.
In some small systems, a single central device decides ahead of time the complete path of every packet. In some other small systems, whichever edge device injects a packet into the network decides ahead of time the complete path of that particular packet. In both of these systems, that route-planning device needs to know a lot of information about what devices are connected to the network and how they are connected to each other. Once it has this information, it can use an algorithm such as A* search algorithm to find the best path.
In high-speed systems, there are so many packets transmitted every second that it is infeasible for a single device to calculate the complete path for each and every packet. Early high-speed systems dealt with this by setting up a circuit switching relay channel once for the first packet between some source and some destination; later packets between that same source and that same destination continue to follow the same path without recalculating until the channel teardown. Later high-speed systems inject packets into the network without any one device ever calculating a complete path for that packet—multiple agents.
In large systems, there are so many connections between devices, and those connections change so frequently, that it is infeasible for any one device to even know how all the devices are connected to each other, much less calculate a complete path through them. Such systems generally use next-hop routing.
Most systems use a deterministic dynamic routing algorithm: When a device chooses a path to a particular final destination, that device always chooses the same path to that destination until it receives information that makes it think some other path is better. A few routing algorithms do not use a deterministic algorithm to find the "best" link for a packet to get from its original source to its final destination. Instead, to avoid congestion in switched systems or network hot spots in packet systems, a few algorithms use a randomized algorithm—Valiant's paradigm—that routes a path to a randomly picked intermediate destination, and from there to its true final destination.[2][3] In many early telephone switches, a randomizer was often used to select the start of a path through a multistage switching fabric.
Multiple agents[edit]
In some networks, routing is complicated by the fact that no single entity is responsible for selecting paths; instead, multiple entities are involved in selecting paths or even parts of a single path. Complications or inefficiency can result if these entities choose paths to optimize their own objectives, which may conflict with the objectives of other participants.
A classic example involves traffic in a road system, in which each driver picks a path that minimizes their travel time. With such routing, the equilibrium routes can be longer than optimal for all drivers. In particular, Braess' paradox shows that adding a new road can lengthen travel times for all drivers.
In another model, for example, used for routing automated guided vehicles (AGVs) on a terminal, reservations are made for each vehicle to prevent simultaneous use of the same part of an infrastructure. This approach is also referred to as context-aware routing.[4]
The Internet is partitioned into autonomous systems (ASs) such as internet service providers (ISPs), each of which controls routes involving its network, at multiple levels. First, AS-level paths are selected via the BGP protocol, which produces a sequence of ASs through which packets flow. Each AS may have multiple paths, offered by neighboring ASs, from which to choose. Its decision often involves business relationships with these neighboring ASs,[5] which may be unrelated to path quality or latency. Second, once an AS-level path has been selected, there are often multiple corresponding router-level paths, in part because two ISPs may be connected in multiple locations. In choosing the single router-level path, it is common practice for each ISP to employ hot-potato routing: sending traffic along the path that minimizes the distance through the ISP's own network—even if that path lengthens the total distance to the destination.
Consider two ISPs, A and B. Each has a presence in New York, connected by a fast link with latency 5 ms—and each has a presence in London connected by a 5 ms link. Suppose both ISPs have trans-Atlantic links that connect their two networks, but A's link has latency 100 ms and B's has latency 120 ms. When routing a message from a source in A 's London network to a destination in B 's New York network, A may choose to immediately send the message to B in London. This saves A the work of sending it along an expensive trans-Atlantic link, but causes the message to experience latency 125 ms when the other route would have been 20 ms faster.
A 2003 measurement study of Internet routes found that, between pairs of neighboring ISPs, more than 30% of paths have inflated latency due to hot-potato routing, with 5% of paths being delayed by at least 12 ms. Inflation due to AS-level path selection, while substantial, was attributed primarily to BGP's lack of a mechanism to directly optimize for latency, rather than to selfish routing policies. It was also suggested that, were an appropriate mechanism in place, ISPs would be willing to cooperate to reduce latency rather than use hot-potato routing.[6]
Such a mechanism was later published by the same authors, first for the case of two ISPs[7] and then for the global case.[8]
Route analytics[edit]
As the Internet and IP networks become mission critical business tools, there has been increased interest in techniques and methods to monitor the routing posture of networks. Incorrect routing or routing issues cause undesirable performance degradation, flapping and/or downtime. Monitoring routing in a network is achieved using route analytics tools and techniques.
See also[edit]
References[edit]
1. ^ RFC 3626
2. ^ Michael Mitzenmacher; Andréa W. Richa; Ramesh Sitaraman. "The Power of Two Random Choices: A Survey of Techniques and Results". Section "Randomized Protocols for Circuit Routing". p. 34.
3. ^ Stefan Haas. "The IEEE 1355 Standard: Developments, Performance and Application in High Energy Physics". 1998. p. 15. quote: "To eliminate network hot spots, ... a two phase routing algorithm. This involves every packet being first sent to a randomly chosen intermediate destination; from the intermediate destination it is forwarded to its final destination. This algorithm, referred to as Universal Routing, is designed to maximize capacity and minimize delay under conditions of heavy load."
4. ^ Jonne Zutt, Arjan J.C. van Gemund, Mathijs M. de Weerdt, and Cees Witteveen (2010). Dealing with Uncertainty in Operational Transport Planning. In R.R. Negenborn and Z. Lukszo and H. Hellendoorn (Eds.) Intelligent Infrastructures, Ch. 14, pp. 355–382. Springer.
5. ^ Matthew Caesar and Jennifer Rexford. BGP routing policies in ISP networks. IEEE Network Magazine, special issue on Interdomain Routing, Nov/Dec 2005.
6. ^ Neil Spring, Ratul Mahajan, and Thomas Anderson. Quantifying the Causes of Path Inflation. Proc. SIGCOMM 2003.
7. ^ Ratul Mahajan, David Wetherall, and Thomas Anderson. Negotiation-Based Routing Between Neighboring ISPs. Proc. NSDI 2005.
8. ^ Ratul Mahajan, David Wetherall, and Thomas Anderson. Mutually Controlled Routing with Independent ISPs. Proc. NSDI 2007.
Further reading[edit]
External links[edit]
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「自己拡張」は「module_function」と同じですか？
extend self`と module_function`は、モジュールのメソッドを呼び出したり、そのモジュールをインクルードした場合に呼び出したりできるようにする2つのルビーの方法です。
これらの方法の最終結果に違いはありますか？
1 Answer
55
`module_function`は与えられたインスタンスメソッドをプライベートにし、それらを複製してパブリックメソッドとしてモジュールのメタクラスに入れます。 `extend self`は、モジュールのシングルトンにすべてのインスタンスメソッドを追加し、それらの可視性を変更しません。
module M
extend self
def a; end
private
def b; end
end
module N
def c; end
private
def d; end
module_function :c, :d
end
class O
include M
include N
end
M.a
M.b # NoMethodError: private method `b' called for M:Module
N.c
N.d
O.new.a
O.new.b # NoMethodError: private method `b' called for O
O.new.c # NoMethodError: private method `c' called for O
O.new.d # NoMethodError: private method `d' called for O
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blob: 8aeac918d4d18c2b9b7e1a974259138db80deda5 [file] [log] [blame]
/* config.h.in. Generated from configure.ac by autoheader. */
/* Define if building universal (internal helper macro) */
#undef AC_APPLE_UNIVERSAL_BUILD
/* Sim debug setting */
#undef DEBUG
/* Define to 1 if translation of program messages to the user's native
language is requested. */
#undef ENABLE_NLS
/* Define to the type of elements in the array set by `getgroups'. Usually
this is either `int' or `gid_t'. */
#undef GETGROUPS_T
/* Define to 1 if you have the `access' function. */
#undef HAVE_ACCESS
/* Define to 1 if you have the `aint' function. */
#undef HAVE_AINT
/* Define to 1 if you have the `anint' function. */
#undef HAVE_ANINT
/* Define to 1 if you have the `cfgetispeed' function. */
#undef HAVE_CFGETISPEED
/* Define to 1 if you have the `cfgetospeed' function. */
#undef HAVE_CFGETOSPEED
/* Define to 1 if you have the `cfsetispeed' function. */
#undef HAVE_CFSETISPEED
/* Define to 1 if you have the `cfsetospeed' function. */
#undef HAVE_CFSETOSPEED
/* Define to 1 if you have the `chdir' function. */
#undef HAVE_CHDIR
/* Define to 1 if you have the `chmod' function. */
#undef HAVE_CHMOD
/* Define to 1 if you have the declaration of `tzname', and to 0 if you don't.
*/
#undef HAVE_DECL_TZNAME
/* Define to 1 if you have the <dirent.h> header file, and it defines `DIR'.
*/
#undef HAVE_DIRENT_H
/* Define to 1 if you have the <dlfcn.h> header file. */
#undef HAVE_DLFCN_H
/* Define to 1 if you have the `dup' function. */
#undef HAVE_DUP
/* Define to 1 if you have the `dup2' function. */
#undef HAVE_DUP2
/* Define to 1 if you have the `execv' function. */
#undef HAVE_EXECV
/* Define to 1 if you have the `execve' function. */
#undef HAVE_EXECVE
/* Define to 1 if you have the `fcntl' function. */
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/* Define to 1 if you have the <fcntl.h> header file. */
#undef HAVE_FCNTL_H
/* Define to 1 if you have the `fork' function. */
#undef HAVE_FORK
/* Define to 1 if you have the <fpu_control.h> header file. */
#undef HAVE_FPU_CONTROL_H
/* Define to 1 if you have the `fstat' function. */
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/* Define to 1 if you have the `fstatfs' function. */
#undef HAVE_FSTATFS
/* Define to 1 if you have the `ftruncate' function. */
#undef HAVE_FTRUNCATE
/* Define to 1 if you have the `getdirentries' function. */
#undef HAVE_GETDIRENTRIES
/* Define to 1 if you have the `getegid' function. */
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/* Define to 1 if you have the `geteuid' function. */
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/* Define to 1 if you have the `getgid' function. */
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/* Define to 1 if you have the `getpid' function. */
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/* Define to 1 if you have the `getppid' function. */
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/* Define to 1 if you have the `getrusage' function. */
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/* Define to 1 if you have the `gettimeofday' function. */
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/* Define to 1 if you have the `getuid' function. */
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/* Define to 1 if you have the <inttypes.h> header file. */
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/* Define to 1 if you have the `ioctl' function. */
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/* Define to 1 if you have the `kill' function. */
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/* Define to 1 if you have the `m' library (-lm). */
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/* Define to 1 if you have the `nsl' library (-lnsl). */
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/* Define to 1 if you have the `socket' library (-lsocket). */
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/* Define to 1 if you have the `link' function. */
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/* Define to 1 if you have the <linux/if_tun.h> header file. */
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/* Define to 1 if you have the <linux/mii.h> header file. */
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/* Define to 1 if you have the <linux/types.h> header file. */
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/* Define to 1 if you have the `lseek' function. */
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/* Define to 1 if you have the <memory.h> header file. */
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/* Define to 1 if you have the `mmap' function. */
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/* Define to 1 if you have the `munmap' function. */
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/* Define to 1 if you have the <netinet/in.h> header file. */
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/* Define to 1 if you have the <netinet/tcp.h> header file. */
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/* Define to 1 if you have the <net/if.h> header file. */
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/* Define to 1 if you have the `pipe' function. */
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/* Define to 1 if you have the `posix_fallocate' function. */
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/* Define to 1 if you have the `rmdir' function. */
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/* Define to 1 if you have the `setgid' function. */
#undef HAVE_SETGID
/* Define to 1 if you have the `setregid' function. */
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/* Define to 1 if you have the `setreuid' function. */
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/* Define to 1 if you have the `setuid' function. */
#undef HAVE_SETUID
/* Define to 1 if you have the `sigaction' function. */
#undef HAVE_SIGACTION
/* Define to 1 if you have the `sigprocmask' function. */
#undef HAVE_SIGPROCMASK
/* Define to 1 if the system has the type `socklen_t'. */
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/* Define to 1 if you have the `sqrt' function. */
#undef HAVE_SQRT
/* Define to 1 if you have the `stat' function. */
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/* Define to 1 if you have the <stdint.h> header file. */
#undef HAVE_STDINT_H
/* Define to 1 if you have the <stdlib.h> header file. */
#undef HAVE_STDLIB_H
/* Define to 1 if you have the <strings.h> header file. */
#undef HAVE_STRINGS_H
/* Define to 1 if you have the <string.h> header file. */
#undef HAVE_STRING_H
/* Define to 1 if you have the `strsignal' function. */
#undef HAVE_STRSIGNAL
/* Define to 1 if `st_atime' is a member of `struct stat'. */
#undef HAVE_STRUCT_STAT_ST_ATIME
/* Define to 1 if `st_blksize' is a member of `struct stat'. */
#undef HAVE_STRUCT_STAT_ST_BLKSIZE
/* Define to 1 if `st_blocks' is a member of `struct stat'. */
#undef HAVE_STRUCT_STAT_ST_BLOCKS
/* Define to 1 if `st_ctime' is a member of `struct stat'. */
#undef HAVE_STRUCT_STAT_ST_CTIME
/* Define to 1 if `st_dev' is a member of `struct stat'. */
#undef HAVE_STRUCT_STAT_ST_DEV
/* Define to 1 if `st_gid' is a member of `struct stat'. */
#undef HAVE_STRUCT_STAT_ST_GID
/* Define to 1 if `st_ino' is a member of `struct stat'. */
#undef HAVE_STRUCT_STAT_ST_INO
/* Define to 1 if `st_mode' is a member of `struct stat'. */
#undef HAVE_STRUCT_STAT_ST_MODE
/* Define to 1 if `st_mtime' is a member of `struct stat'. */
#undef HAVE_STRUCT_STAT_ST_MTIME
/* Define to 1 if `st_nlink' is a member of `struct stat'. */
#undef HAVE_STRUCT_STAT_ST_NLINK
/* Define to 1 if `st_rdev' is a member of `struct stat'. */
#undef HAVE_STRUCT_STAT_ST_RDEV
/* Define to 1 if `st_size' is a member of `struct stat'. */
#undef HAVE_STRUCT_STAT_ST_SIZE
/* Define to 1 if `st_uid' is a member of `struct stat'. */
#undef HAVE_STRUCT_STAT_ST_UID
/* Define to 1 if `tm_zone' is a member of `struct tm'. */
#undef HAVE_STRUCT_TM_TM_ZONE
/* Define to 1 if your `struct stat' has `st_blksize'. Deprecated, use
`HAVE_STRUCT_STAT_ST_BLKSIZE' instead. */
#undef HAVE_ST_BLKSIZE
/* Define to 1 if your `struct stat' has `st_blocks'. Deprecated, use
`HAVE_STRUCT_STAT_ST_BLOCKS' instead. */
#undef HAVE_ST_BLOCKS
/* Define to 1 if your `struct stat' has `st_rdev'. Deprecated, use
`HAVE_STRUCT_STAT_ST_RDEV' instead. */
#undef HAVE_ST_RDEV
/* Define to 1 if you have the `symlink' function. */
#undef HAVE_SYMLINK
/* Define to 1 if you have the <sys/dir.h> header file, and it defines `DIR'.
*/
#undef HAVE_SYS_DIR_H
/* Define to 1 if you have the <sys/ioctl.h> header file. */
#undef HAVE_SYS_IOCTL_H
/* Define to 1 if you have the <sys/mman.h> header file. */
#undef HAVE_SYS_MMAN_H
/* Define to 1 if you have the <sys/mount.h> header file. */
#undef HAVE_SYS_MOUNT_H
/* Define to 1 if you have the <sys/ndir.h> header file, and it defines `DIR'.
*/
#undef HAVE_SYS_NDIR_H
/* Define to 1 if you have the <sys/param.h> header file. */
#undef HAVE_SYS_PARAM_H
/* Define to 1 if you have the <sys/resource.h> header file. */
#undef HAVE_SYS_RESOURCE_H
/* Define to 1 if you have the <sys/socket.h> header file. */
#undef HAVE_SYS_SOCKET_H
/* Define to 1 if you have the <sys/statfs.h> header file. */
#undef HAVE_SYS_STATFS_H
/* Define to 1 if you have the <sys/stat.h> header file. */
#undef HAVE_SYS_STAT_H
/* Define to 1 if you have the <sys/termios.h> header file. */
#undef HAVE_SYS_TERMIOS_H
/* Define to 1 if you have the <sys/termio.h> header file. */
#undef HAVE_SYS_TERMIO_H
/* Define to 1 if you have the <sys/types.h> header file. */
#undef HAVE_SYS_TYPES_H
/* Define to 1 if you have the <sys/vfs.h> header file. */
#undef HAVE_SYS_VFS_H
/* Define to 1 if you have the `tcdrain' function. */
#undef HAVE_TCDRAIN
/* Define to 1 if you have the `tcflow' function. */
#undef HAVE_TCFLOW
/* Define to 1 if you have the `tcflush' function. */
#undef HAVE_TCFLUSH
/* Define to 1 if you have the `tcgetattr' function. */
#undef HAVE_TCGETATTR
/* Define to 1 if you have the `tcgetpgrp' function. */
#undef HAVE_TCGETPGRP
/* Define to 1 if you have the `tcsendbreak' function. */
#undef HAVE_TCSENDBREAK
/* Define to 1 if you have the `tcsetattr' function. */
#undef HAVE_TCSETATTR
/* Define to 1 if you have the `tcsetpgrp' function. */
#undef HAVE_TCSETPGRP
/* Define to 1 if you have the <termios.h> header file. */
#undef HAVE_TERMIOS_H
/* Define to 1 if you have the `time' function. */
#undef HAVE_TIME
/* Define to 1 if your `struct tm' has `tm_zone'. Deprecated, use
`HAVE_STRUCT_TM_TM_ZONE' instead. */
#undef HAVE_TM_ZONE
/* Define to 1 if you have the `truncate' function. */
#undef HAVE_TRUNCATE
/* Define to 1 if you don't have `tm_zone' but do have the external array
`tzname'. */
#undef HAVE_TZNAME
/* Define to 1 if you have the `umask' function. */
#undef HAVE_UMASK
/* Define to 1 if you have the <unistd.h> header file. */
#undef HAVE_UNISTD_H
/* Define to 1 if you have the `unlink' function. */
#undef HAVE_UNLINK
/* Define to 1 if you have the `utime' function. */
#undef HAVE_UTIME
/* Define to 1 if you have the <utime.h> header file. */
#undef HAVE_UTIME_H
/* Define to 1 if you have the <windows.h> header file. */
#undef HAVE_WINDOWS_H
/* Define to 1 if the system has the type `__int128'. */
#undef HAVE___INT128
/* Define to 1 if you have the `__setfpucw' function. */
#undef HAVE___SETFPUCW
/* Define to the sub-directory in which libtool stores uninstalled libraries.
*/
#undef LT_OBJDIR
/* Name of package */
#undef PACKAGE
/* Define to the address where bug reports for this package should be sent. */
#undef PACKAGE_BUGREPORT
/* Define to the full name of this package. */
#undef PACKAGE_NAME
/* Define to the full name and version of this package. */
#undef PACKAGE_STRING
/* Define to the one symbol short name of this package. */
#undef PACKAGE_TARNAME
/* Define to the home page for this package. */
#undef PACKAGE_URL
/* Define to the version of this package. */
#undef PACKAGE_VERSION
/* Additional package description */
#undef PKGVERSION
/* Sim profile settings */
#undef PROFILE
/* Bug reporting address */
#undef REPORT_BUGS_TO
/* Define as the return type of signal handlers (`int' or `void'). */
#undef RETSIGTYPE
/* Define to 1 if you have the ANSI C header files. */
#undef STDC_HEADERS
/* Define to 1 if your <sys/time.h> declares `struct tm'. */
#undef TM_IN_SYS_TIME
/* Enable extensions on AIX 3, Interix. */
#ifndef _ALL_SOURCE
# undef _ALL_SOURCE
#endif
/* Enable GNU extensions on systems that have them. */
#ifndef _GNU_SOURCE
# undef _GNU_SOURCE
#endif
/* Enable threading extensions on Solaris. */
#ifndef _POSIX_PTHREAD_SEMANTICS
# undef _POSIX_PTHREAD_SEMANTICS
#endif
/* Enable extensions on HP NonStop. */
#ifndef _TANDEM_SOURCE
# undef _TANDEM_SOURCE
#endif
/* Enable general extensions on Solaris. */
#ifndef __EXTENSIONS__
# undef __EXTENSIONS__
#endif
/* Version number of package */
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/* Sim alignment settings */
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/* Sim assert settings */
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/* Sim debug setting */
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/* Sim default environment */
#undef WITH_ENVIRONMENT
/* Sim profile settings */
#undef WITH_PROFILE
/* Sim reserved bits setting */
#undef WITH_RESERVED_BITS
/* Sim cache szie */
#undef WITH_SCACHE
/* How to route I/O */
#undef WITH_STDIO
/* Sim endian settings */
#undef WITH_TARGET_BYTE_ORDER
/* Sim trace settings */
#undef WITH_TRACE
/* Define WORDS_BIGENDIAN to 1 if your processor stores words with the most
significant byte first (like Motorola and SPARC, unlike Intel). */
#if defined AC_APPLE_UNIVERSAL_BUILD
# if defined __BIG_ENDIAN__
# define WORDS_BIGENDIAN 1
# endif
#else
# ifndef WORDS_BIGENDIAN
# undef WORDS_BIGENDIAN
# endif
#endif
/* Define to 1 if on MINIX. */
#undef _MINIX
/* Define to 2 if the system does not provide POSIX.1 features except with
this defined. */
#undef _POSIX_1_SOURCE
/* Define to 1 if you need to in order for `stat' and other things to work. */
#undef _POSIX_SOURCE
/* Define to `int' if <sys/types.h> doesn't define. */
#undef gid_t
/* Define to `int' if <sys/types.h> does not define. */
#undef mode_t
/* Define to `long int' if <sys/types.h> does not define. */
#undef off_t
/* Define to `int' if <sys/types.h> does not define. */
#undef pid_t
/* Define to `unsigned int' if <sys/types.h> does not define. */
#undef size_t
/* Define to `int' if <sys/types.h> doesn't define. */
#undef uid_t
|
Changes between Version 7 and Version 8 of Commentary/Compiler/Backends/LLVM/DevelopmentNotes
Ignore:
Timestamp:
Jun 11, 2010 11:06:57 AM (7 years ago)
Author:
dterei
Comment:
move design issues into here
Legend:
Unmodified
Added
Removed
Modified
• Commentary/Compiler/Backends/LLVM/DevelopmentNotes
v7 v8
11[[PageOutline]]
22= Bugs & Other Problems =
3
4This page lists bugs and problems currently known about in the LLVM backend.
5
6= Unsupported GHC Features =
7
8== Threaded ==
9
10Dynamic library support hasn't been tested at all in the LLVM backend. No work has been done on it. Its very unlikely that this feature works in the LLVM backend at the moment.
11
12== TABLES_NEXT_TO_CODE ==
13
14GHC for heap objects places the info table (meta data) and the code adjacent to each other. That is, in memory, the object firstly has a head structure, which consists of a pointer to an info table and a payload structure. The pointer points to the bottom of the info table and the closures code is placed to be straight after the info table, so to jump to the code we can just jump one past the info table pointer. The other way to do this would be to have the info table contain a pointer to the closure code. However this would then require two jumps to get to the code instead of just one jump in the optimised layout. Achieving this layout can create some difficulty, the current back-ends handle it as follows:
15
16 * The NCG can create this layout itself
17 * The C code generator can't. So the [wiki:Commentary/EvilMangler Evil Mangler] rearranges the GCC assembly code to achieve the layout.
18
19There is a build option in GHC to use the unoptimised layout and instead use a pointer to the code in the info table. This layout can be enabled/disabled by using the compiler {{{#def TABLES_NEXT_TO_CODE}}}. As LLVM has no means to achieve the optimised layout and we don't wish to write an LLVM sister for the Evil Mangler, the LLVM back-end currently uses the unoptimised layout. This apparently incurs a performance penalty of 5% (source, Making a ''Fast Curry: Push/Enter vs. Eval/Apply for Higher-order Languages'', Simon Marlow and Simon Peyton Jones, 2004).
320
421= LLVM Bugs =
|
blob: 1333cbdc3ea2fa673b744c2b81b6c311071be704 [file] [log] [blame]
/*
* acpi_numa.c - ACPI NUMA support
*
* Copyright (C) 2002 Takayoshi Kochi <t-kochi@bq.jp.nec.com>
*
* ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
*
* This program is free software; you can redistribute it and/or modify
* it under the terms of the GNU General Public License as published by
* the Free Software Foundation; either version 2 of the License, or
* (at your option) any later version.
*
* This program is distributed in the hope that it will be useful,
* but WITHOUT ANY WARRANTY; without even the implied warranty of
* MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the
* GNU General Public License for more details.
*
* You should have received a copy of the GNU General Public License
* along with this program; if not, write to the Free Software
* Foundation, Inc., 59 Temple Place, Suite 330, Boston, MA 02111-1307 USA
*
* ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
*
*/
#include <linux/module.h>
#include <linux/init.h>
#include <linux/kernel.h>
#include <linux/types.h>
#include <linux/errno.h>
#include <linux/acpi.h>
#include <linux/numa.h>
#define PREFIX "ACPI: "
#define ACPI_NUMA 0x80000000
#define _COMPONENT ACPI_NUMA
ACPI_MODULE_NAME("numa");
static nodemask_t nodes_found_map = NODE_MASK_NONE;
/* maps to convert between proximity domain and logical node ID */
static int pxm_to_node_map[MAX_PXM_DOMAINS]
= { [0 ... MAX_PXM_DOMAINS - 1] = NUMA_NO_NODE };
static int node_to_pxm_map[MAX_NUMNODES]
= { [0 ... MAX_NUMNODES - 1] = PXM_INVAL };
unsigned char acpi_srat_revision __initdata;
int pxm_to_node(int pxm)
{
if (pxm < 0)
return NUMA_NO_NODE;
return pxm_to_node_map[pxm];
}
int node_to_pxm(int node)
{
if (node < 0)
return PXM_INVAL;
return node_to_pxm_map[node];
}
static void __acpi_map_pxm_to_node(int pxm, int node)
{
if (pxm_to_node_map[pxm] == NUMA_NO_NODE || node < pxm_to_node_map[pxm])
pxm_to_node_map[pxm] = node;
if (node_to_pxm_map[node] == PXM_INVAL || pxm < node_to_pxm_map[node])
node_to_pxm_map[node] = pxm;
}
int acpi_map_pxm_to_node(int pxm)
{
int node = pxm_to_node_map[pxm];
if (node == NUMA_NO_NODE) {
if (nodes_weight(nodes_found_map) >= MAX_NUMNODES)
return NUMA_NO_NODE;
node = first_unset_node(nodes_found_map);
__acpi_map_pxm_to_node(pxm, node);
node_set(node, nodes_found_map);
}
return node;
}
static void __init
acpi_table_print_srat_entry(struct acpi_subtable_header *header)
{
ACPI_FUNCTION_NAME("acpi_table_print_srat_entry");
if (!header)
return;
switch (header->type) {
case ACPI_SRAT_TYPE_CPU_AFFINITY:
#ifdef ACPI_DEBUG_OUTPUT
{
struct acpi_srat_cpu_affinity *p =
(struct acpi_srat_cpu_affinity *)header;
ACPI_DEBUG_PRINT((ACPI_DB_INFO,
"SRAT Processor (id[0x%02x] eid[0x%02x]) in proximity domain %d %s\n",
p->apic_id, p->local_sapic_eid,
p->proximity_domain_lo,
(p->flags & ACPI_SRAT_CPU_ENABLED)?
"enabled" : "disabled"));
}
#endif /* ACPI_DEBUG_OUTPUT */
break;
case ACPI_SRAT_TYPE_MEMORY_AFFINITY:
#ifdef ACPI_DEBUG_OUTPUT
{
struct acpi_srat_mem_affinity *p =
(struct acpi_srat_mem_affinity *)header;
ACPI_DEBUG_PRINT((ACPI_DB_INFO,
"SRAT Memory (0x%lx length 0x%lx) in proximity domain %d %s%s%s\n",
(unsigned long)p->base_address,
(unsigned long)p->length,
p->proximity_domain,
(p->flags & ACPI_SRAT_MEM_ENABLED)?
"enabled" : "disabled",
(p->flags & ACPI_SRAT_MEM_HOT_PLUGGABLE)?
" hot-pluggable" : "",
(p->flags & ACPI_SRAT_MEM_NON_VOLATILE)?
" non-volatile" : ""));
}
#endif /* ACPI_DEBUG_OUTPUT */
break;
case ACPI_SRAT_TYPE_X2APIC_CPU_AFFINITY:
#ifdef ACPI_DEBUG_OUTPUT
{
struct acpi_srat_x2apic_cpu_affinity *p =
(struct acpi_srat_x2apic_cpu_affinity *)header;
ACPI_DEBUG_PRINT((ACPI_DB_INFO,
"SRAT Processor (x2apicid[0x%08x]) in"
" proximity domain %d %s\n",
p->apic_id,
p->proximity_domain,
(p->flags & ACPI_SRAT_CPU_ENABLED) ?
"enabled" : "disabled"));
}
#endif /* ACPI_DEBUG_OUTPUT */
break;
default:
printk(KERN_WARNING PREFIX
"Found unsupported SRAT entry (type = 0x%x)\n",
header->type);
break;
}
}
/*
* A lot of BIOS fill in 10 (= no distance) everywhere. This messes
* up the NUMA heuristics which wants the local node to have a smaller
* distance than the others.
* Do some quick checks here and only use the SLIT if it passes.
*/
static int __init slit_valid(struct acpi_table_slit *slit)
{
int i, j;
int d = slit->locality_count;
for (i = 0; i < d; i++) {
for (j = 0; j < d; j++) {
u8 val = slit->entry[d*i + j];
if (i == j) {
if (val != LOCAL_DISTANCE)
return 0;
} else if (val <= LOCAL_DISTANCE)
return 0;
}
}
return 1;
}
static int __init acpi_parse_slit(struct acpi_table_header *table)
{
struct acpi_table_slit *slit = (struct acpi_table_slit *)table;
if (!slit_valid(slit)) {
printk(KERN_INFO "ACPI: SLIT table looks invalid. Not used.\n");
return -EINVAL;
}
acpi_numa_slit_init(slit);
return 0;
}
void __init __weak
acpi_numa_x2apic_affinity_init(struct acpi_srat_x2apic_cpu_affinity *pa)
{
printk(KERN_WARNING PREFIX
"Found unsupported x2apic [0x%08x] SRAT entry\n", pa->apic_id);
return;
}
static int __init
acpi_parse_x2apic_affinity(struct acpi_subtable_header *header,
const unsigned long end)
{
struct acpi_srat_x2apic_cpu_affinity *processor_affinity;
processor_affinity = (struct acpi_srat_x2apic_cpu_affinity *)header;
if (!processor_affinity)
return -EINVAL;
acpi_table_print_srat_entry(header);
/* let architecture-dependent part to do it */
acpi_numa_x2apic_affinity_init(processor_affinity);
return 0;
}
static int __init
acpi_parse_processor_affinity(struct acpi_subtable_header *header,
const unsigned long end)
{
struct acpi_srat_cpu_affinity *processor_affinity;
processor_affinity = (struct acpi_srat_cpu_affinity *)header;
if (!processor_affinity)
return -EINVAL;
acpi_table_print_srat_entry(header);
/* let architecture-dependent part to do it */
acpi_numa_processor_affinity_init(processor_affinity);
return 0;
}
static int __initdata parsed_numa_memblks;
static int __init
acpi_parse_memory_affinity(struct acpi_subtable_header * header,
const unsigned long end)
{
struct acpi_srat_mem_affinity *memory_affinity;
memory_affinity = (struct acpi_srat_mem_affinity *)header;
if (!memory_affinity)
return -EINVAL;
acpi_table_print_srat_entry(header);
/* let architecture-dependent part to do it */
if (!acpi_numa_memory_affinity_init(memory_affinity))
parsed_numa_memblks++;
return 0;
}
static int __init acpi_parse_srat(struct acpi_table_header *table)
{
struct acpi_table_srat *srat = (struct acpi_table_srat *)table;
acpi_srat_revision = srat->header.revision;
/* Real work done in acpi_table_parse_srat below. */
return 0;
}
static int __init
acpi_table_parse_srat(enum acpi_srat_type id,
acpi_tbl_entry_handler handler, unsigned int max_entries)
{
return acpi_table_parse_entries(ACPI_SIG_SRAT,
sizeof(struct acpi_table_srat), id,
handler, max_entries);
}
int __init acpi_numa_init(void)
{
int cnt = 0;
/*
* Should not limit number with cpu num that is from NR_CPUS or nr_cpus=
* SRAT cpu entries could have different order with that in MADT.
* So go over all cpu entries in SRAT to get apicid to node mapping.
*/
/* SRAT: Static Resource Affinity Table */
if (!acpi_table_parse(ACPI_SIG_SRAT, acpi_parse_srat)) {
acpi_table_parse_srat(ACPI_SRAT_TYPE_X2APIC_CPU_AFFINITY,
acpi_parse_x2apic_affinity, 0);
acpi_table_parse_srat(ACPI_SRAT_TYPE_CPU_AFFINITY,
acpi_parse_processor_affinity, 0);
cnt = acpi_table_parse_srat(ACPI_SRAT_TYPE_MEMORY_AFFINITY,
acpi_parse_memory_affinity,
NR_NODE_MEMBLKS);
}
/* SLIT: System Locality Information Table */
acpi_table_parse(ACPI_SIG_SLIT, acpi_parse_slit);
acpi_numa_arch_fixup();
if (cnt < 0)
return cnt;
else if (!parsed_numa_memblks)
return -ENOENT;
return 0;
}
static int acpi_get_pxm(acpi_handle h)
{
unsigned long long pxm;
acpi_status status;
acpi_handle handle;
acpi_handle phandle = h;
do {
handle = phandle;
status = acpi_evaluate_integer(handle, "_PXM", NULL, &pxm);
if (ACPI_SUCCESS(status))
return pxm;
status = acpi_get_parent(handle, &phandle);
} while (ACPI_SUCCESS(status));
return -1;
}
int acpi_get_node(acpi_handle handle)
{
int pxm;
pxm = acpi_get_pxm(handle);
if (pxm < 0 || pxm >= MAX_PXM_DOMAINS)
return NUMA_NO_NODE;
return acpi_map_pxm_to_node(pxm);
}
EXPORT_SYMBOL(acpi_get_node);
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genetic fitness
ge·net·ic fit·ness
in a phenotype, the mean number of surviving offspring that it generates in its lifetime, usually expressed as a fraction or percentage of the average genetic fitness of the population.
Farlex Partner Medical Dictionary © Farlex 2012
ge·net·ic fit·ness
(jĕ-net'ik fit'nĕs)
In a phenotype, the mean number of surviving offspring that it generates in its lifetime, usually expressed as a fraction or percentage of the average genetic fitness of the population.
Medical Dictionary for the Health Professions and Nursing © Farlex 2012
References in periodicals archive ?
Heritability is used as the ratio of genetics fitness variance to total fitness variance (environmental variance plus genetic fitness variance).
LINKS TO LONGEVITY Why these late-acting mutations might lower a person's genetic fitness " their ability to reproduce and spread their genes " remains an open question.
Manning said that body symmetry is believed to be a sign of overall genetic fitness and good physical development, asserting that it has also been correlated with a wide range of attributes including running speed.
The signals kissing provides may provide biological cues for compatibility, genetic fitness, or general health, scientists believe.
He uses Salter's (2004) analysis of genetic similarity coefficients to demonstrate that ethnic nepotism makes sense in terms of genetic fitness and that ethnic groups are, in relation to each other, effectively extended families, implying that ethnic nepotism is simply an extension of nepotism.
In the wild, we will also be able to use the same tools to monitor the genetic fitness of snook populations there as well."
The assumption is that champion trees are genetically superior and cloning them will increase the genetic fitness of future forests.
has a disproportionately larger negative impact compared with an equal amount of increase in resources because the decrease is more likely to cause the organism to die (2) and thereby permanently forgo the possibility of producing offspring in the future that will contribute to its genetic fitness. This intuition is similar to results in models of financial distress and bankruptcy in which firms with large amounts of intangible assets that might disappear in bankruptcy will tend to avoid financial distress by avoiding risky outcomes and by hedging.
However to conserve Caspian brown trout is difficult to be achieved, because there is still impact on the genetic fitness of the wild population, and less success to minimize the impact while still maintaining a fishery of rare fish are observed.
"We know that genetic fitness increases with increased heterozygosity, so it stands to reason that certain areas (called loci) on some chromosomes would remain heterozygous if they have important effects on fitness.
The offspring make mate choices which maximize their own fitness, but because the two parties are not genetically identical these choices do not necessarily maximize the genetic fitness of their parents.
In the culture of nonnative species, competition and hybridization with native species are potential impacts, whereas in the culture of native species, reduction of the genetic fitness of wild populations through introgression with aquaculture strains is a primary concern (Utter & Epifanio 2002).
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Latest Blogs / Blog Details
BUTANE – An Organic Compound
Published Date : February 18, 2019
There are many organic compounds which are so indispensable in the preparation many useful components and chemicals. An organic compound is a chemical compound that contains a carbon atom or a chain of carbon atoms. Organic compounds are divided into alkanes, alkenes, alkynes and alkyls based on the carbon content and the saturation levels. Based on the number of carbons in the compound, the organic compounds are named as ethane, methane, propane etc. as the carbon chain has one, two and three carbon atoms in them respectively. Such organic compounds that have four atoms of carbon in its chain are known as butanes. The term butane refers to the unbranched structure of n-butane isomer. The chemical symbol of butane is C4H10 which denotes that there are four carbon atoms and ten hydrogen atoms. Butanes are produced synthetically from petroleum and used in the manufacture rubber and is used as a fuel and a refrigerator. Butanes are produced in natural gases and is a colourless gas with a faint petroleum like odour. More description and uses of butanes are as follows.
ISOMERS AND PHYSICAL PROPERTIES
All butanes have isomers (i.e. compounds that have the same molecular formula that different structural formula) that almost have similar properties as that of n-butane which is the normal butane. The isomer of n-butane is i-butane (or isobutane) which is called 2-methylpropane. The physical properties of butanes are as follows.
• Butanes are colourless gases.
• They have petroleum or natural gas-like odour.
• Butanes are soluble in water.
• The components of butanes are easily ignitable.
• The vapours of butanes are heavier than air.
• Increased contact with liquid can caused frostbite.
USES
The most primary use of butanes is the uses of butanes are listed below.
• Normal butanes can be used as fuels, refrigerators and in gasoline blending.
• In the manufacture of ethylene and butadiene which are vital constituents of synthetic rubber.
• Isobutane is used in refineries to enhance motor gasoline.
• Butanes are used as feedstock in petrochemicals in steam cracking.
• They are used as a propellant in aerosol sprays and in some deodorants.
• Butane torches are used as alternative for lighters.
HEALTH ISSUES AND RECENT TRENDS
Though butanes offer so much household and commercial uses, there are some serious disadvantages if they are misused. Higher inhalation of butanes may cause euphoria, drowsiness and narcosis. In some cases this may lead to further complications such as high blood pressure and temporary memory loss. When butane enters the blood it may cause immediate intoxication. When butanes attack the throat part, it can lead to serious expansion of throat known as laryngospam. These are some of the dangerous ill effects of butanes.
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