text:
Thoughts on The Eyes of the Skin
Saran July 4, 2020 July 4, 2020 architecture, articles, other information
I've recently had time to thoroughly read over The Eyes of the Skin: Architecture and the Senses by Juhani Pallasmaa, and here's my attempt to distill my understanding of this book into a piece of essay…
The Eyes of the Skin: Architecture and the Senses by Juhani Pallasmaa is one of the significant literature on architecture, highlighting the importance of the relationship between human experiences and the engagement of multiple senses in a space. Pallasmaa expresses his apprehension about the vision-centric appreciation of architecture that has been prevailing in the society. While Pallasmaa explores the beauty of each sense in the context of the embodied human experience, he articulates the necessity of 'several realms of sensory experience which interact and fuse into each other' in order to establish Architecture that 'strengthens the existential experience'1. Furthermore, Pallasmaa discusses architecture concerning the phenomenological qualities of the world and the human experience, including the effects of light and shadows, the flow of time, memory and imagination. Pallasmaa also weaves in his perspective on the rationalism in modern architecture, pointing out that architecture cannot exist purely for functional reasons.
1 Ocularcentrism
While he does not reject vision, Pallasmaa is concerned about the dominance of eyes in recognition of art and architecture that could 'push us into detachment, isolation and exteriority'2. He traces the neglect of the body and senses in contemporary architecture back to the ocular bias of the Western belief explored by philosophers such as René Descartes3. However, at the same time, he reminds us that the other senses, such as hearing had been more significant to humans with oral traditions4. The privilege of the vision in history continues to influence the way we value what we see more than other senses. Referencing Martin Heidegger et al., Pallasmaa further examines the link between the pictorial representation and architecture through the discourse of the modern age characterised by the technological advancements, which increased the speed of our everyday life in myriad ways. He recognises sight 'causing us to live increasingly in a perpetual present, flattened by speed and simultaneity'5, which subsequently transformed images into commodities. Images mass-produced for architectural expressions are not an exception; Pallasmaa warns that 'superficial architectural imagery today, devoid of tectonic logic and a sense of materiality and empathy'6 does not reflect what architecture is about. Pallasmaa emphasises the role of architecture being 'to reconstruct the experience of an undifferentiated interior world, in which we are not mere spectators, but to which we inseparably belong' 7. Since the first publication of the book, the issue of ocularcentrism has exacerbated as sharing images on social media became the means of showcasing 'architecture' to the public. Although there has been further development in utilising moving image (videos) that provides a better subjective experience of space, the dominance of vision in a fixed point of view continues to preoccupy us as a means of 'instant persuasion'8. We the society have not adequately responded to the concerns Pallasmaa raised in this book over 20 years ago.
2 Five Senses?
Though our understanding of senses tends to be a group of individual senses such as sight, hearing, smell, taste and touch, Pallasmaa invites us to see how senses function simultaneously in a complex network. The critical review on how we treat the vision mentioned above has its cause in 'the isolation of the eye outside its natural interaction with other sense modalities'9. Pallasmaa argues that architecture is 'multi-sensory'10, that one experiences it through immersing oneself in space and time, utilising the entirety of the body; it cannot be 'a collection of isolated visual pictures, but in its fully embodied material and spiritual presence'11. Pallasmaa quotes James J Gibson and Steinerian philosophy in describing the possibility of senses categorised in different systems, or more than what we assume12. It reflects on how our society focuses on the individual functions of 'five senses' that are supposedly working on their own. As an attempt to demystify the complex system of human cognition of space, Pallasmaa introduces each of essential sense's uniqueness:
Touch as 'the only sense which can give a sensation of spatial depth'13, that also can 'read(s) the texture, weight, density and temperature of matter'14;
Hearing 'structures and articulates the experience and understanding of space'15 that 'remains as an unconscious background experience'16;
Smell as 'the most persistent memory of any space'17;
Tastes, the 'interior sensation of the mouth' is where 'our sensory experience of the world originates' 18.
Pallasmaa's perspective on senses goes beyond the stereotypical understanding of them; he sees the connections between senses and our memory, consciousness, spatial cognition, emotion and imagination. All of these phenomenological conditions come to life as one sense triggers the other senses, as Pallasmaa mentions 'the eye invites and simulates muscular and tactile sensations' 19. It gives us a new perception on how we experience space, especially in architecture that provides us 'the ground for perception and the horizon of experiencing and understanding the world'20.
3 Phenomenology
It is impossible to detach the concept of phenomenology on Pallasmaa's discourse. Phenomenology explores the ways we experience things and find meanings in them, which is inherently associated with architecture. Pallasmaa considers experiencing space as an active engagement rather than a passive one; citing Melanie Klein, Pallasmaa argues that 'all human interaction implies projection of fragments of the self on to the other person'21. It leads us to imagine how both conscious and subconscious sides of us are engaging with surrounding space all the time. It is a sensation that might have been neglected or unnoticed in the modern age, as we often pay our attention to the overwhelming quantity of imagery around us.
One of the phenomena we encounter in our everyday life is the shadow. While we tend to identify shadows through vision, Pallasmaa illustrates the beauty of deep shadows and darkness as something that 'dim the sharpness of vision, make depth and distance ambiguous, and invite unconscious peripheral vision and tactile fantasy'22. Shadows offer different sensory experiences of space that otherwise shows an entirely different character. Pallasmaa discusses the richness in the ambiguity of the perceived space in contrast to the evenly, brightly lit spaces that 'paralyses the imagination in the same way that homogenisation of space weakens the experience of being, and wipes away the sense of place'23. The darkness of shadows is not there to hinder the sight, but rather to sharpen our senses. Referring to Jun'ichiro Tanizaki, Chinese paintings and Caravaggio and Rembrandt's paintings, Pallasmaa praises that 'the shadow gives shape and life to the object in light.'24. For him, shadows may be seen as a living creature, as he poetically writes 'a constant, deep breathing of shadow and light; shadow inhales and illumination exhales light'.25 Pallasmaa suggests how we treat shadows in space can influence our perception of spatial experiences.
4 Modernism / rationalism
Pallasmaa's discourse on modernist architecture involves the questioning of the rationalist ideology that heavily focuses on the vision and neglects the sensory experience. Pallasmaa points out that 'modernist design at large has housed the intellect and the eye, but it has left the body and the other senses, as well as our memories, imagination and dreams, homeless.'26. He expresses his concerns over conceptualisation of architecture based on functional, rational and intellectual dimensions that 'contributes to the disappearance of its physical, sensual and embodied essence'27. At the same time, Pallasmaa understands modern architects' attempts that aim to go beyond a mere functional architecture, including 'the kinaesthetic and textural architecture of Frank Lloyd Wright, the muscular and tactile buildings of Alvar Aalto, and Louis Kahn's architecture of geometry and gravitas'28. In particular, Pallasmaa praises Alvar Aalto's architecture based on 'sensory realism', appreciated 'in their actual physical and spatial encounter, "in the flesh" of the lived world, not as constructions of idealised vision'29. Pallasmaa pursues the reality of the architecture that considers the humans at the centre of its philosophy.
In conclusion, The Eyes of the Skin represents Pallasmaa's acute understanding of human experiences in the world and how it is crucial for architecture. Pallasmaa's exploration of individual senses, their influences on our perception and the phenomenological conditions we encounter, reveals his belief that 'architecture is the art of reconciliation between ourselves and the world, and this mediation takes place through the senses'30. This book is a gateway to see the world not only through our eyes but through our entire body.
Juhani Pallasmaa, The Eyes of the Skin: Architecture and the Senses, John Wiley & Sons (Chichester), 2012, p 45.
Ibid, p 22.
Ibid, p 69
book, essay, Juhani Pallasmaa, reflection, review, summary, The Eyes of the Skin
Previous Figure-Ground: explore the city from an archi student's point of view
Next STEM x Design Presentation at Year 7 assembly


text:
Fighting The Winnable War
Industry Regulators
TV, Radio & Internet
Film and Literature
Television Channels
The Advertisers
Mardi-Gras 2014
Sexual Behaviour
Abortion & Breast Cancer
AFF Submissions
Pornography – 'the Greatest Cancer In the Church Today'
(The text of this content first appeared at Vision Christian Radio's web site.)
A conference was held in the US recently in an attempt to find ways to stop the tidal wave of pornography sweeping the globe.
Jack Sonneman from the Australian Federation for the Family attended the conference titled the Coalition to End Sexual Exploitation and told 20Twenty host Neil Johnson that it was more than just a talkfest.
Most importantly Jack brought home with him Josh McDowell's latest book 'The Porn Phenomenon'. The book describes porn as the greatest social problem in the world and the greatest encumbrance to the Gospel.
Jack said he was totally and completely shocked by the book's contents and the data contained in the book.
The luminaries attending the conference included the department heads of major US universities, scholars who've run programs for the UN, Harvard, the Department of Defence, Homeland Security, sex slavery and human trafficking experts, the Director of Communications from the house of Representatives and the White House, and many others, plus one of the world's top neuro surgeon's, Dr Don Hilton.
Porn creating a 'supra-normal stimulus' 'It changes the shape of your brain!'
"Dr Hilton pointed out to us that pornography is biologically addictive and it's changing our culture significantly, that it's a major public health hazard, and it's creating what is known as a supra-normal stimulus," Jack said, adding how the stimulus puts into people's minds the desire for the plastic instead of the real.
"He said children's brain receptors are more open to the pleasure sense and that the pornographers are targeting our most vulnerable, the children," Jack revealed, informing that these predators are aiming at the 9 to 11 year old users websites where they can place pop ups to lure children to walk down a destructive pathway.
"Dr Hilton said that looking at porn changes the shape of your brain just like lifting weights changes the shape of your muscles. Shocking stuff!"
'Pornography is the greatest cancer in the church today'
Jack Sonneman then addressed the impact pornography is having on the church and referred to Josh McDowall's book 'The Porn Phenomenon' and quoted this passage from the book.
"About six years ago I began to sense something was seriously wrong. Whatever it was, it was negatively effecting the receptivity of young people to the Gospel."
Jack said Josh McDowall consulted key pastors and Christian leaders and mentioned that Chuck Swindoll encouraged the research. As a result, Josh McDowall believes pornography is the greatest cancer in the church today.
"Dr James Dobson was also very supportive of Josh McDowell's research leading up to the book, but warned him there would be resistance from church leaders."
'Porn the greatest encumbrance to the Gospel in the world'
"We have a problem with pornography in the church today. He says (J. McDowell) that pornography is the greatest encumbrance to the Gospel in the world!" and Jack said the findings reveal that pornography will be mainstream in the church within three to four years.
Jack Sonneman again goes to the source and quotes J McDowell where he writes that every single pastor and Bible student at a recent Christian conference, and there were thousands, every one of them raised their hands admitting to a problem with internet porn.
"He said the church will self-destruct if it does not address the porn problem."
Pornography in the church – 'there's no greater problem'
"There is no greater problem in the world today than pornography in the church," claimed Jack Sonneman.
McDowell's research has discovered that 47 percent of 36 to 60 year olds actively seek out porn. He says 65 percent of 25 to 39 year olds actively seek out porn.
"And shockingly, 81 percent of 13 to 24 year olds actively seek out porn. What also shocked me was the fact that Josh McDowell and The Porn Phenomenon documents that 56 percent of 18 to 24 year-old Christian women actively seek out porn."
Jack Sonneman then referred to an earlier encounter with Dr James Dobson after the Focus on the Family founder had interviewed American serial killer Ted Bundy before his execution.
Ted Bundy had documented the role pornography had played in his life. This led him down a diabolical pathway that included the murder and molestation of little girls.
"This is twenty years ago, when Dr Dobson told me back then, that most Christian men have problems with pornography. We do have a problem with it in the church and the church needs to address the problem," Jack said.
Whom will your daughters marry? 'porn-addicted church leaders?'
Then it got personal for Jack Sonneman after he told Josh McDowell he had six little granddaughters under the age of seven.
"And he said to me, who are your granddaughters going to marry? Are they going to marry a porn addicted church elder, a porn addicted Sunday school teacher, or a porn addicted deacon?"
What is the solution to this porn addiction epidemic if a big stick, shaming and guilt-loading is not going to solve the problem? Jack made some suggestions.
Solution – 'Love the next generation, implement Biblical principles'
"We have to love the next generation enough to implement biblical Christian principles today. We haven't done that."
"We're looking to the experts for the solutions. But the experts don't have them. God has the solution," Jack stressed, saying that we have to embrace only issues that will usher in the kingdom of God on earth as it is in heaven.
"We need to show our children a future filled with hope instead of these increasingly deadly perversions of the pornographers.
Solution – 'We need to take our culture back'
"We have allowed the culture to sexualise our little children. We need to take our culture back," Jack said, but how?
"The only way we can do that, and as this conference pointed out, the enemy is too big, the numbers are too massive, the money is too immense. The problem, if we try to face and fight it in the natural we're going to lose."
So what's the answer? Jack said we have to lift our vision up into the heavenlies.
"As C S Lewis said, 'If we reach for the heavens we get the earth thrown in. If we reach for the earth we get neither.'"
Solution – 'Embrace Godly principles for Godly results'
"That's why we have to reject a lot of the feminist-based solutions and except biblical-based solutions."
Jack Sonneman admitted he's a street-fighter, not a counselor. He said he knows how to protect children and believes that as we embrace Godly principles we will see Godly results that can ultimately protect our children.
"I don't want to see anything ungodly and I don't want to retire. I'm going to continue in this battle until I die," Jack declared.
Solution – 'Men with a porn problem should seek help'
Jack admits, and the statistics back him up, that pornography is a common problem in the church. He said men who are struggling with the problem should not hesitate to seek help.
"They're not alone. Their pastor would not have heard anything they're not going to tell them. They need to realise it's a common problem in the church and they can get help for it."
Jack said not only can they get help for it but they can also be set free from it.
"Don Francisco, a contemporary Christian singer, when he performed some of his greatest work he says he was deeply consumed by an addiction to pornography. And he's now freed from it and talks about it," Jack said, saying other men can do the same.
A solution – 'Men, clean your hearts and minds in Christ Jesus'
"They can let others know that real men don't use pornography and they can become real men by trying to clean up their hearts and their minds in Christ Jesus."
"Looking at porn does have consequences," Jack warned before referring again to neuro-surgeon Dr Don Hilton's findings, that it changes the shape of your brain, before mentioning another disturbing factor.
"They've even done bystander intervention studies that show porn users will not intervene in a sexual assault. In fact today they'll take out their mobile phone and film it instead of intervening," Jack commented.
'No trial justice for rape victims from porn-user inclusive juries'
He said porn users will always trivialise rape, and victims who seek justice at a trial from an Australian jury will not receive it if porn is used among the jury members.
"This is because studies have shown porn users, be they men or women, hand down half the rape sentence of others."
Jack Sonneman said massive exposure to porn, according to the data, the science, and the research, is 4 hours and 48 minutes total over 6 weeks.
Pornography – 'It's prostitution for mass consumption!'
"In fact a university research project comparing heavy, medium and light viewers of porn had to be cancelled because they could find no one in the light viewer of porn category!"
What's the solution? Jack Sonneman said it again – 'Clean up our hearts.'
"If we want to see justice back in our society we have to clean up our hearts and our minds in Christ Jesus.'
"Pornography is nothing more than prostitution for mass consumption."
For further information on the Major International Conference in the US – The Coalition to End Sexual Exploitation …. simply GOOGLE "CESE Summit 2016"
For further information on how to assist the AFF defeat porn in Australia and to lobby the government for opt-in Internet porn provisions, go to www.ausfamily.org
Current AFF campaigns. 1- Protect children in Queensland from unrestricted access to the grossly pornographic imagery in Australian Penthouse magazine. 2- Opt in for Internet porn. 3- Place the same restrictions on X Rated DVDs in the territories as already exists in each and every state in Australia. 4- Outlaw ALL forms of prostitution.
About A.F.F.
We have been full time lobbyists for Aussie families since 1983. AFF is dedicated to upholding Biblical family values, promoting a Biblical Christian worldview, and educating and mobilising concerned individuals to positively affect their homes, communities, country and world.
We not only encourage Christians to be "salt" and "light", but provide credible strategies for doing so. One of our specific goals is the removal of pornography from the family marketplace where children have access.
Contact A.F.F.
Australian Federation for the Family
c/o Grove Post Office
TAS 7109
Subscribe now to the AFF Action Alert. This is how we communicate with our supporters for issues that require timely action.
Please check your mail after pressing the subscribe button.
Action Manual

redpajama_set_name: RedPajamaCommonCrawl


text:
Q: How to make this REST get method in Java? I have the following REST get Request that works successfully:

The result is a XML document that I then want to parse. I tried the same in Java:
I use the following code:
public void getRootService() throws ClientProtocolException, IOException {

    HttpGet httpGet = new HttpGet("https://localhost:9443/ccm/rootservices");
    httpGet.setHeader("Accept", "text/xml");
    HttpResponse response = client.execute(httpGet);
    HttpEntity entity = response.getEntity();
    InputStream in = entity.getContent();
    String projectURL = XMLDocumentParser.parseDocument(in);

    System.out.println(projectURL);
    HttpGet getProjectsRequest = new HttpGet("https://localhost:9443/ccm/process/project-areas");
    getProjectsRequest.setHeader("Content-Type", "application/xml;charset=UTF-8");
    getProjectsRequest.setHeader("Accept-Charset", "UTF-8");
    getProjectsRequest.setHeader("Accept", "application/xml");

    ResponseHandler<String> handler = new BasicResponseHandler();
    String projectResponse = client.execute(getProjectsRequest, handler);
    //String projectResponse = client.execute(getProjectsRequest, handler);

    System.out.println(projectResponse);

}

But how can I do the authentication? I tried to just add another header field for the value "Authorization" but then I don't get the same result.

A: I think you have to create a UsernamePasswordCredentials, something along the lines of (untested);
CredentialsProvider credsProvider = new BasicCredentialsProvider();
credsProvider.setCredentials(
    new AuthScope("somehost", AuthScope.ANY_PORT),
    new UsernamePasswordCredentials("username", "password"));

HttpClient httpclient = new DefaultHttpClient();
httpclient.setCredentialsProvider(credsProvider);

See http://hc.apache.org/httpcomponents-client-ga/tutorial/html/authentication.html
Edit:
Just tried the following code and successfully called a REST service on our dev environment that is BASIC protected.
public static void main(String[] args) throws ClientProtocolException, IOException {
    CredentialsProvider credsProvider = new BasicCredentialsProvider();
    credsProvider.setCredentials(
        new AuthScope("dev.*******.com", AuthScope.ANY_PORT),
        new UsernamePasswordCredentials("*****", "******"));

    DefaultHttpClient client = new DefaultHttpClient();
    client.setCredentialsProvider(credsProvider);

    String url = "http://dev.******.com:18081/path/to/service/id.xml";

    HttpGet get = new HttpGet(url);
    ResponseHandler<String> handler = new BasicResponseHandler();
    String resp = client.execute(get, handler);

    System.out.println(resp);
  }

A: You can explicitly add Authorization header to HttpRequestBase (an abstract class for HttpGet, HttpPost, etc.)
This example shows how Basic Authorization value is made.
String unhashedString = userName + ":" + password;
String hashedString = Base64.encode(unhashedString); //This class doesn't exist, it's for demonstration purpose only.

HttpGet.setHeader("Authorization", "Basic " + hashedString);

In the server, you will have to do the reverse (if you're doing your own implementation.

A: The way I implemented this is to use the session with a standard HTTP controller. They call a login URL with user and password posted and I authenticate the session. Once that's done then all following URLs simply check to make sure the session is authenticated.

A: The authentication mechanism supported will depend on which web server is used to host Rational Team Concert. The Apache Tomcat server uses basic authentication, whereas, WebSphere Application Server supports both basic authentication and form-based authentication.
You can view the detail description here

redpajama_set_name: RedPajamaStackExchange


The E-TAC is specifically designed to meet the rigorous demands of hospitality, healthcare and specialty residential installations, E-TAC's smart technology puts energy control and savings into your hands. Backed by the longest standard warranty in the industry, the E-TAC series also offers the most complete line of accessories available. Features include a dry mode, pre-programmed set point limits and IR remote capability (Remote Sold Separately). The E-TAC series is the ideal choice for superior performance and energy savings.
• Fits a standard 42-in x 16-in wall sleeve.


text:
The Modern Faerie Tales: Tithe, Valiant, Ironside
Tithe: A Modern Faerie Tale
Ironside: A Modern Faerie Tale
Valiant: A Modern Faerie Tale
Home » The Modern Faerie Tales » Valiant: A Modern Faerie Tale
When seventeen-year-old Valerie runs away to New York City, she's trying to escape a life that has utterly betrayed her. Sporting a new identity, she takes up with a gang of squatters who live in the city's labyrinthine subway system.
But there's something eerily beguiling about Val's new friends. And when one talks Val into tracking down the lair of a mysterious creature with whom they are all involved, Val finds herself torn between her newfound affection for an honorable monster and her fear of what her new friends are becoming.
Valiant was the recipient of the first Andre Norton Award for Young Adult Science Fiction and Fantasy. It was also nominated for the Locus Award and the Mytheopeic Award and was one of the ALA's Best Books for Young Adults.
Black spins a spell of a story weaving adolescent subculture, the dark side of the city, and those glimpses of the shadow side that most of us miss. We might all look more closely to see the sprout of horns or a flash of goat feet, sure that the faerie world is real if only we know how to see.
—KLIATT
…beneath its darkness readers find well-rendered characters, a gripping plot, and pure magic.
This is a powerful book…. I love it when a girl learns how to be Valiant.
—Tamora Pierce, author of the Song of the Lioness quartet
An edgy but ultimately life-affirming read.
—Horn Book


He'd suffered a form of stroke- or the dog equivalent- causing him to lose his ability to walk, sit, drink and even eat. Being my clever boy, Blue started eating and drinking again, after a lot of encouragement; we even had him sitting up. After a long hard struggle, the decision was made to put him to rest.
Despite vast improvements, and his determination, we found that he had also suffered damage to his vision, meaning he couldn't see anything down his left side; also damage to part of his brain which controlled balance. All of this, meant that he would be unlikely to be able to walk again, and as a large Border Collie walking was a necessity.
I can hand on heart say that it was the toughest thing I have ever had to witness, but never would I of let him go through it on his own. If completely honest, part of me believes he should of had more time; that there may of been other therapies that could be tried, however between the vets advice, and family discussions, the decision was made.
He had a strong 14 years and 10months of happy, playful life; I honestly believe he enjoyed what he had. Blue was the centre of the family, loved by all. Its very tough to be home without him now, and I cant see that changing any time soon.
I guess despite all of this; all I really want to say is how much I love my Blue and am going to miss him an unbelievable amount..
Next Post The start of my weight challenge..


text:
Q: How to add dynamically created link in React    moveToListSuccess = (listMovedTo, listMovedId) => {
    const link = <a href={`/mylist?id=${listMovedId}`}>{listMovedTo};
    this.showTopMessage('success', `1 item successfully moved to ${link}`);
    this.getSavedListAction();
}

showTopMessage = (type, message) => {
    this.setState({
        showMessage: true,
        message,
        type,
    });
}

It gives me [Object object] when i try and pass link as a parameter since its string concatenation
When the user clicks the link he/she should navigate to page.

And message is being passed here in render
  {showMessage &&

                <MessageBox showIcon={false} hasClose type={type} level="section" onClose={this.closeMessageBox}>
                    {`${message}`}
                </MessageBox>

}

A: Template literals takes primitive types. It doesn't work well with objects
To fix your problem, use a third argument and pass the link object
moveToListSuccess = (listMovedTo, listMovedId) => {
    const link = <a href={`/mylist?id=${listMovedId}`}>{listMovedTo};
    this.showTopMessage('success', "1 item successfully moved to ",link );
    this.getSavedListAction();
}

i wouldn't recommend this approach, but i've provided solution without changing any of your current flow. Set link object to your state as shown below
showTopMessage = (type, message,link) => {
    this.setState({
        showMessage: true,
        message,
        type,
        link
    });
}

You can render as shown below
{showMessage &&

    <MessageBox showIcon={false} hasClose type={type} level="section" onClose={this.closeMessageBox}>
        {message} {link}
    </MessageBox>

}

A: If U want to display a HTML tag in like a string variable. U can use this lib React render html to render your string html.
import renderHTML from 'react-render-html';

{showMessage &&

   <MessageBox showIcon={false} hasClose type={type} level="section" onClose={this.closeMessageBox}>
       {renderHTML(message)}
   </MessageBox>

}


This booster seat protects floors and carpets from spills and messes during meal time. Find your nearest store of contact our Customer Service team for more information.
This booster comes with a countered seat that offers the ultimate support and comfort, keeping the child focus on their meals. It features a 3-point harness that you can adjusts according to your growing child, a removable insert tray for added convenience during food preparation and cleanup, and bottom and rear chair straps that keeps the booster secure. It is suitable for use between 6 months to 4 years of age.


text:
<resources>
    <string name="app_name">GuessMe</string>
    <string name="action_settings">Настройки</string>
    <string name="regular_files_on_server">Файлов на сервере:</string>
    <string name="connect_fail">Ошибка соединения с сервером</string>
    <string name="welcome_1_part1">Привет,</string>
    <string name="welcome_1_part2">Полли!</string>
    <string name="welcome_2_part1">Вспомни,</string>
    <string name="welcome_2_part2">что было</string>
    <string name="welcome_2_part3">раньше?</string>
    <string name="err_get_image_pair">Не удалось загрузить фоточки :(</string>
    <string name="host_hint">Сервер</string>
    <string name="login_hint">Имя пользователя</string>
    <string name="password_hint">Пароль</string>
    <string name="login_dlg_title">Введите данные для входа</string>
</resources>

redpajama_set_name: RedPajamaGithub


text:
<project xmlns="http://maven.apache.org/POM/4.0.0" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"
  xsi:schemaLocation="http://maven.apache.org/POM/4.0.0 http://maven.apache.org/xsd/maven-4.0.0.xsd">
  <modelVersion>4.0.0</modelVersion>

  <groupId>cn.com.yeemin</groupId>
  <artifactId>drools-study</artifactId>
  <version>0.0.1-SNAPSHOT</version>
  <packaging>pom</packaging>

  <name>drools-study</name>
  <url>http://maven.apache.org</url>

  <properties>
    <project.build.sourceEncoding>UTF-8</project.build.sourceEncoding>
  </properties>

  <modules>
  	<module>drools1</module>
  	<module>drools2</module>
  </modules>

  <dependencies>
    <dependency>
      <groupId>junit</groupId>
      <artifactId>junit</artifactId>
      <version>3.8.1</version>
      <scope>test</scope>
    </dependency>
  </dependencies>
</project>


text:
Governor Ron DeSantis Appoints Jesse Biter to the Sarasota Manatee Airport Authority Board Governor Ron DeSantis Announces $348,400 in Grant Awards to Support Rural Florida Economic Development
Governor Ron DeSantis Appoints Dr. Jonathan Weiss to the Alzheimer's Disease Advisory Committee
On February 12, 2021, in News Releases, Recent Appointments, by Staff
Tallahassee, Fla. — Today, Governor Ron DeSantis announced the appointment of Dr. Jonathan Weiss to the Alzheimer's Disease Advisory Committee.
Dr. Jonathan Weiss
Weiss, of Miami, is Director of Strategic Innovation for INSIGHTEC. Previously, he was Consumer Experience and Loyalty Manager for MetroPlus Healthplan, Director of Rehabilitation for Excellent Home Care and a Physical Therapist for Visiting Nurse Service of New York. He currently serves as Director of the Israel Service Organization and the Focused Ultrasound Neuroscience Research Institute. Weiss earned his bachelor's and master's degrees in physical therapy from Touro College and his doctorate in physical therapy from Utica College.


One attractive strategy to treat cancers is to deliver an exogenous enzyme that will convert a non-toxic compound to a highly toxic derivative. The strategy was tested with viral vectors but was disappointing because the efficiency of transduction into tumor cells was too low. Recent reports demonstrated that the limitation can be addressed by using tissue-derived mesenchymal stromal cells (MSCs) to deliver enzyme/prodrug systems that kill adjacent cancer cells through bystander effects. Here we addressed the limitation that tissue-derived MSCs vary in their properties and are difficult to generate in the large numbers needed for clinical applications. We prepared a Feeder Stock of MSCs from induced pluripotent stem cells (iPSs) that provided an extensively expandable source of standardized cells. We then transduced the iPS-derived MSCs to express cytosine deaminase and injected them locally into a mouse xenogeneic model of human breast cancer. After administration of the prodrug (5-fluorocytosine), the transduced iPS-MSCs both limited growth of preformed tumors and decreased lung metastases.
Among the many strategies suggested for the therapy of cancers is the use of an exogenous enzyme to convert a non-toxic compound to a highly toxic derivative, a strategy referred to as gene-directed enzyme/prodrug therapy (GDEPT).1,2 The strategy was initially introduced with the advent of viral gene therapy in the 1990s and extensively tested over >20 years. However, clinical trials using viral vectors were disappointing. The major limitation was the low efficiency of transduction of tumor cells. Solid tumors were particularly resistant because, even with local injection, the viruses did not transduce many cells beyond the needle track. Subsequently, interest in the GDEPT strategy was revived with the possibility of using cells to deliver either viruses with the critical gene or the prodrug-converting enzyme itself.3 Among the cells that have been most extensively tested are the progenitor cells referred to as mesenchymal stem/stromal cells (MSCs).
Because of these features, MSCs transduced to express suicide or killer genes with bystander effects were used in a series of xenogeneic experiments with cancer cells.4,5 Most of the reports have used MSCs that express thymidine kinase from herpes simplex virus that initiates conversion of ganciclovir or related substrates to phosphorylated derivatives that inhibit DNA synthesis (TK/GCV) or cytosine deaminase (CD) from yeast that converts 5-fluorocytosine to chemotherapeutic agent 5-fluorouracil that is further metabolized within cells and incorporated into DNA and RNA (CD/5-fluorocystine (5-FC)). Of the two, the CD/5-FC system had the advantage that 5-fluorouracil freely diffuses from the transduced cells, whereas phosphorylated ganciclovir metabolites from TK/GCV require gap junctions for transmission to cancer cells,14,15 but combinations of the two systems were more effective for inhibition of resistant cancers in some experimental situations.16 Also, most of the experiments were performed with transduced MSCs co-injected with cancer cells or injected directly into or near preformed tumors. Inhibition of tumor growth was consistently observed. In one report, long-term efficacy in suppressing a melanoma was demonstrated by combing MSCs transduced to express CD with an inhibitor of cMet/hepatocyte growth factor signaling.17 In effect, the results demonstrated that local injection of transduced MSCs overcame the problem of delivering adequate amounts of the prodrug-converting enzyme to tumors. Intravenous (IV) administration was also effective in several reports. Lung metastases produced by IV administration of cancer cells were reduced by IV administration of GDEPT MSCs,16,18 an observation consistent with the evidence that most MSCs are trapped in the lung after IV infusion.19 IV infusions of transduced MSCs were also observed to inhibit growth of cancers injected subcutaneously.20,21 However, the homing of MSCs to cancers is not highly efficient,19 and the IV route raises the possibility that it will lower the therapeutic window for the prodrug because the transduced MSCs trapped in other tissues will generate high local levels of the toxic drug and produce unwanted effects on normal cells.
In effect, multiple reports have established the efficacy of local injections of MSCs as vectors for GDEPT. However, a number of issues will need to be addressed in translating the results obtained in mouse xenogeneic models to patients. Two critical issues are the variability encountered with the tissue-derived MSCs and the need to generate the very large number of MSCs required for many clinical applications.
The variability of tissue-derived MSCs is loosely referred to as 'donor variability',22,23,24,25 but it is observed in bone marrow aspirates obtained from the same donor at the same setting6 and different fat deposits.25 Therefore, part of the variation is a result of unguided sampling of tissues. The variability of the MSCs is not only apparent in their varying yields from tissues but also in in vitro properties that include their rates of proliferation, clonogenicity, potential for differentiation and the extent to which the MSCs can be expanded in culture. The variability is also apparent in the few experiments in which the efficacies of different preparations have been compared quantitatively in animal models.24 Use of biomarkers such as expression of the inflammation-modulating protein TSG-6 may help select optimally effective preparations for some disease targets,24 but the development of biomarkers for MSCs is still in its infancy.
One strategy for overcoming the variability of tissue-derived MSCs is to prepare large banks of MSCs from a single donor. The size of the banks, however, is limited by several biological constraints. High initial yields of MSCs can be obtained from tissues, such as fat, umbilical cord and large bone marrow aspirates. The cells can be further expanded in culture within a biological window that varies among different preparations and with culture conditions. For example, optimal preparations of MSCs from human bone marrow26,27 expand rapidly through about 30-population doublings (230=1 billion fold expansion). Thereafter, their rate of propagation slows and they approach cell cycle arrest in a senescent-like state. Use of MSCs for GDEPT, however, requires both genetically transducing the cells and extensively expanding them after transduction. The combined manipulations of transduction and expansion introduce new sources of variability, such as changes in the properties of the MSCs,23,28 different levels of expression of the transduced gene,15 possible shut-down of the transduced gene or selection for non-transduced cells with expansion, site-directed mutagenesis and alterations that change the survival of the cells in vivo. Such variations pose special problems for use of MSCs in GDEPT, as the transduced MSCs must be titered to both the number of MSCs engrafted and the administered dose of the prodrug in vivo. A number of efforts are still in progress, particularly by start-up biotechnology companies, to develop therapies with large banks of tissue-derived MSCs from single donors, but it is not apparent whether the biological window for the expansion of MSCs may limit their size and therefore their applications to common diseases.
As recently described,9 iPS-derived MSCs were prepared from iPS cells generated from whole blood with episomal vectors. The cells were expanded and differentiated through four steps to obtain iPS-MSCs as defined by the loss of expression of embryonic genes and acquisition of features characteristic of MSCs, including spindle-like morphology, typical surface epitopes, clonogenicity and differentiation to osteoblasts and chondrocytes in culture. The first cultures that satisfied these criteria were designated as passage 0 (P0) iPS-MSCs (Figure 1). P0 iPS-MSCs were stored frozen as a Feeder Bank cells for generation of Master Banks as required.
Schematic representation of the Master Bank cells. iPS-derived MSCs were expanded from the P0 Feeder Bank to generate cells for the P6 Working Bank. Cells from the P6 Working Bank were expanded to P7 cells and then P7 cells were transfected with a lentivirus designed to express genes for CD gene and UPRT (CD::UPRT). As indicated in the text, cells from the P0 Feeder Bank could be expanded about 106-fold to generate cells for the P6 Working Bank as needed.
For the experiments here, the P0 cells from the Feeder Bank were expanded to obtain a P6 Working Bank. For the first five passages, the cells were plated at 500 cells/cm2 and incubated for 3–5 days. The P5 cells were expanded once through a perfusion bioreactor (Quantum; Terumo, Lakewood, CO, USA) to provide the P6 Working Bank. The average fold expansion per passage was 9.5±1.80 S.D., and the average population doublings per passage was 3.26±0.317 S.D. Therefore, the P0 cells in the Feeder Bank could be readily expanded about 106-fold to generate cells for the P6 Working Bank.
To transduce the cells, a construct (Figure 2a) was prepared with the CMV promoter driving expression of CD linked to uridine phosphoribosyl transferase (UPRT), a gene combination shown to enhance the expression of CD.17 The CD::UPRT fusion protein was followed by P2A, a spontaneous protein cleavage site, and a gene encoding copGFP, a GFP-like protein with enhanced fluorescence and decreased toxicity.38 The construct was inserted into a lentiviral vector and the virus used to transduce the iPS-MSCs. Essentially all the cells expressed GFP by UV fluorescence microscopy (Figure 2b). Expression of CD::UPRT was assayed by western blotting (Figure 2c) and the expression of copGFP was verified by RT-PCR (Figure 2d). Of note, there was no evidence of silencing of the exogenous genes as the cells were expanded from passage 9 to passage 19. The cells continued to express GFP as determined by microscopy and both genes as assayed by western blotting analysis (Figures 2c, e and f).
Transduced iPS-MSCs. (a) Map of CMV promotor driving expression of the CD::UPRT genes linked with copGFP by P2A sequence for cleavage of the two proteins after translation. (b) Representative images of iPS-MSCs-CD cells expanded to passage 9 after transduction at passage 7. (c) Western blotting of passage 9 iPS-MSCs-CD cells demonstrated the expression of CD::UPRT together with a small amount of the uncleaved proteins. (d) RT-PCR assays confirmed the expression of the transduced genes. (e) Representative images of iPS-MSCs-CD cells demonstrating the expression of GFP after expansion to passages 12, 14 and 18. The passage 18 cells were killed by incubation for 6 days in the presence of 300 μM 5-FC. (f) Western blotting analyses demonstrated that both the GFP gene and the CD::UPRT genes continued to be expressed as the iPS-MSCs-CD cells were expanded through passage 19. Scale bar: 50 μm.
In initial tests for the efficacy of the transduced cells, we carried out in vitro experiments with an aggressive, triple-negative line of breast cancer cells, HCC1806. As expected, the iPS-MSCs-CDs were killed in the presence of 300 μM 5-FC (Figures 3a–c). However, the HCC1806 cells were not (Figures 3d–f). In co-culture experiments, the HCC1806 cells and the transduced cells (iPS-MSCs-CD/5-FC) were plated in a 1 : 1 ratio and then incubated with or without the 300 μM 5-FC. After 6 days, all the cells in the co-culture were killed (Figure 4).
Effects of 5-FC on iPS-MSCs-CDs and HCC1806 in culture. iPS-MSCs-CDs or HCC1806 were cultured for 6 days with or without 300 μM 5-FC. (a) Photomicrographs of iPS-MSCs-CDs cultured±5-FC. (b) iPS-MSCs-CD cells cultured in the absence of 5-FC. (c) iPS-MSCs-CD cells cultured in the presence of 5-FC. (d) Photomicrographs of HCC1806 (labeled with CellTracker Red) cultured±5-FC. (e) HCC1806 cells cultured in the absence of 5-FC. (f) HCC1806 cells cultured in the presence of 5-FC. Scale bar: 50 μm.
Effects of 5-FC on co-cultures of iPS-MSCs-CD and HCC1806. iPS-MSCs-CD and HCC1806 were co-cultured for 6 days with or without 300 μM 5-FC. (a) Representative microscopic images of co-cultures. (b) Growth curve of co-cultured cells in the absence of 5-FC. (c) Growth curve of co-cultured cells in the presence of 5-FC. (d) Photomicrographs of HCC1806 (labeled with propodium iodide) cultured±5-FC. Scale bar: 50 μm.
To test the efficacy of the transduced cells in killing cancers in vivo, we injected 1 : 1 mixtures of the HCC1806 cells and the transduced iPS-MSCs-CDs into the mammary fat pads of NOD/scid mice (Figure 5a). 5-FC was then injected intraperitoneally (i.p.) daily for 5 days in a dose of either 1.5 or 3 mg per mouse. Control mice were injected with the same mixture of the cells and PBS instead of the prodrug. The control mice developed large tumors (Figures 5b–e) and most had to be killed at 28 days because of deteriorating health. In contrast, mice that were injected with a mixture of the cells together with the prodrug did not develop tumors. None were detected by palpation of the mammary glands during the experiments Figure 5c) and none were detected by dissection of the mammary glands at the end of the experiments (Figures). Similar results were obtained with both doses levels of the prodrug tested. In addition, there was a marked difference in lung metastases. Lung metastases were detected by RT-PCR assays for human glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in five of the five control mice that were injected with the mixture of cells and PBS instead of the prodrug (Figure 5g). In contrast, none were detected with the same assay in 10 mice that received the mixture of cells and either dose of the prodrug (P<0.0003, two-tailed Fisher's Exact test).
Effects on tumor growth in mice receiving co-injections of iPS-MSCs-CD and HCC1806. A mixture of 1×106 HCC1806 cells and 1×106 iPS-MSCs-CD were injected into a fourth mammary fat pad of each mouse and then 5-FC or PBS was injected i.p. for 5 consecutive days. (a) Schematic representation of the experiment. (b) Representative images of the mammary glands from treated and control mice before and after killing followed by exposure of the fat pad. (c) Growth curve of the tumor burden for 25 days in mice that received PBS instead of 5-FC. (d) Tumor volume of the treated and control groups on day 28. (e) Tumor weight of the treated and control groups on day 28. (f) Body weights of mice from the treated and control groups on day 28. (g) RT-PCR assays for human GAPDH signal in the mice lungs of the treated and control groups on day 28. (h) Excised tumors of control mice on day 28. Mean (±S.E.M.) tumor growth over time in mice (n=5–6 per group) injected with tumor cells and treated as indicated (***P<0.001; NS, not significant).
To test efficacy of the strategy further, we injected HCC1806 cells into the mammary fat pads of the mice and waited for 10 days for the tumors to develop to a size detectable by palpation (Figure 6a). We then injected the transduced iPS-MSCs-CDs into the tumor or adjacent tissue in the same fat pad. I.p. administration of either dose of the prodrug decreased the size of the tumors as detected by palpation during the course of the experiment (Figure 6c). Either dose also decreased the volume and weight of the tumors at the end of the experiment (Figure 6d). Again, there was a marked difference in lung metastases. Assays by RT-PCR for human GAPDH indicated that all four control mice that received PBS instead of the prodrug developed lung metastases (Figure 7). In contrast, the same assays on lungs of seven mice that received either dose of the prodrug did not detect the levels of human GAPDH that differed from the background obtained with control lungs from mice that did not receive any cell injections (Figure 7; P<0.003, two-tailed Fisher's Exact test).
Effects of injecting iPS-MSCs-CD cells into preformed tumors. HCC1806 (1×106) injected into the fat pads of mice and tumors were allowed to grow for 10 days. Then iPS-MSCs-CD (1×106) were injected into the same fat pad or adjacent tissue followed by five daily i.p. injections of 5-FC or PBS. (a) Schematic representation of the experiment. (b) Representative images of the tumor in the treated and control groups. (c) Tumor burden overtime for 24 days in the treated and control groups. (d) Tumor volume of the treated and control groups on day 26. (e) Tumor weight of the treated and control groups on day 26. (f) Body weight of the anaimals of the treated and control groups on day 26. Mean (±S.E.M.) tumor growth over time in mice (n=6–7 per group) injected with tumor cells and treated as indicated (*P<0.05; **P<0.01; NS, not significant).
Effects on lung metastases of injecting iPS-MSCs-CD cells into preformed mammary tumors. Assays were performed on the lungs from mice from the experiment described in Figure 6. (a) RT-PCR for human GAPDH in the lungs of the treated and control groups on day 26. (b) Real time RT-PCR assays of human GAPDH in the lungs of the treated and control groups on day 26. (c) Representative images of the whole lung, and H&E-stained sections from the treated and control groups. Tumor nodule-rich areas are encircled (blue) in the control group, while the treated groups shows significant inhibition of lung metastases. Mean (±S.E.M.) tumor growth over time in mice (n=6–7 per group) injected with tumor cells and treated as indicated (**P<0.01; NS, not significant), Scale bar: 50 μm.
As demonstrated by multiple recent publications,4,5 MSCs are attractive vectors for delivering prodrug-converting enzymes to cancers. However, several issues must be addressed before the results can be translated to patient therapies. The data presented here address the critical issue of how to prepare an essentially unlimited number of MSCs with invariant properties that are effective for GDEPT.
iPS-derived MSCs have several features that may make them attractive for some therapeutic applications.9 The use of a Feeder Bank as defined here (Figure 1) makes it possible to generate an expandable number of cells that have uniform characteristics. The iPS-derived MSCs were readily transduced with a lentivirus to express levels of CD high enough to produce effective killing of breast cancer cells through a bystander effects both in culture and in vivo. Moreover, the transduced genes continued to be expressed through 10 additional passages. Therefore, the protocol, with some minor adjustments, provides a means of providing the large number of transduced cells required for clinical applications.
When co-injected with cancer cells followed by the prodrug, the iPS-MSCs-CD inhibited development of detectable tumors. In addition, the iPS-MSCs-CD were effective even if injected into preformed tumors. The effectiveness was apparent not only by a decrease in tumor size but also by an inhibition of lung metastases. Also of importance was the observation that the injected iPS-MSCs quickly disappeared from the tumors, even without administration of the prodrug. Therefore, the cells are unlikely to cause any adverse events.
The results support previous observations that local injection of the MSCs transduced to express CD followed by 5-FC may be useful as an adjunct therapy for some patients with cancer.4,5 In the case of breast cancers, the strategy may be appropriate for two subpopulations of patients who do not elect surgery or other inventions: those with very early growths and those with advanced metastatic disease. If desirable, the strategy pursued here could be expanded to introduce the CD gene into safe harbors in the genome with CRISPR/Cas9 or similar strategies36,37 to minimize the risk of insertional mutagenesis and to reduce further the possibility of gene silencing as the cells are expanded.
All animal procedures were approved by the Institutional Animal Care and Use Committee (IACUC) at Texas A&M Health Science Center College of Medicine at Scott & White and conformed to the requirements of the Animal Welfare Act. Female 6–8-week-old NOD/scid obtained from Jackson Laboratory (Bangor, ME, USA) were used for this study. The mice were kept on a 12-h light–dark cycle.
iPS-MSCs were prepared as described previously.9 P3 iPS-MSCs were expanded in culture plasticware to obtain a P4 Master Bank. Cells from the P4 Master Bank were expanded through a further passage in culture plasticware or a final passage in a perfusion bioreactor (Quantum; Terumo), to generate a P6 Working Bank. Further expansion was on plasticware.
For each expansion, viable cells were recovered from frozen vials of about one million cells by thawing the vials and incubating them overnight in 15 cm diameter dishes and in Complete Culture Medium for MSCs (CCM). The CCM19 contained alpha-MEM (Gibco-BRL, Rockville, MD, USA), 17% FBS (lot selected for rapid growth; Atlanta Biologicals, Norcross, GA, USA), 1% penicillin and 100 μg/ml streptomycin and supplemented with either 2 mM L-glutamine or GlutaMAX (Gibco). The cultures were washed with PBS, and adherent cells were lifted with 0.25% trypsin and 1 mM EDTA at 37 °C for 1 to 3 min. For expansion on plasticware, the cells were plated at about 500 cells/cm2 in CCM. The medium was replaced after 3 days, and the cells were harvested when the cultures were 70–90% confluent in 4–5 days. During the passages, the fold expansion varied from 16.3 to 29 and the population doublings from 4.0 to 4.9. Expansion in automated, closed and single-use Quantum Cell Expansion System bioreactor provided by Terumo BCT was performed in accordance with Termumo BCT standard protocols unless otherwise stated. After coating the inner circulatory system with tissue culture grade fibronectin (Sigma), 15×106 cells were loaded onto the inner chamber of the bioreactor to achieve a theoretical density of 500 cells/cm2. The cells were allowed to attach for 24 h with inversion of the hollow fiber bioreactor and cultured in CCM containing a stabilized glutamine supplement (Glutamax, Thermo Fisher, Waltham, MA, USA), at an initial media replenishment rate of 0.1 ml/min. During the culture period, media replenishment was gradually raised to 0.8 ml/min to prevent lactate concentrations reaching 8 mmol/l. The cells were harvested on day 5 by 15 min of exposure to a commercially available trypsin replacement (TrypLE, Thermo Fisher). The fold expansion was 4.8 and the population doubling was 2.7.
Lentiviral constructs (System Biosciences, Mountain View, CA, USA) were based on a third-generation lentiviral vector modified with an insert that contained the CMV promoter driving the expression of CD/UPRT (17; InvivoGen, San Diego, CA, USA) combined with copGFP by P2A sequence.
The lentiviral vectors were generated in HEK293T cells after transient transfection with the X-tremeGENE HP DNA Transfection reagent (Roche, Mannheim, Germany, Cat. No. 06366244001) and lentivector CD, pPACKH1 packaging mix plasmids (SBI, Mountain View, CA, USA, Cat. No. LV500A-1). Lentivirus-containing medium was collected after transfection for 2 days, and cellular debris was cleared by low-speed centrifugation at 1500×g for 5 min. The collected medium was concentrated with the PEG-it virus precipitation solution (SBI, catalog number LV810A-1), and pellets containing viral particles were resuspended with PBS. Lentiviral titers were measured with the Lenti-X qRT-PCR Titration Kit (Clontech, Mountain View, CA, USA, catalog number 631235).
The iPS-MSCs in fresh culture medium were seeded 1×105 cells per well in triplicate in six-well plates. Prior to transfection, the cells were incubated for 24 h at 37 °C in a humidified incubator in an atmosphere of 5–7% CO2. The culture medium was replaced with 1 ml fresh medium containing 100 μg/ml of sterile-filtered protamine sulfate (catalog no. P4020-1G; Sigma-Aldrich, St Louis, MO, USA). The cells were infected with multiplicity of infection (MOI) 10, for 24 h, at 37 °C, and this step was repeated with an MOI of 10 for a further 24 h to achieve maximum transfection efficiency.39 After 48 h and two rounds of transduction, the cells were trypsinized and plated at 500 cells/cm2 in T175 cm2 flasks in MSC culture medium. The fresh culture medium was changed three times a week. After expansion to about 70% confluency in about 5 days, the cells were lifted with trypsin/EDTA and expanded further under the same conditions.
The mRNA (1 μg) was converted to cDNA using the High Capacity cDNA Reverse Transcription Kit (Applied Biosystems, Foster city, CA, USA). The expression of specific mRNAs was assayed using fluorescence-based real-time quantitative PCR (qPCR). qPCR reactions were performed using Fast or SYBR Green PCR Master Mix (Applied Biosystems) in triplicates for each sample. GAPDH was chosen as the reference gene. The amplification cycles were 95 °C for 5 s, 60 °C for 20 s and 72 °C for 15 s for copGFP and CD::UPRT, while the amplification cycles were 95 °C for 20 s, 95 °C for 2 s and 60 °C for 20 s for GAPDH and 18s. Primer probe numbers were catalog number Hs00266705_g1 for human GAPDH (Life Technologies); catalog number 4333760F for 18s eukaryotic endogenous control labeled with FAM probe (Applied Biosystems). Self-designed primers were used for the detection of copGFP with forward primer sequence 5′- CAGCGTGATCTTCACCGACAAG-3′ and reverse primer sequence 5′- GTCCACCACGAAGCTGTAGTAG-3′, with amplicon size 142 bp and for the detection of CD::UPRT gene, the forward primer sequence was 5′- CCTGGGACTCTACACCATCATC-3′ and reverse primer sequence was 5′- GTCAGTCTCCACAATCTGCTTCTG-3′, with amplicon size 139 bp. The SYBR Green master mix (Applied Biosystems) was used for the amplification of copGFP and CD::UPRT gene. At the end of the assay, a melting curve was constructed to evaluate the specificity of the reaction. All quantitative real-time PCR reactions were performed and analyzed using the StepOne Plus Real-Time PCR System (Applied Biosystems) with the comparative ∆∆Ct method.
In the co-culture experiments, the iPS-MSCs-CD cells were labeled with copGFP while HCC1806 cells were labeled with CellTracker Red (catalog number C34552, Thermo Fisher Scientific, Waltham, MA, USA) as recommended by the manufacturer. Very briefly, cells were washed with PBS and 10 μM dye was added to one million cells for 30 min. Afterwards, the unattached dye was removed by PBS washing and centrifugation. For the detection of dead cells, propidium iodide dye (catalog number P3566, Thermo Fisher Scientific) or trypan blue dye (catalog number 15250061, Thermo Fisher Scientific) was used according to the manufacturer's instructions.
Mice were anesthetized with 3% isoflurane in 100% oxygen until anesthetized and killed by i.p. injections of a solution of 80 mg/kg of ketamine and 8 mg/kg of xylazine. Formalin-fixed, paraffin-embedded lung tissues were cut into 8 μm thick sections, stained with hematoxylin/eosin and evaluated by light microscopy.
Protein isolation was performed by cell lysis using RIPA buffer (Sigma-Aldrich) in the presence of protease inhibitors (Roche). Proteins were resolved by electrophoresis on 12% sodium dodecyl sulfate-polyacrylamide gels and transferred onto polyvinylidene fluoride membranes (Hybond-P, Thermo Fisher Scientific). After blocking in PBS containing 0.1% Tween 20 (PBS-T) supplemented with 3% bovine serum albumin for 1 h, membranes were incubated with the following primary antibodies at 4 °C overnight: anti-β actin (catalog number A1978; Sigma-Aldrich), anti-TurboGFP (catalog number PA5-22685; Life Technologies) and CD (catalog number. CD PA1-85365; Thermo Fisher Scientific). Subsequently, membranes were rinsed with PBS-T and incubated with the species-specific horseradish peroxidase-coupled secondary antibodies (dilution 1 : 10000; Jackson ImmunoResearch Laboratories, West Grove, PA, USA) for 1 h at room temperature. Blots were developed using enhanced chemoluminescence reagents (SuperSignal, Thermo Scientific) and the ChemiDoc XRS+ system (Bio-Rad, Hercules, CA, USA).
In one experiment, the HCC1806 breast cancer cells (1×106) and iPS-MSCs (1×106) were co-injected into the fourth mammary fat pad of 6–8-week-old NOD/scid mice, followed by i.p. injection of 3.0 or 1.5 mg of 5-FC in 1.0 ml PBS for 5 consecutive days (treated group). The control group received i.p. injections of PBS. The tumor size was determined every 3 days with a vernier caliper. After 28 days, the mice were killed and the tumors were excised and weighed. Tumor volume was calculated by using the formula: tumor volume (mm3)=1/2 length (mm)×width (mm)2.40 In another set of experiments, 1×106 HCC1806 cells were injected into the mammary fat pad of 6–8-week-old NOD/scid mice to develop tumors first. After 10 days, 1×106 iPS-MSCs transduced with the CD gene were injected into the tumors or adjacent tissue. On the same day, 5-FC injections were started and continued for 5 consecutive days. After 26 days, the tumors were harvested, weighed and size measured as above.
Student's t-test was used to compare two groups. One-way ANOVA was used to compare several groups using GraphPad Prism 5 (GraphPad Software, San Diego, CA, USA). Comparison of tumor frequency between the experimental and control groups was analyzed by a two-tailed Fisher's Exact test. All in vitro experiments were carried out in triplicate unless specified. P<0.05 was considered statistically significant.
Portsmouth D, Hlavaty J, Renner M. Suicide genes for cancer therapy . Mol Aspects Med 2007; 28: 4–41.
Dachs GU, Hunt MA, Syddall S, Singleton DC, Patterson AV. Bystander or no bystander for gene directed enzyme prodrug therapy . Molecules 2009; 14: 4517–4545.
Pereboeva L, Komarova S, Mikheeva G, Krasnykh V, Curiel DT. Approaches to utilize mesenchymal progenitor cells as cellular vehicles . Stem Cells 2003; 21: 389–404.
Amara I, Touati W, Beaune P, de Waziers I. Mesenchymal stem cells as cellular vehicles for prodrug gene therapy against tumors . Biochimie 2014; 105: 4–11.
Ďuriniková E, Kučerová L, Matúšková M. Mesenchymal stromal cells retrovirally transduced with prodrug-converting genes are suitable vehicles for cancer gene therapy . Acta Virol 2014; 58: 1–13.
Prockop DJ, Kota DJ, Bazhanov N, Reger RL. Evolving paradigms for repair of tissues by adult stem/progenitor cells (MSCs) . J Cell Mol Med 2010; 14: 2190–2199.
Keating A.. Mesenchymal stromal cells: new directions . Cell Stem Cell 2012; 10: 709–716.
Miletic H, Fischer Y, Litwak S, Giroglou T, Waerzeggers Y, Winkeler A et al. Bystander killing of malignant glioma by bone marrow-derived tumor-infiltrating progenitor cells expressing a suicide gene . Mol Ther 2007; 15: 1373–1381.
Zhao Q, Gregory CA, Lee RH, Reger RL, Qin L, Hai B et al. MSCs derived from iPSCs with a modified protocol are tumor-tropic but have much less potential to promote tumors than bone marrow MSCs . Proc Natl Acad Sci USA 2015; 112: 530–535.
Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW et al. Mesenchymal stem cells within tumor stroma promote breast cancer metastasis . Nature 2007; 449: 557–563.
Kucerova L, Kovacovicova M, Polak S, Bohac M, Fedeles J, Palencar D et al. Interaction of human adipose tissue-derived mesenchymal stromal cells with breast cancer cells . Neoplasma 2011; 58: 361–370.
Sanchez CG, Penfornis P, Oskowitz AZ, Boonjindasup AG, Cai DZ, Dhule SS et al. Activation of autophagy in mesenchymal stem cells provides tumor stromal support . Carcinogenesis 2011; 32: 964–972.
Sharma RR, Pollock K, Hubel A, McKenna D.. Mesenchymal stem or stromal cells: a review of clinical applications and manufacturing practices . Transfusion 2014; 54: 1418–1437.
Ryu CH, Park KY, Kim SM, Jeong CH, Woo JS, Hou Y et al. Valproic acid enhances anti-tumor effect of mesenchymal stem cell mediated HSV-TK gene therapy in intracranial glioma . Biochem Biophys Res Commun 2012; 421: 585–590.
Nouri FS, Wang X, Hatefi A.. Genetically engineered theranostic mesenchymal stem cells for the evaluation of the anticancer efficacy of enzyme/prodrug systems . J Control Release 2015; 200: 179–187.
Matuskova M, Kozovska Z, Toro L, Durinikova E, Tyciakova S, Cierna Z et al. Combined enzyme/prodrug treatment by genetically engineered AT-MSC exerts synergy and inhibits growth of MDA-MB-231 induced lung metastases . J Exp Clin Cancer Res 2015; 34: 33.
Kucerova L, Skolekova S, Demkova L, Bohovic R, Matuskova M. Long-term efficiency of mesenchymal stromal cell-mediated CD-MSC/5FC therapy in human melanoma xenograft model . Gene Ther 2014; 21: 874–887.
Zhang TY, Huang B, Yuan ZY, Hu YL, Tabata Y, Gao JQ. Gene recombinant bone marrow mesenchymal stem cells as a tumor-targeted suicide gene delivery vehicle in pulmonary metastasis therapy using non-viral transfection . Nanomedicine 2014; 10: 257–267.
Lee RH, Pulin AA, Seo MJ, Kota DJ, Ylostalo J, Larson BL et al. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6 . Cell Stem Cell 2009; 5: 54–63.
Kucerova L, Altanerova V, Matuskova M, Tyciakova S, Altaner C. Adipose tissue-derived human mesenchymal stem cells mediated prodrug cancer gene therapy . Cancer Res 2007; 67: 6304–6313.
Kucerova L, Matuskova M, Pastorakova A, Tyciakova S, Jakubikova J, Bohovic R et al. Cytosine deaminase expressing human mesenchymal stem cells mediated tumour regression in melanoma bearing mice . J Gene Med 2008; 10: 1071–1082.
Phinney DG, Kopen G, Righter W, Webster S, Tremain N, Prockop DJ. Donor variation in the growth properties and osteogenic potential of human marrow stromal cells . J Cell Biochem 1999; 75: 424–436.
Siddappa R, Licht R, van Blitterswijk C, de Boer J. Donor variation and loss of multipotency during in vitro expansion of human mesenchymal stem cells for bone tissue engineering . J Orthop Res 2007; 25: 1029–1041.
Lee RH, Yu JM, Foskett AM, Peltier G, Reneau JC, Bazhanov N et al. TSG-6 as a biomarker to predict efficacy of human mesenchymal stem/progenitor cells (hMSCs) in modulating sterile inflammation in vivo . Proc Natl Acad Sci USA 2014; 111: 16766–16771.
Russo V, Yu C, Belliveau P, Hamilton A, Flynn LE. Comparison of human adipose-derived stem cells isolated from subcutaneous, omental, and intrathoracic adipose tissue depots for regenerative applications . Stem Cells Transl Med 2014; 3: 206–217.
Colter DC, Class R, DiGirolamo CM, Prockop DJ. Rapid expansion of recycling stem cells in cultures of plastic-adherent cells from human bone marrow . Proc Natl Acad Sci USA 2000; 97: 3213–3218.
Larson BL, Ylostalo J, Lee RH, Gregory C, Prockop DJ. Sox11 is expressed in early progenitor human multipotent stromal cells and decreases with extensive expansion of the cells . Tissue Eng Part A 2010; 16: 3385–3394.
Digirolamo CM, Stokes D, Colter D, Phinney DG, Class R, Prockop DJ. Propagation and senescence of human marrow stromal cells in culture: a simple colony-forming assay identifies samples with the greatest potential to propagate and differentiate . Br J Haematol 1999; 107: 275–281.
Jung Y, Bauer G, Nolta JA. Concise review: Induced pluripotent stem cell-derived mesenchymal stem cells: progress toward safe clinical products . Stem Cells 2012; 30: 42–47.
Phillips MD, Kuznetsov SA, Cherman N, Park K, Chen KG, McClendon BN et al. Directed differentiation of human induced pluripotent stem cells toward bone and cartilage: in vitro versus in vivo assays . Stem Cells Transl Med 2014; 3: 867–878.
Yang H, Aprecio RM, Zhou X, Wang Q, Zhang W, Ding Y et al. Therapeutic effect of TSG-6 engineered iPS-derived MSCs on experimental periodontitis in rats: a pilot study . PLoS One 2014; 9: e100285.
Liu J, Chen W, Zhao Z, Xu HH. Effect of NELL1 gene overexpression in iPS-MSCs seeded on calcium phosphate cement . Acta Biomater 2014; 10: 5128–5138.
Hynes K, Menicanin D, Mrozik K, Gronthos S, Bartold PM. Generation of functional mesenchymal stem cells from different induced pluripotent stem cell lines . Stem Cells Dev 2014; 23: 1084–1096.
Tang M, Chen W, Liu J, Weir MD, Cheng L, Xu HH. Human induced pluripotent stem cell-derived mesenchymal stem cell seeding on calcium phosphate scaffold for bone regeneration . Tissue Eng Part A 2014; 20: 1295–1305.
Boreström C, Simonsson S, Enochson L, Bigdeli N, Brantsing C, Ellerström C et al. Footprint-free human induced pluripotent stem cells from articular cartilage with redifferentiation capacity: a first step toward a clinical-grade cell source . Stem Cells Transl Med 2014; 3: 433–447.
Doudna JA, Charpentier E. Genome editing. The new frontier of genome engineering with CRISPR-Cas9 . Science 2014; 346: 1258096.
Peng R, Lin G, Li J. Potential pitfalls of CRISPR/Cas9-mediated genome editing . FEBS J 2015; 283: 1218–1231.
Shagin DA, Barsova EV, Yanushevich YG, Fradkov AF, Lukyanov KA, Labas YA et al. GFP-like proteins as ubiquitous metazoan superfamily: evolution of functional features and structural complexity . Mol Biol Evol 2004; 21: 841–850.
Lin P, Lin Y, Lennon DP, Correa D, Schluchter M, Caplan AI. Efficient lentiviral transduction of human mesenchymal stem cells that preserves proliferation and differentiation capabilities . Stem Cells Transl Med 2012; 1: 886–897.
Sancéau J, Poupon MF, Delattre O, Sastre-Garau X, Wietzerbin J. Strong inhibition of Ewing tumor xenograft growth by combination of human interferon-alpha or interferon-beta with ifosfamide . Oncogene 2002; 21: 7700–7709.
The research was supported in part by NIH grant P40OD011050 and grant RP150637 from the Cancer Prevention and Research in Texas foundation. We thank Terumo BCT for provision of the Quantum Cell Expansion System and associated consumables. We also thank Terumo BCT personnel for their assistance during the expansion procedures.
DJP is chair of the scientific advisory committee and has a small equity position in a biotech company (Temple Therapeutics LLC) with an interest in MSCs. The remaining authors declare no conflict interest.
Correspondence to D J Prockop.


The Areias do Seixo Charme Hotel is definitely the spot to be if you are traveling to Lisbon. The Penthouse Suites consist of 3 bedrooms, living, open fireplace, outdoor Jacuzzi and Barbecue.
The Areias do Seixo Charme Hotel is also very eco-friendly, they have installed geothermal technologies throughout the hotel to heat and cool the water and they plan on installing solar energy in the near future.
This beautiful spa has two treatment rooms, sauna, turkish bath, outdoor heated pool, and relaxation room to really relax you as you are enjoying the beautiful weather and scenery of Portugal.
Question: Does it matter to you if a hotel is eco-friendly?


Dollhouse Miniature Thanksgiving Turkey Cookies - Half Dozen - 1:12 Dollhouse Miniature - The Petite Provisions Co.
Thanksgiving turkeys never looked so cute! These are a half-dozen adorable iced cookies for Thanksgiving! Whether you have a dollhouse or just love all things tiny, these bite-sized iced cookies are too cute to resist!
6 iced Thanksgiving turkey cookies.
Each cookie is approximately 3/8″ in diameter.


In previous blog posts, we've talked about how important it is to track your food intake http://www.methodyyc.com/flexible-dieting-good-for-the-soul/. Training is no different.
The majority of gym-goers exercise with no specific program or do not track their workouts. If you value your time and are serious about progressing (which I know you are), you need to stop doing this.
Nutrition and training go hand-in-hand and they both require continued progression. If you're not tracking, then how do you know where you're at, so you can make changes to your routine and progress?
You're likely guessing how much weight to lift, how many reps and sets you should be performing, or in the case of nutrition, how many calories you should cut. You may get some initial results off the start doing it this way, but you'll be spinning your wheels from here on out.
Don't waste your own time. You need to have a personalized program that aligns with your specific goals. Then, you need to track your workout (weight, sets and reps). To progress, you want volume to increase over time (sets x reps x weight).
That means you need to either focus on lifting the same amount of weight for more sets or reps over time, or lift heavier weights for the same amount of sets and reps over time. Ideally you'd like to see your overall volume increasing on a weekly basis.
The only way you'll be able to see yourself progress is if you keep a steady and consistent workout routine. If you go to the gym four times per week and then skip a whole week, you're not going to get the results you're after.
This all may seem like a lot of work, but so is all the time and effort you put in at the gym. Make that time and effort count.
At Method Fitness, we take all of that work out of our clients' hands. We build individualized programs based on specific goals, track every single workout and hold clients accountable to their goals. Contact us for more information.


The FAITH Coalition will host Emmy award winner, author and HIV/AIDS advocate Marvelyn Brown for "Lift Every Voice: on Faith, Hope and Facing HIV/AIDS" Saturday, June 6 at 4 p.m. at the Beck Cultural Exchange Center, 1927 Dandridge Ave.
The event is free and open to the public. Set Apart Praise Ministry from the Lomax Temple AME Zion Church will also perform. After the program, Samaritan Ministry and the Knox County Health Department will provide free HIV testing, conducted by swabbing the mouth. Brown will sign copies of her book "The Naked Truth: Young, Beautiful and (HIV) Positive." Refreshments will be served.
This event is presented by the FAITH Coalition. Other sponsors include the Knox County Health Department Teen Health Empowerment Program, Beck Cultural Exchange Center, Tennessee Department of Health, Knoxville District AME Zion Church, Austin High School Class of 1964, Central Baptist Church of Bearden, East Tennessee AIDS Fund, Samaritan Ministry, Smoky Mountain Hospice, Tennessee Valley Unitarian Universalist Church, HOPE Center, Walgreens and KAPPI.


text:
NTARUPT
Interested in helping NTARUPT? Follow the steps below!
Ntarupt relies on the generous support of individuals, private businesses, foundations and local funding sources to make a difference in our North Texas' teen birth rates. Achieving reductions in teen birth rates will take a sustained commitment and investment in young people.
Make Your Voice Heard
Make sure your voice is heard by those in control of our policies and finances. Download the document below to find and contact your representative.
Let Us Speak To You
Let us speak at your gathering. The Ntarupt team is available to educate North Texas on how many teens are giving birth in North Texas, how it effects their lives, their children's lives and costs the public, and solutions including advocacy of local, state and federal officials
Ntarupt uses volunteers to help at events and for very targeted work. We need you to help us spread the word, help with events and more.
Come To Our Events
Providing 12 months of birth control pills at once is beneficial, new research says
https://www.usatoday.com/story/news/nation/2019/07/08/birth-control-12-months-pills-gives-women-autonomy-research-says/1669149001/?utm_source=Master+List&utm_campaign=4128fc76f1-EMAIL_CAMPAIGN_2019_6_25_COPY_01&utm_medium=email&utm_term=0_0ac484edbc-4128fc76f1-215694577
Help our mission by donating.
Funding for this website was made possible in part, by Grant No. 5TP1AH000094-04-00 from the Office of Adolescent Health. The views expressed in materials, resources or publications do not necessarily reflect the official policies of the Department of Health and Human Services nor does mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government.


Environmental Protection Vinyl Floor, Environmental ... Environmental Protection Vinyl Floor, ... The top supplying country is China (Mainland), which supply 100% of environmental protection vinyl floor respectively.
KWMChina's 13th Five Year Plan: Environment China's 13th Five Year Plan promotes a cleaner and greener economy, with strong commitments to environmental management and protection.
VOC RegulationEnvironmental Protection Department Environmental Protection Department,content ... multi-purpose lubricants, floor ... Notification Letters to Importers and Manufacturers about the VOC Regulation.
China's 13th Five-Year Plan for Ecological & Environmental ... As of 2015, 66% of China's surface water reached this grade. ... The establishment of a new environmental protection tax is also mentioned in the plan.
China Begins Enforcing Newly Amended Environmental ... The Environmental Protection Law (the EPL) of the People's Republic of China (PRC) was promulgated more than 25 years ago.


text:
The £1billion secret
Published by The Mail on Sunday (11th December, 2016)
The Prime Minister's most senior security adviser has told MPs £1.1 billion of foreign aid spending should be 'kept secret' and only discussed in private.
Sir Mark Lyall Grant also refused to rule out dispersing chunks of the Conflict, Stability and Security Fund that he oversees in countries that use torture.
This new fund was launched last year with more than five times the budget of its predecessor, as part of the Government's move to pour aid into the world's most fragile states and conflict zones.
But it has sparked controversy over handing cash to countries such as Saudi Arabia and Bahrain, where the Foreign Office is spending £2.1 million on the security sector, despite claims of torture.
The CSSF also uses taxpayers' cash to train security officials in Ethiopia, a one-party state holding a British father of three without charge. The country also jails journalists and kills pro-democracy protesters.
Last year a Cabinet row erupted to force the cancellation of a £5.9 million training contract for Saudi prisons in one of the world's most barbaric justice systems.
Despite this, at a summit last week Mrs May told Gulf rulers, including those in Bahrain and Saudi Arabia, that Britain was their 'partner of choice'.
Now it has emerged that Sir Mark, the Prime Minister's national security adviser, told a joint committee on national security strategy two weeks ago that some of the CSSF's 97 projects were 'clearly secret' and they did not want them discussed in public.
He even rejected publication of strategies for individual countries as it might 'offend' those without one, but admitted it was hard to prove impact.
Julian Lewis, chairman of the Defence Select Committee, asked if they should 'tear up the fiction that we are in any way able to hold you to account as to how you are spending this very large sum of money.'
Sir Mark responded by suggesting they 'meet in private' so he could 'share more information'. The former diplomat added that the committee could keep its oversight role and examine spending only if there were private sessions to ensure 'things that need to be kept secret can be kept secret'.
Astonishingly, he accepted it was 'reasonable to assume' there would be 'human rights questions' in some of the 40 countries in which they were spending money, adding that the definition of a questionable human rights record left 'rather a lot of scope for interpretation'.
The rapid spending increase is part of the Government's aim to hit the UN target of spending 0.7 per cent of national income on aid.
Dr Lewis said last night he was alarmed to discover MPs could not monitor such a big slice of the £12 billion aid budget. 'I was surprised by the way large sums are being disposed of in such an unsupervised style,' he said.
There was also an angry response from human rights groups fighting to stop aid going to foreign forces involved in abuses. 'This shadowy fund provides support to security forces in countries where dissidents are routinely arrested, tortured and sentenced to death,' said Harriet McCulloch of Reprieve, which fights against the death penalty.
'It is little surprise that the Government is so keen to draw a veil of secrecy over this programme. They must urgently commit to greater transparency about overseas security spending.'
Last year, it was disclosed that Britain was spending £185 million on foreign police forces in places such as Bangladesh, Congo and Nigeria, despite cuts to domestic forces. Yet even as spending in fragile states was ramped up, the official watchdog criticised UK efforts to promote security and justice for overambitious targets, poor focus and 'naive' repetition of failed initiatives.
'The problem is too much money and too much ambition,' said one former military officer engaged in the sector. 'This results in a lack of credible strategy.'
The source said that officials refused to accept criticism of schemes, adding: 'The public would be upset to see how much of this money is being spent on the ground 'It is not strengthening our national security.'
A Government spokeswoman said the CSSF would publish its first annual report next year and planned to increase 'accessibility of project information'. She added Britain sought to play a leading role in the world to bring about 'positive changes' and protecting human rights was 'a key part' of the fund's role.
Water wars as day zero looms
Europe's Alcatraz: why the continent's most liberal nation plans to dump refugees on a r...
Our image of Africa is hopelessly obsolete
Cash for terror: how the Palestinian Authority duped British backers
Africa's leaders look to move beyond control and charity of aid
A monstrous crime against humanity
Tags: aid, Julian Lewis, Mark Lyall Grant, MoS
Categorised in: Aid & development, home page


text:
Раннє Середньовіччя. Епоха вікінгів. Реконкіста.

У Східній Римській імперії продовжується правління Михаїла I Рангаве. Імператор Заходу Карл Великий править Франкським королівством. Північ Італії належить Франкському королівству, Рим і Равенна під управлінням Папи Римського, герцогства на південь від Римської області незалежні, деякі області на півночі та на півдні належать Візантії. Піренейський півострів окрім Королівства Астурія займає Кордовський емірат. В Англії триває період гептархії. Існують слов'янські держави: Карантанія, як васал Франкського королівства, та Перше Болгарське царство.

Аббасидський халіфат очолює аль-Амін. У Китаї править династія Тан. Велика частина Індії під контролем імперії Пала. В Японії триває період Хей'ан. Хозарський каганат підпорядкував собі кочові народи на великій степовій території між Азовським морем та Аралом. Територію на північ від Китаю займає Уйгурський каганат.

На території лісостепової України в IX столітті літописці згадують слов'янські племена білих хорватів, бужан, волинян, деревлян, дулібів, полян, сіверян, тиверців, уличів. У Північному Причорномор'ї співіснують різні кочові племена, зокрема булгари, хозари, алани, тюрки, угри, кримські готи. Херсонес Таврійський належить Візантії.

Події
 Візантійський василевс Михаїл I Рангаве та Карл Великий підписали мирну угоду, за якою Візантія визнала Карла імператором, але отримала у своє володіння Венецію, Далмацію та Істрію. Венеція отримала дуже вигідне становище між Сходом та Заходом. Заснована Тосканська марка.
 Булгари на чолі з Крумом спустошили Фракію. Облога Дебелта.
 Аль-Мамун взяв в облогу Багдад.
 Королем Італії став Бернард, позашлюбний син Піпіна Італійського.
 Франки взяли Памплону й підкорили собі Країну Басків, але лише номінально. Засновані графство Ампур'яс та Руссільйон.
 Повстання велетів проти франків зазнало поразки.

Народились

Померли

Див. також
 Список керівників держав 812 року
810-ті

redpajama_set_name: RedPajamaWikipedia


Welcome. Six Fried Rice brings power and simplicity to individuals, workgroups, enterprise, and the web through custom web applications and expert advice.
We've built custom web applications for dozens of businesses and non-profit organizations and we're getting pretty darn good at it.
Although we work with many technologies, in most cases, after analysis, our customers decide a web-based application best meets their needs. Usually, they are unfamiliar with this type of development before the project starts, but the benefits speak for themselves.


The research focused on bargaining councils in five industries as statutory institutions for centralised collective bargaining. The purpose was to determine how bargaining councils adapted to the changing environment during the 15-year period from 1995 to 2010, with a particular focus on representivity, the main agreement (wages and conditions of service), benefit funds, dispute resolution and other related developments.
Holtzhausen, M. 2011. A study of four key aspects within five bargaining councils over the period 1995 to 2010. University of Cape Town.


text:
Übersyren (luks. Iwwersiren) – wieś w południowym Luksemburgu, w gminie Schuttrange. Wieś zamieszkuje 616 osób.

Przypisy

Wsie w dystrykcie Luksemburg