text:
Q: How should I ask the IT to enable publishing an apex application on Internet? I made an application in apex, (I barely learning first steps), which I use for testing.
I have both the database and apex installed on my work PC, and the company has his own Oracle database providing webpages to Internet, which at this point has no interaction with my database and applications.
I want to test my application working from Internet. At this point I can only access it from my internal network at work.
I need it to be accessible from anywhere on internet.
I believe that I need to ask the IT department to expose the application to Internet, (to make it accessible from out of the local network), but I do not know the terminology that I need to use.
What is exactly what I need to ask to the IT department, and what information I need to provide?
_
I guess that I need to ask:

*

*To open a firewall to ports 1521, 8080 to that computer, or the
application URL (http://localhost:8080/apex/f?p=###), maybe specifying the programs oracle.exe and tnslsnr.exe

*To start or configure "some service"

*To "expose that computer to Internet"

*Something, I have no clue what.

I guess that I need to provide the mentioned ports, the network name of the (windows) computer , and the URL of the application.

A:
I barely learning first steps
but I do not know the terminology that I need to use.
I have no clue what

Under these conditions, you shouldn't.
If you don't yet understand the requirements and therefore the security implications your IT department is, quite rightly, simply not going to let you publish an application to the public network from their resources.
When you are ready to publish, assuming it is something relevant and useful to the company, ask your IT department what their procedure is for such tasks - it will vary form company to company so the only way to know for sure is to ask them what information they need you ro provide (which will likely include sign-offs from your supervisor and/or others in management and/or the person or team responsible for network security).

A: Leaving aside the entirely valid issues raised in David Spillett's answer - the best way to find out what your IT department would need in order to make your application available outside of your company's network is to ask them.
We don't know anything about you network configuration. We don't know if the machine the application is running on gets its IP address via DHCP (in which case that address would change periodically); what firewall rules are in place, and what all would need to be changed; etc.
When you go to the meeting, you should be prepared with everything you know you may need: at a minimum, I'd cover:

*

*The machine(s) running the apex application.

*All ports required to communicate with the apex application's web interface.

*Current audience for the application.

*Expected traffic.

*Some information on what the application does, and the types of data the it will hold/collect.

First, in most cases the IT organization is responsible, among other things, for making sure that the company's websites stay up and work for their users, internal and external. If you are running this on your personal workstation (or worse, laptop), then the reliability of the site cannot be guaranteed. For testing purposes, this may be adequate; but, you would want to be able to justify why this needs to be globally available for testing purposes, rather than merely available inside the company network. I'm not saying there isn't a reason - it's just a question any responsible IT person would ask.
Even if the apex application is ready for a rollout to the internet at large, they may need to move it and the database it uses to another server or servers, depending on expected traffic.
The IT organization is probably responsible, to one extent or another, for internet security as well (or, at least, concerned with it). They may ask questions about what you've done to guard against common website attacks (SQL injection, for instance). They may even want to do some testing of their own to ensure they don't find any holes before they make the site available.
Again, your IT team may not be directly responsible for compliance, but they are almost certainly involved and concerned. Rules regarding PCI or HIPAA compliance, for instance, are complicated, and violating them can be extremely costly. Hence, the need for info on what data you'll collect and store.
TL;DR While it's good to go in as prepared as possible, don't go in expecting to give them a handful of data and be done. This will probably be just a first meeting, and they'll let you know what more they need.


text:
Election 2016: A Reflection
Failure of the political and media elite fuel Trump and Sanders phenomenons in both parties
Anti-system candidates: Donald Trump and Bernie Sanders
Donald Trump officially won the Republican nomination for President of the United States last night in Cleveland. The question many are asking is: How did the country get here? Consider the following facts and the reasons for the political earthquake become clear.
A silent epidemic
African Americans in the United States can expect to live until age 76, while white Americans are likely to live until age 79, on average there is a 3.4 year difference. This is an improvement over previous years with both African Americans and Hispanic mortality rates steadily dropping. However since 1995 white mortality rates have dropped at a slower rate when compared to other groups. Worse yet between 1999 and 2014 mortality rates among middle class whites have actually increased while that of other racial groups have continued to decline. Main causes of this increased mortality are: suicide, chronic liver diseases and cirrhosis, alcohol and drug poisoning.
This trend is not being repeated in other European countries. According to a December 2015 Princeton study this "silent epidemic" has claimed half a million lives and can be traced to distress in the population with the inability to find work a major factor. There is also new data that points to increasing mortality not only among middle age but also young whites. How does all this relate to the 2016 presidential election? According to Jeff Guo in The Washington Post on March 4, 2016 Donald Trump performed the best in places where middle-aged whites are dying the fastest.
Economic distress
The official government unemployment figure is 4.9% but other reliable and more accurate statistics range between 6.3% on the low end to the U6 unemployment range which is 9.9%. More controversial but accepted in some quarters is John Williams' Shadow Government Stats that places June 2016 unemployment at 22.9%. These numbers provide plenty of room for despair. First is the fact that official numbers promoted in the mass media are not necessarily accurate.
Secondly, the disappearance of higher paying manufacturing jobs has been the result of trade agreements that have negatively impacted U.S. workers but at the same time has benefited and enriched a powerful few. Most of U.S. manufacturing ended up in mainland China and has assisted in modernizing that country and its military which is now expanding in the region and making itself felt worldwide to the detriment of U.S. national and security interests. How has this bipartisan China policy benefited the average American? This is not being discussed on the national stage.
If the political and media elite are unwilling even to address the problem with accurate statistics then what hope is there of solving the problem? This is why the Trump and Sanders phenomenons erupted on the national political scene. Voters are frustrated.
Exacerbating racial tensions
Meanwhile rather than having this national conversation the debate has been returned to the old obsession and the so-called "original sin" of the United States: Race.
Consider for a moment that according to The Washington Post 990 people were killed by police officers in 2015 out of a total of 12.2 million arrests with nearly half of all killed being white non-hispanics followed by a little over a quarter that were African American and 17% who were hispanic. A disturbing subset of data was the statistical breakdown of 93 unarmed individuals killed by the police in 2015 with four out of ten being African American followed by three out of ten being white non-hispanics and nearly two out of ten hispanics. Meanwhile there were 42 police officers shot and killed in 2015.
There is a problem that needs to be addressed but it has been magnified and distorted by the media and political actors to create the sensation of a clear and present danger for African Americans when being stopped by the police facing a great risk of being killed. The high profile killing of police in the United States in reaction to a media campaign demonizing the police will also have an impact in the presidential election.
It is interesting that those publicly mentioned as possibly funding Black Lives Matter have an interest in maintaining the status quo on trade and globalism in the United States and avoiding a national conversation on these two subjects. This brings us to a topic that the political and media elite are at odds with the majority of the citizens of the United States and that is immigration.
Illegal immigration and changing the political culture
Fredo Arias-King served as senior adviser to the National Action Party of Mexico during its presidential campaign in 1999–2000. In July of 2006 he wrote an important paper for the Center for Immigration Studies titled "Immigration and Usurpation: Elites, Power, and the People's Will" about the disconnect between public opinion and elite actions in the United States with regards to illegal immigration.
Arias-King speculated in this paper what motivated U.S. politicians to tolerate and even encourage the phenomenon of illegal immigration and where it could eventually lead predicting the rise of a Trump-like candidate that could seize the immigration issue to respond to the demands of a populace outraged at the lack of response from the political class.
Samuel Huntington speculated that the American "creed" (values and beliefs) cannot be used to openly oppose mass immigration.16 That may change. So far, the immigration debate has centered on the immigrants themselves—whether they are worthy or unworthy. This debate is a red herring, since average Americans are unusually kind and restrained in the face of mass immigration, something that cannot be said about other nations (including Mexico).17 Recent poll findings from Zogby challenge the popular belief that the average American somehow has negative or overtly prejudicial feelings toward Mexicans in particular.18 However, Huntington did not take into account the possibility that the debate could yet be framed in terms of potential usurpation from the political class using immigration as a tool. If an organizeable mass of Americans comes to suspect that mass immigration from Latin America is being used by the political class to undermine their democracy and as a tool to liberate the political elites from the Jeffersonian and Madisonian constraints, then indeed we may witness a reaction—but hopefully not against the immigrants themselves, as they are also objects of elite manipulations in more than one country. The Founding Fathers also prescribed a cure for usurpation. Hopefully the American people will not apply it so literally, for the sake of those legislators.
The conclusion reached by the author that the American political class was using mass immigration to change the electorate in order to make the citizenry more malleable and thus politicians able to get away with being less accountable was a controversial proposition in 2006 but seems much less so today. The loss of faith in governing institutions in the United States by large sectors of the electorate is behind the success of Donald Trump, a business man with no political experience and Bernie Sanders, a socialist with a communist background who honeymooned in the Soviet Union in 1988. However Sanders was against open borders and globalization but his support for an amnesty for 11 million in the United States probably cost him the nomination.
Shadows in the Fall: Foreign policy
Foreign policy failures are felt here in the United States. The argument that we fight them over there to avoid fighting them over here rings hollow in the electorate who are now backing a candidate who opposed the war in Iraq. Terror attacks linked to Islamic extremism have impacted across the nation in recent years: Orlando, Florida (2016), Chattanooga, Tennessee (2015), San Bernardino, California (2015), and Boston, Massachusetts (2013). Meanwhile events in Turkey point to an ominous new turn with Erdogan's consolidation of power, purges, and crushing of the military following what appears to have been a coup with a counter-coup underway that could lead to the rise of a fully Islamic regime in NATO. The cry of "who lost Turkey?" may become a theme in the foreign policy debate in the presidential election in the United States this fall. There are other hot spots in the world and Libya can be blamed directly on Hillary Clinton.
These are trying times for the American Republic and the social, political, and media elite had best wake up, look out for the interests of their fellow citizens, and how to rebuild the middle class or get out of the way.
Labels: Bernie Sanders, Donald Trump, Election 2016, white mortality rates
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redpajama_set_name: RedPajamaCommonCrawl


What makes a good French breakfast?
Croissants, a large group of energy enthusiasts creating a lot of energy.
Under the heading "#Reinvent Energy", NUMA in cooperation with SAP had invited start-ups to discuss digital platforms in the energy sector over a delicious breakfast in Paris. We are delighted having been part of the panel with Opinum and the French energy company engie to talk about how digital platforms will revolutionize the energy world.
More and more French territories want to take control and monitor their energy as well as the related data. Platform Solutions like GRIDS energyCity, the joint product of enersis and Navitas, can help utilities to build new business models. The increased transparency provided with the online platform can also be a basis for sustainable partnerships with public authorities. They will be able to communicate and control their energy strategies more efficiently, as the energyCity platform provides a powerful database and advanced interface.
How this works has been part of a fruitful discussion as well as how citizen can be involved and how data security and privacy can be ensured. Especially the latter is one of the key success factors for any platform!
Would love to continue the discussion over lunch? Get in touch with enersis or Navitas now!
Many thanks to NUMA and SAP France for organizing the event.


The Coaxial Cable Cutter – CCS has a multi-functional blade optimized to cut copper-clad steel (CCS) coaxial cable and other common wires or cables. It has two cutting areas to accommodate different cable types. Now you only need one cutting tool for your voice/data/video installations.


Afoinfoblog is a news and entertainment media outlet whose aim is to keep its viewers and fans updated whenever, however and wherever! We update you on all happenings in selected parts of the world but mostly Africa in particular. We deals with latest news, fashion, lifestyle, event, entertainment and the great gossips. We publish composed tips and general news from across the Globe. Stay connected!!!
If you have any news, advise, or any other thing you want to bring to our notice, reach the admin on :- afodapsy@gmail.com, 08132592237.


text:
"Quorums of the Seventy," Church History Topics
Seventy is an office in the Melchizedek Priesthood. Since 1986, members of the Quorums of the Seventy are general or regional authorities who assist in the administration of the Church across the world. For most of the history of the Church, however, stakes had their own quorums of seventy.
The first members of the seventy were ordained on February 28, 1835, when Joseph Smith began to call and ordain special missionaries to "prune the vineyard for the last time."1 That same month, Oliver Cowdery, David Whitmer, and Martin Harris assisted Joseph Smith in selecting Twelve Apostles, a priesthood quorum of twelve high priests who, like the Apostles in the New Testament, were commissioned to preach the gospel to all the world. According to an instruction on priesthood included in the Doctrine and Covenants, the seventy too were "called to preach the gospel, and to be especial witnesses unto the Gentiles and in all the world," modeled after the Seventy whom Jesus called to preach to the Israelites during His lifetime.2
The instruction also explained that the seventy "form a quorum, equal in authority to that of the Twelve" but that the seventy were to act under the direction of the Apostles, who alone held the "keys" to proclaim the gospel to both Jew and Gentile.3
Additional quorums of seventy were created as additional men were ordained. After Joseph Smith's death in 1844, most elders under the age of 35 were ordained as seventies, and many new quorums were created to accommodate the expanding ranks. By 1846, the number of quorums of seventy had reached 35. Eventually the total number of quorums reached into the hundreds. Most missionaries during the second half of the 19th century were members of these local quorums of seventy.4 A council of seven selected from among each quorum's members presided over a quorum. As a whole, the quorums of seventy were presided over by seven men who constituted the First Council of the Seventy. These men were sustained as General Authorities next to the Quorum of the Twelve in authority. In 1907, Joseph F. Smith taught that the First Council of the Seventy functioned as "assistants to the Twelve Apostles" and were, in one sense, "apostles of the Lord Jesus Christ" sent to preach the gospel throughout the world.5
As Church membership expanded across the globe, it became difficult for the Twelve to fulfill all of their administrative responsibilities. In 1941, the First Presidency began to call a few men as "assistants to the twelve." In 1961, President David O. McKay directed that members of the First Council of Seventy be ordained to the office of high priest and given the authority necessary to "set in order all things pertaining to the stake and the wards, under the direction of the Twelve Apostles."6 In October 1975, President Spencer W. Kimball announced the creation of the First Quorum of Seventy as an additional body of General Authorities, and filled the quorum with the First Council of Seventy, the Assistants to the Twelve, and other newly called Seventies. In October 1986, President Ezra Taft Benson directed local leaders to discontinue local quorums of the seventy and no longer call and ordain men to the office of seventy. Leaders then either directed former members of the local quorums of the seventy to attend elders quorums or ordained them as high priests.
Since 1986, the office of Seventy has remained exclusively an office of general rather than local authority. Members of the Seventy generally retire from active service at age 70, at which time they are granted emeritus status. The founding of a "First" Quorum of Seventy renewed the pattern of Quorums of the Seventy seen during the earliest days of the Church, only on a general as opposed to a local level. In April 1989, the Second Quorum of Seventy was established. The First Presidency established the Third through Eighth Quorums between 1997 and 2005, designating members of these quorums "Area Authorities" and placing them under the direction of the First Quorum of the Seventy. The Seventy today support the Quorum of the Twelve and First Presidency in administering the Church throughout the world, serving as members of Area Presidencies, organizing stakes, and teaching Latter-day Saints in general and local conference settings.
Earl C. Tingey, "The Quorums of the Seventy," Ensign, Aug. 2005, 48–50.
L. Aldin Porter, "A History of the Latter-day Seventy," Ensign, Aug. 2000, 14–20.
The following publications provide further information about this topic. By referring or linking you to these resources, we do not endorse or guarantee the content or the views of the authors.
"Seventy," Encyclopedia of Mormonism, ed. Daniel H. Ludlow (New York: MacMillan, 1992), 1300–1305.
Joseph Young, History of the Organization of the Seventies (Salt Lake City: Deseret News, 1878).
"Minutes, Discourse, and Blessings, 14–15 February 1835," josephsmithpapers.org; "Minutes and Blessings, 28 February 1835–1 March 1835," josephsmithpapers.org. Joseph Young later wrote of a meeting on February 8 during which Joseph Smith told him, "The Lord has made you President of the Seventies." Joseph Young, History of the Organization of the Seventies (Salt Lake City: Deseret News, 1878), 1–2.
D&C 107:25; Luke 10:1–17.
D&C 107:26, 34–35, 38.
See Topic: Early Missionaries.
Joseph F. Smith, in Conference Report, Apr. 1907, 5–6.
David O. McKay, "Except a Man Be Born Again … ," Improvement Era, vol. 65, no. 1 (Jan. 1962), 42.


REV Group REVG, +1.99% today announced that it is planning to release its first quarter 2019 results after the market close on Wednesday, March 6, 2019. The results will be discussed during a live webcast the following morning on March 7, 2019 beginning at 11:00 a.m. ET.To access the webcast, investors should go towww.revgroup.comat least 15 minutes prior to the event. Slides for the webcast will be available on the website shortly before the start of the call.
The conference call can also be accessed by dialing 1-877-407-3982 (domestic) or 1-201-493-6780 (international) and asking for the REV Group First Quarter Fiscal 2019 Earnings Conference Call. A telephonic replay will be available approximately three hours after the call and can be accessed by dialing 1-844-512-2921, or for international callers 1-412-317-6671, and providing the passcode 13687873. The telephonic replay will be available until 11:59 pm (Eastern Time) on March 21, 2019.


1. A multitude of mobile self-tracking applications currently exists for patients, yet few are designed by patients and from the patient perspective. Most collected data is intended for researchers and pharmaceutical companies, while few focus on collecting data first and foremost to be beneficial to the patient. The developers of current major health related apps have included ePatients in the beta testing phases, where it is often to late for an ePatients feedback to be effectively incorporated.
2. An elite team of autoimmune arthritis experts was assembled by CreakyJoints.org to create the "Goal Machine". The app helps patients set, track and achieve their life goals – and then (if they wish) share it with us, their friends/family, but most importantly, their doctor. The "Goal Machine" makes self-tracking easy and fun for the patient, while creating data the patient can take to their medical appointments and organically improve care and the doctor/patient relationship, while encouraging patients to be goal-oriented active partners in their own care. By sourcing the current unmet needs in mobile applications directly from patients first, the information was then turned over to a team of technologists who worked in tandem with the patients, not separate from.
3. While the "Goal Machine" is still in production, it is soon slated for beta testing, and will be available to the patient community in early summer. We found that many times patients don't adequately communicate with their physician how they're doing as a person: their goals and dreams, how their autoimmune arthritis limits them, and how they could define success better. Many times it is not asked of the patient what they want to do in life, and whether their arthritis is holding them back from doing it. From ePatient input, it became clear that patients need a one-stop mobile application for tracking symptoms, finding vetted information, receiving support from their disease community, setting up medication reminders, keeping a schedule for appointments, saving contact and emergency information, finding ways to alleviate symptoms, and finally having an intelligent way to easily share this information with their team of doctors.
4. Most patients have difficulty articulating and remembering their recent symptoms and concerns, finding patients like them, and reliable answers to disease specific questions. By putting all patient needs and desires in one place, they will be better able to share an accurate picture of their health with their healthcare professionals, and reach not only their medical goals but their personal ones as well.


text:
The REAL reason Teddy Riner won't do MMA
Y-Chromosome
Location : The Great White North
by Y-Chromosome on Thu Apr 07, 2016 6:12 am
As counter-intuitive as it may seem to be making more money at an amateur sport than at a pro sport, that seems to be the case.
Compare the purses for UFC 193...
http://www.thecelebritiesnetworth.com/2015/11/ronda-rousey-vs-holly-holm-purse-payout.html
... with what Teddy is reportedly worth.
http://fr.mediamass.net/people/teddy-riner/plus-gros-salaire.html
BTW it's 245 MILLION Euros, if you're having trouble reading the article.
So easy to look down your nose at an activity when you're making 100 X the money doing another one.
Re: The REAL reason Teddy Riner won't do MMA
by Anatol on Thu Apr 07, 2016 10:14 am
Was this story about Riner and Money launched at the 1st of April?
http://en.mediamass.net/blog/mediamass-project
by Y-Chromosome on Fri Apr 08, 2016 3:22 am
Oh shnoot. I know the onion, but I can't be expected to keep up with every hoax site that comes up.
He does make a lot of money though. Perhaps not hundreds of millions but definitely millions because he was quoted complaining about the French taxation rate levied on revenues exceeding 1M €. He's had sponsorship deals with Adidas and been doing things like voicing Disney characters in French.
by Anatol on Sat Apr 09, 2016 3:42 am
To put Teddy Riner's annual income
(400.000 Euro from Judo Club plus maybe 2 Mio from sponsors and advertising)
into perspective:
http://www.forbes.com/athletes/list/#tab:overall
But he is maybe number 3 of the top 10 Judoka annual income list:
Number 2 is Ronda Rousey (6.5 Mio USD in 2015)
» 300746909056 - Nike Elite knockoff could fool some buyers...
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A solitary coping stone provides evidence as to the location of the infilled lock.
It will also be noted, as with the Middle Lock, that the ground is clearly raised here, with the raised portion clearly rectangular in shape.
The canoes are probably in South Cerney Lower Lock, with the Middle Lock behind.
The date range of this photo is listed as being between 1860 - 1922. However, if taken at a similar time to others in this series by the same photographer, it would place the date closer to 1904.


Ground, neutral and earth ground are three basic concepts of Electrical Engineering. In this post, you'll learn the difference between them.
The electrical current in any circuit travels from the positive terminal of the battery passes through the load and then flows back to the negative terminal.
The electrical ground in any circuit is a common reference point. The ground node is considered at a potential difference of zero and all other readings are taken with the reference of the ground.
The figure below displays a voltage divider circuit with two resistors.
The point G represents reference point with potential 0. Whereas point 1 represents reference point 1. Now if we say that potential difference at point 1 is 12 V. We actually mean that with reference to point G the potential at 1 is 12 V. Similarly at point 2 the potential of 7 V means we are comparing that point with the reference G.
The neutral is a return conductor which carries current back to the source. In the previous circuit, the wire which connects 7 V resistor to the negative terminal of the battery is neutral.
The neutral in the previous circuit is highlighted with black colored wire for sake of understanding.
The earth ground refers to a rod which is inserted into the earth soil.
The metallic body of the appliance is usually connected to the earth ground for providing protection.


From "Thinking, Fast and Slow." Emphasis mine.
If you quote a source, choose one with a name that is easy to pronounce. Participants in an experiment were asked to evaluate the prospects of fictitious Turkish companies on the basis of reports from two brokerage firms. For each stock, one of the reports came from an easily pronounced name (e.g., Artan) and the other report came from a firm with an unfortunate name (e.g., Taahhut). The reports sometimes disagreed. The best procedure for the observers would have been to average the two reports, but this is not what they did. They gave much more weight to the report from Artan than to the report from Taahhut. Remember that System 2 is lazy and that mental effort is aversive. If possible, the recipients of your message want to stay away from anything that reminds them of effort, including a source with a complicated name.


The Treasury regulations at issue in Altera Corp. v. Commissioner condition the validity of controlled taxpayers' income allocation under a cost-sharing agreement upon the requirement that the controlled parties share all costs, including stock-based compensation costs, proportionately with the benefits they expect to receive from joint development of intangibles. Amici are tax professors who conclude that these regulations are not arbitrary and capricious under Section 706(2)(A) of the Administrative Procedure Act, but rather are a valid and reasonable exercise of the responsibility of the Treasury Department to administer Section 482 of the Internal Revenue Code.
We concur with the government's argument before this Court that coordinating amendments promulgated with Treas. Reg. § 1.482-7(d)(2) vitiate the Tax Court's analysis in Xilinx that the cost-sharing regulation conflicts with the arm's-length standard. We also agree that Treasury's commensurate-with-income authority under the second sentence of Section 482 provides an independent basis for upholding the cost-sharing regulation, as argued in an amicus brief submitted in this case by Anne Alstott et al. The purpose of this amicus brief is to offer an alternative argument for the validity of the cost-sharing regulation under what the government in its brief called the "traditional" view of the arms' length standard, which depends on analysis of what unrelated parties would have done in comparable circumstances, and to which evidence from uncontrolled transactions, properly adjusted, could be relevant.
In Part I we argue that even if this Court accepts the argument that comparable uncontrolled transactions should be analyzed as part of the arm's-length standard, Treasury reasonably decided not to incorporate into the cost-sharing regulations the stock-based compensation sharing practices of unrelated parties engaged in joint ventures. Ignoring stock-compensation costs in controlled joint development agreements would violate the arm's length principle, notwithstanding evidence that supposedly shows that uncontrolled parties ignore such costs. In Part II of this brief, we argue that Treasury's administrative process was valid, not arbitrary and capricious. We also argue that Treasury's regulatory interpretations merit deference.


Finding out what's new at Stitch-Maps.com just got easier. The "Keep in touch" section at the bottom of each page just got a link for a new RSS feed.
Add the Swatch photos feed to your favorite feed reader, and you'll get notified anytime someone contributes a swatch photo. Pretty slick, eh?
This new RSS feed joins the News articles and Stitch patterns feeds, which – no surprise here – let you know about the latest news articles and stitch patterns. Myself, I watch all these feeds with the Netvibes feed reader, but I understand that Feedly is pretty popular too.


text:
<?php
/**
 * Created by PhpStorm.
 * User: wes_x
 * Date: 11/09/2016
 * Time: 16:54
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class Tipos extends CI_Controller
{
    public function __construct()
    {
        parent::__construct();
        $online = $this->session->userdata("online");
        if(!isset($online))
        {
            redirect('Login');
        }
        $this->load->model("News_model","news");
    }

    public function index()
    {
        $Data['opcoes'] = $this->news->get_tipos();
        $Data['title'] = "Loki News - Tipos";
        $Data['tipos'] = $this->news->listTipos();
        $this->load->view('layouts/header', $Data);
        $this->load->view('layouts/menu');
        $this->load->view('pages/tipos',$Data);
        $this->load->view('layouts/modals', $Data);
        $this->load->view('layouts/footer');
    }

    public function settipo()
    {
        $nome = $this->input->post("nome");
        $this->news->setTipos($nome);
    }

    public function droptipo()
    {
        $codigo = $this->input->post("codigo");
        $this->news->dropTipo($codigo);
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}

redpajama_set_name: RedPajamaGithub


When CultureMap launched in Houston in the fall 2009, our entire staff fit into a room about the size of a closet in a low-slung office building near Rice Village. There was only one long table that took up most of the room and we huddled around it with our laptops, knee-to-knee, clicking away.
Though we were small and unknown, we were excited at the prospect of creating something new and different in the media world. We set out to design a lifestyle website bringing the latest, up-to-the-minute scoop on society, food, fashion, sports, the arts, city life and real estate on an around-the-clock basis to a public hungry for information. We wanted to sort through the clutter and offer a place for lively, intelligent discussion.
At a time when smartphones were not quite as prevalent, the home page featured a big map of Houston, known as a "mapazine," with nine stories of the day geo-sourced to a pinpointed location, so readers could easily determine the place when clicking onto an article.
Our definition of "culture" has always been broad, ranging from fine arts and fine dining to the latest drama on local and national celebrities that dominate conversation, along with debates on hot-button issues.
The big map is long gone, but we think our mission has remained the same: To be first, fast and foremost with highlights — along with occasional lowlights — about Houston and the world.
Our definition of "culture" has always been broad, ranging from fine arts and fine dining to the latest gossip about local and national celebrities that dominate conversation, along with debates on such hot-button issues as what to do with the Astrodome and Jeremy Lin's role with the Houston Rockets to the Houston Equal Rights Ordinance. Just about anything Houstonians are talking about is fair game.
As we have expanded to new cities (Austin in 2011 and Dallas in 2012 so far), we've taken on a larger focus, but we've strived to hold onto what we wanted to be from the beginning: A publication that explains our sense of place — and have a good time doing it.
Social happenings have always been popular CultureMap offerings — with CultureMap editor-at-large Shelby Hodge's coverage, that's a given — but, over the past five years interest has zoomed in other areas, including restaurants and bars with staff writer Eric Sandler breaking scoops on the local dining scene; real estate, where contributor Ralph Bivins and staffer Barbara Kuntz look at the latest trends and homes for sale; and sports, where CultureMap network news director Chris Baldwin regularly entertains and infuriates readers with his strong opinions on the Texans, Rockets and Astros. Joel Luks' arts coverage and amazing videos also have a strong following.
When we launched, we bragged in a press release that our photos dwarfed the competition with "their massive 800 x 600 size, as opposed to the standard 300 pixels offered by competitors." Now, our standard is twice that size. Our home page was designed to make it easy to read, with the size slimmed down to be more readable on a mobile device, and another makeover is on the way. One thing we've learned is you can't stand still in today's rapidly changing media world.
We may be only 5, but we like to think we're advanced for our age.
While we will always anticipate the future, we think it's OK to look back and have some fun reminiscing a bit about our exploits and occasional foibles over the last five years.
So over the next five weeks, leading up to our fifth birthday celebration on Oct. 10 (tickets are available here) at the new JW Marriott Downtown Houston, we will revisit the best — and worst — of CultureMap's past on these pages. Among the topics we will look at are our Five Best Stories Of All Time, our Five Best Celebrity Encounters, Five Top Restaurant Openings and Unexpected Closings, Five Best Ballgowns, Five Most Controversial Stories — well, you get the idea.
As always, we welcome your suggestions for ways to look at our last five years, along with comments about anything and everything. Some of you have never been shy about vehemently disagreeing with us, and while the pointed barbs sometimes hurt, we've learned a lot from what you've had to say.
That remains our goal as we look to the next five years — and beyond.


The Princethorpe Foundation is thrilled to have been shortlisted in two categories in the Independent School of the Year Awards.
The Foundation's senior school, Princethorpe College, has been shortlisted for Independent School of the Year - Student Careers Programme. Whilst Foundation junior school, Crackley Hall, has been shortlisted for the coveted Independent Prep School of the Year. They were both selected ahead of hundreds of independent schools from across the country who had entered the awards.
The Awards Scheme is in its inaugural year and has been introduced to celebrate the independent education sector, showcase excellence in student experience and recognise the varied and imaginative way in which independent schools prepare young people for their future lives.


There was a time when complaining about poor service/products meant customers had to speak one-on-one with a manager. But with the proliferation of online business listings on sites like Yelp, TripAdvisor, Google Maps, etc., it's becoming easier and easier for customers to share their experiences directly and publicly. This leaves businesses struggling to control their online reputation. In the digital age, negative feedback can go viral – and a poor online reputation can be detrimental to a business.
The study compared the star rating of specific hotels on TripAdvisor, using the same hotels on Expedia (where the reviews were not responded to) as a control group. This way, factors such as renovations or the addition of facilities or amenities could be discarded in any changes in average star ratings.
They discovered that, on average, hotels that were responding to reviews received both more reviews (12% increase) and received a 0.12-star rating increase. This might seem nominal – but remember these sites display average star ratings (on a scale of 1 horrendous to 5 spectacular) rounded to the nearest .5-star. That means if you are at 4.21 stars you will display as a 4-star average whereas if you are at 4.33 you will display at 4.5.
Really what you are wanting to portray in the response is that you understand a negative experience happened and that you are there to help resolve the issue and hear the complaint. Some people just want to be heard. For the most part, you can't remove reviews (unless they contain vulgar language), so if you demonstrate you are listening and willing to help, your online reputation will reflect this.
These findings can really help businesses justify spending both the time and money to get a grip on the online reputations. When there is a direct correlation between the response and an improved rating it just makes sense. If done the right way, the insights that come from engaging with customer feedback can prove invaluable.
Patrick Hagarty is our Sales Support Specialist. For more information on how ConvergenSEE can help you manage online reviews, get in touch!


text:
Comebacks: an analysis
by Richard West-Soley January 9, 2006 2:26 pm 89 views
Every year, former Eurovision Song Contest participants take the risk of entering their national selection again. But more often than not, the risk does not pay off.
Vanessa Chinitor is the first victim of the trend this year. She performed for Belgium at the 1999 contest in Jerusalem. Yesterday night, she failed even to get through the first qualifier of the Belgian selection Eurosong 2006.
A look back at past years confirms the pattern. Despite the commercial success and popularity of her 1996 entry for the UK, Gina G ended up a dismal last place in the 2005 UK selection. Nanne Grönvall achieved third place as part of One More Time for Sweden in 1996. She tried to represent both the UK (2001) and Sweden again (1998, 2005) but was denied the opportunity. Fame, fresh from a top five placing in 2003, tried and failed to represent Sweden in 2004.
The trend is not new. Kate Guldbrandsen sang Norway to a confident ninth position in 1987, but remained unplaced in the 1989 Melodi Grand Prix with Naerhet. The 1982 German selection saw a whole clutch of former participants fail: Séverine (Monaco 1971), Paola (Switzerland 1969 and 1980), Jürgen Marcus (Luxembourg 1976) and Mary Roos (Germany 1972 and later 1984). Germans were clearly in the mood for something new that year!
Once bitten, twice shy?
Tor Endresen never even made it to a Eurovision Song Contest final in nearly ten years of trying. When he finally did top the poll to sing for Norway, he ended up last in Dublin in 1997. Little wonder, perhaps, that Norwegian voters were reluctant to award him a second chance for his subsequent attempts in 1999 and 2005!
Comeback kings and queens
The story is not all bad, though. Some performers succeed in a comeback and return to the Eurovision Song Contest stage. Chiara bettered her 1998 third place to second for Malta in 2005. Roger Pontare won Swedish hearts as a solo singer in 2000, improving on his 1994 placing singing with Marie Bergman. Darja �vajger made a successful debut for Slovenia in 1995, and was selected once more in 1999. Hot Eyes made it a hat-trick for Denmark, winning no fewer than three Danish selections in the 1980s. Alone, however, lead singer Kirsten Siggård was left unplaced by Danes in 1990.
Hanne Krogh and Elisabeth Andreasson made the ultimate improvement. Apart, they achieved at best eighth and at worst, 17th place. Together, the provided Norway with its first winner in 1985. Sadly for Hanne, success was elusive, and as part of Just 4 Fun she sank back down to 17th place in 1991. Luckily, Elisabeth returned in 1996 to bring Norway to a celebrated second place on home ground.
Successful comebacks at the national stage are by no means always followed by success on the international stage. Fellow Norwegian Ketil Stokkan may have wished his second Norwegian entry hadn�t topped the 1990 selection � he ended up joint last at the Eurovision Song Contest in Zagreb.
Only Johnny Logan has achieved the ultimate: a double whammy, winning both the Irish selection and Eurovision Song Contest in 1980 and 1987. As a writer, he came back to win both again in 1992. But even he stumbled as a writer of the Dutch hopeful How does it feel in the 2005 semifinals.
Fabrizio Faniello returned to the Maltese national final in 2004, finishing third. In 2005 he dropped to a 12th place and he's testing his luck once again in this year's Maltese final.
Ich Troje, Carola, Vicky Leandros, Barbara Dex and Geir Rønning will be amongst those hoping for a return of former good luck in this year�s national selections. Is it a risk worth taking?
Richard West-Soley
Richard's ESC history began way back in 1992, when he discovered the contest could fuel his passion for music and languages. Since then, it's been there at every corner for him in some way or another. He joined the esctoday.com team back in 2006, and quickly developed a love for writing about the contest. In his other life, he heads the development team at the learning resources company Linguascope, and writes about all aspects of language learning on the site Polyglossic.com.
NRK exclusively reacts on critics
Audio samples second Belgian qualifier online


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Lok Sabha Election 2019
Jaya Prada likely to join BJP, may contest against Azam Khan in Rampur: Sources
According To Sources, The Former Samajwadi Party (SP) Leader May Contest Next Month's Lok Sabha Elections From Rampur Against Azam Khan.
News Nation Bureau | Edited By : Shashikant Sharma | Updated on: 25 Mar 2019, 01:37:20 PM
Less than a month ahead of the Lok Sabha elections, veteran Bollywood actress Jaya Prada is likely to join the Bharatiya Janata Party (BJP). According to sources, the former Samajwadi Party (SP) leader may contest Lok Sabha elections from Rampur against Azam Khan who has been named by the SP its candidate from the constituency.
Jaya Prada, who started her political journey with Telugu Desam Party (TDP) in 1994 on the invitation from its founder NT Rama Rao. However, she quit the party following differences with Andhra Pradesh Chief Minister N Chandrababu Naidu and joined the Samajwadi Party. She contested the 2004 Lok Sabha elections on SP's ticket from Rampur and won the constituency by a margin of over 85,000 votes.
The actress-turned-politician has a bitter rivalry with Azam Khan, whom she had accused of distributing her nude pictures. Despite the controversy, she contested the 2009 general elections on a Samajwadi Party ticket from Rampur and won again.
In 2010, the Samajwadi Party expelled her from the primary membership of the party over her alleged involvement in anti-party activities. The decision was taken after she openly supported the former General Secretary of the Samajwadi Party, Amar Singh.
Later, she floated her own party along with Amar Singh. Her party, the Rashtriya Lok Manch had even contested the 2012 Uttar Pradesh Assembly elections but failed to win a single seat.
Interestingly, Amar Singh, whom she considers her "godfather", has been in close touch with the BJP over the years. Recently, he even added "chowkidar" to his name on Twitter in support of Prime Minister Narendra Modi's "Main Bhi Chowkidar" campaign.
For all the Latest Election News, Lok Sabha Election 2019 News, Download News Nation Android and iOS Mobile Apps.
First Published : 25 Mar 2019, 12:56:18 PM
Jaya Prada Likely To Join BJP May Contest Against Samajwadi Party's Azam Khan In Rampur


Summer is arguably the best time to hike your favorite trail- long days and the clear blue sky above. Paradoxically, your body thinks the opposite. The heat can bake you into a human muffin, scorching your skin, drying you out, and making you re-think every decision you ever made in life that lead to that moment.
Weather works mysteriously. The cloudless skies may turn grey during your hike. Check the weather reports before you head out to not get caught in an unfavorable situation. Remember, humidity equals chances of a downpour. High temperatures also invite thunderstorms.
11am to 3pm is the most unfavorable time to hike. The heat will make it really unpleasant. So, start your hike early in the morning or in the evening, if the trail is short. For longer trails, try to get your elevation gain over with before the midday heat rains down. Use the downtime to take a break and replenish your reserves.
Remember, extra weight means an extra expenditure of energy. Pack light carrying only the essentials.
The human body loses a liter of water every hour on a regular hike. Under the hot sun, the amount increases. So, make sure to pack enough water before heading out. Section Hiker recommends starting hydrating yourself a few days prior to the day of the hike. Keep sipping water at regular intervals keeping in mind that the body can only absorb only half a liter of water every hour. You can carry a water purification system and purification tablets apart from your hydration bladder if the trail offers freshwater.
Dehydration gives way to exhaustion and heat stroke which can prove to be fatal. So, remember to HYDRATE!
The thought of stripping down to the bare minimum may cross your mind, but DO NOT! Wear more clothes while hiking in hot situations. Long sleeve shirts are your best buddies that will keep you protected. The only catch is that your clothes should be loosely fitted, and the fabric breathable. Wearing multiple layers of light fabric provides insulation. You can also wear a layer of synthetic clothes that will work to absorb moisture from all the sweating (you will, a lot) and prevent chafing.
You could also consider getting yourself a hiking outfit. Hats, sunglasses, sunscreen, and moisture absorbing socks are other things that you should consider to keep your hike from turning into a nightmare.
Here is a fun fact about sunburns you may not have known.
Sweating not only makes you lose water from your body but electrolytes as well. Potassium and sodium are the two most important electrolytes and are instrumental in replenishing your energy levels. Sports drinks, snacks with complex carbs, and electrolyte drink mixes are a great way of replenishing the lost electrolytes. Fruits and energy bars are a great source of electrolytes too.
Did you know that a shady place is 9-10 degrees cooler than out in the sun? So, choose a well-shaded to halt your hike. Pull off your boots, letting your feet breathe. Allow the sweat from your body to evaporate and lower the temperature. It is recommended to rest every 2 hours. Utilize this time to eat, drink, and allow your muscles to recover.
Extra pair of undergarments and socks will help you prevent chafing and blisters from the sweat-soaked clothes. Change them during your midday downtime. Bug spray should also be considered as a combination hot weather and sweat equals pestering bugs.
The body may not be in the same plane as your objective. Do not push yourself too hard. Familiarize yourself with the symptoms of heat stroke. If your partner or you feel dizzy, abandon the hike and seek medical assistance immediately!
Previous readingTop 10 Activities You Cannot Afford to Miss When Visiting the United States!


The Thermarest ProLite™ mattresses is tailor-made for anyone seeking lightweight three-season comfort. In this mattress, minimal weight and packed size are as much a priority as reliable performance and comfort. The result is a mattress that is ideal for high-mileage, high-speed journeys where weight and warmth are key. Stuff sack included.
The lightest self-inflating mattress Therm-a-Rest® makes.


So, this version of SkieNET is something I whipped up basically completely from scratch in a day.
Still some kinks to work out, but I'll tackle them as they come my way. I don't foresee any robot invasions any time soon, but you never know.
If you have any suggestions that don't include things like "just use Wordpress" or "just use Drupal", feel free to drop me a line.
I'm going to work on a comments interface and such some time soon.
I fixed images in posts to be mobile friendly, I think.


Secretary of State Hillary Clinton walks with Representative Nita Lowey after a drop-by breakfast with Special Envoy Richard Holbrooke and Representative Lowey at the State Department in Washington, D.C. on Sept. 16, 2009.
Posted on 11/04/2009 by Melissa Golden. This entry was posted in . Bookmark the permalink.


To meet the rapid growth of wireless applications and multimedia services, the development of wireless communications that is able to provide higher data rates and more reliable communications while maintaining satisfactory quality of service is required. Multiple-input multiple-output (MIMO) system has shown tremendous potential to be an excellent approach for solving this problem by providing multiplexing and spatial diversity gains without requiring additional radio resources, such as bandwidth and power. However, the size and complexity limitations of wireless mobile devices mean that MIMO systems may possibly be unfeasible, especially for the uplink. For this reason, cooperative communications has been proposed and its potential benefits have attracted much research attention in the past few years. The idea of this technique is to utilize the broadcast nature of wireless signals by exploiting the fact that a signal intended for a particular destination node can be overheard at neighboring nodes, and thus these nodes can help each other to create a virtual MIMO system. Spectral efficiency (multiplexing gain) and reliability (diversity gain) are the two most important features of cooperative communication protocols. Many cooperative communication protocols are able to achieve full spatial diversity gain, but fail to exploit the multiplexing gain. It is observed in many cases that the multiplexing gain is reduced to one-half due to the half-duplex constraint of the relay. Thus, in this thesis, we investigate cooperative communications protocols that are able to enhance this spectral efficiency (recover multiplexing loss) and improve the corresponding reliability in wireless networks. Specifically, we first analyze the performance of amplify-and-forward (AF) two-path, also known as successive half-duplex, relaying protocol where two-relays are utilized to alternate between transmission and reception modes. This protocol is very interesting, but less studied in the literature due to inter-relay interference inherent in this protocol.


Dogs don't speak "human." It is important for dog owners to comprehend the way dogs communicate if they are to understand their needs. Knowing how your dog is wired to communicate will also take some of the mystery out of training.
One of the most famous places to find puppies for sale is the internet. One of the many advantage of online pet shops is that you have plenty of options to choose from. However, if you don't pick a reputable website, you may get an unhealthy dog or none at all.
So you've bought home a Siberian Husky puppy. One of the first challenges is potty training. Another term for this is simply "housebreaking". From the very beginning, you must start to process of teaching your dog where she can eliminate and that she must hold on when left by herself.
I have also observed the resentment, but now it is a resentment that moves them to act. As they are treated with hostility, they experience the counter-hostility or the resentment, and since they have not been inhibited they lack self-control.
Ticks are a very serious threat to your dogs health. There are ways to get rid of as well as prevent these tiny pests from threatening your dogs health.
This article talks about dog bathing. You will get to know tips on dog bathing.
The list of inherited disorders in dogs is almost endless. Almost any other part of the body is represented by a minor or a major health concern.
What do you do when your dog gets spooked by something? How do you teach your dog to handle new or scary situations? How do you react to your dog when she is scared?


The very notion of teachers shouldering more pension burden has the Chicago Teachers Union talking strike.
Chicago can solve its own financial problems.
To rescue his city from utter financial collapse, Mayor Rahm Emanuel is resurrecting an old whine: You suburban and downstate folks are to blame, and now you have to fix it.
Chicago is the state's "economic engine," he said in several appearances, as if that is reason enough for Illinois taxpayers to ship more than $800 million to the city, including $480 million for its deeply underfunded teacher pensions.
It's a matter of seeking "pension equity," he said, meaning that Chicago Public Schools is the only system in the state required to fund its own teacher pensions. Illinois taxpayers pay for every other district's pension costs.
So, Emanuel's reasoning goes, why should Chicago have to pay for its own pensions, when no one else does?
It's a deceptively attractive argument.
Giving $480 million to Chicago isn't the only way to make everything fair. The state also could require that suburban and downstate schools pay for their own teacher pensions. End state-mandated pension standards for those districts, such as retirement age, and require each district to separately negotiate what they can afford. Save everyone some money.
That would make too much sense, and it won't happen because the powerful teachers lobby would much rather prefer to have (higher) statewide standards set in Springfield than have to negotiate pension benefits separately with hundreds of school boards.
Emanuel's equity argument also is faulty in another way: CPS already gets proportionately more state aid than other schools. According to the conservative Illinois Policy Institute, Chicago benefits from the way the state calculates how much financial aid it gives to CPS. Those technical and confusing formulas take into account such factors as poverty rate, attendance, special education and property tax levels.
All of those factors work in Chicago's favor, said Ted Dabrowski, the institute's vice president of policy. The whole state-funding scheme, he added, is "outdated, convoluted and political." And certainly not as easily described in a sound bite as Emanuel's fairness doctrine.
Dabrowski said in his study, "The current narrative is that historically CPS didn't have enough money to fund both teacher pensions and the classroom — that it had no choice but to shortchange pensions."
Not true, he said. His study, "CPS Pensions: From Retirement Security to Political Slush Fund," argues that revenues never were the problem. "Illinois and Chicago taxpayers contributed more than enough money to pay for both, had the funds just been properly managed."
For example, at CPS leadership's urging, the state legislature allowed the district to skip years of mandated payments into the pension fund. The Chicago Teachers Union objected but didn't do much to stop the diversions.
In reality, when it came to what the CTU most wanted in its 2012 strike, it chose pay increases over fixing the pension underfunding, which then stood at $8 billion. Higher salaries, in turn, increased pension obligations. As a result, Chicago teachers' lifetime earnings are among the highest for the nation's largest U.S. school systems, according to a 2014 analysis by the National Council on Teacher Quality.
Chicago Public Schools CEO Forrest Claypool asserted in an op-ed in Monday's Tribune that in the past five years, state funding of Chicago schools has declined while aid to other schools has "soared."
In reality, if you take a different time frame, it's the state funding of Chicago schools that has soared, according to Illinois Board of Education data cited by Illinois Policy Institute. Since 1998, state funding of CPS has grown at 1.5 times the rate of inflation. State and federal aid in fiscal year 2014 accounted for more than half of CPS revenue.
The battle over who's getting shorted — Chicago, the suburbs, collar counties or downstate — on school, transit and other state aid is an endless fool's game without clear winners. Chicago needs to look more to itself for answers. The policy institute suggests several worthy steps, such as teachers paying for their own pensions or switching to self-managed pension funds. Other ideas abound.
Even the whiff of that idea has the Chicago Teachers Union talking strike, as if they were facing destitution. Everyone else — from Chicago property taxpayers to state and federal taxpayers — is paying a reasonable and responsible share. It's time for Chicago teachers to do their part.
Dennis Byrne, a Chicago writer, blogs in The Barbershop at www.chicagonow.com.


text:
package laol.ast;

import apfe.runtime.Sequence;

/**
 *
 * @author gburdell
 */
public class BaseClassInitializer extends Item {

    public BaseClassInitializer(final laol.parser.apfe.BaseClassInitializer decl) {
        super(decl);
        final Sequence seq = asSequence();
        m_baseName = getIdent(seq, 0).getId();
        m_decl = oneOrNone(seq, 2);
    }

    public String getBaseName() {
        return m_baseName;
    }

    public ParamExpressionList getInitializer() {
        return m_decl;
    }

    private final String m_baseName;
    private final ParamExpressionList m_decl;
}


text:
Multi-gene deletion creates model for Angelman syndrome
by Deborah Rudacille / 7 October 2010
Genes, Signs & Symptoms, The Brain
Modest mouse: A new Angelman syndrome model mirrors the severe epilepsy, learning and memory problems seen in people with the disorder.
A new mouse model of Angelman syndrome that knocks out a large stretch of a key chromosome is clarifying some of the molecular mechanisms underlying the more severe forms of the disorder.
Angelman syndrome, which is characterized by stunted language and arrested cognitive development, is caused by a maternal deletion in the UBE3A gene. The gene is located in the chromosomal region 15q11-13, implicated in both Angelman and some cases of autism.
Previous mouse models have knocked out UBE3A, but in engineering the new model, researchers also inactivated the neighboring GABRB3 gene and deleted the ATP10A gene.
Mice with the larger deletion have more seizures and more severe motor, learning and memory problems than those in which only UBE3A is inactivated, the team reported in PLoS One in September1.
"The new mouse allows us to dissect the contributions of GABRB3 and ATP10A to the more severe phenotype," says Ben Philpot, associate professor of cell and molecular physiology at the University of North Carolina, Chapel Hill, who was not involved in the research.
Deficits in the mice mirror effects in people known to have large chromosomal deletions in the 15q11-13 region. Many of these people have severe forms of epilepsy and are less likely than those without the deletions to develop language beyond a few words, "likely due to the added genes deleted," says Philpot.
The model could also help researchers determine which copies of these genes are turned off or 'silenced,' a process known as imprinting.
"The new mouse allows us to distinguish expression from paternal and maternal copies of genes using common techniques," says Arthur Beaudet, professor and chair of the department of molecular and human genetics at Baylor College of Medicine in Houston.
Neighborhood watch:
In the new study, mice with mutated copies of both maternal and paternal copies of UBE3A, GABRB3 and ATP10A died soon after birth. Mice with mutated copies from the father showed none of the deleterious effects observed in those that inherited the mutated genes from their mothers.
The study confirms previous reports that only the maternal version of UBE3A is expressed in the brain2. However, the researchers found that both maternal and paternal GABRB3 and ATP10A code for protein throughout the mouse brain.
Earlier studies of GABRB3 and ATP10A had reported conflicting results, with some finding that only maternal ATP10A is expressed in human brain tissue, and others finding that both maternal and paternal genes are expressed3. Studies with mice have been similarly inconclusive4,5.
"The imprinting data is not clear-cut," says lead investigator Yong-hui Jiang, assistant professor of neurobiology at Duke University. "We can't rule out the possibility, but our studies with mice have not confirmed it, either."
Jiang developed the first mouse model of Angelman syndrome as a graduate student in Beaudet's lab. The team reported in 1998 that Angelman syndrome stems from mutations in the maternal copy of UBE3A.
Early mouse models of Angelman have helped characterize some of the mechanisms that underlie the symptoms of the disorder, illuminating how UBE3A helps regulate the development of synaptic circuits — the networks of neuronal connections designed to process information.
But it was clear early on that a larger mutation in the 15q11-13 region has more severe effects. Given their proximity to UBE3A, GABRB3 and, to a lesser extent, ATP10A, were likely culprits.
Likely candidates:
GABRB3 encodes a protein that helps build GABA receptors, which control inhibitory signals in the brain. Researchers have long known that GABA signaling plays a role in epilepsy.
More than 90 percent of children with Angelman syndrome have epilepsy, and children with the larger deletion have more severe forms of the condition.
Last year, a group of researchers reported finding a rare variant of GABRB3 in families with autism. They calculated that people with the variant are six times more likely to develop autism than are controls.
The researchers also discovered that the variant is more likely to be inherited from the maternal than the paternal chromosome.
By contrast, ATP10A's precise role in Angelman syndrome remains unknown. Jiang plans to create mice in which ATP10A alone is knocked out to explore the gene's role.
The new mouse is not a perfect match for Angelman in humans. Though the gene deletions in people lead to a loss of language, the young mice in the new study actually vocalize more.
Rats with gene deletions in the same region also seem to chirp more — a possible correlate for human laughter, according to some researchers6. This makes sense, given the generally sunny temperament of people with Angelman syndrome.
But looking for exact parallels between rodent and human behavior is a dicey business, Philpot notes. "People sometimes want mouse behavior to recapitulate exactly what you see in humans, but just because we're not seeing that here doesn't mean the mouse isn't a valid model," he says. "We can't expect mice to behave the same way as humans."
Jiang Y.H. et al. PLoS One 5, e12278 (2010) PubMed
Rouguelle C. et al. Nat. Genet. 17, 14-15 (1997) PubMed
Hogart A. et al. Hum. Genet. 124, 235-242 (2008) PubMed
Kashiwagi A. et al. J. Hum. Genet. 48, 194-198 (2003) PubMed
Kayashima T. et al. Genomics 81, 644-647 (2003) PubMed
Pansepp J. and J. Burgdorf Physiol. Behav. 79, 533-547 (2003) PubMed
TAGS: 15q11-13, Angelman syndrome, autism, epilepsy, GABA, imprinting, inhibitory signaling, language, mouse models, rare variants, synapses, UBE3A, vocalization