Monday, June 24, 2013

Powerful gene-editing tool appears to cause off-target mutations in human cells

June 23, 2013 ? In the past year a group of synthetic proteins called CRISPR-Cas RNA-guided nucleases (RGNs) have generated great excitement in the scientific community as gene-editing tools. Exploiting a method that some bacteria use to combat viruses and other pathogens, CRISPR-Cas RGNs can cut through DNA strands at specific sites, allowing the insertion of new genetic material. However, a team of Massachusetts General Hospital (MGH) researchers has found a significant limitation to the use of CRISPR-Cas RGNs, production of unwanted DNA mutations at sites other than the desired target.

"We found that expression of CRISPR-Cas RGNs in human cells can have off-target effects that, surprisingly, can occur at sites with significant sequence differences from the targeted DNA site," says J. Keith Joung, MD, PhD, associate chief for Research in the Massachusetts General Hospital (MGH) Department of Pathology and co-senior author of the report receiving online publication in Nature Biotechnology. "RGNs continue to have tremendous advantages over other genome editing technologies, but these findings have now focused our work on improving their precision."

Consisting of a DNA-cutting enzyme called Cas 9, coupled with a short, 20-nucleotide segment of RNA that matches the target DNA segment, CRISPR-Cas RGNs mimic the primitive immune systems of certain bacteria. When these microbes are infected by viruses or other organisms, they copy a segment of the invader's genetic code and incorporate it into their DNA, passing it on to future bacterial generations. If the same pathogen is encountered in the future, the bacterial enzyme called Cas9, guided by an RNA sequence the matches the copied DNA segment, inactivates the pathogen by cutting its DNA at the target site.

About a year ago, scientists reported the first use of programmed CRISPR-Cas RGNs to target and cut specific DNA sites. Since then several research teams, including Joung's, have succesfully used CRISPR-Cas RGNs to make genomic changes in fruit flies, zebrafish, mice and in human cells -- including induced pluripotent stem cells which have many of the characteristics of embryonic stem cells. The technology's reliance on such a short RNA segment makes CRISPR-Cas RGNs much easier to use than other gene-editing tools called zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), and RGNs can be programmed to introduce several genetic changes at the same time.

However, the possibility that CRISPR-Cas RGNs might cause additional, unwanted genetic changes has been largely unexplored, so Joung's team set out to investigate the occurrence of "off-target" mutations in human cells expressing CRISPR-Cas RGNs. Since the interaction between the guiding RNA segment and the target DNA relies on only 20 nucleotides, they hypothesized that the RNA might also recognize DNA segments that differed from the target by a few nucleotides.

Although previous studies had found that a single-nucleotide mismatch could prevent the action of some CRISPR-Cas RGNs, the MGH team's experiments in human cell lines found multiple instances in which mismatches of as many as five nucleotides did not prevent cleavage of an off-target DNA segment. They also found that the rates of mutation at off-target sites could be as high or even higher than at the targeted site, something that has not been observed with off-target mutations associated with ZFNs or TALENs.

"Our results don't mean that RGNs cannot be important research tools, but they do mean that researchers need to account for these potentially confounding effects in their experiments. They also suggest that the existing RGN platform may not be ready for therapeutic applications," says Joung, who is an associate professor of Pathology at Harvard Medical School. "We are now working on ways to reduce these off-target effects, along with methods to identify all potential off-target sites of any given RGN in human cells so that we can assess whether any second-generation RGN platforms that are developed will be actually more precise on a genome-wide scale. I am optimistic that we can further engineer this system to achieve greater specificity so that it might be used for therapy of human diseases."

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/top_health/~3/k3Z12VMmz6k/130623145102.htm

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Sunday, June 23, 2013

Gerrit Cole pitches Pirates past Angels 5-2

ANAHEIM, Calif. (AP) ? Gerrit Cole pitched four-hit ball into the seventh inning in his native Orange County, earning his third straight victory to open his major league career in the Pittsburgh Pirates' 5-2 win over the Los Angeles Angels on Friday night.

The Pirates' 22-year-old right-hander out of Orange Lutheran High School and UCLA dazzled the Angels in his first career road start, repeatedly hitting 100 mph on Angel Stadium's radar gun. He struck out five and retired 11 straight before Albert Pujols' leadoff homer in the seventh.

Cole (3-0) outpitched Angels ace Jered Weaver (1-4), who yielded nine hits and four runs over six rocky innings in his fourth straight winless start.

Pedro Alvarez and Jordy Mercer homered in the second inning of the Pirates' first game in Anaheim since 2007.

Source: http://news.yahoo.com/gerrit-cole-pitches-pirates-past-angels-5-2-050903374.html

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Communications Surveillance, Protest and Control? | Paul Bernal's ...

Protest against the badger cull in Bristol

What is the real reason that certain of the authorities are so keen on universal surveillance of communications data? Is it the fight against terrorism? It doesn?t seem very likely. It?s a supremely ineffective method of dealing with terrorism at best ? even the examples quoted by the security services as ?proof? that it works have pretty much all been swiftly debunked (see for example here). In practice, it seems, targeted, intelligence-driven, almost ?traditional? methods seem to do the job far better. So why do the authorities all around the globe seem to be so enthusiastic about communications surveillance? One word: control

Control is the key

Despotic regimes have always wanted to have as complete a level of surveillance as possible ? they want to know what is going on, who is meeting who, what they?re talking about, what they?re planning. That way, they can get control over their people. They can find subversives and dissidents, they can infiltrate those who resist or plot against them, they can snuff out the plans of their enemies before they gather sufficient momentum to have a real effect. That?s been fundamental to pretty much every oppressive regime throughout history ? and the capabilities of the internet, and in particular of internet surveillance, offer possibilities beyond the dreams of the despots of yesteryear. However, it?s not just despots who like surveillance ? or rather, it?s not just those that we usually label as ?despots? who like it. It?s anyone who wants more control ? or who thinks that things are going out of control. It?s those concerned with ?public order?. It?s those concerned with ?protest?. That, sadly, means it?s all of our governments today ? even that in the UK.

Snooping on the badger-cull protestors

News came out this week that ?Whitehall chiefs scan Twitter to head off badger protests?. As reported to the BBC, ??[t]he Department for Rural Affairs uses ?horizon scanning? software to gain an ?early warning? of public protests.? Relatively speaking, this is a primitive form of snooping ? and a legal one, since it scans public messages on social media services such as twitter. This isn?t a secret plan like PRISM, but an official and key part of the government?s communication plan ? but it reveals a good deal about how the government (and other authorities) see the potential of communications surveillance. If they can find out what people are thinking and planning, they can nip protests in the bud.

Pretty much all of this, of course, is legal, and much of it is justifiable in ?public order? terms ? but as anyone who saw the recent and deeply shocking revelations that the McLibel leaflet was co-written by an undercover police officer who had infiltrated an environmental campaign group would know, the tactics and techniques used by ?law enforcement? to deal with protestors and related groups can often stretch not just the law but our imaginations. Ideas presented and proposed for good or at least defensible reasons can easily morph into something much more sinister. Give the authorities leeway, and they use it?

The real use of communications surveillance?

?which is what, it seems likely, is one of the keys behind the enthusiasm for all kinds of communications surveillance, from the Snoopers? Charter in the UK to PRISM and so forth in the US, to all the massive new programme in India etc. They know that if they have full surveillance capabilities their ability to control what is happening will be magnified enormously. Not only can they effectively unmask protestors, they can find out who their friends are, what websites they visit, where they?re planning to meet and so on. If they take it a few steps further, they can ?block them from communicating with each other, shut down their blogs ? or warn them off with anonymous threatening emails, or leak their details to their enemies.

Does this sound far-fetched? Perhaps, but not nearly as far fetched as the McLibel story, let alone the other horrendous details surrounding police infiltration of environmental and anti-racist groups. What?s more, most of the surveillance systems planned are designed for precisely this kind of surveillance ? linking into Facebook, Google etc is far better at this that it is at fighting terrorism, paedophilia etc. Terrorists and paedophiles don?t do their planning on Facebook etc ? but those organising legal, peaceful protests like that against the badger cull DO. Terrorists and paedophiles do everything they can to keep ?dark? ? and they learn how to do so, what technology to use to bypass the authorities. Peaceful protesters don?t ? they don?t often feel that they need to, and they don?t have the capabilities. They?re the obvious targets of this kind of thing: universal internet surveillance isn?t so much about fighting the big things as it is about keeping ?public order?.

Whether that is an acceptable thing is another story. Public order IS important ? but so is the right to protest, and not just in countries like Turkey. Protest is fundamental to our democracy, to our freedom of expression, to our ability to hold our governments to account. It?s important everywhere, and letting the authorities design and operate systems to stifle and control it is something about which we should be very wary.

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Source: http://paulbernal.wordpress.com/2013/06/23/communications-surveillance-protest-and-control/

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Excellent Services Offered By The Indianapolis Paving - Tools and ...

Excellent Services Offered By The Indianapolis Paving

1 views This article is copyright free and is published in Tools and Equipment ? Home Improvement Joined: Jun 05, 2012

3994 articles

Pavers are the dry mix piece of concrete that commonly used for exterior landscaping and it is forms interlocking concrete pavements. Pavement can be used by any one as it enhances the standard of particular place as well as provide ease too the person who use it. There are several companies in USA that use to offer tremendous services and Indianapolis Paving services are highly known and preferred by all and they use to provide excellent services to the customers.
For the pavement services it is very much essential that one should have the services that are offered by the careful service provider who takes care of quality.

Quality Pavers

There are several service providers available and they use to offer trustworthy services along with quality workmanship and excellent customer services with the exceptional results. They use to offer excellent seal coating and asphalt repairing and replacement solutions according to the need of customers. It includes the services like asphalt paving, hot rubberized sealing for cracks, seal coating, full depth replacement, asphalt mining, patching, design and layout striping, concrete installation and repair, free estimates and drain collars and many more. They use to provide their clients with the excellent services with punctuality and best thing is that all the projects are same for them.

Driveway Maintenance services

It is quite known that pavements are widely used for the driveways and along with the paving services it is also essential for these companies to provide proper maintenance services too. These companies use to offer highly skilled teams that result in quality pavement installation as well as its proper repairing and maintenance too. They use to provide excellent workmanship and customer dedicated a service that enhances the customer?s attraction and recommendation and most important is that they are having great experience in the pavement services.

Exceptional results

The tremendous growth of Indianapolis paving is just because of their quality services and exceptional results that please their customer to take the services from here. If you are also looking for the excellent services that are offered for the pavement then you must analyze the services on the basis of work experience and quality they provide with previous work records. There are several of pavements services that are offered by the service provider like parking lots as well as sidewalks and also paving including curbs and driveways along with the stamped services with the new construction and also removal or replacement services with the asphalt too.

About author: William Klein

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Source: http://www.zuarticles.com/article-details/excellent-services-offered-by-the-indianapolis-paving.html

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Saturday, June 22, 2013

Obama to Include Existing Plants in Pollution Plan (WSJ)

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Source: http://news.feedzilla.com/en_us/stories/politics/top-stories/314562575?client_source=feed&format=rss

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Kardashian baby name: the science of how names shape us

Kardashian baby name: some studies have linked unusual names to numerous disadvantages later in life. As for the Kardashian baby name, it remains to be seen.

By Elizabeth Barber,?Contributor / June 21, 2013

Kardashian baby name: This 2012 photo shows singer Kanye West, left, talking to his girlfriend Kim Kardashian before an NBA basketball game between the Miami Heat and the New York Knicks in Miami. A birth certificate released by the Los Angeles County Dept. of Public Health shows that the couple's daughter North West, was born last Saturday in Los Angeles.

Alan Diaz/AP

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Kim Kardashian, for reasons that are not yet clear, has named her baby North West.

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It's an odd choice that's unlikely to much affect Kanye West's and Kardashian's little girl ? but, for a child born to non-famous parents, is a name that might critically shape who she grows up to be. Without the gilded Kardashian name to guarantee her success, that non-celebrity girl might struggle to fend off bullies, get hired, and overall surmount other people?s ? and eventually her own ? low expectations for her future.

Studies have increasingly shown that names are a highly relevant factor is how others perceive us and we perceive ourselves. In 2010, David Figlio of Northwestern University in Illinois analyzed names from millions of birth certificates for the probability that the name belonged to someone of low socioeconomic status ? children whose names met those criteria would go to be discriminated against throughout life, he found. Similarly, a 2003 study from The National Bureau of Economic Research found that resumes with White-sounding names receive 50 percent more callbacks for interviews than resumes with African-American-sounding names.

The significance of that research has grown in recent years, as baby names have become increasingly more unusual. In 2010, a British study of some 3,000 parents found that one-in-five of them regretted the name they had selected for their children, in that case often an unusual name or one with a strange spelling. That finding wasn?t surprising to scientists, since a growing crop of studies have linked unusual names to numerous disadvantages in life.

Much of how we perceive the world is unconscious, and our latent biases against particular names are often influential in how we treat people. A 2011 informal survey that combed baby name conversations on online message boards found that the names perceived to be highly trendy are the biggest culprits in jolting those biases and that those names often end up capping our lists of the most hated names.

Source: http://rss.csmonitor.com/~r/feeds/science/~3/8qmeDm82OMA/Kardashian-baby-name-the-science-of-how-names-shape-us

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Asteroid-mining firm meets $1 million crowd-funding goal

Thu Jun 20, 2013 7:52pm EDT

(Reuters) - A start-up asteroid mining firm that launched a crowd-funding campaign to gauge interest in a planned space telescope reached its $1 million goal, company officials said on Thursday.

Bellevue, Washington-based Planetary Resources intends to build and operate telescopes to hunt for asteroids orbiting near Earth and robotic spacecraft to mine them.

The company, whose financial backers include Google's founders, also envisions a companion educational and outreach program to let students, museums and armchair astronomers make use of the first telescrope that Planetary Resources plans to build, called Arkyd.

Three weeks ago, Planetary Resources launched a crowd-funding initiative on Kickstarter to assess interest in the project and set a goal of raising $1 million by June 30.

"It surpassed that amount Wednesday night," company spokeswoman Stacey Tearne wrote in an email.

"We currently have 12,000-plus backers who have pledged just over $1.07 million," Tearne said.

For a pledge of $25, participants can make use of a "space photo booth," by sending a picture to be displayed on the telescope so a remote camera can snap an image, with Earth in the background, and transmit it back.

For $200, participants can actually use the telescope to look at an astronomical object.

The Kickstarter campaign complements the company's ongoing efforts to design and build Arkyd. Investors include Google executives Larry Page and Eric Schmidt, as well as Ross Perot Jr., chairman of the real estate development firm Hillwood and The Perot Group.

(Editing by Kevin Gray; Editing by Steve Orlofsky)

Source: http://feeds.reuters.com/~r/reuters/scienceNews/~3/GZk4Rnqjeds/story01.htm

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