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2013 Geneva Spring Regatta - 4th and Final Race
24 May 2013
First - Congratulations to Vincent Porter and Team on the I-2 for their victory.
Sailors showed up Sunday morning for the final races to a calm lake with patches of wind here and there to tickle the RC just enough that they would go out and check conditions. Finally 45 minutes before the noon deadline the RC announced a warning signal would happen at 11:40 for the final race of the regatta. The wind was SE 7-9 mph by the start time and built to 10-14 mph by the finish with one course change as the wind backed some after the first leg. A W5 course was set and leg times were: 8 minutes upwind, 6 downwind, 10 up, 5 down, and 9 up to the finish. It did not seem like a short course at all. These boats are just so darn fast!
Brian Porter (I-49) meant business after being LAST around a leeward mark the day before [I guess that is what happens when you poke an E-Scow legend in a class news article]. Brian wanted the leeward end and took it with good speed heading for the point where he tacked to port crossing all but Chris Jewett (M3). They were followed by Matt Schmidt (V-736), Augie Barkow V-37), Vincent Porter (I-2), Jeff Bonanni (LE-73), Peter Strothman (I-9), and Rob Mahony (J-515). The first downwind was a long starboard and only one boat jibed away in the first three quarters of a mile, and no, it did not help them catch up! Augie Barkow and Peter Strothman edged up in the standings on the next two legs at the expense of Matt Schmidt and Chris Jewett. Barkow had a quick tack onto a good shift at the leeward mark and moved into the lead which he held onto for a lap. Brian Porter got by Augie Barkow on the last upwind leg but Peter Strothman and Matt Schmidt were close and all four boats were going for max speed to get any advantage they could. Barkow had to wait until the last 400 yards before initiating a tacking duel or risk of losing Strothman and Schmidt. Porter made 3-4 covering tacks and Barkow was not able to escape and finished a very close second. Next was Strothman, Schmidt, Jeff Bonanni, Vincent Porter, and Tim Sugar (H-8) sailing very solid and steadily moving up 7 places in the race.
For regatta second place Lee Alnes (W-25) was in a fight with David Strothman (M-10). Lee had to keep at least one boat between them in the race to finish second for the regatta. David made it easier as 8 boats separated them at the first mark but at each mark Strothman was closing in. He fell short by a couple of boats by the finish.


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Irie Blue Hole Adventure Tour from Ocho Rios - Group Special
- Duration: 5 Hours (approx.)
- Product code: P0AQQ1
Plan a visit to the Island Gully Falls and Blue Hole in the scenic tropical hills of St. Ann. This lagoon-like pool fed by the cool river waters flowing down from higher elevations will be an experience to remember.
- Hotel pick up & drop off
- Scenic drive into the countryside
- Spend the time filled with splashing, high diving and rope swinging like Tarzan
- Complimentary lunch stop (Meals not included)
Your Blue Hole adventure starts with your pick up at your hotel lobby or the Ocho Rios cruise terminal and you are driven in comfort on a scenic roadway to the Cascade Rainforest.
At the Island Gully Falls and Blue Hole, you will enjoy rustic nature at its best. Jump, dive or swing from ropes into the pristine watering hole. Swim under the waterfall and discover hidden caves or just sit on a rock and relax under the calming waters of the falls.
Hike along the stream and discover more pools and waterfalls or relax on a rock and just absorb the sun's rays, all while in the capable hands of expert tour guides.
On the way back enjoy lunch at one of Jamaica's famous jerk centres and enjoy the delicious meal with an ice cold Red Stripe beer or tropical fruit drinks before heading back to your hotel or cruise ship with a heart filled with Jamaica!
- Hotel/Port pick up and drop off
- All Admission Fees
- Well-appointed Private air-conditioned vehicles
- English Speaking Guide
- Meals and Drinks
- Gratuity (Optional)
- Confirmation will be received at time of booking
- Minimum numbers apply (21 persons). There is a possibility of cancellation after confirmation if there are not enough passengers to meet requirements. In the event of this occurring, you will be offered an alternative or full refund.
- Children must be accompanied by an adult
- Not suitable for pregnant women or persons with back problems
- Dress code is smart casual, wear swim wear under your cloths and water shoes
- Not Wheelchair accessible

subset: commoncrawl


text:
Max Payne 3 Vincent Gognitti
Juliet Starling Rockabilly instead of niko released.
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TO SUPPORT ME, Please pay attention for the advertisement of my page. My Old Blog:GTAIV-Skins.blogspot.com
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text:
Interstitial keratitis is inflammation of the tissue of the cornea, the clear window on the front of the eye. The condition can lead to vision loss.
Alternative Names
Keratitis interstitial
Causes, incidence, and risk factors
Interstitial keratitis is a serious condition in which blood vessels grow into the cornea. Such growth can cause loss of the normal clearness of the cornea. This condition is often caused by infections.
Syphilis is the most common cause of interstitial keratitis, but rare causes include:
- Autoimmune diseases, like
rheumatoid arthritisand sarcoidosis Leprosy Lyme disease Tuberculosis
In the United States, most cases of syphilis are recognized and treated before this eye condition develops. However, interstitial keratitis remains the most common cause of blindness in the world.
Eye pain
- Excessive tearing
- Sensitivity to light (
Signs and tests
Interstitial keratitis can be easily diagnosed by
The underlying disease must be treated. Treating the cornea with corticosteroid drops may minimize scarring and help keep the cornea clear.
Once the active inflammation has passed, the cornea is left severely scarred and with abnormal blood vessels. The only way to restore vision at this stage is with a cornea transplant.
Expectations (prognosis)
Diagnosing and treating interstitial keratitis and its cause early can preserve the clear cornea and good vision.
A corneal transplantation is not as successful for interstitial keratitis as it is for most other corneal diseases. The presence of blood vessels in the diseased cornea brings white blood cells to the newly transplanted cornea and increases the risk of rejection.
Calling your health care provider
All patients with interstitial keratitis will be closely followed by an ophthalmologist and a medical specialist with expertise in the underlying disease. Any worsening pain, increasing redness, or decreasing vision should be evaluated immediately. This is particularly crucial for patients with corneal transplants.
Prevention consists of avoiding the underlying infection, and if infected, receiving prompt and thorough treatment and follow-up.
Ginsberg SP. Corneal problems in systemic disease. In: Tasman W, Jaeger EA, eds. Duanes Ophthalmology. 15th ed. Philadelphia, Pa: Lippincott Williams & Wilkins;2009:chap 43.
Bouchard CS. Noninfectious keratitis. In: Yanoff M, Duker JS, eds. Ophthalmology. 3rd ed. St. Louis, Mo: Mosby Elsevier;2008:chap 4.17.
Review Date:
Reviewed By:
Linda J. Vorvick, MD, Medical Director and Director of Didactic Curriculum, MEDEX Northwest Division of Physician Assistant Studies, Department of Family Medicine, UW Medicine, School of Medicine, University of Washington. Franklin W. Lusby, MD, Ophthalmologist, Lusby Vision Institute, La Jolla, California. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.


text:
Automatically playing similar songs. To disable, switch Autoplay to 'OFF' under Settings
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Boulez: Piano Sonatas Nos. 1-3
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text:
Thirty years ago this week, this column reported that, "Castle Valley residents were a little surprised to wake up to a fresh covering of snow last Saturday morning. Some areas received about four or five inches of powder while others received just a trace. The folks in Castleton measured a foot of snow, forcing some residents like Al and Ginny Duncan to stay home until the stuff melted.
"Alvie Johnston came to the rescue of many families there by clearing their driveways with his tractor and blade."
In other news in that column 30 years ago this week, it was reported that the Castle Valley Institute (now Day Star Academy) was to offer a musical program entitled "The Second Coming of Christ." The program was presented previously in Provo and Salt Lake City.
Linda Jarman, a member of the Castle Valley Property Owner's Association, was asking for support from residents at the association meetings. Attendance was rather poor and she said the POA needed the people to come out.
We used to have a lot of kids living in Castle Valley. At one point there were two school buses based out here to handle the throng of students who attended the Moab schools. Over the years the numbers have dwindled until a small bus is all that is required to handle our students who receive their education in Moab.
As a school bus driver 20 years ago, I was impressed to pass along an observation in "Castle Valley Comments" that I noticed about our kids. I wrote: "I know I'm being a little biased when I mention this, but I've always thought that Castle Valley kids are above average. In fact, author Garrison Keillor's statement in his best-selling book, "Lake Wobegon Days," that says their women are strong, their men are good looking and their children are above average, reminds me of Castle Valley folks.
"I was impressed to read that in Grand County High School's honor roll for the second term, 14 of the valley's 18 high school students were listed among that honor roll group, an impressive 78 percent of them."
Today, our women are probably still pretty strong, our men have become aesthetically challenged and we have very few children in high school.
Twenty years ago this week, the fire department had a fire call to Creekside Lane. "A small but potentially dangerous fire occurred last Friday, Feb. 12, at the home of Chuck Jenks on Creekside Lane," the column noted. "Jenks was separating a small stove from a propane tank when propane escaped and was ignited by a nearby water heater.
"The blaze caused about $300 in damage before it was controlled. The Castle Valley Fire Department immediately responded to the incident. Jenks brother, Ken, who was visiting, suffered minor burns and smoke inhalation, but was not hospitalized."
Today, the Castle Valley Fire Department is nearing the 36th anniversary of when it received a state surplus 1,200-gallon fire truck and began to be organized as a fire department. In 1977, a picture appeared in The Times-Independent showing county and fire officials receiving the "key" to the vehicle. I don't know what key they used because those old military trucks didn't have keys. Anyway, the department began to slowly build a fire house from the receipts from barbecues put on by the volunteer firemen and women and basketball games against the Moab Fire Department. The department now has nine vehicles, five owned by the department and four state surplus engines. The 18 volunteers are constantly receiving instruction from semi-weekly training meetings and other sources. Last month, six members attended a winter fire school in St George, Utah, and in May, others will attend an annual engine training course sponsored by the State Division of Forestry, Fire and State Lands. The department will also soon receive 12 used self-contained breathing apparatus (SCBA) units from the city of Price to replace the department's older, outdated units.
The foundation drilling work on the Colorado River Pathway Project is expected to finish next week. The next phase, requiring nighttime closures of state Route 128, will likely take place over the next few weeks as subcontractors and project engineers confirm their schedules.
This column will advise when this next phase involving full nighttime closures will take place. Signs on the road at both ends of the project will also advise motorists well in advance of the occurrence.


text:
Friday 05 October
Reforestation facts
- Reforestation usually involves replanting areas of forest which have previously been damaged or destroyed, using native tree species.
- Reforestation is of great importance, as estimates suggest that at the current rate of deforestation, there may be no rainforest left within 100 years.
- Huge areas of forest have already been lost, for example, only around eight percent of the Atlantic forest in South America now remains.


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By Doug Oakley
Staff Writer
Bay Area News Group
BERKELEY -- In an attempt to prevent the next school shooting from happening here, the Berkeley school district will spend about $2 million on "armed intruder" training and security devices to prevent or reduce deaths in the event someone comes on campus with a gun.
The school board last year hired two security consultants at a cost of $70,000 to look at all 20 schools following the Dec. 14, 2012, massacre of 20 first-graders and six adults at the Sandy Hook Elementary School in Newtown, Conn.
"The incident at Sandy Hook has made us all aware of the need to be prepared at all our schools," Superintendent Donald Evans said at Wednesday's meeting.
The board voted 2-1 with two members absent to spend money on armed intruder training, the purchase of public address systems and classroom door locks for all the schools.
The district also plans to install live video cameras in all the schools so that someone can monitor them and use a public address system to warn students and teachers in the event of a shooting.
But the board balked at approving the purchase of the video cameras until it formulates a privacy policy on their use, even though nine schools already have some form of cameras installed on campus.
"We don't feel installing cameras is the answer to student safety," said Paula Phillips, president of the Council of Classified Employees. "We don't want them to be used as a gotcha tool, an evaluation tool or a discipline tool."
Board member Julie Sinai said she wants to make sure the cameras don't invade privacy.
"Cameras are somewhat controversial, and I don't want to adopt this without any knowledge of the community that we are having this conversation," Sinai said. "But I support the idea of using cameras to deal with an armed intruder."
In its assessment of Berkeley school security, Dimensions Unlimited said principals at every school told them campus public address systems, which could be used to warn teachers and students, are currently "nonexistent, not operating or deficient in some way. Each site also identified problems with communicating with the district office in emergencies and on a day-to-day basis by radio or telephone."
Edu-Safe Associates found that although each school has a well-thought-out, written emergency plan, "staff and faculty were unfamiliar with much of the information contained in the safety plans."
Susan Craig, director of student services, said classroom door locks will be phased in at all schools over several years. She said the consultants view live video cameras, combined with a public address system to warn of a shooter on campus, as having a higher degree of security than do classroom door locks.
"From our understanding of the concern, having a functioning camera system is a better response," said Lew Jones, director of facilities.
The consultants hired by the school district also recommended having a Berkeley police officer stationed at every school. Doing so would cost $200,000 a year per school and is deemed too costly, Craig said.
Contact Doug Oakley at 925-234-1699. Follow him on Twitter at www.twitter.com/douglasoakley


text:
Police issue warrant for Queen Elsa after town is hit by freezing temperatures
SLIDELL, Louisiana (SBG) —
Louisiana police need your help in finding a suspect wanted for the dangerously low temperatures that recently hit the area.
The Slidell Police Department shared the wanted poster Tuesday and is offering a whopping $100,000,000 for her -- dead or alive.
Approach with caution!


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In his first national television interview since the NYSE terrorist plot was revealed, former New York Stock Exchange Chairman and CEO Richard "Dick" Grasso congratulated authorities while expressing reservations.
Continue Reading Below
"The government has a responsibility to … become transparent," Grasso told FOX Business' Neil Cavuto on Wednesday in an exclusive interview. "They're losing the confidence of the American people."
FBI Deputy Director Sean Joyce testified on Tuesday that the NSA's controversial surveillance of telephone and Internet communications foiled more than 50 terrorist plots, including one to bomb the Big Board. "The New York Stock exchange is the symbol of America's economic excellence," Grasso said. "Those who want to bring the country down look upon the stock exchange as a proxy … in essence, the assault and perhaps extinguishment of our way of life." Cavuto questioned the secret surveillance program's effectiveness and pressed the former exchange head on whether he believed lives were indeed saved. "Three thousand people died that day in September because we weren't doing the things that needed to be done," Grasso responded, referring to the September 11, 2001 terrorist attacks. "We followed Bin Laden in the latter part of the '90s. We had a shot at him. We didn't take it. Who knows whether (we) had taken that shot, 9-11 would have never occurred." The former NYSE chief reminded Cavuto the stock exchange was subject to acts of terror several times prior to 1993's first world trade center bombing. "In 1979, the FLN blew up a small explosive on a Sunday evening in front of our broad street entrance." Grasso said. "And then in 1989, an activist group actually got on to the trading floor, penetrating our security." "The stock exchange represents a plumb," Grasso said, "to those who hate our way of life."


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Packers Pound Vikings Sunday Night
The Green Bay Packers offense sliced and diced a porous Vikings defense in a 44-31 win Sunday night at the Metrodome.
The Vikings looked to have the early momentum after Cordarrelle Patterson returned the game's opening kickoff 109 yards to the end zone for a 7-0 lead. Patterson's score tied an NFL record, set by Antonio Cromartie of San Diego at the Dome.
However, the Vikings defense could not stop the Packers, who converted 13/18 third downs and went 2-2 on fourth down conversions.
Green Bay never had to punt and never turned the ball over, while mounting scoring drives of 90, 70, 80, 93, 80, 74, 53 and 16 yards, respectively.
Meanwhile, the Vikings offense could not get anything going with Christian Ponder at quarterback. The previously benched signal caller was 14/21 for 145 yards and was sacked three times.
His Packers counterpart, Aaron Rodgers was an efficient 24/29 for 285 yards with two touchdowns.
The 1-6 Vikings are in Dallas next week to take on Tony Romo and the Cowboys.


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If your ex is showing you a little bit of interest, or seems more interested in going out and spending time with you than before, or if you notice signs that your ex is trying to flirt with you, then it's okay to be a little hopeful but you need to avoid jumping the gun.
Are you asking yourself "does my ex want to get back with me"? These are definitely very common signs that your ex is interested in getting you back. But even if you want to get back with your ex, you should not simply jump into things. The best way to play things is to play hard to get (in moderation), which is probably what your ex will best respond to anyway.
If you simply jump into things full force, then you may find your ex pushing you back again. In fact, if your ex is giving indications that he or she wants you back, then the odds are, it was you playing hard to get that led to the renewed interest in the first place. Usually when you break up with your ex, or he or she breaks up with you, there is a natural level of missing one another, or longing to get back together. This is especially true following a relationship of a year or longer.
Your ex is probably going to miss you no matter what, because of how many memories were shared together during this period of time. But there are other emotions that come into play including past regrets. If you are wondering "does my ex want to get back with me" the odds are that your ex may be thinking the same thing for the same reasons. Sometimes when an ex shows interest again following a break up however, it is only a game. They may see that you love them, and they may simply be trying to get attention, without actually intending to get you back. So, unless your ex really seems genuinely interested in spending time with you, they may just be passing the time because they have no other prospects on the horizon.
And worst of all they may see this as away to get revenge for some perceived wrong. This is why it is important not to jump the gun, and why you should focus on reading into the situation before you act on it. This is common, and a lot of people find
themselves wondering "does my ex want to get back with me?", but the truth is, its better to get a feel for the situation before you act. In reality, if your ex does want to get back with you, playing hard to get (in moderation) is the best scenario because it will prevent you from getting hurt if your ex is not really serious about getting back with you.


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'Weave Housing' is a design proposal for an urban mixed use complex in Denver CO, with 160 apartment units, retail and parking. Inspired by a children's potholder loom, the facade texture supports multiple interior apartment arrangements with units occupying one or two bays in width, and one or two levels in height, allowing for flexibility and plan variety. By weaving occupiable volumes across the facade, private balconies and overhangs are created, establishing zones of natural shading and meeting the desired passive energy strategy. The long dimension of each apartment unit is stretched parallel to the corridors, taking advantage of natural light and views while minimizing the depth light is asked to penetrate the space.
- Architects: Meridian 105 Architecture
- Project Location: Denver, Colorado


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Ring out, wild bells, to the wild sky,
The flying cloud, the frosty light:
The year is dying in the night;
Ring out, wild bells, and let him die.
Ring out the old, ring in the new,
Ring, happy bells, across the snow:
The year is going, let him go;
Ring out the false, ring in the true.
Ring out the grief that saps the mind
For those that here we see no more;
Ring out the feud of rich and poor,
Ring in redress to all mankind.
Ring out a slowly dying cause,
And ancient forms of party strife;
Ring in the nobler modes of life,
With sweeter manners, purer laws.
Ring out the want, the care, the sin,
The faithless coldness of the times;
Ring out, ring out my mournful rhymes
But ring the fuller minstrel in.
Ring out false pride in place and blood,
The civic slander and the spite;
Ring in the love of truth and right,
Ring in the common love of good.
Ring out old shapes of foul disease;
Ring out the narrowing lust of gold;
Ring out the thousand wars of old,
Ring in the thousand years of peace.
These lines, taken from Alfred, Lord Tennyson's 'Ring Out, Wild Bells', a part of the elegy 'In Memoriam' written for Arthur Henry Hallam, seem fitting to mark the turning of this year into the next.
May the New Year bring health, wealth and happiness to each one of you and your families.


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Brand Label: Baccarat
ITEM MOVED TO ARCHIVE: On January 30, 2018 5:24 pm, Fashion Stylist Online noted this item may be out of stock at Bergdorf Goodman because it was not referenced in their latest online catalog. If this item is out of stock at Bergdorf Goodman, you may be able to find similar fashions sold there or elsewhere on our Baccarat Designer Brand Directory.
Available for Purchase Online at Bergdorf Goodman for $175.00Pin It
Handcrafted of full-lead crystal. 3.375"W x 2.5"T. Made in France.
Shop other brand label items from Baccarat on FashionStylist.com.
This item was published for sale online by Bergdorf Goodman on January 30, 2018 10:54 am and last updated by us January 30, 2018 5:24 pm.
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New promo codes and links offering limited time promotions, sales coupons, and special offers on Baccarat designer fashions and accessories will be posted on each designer label apparel page. For the latest up to date information on this Baccarat Lucky Butterfly Blue Iridescent Figurine fashion item, including product specifications, ordering options, pricing, shipping details, high resolution pictures, shopper comments, and other sales media, visit the Bergdorf Goodman Online Store.


text:
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For carrying out section 301 and title IV of the Public Health Services Act with respect to human genome research [$516,028,000] $533,959,000 (Public Law 111-117, Consolidated Appropriations Act, 2010.)
|Sources of Funding
|FY 2009 Actual
|FY 2010 Enacted
|Type 1 Diabetes
|Subtotal, adjusted appropriation
|Real transfer under Director's one-percent transfer authority (GEI)
|Real transfer to Global Fund to fight HIV/AIDS, Malaria and Tuberculosis
|Comparative transfer to NLM for NCBI, Public Access
|Comparative transfer under Director's one-percent transfer authroity (GEI)
|Comparative transfer to the Global Fund to fight HIV/AIDS, Malaria and Tuberculosis
|Comparative transfer from DHHS for Autism
|Subtotal, adjusted budget authority
|Unobligated balance, start of year
|Unobligated balance, end of year
|Subtotal, adjusted budget authority
|Unobligated balance lapsing
|Total obligations
1/ Excludes the following amounts for reimbursable activities carried out by this account:
Excludes $247,328 in FY 2009; $116,985 in FY 2010; and $166,862 in FY 2011 for royalties.
Includes FTEs which are reimbursed from the NIH Roadmap for Medical Research.
FTTP = Full-time temporary equivalent
FTE = Full-time equivalent
Major changes by budget mechanism and/or budget activity detail are briefly described below. Note that there may be overlap between budget mechanism and activity detail and these highlights will not sum to the total change for the FY 2011 budget request for NHGRI, which is $18.083 million more than the FY 2010 Enacted level, for a total of $533.959 million.
Research Project Grants (RPGs) (+$6.738 million, total $176.126 million):The NIH Budget policy for RPGs in FY 2011 provides a two percent inflationary increase in noncompeting awards and a two percent increase in the average cost for competing RPGs. NHGRI will support a total of 257 Research Project Grant (RPG) awards in FY 2011. Noncompeting awards will decrease by 35 awards and $16.860 million. Competing RPGs will increase by 33 awards and $21.700 million. NHGRI will continue to support new investigators and to maintain an adequate number of competing RPGs.
Research Centers (+$5.805 million; total $199.309 million): The FY 2011 budget policy provides a three percent increase. The number of research centers is expected to increase by two to 40 in FY 2011.
Comparative Genomic Sequencing (-$10 million; total $25 million): This decrease represents a continuation of on-going reprioritization and is balanced by increases in the Medical Sequencing and The Cancer Genome Atlas large scale sequencing components (see below). This will allow the Institute to devote a larger proportion of the overall large-scale sequencing effort in FY 2011 to projects directed toward understanding disease.
Medical Sequencing (+$5.811; total $44.681 million): Medical sequencing continues to be an area of growth for the NHGRI. With large-scale sequencing now completely transitioned to the next-generation sequencing instruments, many new opportunities have been created to apply genomic tools to the study of human disease and the application of that information to the development of new approaches to disease management.
The Cancer Genome Atlas (+$8 million; total $43 million): Now in its full-scale production phase, the TCGA effort will be generating enormous amounts of data that will change the face of cancer research. The increase in FY2011 is necessary to maintain the pace of the program, which received significant support from ARRA funds in FY 2009 and FY 2010.
Section 301 and title IV of the Public Health Service Act, as amended.
This document provides justification for the Fiscal Year (FY) 2011 activities of the National Human Genome Research Institute (NHGRI), including HIV/AIDS activities. Details of the FY 2011 HIV/AIDS activities are in the "Office of AIDS Research (OAR)" Section of the Overview. Details on the Common Fund are located in the Overview, Volume One. Program funds are allocated as follows: Competitive Grants/Cooperative Agreements; Contracts; Direct Federal/Intramural and Other.
In 2003, the National Human Genome Research Institute (NHGRI) oversaw the completion of the Human Genome Project, one of the most ambitious collaborative scientific achievements in history. In the years that have followed, NHGRI has built on that initial success by supporting research to increase understanding of the human genome, drive down the cost of sequencing, and apply the new knowledge and genomic tools to improve preventive and therapeutic health strategies. In this way, NHGRI is creating the necessary framework for a future in which genomic medicine plays a significant role in the health and wellbeing of the nation.
Both independently and in conjunction with other Institutes and Centers, NHGRI continues to support genome-wide association studies (GWAS) that have uncovered many genetic factors associated with common diseases. These are a vital step in the pathway that leads from the Human Genome Project to a future in which genomic medicine is commonplace.
The Genes, Environment and Health Initiative (GEI) is building tools and a knowledge base to allow better understanding of the interplay of the genome with environmental factors (ranging from diet to physical activity to exposure to pollutants) in health. GEI is examining this interplay in some of the leading causes of morbidity and mortality in the Nation, such as cardiovascular disease and type 2 diabetes, as well other conditions such as lung cancer and addiction.
NHGRI's Medical Sequencing Program is currently gathering genomic sequence data from individuals to gain more information about specific genes and their relationship to disease. The NHGRI-funded sequencing centers across the country are advancing understanding of common diseases such as cardiovascular disease, diabetes, and metabolic syndrome, as well as rarer ones. Gaining a better understanding of the genetic underpinnings of disease and of individual disease predispositions will translate to better treatments for tens of millions of Americans.
In addition to funding studies that elucidate the functions of our genomes and how they influence our health, NHGRI has driven development of revolutionary new technologies that are lowering the price and increasing the speed with which we can read genetic data. NHGRI's funding of technology development has reduced sequencing costs over 100 fold since 2004, when an individual's complete genome sequence cost about $10 million. By the end of 2009, it cost less than $50,000. The "$1000 Genome Project" is on track to reduce whole genome sequencing costs to a fraction of even that, so that genetic analysis will be no more expensive than many routine medical tests. Although vendors of DNA sequencing instruments or services publicly describe their costs of generating a human genomic sequence as $10,000 or even less, these figures generally represent only the cost of the actual reagents (supplies) used in the sequencing process. However, the actual costs must be the focus of the reduction. The actual costs are referred to as "fully loaded costs", i.e., what it actually takes to produce useful data, including reagents, personnel, instrument amortization, facilities and other overhead costs, and computational analysis. Seventeen groups of scientists are funded as part of NHGRI's technology development effort, which was singled out as NHGRI's Signature Project for funding under the 2009 American Recovery and Reinvestment Act, due to its significance for the broader NHGRI and NIH portfolios. The ability to sequence many more genomes faster and cheaper brings a new set of challenges. Chief among these is coping with the huge datasets that are generated, since each genome represents many gigabytes of information. Thus, NHGRI is funding projects to create the computational genomic tools necessary to store, assemble, and analyze the data, as well as to share those results with the scientific community to maximize the return on the public's investment in this research.
NHGRI's population genomics programs are helping to explore the use of electronic health records to integrate genomic information into routine clinical care. Coupled with several NHGRI-funded pharmacogenomics studies (studies of how individual genetic variations affect drug metabolism) that will be launched soon, these efforts have the potential to assist clinicians in prescribing the right drug for the right patient and to reduce adverse drug reactions. The ability to know in advance whether or not a particular drug will be ineffective or have a greater potential for an adverse drug event in a particular individual should improve health and reduce healthcare costs. NHGRI-funded pharmacogenomics studies will examine hormone therapy's effects on cardiovascular diseases and diabetes, vitamin therapy to prevent stroke, chemotherapy for breast cancer, and statin therapy for high cholesterol levels.
Programs such as these will create the knowledge and tools to allow individual patients to use their genetic information in the clinic, but NHGRI is also working to ensure that novel and effective therapeutics are available. There are nearly 7,000 rare disorders, but pharmaceutical development has ignored the vast majority due to the low economic incentive in the private sector to assume the high risk and high cost of drug development for diseases that affect relatively few people. Similarly, many diseases with profound public health impact in the developing world are neglected because of the low prospect for return on the investment in drug development for them. The NIH Therapeutics for Rare and Neglected Diseases program, or TRND, is a program created in May 2009 and operated by NHGRI to help address this problem. In synergy with the NIH Chemical Genomics Center (also operated by NHGRI), the two programs comprise the first integrated drug development pipeline to produce new treatments for rare and neglected diseases.
Beyond the scourge of rare and neglected diseases, cardiovascular disease, diabetes, and other common conditions that challenge the industrialized world are increasingly global in their impact. The NHGRI-administered Center for Research on Genomics and Global Health (CRGGH) is helping address these issues, using genomic tools to understand the interplay between obesity, hypertension, and diabetes in different human populations, with a focus on African-American and African populations. Findings from CRGGH will inform discussions about health disparities, whether between different ethnic groups in the United States or between nations.
Throughout all these programs, NHGRI is helping to train the next generation of scientists and scientist-clinicians through its funding for Centers of Excellence in Genomic Science and Centers for Excellence in Ethical, Legal, and Social Implications Research. Through these basic, translational, clinical, and educational efforts, NHGRI is moving us rapidly closer to a day when personalized medicine is a literally lifesaving and commonplace reality.
Overall Budget Policy: The FY 2011 request for NHGRI is $533.959 million, an increase of $18.083 million or +3.5 percent over the FY 2010 Enacted level. NHGRI is increasing funding for Medical Sequencing and The Cancer Genome Atlas while proportionally decreasing funding for Comparative Genomics Sequencing. This will allow the NHGRI to devote a larger proportion of the overall large-scale sequencing effort in FY 2011 to projects directed toward understanding disease. Funds are included in R&D contracts to support several trans-NIH initiatives, such as the Therapeutics for Rare and Neglected Diseases program (TRND), the Basic Behavioral and Social Sciences Opportunity Network (OppNet), and support for a new synchrotron at the Brookhaven National Laboratory, as well as increased support for other HHS agencies through the program evaluation set-aside. In FY 2011, NHGRI will support new investigators on R01 equivalent awards at success rates equivalent to those of established investigators submitting new R01 equivalent applications.
Program Descriptions and Accomplishments
Basic Genomics
Among the primary objectives of contemporary biomedical research are to define how the human genome functions, understand how its malfunctions lead to specific diseases, and use that knowledge to develop new preventive strategies, diagnostic methods, and therapies. The NHGRI extramural program provides a unique window into these questions for the entire biomedical research enterprise. By supporting the development and use of high throughput methods to produce high quality, large datasets comprising both comprehensive descriptions of the human genome sequence in healthy and diseased individuals, and the genomes of other organisms, NHGRI supports research across all disease states by researchers around the world.
The Comparative Genomic Sequencing program generates genomic sequence data from many sources to further understanding of the human genome by revealing its functional components. Comparison of the genome sequence of humans with those of both closely and distantly related organisms identifies regions of similarity and difference. Such comparisons can identify similar regions of genomes that can be inferred to have been preserved throughout evolution because they are involved in critical biological functions, while regions of differences can be inferred to be associated with human-specific functions. Such knowledge can lead to insights into the evolution, structure, and function of human genes and can point to new paths to combat human disease. Currently, the genomes of 197 organisms are either in the sequencing pipeline or have been completely sequenced using NHGRI funding. Ongoing sequencing targets include non-human primates and other mammals; fungi, including multiple strains of yeast; and other disease-causing organisms, such as parasites and their host vectors. NHGRI funds this work in three large-scale sequencing centers that are worldrenowned for their cost effective, high quality work. Recent highlights of this sequencing program include the publication of the genome of domestic cattle, the first livestock mammal to have its genetic blueprint sequenced and analyzed.
Budget Policy: The FY 2011 budget estimate for Comparative Genomic Sequencing is $25.000 million, a decrease of $10.000 million or -28.6 percent over the FY 2010 Enacted level. This decrease represents a continuation of on-going reprioritization and is balanced by increases in the Medical Sequencing and The Cancer Genome Atlas large-scale sequencing components (see below), so that the total amount of NHGRI spending on large-scale sequencing will remain constant. This will allow the Institute to devote a larger proportion of the overall large-scale sequencing effort in FY 2011 to projects directed toward understanding disease, specifically, Medical Sequencing (see below) and The Cancer Genome Atlas (see below). The activity in Comparative Genomic Sequencing will continue the NHGRI's signature efforts to generate the genomic sequence data from many sources; these data represent a key resource which, along with other data sets such as those from the ENCODE and modENCODE projects (see below), are needed to reveal the functional components of the human genome.
NHGRI's medical sequencing program was initiated in 2006 to drive continued improvement in DNA sequencing technologies and to produce data critical for biomedical research. A number of studies currently are underway to identify the genes responsible for several relatively rare disorders; to survey the range of gene variants that contribute to certain common diseases; to better characterize the genomic regions containing genetic components underlying many common diseases, such as diabetes, breast cancer, schizophrenia, and Crohn's disease; and ,in collaboration with the National Institute of Allergy and Infectious Disease (NIAID), to sequence the genomes of important human pathogens, such as those that cause malaria and sleeping sickness, and their invertebrate vectors. Recently, NHGRI reached one of the goals of its Sequencing Technology Program (see below), using next-generation sequencing technologies to sequence the complete genome of an individual for approximately $100,000. Anticipated continued decreases in this cost will make it increasingly affordable to sequence samples from a large number of patients, not only in gene regions, but across the entire genome.
Budget Policy: The FY 2011 budget estimate for Medical Sequencing is $44.681 million, an increase of $5.811 million or 14.9 percent over the FY 2010 Enacted level. Medical sequencing continues to be an area of growth for the NHGRI. With large-scale sequencing now completely transitioned to the next-generation sequencing instruments, many new opportunities have been created to apply genomic tools to the study of human disease and the application of that information to the development of new approaches to disease management. In FY 2011, the NHGRI will continue to increase the proportion of its Large-Scale Sequencing program funds that support Medical Sequencing component. Many of the new opportunities will be pursued in collaboration with other NIH ICs.
All cancers are diseases of the genome, as they result from DNA mutations and epigenetic changes that lead to uncontrolled cell growth. The Cancer Genome Atlas (TCGA), a collaborative program of NHGRI and the National Cancer Institute, applies NHGRI's unprecedented capability for genomic analysis to the problem of cancer by developing a comprehensive catalog of the many genomic alterations that occur in major types of cancer, and rapidly providing these data to the research community. Taking advantage of recent advances in genomic characterization technologies, tumor and matched normal tissue samples can be analyzed for gene mutations, chromosomal rearrangements, copy number variation, gene expression alteration, and changes in epigenetic modifications. In its pilot phase, TCGA met several objectives, mostimportantly the demonstration of the feasibility and value of a genomic analysis of the genomes of specific tumor types. TCGA's first undertaking, which focused on brain cancer, demonstrated in FY 2009 the technical feasibility and potential clinical utility of large-scale, multi-dimensional analysis of cancer genomes. Comprehensive characterization of ovarian cancer, the second tumor type tackled by TCGA, is opening new avenues of research for diagnosis and treatment of this devastating disease. With successful completion of the pilot phase in 2009, TCGA is expanding, with a plan to investigate 20 to 25 additional tumor types by 2015.
Budget Policy: The FY 2011 budget estimate for TCGA is $43.000 million, an increase of $8.000 million or 22.9 percent over the FY 2010 Enacted level. Now in its full-scale production phase, the TCGA effort will be generating enormous amounts of data that will change the face of cancer research. The increase in FY2011 is necessary to maintain the pace of the program, which received significant support from ARRA funds in FY 2009 and FY 2010.
NHGRI supports research to identify and characterize the function of all parts of the genome and to understand their biological relevance. Efforts to uncover functional elements are not limited to the human genome, since understanding the genomes of other, "model," organisms can also give insight into the structure and function of the human genome. The major activities in this area are the ENCODE and modENCODE projects. ENCODE, the ENCyclopedia Of DNA Elements, is an international research consortium organized by the NHGRI to identify all functional elements in the human genome. Until recently, most studies of genome function have focused on the small fraction of the genome that contains protein-coding genes, overlooking the many other parts of the human genetic blueprint important to biological function. ENCODE is designed to take advantage of new analytical technologies, including next-generation sequencing, that can be applied at high throughput to identify all of the coding and noncoding (regulatory) elements in the human genome. The data, as with other NHGRI resource projects, are made available rapidly, prior to publication, through the ENCODE Data Coordination Center and other public databases. Analysis of the data is ongoing and promises to lead to new ways of thinking about the genome that will result in an enhanced understanding and improvement of human health. The Model Organism ENCODE (modENCODE) Project extends the ENCODE approach to two model organisms that are widely used in biomedical research, the fruit fly, and the round worm. The introduction of next-generation sequencing technology into both the ENCODE and modENCODE projects has resulted in a dramatic increase in the amount and quality of data without a significant increase in cost. The data that the modENCODE project produces already are providing important insights into the biology of these organisms, as well as providing a valuable tool for comparative studies aimed at understanding human biology.
Budget Policy: The FY 2011 budget estimate for Genomic Function is $57.433 million, an increase of $1.943 million or 3.5 percent over the FY 2010 Enacted level. Activity in Genomic Function will remain essentially constant, maintaining the proportion of the NHGRI extramural budget devoted to this area. One reason why this can be done is that the introduction of next-generation sequencing technology has enabled a significant increase in the amount of data generated without an increase in cost. The Institute also will continue to fund meritorious investigator-initiated applications submitted in response to announcements that encourage new technologies and new approaches to the analysis of genomic function.
Although the genome sequence variation between two people is less than one percent, this tiny difference underlies a variety of observable characteristics ranging from the benign, such as hair or eye color, to disease, such as diabetes, cancer, Alzheimer's, or heart disease. NHGRI began the comprehensive, genome-wide mapping of human variation by leading the International HapMap Project, which charted the common patterns of genetic variation in the world's population, specifically the single letter spelling variations in our genome's alphabet known as single nucleotide polymorphisms, or SNPs. To get an even more detailed description of human genetic variation, the 1,000 Genomes Project is sequencing the genomes of approximately 1,200 people from around the world to produce a new map of the human genome that will provide a view of biomedically relevant DNA variations at a very high resolution. As with other major human genome reference projects, data from the 1,000 Genomes Project will be made swiftly available to the worldwide scientific community through freely accessible public databases. In addition, larger scale genomic variants, involving a few thousand to more than a million bases, are now thought to be a significant cause of disease. NHGRI has initiated several projects to characterize such "structural variation" in the human genome. Moreover, significant information about human structural variation will result from the 1,000 Genomes project..
Budget Policy: The FY 2011 budget estimate for Genomic Variation is $17.296 million, an increase of $585 thousand or 3.5 percent over the FY 2010 Enacted level. Activity in Genomic Variation will remain essentially constant, maintaining the proportion of the NHGRI extramural budget devoted to this area. The primary emphasis within this program will be on the full-scale implementation of the 1000 Genomes Project, which has expanded to include the analysis of structural variation in the human genome in light of the increasing amount of evidence that structural variants contribute significantly to human disease. The Institute also will continue to fund meritorious investigatorinitiated applications submitted in response to announcements that encourage new technologies and new approaches to the analysis of genetic variation, and the role that genetic variation plays in the determination of human disease, disease susceptibility, and environmental sensitivities.
New genomic methods, such as next generation sequencing, along with attempts to correlate sequence data with other biological data, have led to a rapid rise in the volume and complexity of genomic data. As the costs of generating genomic data continue to decrease in the future, the rate of data production will increase even more rapidly, and the effort required to manage the data and make them available to the entire scientific community will increase significantly. NHGRI supports a program in computational genomics research to develop new computational methods that will facilitate the acquisition, analysis, and dissemination of the data generated in genome-wide studies. Through this program, NHGRI supports the development of new technologies and new analytical approaches to the emerging challenge of how to analyze the enormous amount of data generated by large-scale, genomic studies and how to make such large datasets available to the broad research community. NHGRI will continue its support for genomic databases because these are essential resources that link biological data to genome sequence information and are utilized worldwide to accelerate biomedical research. Along with these resources, NHGRI will continue to encourage investigatorinitiated research to develop robust software tools to improve on the utility of these genomic databases and the ability to analyze genomic data.
Budget Policy: The FY 2011 budget estimate for Computational Genomics is $52.576 million, an increase of $1.778 million or 3.5 percent over the FY 2010 Enacted level. Activity in Computational Genomics will remain essentially constant, maintaining the proportion of the NHGRI extramural budget devoted to this area. Effort will be directed to increasing the efficiency of data storage and distribution mechanisms, as the amount of data that needs to be processed has increased significantly with the introduction of next-generation sequencing and other new genomic technologies. In FY 2011, the NHGRI will continue its support for the essential biomedical research resource represented by genomic databases. The Institute also will continue to fund meritorious investigator-initiated applications submitted in response to announcements that encourage new technologies and new approaches to the rapidly emerging issue of public access to large genomic datasets.
The mission of NHGRI's technology development programs is to make DNA sequencing and other genomic analyses faster and more cost effective for use in medical research and, eventually, health care. The cost of DNA sequencing has fallen dramatically, by a factor of more than 100, over the past decade and continues to fall due, in large part, to research supported by NHGRI. The ability to sequence an individual genome inexpensively would not only further biomedical research, but would enable health care professionals to tailor diagnosis, treatment, and prevention strategies to each person's own genetic profile. After the completion of the Human Genome Program, NHGRI continued to support the development of new technology, and in 2004 started a program to drive sequencing costs down from approximately $10 million for a genome the size of the human to $100,000 within five years. In 2009, that goal was exceeded. To do so, NHGRI funded seventeen teams of investigators who worked toward those goals, several of whom also participated in private sector efforts with similar goals. But $100,000 per genome does not put sequencing into the realm of a diagnostic technology, so NHGRI is continuing its sequencing technology development efforts. Now the majority of effort is to achieve another 100-fold reduction in cost, to $1,000 or less for a high quality sequence of a human genome. Seventeen groups of investigators are actively supported to work toward that goal, and in FY 2009 ten new awards or extensions of existing awards were made to accelerate progress.
Budget Policy: The FY 2011 budget estimate for Technology Development is $48.032 million, an increase of $1.624 million or 3.5 percent over the FY 2010 Enacted level. The NHGRI will continue in FY 2011 its ground-breaking efforts to reduce the cost of DNA sequencing so that this technology, which is increasingly become central to biomedical research, can become a widely disseminated research tool and, beyond that, a tool for individual healthcare. The Institute also will continue to fund meritorious investigator-initiated applications submitted in response to announcements that encourage the development of new technologies for biomedical and translational research.
FY 2010 Level: $25.000 million
FY 2011 Level: $25.875 million
Change +0.875 million
Having sequenced the human genome (and the genomes of a number of other organisms to aid the annotation of the human sequence), the NHGRI is intensifying its focus on realizing the long-range objective of making sequencing a tool for both research and medical practice. As more is learned from sequencing and other research deciphering the genome's role in disease, and as the cost of sequencing decreases, sequence information will become ever more integral to both biomedical research and the provision of medically relevant information to individuals. The NHGRI selected advancing sequencing technology as its ARRA Signature Project. In addition, the NHGRI continues other efforts to improve technologies sufficiently to produce a high quality human genome sequence for $1,000 or less. The "$1000 genome initiative" has already led to successful commercialization of technologies that received significant NHGRI research support. The definition of "sequencing" is expanding, so that new systems allow simultaneous collection of multiple different kinds of genomic datasets on a single platform; this capacity should accelerate the transition from research to clinical systems.
And, advances over the next two years are expected to be as stunning as those over the previous two. New technologies are already increasing the pace for sequencing projects such as The Cancer Genome Atlas (TCGA) and The 1000 Genomes Project. Only two years ago, costs for projects such as TCGA and 1000 Genomes would have been prohibitive. However, they are now possible because of stunning advances in technology and in our understanding of the human genome that are continuing to reduce costs.
Multi-investigator, interdisciplinary research teams that can use and expand the data sets and technologies developed by the Human Genome Project are crucial to develop novel and innovative genomic research projects and to foster the wider application of comprehensive, high-throughput genomics methods to the study of human biology and disease. Started in FY 2001, the NHGRI's Centers of Excellence in Genomic Science (CEGS) program supports the formation of such teams and provides focal points across the country to provide education and training about genomic research opportunities to members of under-represented population groups. In FY 2009, NHGRI announced grants to establish two new CEGS (one focused on psychiatric conditions and a second on regulation of the expression of genes during health and disease) and renewed support of two CEGS (one studying epigenetic changes and the other variations found in the human population and how these are related to disease).
Budget Policy: The FY 2011 budget estimate for Other Basic Genomics is $60.315 million, an increase of $2.042 million or 3.5 percent over the FY 2010 Enacted level. In FY 2011, the NHGRI will continue to support the CEGS program in its efforts to stimulate highly innovative research approaches that will substantially advance genomic approaches to the study of a biological problem, and to foster the wider application of comprehensive, high-throughput genomics methods to the study of human biology and disease. The Institute will also continue to fund meritorious investigator-initiated applications that will increase the ability of genomics to have a major impact on the progress of biomedical and translational research.
NHGRI is strongly committed to translating the information gleaned from studies of genomic function and variation into clinical applications. Diseases arise from a complex interplay between genes and environment; therefore, DNA variations, regulatory elements, and external factors acting "on" the genome must all be considered in diagnosing and treating patients. Understanding this interplay will revolutionize our approach to health and health care, allowing not only much more accurate prediction of disease, but, ultimately, individually-based disease prevention and treatment. In FY 2009, Genes, Environment and Health Initiative (GEI) programs in functional and translational studies and systems biology took the first steps in determining the role of GWA-defined genetic variants in disease, and using that information in clinical care. An FY 2010 GEI project is aimed at identifying all the genetic variants, even those that are quite rare, in a region of GWA-defined association through extensive sequencing in large numbers of individuals. Another "bench to bedside" translational research project is an innovative study, in collaboration with the National Heart, Lung and Blood Institute, to evaluate the use of genetic variants to personalize the dosing of a commonly-used and potentially risky medication, warfarin. Ongoing population genomics projects initiated in FY 2007 examine the unique challenges and opportunities for conducting genomic research presented by biorepositories linked to electronic medical records (EMR), and the development of standardized disease and exposure measures for this research. In particular, using EMR to define diseases and exposures in standardized ways can greatly accelerate genomic research in routine clinical care and the translation of that research to direct clinical applications. In FY 2008, NHGRI initiated a four-year, $31 million project to gain a better understanding of how specific genetic variants identified by GWA and similar studies act to influence the risk of diabetes, heart disease, cancer, and other common diseases. Scientists have already discovered more than 400 genetic variants in association with over 100 diseases and clinical traits such as cancer, cholesterol levels, and lipid levels. In FY2009, the NHGRI expects to announce a major new program to identify genetic variants associated with treatment response, using GWA in randomized clinical trials.
Budget Policy:The FY 2011 budget estimate for Population Genomics is $34.329 million, an increase of $1.161 million or 3.5 percent over the FY 2010 Enacted level. Activity in Population Genomics will remain essentially constant, maintaining the proportion of the NHGRI extramural budget devoted to this area. The NHGRI will continue in FY 2011 to support this area of research as the combination of advances in genomics with cutting-edge approaches to population studies remains of very high programmatic interest as an important strategy for addressing problems of human health. The Institute also will continue to fund meritorious investigator-initiated applications, and to collaborate with other NIH Institutes/Centers in the area of population genomics.
As the use of genetics and genomics in translational and clinical studies continues to increase, the importance of addressing the ethical, legal, and social implications (ELSI) of the results of genetic and genomic research will grow as well. NHGRI addresses such issues through its ELSI Research Program and through public consultation and community engagement activities that identify and respond to culturally specific concerns and provide participating communities opportunities for input into the design of genetic and genomic research. An important component of the ELSI program is the Centers of Excellence in ELSI Research (CEERs) program. The CEERs were established to: 1) foster the multi-disciplinary approaches necessary to make advances in understanding the issues that progress in genomic science will raise, 2) conduct ELSI research to inform the development of research, health, and public policies and practices and, 3) train the next generation of ELSI researchers. Four CEERs were originally established around the country in FY 2004 and in FY 2008 two new centers were funded. In FY 2010, the original Centers are applying for competitive renewal, which will provide NHGRI with an excellent opportunity to assess accomplishments of the CEER program and determine the on-going role that this component will play in the Institute's ELSI program.
Budget Policy: The FY 2011 budget estimate for ELSI is $19.668 million, an increase of $665 thousand or 3.5 percent over the FY 2010 Enacted level. The ELSI budget is legislatively mandated at 5.0 percent of the total NHGRI extramural budget. In FY 2010, the NHGRI will continue to support the ELSI research program in its efforts to anticipate and address the social, legal, and ethical issues that will arise from new information about the human genome and the genetic contribution to human disease, and new approaches to applying that information to the improvement of human health.
Researchers within the NHGRI Division of Intramural Research continue to identify and characterize the genetic components of both rare and common diseases. NHGRI research groups have recently identified a gene containing variants associated with an increased susceptibility to lung cancer in family members with a history of the disease and made similar important advances in unraveling the genetic basis for melanoma, the deadliest form of skin cancer. NHGRI intramural investigators plan to continue expanding their collective focus on translational research in FY 2011. One notable advance in this area is a transdisciplinary program to characterize fully the complete set of microbes growing on human skin (the skin microbiome). Meanwhile, two NHGRI intramural clinical genomics initiatives are reaching a mature and productive stage. The first, called ClinSeq, is a pilot study aimed at developing the technologic and procedural infrastructure to facilitate large-scale genome sequencing in a clinical research setting. The second, called Multiplex, is a study intended to evaluate patients' reactions to genetic susceptibility testing for several common health conditions. Together, these two initiatives are providing a foundation for studies in genetic-based personalized medicine. The NIH Undiagnosed Diseases Program, a clinical research program to study patients with mysterious conditions that have long eluded diagnosis, is now in full stride; over 2,350 inquires have already been evaluated for potential participation and over 100 patients have been admitted into the program.
Budget Policy: The FY 2011 budget estimate for Intramural Research is $107.987 million, an increase of $3.348 million or +3.2 percent over the FY 2010 Enacted level. This increase will facilitate growth in four major areas: (1) The addition of 2-3 new Tenure-Track/Tenured Investigators working in cancer genetics, human genetics, and social and behavioral research, who will arrive at the end of FY 2010 following rigorous searches and recruitments; (2) The addition of personnel to strengthen the Institute's translational and clinical research programs. This will include the recruitment of additional physician-scientists and other health professionals with expertise in clinical research. It also includes continued growth of our flagship intramural clinical genomics projects ClinSeq and growth to support the Undiagnosed Diseases Program; (3) Continued acquisition and implementation of 'next-generation' technologies for performing large-scale DNA sequencing. Genomics continues to see major growth in terms of new methods for obtaining very large amounts of DNA sequence data at lower costs. The NHGRI Intramural Program will continue to implement these powerful new DNA sequencing technologies in FY 2011. This is requiring substantial expansion of computational infrastructure as well as increased bioinformatics and computational staffing. Note that these new technologies are increasingly being applied to clinical research projects; and (4) Continued growth of a trans-disciplinary program to explore the skin's microbiome-- all of the genomes of the microbes that inhabit human skin. This effort will help to define the delicate balance between our own cells and the millions of bacteria and other single-celled microbes that live on the skin's surface, one of the body's first lines of defense against illness and injury.
FY 2010 Level: $24.000 million
FY 2011 Level: $50.000 million
Change +26.000 million
In May 2009, NIH launched the Therapeutics for Rare and Neglected Diseases program (TRND). In synergy with the NIH Chemical Genomics Center (NCGC), these two programs now comprise the first integrated, drug development pipeline designed to produce new treatments for rare and neglected diseases.
There are nearly 7,000 "rare" disorders (ones that affect fewer than 200,000 Americans), but pharmaceutical development has ignored the vast majority, due to the low prospect for economic return. Other, more common diseases, are "neglected" because they primarily affect populations that have little money to pay for new drugs.
TRND will focus on the pre-clinical stage of drug development that is vital to meet the FDA's requirements for human testing of new drugs. It will bridge the wide gap in time and resources that too often exists between basic research and human testing of new drugs. The effort is grounded in, but aims to improve upon, existing processes for drug development in the pharmaceutical industry. TRND will work closely with disease-specific experts on selected projects, both leveraging the inhouse scientific capabilities needed for much preclinical development work and contracting out other parts, as scientific opportunities dictate. The NIH Office of Rare Diseases Research will oversee the program, and the NHGRI (which also operates the NCGC) will administer TRND's laboratory operations. This revolutionary initiative will stimulate important research collaborations involving other NIH components and academic and private sector scientists.
NHGRI's Office of the Director, part of the RMS program, oversees the operation of the Institute and includes a number of component parts. Major ongoing initiatives for which the Office of the Director provides key leadership and financial support include National DNA Day, the U.S. Surgeon General's Family History Initiative, and the development of genetics education resources for health professionals. DNA Day is an annual opportunity to educate students about genetics and genomics and to use this cutting edge field to spark their interest in science. The U.S. Surgeon General's Family History Initiative is a coordinated multi-agency effort to encourage all American families to learn more about their family health history and to employ it in preventive health care. To expand the initiative's reach and public benefit, NHGRI continues to collaborate across federal agencies to enhance the family history tool's capabilities and to engage in demonstration projects to develop evidence regarding the tool's utility, including as part of electronic health records. Projects to promote the public's awareness and participation in the initiative will also be pursued. NHGRI is taking a leadership role in facilitating the development, pilot testing, and dissemination of interdisciplinary webbased genetics educational resources for all health care professionals.
Budget Policy: The FY 2011 budget estimate for research management and support is $23.642 million, an increase of $1.126 million or 5.0 percent over the FY 2010 Enacted level. In FY 2011, the NHGRI plans to continue to develop ongoing initiatives for which the Office of the Director provides leadership and financial support. Such programs within the Office of Policy, Communication, and Education include National DNA Day, the U.S. Surgeon General's Family History Initiative, and outreach and informational resources for the general public through community and web-based activities. In addition, the NHGRI is enhancing the Risk Management Program, which includes business process reengineering, setting up new procedures and tools to ensure our continued prudent use of RMS funds. RMS funds will be used to continue funding the activities mentioned above to support the infrastructure that allows the NHGRI to pursue and achieve its mission.
NHGRI is the lead Institute for the Connectivity Map supported through the NIH Common Fund. In addition, NHGRI is a co-lead for the Common Fund-supported Molecular Libraries initiatives, including: 1) NIH Chemical Genomics Center (NCGC); 2) Cheminformatics Computing Centers (virtual synthesis, virtual screening, other applications, and R&D on new tools); and, 3) Robotics/Instrumentation Technology Development. NHGRI also co-leads the new Common Fund-supported Human Microbiome Project. An early example of the kind of work that can be expected from NCGC was the discovery of a possible therapy for schistosomiasis, a parasitic disease that affects more than 200 million people in the developing world. Working with researchers from Illinois State University, NCGC's high-throughput screening assays discovered that a class of compounds called oxadiazoles possesses the ability to inhibit a certain enzyme that is essential for the Schistosoma parasites to survive. The Human Microbiome Project (HMP) is a trans-NIH program that aims to expand upon traditional microbiology and discover what microbial communities exist in different parts of the human body and how they might change with disease. In a healthy adult, the number of microbial cells outnumbers those of the human host, but remarkably little has been known until now about how these microbes behave in vivo. HMP makes use of a metagenomic approach that reveals data about entire human-associated microbial communities. In 2009, data gathered by an NHGRI-led team revealed unexpected bacterial diversity on human skin that, it is hoped, will lead to advances in understanding a range of disorders, such as eczema, psoriasis, and acne.
Recovery Act Funding: $127.035 million
In FY 2009, NHGRI received $127.0 million under the Recovery Act. Of this amount, $77.9 million was obligated in FY 2009 and $49.1 million will be obligated in FY 2010. These funds are stimulating ground-breaking research ranging from studies aimed at understanding the human genome to those intended to lead to improvements in the prevention, diagnosis and treatment of human illness. NHGRI's signature initiative is the development of technologies that can sequence a human genome for $1,000 or less. The availability of truly inexpensive genomic sequencing has the potential to revolutionize health and medicine. NHGRI is also funding medical sequencing initiatives which allow individual research labs to implement newer sequencing technologies to identify and understand the genetic roots of a disease or trait. In addition, NHGRI is funding: the development of computational tools to work with the large volumes of data generated through sequencing and other NHGRI research activities, projects that will move us toward fully realizing the benefits of population-based genomic research such as genome wide association studies, research on the Ethical, Legal and Social Implications of genome research, and methods to conduct high-throughput studies that can catalog and examine the relationship between cell function and its response to perturbations.
Last Reviewed: February 22, 2012


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Turnaround at Norsk Gjenvinning (A)
Keywords: change management; change leadership; Crime and Corruption; governance; Compliance; waste management; Environmental Impact; social responsibility; industry regulation; regulatory enforcement; Leading Change; Change Management; Crime and Corruption; Governance Compliance; Wastes and Waste Processing;
Citation:Serafeim, George, and Shannon Gombos. "Turnaround at Norsk Gjenvinning (A)." Harvard Business School Case 116-012, August 2015. (Revised October 2017.) View Details


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Quincy Jones denies casino mogul made threats
LOS ANGELES (AP) — Quincy Jones says he never told porn producer Joe Francis that casino mogul Steve Wynn threatened to kill him and have him buried in the desert.
The Grammy-winning record producer testified Thursday in Wynn's slander trial against Francis, which focuses on claims by the "Girls Gone Wild" founder that the casino creator vehemently denies.
Francis says Jones told him about Wynn's threats. Wynn denies ever threatening Francis and says the soft porn producer's accusations have the potential to damage his casinos, which include the Wynn and Encore in Las Vegas.
Jones says he never heard Wynn threaten Francis. He says Francis' accusations sound like a scene from "Scarface."
The producer also backed up Wynn's testimony that he never sent an email to Jones.


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How come no one has mentioned Rufus and Alicia from Valkyrie Profile 2: Silmeria? If there was one relationship in an RPG that felt natural it was this one. I was nearly in tears at the end. They had to go through a lot together and they had to rely on each other.
But that's such a common fantasy trope, though. Not just in video games but in movies too. How many "teen beat" movies feature the whole "cute childhood friend who was under your nose all along" plotline? Yeah, perhaps the "childhood friend" thing is played out, but it will never die. Especially in the realm of love adventures. Every love adventure needs the trophy girl, the childhood friend, the moe klutz, the tsundere, and the wildcard (sometimes it's an older woman.)Then again, JRPG romances always end badly. Think about how many JRPG protagonists still have both parents. When a JRPG couple hooks up, one WILL die.
Speaking of love triangles and friends.Has this thread mentioned Vyse x Aika x Fina?
Karin & Her Son :P
As I recall, in the ending, you end up with an immortal Rufus watching a reincarnated child Alicia. Creepiness is then turned up to 11.


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The CDC recently released the names of the top 15 cities across the United States that have the highest herpes rate. The center said that the top 5 cities from the list had 40% infection rate which was the result of sexually active young people in those cities.
Here's a list of all 15 cities with highest herpes rate that was released by the Center for Disease Control: READ MORE


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18-Year-Old High School Basketball Star "Tony Farmer" Collapses In Court After Being Sentenced To Prison For Kidnapping His Ex!
"An Ohio high school basketball star collapsed in court Tuesday after receiving a three-year prison sentence. You can hear 18-year-old Tony Farmer question his lawyer in disbelief as the judge read the verdict, which sounded like he would spend several years in prison. Then, his knees buckled and he collapsed. He remained on the ground briefly before being pulled to his feet by a sheriff's deputy. Farmer is accused of kidnapping, assaulting and threatening his ex-girlfriend, Andrea Lane, last April. Farmer, who is 6'7", was ranked among the top 100 high school players in the country and was being recruited by several major colleges." - 5 News
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NEW YORK (The White House says President Barack Obama and Nigerian President Goodluck Jonathan have reaffirmed their commitment to fighting terrorism, including ending an insurgency in northern Nigeria.
The two leaders met Monday in New York. Obama stressed a comprehensive anti-terror approach that calls for creating economic opportunity and protecting human rights. During remarks to the media, Obama said ensuring that governments are responsive to people's needs is the best way to undermine the agenda of radical groups like Boko Haram.
Boko Haram's violence occurs mostly in northern Nigeria. Obama called it one of the most vicious terrorist organizations in the world.
The White House says Obama also restated U.S. support for strengthening transparent, democratic governance, and of making sure upcoming Nigerian elections in 2015 are peaceful, transparent and credible.


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My nams is Shiran, I'm 18 y.o and I live- as you already sow- in Israel, home of the Jewish nation.
I discovered the atheism when I was 15 y.o accidentaly. I was searching for something in google (don't remember what) and I came out with a Jewish atheist website- and I started to read.
Though I am a non-believer, I am a Jewish by my ethnicity.
I guess I should tell about my self things like hobbies and stuff....well, I like to read books, and a lot of them. And I LOVE Latin America, and someday (after my military service) I will be doing a long-term backpacking trip all around South and Central America (so, if there are any people here living in Latin America I'll be more then glad to talk to him/her:))
well, that's all guysXD
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