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Tech Beat - April 12, 2011

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Editor: Michael Baum
Date created: April 12, 2011
Date Modified: April 12, 2011 
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New NIST SRM Helps Improve Diagnosis of Huntington's Disease

A new Standard Reference Material (SRM) from the National Institute of Standards and Technology (NIST) will help clinical genetics labs accurately diagnose Huntington’s disease, an inherited degenerative brain disorder that usually begins between ages 35 and 50 and progressively leads to physical impairment, dementia and death. A person whose mother or father developed Huntington’s disease has a 50-50 chance of getting the currently incurable disease.

Graphic showing the excessive repetitions of the cytosine-adenine-guanine (CAG) nucleotide sequence in a gene from a Huntington's disease patient
Graphic showing the excessive repetitions of the cytosine-adenine-guanine (CAG) nucleotide sequence in a gene from a Huntington's disease patient (bottom) compared to a gene from a person without the neurodegenerative disorder (top).
Credit: National Institute of General Medical Sciences, National Institutes of Health
View hi-resolution image

Huntington’s disease results from a genetic mutation affecting approximately one in 10,000 persons. The mutation is characterized by an excessive number of repeats of a sequence of three nucleotides (the chemical building blocks of DNA), cytosine-adenine-guanine (CAG), located on the fourth of the 23 pairs of chromosomes found in every human cell. Since 1993, a genetic test has been available to count the number of CAG “triplet repeats” that exist, determining if a person will develop Huntington’s disease, and if so, how severe it will be.

Individuals with up to 26 repeats are normal. Individuals with 27 to 35 repeats also are unaffected, but the number of repeats can increase in their children. Individuals with 36 to 39 repeats may or may not develop symptoms of Huntington’s disease; however, if they do, it will likely be at a much later onset and slower progression than more pronounced cases. Individuals with 40 or more repeats will definitely be affected, while individuals with 60 or more repeats will develop symptoms in childhood.

Electing to be tested for Huntington’s disease is an extremely difficult choice. Since a positive diagnosis undoubtedly will affect decisions about careers, relationships, having children and other life events, there is no room for error. But errors can occur sometimes because the test requires making many copies of the patient’s DNA using the polymerase chain reaction (PCR), the standard technique for “amplifying” or making multiple copies of a DNA molecule. On rare occasions, PCR creates extraneous CAG repeats—an anomaly known as “stutter”—that make the triplet count appear higher than it really is.

Measures of the overall length of the DNA molecule—and in turn, the CAG repeat count—are greatly improved when the new NIST reference, SRM 2393, “CAG Repeat Length Mutation in Huntington’s Disease,” is used as a quality control. The SRM consists of six samples of DNA measured and certified by NIST for triplet repeats ranging in number from 15 to 75. The certified values are free of stutter, providing genetic screeners a more viable standard with which to compare a patient’s DNA sample.

SRM 2393 joins more than 50 reference materials produced by NIST for quality control in clinical testing. It also is the latest response by NIST to the call from the health care community for higher-order reference materials for genetic diagnostic tests (the last being an SRM to improve the accuracy of Fragile X syndrome diagnoses). Standard Reference Materials are among the most widely distributed and used products from NIST. The agency prepares, analyzes and distributes about 1,300 different materials that are used throughout the world to check the accuracy of instruments, validate test procedures and serve as the basis for quality control standards worldwide.

To get information on purchasing SRM 2393 and download the certificate, go to https://www-s.nist.gov/srmors/view_detail.cfm?srm=2393.

Media Contact: Michael E. Newman, michael.newman@nist.gov, 301-975-3025

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Free Online Tool Aids Decisions on Fire Sprinkler Systems for Homes

For the many states, communities, new-home builders and prospective buyers now mulling over the pluses and minuses of installing residential fire suppression sprinklers, the National Institute of Standards and Technology (NIST) has developed a free online tool to help them sort through the costs and benefits of the technology.

fire sprinkler
Courtesy: Shutterstock/Justin Kral

NIST's new, Web-based "sprinkler use decisioning" tool, developed by information technology specialist Priya Lavappa and economist David Butry, enables experts and non-experts alike to assess the cost-effectiveness of fire sprinklers for their particular jurisdiction, development, or dwelling.

Fewer than 5 percent of U.S. homes are equipped with fire suppression sprinklers, but recent developments have moved the cost-benefit debate into the mainstream. The latest version of the International Residential Code calls for fire sprinklers to be installed in new one and two-family residential dwellings and townhouses, starting Jan. 1, 2011. Some other model building codes follow suit.

More than 200 communities and a handful of states, including California, Maryland, and South Carolina, have adopted the code. So has Pennsylvania. But the Pennsylvania House of Representatives recently voted to repeal the mandate, sending the measure on to the State Senate for its consideration. Debate and disagreement over proposed sprinkler ordinances have flared in other areas as well.

The NIST tool can help to inform these kinds of policy discussions, providing the means for "apples to apples" comparisons of different installation scenarios. It is based on the economic framework that Butry and other NIST researchers developed in their 2007 report, Benefit-Cost Analysis of Residential Fire Sprinkler Systems.*

Users can input their own data to supply values for categories of costs and benefits in the model. They also can opt for a combination of user-defined data and national or local statistics. The NIST developers mined the National Fire Incident Reporting System (NFIRS) to assemble national and city-level data on fire risk, fire fatality and injury rates, property loss, and other figures of merit. NFIRS contains fire-related data for more than 1,300 cities.

By researching and supplying their own data on local sprinkler installation and maintenance costs, insurance premiums and credits, value of the house and contents, discount rate and other variables, users can get a realistic estimate of the cost-effectiveness, or "present value net benefits," of an investment in a sprinkler system.

The tool supports two types of analyses. A baseline analysis yields a single present value estimate for each benefit and cost and an overall estimate of "present value net benefits." The tool's sensitivity analysis allows users to input maximum and minimum values for each input. Through the sensitivity analysis, they can assess the soundness of their estimates of individual costs and benefits.

"With this type, you can also identify the largest and smallest drivers of the total economic performance of sprinklers," Butry explains.

For local government officials contemplating whether to add the sprinkler requirement to their building codes, Butry recommends running analyses for a variety of house sizes to explore the benefit-cost performance of sprinkler systems in a community with a diversity of residential styles and sizes.

You can check out NIST's new sprinkler use decisioning tool at: http://ws680.nist.gov/firesprinkler/default.aspx.

*Available at: http://www.nist.gov/manuscript-publication-search.cfm?pub_id=860105

Media Contact: Mark Bello, mark.bello@nist.gov, 301-975-3776

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Sharpened Focus: Improving the Numbers, Utility of Medical Imaging

The idea of probing the body's interior with radiation stretches back to experiments with X rays in the 1800s, but more than a century later, images taken with radiological scans still are not considered reliable enough to, for example, serve as the sole indicator of the efficacy of a cancer treatment. Lisa Karam, a biochemist at the National Institute of Standards and Technology (NIST) and a few dozen of her colleagues across North America have set out to change that.

xray
X-ray image of a length standard for medical CT. The standard is made of six rows of polytetrafluoroethelyene (PTFE) balls held in place with plastic spacers. (Center of image, assembly is approx. 96 mm long.) Using a CT image, it is possible to determine the spacing of the centroids of these balls to within approximately 0.1 mm.
Credit: NIST Ionizing Radiation Division

The group of radiology specialists from a number of institutions has recently published* a pair of papers that Karam describes as part of a major effort to turn medical imaging—CT scans, PET scans, MRIs, X rays and the like—into a quantitative research tool, one that produces reliable numbers. Karam says her hope is that the group's efforts will enable scientists to determine whether a new drug or treatment method is working within weeks rather than months or years, thereby cutting down on the time it takes to get an effective new therapy approved for patients.

"Let's say doctors are studying an experimental drug that might destroy lung tumors," says Karam, "CT scans might show that patients' lung tumors shrink after a few weeks on the drug, but regulators would not accept this as evidence that the drug works because legitimate concerns exist about other variables that might be responsible for the apparent change in the image. What we want to do is get control over enough of those variables so that these concerns will fall away."

The many coauthors of the two papers are members of a subgroup of the Radiological Society of North America called the Quantitative Imaging Biomarker Alliance (QIBA). NIST's primary role, Karam says, is in helping to get control of anything involved in the imaging process that has to do with measurable physical values, from the radiation beams to the properties of the tissues being imaged.

In the example of lung tumors, Karam says, one problem is that lung tissue has a spongy quality and moves during the scan as a patient breathes. "If a patient moves a couple of millimeters during a scan, it can affect your measurement of a 10-mm tumor," she says. "So we are creating a plastic 'benchmark' that can be used to quantify this movement and account for it in the image analysis. We also are creating objects of defined density to calibrate scanners, so you can be sure of what you are measuring even if the surrounding tissue's density varies."

The first of the two papers discusses how the radiology community can best come together to make quantitative imaging the norm in medicine; the second, how to overcome longstanding issues that have discouraged the health care community from supporting the idea. Karam says more papers from QIBA are in the works: a near-term goal is to offer a method of handling data so that it can be useful in evaluating treatment methods.

"We're trying to develop a milieu for medical imaging," Karam says. "We want to show the world that a medical image can be a useful tool for medical decision making. It can give you hard numbers you can take to your insurance company and use as justification to get treatment."

* A. J. Buckler, H. J.W.L. Aerts, B. Bendriem, C. Bendtsen, R. Boellaard, J.M. Boone, L. Bresolin, D. Burstein, P.E. Cole, J.J. Conklin, G.S. Dorfman, P.S. Douglas, N.R. Dunnick, W. Eidsaunet, C. Elsinger, R. A. Frank, C. Gatsonis, M.L. Giger, D. Gustafson, S.N. Gupta, O.S. Hoekstra, E.F. Jackson, L. Karam, G.J. Kelloff, P.E. Kinahan, G. McLennan, C. G. Miller, P.D. Mozley, K.E. Muller, K. O'Donnell, R. Patt, D. Raunig, M. Rosen, H. Rupani, L.H. Schwartz, B.A. Siegel, A.G. Sorensen, R.L. Wahl, J.C. Waterton, W. Wolf, G. Zahlmann, B. Zimmerman and D.C. Sullivan. A collaborative enterprise for multi-stakeholder participation in the advancement of quantitative imaging. Radiology. March 2011. 258:906-914, doi:10.1148/radiol.10100799.
____. Quantitative imaging test approval and biomarker qualification: Interrelated but distinct activities. Radiology. Published online Feb. 15, 2011, doi:10.1148/radiol.10100800.

Media Contact: Chad Boutin, boutin@nist.gov, 301-975-4261

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The Heat Is On: NIST Zeroes In On Energy Consumption of Ice Makers

In tests of four different types of new refrigerators, National Institute of Standards and Technology (NIST) researchers found that ice makers increased rated energy consumption by 12 to 20 percent. About three-fourths of that additional energy cost is due to the electric heaters used to release the ice bits from the molds.

ice maker
One of four types tested by NIST researchers, this top-mount refrigerator freezer was outfitted with three thermocouples in each compartment, sampling the temperature every 30 seconds. In all units tested, about three-quarters of ice-maker energy consumption was directly and indirectly attributed to the electric heaters used to free ice from molds
Credit: NIST | View hi-resolution left image | View hi-resolution right image
refrigerator

With only one-fourth of the extra energy actually used to cool and freeze water, "there are substantial opportunities for efficiency improvements merely by optimizing the operations of the heaters associated with the ice makers" or by introducing a more efficient alternative technology, report NIST mechanical engineer David Yashar and guest researcher Ki-Jung Park.*

Since refrigerators account for 8 percent of the total energy consumed by 111 million U.S. households according to the Department of Energy (DOE), the potential savings are significant.

Currently, ice maker energy consumption is not reflected in federal minimum efficiency standards for refrigerators or in the voluntary Energy Star program, which requires energy usage to be significantly lower than the regulatory limit.

DOE, which helped to fund the NIST study, has announced that it will increase the minimum efficiency standard by 25 percent over the current level, starting in 2014. DOE also intends to incorporate the energy used by ice makers into their regulatory test. Because no widely accepted test for ice makers was available when they announced these intentions, DOE plans to add 84 kilowatt hours to the energy efficiency rating of every refrigerator equipped with an ice maker, Yashar explains.

Once a reliable, straightforward test is available, he adds, DOE will eliminate the "placeholder" energy consumption and use actual ice maker test results in efficiency ratings.

To speed progress along this path, Yashar and Park evaluated several different approaches to measure the energy consumption of ice makers. Their goal was to identify a method that consistently yielded accurate results but did not add substantially to the complexity of appliance energy consumption tests under current regulations.

Yashar and Park examined four refrigerators, which sampled a variety of ice maker technologies. Their study used a uniform test setup, consistent with current regulatory procedures, and measured the energy consumption of the four units while their ice makers were actively producing ice and, again, while the ice makers were not operational.

The results point the way to a standard test methodology that appears promising for several different ice maker technologies and configurations. Next steps include sharing their approach with other laboratories, which also will test ice makers and compare results for similar units. Also, Yashar says he intends to evaluate the measurement techniques on other styles of automatic ice makers.

*D.A. Yashar and K.J. Park, Energy Consumption of Automatic Ice Makers Installed in Domestic Refrigerators. NIST Technical Note 1697, April 2011.
Edited on Apr. 14 2011 to make minor correction to photo caption.

Media Contact: Mark Bello, mark.bello@nist.gov, 301-975-3776

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Crowdsourcing Science History: NIST Digital Archives Seeks Help in Identifying Mystery Artifacts

Do you hold the key to solving some gadget mysteries from the last century of U.S. science and technology? In its 110 years, the National Institute of Standards and Technology (NIST) has made many innovations in the way we measure things, from basic quantities like the volt and nanometer to specialized questions like the purity of sugar.

wafer tube
Project Tinkertoy Wafer Tube Amplifier
Credit: NIST Digital Archives
View hi-resolution image
instrument
Metal Instrument in Wood Case
Credit: NIST Digital Archives
View hi-resolution image

A new website, the NIST Digital Archives (http://nistdigitalarchives.contentdm.oclc.org/), is exhibiting images of historically significant scientific instruments used to obtain these measures, in addition to providing access to full-text publications from the agency's history. (To end the suspense, you measure sugar with a saccharimeter.) NIST is inviting enthusiasts to participate in describing some of the hundreds of historical objects collected through the decades. Some of the artifacts are unidentified or need more descriptive information. Visitors to the site can view the items and offer clues about the history and origins of some of these important artifacts.

The artifacts are in the collection of scientific instruments in the NIST Museum, located on the NIST campus in Gaithersburg, Md., and can be viewed on the NIST Museum Artifacts* portion of the new Website. Most of the artifacts are well-documented, such as a 1950s creation known as the Project Tinkertoy Wafer Tube Amplifier. It is a 45 rpm record player built as a part of Project Tinkertoy, an endeavor to develop mechanical production methods for electronic equipment using standardized components. However, some artifacts remain a mystery, such as the enigmatic brass-colored, crank-like Metal Instrument in Wood Case.

"We have some artifacts in our collection we want to identify, so we thought we could exhibit them online and ask for help," says NIST Digital Services Librarian Regina Avila. "It was fun to photograph them, but challenging. Some artifacts were broken, others had missing pieces. Some were heavy and others were fragile." Currently, 137 artifacts are on the site, and hundreds more will be added in the coming months.

The digital archive also contains some NIST publications, including the Journal of Research of the National Institute of Standards and Technology**, which covers the broad range of research undertaken by NIST research staff, focusing on measurement methodology. Visitors can access full-text papers from the journal dating from 1981 to the present. Pre-1981 papers are being added to the collection on an ongoing basis with the goal of making available all papers back to 1904.

NIST's Information Services Office (ISO), which has won several awards including Federal Library of the Year in 2003 and 2008, is responsible for creating, maintaining and disseminating NIST's knowledge base, including its history. The NIST Digital Archives is part of the ISO's Museum and History Program, which collects, conserves and exhibits significant NIST artifacts and records to provide institutional memory and demonstrate NIST's contributions to the development of standards, technology and science. This digital archive is the realization of an effort to provide better access to our historical assets. "We were looking for a mechanism for making the information about NIST's scientific contributions more widely available to the public," says Barbara Silcox, the NIST Program Manager for Digital Information Services. Future collections in the NIST Digital Archives will include images of historical photographs from NIST, items from the NIST Oral History collection and video recordings of selected NIST Colloquia.

Those with information on any of the items in the NIST Digital Archives Museum Artifacts Collection should send an e-mail to nda@nist.gov. NIST will update the site as it obtains information on the artifacts.

* http://nistdigitalarchives.contentdm.oclc.org/cdm4/index_p15421coll3.php?CISOROOT=/p15421coll3
** http://nistdigitalarchives.contentdm.oclc.org/cdm4/index_p13011coll6.php?CISOROOT=/p13011coll6

Media Contact: Ben Stein, ben.stein@nist.gov, 301-975-3097

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NIST/JILA Physicist Wins Optical Society's Meggers Award

Steven Cundiff, a physicist at the National Institute of Standards and Technology (NIST), has received the 2011 William F. Meggers Award from the Optical Society of America (OSA).

The Meggers Award recognizes outstanding work in spectroscopy, the study and measurement of interactions between light and matter. Cundiff, a Fellow of JILA, a joint institute of NIST and the University of Colorado Boulder, is cited for "contributions to the field of ultrafast spectroscopy of semiconductors, including multidimensional Fourier transform techniques, and for contributions to the development of femtosecond frequency comb technology."

Highlights of Cundiff's recent research can be found in Tech Beat articles "Electronic 'Crowd Behavior' Revealed in Semiconductors" (July 6, 2007, at www.nist.gov/public_affairs/techbeat/tb2007_0706.htm#semiconductor), "NIST/JILA 'Dark Pulse Laser' Produces Bursts of … Almost Nothing" (June 9, 2010, at  www.nist.gov/public_affairs/tech-beat/tb20100609.cfm#dark), and  "New Wave: JILA Develops Efficient Source of Terahertz Radiation" (Jan. 19, 2011, at  www.nist.gov/public_affairs/tech-beat/tb20110119.cfm#radiation). Background on optical frequency combs is available at www.nist.gov/public_affairs/releases/frequency_combs.cfm.

Meggers was a prominent scientist who worked at NIST (then called the National Bureau of Standards) from 1914 to 1958 and is considered by many to be the founder of the American field of spectroscopy. More information on OSA's annual awards and medals is available at www.osa.org/About_Osa/Newsroom/News_Releases/Releases/04.2011/OSABestowsAwards.aspx. Previous Meggers Award winners, who include a number of NIST scientists, are listed at www.osa.org/awards_and_grants/awards/award_description/meggersaward/default.aspx.

Media Contact: Laura Ost, laura.ost@nist.gov, 303-497-4880

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