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Tech Beat - February 25, 2014

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Editor: Michael Baum
Date created: February 25, 2014
Date Modified: February 25, 2014 
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'How Well Did You Sequence that Genome?' NIST, Consortium Partners Have Answer

In December 2013, the U.S. Food and Drug Administration approved the first high-throughput DNA sequencer (also known commonly as a "gene sequencer"), an instrument that allows laboratories to quickly and efficiently sequence a person's DNA for genetic testing, medical diagnoses and perhaps one day, customized drug therapies. Helping get the new device approved was another first: the initial use of a reference set of standard genotypes, or "coded blueprints" of a person's genetic traits. The standard genotypes were created by the National Institute of Standards and Technology (NIST) and collaborators within the NIST-hosted Genome in a Bottle consortium.

dna under uv light
Purified DNA fluorescing orange under ultraviolet light.
Credit: Mitchell/National Cancer Institute
high resolution image

"Two years ago, NIST hosted Genome in a Bottle—a group that includes stakeholders from industry, academia and the federal government—to develop reference materials that could measure the performance of equipment, reagents and mathematical algorithms used for clinical human genome sequencing," says NIST biomedical engineer Justin Zook. "Our goal is to provide well-characterized, whole genome standards that will tell a laboratory how well its sequencing process is working, sort of a 'meter stick of the genome.'"

Modern DNA sequencers take a genetic sample in the form of long strings of DNA and randomly chop the DNA into small pieces that can be individually analyzed to determine their sequence of letters from the genetic alphabet. Then, bioinformaticians apply complex mathematical algorithms to identify from which part of the genome the pieces originated. These pieces can then be compared to a defined "reference sequence" to identify where mutations have occurred in specific genes.

There are several different DNA sequencing technologies and computer algorithms to do this very complex analysis, and it's known that for any given sample, they will produce similar, but not identical results. Built-in biases as well as what are essentially "blind spots" for certain possible sequences contribute to uncertainties or errors in the sequence analysis. "These biases can lead to hundreds of thousands of differences between sequencing technologies and algorithms for the same human genome," Zook says.

In a recent paper in Nature Biotechnology,* Zook and his colleagues describe the methods used to make the Genome in a Bottle consortium's pilot set of genotype reference materials. The source DNA, known as NA12878, was taken from a single person. The reference set is essentially the first complete human genome to have been extensively sequenced and re-sequenced by multiple techniques, with the results weighted and analyzed to eliminate as much variation and error as possible.

"We minimized bias in our reference materials toward any specific DNA sequencing method by comparing and integrating data from 14 sequencing experiments generated by five different sequencing platforms," Zook says.

The findings in the Nature Biotechnology paper are publicly available from the Genome in a Bottle website, www.genomeinabottle.org. In addition, the Genome Comparison and Analytic Testing (GCAT) website enables real-time benchmarking of any DNA sequencing method using the paper's results. The research was conducted by a team of scientists at NIST; Harvard University; the Virginia Bioinformatics Institute at Virginia Tech University; and an Austin, Texas, genetic company, Arpeggi Inc. (now part of Gene by Gene Ltd.).

After characterizing the NA12878 pilot, samples of the DNA will be issued as a NIST Reference Material. The Genome in a Bottle consortium also plans to develop well-characterized whole genome reference materials from two genetically diverse groups: Asians and Ashkenazi Jews. Both reference sets will include sequenced genes from father-mother-child "trios" to utilize genetic links between family members.

For more information on the Genome in a Bottle consortium, go to www.genomeinabottle.org.

*J.M. Zook, B. Chapman, J. Wang, D. Mittelman, O. Hofmann, W. Hide and M. Salit. Integrating human sequence data sets provides a resource of benchmark SNP and indel genotype calls. Nature Biotechnology Published online Feb. 16, 2014. doi:10.1038/nbt.2835

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

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Stirred, Then Shaken: NIST Atomtronic Study May Pave the Way for New Devices

This animation represents the laser (in blue) stirring a Bose-Einstein Condensate (gold). The process revealed that BECs possess hysteresis, a type of "memory" that might make them useful for data storage in future atomtronic devices.

Credit: Eckel/NIST

While pursuing the goal of turning a cloud of ultracold atoms into a completely new kind of circuit element, physicists at the National Institute of Standards and Technology (NIST) have demonstrated* that such a cloud—known as a Bose-Einstein condensate (BEC)—can display a sort of "memory."

The findings, featured as the cover article of the Feb. 12, 2014, issue of Nature, pave the way for a host of novel devices based on "atomtronics," an emerging field that offers an alternative to conventional electronics.

Just as electronic devices manipulate the flow of electrons, atomtronic devices manipulate the flow of atoms. Since atoms have properties that are very different from electrons, atomtronic devices have the potential to go beyond the capabilities of electronics. The newfound effect of the BEC could be an important tool for constructing atomtronic devices similar to computer memory, according to the research team's leader, Gretchen Campbell.

A BEC, a gas of atoms cooled to nearly absolute zero, is an exotic form of matter that exhibits superfluidity—flow without resistance. This and other properties make BECs potentially useful in atomtronics. The field is still in its infancy though, so the team is exploring BEC-based analogs to well-understood devices. In this study, they looked at ways to make a BEC rotate, knowledge that might one day produce more sensitive rotation sensors.

The team created a BEC out of about 400,000 sodium atoms suspended by laser beams, which corralled the BEC into a doughnut-shaped cloud about as wide as a strand of hair is thick. Another laser acted as a "slotted spoon" that stirred the cloud, making the doughnut spin like a wheel. While stirring their BEC, the researchers saw some behavior they expected—and some they didn't.

"A stirred BEC flows only at certain velocities—starting with the spoon at rest, as one stirs more rapidly, the BEC initially stays at rest, then suddenly, at a 'critical' stirring rate, starts to flow," says Campbell, a NIST physicist. "Curiously, the stirring rate at which the BEC jumps into motion is not the same as the stirring rate to get the BEC to jump back to rest; in some cases, one even has to stir backwards."

A similar effect exists in a magnetic hard disk drive: the magnetic field needed to change a memory bit differs depending on whether you are changing a zero to a one or vice versa. This effect, called "hysteresis," gives the hard drive stability, allowing it to store computer data. In principle, information also could be stored in the flow state of an atomtronic circuit, and an advantage of a BEC system is that the stability of the hysteresis can be tuned by changing the properties of the laser "spoon."

What surprised the team was that the most common, albeit imperfect, theory of BECs did not predict correctly how changing the stirring laser—altering the size of the slots in the spoon, as it were—changes the stirring rate at which the BEC switches from one velocity to another. This unexpected finding implies there is something the most common theory of BECs has left out.

"Nevertheless, the demonstration of hysteresis in an atomtronic device opens up lots of possibilities," Campbell says. "It might now be possible to make a host of atomtronic devices such as switches, more sensitive gyroscopes or maybe even a different type of a quantum computer."

*S. Eckel, J.G. Lee, F. Jendrzejewski, N. Murray, C.W. Clark, C.J. Lobb, W.D. Phillips, M. Edwards and G.K. Campbell. Hysteresis in aquantized superfluid 'atomtronic' circuit. Nature, Feb. 12, 2014. doi:10.1038/nature12958.

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

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NIST Microanalysis Technique Makes the Most of Small Nanoparticle Samples

Researchers from the National Institute of Standards and Technology (NIST) and the Food and Drug Administration (FDA) have demonstrated that they can make sensitive chemical analyses of minute samples of nanoparticles by, essentially, roasting them on top of a quartz crystal. The NIST-developed technique, "microscale thermogravimetric analysis," holds promise for studying nanomaterials in biology and the environment, where sample sizes often are quite small and larger-scale analysis won't work.*

sample deposit
m-tga oven
Small piezoelectric quartz crystals are the key to micro thermogavimetric analysis. Minute amounts of the test sample are deposited on the crystals (top) and they are baked under controlled conditions (bottom). Mass changes are detected by changes in the crystal frequency.
Credit: Kar/NIST
top high resolution image | bottom high resolution image

Chemical analysis of nanoparticles is a challenging task, and not just because they're small. They're also complicated. They can become coated with other materials in their environment, and the question becomes, what materials? Or they might have been engineered with a coating, perhaps to provide anchor points for drug molecules, and then the question can be, how complete is the coating? In nanoelectronics, the question may be, how pure is the sample and just what are the impurities?

Researchers have an alphabetic array of tools for this, including scanning, transmission or atomic force microscopy (SEM/TEM/AFM); dynamic light scattering (DLS); nuclear magnetic resonance (NMR); and sundry spectrometry techniques, but they all have a variety of limitations, including complex sample preparation or the difficulty of analyzing enough particles to get a statistically significant result.

On the other hand, one technique, thermogravimetric analysis (TGA) is quite straight-forward. The sample is heated and monitored for changes in mass as the temperature increases. Sudden changes in mass correlate with the energies needed to decompose, oxidize, dehydrate or otherwise chemically change components in the sample. If you have some idea of what you start with, TGA can tell you much more, but it requires pretty substantial sample sizes.

NIST's technique is essentially the same except that a small piezoelectric quartz crystal is substituted for the mass scale. A tiny amount of a nanomaterial sample deposited on the crystal dampens the crystal's resonant frequency, and as the sample grows lighter, the frequency shifts. NIST researchers originally applied it to measure the purity of carbon nanotube samples.**

In this latest paper, the research team tested the utility of microTGA on typical nanomaterial analysis problems, including assessing the purity of carbon nanotubes, determining the amount of surface-bound ligands (i.e., molecular anchors) on gold nanoparticles, and testing for the presence of PEG, a polymer commonly used in medicine on silicon oxide nanoparticles.

"Our results are a pretty close match to other techniques," reports NIST analytical chemist Elisabeth Mansfield, "but using far less of a sample."

In fact, the team reports, microTGA gets results using samples a thousand times smaller than conventional techniques. It can work with one microgram of sample and detect mass changes of less than a nanogram. "That's important because you often don't have much of a sample.," Mansfield says," If you're pulling nanoparticles out of a water sample from the environment to measure how much exists in a real world sample, you're going to have very little to work with."

"In nanomedicine, the surface chemistry is oftentimes critically important to the performance of the nanomaterial," notes FDA chemist Katherine Tyner. "When working with real life samples, we may only have a very small sample amount. MicroTGA allows us to obtain information that we otherwise would not be able to get with conventional techniques."

*E. Mansfield , K.M. Tyner, C.M. Poling and J.L. Blacklock. Determination of nanoparticle tsurface coatings and nanoparticle purity using microscale thermogravimetric analysis. Anal. Chem., 2014, 86 (3), pp 1478–1484 DOI: 10.1021/ac402888v.
**See the November 2010 NIST story "Quartz Crystal Microbalances Enable New Microscale Analytic Technique" at www.nist.gov/public_affairs/tech-beat/tb20101124.cfm#qcm.

Media Contact: Michael Baum, michael.baum@nist.gov, 301-975-2763

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NIST Requests Comments on its Cryptographic Standards Process

As part of a review of its cryptographic standards development process, the National Institute of Standards and Technology (NIST) is requesting public comment on a new draft document that describes how the agency develops those standards. NIST Cryptographic Standards and Guidelines Development Process (NIST IR 7977) outlines the principles, processes and procedures of NIST's cryptographic standards efforts.

NIST is responsible for developing standards, guidelines, tools and metrics to protect non-national security federal information systems. To ensure it provides high-quality, cost-effective security mechanisms, NIST works closely with a broad stakeholder community to select, define and promulgate its standards and guidelines.

In November 2013, NIST announced it would review its cryptographic standards development process after concerns were raised about the security of a cryptographic algorithm in NIST Special Publication 800-90, which was originally published in 2006 (an updated version, 800-90A, was published in 2007). Based on those concerns, that publication was re-issued in September 2013 for a new period of public review and is being revised to address comments received.

With the draft NIST IR 7977, NIST is seeking feedback on how it develops its documents; engages experts in industry, academia and government; and communicates with stakeholders. Public comments will be posted on the NIST website and used to create a revised document. NIST will then review its existing standards and guidelines to ensure they adhere to the principles laid out in NIST IR 7977. "If any issues are found," said NIST's Donna Dodson, who oversees the process, "they will be addressed as quickly as possible."

The draft version of NIST IR 7977 and questions for reviewers can be found in the Computer Security Resource Center at http://csrc.nist.gov/. Comments may be submitted to crypto-review@nist.gov by April 18, 2014.

Related links:

Media Contact: Jennifer Huergo, jennifer.huergo@nist.gov, 301-975-6343

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NIST SBIR Program Soliciting Proposals

The National Institute of Standards and Technology (NIST), through its Small Business Innovation Research (SBIR) program, invites small businesses to submit proposals for solutions to technology challenges in the areas of cyber-physical systems, cybersecurity, health care, manufacturing and technology transfer.

"We are pleased to now offer the SBIR awards as cooperative agreement grants, which allow for more flexibility in how companies can address the technology challenges," said NIST's Associate Director for Innovation and Industrial Services Phillip Singerman. "Our goal is to foster greater innovation."

SBIR Phase I awards provide up to $90,000 over a performance period of seven months and are intended to determine the feasibility of the proposed research. Phase I awardees are eligible to submit proposals for Phase II funding to further develop their technology.

Proposals may be submitted to develop the following topics:

  • compact, rapid electro-optic laser scanner for absolute 3D imaging
  • computer-aided standards development (CASD)—a software tool to automate the process of standards development
  • cryptographic acceleration for border gateway protocol security (BGPSEC)
  • erbium-based diode-pumped solid-state (DPSS) lasers for remote sensing
  • instrument to detect aerosolized-droplet dose delivery of vaccines
  • NIST tech transfer
  • precision specimen control for transmission scanning electron microscopy
  • predictive modeling tools for metal-based additive manufacturing
  • privacy-preserving tools for federated authentication models
  • production of NIST/University of California San Francisco breast phantom for magnetic resonance imaging (MRI)
  • residential heat pump fault detection and diagnostic data logger
  • secure email agent using the domain name system (DNS) as a trust infrastructure
  • silicon single-photon avalanche diodes with detection efficiency that exceeds 95 percent
  • technology for separation of carbon nanotubes
  • ultra-sensitive and wide dynamic range, cavity ring-down spectroscopy system for detection of ozone

The NIST SBIR program identifies and solicits proposal in subtopics that fall within NIST's mission. Details of this competition are available at the Grants.gov website under Federal Funding Opportunity 2014-NIST-SBIR-01.The full announcement, with information on eligibility, other requirements and proposal submission instructions, is available at www.grants.gov/web/grants/view-opportunity.html?oppId=251550. Proposals must be submitted by May 2, 2014.

For general information about the NIST SBIR program, call (301) 975-4188 or email sbir@nist.gov.

Media Contact: Jennifer Huergo, jennifer.huergo@nist.gov, 301-975-6343

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Perspective: Weights and Measures Week 2014 — Making Sure the Marketplace Measures Up

Commentary by Mark Esser.

condemned scales
Scales condemned by the Seattle Department of Weights and Measures, 1917.
Credit: Courtesy Seattle Municipal Archives/Creative Commons

Every year, we hear scattered stories of inaccurate measures. Gas pumps, grocery scales, grocery scanners, incorrectly labeled products. Considering the many thousands of devices in the average inspector's jurisdiction, it's a testament to the tenacity of the weights and measures officials that we don't hear these stories more often.

Incorrect measures are not always the result of criminal activity. The world is an imperfect place, and these devices get out of whack. It's the job of the weights and measures inspector to see that many different scales are put right again.

Weights and Measures Week is held March 1-7 every year to commemorate President John Adams's signing of the first U.S. weights and measures law on March 2, 1799. The National Conference on Weights and Measures (NCWM) has declared this year's Weights and Measures Week will be a celebration of our weights and measures officials, the women and men who work every day to make sure the marketplace measures up.

One of the principal reasons Congress founded the National Institute of Standards and Technology (NIST) in 1901 was to provide definitive standards for weights and measures to regulate interstate and international commerce. At the time, there were eight different measures for the gallon, at least four different feet, and a hodgepodge of other measurements that varied from state to state, and sometimes even within states.

While states worked to ensure that their markets were fair to businesses and consumers alike, there were no definitive standards and no national infrastructure to calibrate measuring and weighing instruments. All people could do was hope that they were getting a fair deal.

While this may have worked to some degree on the state and local levels, interstate and international transactions were another story. Buyers, sellers … no one could be sure if they were getting their money's worth. And the unscrupulous fed on this uncertainty.

NIST, or the National Bureau of Standards as it was known at that time, established the National Conference on Weights and Measures (NCWM) in 1905 to put the marketplace on a fair and firm foundation and give the burgeoning network of state weights and measures officials the tools they needed to do their jobs.

NIST still performs these services today and is constantly working to deliver the highest quality training to inspectors wherever they are.

In the past year, the NIST Office of Weights and Measures (OWM) has achieved an "Authorized Provider" accreditation from the International Association for Continuing Education and Training (IACET). IACET Authorized Providers are the only organizations approved to offer IACET Continuing Education Units (CEUs), which certify that IACET has evaluated the NIST OWM training program and found it to be compliant with internationally accepted standards.

Many states require that their weights and measures officials receive training throughout their careers. Using an accredited training organization gives those officials confidence that the training they will receive is of high quality.

The NIST OWM has, and continues to expand, their online offerings to better accommodate their customers' schedules and budgets. NIST has trained more than 600 weights and measures personnel in the past year.

And while NIST enjoys the opportunity to train weights and measures inspectors directly, our annual capacity is limited. So, NIST is teaming with the NCWM to "train the trainers." This invitation-only effort will teach select weights and measures officials to become great teachers and provide them with a professional certification as proof.

Forty people have successfully completed the Train the Trainer in the past year.

"I had one of our trained instructors tell me just last week how they have applied concepts from our measurement courses and instructional methods into all of the other training they are doing and what an impact it has had," says NIST program leader Georgia Harris. "They have been able to train hundreds of other measurement professionals in the past couple of years, including applying these concepts in other measurement fields such as forensics. Our train the trainer effort has a multiplying effect—we've trained one and they can each train hundreds!"

Our weights and measures inspectors are an integral part of the American economy. They are our foot soldiers out on the streets and in the stores every day making sure everything measures up. If you see one this week at the gas station or the grocery store, please remember to say hello and say thanks.

Media Contact: Mark Esser, mark.esser@nist.gov, 301-975-8735

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Find the Path to Performance Excellence at 2014 Quest Conference

For organizations seeking insight toward improved performance and results, the annual Quest for Excellence® conference is the definitive showcase of best practices from the winners of the Malcolm Baldrige National Quality Award—the nation's highest honor for performance excellence and innovation. Registration is now open for the 26th annual conference, April 6-9, 2014, in Baltimore, Md.

Kanter and Ryan
Keynote speakers at the 26th annual Quest for Excellence conference this April will be Rosabeth Kanter (l), Harvard Business School, a world-renown expert on strategy, innovation and leadership for change, and Sister Mary Jean Ryan (r), SSM Health Care, a distinguished icon in the health care quality movement who led the organization that won the first Baldrige Award in health care in 2002.
Credit: Harvard Business School and SSM Health Care
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The conference includes an invitation for registrants to attend a ceremony and reception on Sunday evening, April 6, honoring the 2013 recipients of the Baldrige Award:

  • In the education category, the Pewaukee School District, Pewaukee, Wis.
  • In the health care category, Sutter Davis Hospital, Davis, Calif.

Additionally, registrants have the option to participate on Sunday, April 6, in pre-conference workshops (for beginner and intermediate users of the Baldrige Criteria for Performance Excellence) during the day.

This year's Quest will feature in-depth plenary sessions featuring the senior executives of the 2013 recipients, and numerous concurrent sessions, including:

  • Presentations by each of the 2013 recipients on their successful use of the seven categories of the Baldrige Criteria for Performance Excellence, including leadership, strategic planning, customer focus and other areas critical to organizational performance; and
  • Presentations featuring the strategies, best practices and insights of 17 past Baldrige Award recipients in the categories of manufacturing, service, small business, education and health care.

The Quest for Excellence® conference will be highlighted by two keynote addresses. The first, on Monday, April 7, will be given by Rosabeth Moss Kanter, Ernest L. Arbuckle Professor at the Harvard Business School, and chair and director, Harvard University Advanced Leadership Initiative. Through teaching, writing and direct consultation to major corporations and governments, Kanter has guided leaders worldwide in strategy, innovation and leadership for change. She has been repeatedly named as one of the world's "50 most powerful women" by the Times of London and as one of the "50 most influential business thinkers" by the Thinkers 50 management ranking. Formerly editor of the Harvard Business Review, Kanter's books include The Change Masters, When Giants Learn to Dance and SuperCorp: How Vanguard Companies Create Innovation, Profits, Growth, and Social Good (2009).

The second keynote, on Wednesday, April 9, will feature Sister Mary Jean Ryan, board chair and former president/CEO of SSM Health Care(St. Louis, Mo.), the first Baldrige Award recipient in the health care category in 2002. Internationally known as an inspiring speaker and leader in the health care quality movement, Ryan has been named one of the most powerful people in health care by Modern Healthcare magazine for the past eight years. She is the author or co-author of three books on performance excellence: On Becoming Exceptional: SSM Health Care's Journey to Baldrige and Beyond; Improving Health Care: 14 Case Studies from Leading Practitioners; and CQI and the Renovation of an American Health Care System.

Sign up by March 10, 2014, for a discounted registration fee. The registration site is www.nist.gov/baldrige/qe.

For more about the Baldrige Performance Excellence Program, call (301) 975-2036 or e-mail baldrige@nist.gov.

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

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NIST Invites Applications for the 2014 Standards Services Curricula Development Program

The National Institute of Standards and Technology (NIST) is offering financial support for the development of curricula with standards and standardization content at colleges and universities.

college classroom - copyright Igor Mojzes from Fotolia
Credit: ©Igor Mojzes/Fotolia.com

"By integrating standards and standardization into the curriculum at U.S. colleges and universities and raising students' awareness of how standards support innovation and competitiveness, we begin to introduce the next generation to the importance of standardization in the global economy," says Gordon Gillerman, chief of NIST Standards Services.

NIST anticipates funding approximately two to eight projects in the $25,000 to $75,000 range. Projects are anticipated to run 12 to 18 months. Complete details on the Standards Services Curricula Development Cooperative Agreement Program, including eligibility and details on the application/proposal process are available on Grants.gov under Federal Funding Opportunity 2014-NIST-SSCD-01.

Applications must be received no later than 11:59 p.m. Eastern Time, Monday, March 31, 2014.

Additional information on NIST work in standards education is available on the NIST Global Standards Information website.

Media Contact: Mark Esser, mark.esser@nist.gov, 301-975-8735

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