In This Issue...
Cellular Landscaping: Predicting How, and How Fast, Cells Will Change
A research team at the National Institute of Standards and Technology (NIST) has developed a model* for making quantifiable predictions of how a group of cells will react and change in response to a given environment or stimulus—and how quickly. The NIST model, in principle, makes it possible to assign reliable numbers to the complex evolution of a population of cells, a critical capability for efficient biomanufacturing as well as for the safety of stem cell-based therapies, among other applications.
The behavior and fate of cells are only partially determined by their DNA. A living cell reacts to both its internal and external environment—the concentration of a particular protein inside itself or the chemistry of its surroundings, for example—and those reactions are inherently probabilistic. You can't predict the future of any given cell with certainty.
This inherent uncertainty has consequences, according to NIST biochemist Anne Plant. "In the stem cell area in particular, there's a real safety and effectiveness issue because it's very hard to get 100 percent terminal differentiation of stem cells in a culture," she says. This could be problematic, because a therapist wishing to produce, say, heart muscle cells for a patient, might not want to introduce the wild card of undifferentiated stem cells. "Or effectiveness may be dependent on a mixture of cells at different stages of differentiation. One of the things that is impossible to predict at the moment is: if you waited longer, would the number of differentiated versus nondifferentiated cells change? Or if you were to just separate out the differentiated cells, does that really remove all the nondifferentiated cells? Or could some of them revert back?" says Plant.
The NIST experiments did not use stem cells, but rather fibroblasts, a common model cell for experiments. The team also used a standard tracking technique, modifying a gene of interest—in this case, one that codes for a protein involved in building the extracellular support matrix in tissues—by adding a snippet that codes for a small fluorescent molecule. The more a given cell activates or expresses the gene, the brighter it glows under appropriate light. The team then monitored the cell culture under a microscope, taking an image every 15 minutes for over 40 hours to record the fluctuations in cell behavior, the cells waxing and waning in the degree to which they express the fluorescent gene.
Custom software developed at NIST was used to analyze each image. Both time-lapse data from individual cells and time-independent data from the entire population of cells went into a statistical model. The resulting graph of peaks and valleys, called a landscape, says Plant, "mathematically describes the range of possible cell responses and how likely it is for cells to exhibit these responses." In addition, she says, the time analysis provides kinetic information: how much will a cell likely fluctuate between states, and how quickly?
The combination makes it possible to predict the time it will take for a given percentage of cells to change their characteristics. For biomanufacturing, it means a finer control over cell-based processes. If applied to stem cells, the technique could be useful in predicting how quickly the cells differentiate and the probability of having undifferentiated cells present at any point in time.
* D.R. Sisan, M. Halter, J.B. Hubbard and A.L. Plant. Predicting rates of cell state change caused by stochastic fluctuations using a data-driven landscape model. PNAS 2012 ; published ahead of print October 30, 2012, doi:10.1073/pnas.1207544109.
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NIST, UMD Celebrate 25 Years of Research Partnership at IBBR
Officials and researchers from the University of Maryland (UMD) and the National Institute of Standards and Technology (NIST) gathered on Oct. 25, 2012, to celebrate the 25th anniversary of the two institutions' ongoing collaboration to advance bioscience and biotechnology through their combined expertise in the biological and quantitative sciences, medicine and engineering.
The anniversary program at the Institute for Bioscience and Biotechnology Research (IBBR) near Gaithersburg, Md., included a scientific seminar and a ceremony recognizing two of the collaboration's guiding principals, Rita Colwell, Distinguished University Professor at the University of Maryland at College Park (UMCP), and Willie E. May, the NIST Associate Director for Laboratory Programs.
"IBBR is a model for government and public-private collaboration," said Under Secretary of Commerce for Standards and Technology and NIST Director Patrick Gallagher. "Just 25 years after its founding, actually a rather short time in research years, it is an internationally recognized organization."
The partnership between the two research institutions began in the late 1980s with the creation of the Center for Advanced Research in Biotechnology (CARB). CARB was a joint effort of UMD, NIST and the Montgomery County, Md., government, which leased land and financed the construction of the initial CARB facility. Since then, the partnership has grown to encompass additional UMD research centers, including the Center for Biosystems Research (CBR) in College Park, Md., and the University of Maryland-Baltimore's Center for Biomolecular Therapeutics.*
In 2010, CARB and CBR were formally merged into the IBBR, where recently, NIST and the University of Maryland have established a Partnership for the Advancement of Complex Therapeutics with the mission of accelerating the development of measurement science, technologies and standards in the area of complex therapeutics and the diagnostics that support their clinical utility. The initial focus will be on protein biologic drugs and vaccines.
IBBR researchers, drawn from UMD and NIST, work in the areas of structural biology, biophysics, genomics and proteomics, nanobiotechnology, pathobiology, and computational biology. The institution established an early reputation for determining the molecular structure of proteins, one of the core problems in biotechnology. IBBR research has helped to better understand basic protein interactions involved in autoimmune disorders and the mechanisms and possible counter actions for antibiotic resistance, and developed ways to improve the stability of proteins for biotechnology applications. One protein engineered by IBBR researchers has been licensed and applied to tasks as varied as improving stain-removal properties of laundry detergents and purifying other proteins for analysis.
For other examples of IBBR research, see "'Kissing' RNA and HIV-1: Unraveling the Details" (Jan. 30, 2004) at http://www.nist.gov/public_affairs/techbeat/tb2004_0130.htm#kissing, "Long-Sought Protein Structure May Help Reveal How 'Gene Switch' Works" (Feb. 6, 2009) at www.nist.gov/public_affairs/releases/tuberculosis.cfm, and "Fish Flu: Genetics Approach May Lead to Treatment" (Nov. 8, 2011) at www.nist.gov/public_affairs/tech-beat/tb20111108.cfm#fishflu.
More information on the IBBR is available at http://www.ibbr.umd.edu/.
* See the 2007 announcement,"NIST, UMBI to Expand Cooperation in Bioresearch" at www.nist.gov/public_affairs/tech-beat/tb20070816.cfm#umbi.
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Princeton/NIST Collaboration Puts Wheels on the Quantum Bus
In yet another step toward the realization of a practical quantum computer, scientists working at Princeton and the Joint Quantum Institute (JQI) have shown how a major hurdle in transferring information from one quantum bit, or qubit, to another might be overcome.* Their so-called "quantum bus" provides the link that would enable quantum processors to perform complex computations.
The JQI is a collaborative institute of the National Institute of Standards and Technology (NIST) and the University of Maryland College Park.
Qubits are unlike a classical bit because they can be not only a 1 or 0 but also both, simultaneously. This property of qubits, called superposition, helps give quantum computers a tremendous advantage over conventional computers when doing certain types of calculations. But these quantum states are fragile and short-lived, which makes designing ways for them to perform basic functions, such as getting qubits to talk to one another—or "coupling"—difficult.
"In order to couple qubits, we need to be able to move information about one to the other," says NIST physicist Jacob Taylor. "There are a few ways that this can be done and they usually involve moving around the particles themselves, which is very difficult to do quickly without destabilizing their spins—which are carrying the information—or transferring information about the spins to light. While this is easier than moving the particles themselves, the interaction between light and matter is generally very weak."
Taylor says you can think of their solution sort of like playing doubles tennis.
"Whether or not a team will be able to return a serve depends entirely on how well they play together," says Taylor. "If they are complementing each other, with one playing the front half of the court and the other playing the back half, they will be able to return the serve to the other set of players. If they are both trying to play in the front court or the back court they won't be able to return the serve and the ball will go past them. Similarly, if the spins of the electrons are complementary, their field will affect the field of the photon as it goes past, and the photon will carry the information about the electrons' spin to the other qubit. When the spins are not coupled, they will not affect the photon and no information will go to the other qubit."
The Princeton/JQI team's quantum bus is a hybrid system that marries two known quantum technologies—spin-orbit qubits and circuit quantum electrodynamics—with some tweaks. The spin-orbit qubits are a pair of indium-arsenide quantum dots that have been engineered to enable strong coupling between the spins of the electrons trapped inside the dot and the electrons' positions within the dot. This in turn allows the magnetic field of the qubit, comprising spins, to couple with the field of microwave photons traveling through a connected superconducting cavity.
The structure makes it possible for information about the qubits' spin to be transferred to the microwave cavity, which, with some additional tweaks could be transferred to another qubit.
The experiment, which was the culmination of five years of effort, took place at Princeton University. NIST/JQI provided assistance with the quantum theory.
* K.D. Petersson, L.W. McFaul, M.D. Schroer, M. Jung, J.M. Taylor, A.A. Houck and J.R. Petta. Circuit quantum electrodynamics with a spin qubit. Nature 490, 380–383 (18 October 2012) doi:10.1038/nature11559
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NIST Provides Draft Guidelines to Secure Mobile Devices
The National Institute of Standards and Technology (NIST) has published draft guidelines that outline the baseline security technologies mobile devices should include to protect the information they handle. Smart phones, tablets and other mobile devices, whether personal or "organization-issued," are increasingly used in business and government. NIST's goal in issuing the new guidelines is to accelerate industry efforts to implement these technologies for more cyber-secure mobile devices.
Securing these tools, especially employee-owned products, is becoming increasingly important for companies and government agencies with the growing popularity—and capability—of the devices. Many organizations allow employees to use their own smart phones and tablets, even though their use increases cybersecurity risks to the organization's networks, data and resources.
Guidelines on Hardware-Rooted Security in Mobile Devices defines the fundamental security components and capabilities needed to enable more secure use of products.
"Many current mobile devices lack a firm foundation from which to build security and trust," explains NIST lead for Hardware-Rooted Security Andrew Regenscheid, one of the publication's authors. "These guidelines are intended to help designers of next-generation mobile phones and tablets improve security through the use of highly trustworthy components, called roots of trust, that perform vital security functions." On laptop and desktop systems, these roots of trust are often implemented in a separate security computer chip that cannot be tampered with, but the power and space constraints in mobile devices could lead manufacturers to pursue other approaches such as leveraging security features built into the processors these products use, he says.
The NIST guidelines are centered on three security capabilities to address known mobile device security challenges. They are device integrity, isolation and protected storage. A tablet or phone supporting device integrity can provide information about its configuration, health and operating status that can be verified by the organization whose information is being accessed. Isolation capabilities are intended to keep personal and organization data components and processes separate. That way, personal applications should not be able to interfere with the organization's secure operations on the device. Protected storage keeps data safe using cryptography and restricting access to information.
To attain the security capabilities, the guidelines recommend that every mobile device implement three security components. These are foundational security elements that can be used by the device's operating system and its applications. They are:
The authors of Guidelines on Hardware-Rooted Security in Mobile Devices, Special Publication 800-164 (Draft) request comments to improve the draft. The publication may be downloaded from http://csrc.nist.gov/publications/PubsDrafts.html#SP-800-164. Please submit comments by December 14, 2012, to firstname.lastname@example.org.
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New NIST Web Resource Hosts Federal Research Technology Transfer Plans
A new website has been launched by the National Institute of Standards and Technology (NIST) to serve as a central resource for technology transfer plans developed by agencies with federal research laboratories.
The plans were developed in response to an Oct. 28, 2011, Presidential Memorandum that directed agencies doing research and development to foster innovation by increasing the rate of technology transfer to private-sector organizations so that research results could be adapted for use in the marketplace.
The plans from 13 federal agencies include agency-defined goals and metrics to measure progress and evaluate the success of new efforts that encourage technology transfer activities. This effort supports the policy of using innovation as a tool to increase economic growth, create jobs, and enhance global competitiveness of U.S. industries.
As part of its own effort to accelerate technology transfer, NIST plans to revise its definition of technology transfer to more accurately report and evaluate a broad range of technical activities. This will lead to expanded metrics tracking the use of Standard Reference Materials and Data, patents and licenses, and collaborations. New metrics will cover software downloads, postdoctoral and guest researchers, and start-up companies, among others.
NIST develops basic science foundations for many technologies with long horizons for eventual commercialization, while other NIST activities benefit the economy through facilitation of consensus standards for trade. As one mechanism for tracking technology transfer activities, the agency plans to expand a database on staff participation in private-sector consensus standards committees. The expanded Standards Committee Participation Database will go beyond statutory requirements for data collection regarding staff participation in committees and on standards developed through their efforts.
In addition to NIST, the DOC technology transfer report includes plans from the:
The agency reports for “Accelerating Technology Transfer and Commercialization of Federal Research in Support of High-Growth Businesses” are available at www.nist.gov/tpo/publications/agency-responses-presidential-memo.cfm.
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Deborah Jin of JILA Selected for 2013 Women in Science Award
Deborah Jin, a physicist at the National Institute of Standards and Technology (NIST) who works at JILA, has been selected as the North American recipient for the 2013 For Women in Science Awards.
JILA is a joint institute of NIST and the University of Colorado Boulder.
The award is given annually by the L’Oréal Foundation and UNESCO as part of an international program recognizing women in science and supporting scientific vocations. Five women scientists are recognized each year, one for each of five regions of the world. Since the program was created in 1998, it has honored 77 outstanding women scientists from around the world.
“These five outstanding women scientists have given the world a better understanding of how nature works,” UNESCO Director-General Irina Bokova said in a news release. “Their pioneering research and discoveries have changed the way we think in various areas of the physical sciences and opened new frontiers in science and technology. Such key developments have the potential to transform our society. Their work, their dedication, serves as an inspiration to us all.”
Jin was cited “for having been the first to cool down molecules so much that she can observe chemical reactions in slow motion, which may help further understanding of molecular processes which are important for medicine or new energy sources.”
“The award is definitely an honor,” Jin says. “Part of that comes from the fact it’s just not a local thing, it’s a worldwide program. It will be fun to meet the award winners from other areas, people that I otherwise might not meet, and hear their perspectives.”
The awards will be officially presented in Paris on March 28th, 2013. Each For Women in Science winner receives $100,000.
Jin is a NIST/JILA Fellow and is a world leader in advancing understanding of quantum mechanics, the seemingly curious rules that govern the behavior of atoms and smaller particles. Jin was cited for her work chilling ultracold molecules enough to observe chemical reactions, which may help create practical tools for “designer chemistry” and other applications such as precision measurement.*
Jin is a member of the National Academy of Sciences and winner of numerous previous awards, including the 2008 Benjamin Franklin Medal in Physics and a 2003 John D. and Catherine T. MacArthur Fellowship, commonly called a “genius grant.”
Information about the awards program can be found at www.forwomeninscience.com. This is the second time a NIST-affiliated scientist has won a Women in Science award.**
* See NIST’s 2010 news story, “Seeing the Quantum in Chemistry: JILA Scientists Control Chemical Reactions of Ultracold Molecules,” at www.nist.gov/pml/div689/ultracold_021110.cfm.
** Johanna Levelt Sengers, a scientist emeritus at NIST, was selected as the North American recipient for the 2003 Women in Science Awards. In her 40 years at NIST Levelt Sengers made internationally recognized contributions, both theoretical and experimental, to the fields of thermodynamics and critical phenomena of fluids.
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