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Tech Beat - December 1, 2009

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Editor: Michael Baum
Date created: November 5, 2010
Date Modified: November 5, 2010 
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Nervy Research: Researchers Take Initial Look at Ion Channels in a Model System

Before one of your muscles can twitch, before the thought telling it to flex can race down your nerve, a tiny floodgate of sorts--called an ion channel--must open in the surface of each cell in these organs to let in the chemical signals that spur the cell to action. New research* at the National Institute of Standards and Technology (NIST) has allowed scientists to observe ion channels within the surface membrane for the first time, potentially offering insights for future drug development.

illustration of neutron diffraction

An imaging technique known as neutron diffraction, used along with molecular simulations, revealed that an ion channel’s voltage sensing domain (red, yellow and blue molecule at center) perturbs the two-layered cell membrane that surrounds it (yellow surfaces), causing the membrane to thin slightly.

Credit: NIST
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Because they function as gatekeepers for messages passing among nerve cells, ion channels are the target of a host of drugs that treat psychological and neurological issues. But because the proteins that form the channels are hard to observe, obtaining knowledge of their operation has proved difficult. Studies of the proteins have been limited to either the molecules in isolation or dried and crystallized to get an idea of their structures. Now, a multi-institutional team working at NIST’s Center for Neutron Research (NCNR) has provided a glimpse of the proteins in their naturally occurring form and interacting with the surrounding cell membrane.

The findings, just reported in the journal Nature, improve our understanding of the moving portion of the ion channel that responds to voltage differences across the cell membrane, according to team leader Stephen White. While the work may not be of practical medical use for some time, he says, it is a useful step toward understanding how signals travel—particularly among neurons.

“All of the communications in the body are electrical,” says White, a biophysicist at the University of California, Irvine. “The motion of life depends on ion channels responding to voltage differences, so that they open and close at just the right moment, controlling the use of energy. Without them, nothing would happen in the body.”

By investigating this portion of the ion channel, called a voltage-sensing domain, the team has provided science’s first glimpse of how an ion channel’s shape and motion affects the cell membrane, which in turn helps protect and stabilize the proteins that form the channel. White says further research could lead to a complete picture of how ion channels function.

“We still can’t see in detail how the gate opens and closes, but that’s our eventual goal,” White says. “We hope that someday we’ll be able to detect the motion of these voltage-sensing domains in their up and down states.”

The research team, jointly headed by White and Kenton Swartz of the National Institute of Neurological Disorders and Stroke (NINDS), also includes scientists from the University of Missouri, the National Institute of Alcohol Abuse and Alcoholism and the NCNR. Funding for the study was provided by the National Science Foundation, the National Institute of General Medical Sciences and NINDS.

* D. Krepkiy, M. Mihailescu, J.A. Freites, E.V. Schow, D.L. Worcester, K. Gawrisch, D.J. Tobias, S.H. White and K. Swartz. Structure and hydration of membranes embedded with voltage-sensing domains. Nature, 462, pp. 473-479 (Nov. 26, 2009), doi:10.1038/nature08542.

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

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NIST Researchers Put a New Spin on Atomic Musical Chairs

Researchers from the National Institute of Standards and Technology (NIST) and the Naval Research Laboratory have developed a new way to introduce magnetic impurities in a semiconductor crystal by prodding it with a scanning tunneling microscope (STM). Detailed in a recent paper,* this technique will enable researchers to selectively implant atoms in a crystal one at a time to learn about its electrical and magnetic properties on the atomic scale.

a STM image

[Left] An atomic-resolution scanning tunneling microscopy (STM) image of an indium arsenide crystal surface where a manganese atom has been inserted in place of one of the indium atoms. The displaced indium atom appears as the bright yellow feature on the surface; the embedded manganese atom is only evident by its effect on the neighboring arsenic atoms (the dumbbell-shaped yellow feature). [Right] The theoretical simulation of the STM image after the atoms finish playing musical chairs, illustrating the origin of the features seen in the experiment.

Credit: Steven Erwin, Naval Research Laboratory
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A better understanding of these properties is fundamental to the development of “spintronics,” electronic devices that will use electron spin, a characteristic of magnetism, instead of charge for storing information. Spintronics could increase the performance of electronic devices while reducing power usage and production costs.

Electronics manufacturers commonly introduce impurities into semiconducting crystals to change how well the material will conduct electricity. Researchers also can introduce impurities that induce a semiconductor to become magnetic. In these dilute magnetic semiconductors (DMS), the added impurity atoms typically must displace one of the original atoms in the crystal structure to become “active.” One of the goals of DMS materials research is to achieve higher operating temperatures by making sure all the doped magnetic impurity atoms are activated. Knowing how the impurity atoms get into the host crystal lattice sites is essential to this process.

The experiments involved depositing single manganese atoms onto an indium arsenide surface. To become active and magnetize the DMS, the manganese atom must take a chair from one of the indium atoms by occupying an indium lattice site. Using the STM probe tip, the NIST researchers zapped an indium atom with sufficient voltage to dislodge it from its place in the lattice and switch places with the manganese atom. In this way the researchers can choose where and which manganese atom they want to make active.

Because the exchange happens very quickly, researchers cannot see what path the atoms take when made to play musical chairs. To find the pathway, researchers at the Naval Research Laboratory made theoretical models of the atomic motions and identified two possible avenues for the exchange to occur. The group selected the correct pathway by comparing the calculation results with the experimental STM findings.

This work was supported in part by the Korea Research Foundation grant program (MOEHRD)**, the Office of Naval Research and the NIST-CNST/UMD-NanoCenter Cooperative Agreement. Computations were performed at the Department of Defense Major Shared Resource Center at the Air Force Research Laboratory at the Wright-Patterson Air Force Base in Ohio.

* Y.J. Song, S.C. Erwin, G.M. Rutter, P.N. First, N.B. Zhitenev and J.A. Stroscio. Making Mn substitutional impurities in InAs using a scanning tunneling microscope. Nano Letters. Published online Sept. 29, 2009. http://pubs.acs.org/doi/full/10.1021/nl902575g

Edited on Dec. 2, 2009 to improve illustration captions.

** KRF-2006-214-C00022

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

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Combining Nanotubes and Antibodies for Breast Cancer ‘Search and Destroy’ Missions

Single-walled nanotubes--cylinders of carbon about a nanometer in diameter--have been highly touted for potential applications such as ultrastrong fibers, electrical wires in molecular devices, or hydrogen storage components for fuel cells. Thanks to a new development by researchers at the National Institute of Standards and Technology (NIST) and five partners, you can add one more application to the list: detection and destruction of an aggressive form of breast cancer.

tumor cells

Photomicrographs demonstrate the dramatic impact of using nanotubes to selectively locate and destroy HER2 breast cancer tumors. Tumor cells on the left were treated only with antibodies against the HER2 protein and then irradiated with near-infrared light. Those on the right were treated with a complex of antibodies and nanotubes and then irradiated. Both cultures then were stained with fluorescent dye—green color indicates live cells while red marks areas where cells have been killed.

Credit: NIST
View hi-resolution image.

HER2 is one of a family of genes that help regulate the growth and proliferation of human cells. Normal cells have two copies of HER2, but about 20 to 25 percent of breast cancer cells have multiple copies of the gene, resulting in the overproduction of a HER2-encoded protein (called HER2 and designated in Roman type versus italics for the gene) that is associated with particularly fast growing and difficult to treat tumors. About 40,000 women in the United States are diagnosed annually with this form of breast cancer.

In a recently published paper in BMC Cancer,* the NIST-led research team bonded an antibody that has been created to attack the HER2 protein, chicken immunoglobulin Y (IgY), to short nanotubes (about 90 nanometers long, or 5,000 times shorter than an amoeba). Both halves of the special combination—the antibody and the nanotube—have critical roles to play in selectively hunting down the HER2 tumor cells and eliminating them.

First, the broad genetic differences between avian and human species means that the chicken IgY antibody to HER2 reacts strongly with the target protein expressed on tumor cells while ignoring normal cells with other human proteins. The carbon nanotubes attached to the antibodies also become linked to the HER2 tumors.

Two unique optical properties of carbon nanotubes allow this link to be exploited for improved detection and destruction of HER2 breast cancer cells. Near-infrared laser light at a wavelength of 785 nanometers reflects intensely off the nanotubes, and this strong signal is easily detected by a technique called Raman spectroscopy. Increase the laser light’s wavelength to 808, nanometers and it will be absorbed by the nanotubes, incinerating them and anything to which they’re attached—in this case, the HER2 tumor cells.

The experiment described in the BMC Cancer paper was conducted in laboratory cell cultures. Using the HER2 IgY-nanotube complex to selectively identify and target HER2 tumors resulted in a nearly 100 percent eradication of the cancer cells while nearby normal cells remained unharmed. In comparison, there only was a slight reduction in cancer cells for cultures treated with anti-HER2 antibody alone.

The next step for the research team is to conduct mouse trials of the HER2 IgY-nanotube complex to see if the dramatic cancer-killing ability works in animals as well as it does in the lab. In a separate but related project, the team hopes to use a nanotube-antibody combination against another tumor cell protein, MUC4, to treat pancreatic cancer.

The research was funded under an interagency agreement between NIST and the National Cancer Institute (NCI), and in part by a grant from the National Science Foundation. Along with scientists from NIST, the research team included members from Rutgers University, Cornell University, the New Jersey Institute of Technology, NCI and Translabion, a private company located in Clarksburg, Md.

* Y. Xiao, X. Gao, O. Taratula, S. Treado, A. Urbas, R.D. Holbrook, R.E. Cavicchi, C.T. Avedisian, S. Mitra, R. Savla, P.D. Wagner, S. Srivastava and H. He. Anti-HER2 IgY antibody-functionalized single-walled carbon nanotubes for detection and selective destruction of breast cancer cells. BMC Cancer, Vol. 9, No. 351, published online Oct. 2, 2009.

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

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NIST Develops Experimental Validation Tool for Cell Phone Forensics

Viewers of TV dramas don't focus on the technology behind how a forensics crime team tracks a terrorist or drug ring using cell phone data, but scientists at the National Institute of Standards and Technology (NIST) do. NIST researchers have developed a new technique aimed at improving the validation of a crime lab's cell phone forensics tools. Early experiments show promise for easier, faster and more rigorous assessments than with existing methods.

sim chip

Copyright kenny1/Shutterstock

Cell phones reveal much about our daily communications—the who, when and what of our calls and texts. A small chip card within most phones, called an identity module, stores this and other data for a subscriber. A subscriber identity module (SIM) accommodates phonebook entries, recently dialed numbers, text messages and cellular carrier information. Forensic examiners use off-the-shelf software tools to extract the data, allowing them to “connect the dots” in a criminal case such as identifying affiliations or detecting mobile phone activity around the time of an event.

But for this information to be used as evidence in court or other formal proceedings, the software tools that forensic teams employ are normally validated to determine suitability for use. Currently, preparing test materials for assessing cell phone tools is labor intensive and may require learning new command languages to perform the process.

NIST scientists detail their proof-of-concept research in a NIST Interagency Report, Mobile Forensic Reference Materials: A Methodology and Reification (available online at http://csrc.nist.gov/publications/nistir/ir7617/nistir-7617.pdf.) They also developed an experimental application, called SIMfill, and a preliminary test dataset that follows the methodology described in the report. SIMfill can be used to automatically upload cell phone data such as phone numbers and text messages to “populate” test SIMs that can then be recovered by forensic cell phone tools. In this way, examiners can use SIMfill as one method to assess the quality of their off-the-shelf tool.

The SIMfill software and dataset may be downloaded for free at http://csrc.nist.gov/groups/SNS/mobile_security/mobile_forensics_software.html.

“In this report,” explains coauthor Wayne Jansen, “we document the results of a recent experiment with a number of commonly used mobile phone forensics tools. No tool was found to work perfectly and some worked poorly on fairly simple test cases.”

The automated features of the applications and XML representation of test data allow technicians to develop new test cases easily. This offers a simple alternative to using manual means or specialized tools with higher learning curves. The data can be adapted to different languages with alternate character sets.

“Our research was a proof of concept,” Jansen says. “Hopefully, forensic examiners will use our work to validate mobile forensics tools thoroughly before they employ them.” The next step in the research is open. Scientists could expand the technique for mobile handsets and other types of identity modules, or the forensic community could decide to adopt this dataset and application as an open source project, according to Jansen.

Media Contact: Evelyn Brown, evelyn.brown@nist.gov, 301-975-5661

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Smart Grid Interoperability Panel Launched; Governing Board Elected

The inaugural meeting of the Smart Grid Interoperability Panel (SGIP), a new forum to provide technical support to the National Institute of Standards and Technology (NIST) as it coordinates standards for a modernized electric power system, elected 20 members to its governing board on Nov. 19. The new consensus-driven organization provides an open process for businesses and other stakeholder groups to participate in coordinating and accelerating development of standards for the evolving Smart Grid.

Starting with an initial membership of more than 370 organizations spread among 22 stakeholder categories, the SGIP has three primary functions:

  • Provide technical guidance to NIST to facilitate development of standards for a secure, interoperable Smart Grid;
  • Specify testing and certification requirements necessary to assess the interoperability Smart Grid-related equipment, software, and services; and
  • Oversee the performance of activities intended to expedite the development of interoperability and cyber security specifications by standards development organizations.


NIST is now completing its Framework and Roadmap for Smart Grid Interoperability Standards, Release 1.0, which has undergone public review and comment. The SGIP will further strengthen this roadmapping effort in collaboration with NIST.

“The panel will ensure that the perspectives of the many diverse constituencies—from utility to consumer and from appliance manufacturer to wind or solar farm—are represented in decision-making on standards needed to achieve the Smart Grid vision,” says George Arnold, NIST’s national coordinator for Smart Grid interoperability. “It will provide an open, consensus-based process for stakeholder participation.”

Members in 17 of the 22 SGIP stakeholder categories elected a representative to the governing board, which will prioritize the work of the SGIP and consult regularly with standards development organizations, user groups and others directly involved in standardization efforts. In addition, the entire membership voted on three at-large board members. Because of a tie, a run-off election will be held for the board seat in the stakeholder category representing “standards and specification development organizations.”

Full details, including the list of elected members of the SGIP governing board are in the NIST news release “Smart Grid Interoperability Panel Launched; Governing Board Elected.”

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

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Quicklinks

NIST on Facebook and Twitter

The National Institute of Standards and Technology (NIST) now has a fan page on the popular social networking site, Facebook, and the microblogging service Twitter. Become a fan or follow us to receive the latest news, videos, photos and other media, event announcements, job postings and more.

You can find NIST on Facebook at https://www.facebook.com/usnistgov and on Twitter as usnistgov.

We hope the new site will be a good way to keep up with what’s happening at NIST, to network with others interested in NIST activities, and to submit your comments and questions.

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

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NIST Staff Recognized in Annual Commerce Department Awards

Fourteen staff members at the National Institute of Standards and Technology (NIST) have received one of this year’s Department of Commerce Gold Medals and an additional 23 have received Commerce Silver Medals. The medals represent the two highest honors given by the department for exceptional work in the service of the Commerce Department or one of its agencies.

Details of the NIST award winners may be read at “37 Employees Earn DOC Awards.”

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

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