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[Sandia Lab News]

Vol. 54, No. 17        August 23, 2002
[Sandia National Laboratories]

Albuquerque, New Mexico 87185-0165    ||   Livermore, California 94550-0969
Tonopah, Nevada; Nevada Test Site; Amarillo, Texas

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Diagnosing, preventing illnesses using microarray technology For Sandians at the Yucca Mountain Project, 'the real challenge is ahead of us' New compound may immobilize AIDS virus and some radionuclides Sandia tests new security assessment tool with help from real communities Transparent shielding system

Sandia/UNM collaborations may lead to new ways to diagnose, prevent illnesses using microarray technology

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By Chris Burroughs

Collaborations between Sandia and the University of New Mexico (UNM) may lead to a greater understanding of genomics and ultimately to new ways to diagnose, treat, and prevent illnesses.

George Davidson (9200) and David Haaland (1812) have been working with UNM researchers on two different projects using several of the same microarray scanning and computing technologies.

One research endeavor -- initially funded through an internal Sandia Laboratory Directed Research and Development (LDRD) award and followed by grants from the W.M. Keck Foundation and National Institutes of Health (NIH) -- involves Sandia, the UNM Cancer Research and Treatment Center (CRTC), and UNM High Performance Computing Education and Research Center (HPCERC). Using Sandia-developed software and computing capabilities, they are evaluating thousands of genes from some of the 100,000 tissue samples from leukemia patients maintained at the CRTC.

Eventually, higher throughput in these studies will be achieved with new Sandia microarray scanning technology. The goal is to determine pathological gene expressions in these cancer cells. This information will be useful for assigning patients to different treatment protocols and may ultimately lead to the development of drugs specifically targeted to these cancers.

In the other project, Dave and George are collaborating with Maggie Werner-Washburne, a UNM biology professor, to improve microarray analysis techniques and the interpretation of data from microarray experiments. Focusing on yeast cells, the fundamental research is now promising to provide better understanding of how cells transition from a quiescent to a growing state, which is involved in wound responses, cancer, and germination of spores, and the complex response of cells to bioagents. This more applied research is contributing to enhanced instruments and sensors to combat bio-threats.

Werner-Washburne work

The work with Werner-Washburne came first, emerging from discussions while she was the program director for Microbial Genetics at the National Science Foundation (NSF) in Washington, D.C. She returned to UNM to help create and lead a group of like-minded researchers interested in exploiting the genomics revolution and helping New Mexico laboratories develop these technologies.

George and Werner-Washburne began developing strong ties between the biology department and Sandia, which included training students and building the required equipment. The work was partially funded by a three-year University Research LDRD grant that began in 1999.

The research had three objectives -- the most important being the establishment of viable biotech research collaborations between the two institutions. The second goal was to enable local microarray experiments and to develop the methods and process controls necessary to achieve high-quality results. The third was to research the issues of gene expression of yeast cells in quiescence and during re-entry into the cell cycle.

"The collaborations between Sandia and UNM have been quite successful," George says. "Importantly, we jointly developed the ability to conduct and analyze microarray experiments using either commercial gene array membranes or arrays printed on glass slides at the UNM Biology Department."

However, it became apparent that the commercial scanners for reading these arrays could be greatly improved, which led to David Haaland's involvement.

"Maggie and I talked about our research when we would run into each other in our neighborhood park. At the time Maggie was working with microarray technology using two fluorescent dyes to study gene expression of yeast cells, and I was doing hyperspectral imaging in the infrared," David says. "It became apparent that the hyperspectral imaging could be useful in Maggie's efforts."

Werner-Washburne says that the Sandia collaborations started during their walks in the park have been particularly rewarding.

"As a result of our Sandia collaborations, we have been able to take a systems approach to this problem," she says. "There are very few laboratories in the country that effectively incorporate biologists, computer scientists, chemists, mathematicians, and engineers at this level. It is the future of genomics, and we have a unique opportunity to make important contributions and have fun at the same time."

W.M. Keck Foundation

About a year into the Sandia/Werner-Washburne project, the W.M. Keck Foundation of California awarded the UNM Health Sciences Center, which has the largest leukemia tissue repository in the world, and Sandia a $1 million grant to apply microarray research to leukemia.

George says that the "attractive part of the proposal was the combination of high-performance computing capability and instrumentation technologies at Sandia with the unique tissue repositories at UNM."

This potent combination is directed toward learning what causes the cancer and which drugs and therapies might be tailored to each individual patient for optimal treatment.

"It is our hope for the future that such studies will allow us to develop specific and more effective therapies targeted to each individual patient," says Cheryl Willman, CRTC director and principal investigator of the Keck grant.

Of the $1 million, UNM received 70 percent, and George and David share 30 percent. The CRTC handles all clinical interactions and the laboratory preparations, including scanning the slides with commercial equipment. Those data are then analyzed using new methods developed by George, David, Shawn Martin (9212), and the computer scientists from the HPCERC. David is also developing a powerful hyperspectral imaging scanning device that will greatly improve on the commercial scanner now in use.

VP1000 Al Romig says the collaborative work between UNM and Sandia is an example of a scientific win-win situation.

"Sandia's high throughput methodology, from the microarray scanners to the mathematical tools for data extraction, will have a major impact on a variety of bioscience and technology studies, from basic research of disease to mitigating the biothreat from emergent diseases and terrorism," Al says. "It's simply another example of Sandia's expertise in physical science, engineering, and computing applied to biological problems. It represents a true scientific win-win. There are problems that are intractable with traditional tools of bioscience, yet attacking them allows Sandia to nurture its own competencies to the benefit of all of our national security problems." - Chris Burroughs

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For Sandians at the Yucca Mountain Project, 'the real challenge is ahead of us'

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By Will Keener

It's been an interesting year for a contingent of Sandians, hunkered down below the political horizon and working hard on Nevada's Yucca Mountain Project. Although this fight is far from over, Sandia's efforts have earned high marks from a number of sources.

"This is a perfect example of exceptional service in the national interest," says Andrew Orrell, who heads Sandia's Yucca Mountain Project Dept. 6850. "There are not many programs that are singularly reviewed with such scrutiny and directly approved by the President himself and by the Congress."

The process of recommending the site to President Bush from Secretary of Energy Abraham and entertaining a debate in Congress over the issue has taken much of the year. But July 9, the US Senate added its approval to that of the House, voting in favor of proceeding with the project. The congressional joint resolution was signed as expected by President Bush July 23, effectively designating the Yucca Mountain site for development as a proposed repository for the nation's spent nuclear fuel and high-level waste.

The action clears the way for the next process -- submission of a license application by DOE to the Nuclear Regulatory Commission to obtain construction authorization. The overall process is expected to take several years and will be played out to a background of lawsuits and protests from various interests opposed to the repository, particularly the state of Nevada.

"We were confident that the project would be approved based on the technical arguments, but considering the significant political and legal maneuvering prior to the vote, we couldn't be certain of the outcome," Andrew says of the recent stamp of approval. "It was a significant moment for us and we've tried to emphasize that in our employee recognition efforts. This decision was based on two decades of work and there are literally hundreds of people at Sandia who contributed to it and who should be rightfully proud of the accomplishment."

The challenge ahead

While morale is high among Sandians on the project, Andrew cautions, "We fully recognize the future environment is going to be stressful. The real challenge is ahead of us with the preparation and defense of the license application. There is a tremendous amount of work ahead."

"Our customers are very demanding and rightly so," says Cliff Howard, acting manager of Repository Test and Analysis Dept. 6855. "They are under a lot of pressure to deliver on schedule high-quality products that can stand up to the scrutiny of oversight groups and critical review organizations."

With its experience base from the Waste Isolation Pilot Project (WIPP) and technical support from matrixed staff in other Labs organizations (including Geosciences Center 6100), Sandia is making a difference in the Nevada project. However, unlike WIPP -- where Sandia led the scientific effort -- this work is being done under DOE's management and operations contractor, the Bechtel-SAIC Company, supported by participants from several national labs, the US Geological Survey, and commercial contractors.

"We've been very successful in transferring our expertise and experience from WIPP to this project. Sandians are now routinely called upon for discussions regarding successful licensing strategies for technical, managerial, and organizational issues," Andrew says. "It is a great pleasure to know our Sandia staff have this kind of impact on these first-of-kind projects." Sandia was able to directly contribute to a substantial number of key documents used by Secretary Abraham to recommend the site to the President this year, he adds.

For the past two decades, Sandia has assisted in the project's site characterization effort in a number of specific areas including technical management, field and lab-scale testing, data collection, modeling and analysis for both engineered and natural systems, and long-term performance assessment.

Sandia's present workforce on the Yucca Mountain Project includes about 35 technical staff members, 15 support staff, and four managers, distributed between Las Vegas and Albuquerque. Present Labs budget for the project is about $14 million. Fifteen of the staff and two managers are currently in Las Vegas.

Key Labs roles

The Las Vegas contingent is co-located with Bechtel-SAIC in Las Vegas, where several Sandia team members hold key management and technical roles in the project organization. Sandia has earned kudos from the managing and operations contractor for its technical contribution, quality practices and performance on cost and schedule.

Cliff's department (6855) is located in Las Vegas and focuses on laboratory and field-testing to supply data needs for Sandia and other project organizations. "Our work in testing always demands innovative engineering," he says of the many first-of-a-kind, high-visibility tests his group conducts.

Albuquerque technical staff do everything from analysis of field test data to interpreting results of million-year simulations of the entire repository system. "The Albuquerque and Las Vegas departments are really seamless and work well as a team, Andrew says. "The majority of our technical effort is accomplished in Albuquerque, while other key efforts are staffed in Las Vegas."

Hong-Nian Jow's Subsystems Performance Assessment Dept. 6852 in Albuquerque works closely with Cliff's staff and other project participants to take experimental data and build it into process and systems models of the natural and engineered barrier systems. Uncertainties are inherent in estimates and observations from a few years of test data extrapolated to tens of thousands of years in model simulations. Models are often simplifications of vastly more detailed information developed by field and laboratory testing and complex component modeling, explains Hong-Nian. "We need to be able to describe the technical basis for our models, defend their appropriateness and be clear about acknowledging the uncertainty in our results."

Finally, these models are adapted for use in various ways by Peter Swift's Total Systems Performance Assessment Dept. 6851. Developing a scientifically sound analysis of a system as large and complex as Yucca Mountain is a multilayered process, Peter explains. "Work at each level of the process must meet the highest standards, and must be integrated carefully with the upstream and downstream users within the project."

Peter sees the greatest challenge for his group as "one of communication. Skeptical technical audiences, both within the project and externally, reasonably ask why they should trust our estimates of system-level performance over hundreds of thousands of years. Sound programmatic decisions about the site should be based on a full understanding of our uncertainty about how it will perform. We need to communicate that understanding to a broad range of audiences." - - Will Keener

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New compound may immobilize AIDS virus and some radionuclides

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By Neal Singer

A compound that could potentially immobilize the AIDS virus or selectively extract radionuclides from nuclear wastes at various US high-level storage sites has been developed by a Sandia researcher who wasn't even looking for it.

An article in the Aug. 9 Science describes characteristics of the newly discovered, extremely active compound, called niobium heteropolyanions (hetero-poly-an-ions) or HPAs.

"It wasn't difficult to synthesize, it was luck," lead researcher May Nyman (6118) says of her discovery. "I wasn't going after it intentionally, but after I found it, I realized I had something new and exciting."

May found the right conditions to synthesize the first niobium HPA, and then tweaked to create an assortment of them.

The entities became the first niobium HPAs ever reported, formed inexpensively at the relatively benign and easily achievable temperature and pressure of boiling water.

Unlike other HPAs, niobium HPAs are basic rather than acidic, which means they can survive longer and possibly even thrive in the generally basic or neutral environments of radioactive wastes and blood, respectively.

Preliminary work with the Savannah River site indicates that the new compounds do indeed selectively remove certain radionuclides from their waste solutions.

To bind viruses, researchers have tested a host of HPA compositions, says May. "In these exhaustive studies, it's been found that HPAs with small amounts of iron or niobium have an especially strong binding effect. Now we have HPAs that are completely niobium."

HPAs in the form of oxides of vanadium, tungsten, and molybdenum have been known to researchers since the late 19th century. The compounds' peripheries consist of voraciously active oxygen ions. These have long intrigued researchers because of their capabilities to do much useful chemistry, including bind viruses and large metal atoms such as some radionuclides.

Once such compounds bind with an AIDs virus, the virus is no longer capable of entering a cell to damage it. HPAs may also bind with radionuclides called actinides, which removes them from the mixture by phase separation for easier and safer storage.

While previously known HPAs were made cheaply and easily at room temperatures and pressures, they were known to be stable only in acid environments.

This behavior means they cannot function well in blood as antiviral agents, because blood is neither acidic nor basic but instead is neutral.

Even worse, the liquid nuclear wastes at most DOE waste sites -- for example, Hanford, Savannah River, and Oak Ridge -- are extremely basic. These environments attack acidic compounds and cause them to fall apart, says May.

May's discovery of the base-stable HPA came about when Sandia was called upon by the Savannah River site to find the cause of a clogging problem at the site's attempts to extract a dangerously radioactive isotope of cesium. The extraction called for passing nuclear waste solution through a column of pebble-sized materials called zeolites that sequester cesium into tiny pores. She found that the zeolites contained small amounts of an impurity that forms during manufacturing. The acidic manufacturing treatment of the zeolites led to column-clogging behavior of the impurity. Identifying the problem concluded her task, but scientific curiosity led her to attempt to create the compound as an independent entity.

"I was curious to see if I could synthesize it pure, rather than leave it merely as a discovered impurity," says May.

Her research on developing and utilizing HPAs will be soon be supported by two Laboratory Directed Research and Development grants, as well as the Environmental Management Science Project out of the DOE Office of Science in collaboration with the Savannah River site.

"One man's trash is another's treasure," May says of her experience. "What used to be clogging columns could now be taking out radionuclides, so it can be Savannah River's and DOE's treasure in the end, as well."

May's co-authors include Francois Bonhomme and Jim Krumhansl (6118), Todd Alam and Brian Cherry (1811), Mark Rodriguez (1822), Tina Nenoff (6233), and Amy Sattler (former summer intern). -- Neal Singer

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Sandia tests new security assessment tool with help from real communities

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By John German

By this fall Sandia's security experts will be adding to their list of risk-assessment tools a scientific methodology for making entire communities more resistant to terrorism.

The new Community Vulnerability Assessment Methodology (CVAM) will join a family of other Sandia-developed VAMs for government buildings, dams, power transmission systems, chemical plants, and water distribution systems that already have helped plug gaps in the nation's security apparatus.

The VAMs have been created in Security Systems & Technology Center 5800, drawing on expertise gained from Sandia's years as the lead DOE lab for nuclear facility security.

CVAM has been in the works for more than two years, since long before Sept. 11, says project leader Gloria Chavez (5845). The project is funded by the National Institute of Justice's Office of Science and Technology.

CVAM is being developed as part of a Memorandum of Understanding between Sandia and Public Technologies, Inc., a nonprofit technology organization of the National League of Cities, the National Association of Counties, and the International City/County Management Association.

Training the trainers

Seven metro areas soon will have benefited from the development and testing of the new methodology, says Gloria.

Some two years ago Sandia began collaborating with community leaders in Sterling Heights, Mich., north of Detroit, to begin developing a prototype assessment process. Developmental assessments of Bismarck, N.D., and Dade County (Miami), Fla., followed.

Early this month, Sandia began pilot testing the CVAM prototype in a joint project with Hennepin County, Minn. (the Minneapolis-St. Paul area). More pilot tests are planned for this fall with Tucson, Ariz., Norfolk, Va., and Rochester, N.Y.

By October, says Gloria, Sandia should have CVAM copyrighted.

The Labs likely would license the methodology to security training firms and train their trainers in its use. The security firms, then, would put the tool into the hands of hundreds of communities nationwide via their own train-the-trainer workshops, during which local community leaders and security professionals learn to conduct the vulnerability assessments themselves.

"We use the train-the-trainer method because we don't have the resources to conduct all of the training needed to reach all the interested communities," says Gordon Smith, Manager of Public Safety Technologies Dept. 5845.

Identifying targets

The CVAM process requires a community's leaders to first identify 10 to 20 facilities they feel are potential security targets, either because of their symbolic value or because of the possibility of severe consequences if an attack were successful.

Then CVAM takes the leaders, step-by-step, through a scientific risk-assessment process that helps them define threats, analyze consequences, and evaluate the effectiveness of current security measures.

After this risk assessment process is complete, the CVAM user has quantitative risk values for each facility to help prioritize where to spend scarce security funding.

Following this rigorous, consistent process typically reveals security vulnerabilities the community didn't know it had, says Gloria, as well as potential security improvements for known vulnerabilities.

Taking expertise to local level

To kick off the Hennepin County pilot assessment, Gloria, Ray Page (5845), Skip Metcalf, and Jimmy Woods (both contractors) ran a five-day workshop in early August for local officials, during which the Sandians provided training on the VAM process and helped the officials prioritize critical facilities.

The Sandia team then conducted assessments of four facilities from Hennepin's list of targets. Local officials participated in the assessments and will conduct assessments on their own of the remaining facilities.

The lists of facilities identified by communities are sensitive, says Gloria, but they typically include medical facilities, financial institutions, tourist attractions, gathering places, corporate offices, infrastructures, hazmat facilities, transportation centers (such as ports or railyards), and educational institutions.

"This training will bring some of the security expertise available at the national level to bear on public safety issues at the county and city levels," says Hennepin County Department of Corrections Planning Director Fred LaFleur, who also heads the County's readiness group.

Consistent analyses

The real value of CVAM, says Gloria, is that it provides a consistent method of analyzing and prioritizing real security risks, identifying which facilities have the greatest threat potentials, and assigning appropriate resources to correcting vulnerabilities.

"It's a tool to improve security before an attack occurs, not a response tool," she says. "But how effective it is depends on how thoroughly communities look at their facilities." -- John German

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Transparent shielding system designed to stop flying machine debris could protect VIPs, cops, or buildings from rioters, bomb blasts, gunfire

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By John German

Protecting workers from heavy debris hurtling away from high-speed rotating machinery is usually accomplished with lots of concrete, steel, and soil.

But Keith Snyder of Test Equipment Design Dept. 2955, faced with designing such a "secondary containment system" for a large high-speed centrifuge at Sandia's Weapons Evaluation Test Lab at the Pantex Plant in Amarillo, Texas, and doing it on a limited budget, had a better idea.

Keith combined several commercially available products into a unique shielding system that is far less expensive and quicker to build than the 4-foot-thick concrete walls or underground test facilities normally relied on for machine containment.

Furthermore, the system he designed and patented has post-9/11 security applications beyond the laboratory safety uses he originally envisioned.

Safety for less

Keith's solution is sheets of polycarbonate (clear plastic, often referred to as Lexan(r), a common brand name) glazed into frames made from Unistrut (r), commercially available pre-drilled steel bracings that, like pieces of a giant erector set, can be combined in a variety of configurations. In industrial settings, Unistrut is used to create overhead tracks for electrical conduit, racks, shelving, stairs, and other structures.

But Unistrut isn't typically used as a barrier. Therein lies the commodity of Keith's idea. His novel combination of struts, polycarbonate sheets, and window glazing presented some intriguing new possibilities.

For machine containment, the impact-resistant transparent sheets provide the advantage of allowing operators to safely see the machinery behind the barrier during operation, says Keith, who studied several glazing and Unistrut bracing configurations to make sure the barrier could contain whatever was flung at it by the machine.

In particular, a series of projectile impact tests conducted at the Southwest Research Institute (San Antonio, Tex.) examined how load is transferred and absorbed by the polycarbonate and bracing system when the barrier is struck by flying objects in the worst-case centrifuge mishaps.

The first such barrier was installed around the Pantex centrifuge about two years ago, after Keith made the case that it was a viable alternative to constructing a $300,000 concrete bunker around the centrifuge to stop any flying debris that escapes from the machine's "primary containment" (the safety shielding built into the centrifuge) -- or stop the centrifuge itself -- in a serious accident.

"We built the first barrier in four days for about $30,000," he says.

Crowd control, VIP protection

Sept. 11 gave Keith some ideas about the braced Lexan for security applications.

Three-quarter-inch-thick Lexan is rated as bullet-proof against small arms fire, he says, so the Unistrut/polycarbonate combo would make good guard booths, for instance.

He also envisions see-through, modular, easy-to-install barriers for public gatherings to shield people from bomb blast shrapnel, protection for important functionaries who might be targets of assassins or terrorist small-arms fire during public appearances, and crowd-control walls to keep police safe and separate from rioting mobs.

More testing needs to be conducted to prove the validity of the barrier system for some security applications, he says. In particular, little data exists regarding lower-velocity impacts, such as from grenade shrapnel or objects hurled in riot situations.

Sandia recently received a US patent on the modular shield system for both machine-containment and security applications. Keith says he'd be interested in sharing the shield design and performing testing to release this system for public use, should the need arise.

More about the project is available at http://www.sandia.gov/security/Security_Barrier. -- John German

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Last modified: August 22, 2002

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