This close-up view of the drug binding site within the HIV protease shows that the active site is a cavity inside the HIV. Kaletra fits inside this cavity, much like a key fits into a lock, blocking the material from replicating. X-ray crystallography studies at the APS provided the scientific details of how the atoms of Kaletra interact with the viral protein.

Sept. 5, 2006 -- Some of this week's stories:

HIV drug designed at APS saving thousands

Back in 1996, when Argonne's Advanced Photon Source first turned on its brilliant beam of X-rays, scientists from around the world were excited by the possibilities. Now, ten years later, one of those “possibilities” is saving thousands of lives.

One of the early research projects undertaken at the Advanced Photon Source, the source of the Western Hemisphere's most brilliant X-ray beams, was an examination of the Acquired Immune Deficiency Syndrome (AIDS) Human Immunodeficiency Virus, or HIV. Designing an effective anti-HIV drug requires very precise design: the drug must be very target-specific so that it impacts only the point where the drug can be most effective. The design must fit the particular structure of the target molecule, while being flexible enough to accommodate changes in that structure. Using X-ray crystallography, researchers found the points of attack of the HIV protease inhibitors — agents that block the breakdown of proteins. Protease inhibitors stop HIV from making new copies of itself by blocking the last step in the process, when the virus attempts to replicate.

Out of that discovery came the drug Kaletra®, now the most-prescribed drug in its class for AIDS therapy and a product of Abbott Laboratories, which was one of the earliest users of the Advanced Photon Source. Abbott Labs is part of the Industrial Macromolecular Crystallography Association (IMCA), which operates one of the beamlines at the Advanced Photon Source through a contract with the Consortium for Advanced Radiation Sources (CARS) at The University of Chicago. Researchers took a close-up view of the protein called the HIV protease, revealing the atomic details of how compounds interact with the protein.

“This premier national research facility, funded by the Department's Office of Basic Energy Sciences, provides the brightest X-ray beams in the Western Hemisphere to more than 5,000 scientists from around the United States and the world,” said Murray Gibson, Argonne associate laboratory director for scientific user facilities. “These scientists come to the APS from universities, industry, medical schools, and other research institutions, bringing with them ideas for new discoveries in nearly every scientific discipline. They bring their ideas to the APS because our X-ray beams let them collect data in unprecedented detail and in amazingly short time frames. The knowledge they gain promises to have real and positive impact on our technologies, our health, our economy, and our fundamental understanding of the materials that make up our world.”

“The development of Kaletra is an excellent example of the critical path of drug discovery used by pharmaceutical companies,” said Jonathan Greer, vice president of research for Abbott Labs. “The first leg of the critical path is discovery, as we identify the target and generate leads toward appropriate drug properties; second is development, as the target is validated and the leads optimized, demonstrating the safety and efficacy of the drug candidate. The new technologies that help with this process, in addition to molecular crystallography and the X-ray techniques available at the APS, are high-throughput screening and chemistry, protein biochemistry, automation and the range of genomics and proteomics processes.”

One of the challenges facing structural biologists and indeed much of biology has been the slow pace, often measured in months or years, of determining the structures of biomolecules that are important for advances in energy, health and the environment. The use of the Department of Energy-funded user facility allows researchers to speed the process of structure determination, narrowing the gap between the current pace of discovery and the ability of scientists to have access to new information. Because the research done at the Advanced Photon Source by Abbott Labs researchers was proprietary, the company reimbursed costs of using the facility for its research. In addition, as a part of the IMCA organization Abbott helped fund construction of the IMCA beamlines at the APS, which are available to non-IMCA researchers through the APS general user program.

Abbott researchers began clinical trials with Kaletra in the late 1990s and the longest clinical study of any HIV treatment — seven years — ended in late 2005 with data demonstrating that patients taking Kaletra in combination with other antiretroviral agents maintained an undetectable viral load (amount of virus in the blood) of less than 50 copies per milliliter. It is commonly remarked that Kaletra is a drug that helped turn a situation where patients were dying from AIDS to a situation where patients are living with AIDS.

Abbott has been a leader in HIV research since the early years of the epidemic. In 1985, the company developed the first licensed test to detect HIV antibodies in the blood, and remains a leader in HIV diagnostics. Abbott retroviral and hepatitis tests are used to screen more than half of the world's donated blood supply.

Argonne featured on World News Tonight

An ABC News story on the resurgence of demand for diesel-powered automobiles, featuring Center for Transportation Research Director Don Hillebrand, aired nationally on ABC World News Tonight Aug. 19.

A text version of the story is online, and a video clip will appear on monitors in the Building 213 Cafeteria.

Working safely: assessments lead to ‘best in class' results

Bob Mccook, ESH/QA director

Argonne's success depends on how well its products and services satisfy the requirements and expectations of its customers. In order to achieve the highest level of success, to be considered “best in class” and to gain a reputation as the “go-to” organization for new and follow-on work, day-to-day operations at Argonne must focus on customer requirements and expectations. The lab environment must embrace learning from, and sharing, experiences in the interest of continuous product, service and performance improvement.

The assessment of day-to-day activities by line management provides ongoing evaluation of management systems and processes and builds confidence in an organization's ability to meet customer expectations. These assessments provide objective evidence of areas where improvement is needed to achieve organizational goals and objectives, and where assessment results, both good and bad, are shared within the organization as a tool to improve overall performance. Mistakes and successes should be shared so that others can avoid the same or similar mistakes or adopt a method or process that has proven to be successful.

At some level, customer products and services and the programs, systems and processes that deliver them can all be assessed each and every day here at Argonne. Environment, safety & health (ES&H), quality assurance, radiological safety, safeguards and security activities are also considered products and services, and are subject to assessment.

In order for our assessment program to be successful we must become self-critical — able to identify and share our strengths and to recognize and address our weaknesses. We must knock down barriers that prevent us from sharing information, particularly information that will improve our processes and help us grow as a team. It is not always about getting an “A” on the exam; it is about continuous improvement.

Over the next couple of weeks and months, you will hear about efforts at the laboratory to improve our self-assessment processes, including management assessments. The greatest rigor and frequency of these assessments should be on items, services, programs and processes that contribute the greatest risk to quality, safety, environmental compliance, credibility, cost and the overall science mission here at the laboratory. While new procedures and training will be developed, the intention will be to incorporate, to the greatest extent possible, self-assessment practices currently being implemented but for which we are not taking full advantage in terms of documenting results and identifying strengths and weaknesses. Not documenting results and identifying strength and weaknesses puts us at a disadvantage when customers and third-party assessments identify issues or weaknesses that we may be aware of but did not document or did not resolve. Not correcting issues in the work place, either because we did not find them, or did not correct them when we did find them, puts us at risk for accidents, injuries and events as well as customer expectations that are not met and organizational goals and objectives that are not achieved.

In the regulatory world, an effective assessment process in conjunction with prompt identification of issues and weaknesses and the development and implementation of timely and appropriate corrective actions may be mitigating factors in determining civil and criminal enforcement citations and penalties. An effective assessment process can also result in improved customer and regulator confidence, which can equate to a reduction in external oversight and assessments. This translates to lower outside interface costs for the organization.

The 2005 assessment and report by the U.S. Department of Energy's Office of Assessments (OA) identified a number of weaknesses within our processes and how we implement them. Recovering from those issues continues to strain the organization more than a year later. As painful as the OA and its aftermath is to the laboratory, it has become the driving force for a renewed focus: a focus on learning, sharing, and improving what we do and how we do it.

Much of the information included in this article was taken from DOE Guide 414.1-1A “Management Assessment and Independent Assessment Guide” for use with 10CFR, Part 830, Subpart A and DOE O414.1A, Quality Assurance. Even the casual observer can see that management assessment is not just about compliance to the contract requirements, regulations and DOE orders. It is about common sense, good business practice, successful experiments, getting 100 percent of the data, achieving goals, meeting organizational objectives and good old-fashioned customer satisfaction — it is about being successful. This can translate into being “best in class.” That translates into Argonne being the laboratory where customers or sponsors prefer their science and research be accomplished.

French energy research topic of colloquium

Bernard Bigot (above), high commissioner for atomic energy for the French Atomic Energy Commission (CEA), will speak at a special colloquium Thursday, Sept. 7, in the Building 402 Auditorium. Bigot's talk, “French Expertise in Clean Energy Technologies: Tools for Energy Independence,” will begin at 9:30 a.m. All employees whose schedules permit are welcome to attend.

Bigot will be joined by Edouard Freund, executive vice president for research and development of Institut Français du Pétrole, and Claude Roy, advisor to the French government for biomass utilization. The three are part of a delegation visiting Argonne for an overview of the laboratory's activities in energy and biofuels.

Bigot is a leader in research, development and innovation in energy, information and health technologies and defense and national security. The CEA's goals are to become the leading technological research organization in Europe and to ensure France's nuclear deterrent remains effective.

Bigot has held several positions in research and higher education, including director of the cabinet of the minister in charge of research and new technologies, and deputy-director of the cabinet of the minister in charge of youth, national education and research. He has written more than 65 articles for international journals.

Bigot has been awarded France's National Order of Merit and the Légion of Honor.

New members join university's Board of Governors for Argonne

The University of Chicago has named two new members to its Board of Governors for Argonne National Laboratory.

The university, which operates Argonne for the Department of Energy, names the board members to help oversee and guide Argonne research, operations and management. Members of the board are chosen from faculty, administrators and trustees of The University of Chicago, from other universities, from national and international organizations, and from industry. In addition, the director of Argonne is an ex-officio member of the board.

The new members are Deborah L. Wince-Smith, president of the Council on Competitiveness, and Mary Fanett Wheeler, professor of aerospace engineering and engineering mechanics, petroleum and geosystems engineering and Ernest and Virginia Cockrell Chair in Engineering at the University of Texas at Austin.

“We are very grateful to these highly distinguished leaders in their respective fields for agreeing to serve on the board of governors,” said Thomas F. Rosenbaum, vice president for research and for Argonne National Laboratory, The University of Chicago. “These appointments further strengthen the laboratory's commitment to keep the U.S. globally competitive through innovation, collaboration and world-class multidisciplinary research and development.”

Wince-Smith is an internationally recognized expert on science and technology policy, innovation strategy, regional economic development and global competition. She serves on a number of boards and committees, including the board of directors of the NASDAQ Stock Market, the National Science Board's Task Force on Transformative Research, the Secretary of Energy Advisory Board's Task Force on Nuclear Power, the National Research Council's Committee on Innovation Models for Aerospace Technologies, the University of California President's Council for Los Alamos and Lawrence Livermore National Laboratories, and the University of Pennsylvania Museum of Archaeology and Anthropology.

Wheeler is a world-renowned expert in massive parallel-processing. She became a faculty member of The University of Texas at Austin in 1995 and is presently director of the Center for Subsurface Modeling in the Institute for Computational and Applied Mathematics.

Wheeler's research interests include numerical solution of partial differential systems with application to the modeling of subsurface and surface flows and parallel computation. Her current work has emphasized multiscale mixed finite element and discontinuous Galerkin methods for modeling reactive multi-phase flow and transport in a heterogeneous porous media, with the goal of simulating these systems on parallel computing platforms.

Wheeler has published more than 150 technical papers and edited seven books. She is currently an editor of nine technical journals, managing editor of Computational Geosciences, and a founding member of the SIAM Activity Group in Geosciences.

Author, astrophysicist to speak at APS colloquium

Internationally-known astrophysicist Mario Livio, author of “The Equation That Couldn't Be Solved,” will speak at an Advanced Photon Source Colloquium Wednesday, Sept. 6.

Livio, senior astrophysicist at the Hubble Space Telescope Science Institute, and the previous head of the institute's Science Division, will discuss the history of group theory, the mathematical language that describes symmetry, a force that he says explains much about the aesthetics of the world, from the choosing of mates to the Rubik's cube, Bach's composition, the physics of subatomic particles and the popularity of Anna Kournikova.

The talk will begin at 3 p.m. in the Building 402 auditorium.

Livio was a professor of physics in the physics department of the Technion-Israel Institute of Technology from 1981 until 1991.

In the past decade, Livio's research has focused particularly on the topics of supernova explosions and their use in cosmology to determine the rate of expansion of the universe, on the nature of “dark energy,” on the formation of black holes and the possibility to extract energy from them, on the formation of planets in disks around young stars, and on the emergence of intelligent life in the universe. He has published more than 400 scientific papers.

Livio is also the author of “The Accelerating Universe,” which discusses the “beauty” of fundamental theories of the universe, and “The Golden Ratio,” which won the Peano Prize for 2003, and the International Pythagoras Prize for 2004, as the best popular book on mathematics.

Battery partnership garners award

Air Products and Chemicals of Allentown, Penn., has given Argonne its 4th annual External Collaboration Award. The award recognizes researchers in the Battery Technology Department of Argonne's Chemical Engineering Division for their work in evaluating Air Products' new electrolyte salts, citing the group's understanding of the technology and needs of the lithium-ion battery industry, as well as the direction the industry is taking toward hybrid vehicles. From left to right are researchers Andrew Jansen, Jun Liu, Zonghai Chen, Group Leader Khalil Amine, and Battery Technology Department Manager Gary Henriksen (all CMT) Photo by George Joch.

Ar'Gang

NEW ARRIVALS

A girl, Madalynn Grace, born March 20 to Jessie (C&PA) and Michael Skwarek (CIS) and proud grandmother Mary Kay Skwarek (CIS). A boy born Sept. 11, 2005 to Qun Shen (XSD) and Jun Wang (APS); a boy born April 21 to Martin de Jonge (XSD) and Amelia Liu (MSD); a boy born May 26 to Sophia and Barry Lai (XSD); a boy, Anthony Ray, born to Jennifer and Jeff Ullian (EQO); a boy, Aidan Torrance, born May 22 to Amy and Ti Leggett (MCS); a girl, Jaidee Gwynne, born June 8 to Anna and Peter Lane (MCS); granddaughters, Kaitlyn and Kiersten, born to Alice Birmingham (EQO-AS); twins, Clement and Ava-Lia, born to Lia and Christos Stamoudis (EQO-AS); a boy, Evan Joseph, born to Jackie and Brian Weder (EQO-TR); a granddaughter, Chesterine Cecila, born July 19 to George Vasiopulos (IPNS); a grandson, Trevor Daniel, born May 13 to Roberta Gianpetro (TSD); a granddaughter, Lilly Lynn, born to Harry (PFS-BM) and Ella Cavett (PFS-CU); a grandson, Gavin, born to Nora and Neil MacDonald (PFS-BM).

ACHIEVEMENTS

Congratulations to Marjorie Brockman (OCF-PRO), on her published book of poems about the Vietnam War and the soldiers who served in the war.

WEDDINGS/ENGAGEMENTS

Congratulations to Ken Dritz (DIS) on his marriage to Joann Jackson in July; Laurie Culbert (TSD) on her July 21 marriage to John R. Havey; Floyd Bennett (TSD) on his daughter Geneieve's July 12 marriage.

GET WELL

Get well to Debra Ritchie (TSD).

WELCOME

PFS-CU welcomes Brian Fisera, Mark Merker, David Prokop, Fernando Ocampo and Bruno Orosz. TSD welcomes Joseph Harmon and Todd Morris. PFS-BM welcomes Art Shelton, Dennis McKenna and Brian Milke.

FAREWELL

Good luck to Kelly Cummings (LEG), Bill Basaraba (PFS-BM) and Shannon Savage (TSD) who have all left the laboratory.

PROMOTIONS

Promotions reported to Ar'Gang this month include: Irving Vaughn (PFS-CU) promoted to janitor group leader; Marty Vondra (PFS-BM) promoted to foreman and Charles Greenwood (PFS-BM) promoted to Maintenance Mechanic I.

CONDOLENCES

Our condolences to Gary Zeman (EQO) on the death of his mother; Bob Wynveen (EQO) on the death of his mother; Brad Stacy (EQO) on the death of his father; Jason Dunkin (PFS-CU) on the death of his mother; Tim Tess (EQO) on the death of his brother; Judy Beumer (MCS) on the death of her father; Mark Langguth (LEG) on the death of his father; Kim Young (PFS-CU) on the death of her brother and grandmother; Anthony Young (PFS-CU) on the death of his father-in-law; Todd Morris (TSD) on the death of his father; Mary Jo Koelbl (TSD) on the death of her mother; Madonna Pence (TSD) on the death of her mother.

Dell laptop batteries can be exchanged at CIS Help Desk

Argonne's Computing and Information Systems Division (CIS) is working with Dell in a coordinated effort to replace “recalled” Dell batteries for Argonne-owned laptops. Instructions for identifying and exchanging recalled batteries that were purchased by Argonne are online.

Suspect laptop batteries may be exchanged at the CIS Help Desk in Building 222. Before transporting the batteries, cover the terminals with adhesive tape to prevent the risk of a short-circuit. Because of transportation regulations, individuals should not coordinate an exchange of these batteries directly with Dell.

In cooperation with the U.S. Consumer Product Safety Commission and other regulatory agencies, Dell is voluntarily recalling certain batteries with cells manufactured by Sony and offering free replacements. Under rare conditions, it is possible for these batteries to overheat, which could pose a risk of fire. Some Dell notebook computers sold between April 1, 2004, and July 18, 2006, may be affected.

For more information, or assistance in determining if a battery is eligible for exchange, contact the CIS Help Desk at 2-9999, option 2, or help@anl.gov.

Service Awards for September include:

35 Years

James M. Cruz (PFS), Gopal K. Shenoy (XSD), David Spence (NE)

30 Years

Alex Hamilton (PFS), Kimberly A. Lindgren (NOD), James F. Miller (CMT), David G. Underwood (HEP)

20 Years

Robert E. Blair (HEP), Robert W. Dunford (CHM), Wei Gai (HEP), Sai-Chi Mo (NE), Cynthia Powell-Tagoe (PFS), Christine T. Snyder (CMT)

15 Years

Regina Buckley (PME), Michael Douell (ASD), Ann E. Murray (ES), Anne Wyand Owens (XSD), Montez L. Poe (PFS)

10 Years

Orlando H. Auciello (MSD), Zhonghou Cai (XSD), Thomas Gog (XSD), Carol G. Lepzelter Berry (TSD), Nicholas S. Sereno (ASD), Peggy A. Stepuszek (HR), Jennifer Tucker (EQO), Rikutaro Yoshida (HEP)

5 Years

Sandra Gail Biedron (AST), Jakub P. Dobrzynski (ET), Rosa P. Foote (SCD), Joel P. Fuerst (PHY), Evangeline S. Gohoure (HR), Valentyn Novosad (MSD), Rakesh A. Patel (BIO), Ronald M. Scott (PFS),Catherine L. Westfall (OTD), Wenhua Yu (ET)