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May 5, 2003 -- Some of this week's stories: Research offers clues to Alzheimer’s plaques Walker named acting national security ALD DuPont VP to speak at colloquium Management Corner: Safety LDRD results are topic of symposium Ask the Directorate: SARS

Research offers clues to Alzheimer’s plaques

By Dave Jacqué

Researchers from Argonne and the University of Chicago have developed methods to directly observe the structure and growth of microscopic filaments that form the characteristic plaques found in the brains of those with Alzheimer’s Disease.

No one knows if these “β-amyloid plaques” cause the disease, or are merely a symptom. But as America ages -- people over 85 are the fastest-growing segment of the population, and 30 to 40 percent of them will contract the disease -- every clue may help medical science slow or stop the coming epidemic.

“The three-dimensional structure of the entire β-amyloid fibril is the largest noncrystalline structure ever characterized,” said P. Thiyagarajan (IPNS), one of the project’s principal investigators.

Previous research in the field had shown that each plaque is a tangle of millions of ribbon-like peptide chains called β-amyloid fibrils. Peptides are chains of amino acids, simple organic compounds that form the building blocks of proteins. Inside the body’s cells, amino acids are used for growth, maintenance, and repair. Some peptides are needed for physiological processes; others have antibacterial properties.

Amyloid peptides are chains of 40 to 42 amino acid residues. Due to their unique chemical architecture, consisting of water-loving and water-avoiding amino acid sequences, Alzheimer’s peptides “self-assemble” to form tangles of fibrils in the brains of persons with Alzheimer’s Disease.

Alzheimer’s peptides seem to associate laterally, stacking on top of the other to form ribbon-like structures. The ribbon-like structures further associate to form thick twisting fibrils. Inside the brain, these fibrils can further associate and form insoluble plaques.

The insolubility of these large peptides prevented researchers from carrying out studies of their self-assembly. Due to the lack of detailed structural information, little progress had been made on understanding fibril structure and self-assembly -- crucial to identifying targets for potential drug candidates.

But now, a breakthrough in this field has come from the collaborative work of Argonne scientists Robert Botto (CHM), David Gregory (CHM) and Thiyagarajan with two University of Chicago groups -- David Lynn and his students Tim Burkoth and David Morgan from the Chemistry Department, and Stephen Meredith and student T.L.S. Benzinger from the Pathology Department.

Through a careful analysis of the Alzheimer’s peptide, the researchers found the strategic sites where amino acids can be removed such that the “truncated peptide” still would form fibrils just like the whole peptide.

“This finding makes it possible to study the actual assembly process of the whole peptide,” said Thiyagarajan (IPNS). Since the truncated peptide is less complex than the whole peptide, it would be possible to analyze its self-assembly process and the fibril structure with spectroscopic and scattering techniques.

To prevent the individual fibrils from sticking together, researchers added polyethylene glycol -- a water-soluble polymer -- to the hydrophobic (water-avoiding) side of each peptide. “This served as an extremely crucial step,” Thiyagarajan said, “as it allowed us to isolate and study individual fibrils, which was instrumental to determining their structure.”

In addition to electron microscopy studies on the fibrils at the University of Chicago, solid-state nuclear magnetic resonance (NMR) studies were performed at Botto’s lab at Argonne. The researchers replaced specific amino acids in the truncated peptide, one at a time, with those containing carbon-13 isotope, enabling them to measure the distances between carbon atoms with a precision down to two-tenths of an Angstrom (one hundred-millionth of a centimeter). NMR gave the local structure and organization of the peptides in the fibril. “Having the NMR facility here at Argonne was an important part of an excellent collaboration,” Thiyagarajan said.

Once the researchers deduced the atomic structure and the orientation of the peptide chains, they began to investigate the fibril’s structural hierarchy as well as its self-assembly mechanism. Small-angle neutron scattering at Argonne’s Intense Pulsed Neutron Source let them monitor the fibril’s initiation and growth in solution. These studies revealed that the fibrils form faster when the solution’s pH is higher.

Results on the radius and the molecular weight from the small-angle neutron scattering analyses showed that six peptide ribbons are laminated together, 10 Angstroms apart, by weak bonding between corresponding hydrogen atoms along each peptide molecule. These strands gently twist in a clockwise direction to form the helical structures seen in electron micrographs.

Walker named acting
national security ALD

Starnes E. Walker III has been named acting associate laboratory director for national security. The new position was created by Argonne Director Hermann Grunder to strengthen Argonne’s ability to contribute to national and homeland security.

Walker will provide leadership for several divisions and advise and guide research and development efforts in the other ALDships in the national and homeland security arenas. He joined Argonne early this year as deputy associate laboratory director for energy and environmental science and technology; most recently, he held the position of senior advisor for science and technology at the Defense Threat Reduction Agency.

Associate Laboratory Director Harvey Drucker spent the past 18 months coordinating Argonne’s national and homeland security efforts while continuing to lead the laboratory’s energy, environmental science and technology research divisions.

In other management transitions:

Beverly Hartline has stepped down from her position as deputy laboratory director to concentrate more fully on bringing the Center for Nanoscale Materials to life.

“In the past two years,” said Argonne Director Hermann Grunder, “Bev has provided significant leadership for our success and progress in integrating across the science and technology activities of the laboratory, improving contractual performance, managing laboratory-directed research and development, organizing the Rare Isotope Accelerator efforts, strengthening Environment, Safety, Security and Health, enhancing diversity awareness, and in many other areas. She will continue to lead the Center for Nanoscale Materials as associate laboratory director-at-large as we await a permanent director.”

W. Robert Logan will serve as acting deputy laboratory director. He has extensive management and contract expertise based on his career in both the public and private sectors, and has been responsible for performance on contracts with a number of federal entities for engineering, construction, environmental, planning and compliance services. He has more than 25 years of experience with government, national laboratory and university programs.

Don Joyce has been promoted to deputy laboratory director. “Don has taken on significant programmatic responsibility over the past year and has done an outstanding job,” Grunder said, citing as an example the “six-lab agreement” on nuclear energy which the secretary and under-secretary of energy have declared as policy.

DuPont VP to speak at colloquium

“Safety, Health and Environmental Excellence: The Foundation of Business Excellence” will be the topic of a Director’s Special Colloquium by Paul Tebo, DuPont’s vice president for environment, safety and health.

The colloquium will begin at 11 a.m. in the conference center in Argonne-East’s Building 402.

Tebo has more than 34 years of professional and management experience in research, engineering, planning, telecommunications and business.

Tebo has global responsibility for integrating safety, health and environmental excellence as a core business strategy, and for positioning DuPont’s efforts externally. He has championed DuPont’s “The Goal Is ‘0’” approach to environmental stewardship, and helped shape DuPont’s commitment to “sustainable growth,” including ambitious renewable energy and resource targets for 2010.

Prior to his current appointment in January 1993, he served as vice president and general manager for DuPont’s global petrochemicals business unit.

Tebo is former chair of the board of trustees of The Keystone Center and currently serves on the board of directors of the Stroud Water Research Center. He has also served as national director of the American Institute of Chemical Engineers, as well as on several university committees. Tebo received the Monroe J. Rathbone Outstanding Alumni Award from Lehigh University.

MANAGEMENT CORNER

‘Minor’ injuries should
be reported, every time

By Adam Cohen, director,  ESH and QA Oversight

The phone rang. The employee turned to answer it, and whacked a knuckle on the edge of the desk. Ouch! After taking the message, the employee noticed the skin was split on the right thumb. The employee washed the thumb and applied a bandage. Ten days later the employee was in the emergency room in severe pain, the thumb swollen and a red streak running up the forearm -- cellulitis. The employee spent two days in the hospital receiving antibiotics through an intravenous drip.

This incident occurred at Argonne-East earlier this year, and points up the need to visit the Medical Department for any injury, however minor it may seem at the time. Several times in recent months, employees have ignored minor symptoms -- a twinge in the back after lifting a heavy object, for example -- only to have it snowball later into a major problem resulting in lost work days. If they’d gone to the Medical Department right away, they may have been evaluated by a qualified and experienced physician. If necessary, the injury would have been properly cleansed and bandaged, then monitored until full recovery.

It’s the responsibility of every Argonne employee to be knowledgeable about their work and the associated hazards and controls, consistently choose to work safely, to follow the rules and to use the five-step Integrated Safety Management process. Employees should proactively look out for the safety of themselves and co-workers and for the environment; and be generally aware of their surroundings and possible impacts on their work and safety.

Argonne has an excellent safety record, as the chart shows. That record is not only good compared to other U.S. Department of Energy laboratories; it stands up well to comparable private industry settings. It could always be better, though -- and the ultimate goal is always zero injuries.

No one should ignore an injury, however small, to help keep the number of recordable cases low, or because it’s a hassle, or because it means an hour or two away from an important project.

Getting a physician involved early will minimize the possibility of an injury or illness becoming more serious. This is important for employees, and for Argonne’s safety record. It’s a win-win for everyone, and that’s the real measure of success.

LDRD results are topic of symposium

The 20th in a series of mini-symposia on the results of laboratory-directed research and development (LDRD) projects will be held Monday, May 5, from 2-4 p.m. in Argonne-East’s Building 402, Conference Room E1100-E1200. All employees whose schedules permit are invited to attend.

2 p.m. -- “Molten Oxide Electrolysis: A Basis for Carbon-Free Steel Production” by John Hryn (ES)

2:15 p.m. -- “Advanced Fast Reactor (AFR-300) Design Studies: Evaluation of Coupled Core Design and Heat Removal Systems for Superior Passive Safety Performance” by Tom Fanning (NE)

2:30 p.m. -- “A New Process for Groundwater Decontamination Using Cooking Oils” by Hassan Arafat (CMT)

2:45 p.m. -- “Support Vector Machine Algorithms to Merge Protein Structural Analysis and Machine Learning” by Nela Zavaljevski (NE)

3 p.m. -- Break

3:15 p.m. -- “Counter Terrorism Application of Agent Based Simulation” by Michael North (DIS)

3:30 p.m. -- “Magnetically Stabilized Metal Clusters” by Mark Knickelbein (CHM)

3:45 p.m. -- “Development of Anodes for Actinide Electrolysis” by Jim Willit (CMT)

ASK THE DIRECTORATE

SARS prompts concerns
about China travel

Q: What is the procedure for screening individuals who have recently traveled to China and are returning to work? Are these people required to get a medical clearance? What is being done to protect the health of employees at Argonne?

A: At present, the Centers for Disease Control (CDC) does not recommend quarantining individuals returning from China. Thus, those returning from affected areas who are not sick and who have not been in contact with individuals suffering from SARS (Severe Acute Respiratory Syndrome) may return directly to duty.

Individuals from China or other SARS hotspots who have symptoms of the disease should not return to the laboratory. These symptoms include any combination of aching joints, headache, fever of over 100.4 degrees, dry cough, shortness of breath, or other respiratory symptoms. Instead, they should call (630) 252-2800 and ask a staff physician how to proceed.

If someone was unknowingly exposed during the preceding 10 to 12 days, they still may become ill with SARS after they return to work. Such individuals who become ill while on duty should call ext. 2-2800 and ask a staff physician for instructions before leaving their work stations.

In line with CDC instructions, the Argonne Medical Department is advising people planning elective or non-essential travel to such SARS hotspots as Beijing, Hong Kong, Shanxi and Guangdong provinces in China and Singapore to postpone their trips until further notice. If going to one of these locations is a necessity, talk to a staff physician.

Currently, there is no satisfactory approved treatment for SARS. The medical department will be referring individuals to their own practitioners for personal care. Since there has not been enough time since the outbreak of SARS for medical literature to appear, the best resource for information is the CDC Web site. There are reports that combinations of ribovin and steroids are being used in individuals with progressive SARS, but this is an unproven treatment.

The medical department staff will be pleased to work with any individual who has concerns about travel, visitors or questions of personal exposure.

“Ask the Directorate” lets employees ask senior Argonne management direct questions about the laboratory’s operations, policy, strategy, mission, budget and goals. Employees should continue to refer job- or workplace-specific questions to their immediate supervisors.

Employees may submit questions to askthedirectorate@anl.gov or fax them to 2-5274. Only questions that include the name of the questioner and contact information, such as e-mail address, office extension or fax number, will be answered.

Prudential clarifies
guaranteed account rate

Prudential Financial has announced a clarification in its guaranteed interest account (GIA) for the 2nd quarter 2003. The GIA rates are:

Prudential Plans 5017 and 4245* -- 6% though 07/01/02 – 06/30/03, earned though 06/30/03

Prudential Plan 7680 --3.50% though 04/01/03 – 06/30/03, earned through 12/31/04

Prudential Plan 4643 -- 3.25% through 04/01/03 – 06/30/03, earned through 12/31/04

(* Only available to non-staff participants)

Club gauges interest
in race outing

Argonne Club is gauging interest in an outing to the Route 66 Speedway in Joliet to see the Lucas Oil NHRA Nationals Friday, May 30, Saturday, May 31, or Sunday, June 1.

Ticket prices will depend on the number of attendees. Employees interested in attending should contact Christine Andorf (PBC-HP) at ext 2-5153 or candorf@anl.gov.

Joliet college offers
on-site registration

Registration for Joliet Junior College fall classes will be offered on Monday, May 5, at Argonne-East.

College representatives will be available in the Human Resources offices in Building 201 from 10:30 a.m. to 1 p.m. to register students for fall 2003 classes. Employees must bring completed and approved educational assistance forms (ANL-89) to the registration.

Call Betty Iwan at ext. 2-3410 for information.

Program allows foreign children, spouses
of employees to receive driver’s licenses

A pilot program started by the Illinois Secretary of State’s office will allow foreign children and spouses of Argonne-East employees who cannot obtain work-related Social Security numbers to receive an Illinois driver’s license.

Anyone interested in obtaining an Illinois driver’s license must apply for a non-work Social Security number based on his or her Immigration and Naturalization Service documentation and should schedule an appointment with the Illinois Secretary of State’s office.

Applicants will need to present information about where they plan on applying for their non-work Social Security number along with acceptable forms of identification. These may include I-551 alien registration cards, I-688 temporary resident cards or I-94 arrival and departure records with valid passports.

A letter from Argonne must also be provided for each applicant. The letter should describe the place of residence, the relationship of the applicant to the employee and the duration of the employee’s work at Argonne. To receive a letter, call Nancy Griparis (HR) at ext. 2-2967 or e-mail ngriparis@anl.gov.

Applicants must provide proof of insurance for the vehicle they will be using for the driver’s test, and the vehicle must pass a safety inspection.

In addition, applicants must pass the required vision screening and written exams. Oral exams may also be given, but interpreters, provided by the applicant, are allowed.

Only a limited number of facilities will participate in the program and appointments are necessary. Currently, May 5, May 12 and May 29 are available for appointments. To schedule an appointment in the Chicago Metro Area, call (312) 814-1132.

Dermatologist will
screen for skin cancer

Skin cancer screening will take place at Argonne-East Wednesday, May 7, in the Medical Department in Building 201.

Edward Keuer, a board certified dermatologist with Loyola University, will conduct a visual skin examination to assess any problems or abnormalities of the skin.

Participants will receive educational materials and an individual report with a written diagnosis.

Registration deadline is Monday, May 5. The cost is $50; checks should be made payable to Preventures.

For more information, contact the Medical Department at ext. 2-2807 or ext. 2-2800.

HR CLASSES

Human Resources has scheduled the following classes in May at Argonne-East:

“Brown Bag Lunch: Developing Positive Assertiveness” (HR278) -- Tuesday, May 13, 11:30 a.m. to 1 p.m., Building 201, Room 238. Develop positive assertiveness by using a step-by-step approach. Learn to think assertively, feel confident and behave positively.

“Myers-Briggs: Style and Strengths in the Workplace” (HR258) -- Wednesday, May 21, 1-5 p.m., Building 212, Room A157. Participants will learn about their preferred methods of filtering information, making judgments, planning and problem solving, and how it affects their work style and relationships. All results are kept confidential and returned. Register by Monday, May 5.

“Brown Bag Lunch: Follow the Money Trail” (HR285) -- Thursday, May 22, 11:30 a.m. to 1 p.m., Building 362, Room F108. This class covers the direct funding process, including indirect expense rates, the management and proposal planning system, and sources of funding at Argonne.

“Conflict and Communication Skills in the Workplace” (HR269) -- Thursday, May 29, 8:30 a.m. to 5 p.m., Building 201, Room 190. This interactive course will let participants explore, develop, and practice specific conflict management and communication skills.

To enroll, contact a Training Management System representative. Call Betty Iwan (HR) at ext. 2-3410 for more information. For a complete description of courses, visit the Inside Argonne Web site. Click on “Resources,” then “Professional Development.”