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Berkeley Lab Currents

May 29, 1998


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Breakthrough in X-Ray Microscopy Gives New View Inside Living Cells

By Lynn Yarris

What has been one of the better kept secrets on the Hill will soon be a secret no longer, and the view inside living cells will be better for it. Carolyn Larabell, a cell biologist and microscopist with the Life Sciences Division, working with Werner Myer-Illse, a physicist and x-ray microscopist with the Materials Sciences Division, plus other researchers from both divisions, has developed a technique for using x-ray microscopy to obtain unprecedented images of labeled proteins inside of whole cells in a hydrated state. Among many other things, this technique may help scientists resolve the long-standing debate over whether or not the cell nucleus has an organized internal structure.

Using the x-ray microscopy beamline (XM-1) at the ALS, Larabell, Myer-Illse and their collaborators have produced images of intact hydrated cells that many scientists will have to see to believe. Compared to the 200 nanometer resolution in images obtained with the best visible light microscopes, the images produced with the soft (low energy) x-ray beams at XM-1 showed a resolution between 40 and 50 nanometers. Plus, these cells did not have to be stained in order to obtain high contrast images of cell structures.

"Soft x-ray microscopy could make a major contribution to the understanding of cell function and structure," Larabell says. "We have demonstrated a practical technique that gives cell biologists a whole new way of looking at their samples."

In perhaps no other scientific field does the adage "form follows function" hold more true than in biology, especially the biology of living cells, which is why our knowledge of cells starts with imaging. Throughout the 1990s, the best images of protein localizations in cells have probably come from confocal microscopy, a technique whereby blurring is avoided through the collection of thousands of pin-points of laser light. These pinpoints of collected light can be assembled into highly-focused images that are unmatched for contrast and clarity by conventional visible light micros-copy. Used in combination with fluorescent-labeling, in which fluorescently-tagged antibodies bind to specific proteins for identification, confocal microscopy has lit the way for many of the recent advances in cell biology. However, the information obtained will always be limited by the technique's relatively low spatial resolution. Electron microscopy provides outstanding resolution (down to one-tenth of a nanometer), but cells must be sectioned off into tissue-thin slices for imaging because even highly-energized electrons are poor penetrators. Also, the cell slices must be dehydrated, as electron microscopy can only be done in a vacuum.

"To section the cells, you have to first embed them in plastic, otherwise it's like trying to section a raw egg," says Larabell, who is highly experienced with both confocal and electron microscopy. "The chemicals used for dehydration and embedding in plastic can result in the loss of proteins, and the plastic can interfere with the ability of the antibodies to bind to the protein."

The need has been, she says, for an alternative form of microscopy that provides higher resolution information on thick hydrated cells without requiring elaborate specimen preparation.

As Larabell and her collaborators are showing, soft x-ray microscopy fits the bill.

A key to the success at XM-1 lies in how the cells are prepared for imaging. After being treated with a fixing agent to lock their proteins into position, the cells are washed in a special detergent that removes the lipids in their outer membrane. This yields a cell surface that is perforated with holes through which antibodies coated with a cluster of fluorescent and nano-sized gold particles can be introduced.

Inside the cell, the fluorogold-labeled antibodies attach themselves to specific proteins, including those within the nuclei. Because the nano-sized particles of gold are too small to be seen even with x-rays, prior to imaging at XM-1 the treated cells are enhanced with a coating of silver, similar to the use of silver emulsions to bring out images on photographic film.

Larabell's experiences with both visible light and electron microscopy were crucial to her developing this unique method of preparing cells for soft x-ray imaging. She also credits her success with being "flexible" about her protocols.

"Microscopists who work with (visible) light tend to use fast but harsh cell preparation techniques because at that resolution, they won't see their mistakes," she says. "With electron microscopy, every flaw is (literally) magnified so the preparation techniques are incredibly arduous. Having worked with both, I'm willing to change my protocols to find the best and most efficient."

Another key to the success at XM-1 has to do with the capabilities of the facility itself. XM-1 is a direct-imaging transmission x-ray microscope operating off an ALS bend-magnet beamline (6.1.2) under the direction of Meyer-Ilse of the Center for X-ray Optics, who was responsible for the facility's creation.

Members of Meyer-Ilse's team include CXRO's John Brown and Ajit Nair, who have been collaborators on the cell imaging work, along with Sophie Lelievre and Donna Hama-moto of Life Sciences Division.

The photon-energy range of XM-1 extends from 250 to 950 electron volts, a range that covers the so-called "water window"--the energy span over which water is transparent to x-rays, but carbon-containing materials are not. This means that high-contrast images of proteins and other interior cell structures can be obtained at XM-1 without the need for staining.

The combination of fluorogold-labeling and XM-1 has already been used to obtain detailed information on the distribution within cell nuclei of a "splicing factor" protein that plays an important role in the expression of certain genes.

This proof-of-principle experiment can be considered a preview of coming attractions.

Among the first areas to be explored will no doubt be the cell nucleus itself. The cell nucleus has been called one of the best known but least understood of all cell organelles, with some biologists arguing it has a distinct substructure, and others arguing that it is merely a membrane-bound sack full of DNA and other molecules. A major goal of cell biology is to finally resolve this dispute and get a better handle on nuclear organization.

Another major target for x-ray microscopy will be to investigate the interactions between cell interiors and a mass of protein support "scaffolding" outside the cell called the extracelluar matrix (ECM). LSD director Mina Bissell has demonstrated that breakdowns in the normal interaction between the interior of a cell and its ECM can lead to breast cancer.

X-ray microscopy could also be used to view other critical interactions, such as those between the cell's outer surface and its cytoplasm, between the cytoplasm and the nucleus, and even between the nucleus and the chromosomes.

Says Larabell, "We hope x-ray microscopy will help answer a lot of questions no other imaging technique can."

Photo: The microscopy images captured by Carolyn Larabell of the Life Sciences Division have graced the covers of numerous science publications. (XBD9805-01426.tif)

Photo: With the combination of ALS x-rays and a new protein-labeling technique, scientists can see the distribution of the nucleoli within the nucleus of a mammary epithelial cell. (nucleus3.tiff)

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Chinese and U.S. Scientists Discuss Future of Energy Technologies

A ten-member delegation representing the Chinese Academy of Sciences arrived at Berkeley Lab on Monday, May 18, for two days of meetings with representatives of the U.S. National Academy of Sciences and the U.S. energy industry. The visit underscored the close and growing scientific links between the two countries.

The Committee on Cooperation in the Energy Futures of China and the United States is preparing a report that will suggest areas of cooperation between the two nations in the research and development of cleaner, more energy efficient technologies. The environmental consequences of energy use and related technologies were also addressed.

The Chinese delegation was led by Lu Yongxiang, president of the Chinese Academy of Sciences, while Nobel laureate Sherwood Rowland represented the U.S. National Academy. Other members of the Chinese contingent included Zhou Fengqi, director of the Energy Research Institute of the State Plan-ning Commission, Fan Weitang, President of the China Coal Society, and Yan Luguang, director of the Academy's Institute of Electrical Engineering. Participants in the U.S. group included Environmental Energy Technologies Division Director Mark Levine, who hosted the event, and Richard Balzhiser, past president of the Electric Power Research Institute.

On May 20 the Chinese delegates took a tour of Berkeley Lab. At the Energy Efficient Fixtures Laboratory, members of the delegation saw the compact fluorescent torchiere developed there and talked with Lighting Group head Michael Siminovitch about other efficient lighting projects.

"The Chinese delegates were very excited to see the evolution of compact fluorescent fixtures, and showed great interest in using energy efficient fixtures for the home," Siminovitch said. "Judging by their comments and questions I could tell they were very familiar with the technology and committed to using it in their country."

A highlight of the tour of Berkeley Lab was the stop at the Advanced Light Source. ALS Director Brian Kincaid and Alfred Schlachter led the group through a variety of beam lines and projects in the life, physical and materials sciences.

The group also visited the National Energy Research Scientific Computing Center (NERSC), ESNet and the Visualization Lab, where they were hosted by Computing Sciences Dir-ectorate Deputy Sandy Merola. EET Division's Mary Quinby-Hunt discussed her study of light scattering off of particles such as diesel exhaust using NERSC computer time.

Mike Chartock, head of the Office for Planning and Communications, welcomed the group in the Bldg. 50 lobby and guided them through the Lab's history, achievements and historical displays.

Photo: Advanced Light Source Director Brian Kincaid discusses accelerator physics with a delegation of high-ranking officials from the Chinese Academy of Sciences. (chinese.tiff) Photo by Don Fike

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Record Number of Interns Expected This Summer

By Paul Preuss

Operating for the first time with help from the Department of Energy's Energy Research Undergraduate Laboratory Fellowships (ERULFs), Berkeley Lab's summer intern program for college undergraduates is "revived and up and running," according to Laurel Egenberger of the Lab's Center for Science and Engineering Education (CSEE).

"We have 50 interns this year, up from 40 last year," says Egenberger, "and for the first time some of our interns will come from a cooperative program with Contra Costa College in San Pablo--a rigorous science education program for kids who are preparing to major in science in four-year institutions."

Undergraduate interns will be found throughout the Lab starting as early as next week: in Engineering, Physics, Earth Sciences, Physical Biosciences, Environmental Energy Technologies, and the National Center for Electron Microscopy in the Materials Sciences Division. In the Life Sciences Division, a number of students who have already completed four-week workshops in biotechnology will be returning for 10-week research programs.

Interns not only work with individual mentors on specific research projects, they also spend time in seminars and other kinds of "book learning." Reports of their research are featured in an annual student poster session, this year scheduled for Aug. 5.

"One of the more interesting intern projects is that they make their own web pages," Egenberger says. "They not only learn science but they learn how to get their results out into the world." One of last year's interns, Eli Kintisch, who worked with Edward Berry in the Structural Biology Division (now known as the Physical Biosciences Division) is taking science communication a step further and will come back to spend this summer with the Public Information Department.

One aim of the web page projects is to interest high- and middle-school students in the range of scientific work available to young people at Berkeley Lab. A sampling of web pages from the past three years--some of them wildly colorful--can be found on the CSEE website at http://csee.lbl.gov/StudentPages.html.

The Lab has an active summer internship program for local-area high school students as well. The program is directed by CSEE's Marva Wilkins, who has kept the program going with what she calls "creative funding." This summer, high school interns will be found at the Advanced Light Source, for instance, building web pages based on interviews with scientists; others will be learning techniques of magnetic resonance imaging in the Medical Services Department of Life Sciences, studying building science in Environmental Energy Technologies, working on high energy physics projects in the Accelerator and Fusion Research Division, and doing astrophysics.

To learn more about internship at Berkeley Lab, including how students can apply for ERULF aid in future seasons, visit the CSEE web site at http://csee.lbl.gov/.

Photo: Students participating in last year's internship program concluded their experience at Berkeley Lab with a special poster session in which they exhibited their work and shared the results with fellow students and Lab employees. Photo by Don Fike

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State of the Lab Today

Berkeley Lab Director Charles V. Shank will present his annual State of the Laboratory address today at noon in the Bldg. 50 auditorium. A remote video link is being set up in the Bldg. 66 auditorium.

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News Digest

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Washington News

Next Generation Internet caught in jurisdiction spat

A jurisdictional dispute between two House chairmen may disrupt plans to authorize federal funds for DOE and other agencies to improve the Internet. Rep. Curt Weldon (R-Pa), chairman of the House National Security subcommittee on military R&D, has announced he plans to rewrite a bill supporting the Next Generation Internet after the House Science Committee last week approved an authorization bill that included NGI-related work at the Pentagon.

Weldon made his announcement after Science Committee Chairman F. James Sensenbrenner Jr.(R-Wis) refused to allow Weldon to offer an amendment that would have limited the NGI bill to activities at DOE, the Commerce Department, NASA, and the NSF--agencies whose R&D programs are clearly within the committee's jurisdiction. In response, an angry Weldon told reporters that the Science Committee has no right to authorize DOD activities, and added that his amendment limiting the measure to the other four civilian agencies would have expedited its passage through Congress.

Weldon was especially critical of Sensenbrenner for not only denying him an opportunity to offer his amendment but for refusing to allow him and other members of the Science Committee to make opening statements on the NGI bill (H.R. 3332). "The absolute arrogance of the chairman and the committee staff could kill this whole measure," Weldon said.

One of NGI's initial goals is to set up 100 test sites where Internet speeds would be 100 times faster than today's network and 10 sites 1,000 times faster than today's. NGI received $100 million in appropriations this year, despite not having been authorized by Congress. DOE did not receive any of the money, but the department hopes to begin participating in the program in FY99.

Attempt to kill DOE and slash budget dropped

House Budget Committee Chair-man John Kasich has dropped a list of spending cuts from a proposed FY99 budget after members of his own party joined the White House in criticizing the Ohio Republican's plan as too severe. The proposal, which would have slashed spending by more than $100 billion over the next five years, also called for the elimination of both DOE and the Commerce Department.

The plan lacked strong support among other House Republicans, including appropriations Committee members who believe they should decide where to cut federal spending. Kasich's proposal to abolish the DOE angered even those House members who have never been friends of the agency. They have suggested that this latest call to eliminate the department was based more on political considerations than a conviction that DOE is not needed.

--Lynn Yarris

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In Memoriam: Earl Randall Parker

By Monica Friedlander

Renowned metallurgist Earl Randall Parker, who was instrumental in starting a research program in material sciences at Berkeley Lab, died on May 9 at the University of California Medical Center in Sacramento. He was 85.

A holder of the National Medal of Science and a member of the National Academy of Engineering, Parker held joint appointments at Berkeley Lab and U.C. Berkeley, where he taught materials science and mineral engineering.

Parker's career started more than three decades ago when he came to UC Berkeley in 1944. His pioneering work in the properties of materials won him numerous awards as well as the respect of his colleagues.

"He was one of the grand old men of metallurgy, particularly steel technology," said Robert O. Ritchie of the Lab's Materials Sciences Division and professor of materials science and mineral engineering at U.C. Berkeley. "He had an influence on all aspects of materials science."

Parker's research in the changing properties of materials led to the development of high-strength materials and means to detect and fix internal defects of metals. During World War II, for example, he found a way to fix a major problem with the steel used to build the Liberty Ships that carried supplies in the war effort. Many of the ships would break because of cracks in the welded steel. In 1944 Parker found the weak link and supplied a solution.

During the 1960s Parker and UC Berkeley colleague Victor F. Zackay developed the Transformation Induced Plasticity Steels (TRIP), a new alloy that had unprecedented strength and resistance to fracture.

At U.C. Berkeley Parker chaired the Department of Mineral Techno-logy from 1953 to 1957 and again from 1965 to 1966.

"He was one of the giants of the department and was really responsible for the department getting heavily involved in research," said Professor Douglas Fuerstenau of UC Berkeley.

In his later years his interests shifted to the study of ceramics.

Parker also lobbied the Depart-ment of Energy to establish what would eventually become Berkeley Lab's Material Sciences Division--originally the Inorganic Materials Research Division.

In 1980 Parker was awarded the National Medal of Science, the nation's highest honor for a scientist. His many honors include fellowship in the American Physical Society, the American Society for Metals, and the American Institute of Mining, Metal-lurgical and Petroleum Engineers. He was also one-time president of the American Society for Metals.

A distinguished teacher and mentor who oversaw nearly 100 doctoral dissertations, Parker was awarded the Distinguished Teaching Award from the Berkeley Division of the Acade-mic Senate. Upon his retirement in 1978 he received the Berkeley Citation, the highest honor bestowed by U.C. Berkeley.

Parker was born in Denver and worked for General Electric Company in Schenectaday, New York, before coming to Berkeley.

Parker is survived by his wife, Agnes Parker, daughter Margaret Sullivan, son William Parker, and three grandchildren. A memorial was held on May 13 in Walnut Creek. Contributions may be made to the Hanna Boys Center, P.O. Box 100, Sonoma, CA 95476.

Photo: Earl Randall Parker (parker.tiff)

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City Council Tones Down Anti-DARHT Language in Letter to Lab

Responding to the City Attorney's cautions about potential legal issues, the Berkeley City Council has authorized a letter opposing Berkeley Lab's DARHT accelerator project with language that modifies an earlier, more strongly worded resolution.

At its May 5 meeting, the City Council passed without discussion a four-paragraph letter to Laboratory Director Charles Shank and the Regents of the University of Calif-ornia, which "formally requests that the University of California and LBNL cease and desist work for nuclear weapons, including work on the DARHT facility."

The letter does not characterize the Lab as violating the Nuclear Free Berkeley Act, as stated in an earlier version, and acknowledges that provisions of the act "may be unenforceable as to LBNL." It further states its conclusion that construction of the linear induction accelerator for the Dual Axis Radiographic Hydrody-namic Test (DARHT) facility in Los Alamos is "nuclear weapons work."

As he has on previous occasions, Director Shank said he will inform the City that he does not consider the Laboratory's accelerator project "work for nuclear weapons," and he will point out that it is non-nuclear, unclassified, and consistent with the type of activity Berkeley Lab has conducted since its inception.

Shank will also point out the parallels between this partnership with Los Alamos and the Department of Energy's Academic Strategic Alliance Program. In the latter, five distinguished U.S. universities--Stanford, Caltech, University of Illinois Urbana-Champaign, University of Utah, and University of Chicago--are collaborating with DOE labs on the Accelerated Strategic Computing Initiative (ASCI), a critical element in America's science-based stockpile stewardship program. ASCI and DARHT are both being advanced, in part, to develop technology that simulates weapons systems to ensure U.S. security without actual testing, in compliance with the Comprehensive Test Ban Treaty.

Moreover, both programs address challenging problems in science and engineering, some of which will have far-reaching implications throughout society. In Berkeley Lab's case, the accelerator work will help maintain programmatic excellence in the inertial confinement fusion field, Shank said.

The accelerator will be the second axis of DARHT, an x-ray machine which will be strong enough to see through metals.

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Around the Lab

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NERSC-SLAC Collaborations Apply Scientific Computing To Experimental High Energy and Nuclear Physics

By Jon Bashor

Berkeley Lab and the Stanford Linear Accelerator Center have a long history of collaboration stemming from their high energy physics research. Now the two facilities are leveraging their resources in the cutting edge area of scientific computing.

Examples range from sharing experiences with software applications to developing new systems for gathering, organizing and analyzing data from the upcoming series of particle experiments known as BaBar.

Enhancing scientific computing among DOE labs was one of the objectives of the 1996 move of the Energy Sci-ences Network and the National Energy Research Scientific Computing Center (NERSC) to Berkeley Lab. Richard Mount, director of SLAC Computing Services, says the move is already bridging what had been a big gap between the scientific computing community and the scientific data processing fraternity within high energy and nuclear physics.

The proximity of the two DOE facilities, combined with the convergence of scientific computing and scientific data processing, are providing new avenues for cooperation.

"There has been a real effort by NERSC to move into scientific computing and scientific data management," Mount said. "There is also a strong direction in high energy physics toward increasingly data intensive experiments. We're seeing a strong effort to seek out common solutions, to seek out new possibilities."

One focal point of this effort is DOE's High Energy and Nuclear Physics Data Grand Challenge to develop tools to allow high energy and nuclear physicists to analyze and manage the massive amounts of data from future experiments, such as those planned for the Relativistic Heavy Ion Collider at Brookhaven National Lab. These experiments, aimed at understanding quarks and other exotic forms of matter formed in the wake of the Big Bang, will generate huge amounts of data--hundreds of terabytes a year.

A large part of the challenge in the early stages will be to predict data-access and computational problems and find ways to solve them. NERSC and SLAC are both working on the problem.

The Computing Sciences organization at Berkeley Lab has several groups working on scientific computing solutions to high energy physics problems. These include the Visualization, Distributed Collaboration, HENP Support, Scientific Computing, Scientific Data Management, and HEP Computing groups.

"The scientific computing problems challenging high energy physics are also showing up in other fields of research," says NERSC director Horst Simon. "Genomics researchers also must find ways to organize and access vast banks of data. Computing Sciences is working on solutions covering many aspects of research, from gathering data from experiments, to organizing, analyzing and presenting the data in useful ways."

For example, the six-person HENP Support Group in the Lab's Information and Computing Sciences Division is designing computer tools to help with the BaBar experiments to be conducted at the "B Factory" being built at SLAC. The goal is to measure the decays of subatomic particles and anti-particles known as mesons. To acquire a sufficient sample of those decays that can reveal fundamental differences between matter and anti-matter, researchers will need to perform up to one billion experiments a year, yielding 150 terabytes of data. They will then need powerful statistical analysis tools to analyze the information.

"This is the most advanced software project in high energy nuclear physics today," said Information and Computing Sciences Division leader Stu Loken. "Ex-periments at future particle detectors will depend on the work we're doing for BaBar."

About 500 physicists in 10 countries are participating in this project and need access to the data, which will be stored in NERSC's High Performance Storage Systems. "We really feel we are welcome collaborators," Mount said.

This situation is a turnaround from the early 1980s, when high energy physics experiment data were recorded on magnetic tapes, and it was not uncommon to fill 10,000 tapes with data. Showing up at a supercomputing center with the equivalent of two truckloads of tape to process did not produce a warm reception at a time when the machines were less powerful, with limited tape handling facilities, Mount said.

To enhance the collaboration between the two facilities, SLAC now provides office space to NERSC employees who live in the South Bay and Peninsula and choose to telecommute. Employees from both facilities routinely work at each other's sites, applying their expertise and drawing upon that of their counterparts. And Berkeley Lab's Stu Loken and Carl Eben, deputy division leader of ICSD, serve on SLAC's computing review committee.

"Our respective resources put us in a unique position to contribute to the Department of Energy and the nation as a whole," Mount said. "I see this growing cooperation as a strategic effort, not just a technical sideline."

Photo: Berkeley Lab is designing computer tools to help with the BaBar experiments to be conducted at the "B Factory" being built at SLAC. BaBar's magnet is shown above. (babar2.pict)

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Computer Corner

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Year 2000 Reminder

With 582 days to go until the turn of the century, there's still time to find out if your system is vulnerable to the much-feared Year 2000 computer problem, and if so, what you can do to protect your computer.

According to Mark Rosenberg, leader of the Computing Infrastructure Technology Group, the employees most likely to encounter a computer problem are those using PCs made before mid-1994. Users of Apple Macintosh and UNIX-based computers will not run into any operating system problems, Rosenberg says. Most current commercial software packages have also eliminated the problem.

Whatever problems will occur stem from older computer designs which allocated only two spaces for recording the year in any date-sensitive application. For instance, the year 1998 shows up as 98, and the year 2000 will be 00, which some computers could interpret as 1900. While some dire consequences have been predicted, for most desktop systems the problem is more likely to be irritating than debilitating.

As a result of the possible implications, the U.S. Government has required all its agencies and facilities to ensure that computer systems are "Year 2000 compliant." According to Rosenberg, the major systems at the Lab have been examined and are either already in compliance, or will be replaced by compliant systems before the year 2000 becomes an issue.

For more information about Year 2000 ("y2k") issues, visit the Lab's web site at http://www.lbl.gov/ICSD/CIS/y2k.html.

Dave F. Stevens, the Lab's liaison to DOE for Year 2000 compliance issues, also suggests this list of related websites:

Department of Energy: http://websparc.hr.doe.gov/year2000/"

General Services Administration: http://www.itpolicy.gsa.gov/mks/yr2000/y2khome.htm

National Institute of Standards and Technology: http://www.nist.gov/y2k/

Apple Computers: http://www.apple.com/macos/info/2000.html

IBM: http://www.ibm.com/year2000

Micron Electronics: http://www.micronpc.com/about/year2000/index.html

Silicon Graphics Inc.: http://www.sgi.com/features/1998/jan/y2k

Sun Microsystems: http://www.sun.com/y2000

--Jon Bashor

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REACHING OUT TO THE COMMUNITY

Graduate Students Invited to Speak and Lead Tours

The Community Relations Office invites graduate students at Berkeley Lab to participate in the Lab's growing tour program, thereby gaining speaking and community outreach experience. Speakers and tour leaders communicate with mostly non-scientific audiences about scientific research being conducted at Berkeley Lab. The Community Relations Office will provide the necessary training.

More than 300 people toured the Lab during the month of May, including Bay Area visitors, community groups and science students. The Lab anticipates that the number of tour requests will grow during the summer months.

Berkeley Lab offers two-hour public tours on Fridays (usually the second and fourth Friday of the month). Student classes are encouraged to visit on Mondays.

For more information about the program, contact Terry Powell by phone or e-mail at X4387 or [email protected].

Photo: Badge

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Lab Visitor Badges

Visitors participating in tours of Berkeley Lab will now be easily recognizable by their distinctive, colorful new lapel buttons designed by PID's Niza Hanany.

Employees are encouraged to assist visitors unfamiliar with the Lab.

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Gene Therapy Giants and Journalists Converge on the Hill for Conference

By David Gilbert

While pharmaceutical companies sift through vast libraries of chemical compounds to come up with the magic bullets that may one day help subdue diseases, biotechnology companies pursue alternative strategies known collectively as gene therapy. Gene therapy attacks diseases by replacing defective or missing genes--long strands of DNA which code for production of a particular protein--with normal copies of the genes to restore normal cell function.

As gene therapy has moved from laboratory into clinical trials, the technology has been refined to the basic areas of gene identification, gene expression and gene delivery. With volumes of DNA sequence information being revealed through the Human Genome Project--in which Berkeley Lab plays a major role--new genes are identified on a daily basis, providing more fuel for the promise of gene therapy. Challenges remain in the areas of developing appropriate vehicles for the expression and delivery of these genes into patients.

The state of this technology and its prospects for the future was the subject of a conference hosted by Berkeley Lab on May 13.

One of Life Sciences Division's largest industrial partners, Gencell--the gene therapy subsidiary of pharmaceutical giant Rhône-Poulenc Rorer (RPR)--gathered more than 30 international business journalists on the Hill--from Le Monde to The Times of London--to hear the gene therapy gospel from biotech industry experts.

The event was kicked off by the self-professed "biogoddess" Cynthia Robbins-Roth. Founder of BioVenture Publishing Inc. and BioVenture Consultants, Robbins-Roth has been a biotech industry mainstay since 1981. The tall order of the day for her was to explain to business reporters the basics of biology, from DNA to gene therapy, all in an hour and with simultaneous translation into French.

Constance McKee, president of Xavos Corporation, a start-up company developing drug delivery technology for improved treatment of viral diseases and conditions which affect the peripheral nervous system, outlined the industry players and later commented on the significance of gene therapy.

"It is not just the technologies in gene therapy that are causing a revolution," she said. "Gene therapy will affect the entire chain of events in the health care delivery system as we know it. One of the key challenges to the industry will be to bring gene therapy technologies into conformity with the current health care delivery system: training doctors and nurses in medical and nursing schools, doctors offices, specialized treatment centers, and hospitals, to administer new therapies."

Over lunch, Elizabeth Silverman, a senior research analyst focusing on genomics and new technologies related to drug discovery, provided a prospectus on the latest market developments.

Berkeley Lab's own Eddy Rubin, head of the Life Sciences Division's Department of Genome Sciences, provided the view from the interface of academia and industry. Rubin described his lab's studies entailing the use of genetically engineered mice to decipher and add biological value to the data flowing from DOE's human genome sequencing program.

Linkages, both with academic institutions and start-up companies, are critical to the rapid delivery of gene therapies to the market, said RPR Senior Vice President of Research Thierry Soursac. In 1994 Rhône-Poulenc Rorer launched RPR Gencell as an integrated division dedicated to the discovery, development, production and marketing of gene therapy products. David Nance, president & CEO of Texas-based Introgen Therapeutics, Inc., a leader in the field of anti-cancer gene therapy products, echoed the importance of establishing linkages from the perspective of an entrepreneur. Through its own discovery and partnerships with various biotechnology companies and research institutes worldwide, including Berkeley Lab, Gencell has sought to accelerate the development of novel gene-based therapies in the areas of oncology, cardiovascular diseases and disorders of the central nervous system.

Soursac said that Gencell's long-term investment in the future of gene therapy is paying off in the near term, with two projects currently in clinical trials and five in preclinical, three of which are expected to enter the clinical phase by 1999.

The industry executives as well as the journalists concluded their day at the Lab with tours of the user facilities, including NERSC and the ALS.

Photo: Industry leader Cynthia Robbins-Roth gave an overview of genetics and gene therapy during a recent conference held at Berkeley Lab. (XBD9805-01378.tif)

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Berkeley Lab Hosts High Energy Physics Advisory Panel

By Lynn Yarris

Members of the High Energy Physics Advisory Panel (HEPAP) meeting at Berkeley Lab on May 14-15 were treated to a walking tour of the Microsys-tems Laboratory (MSL), where radiation detectors for high-energy physics are fabricated on silicon wafers, and a virtual tour of BaBar, the B-meson detector for the PEP-II collider being built at the Stanford Linear Accelerator Center. They were also presented with up-to-the-minute status reports on major high energy physics projects and received a response from the university representative to the HEPAP subpanel report on "Planning for the Future of U.S. High Energy Physics."

The two-day meeting, chaired by Michael Witherell of UC Santa Barbara, devoted a substantial portion of time to presentations on high-energy physics programs at Berkeley Lab.

That Berkeley Lab's high energy physics program has remained so robust despite the fact that big machines are no longer built and operated here seemed to impress the HEPAP members. Peter Rosen, associate director for High Energy and Nuclear Physics in DOE's Office of Energy Research, called the Lab a model for facilities in the future when the big machines of high energy physics may no longer be built anywhere in the United States. He also praised the Lab for its ability to "couple" physics and engineering capabilities.

Said Witherell, "The high energy physics program at Berkeley Lab plays a unique role in many of the experiments that are central to our field."

Deputy Lab director Pier Oddone welcomed the HEPAP members to the Lab, and Physics Division director James Siegrist gave them an overview of the Lab's high-energy physics program. The tour of the MSL was led by Helmuth Spieler, and the virtual tour of BaBar was conducted by Natalie Roe. Other Berkeley Lab presenters included Kevin Einsweiler, Bill Turner, Stu Loken, John Corlett, Saul Perlmutter, Jim Leighton, and Michael Barnett.

HEPAP members also received reports on Berkeley Lab contributions to the Large Hadron Collider (LHC) at CERN; the proposed Next Linear Collider to be built at SLAC and the Muon Collider to be built at Fermilab; the computational support available through NERSC and ESNet; the supercomputing and high-speed networking systems based here; particle astrophysics, including the supernova search; and QuarkNet, an educational outreach proposal that would involve U.S. high school students in the LHC turn-on and Tevatron Run 2 events.

HEPAP members were told that all of the key personnel in the U.S. LHC project, with the exception of the program manager, have been assigned. For ATLAS, the general purpose proton-proton detector at the LHC, the project management plan has been approved, Brookhaven's host laboratory role is in place and a status review has been scheduled for early September. A status review of the accelerator portion of the U.S. LHC project has been scheduled for October now that Fermilab's lead laboratory oversight role is in place.

The university response to the HEPAP subpanel report, which was chaired by Fred Gilman of Carnegie Mellon University, was generally favorable, praising the report for recognizing that university budgets for high energy physics research decreased during a period when DOE budgets for those programs increased. The report, given by Eugene Beier of the University of Pennsylvania, found DOE's response to the Gilman subpanel "encouraging" but described the response from the National Science Foundation as "less encouraging."

Photo: Michael Witherell of UC Santa Barbara, shown here calling for order, chaired a two-day meeting of the High Energy Physics Advisory Panel held at Berkeley Lab earlier this month. (XBD9805-01416.tif) Photo by Don Fike

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Bulletin Board

===================

Workshops on Retirement Savings & Investment

The Benefits Office is organizing three educational retirement workshops on the topics of "Making the Most of Your Workplace Savings Plan" (June 5), Investment Basics (June 11), and "Are you Ready to Retire" (June 12).

The informal, interactive workshops will be held at noon in the Bldg. 50 auditorium and will be led by a representative from Fidelity Investments.

===================

New Courier Service

The Facilities Department is providing the Lab with a new, rush courier service with pick up and delivery both on- and off-site. Transportation can deliver up to 2,000 pounds anywhere in the Bay Area or in central or northern California. There is no minimum weight requirement.

For on-site door-to-door service, materials will be delivered within one hour. For off-site service, a driver is available during normal business hours for same-day pick up and delivery, with rush service depending on destination. Off hour pick-ups and deliveries are referred to IDS Courier Service (548-3263).

To request a pick up, call Peggy Patterson at X5404.

===================

Guaranteed Ride Home Program

Alameda County's "Guaranteed Ride Home Program" helps employees facing specific difficulties--such as family illness, unscheduled overtime, or ridesharing breakdowns--to get safely back home as long as they walked, biked, carpooled or took public transportation on the day the ride home is to be used.

To be eligible for Guaranteed Ride Home, you must be a permanent full- or part-time employee, live within 100 miles of Berkeley Lab, and pre-register with the program. To learn more about the program or to register, call Marilynn at X8605.

===================

Pick Up Your A's Tickets Next Week

If you ordered tickets for the June 6 Oakland A's game you can pick them up in the foyer of the cafeteria the week of June 1 through June 5 from noon to 1 p.m. For further information call Jacqueline Noble at X4762.

===================

DC Expo on Renewable Energy

Photo: Moira Howard-Jeweler of Berkeley Lab's Washington DC office discusses energy-efficient technologies with a visitor at the recent Expo sponsored by the House Renewable Energy Caucus and held on May 21 on Capitol Hill. The Lab's exhibit, submitted by the Environmental Energy Technologies Division, featured live demonstrations of UV Waterworks, "cool" (high-albedo) roofing material, and energy-efficient compact fluorescent lamps. Officials included at least two dozen members of Congress, Department of Energy Secretary Federico Peña, Assistant Secretary Dan Reicher, Undersecretary Ernest Moniz, and Martha Krebs, director of the Office of Energy Research. The attendance was estimated at 2,800 -- about double that of last year's event. (doe pix)

===================

Library Training Sessions

Next month Berkeley Lab's Library is offering a series of short (20 to 30 minute) small-group training sessions on the following topics:

*UnCover is an online article delivery service, a table of contents database, and a keyword index to nearly 17,000 periodicals. Users can order documents from the desktop and have them delivered by fax.

For more information or to reserve space, contact Jhane Beck at X4622.

===================

Application Deadline for CalPERS Long-Term Care Program

The application period for the CalPERS Long-Term Care Program, which offers long-term care benefits to all California public employees, teachers, retirees, and their eligible family members, ends June 30. With more than one hundred thousand members, the program is one of the largest of its kind in the nation.

Long-term personal care is not covered by health insurance, Medicare or Medigap and is extremely expensive. Statistics indicate that six out of every 10 people over age 65 will require some type of long-term care, and this is where CalPERS can make a big difference.

To receive an enrollment kit, call (800) 266-1050 or visit the website at http://www.calpers.ca.gov/ltc.

===================

Energy Technologies Teleconference

On Tuesday, June 2, Berkeley Lab will host a live satellite transmission of a national interactive teleconference on "Energy Technology Solutions for the 90's and Beyond," organized by the U.S. Department of Energy's Office of Fede-ral Energy Management. The event will be held from 11 a.m. to 12:30 p.m. and will be broadcast in the Bldg. 50 auditorium. Issues will include the use of energy efficient technologies, photovoltaics, solar hot water, energy effective lighting, and lighting control systems. Open discussion will follow.

To reserve your space, call JoAnne Lambert at X5297.

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Non-Academic Job Search Workshops

The LBNL-Postdoctoral Society presents the fourth in a series of effective communication and career workshops, to be held on four consecutive Mondays in June from 4 to 7:30 p.m in 10 Evans Hall on the UC Berkeley campus. The workshops are open to all Lab personnel. The preliminary programs for the four sessions are:

Snacks and refreshments will be served at each session.

===================

Weight Watchers Open Meeting

An informational lunch-time meeting previewing the new Weight Watchers weight loss plan to be offered at Berkeley Lab will be held on Tuesday, June 2, at noon in Bldg. 26. The new series starts on June 9, with sessions every Tuesday. The promotional price for the summer series is $8.95 per week. For more information contact Health Services at X6266.

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Be Part of Currents!

Do you have an interesting story or anecdote to tell?

Did you or one of your colleagues accomplish something that you think others would like to hear about?

Are you working on some interesting research?

Do you have a picture you would like published in Currents?

If so, please send your suggestions to msfriedlander@ lbl.gov. We cannot publish every item submitted, but we will consider all your suggestions.

MAY 29--JUNE 12, 1998

General Interest

29 Friday

State of the Lab Address
Noon, Bldg. 50 auditorium Video link in Bldg. 66 auditorium

2 Tuesday

Teleconference on Energy Technologies
Live broadcast, noon, Bldg 50 auditorium

Weight Watchers Informational Meeting
Noon, Bldg. 26

4 Thursday

Non-Academic Job Search
LBNL Postdoctoral Society workshop 4-7:30 p.m., 10 Evans Hall, UCB

5 Friday

Retirement Savings Workshop
"Making the Most of Your Workplace Savings Plan" Noon, Bldg. 50 auditorium

9 Tuesday

Weight Watchers
New series starts, noon, Bldg. 26-109

10 Wednesday

Music Club
General meeting, noon, lower cafeteria

11 Thursday

Shoemobile
7:30 a.m.- 4:30 p.m., cafeteria parking lot

Retirement Investment Workshop
"Investment Basics" Noon, Bldg. 50 auditorium

African American Employees Association
General meeting, noon, Bldg. 90-1099

Non-Academic Job Search
LBNL Postdoctoral Society workshop 4-7:30 p.m., 10 Evans Hall, UCB

12 Friday

Retirement Savings and Investment Workshop
"Are You Ready to Retire?" Noon, Bldg. 50 auditorium

===================

Seminars & Lectures

JUNE 2, Tuesday

NERSC Lectures
"The Future of Computing: A High Energy/Nuclear Physics Viewpoint" will be presented by Richard Mount, director of Computing Services at the Stanford Linear Accelerator Center. (Rescheduled from an earlier date.)
2 p.m., Bldg. 50 auditorium

"An Overview of High Energy Nuclear Physics Support Group" will be presented by Craig Tull of NERSC.
3:30 p.m., Bldg 50 auditorium

Life Sciences Division
"Approaches to Prostate and Bladder Cancer: Nuclear Matrix and Vitamin D" will be presented by Robert Getzenberg of the Cancer Institute, University of Pittsburgh.
4 p.m., Bldg. 66 auditorium. Refreshments will be served.

JUNE 3, Wednesday

Life Sciences Division
"Gerontogenes in the Nematode: Relevance to Mammalian Aging" will be presented by Thomas E. Johnson of the University of Colorado at Boulder.
4 p.m., Bldg. 66 auditorium Refreshments will be served.

JUNE 10, Wednesday

Nuclear Science Division Colloquium
"Chaos and Non-linear Dynamics" will be presented by Wolfgang Bauer of MSU.
11 a.m., Bldg. 50 auditorium

NCEM Symposium
Electron Microscopy in Science & Technology
Thursday, June 25

The National Center for Electron Microscopy at Berkeley Lab is organizing a symposium featuring a series of talks on recent forefront applications of electron optical characterization to problems in fundamental and applied science. The event will be held on June 25 from 1 to 5 p.m. in the Bldg. 66 auditorium. An open house at NCEM (Bldg. 72) will follow the symposium. Participants will tour the facility and view demonstrations of new instruments.

Items for the calendars may be sent via e-mail to currents_calendar@ lbl.gov, faxed to X6641 or mailed to Bldg. 65B. The deadline for the June 12 issue is 5 p.m. Monday, June 8.

===================

Golf Club Results

The May 23 tournament was held at Oakmont Country Club in Santa Rosa. The next event is scheduled for June 6 at Rancho Solano. Members and guests are welcome. For more information contact Denny Parra at 486-4598.

Point leaders

16 points: Ron Gervasoni, Denny Parra, Ralph Sallee

14 points: Gary Palmer

12 points: Mark Campagna

11 points: Eric Van Nieuwburg, John Bowers

10 points: Ken Rivera

===================

Flea Market

Autos/Supplies

`79 BEETLE Convertible, new top, CD, good cond, $4200/b.o., Stu, 525-2367 (evenings)

`82 SEARAY, 22.5 ft, 260 Merc outdrive, sleeps 4, head, galley, 310 hrs, delta canvas, vhf, depth sounder, trim tabs, very good cond, incl Trailrite tandem axle trailer, $9500/b.o. Bob, 376-2211

`84 TOYOTA Tercel, 120K mi, am/fm/tape, excellent condition, very reliable, all records, $1100, avail 6/28, Diana, 526-2741

`86 NISSAN 4x4, extra cab w/ camper shell, over $5K in accessories w/ all receipts, very nice cond, $5800, Linda, 464-0690

`87 TOYOTA 4 Runner SR5, 107K mi, one owner, p/s, p/b, a/c, 5 spd m/t, 2.4L I4, auto hubs, alloy wheels, silver/black exterior, gray cloth interior, tube bumpers, 2" receiver hitch, electric rear window, deluxe am/fm/cassette, $8000, Alan, 758-7104 (evenings)

`90 TOYOTA Camry, dk gray, good cond, 91K mi, a/c, new tires, $5500/b.o., Leslie, X4007, 522-4213

`91 CAPRICE, burgundy, immaculate interior, loaded, good body, $4280, Helen, X5746, 522-4164

`92 FORD Tempo GL, first V6 series, lic. tag Oct 98, 4 dr, 3.0 liter, 45K mi, orig owner, serviced quarterly, mocha w/ lt. taupe interior, equipped w/ a/t, a/c, pwr/s, pwr windows & locks, new front brakes, rear window defogger, electric trunk release, tilt wheel, cruise control, stereo am/fm/cassette, $5,500, Virginia, X4383

`93 SUNFISH Sailboat w/ trailer, some accessories, exc cond, white & aqua, has never sailed in saltwater, $1800/b.o., John, 531-1739 (evenings)

`94 FORD Mustang, silver, 3.8L, air, cd, a/b, fully loaded, 53K mi, warranty, $12,000/b.o, Lisa, X5314, (925) 906-9786

TRAVEL Trailer, 13 ft, `70's Cardinal, good gas stove & refrigerator, queen-sized bed/dinette, + fold-down bunk, separate enclosed toilet, $1000, Phila, 848-9156

TRAILER, w/lights for hauling, 2 wheel, 4X6, Helen, X5746, 522-4164

Housing

ALBANY, 2 bdrm, 2 bth, bay view spacious condo, avail 7/15, incl gym use, pool, tennis courts & other facilities, bldg complex has security & one garage space, $1150/mo, MS, (925) 631-0510

ALBANY, house, 2 bdrm, unfurn, 1 bth, hardwood floors, frplc, sunny deck, yard w/tree, lg useable basement, garage w/auto-door, wash/dry, 1/2 blk to Solano Ave, close to elementary school, avail 8/1, cats negotiable, year lease, $1850/mo, Tom, X5704

BERKELEY HILLS, studio apt, edge of Tilden Park, views, decks, parking, semi-furn, w-w carpet, modern kitchen, dishwasher, lg bthrm, very quiet neighborhood, private entrance, storage, alarm, nr #65 & #67 bus line, no smokers, no pets, one person only, electricity & other util incl, avail 7/1, $750/mo, Evan, X6784, 525-7655

EL CERRITO, 3 bdrm, 2 bth house w/ yard, fully furn, hot tub, residential neighborhood, 20 min by car to LBNL, avail July-Sept., $1250/mo incl util, no smokers, Art, 237-4654

NORTH BERKELEY, 1 bdrm and studio, completely furn, short term, 4 blks from LBNL shuttle, non smokers, pets accepted, avail 6/20, Viki, 549-1876

Miscellaneous

BED, platform for dbl bed, real wood, very study, $30, Jon, X5849 or 527-0285

DINING ROOM TABLE w/ two leaves, $40; 50W speakers, $25 pair; woman's medium wetsuit, $30; Sony CD boombox, $25; Nikon underwater camera, $40; misc cheap windsurfing equipment, Erik, X6435, 848-4675

FUTON & FRAME, $30; desk, $35; bookcase, $7; dresser, $25; AT&T cordless phone, $25, Michelle, 849-9572

GARDEN CHIPPER/SHREDDER for mulching garden cuttings, Sears, 8 h.p. Tecumseh engine, good cond, $500/b.o. Charlie, X4658, (925) 283-6111

GOLF CLUBS & BAG, 2-sw graphite s-shaft, good cond, bag has stand, also 1, 3&5 wood, $400/b.o., Ron, X5029

KIMBALL "Syntheswinger" organ, mint cond, 3-3 cushion sofas: taupe w/ 2 recliners built-in, 7' bottle green, carmel naughahyde; king bed, 2 single beds; 2 gold upholstered recliners; 2 24" girls bikes; 6' coffee table w/ lower shelf; regulation pool table (1" slate); 2 dbl chests of drawers w/ mirrors, Helen, X5746, 522-4164

MACINTOSH CENTRIS 610, 20 Mb RAM, 1 Gb hard disk, ext. CD-ROM, ext. ZIP drive, 28K Sportster fax modem w/ voice mail, 14" color monitor, mouse, keyboard, software, $600, Andre, X6745

MACINTOSH QUADRA 700 w/ 240 mb, hd, 20 mb hd, Apple enhanced keyboard, apply mouse and a Sony 15" Multiscan, 100 sf, $500, Leon, X4767

MIRROR W/ MEDICINE CABINET, electronic typewriter (needs some repair), steel wine rack, beige sofa, mattress pad, Susan, X7366

MOVING SALE, sofabed; queen size mattress w/ frame; upright vacuum cleaner, small desk, Macintosh Performa 6100 CD, Esteban, X6893, 547-5278

SOFA, $35; Area Rug, $8; AT&T 2-line remote answer system, $10; pair of Pioneer car speakers, $30; GE Rangetop Microwave, $200, Yunian or Ching, 841-2140

SOFA & LOVESEAT, classic carved oak frame, quality upholstery, very comfortable, very good cond, $1000/pr or $650/sofa and $450/loveseat; coffee table, carved oak, $200 alone or $150 w/ sofa; TV & VCR, brass handles, beveled glass dbl doors, exc cond, $1750; photos, Susan, 548-9315

STOVE, Classic `50's O'Keefe & Merritt, 35" chrome top, stainless steel griddle; $650; Magic Chef stove, electronic ignition, $125, Viki, 549-1876 (evenings)

TREADMILL, Vitamaster 550, 1.5 to 4.0 mph, $120, Jacki, X4762

YAKIMA rack equip, pair of 48" bars, $20; Q Stretch kit, $60; Q11 clips, 2 pr, $20, Chris, 528-9809

Wanted

APT, 1 bdrm w/ balc or sm terrace for visiting scientist from Germany, non smoker, 7/1 for at least 1 yr, Berkeley area, Klaus, X2232, 559-1031

BICYCLE, woman's w/ foot brake, Ruth, 526-2007

BUNK BEDS, ok if needs refinishing, cheap or free, Shirley or Don, 527-0697

CANNONDALE mtn bike, red alum frame, 21" downhill type, rack, rear mirror, 18 spd, Suntour xc components, $275, Erhard, X4739, 549-1772

CANNONDALE bike rack, fits in bed of small pickup (Ford Ranger, etc), holds two bikes w/ quick disconnect front tire, has brackets to hold the disconnected front tires also, $50; full sized futon w/ futon bed frame & two mattresses, $100, Robert, 495-2278

HOUSING for visiting scientist & family from France, 3 bdrm house in El Cerrito, Albany or Kensington for 2 yrs, from 7/98, family already in Bay Area, Thiebaut, X7030, 233-4042

HOUSING for visiting scientist, wife & 14 yr old, furn, 2-3 bdrm apt/house, Aug. `98-99, dates flexible, e-mail: radmilovic@ elab.tmf.bg.ac.yu, or Jane, X6036

HOUSING for visiting scientist & family (one child), seeking 1+ or 2 bdrm apt/house for 1-2 yrs in Berkeley, Albany, Oakland or El Cerrito, Erol, 495-2901

SOCCER PLAYERS, for LBNL Soccer Club, to play in a semi-competitive corporate league this summer, June-Aug., games mostly on Sundays am or early pm, one practice during the week, must make commitment to play in at least 70% of games, goalies welcome, Peter, X4157, 525-3290

Vacation

TAHOE KEYS at South Lake Tahoe, 3 bdrm, 2.5 bth, on the water fenced yard, quiet area, close to many attractions, great views of water & mtns, $150/night, 2 night min, Bob, 376-2211

TAHOE vacation house, 3 queens, 4 twins, (also sofabeds) spacious, pool table, w/d, dw, micro, VCR, catv, quiet area, $175/night, $1050/week, Neela, X7423

Free

NETHERLAND DWARF RABBITS, two small males, w/ cages, you must haul, Robert, 495-2278

THREE BLACK KITTENS, rescued from life on the street, very cute, 2 long haired, one short haired, probably 6-8 weeks old, cat is box trained, very playful, Robin, X4141

FLEA MARKET items may be e-mailed to fleamarket@ lbl.gov, faxed to X6641, or mailed to Bldg. 65B. The deadline for the June 12 issue is Friday, June 5.

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CAFETERIA MENU

===================

Flea Market ad policy

Due to the large volume of ads received each week, ads are accepted only from LBNL employees, retirees, and on-site DOE personnel. No other ads will be accepted. We encourage past contributors to the Flea Market to use other local services, such as LBNL's online housing listing (call X6198 for information), and the UC Housing Office.

Please note also: