Contents of this Issue:
1. Science Highlight —
Anthrax Toxin - Working Towards an Antidote
(contact: Thiang Yian Wong,
tywong@burnham.org)
Anthrax makes a deadly cocktail of three toxin proteins that flood the bloodstream, leading to rapid death if the infection is not diagnosed and treated in its early stages. Even antibiotic treatments can fail when the Anthrax bacterium, Bacillus anthracis, has already produced lethal levels of toxins. The poisonous protein called Lethal Factor (LF) rapidly blocks signals to recruit immune cells to fight the infection. Another enzyme Edema Factor (EF) causes the release of fluid into the lungs and is deadly on its own. Protective Antigen (PA) facilitates the entry of these toxin proteins across the cell membrane, and into target cells, through its complex pore-forming channel.
LF is the greatest source of damage in highly fatal cases of inhalation anthrax. An anti-toxin that stops LF would be a vital addition to combined therapy with existing treatments (antibiotics, anti-PA antibodies, critical care). Scientists from The Burnham Institute in La Jolla, California, together with colleagues at the Harvard Medical School and the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) have taken a big step forward in developing a drug to inhibit the LF toxin. The group screened small molecules from the National Cancer Institute Diversity Set to identify chemical compounds that can block LF. They made crystals of LF bound to these candidate inhibitors and used the SSRL facility to analyze the interactions of these compounds with LF. The research concluded that the most effective inhibitors targeted the active center via hydrophobic interactions and also deprived LF of zinc. The scientists are now working on chemically generating even better inhibitors.
For more information on this work see:
http://www-ssrl.slac.stanford.edu/research/highlights_archive/anthrax2.html
or
http://www-ssrl.slac.stanford.edu/research/highlights_archive/anthrax2.pdf
2. Linac Coherent Light Source Project Update
(contacts: John Galayda,
galayda@slac.stanford.edu)
The Linac Coherent Light Source Project will shift into high gear with FY2005 funding. The President's Budget provides $4M R&D, $20M for engineering design, and $30M to build the following:
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The LCLS Scientific Advisory Committee will meet in early July to review the first group of proposals for experiment stations, scientific experiments and specialized instrumentation matched to the extraordinary capabilities of the Facility. Over 250 scientists from around the world associated with 29 letters of intent have notified SSRL of their interest in the LCLS program. With the guidance of the SAC, a set of teams focused on designing and building the first phase of LCLS experiments will be formed and plans made to take the next steps to be ready for first LCLS x-ray laser beams in 2008.
3. Progress Made During SPPS Spring Run
(contacts: Jerry Hastings,
jbh@slac.stanford.edu; John Arthur, jarthur@slac.stanford.edu)
The SPPS has just finished the spring 2004 running period with significant progress on both electron beam-photon beam timing and studies of non-thermal melting. A critical issue for next generation linear accelerator based light sources (both spontaneous like SPPS and amplified like LCLS) is the relative timing between a pump (typically a conventional ultra-fast laser) and the x-ray beam that probes the sample at a delayed time. Unlike "conventional" pump-probe studies where both the pump and probe are derived from the same laser, thereby ensuring timing fidelity, these new sources will often need to determine the time delay on a pulse-by-pulse basis. During our recent running period we correlated the signal from our electro-optic electron beam diagnostics with the ultra-fast decay of x-ray intensity from a laser-pumped non-thermal melting experiment. The relative jitter between these two was 30 femto-seconds rms.
The non-thermal melting experiment broke new ground as well. In all previous studies, only the lowest-order Bragg peak (111) from the diamond cubic (Si and Ge) and zinc blende (InSb and GaAs) crystals was measured in a number of very beautiful experiments as a function of time, laser fluence, and penetration depth. The single pulse studies at SPPS have been extended to the next lowest order Bragg peak, the InSb (220), and its evolution with time and laser fluence was studied in detail. With this new experiment, still being analyzed, we are gaining insight into the atomic motions that coincide with the decay of the Bragg scattered intensity on a few-hundred femto-second time scale, a time frame significantly faster than achieved in earlier studies with storage ring based synchrotron sources.
The next running period for SPPS in winter 2004 will focus on establishing the routine use of the electro-optic timing to permit ultra-fast diffraction studies that cannot be accomplished in a 'single pulse'.
4. William E. Spicer, 1929 - 2004,
Cofounder of SSRL and Pioneer in Photoemission Spectroscopy
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5. Welcoming Visitors to SSRL
(contact: Keith Hodgson,
hodgson)
SSRL hosted a number of visitors in June starting with Lord Sainsbury, the U.K. Under Secretary for Science and Innovation, on Tuesday, June 8. Ari Patrinos, Director of the DOE Office of Biological and Environmental Research was also here on June 8. Dr. Patrinos visited SSRL and Bio-X (on campus). Senator Ted Stevens, Chairman of the U.S. Senate Appropriations Committee and Sean O'Keefe, Head of NASA, visited SSRL on Saturday, June 12. A group of Australians including Rod Hill, Ian Madsen, Mike Lawrence and Chris Langslow from the Commonwealth Scientific and Industrial Research Organization (CSIRO), a Foundation Partner in the Australian Synchrotron, visited on June 21, as did South Africans Charles Mills of the Department of Trade and Industry and Pontsho Maruping of the Department of Science and Technology. Discussion of SSRL's scientific program and a tour of the experimental floor were on the agenda for all of these visits.
6. User Operations
(contact: Cathy Knotts,
knotts@slac.stanford.edu)
The delivery rate for beam to users so far this experimental run is 96.5%. A problem occurred last week when the pulse forming network (PFN) in the booster failed the afternoon of Sunday, June 20. This equipment failure made it impossible to inject beam into SPEAR until the problem was resolved the evening of June 22. Although the beam decayed during the period the booster was down, users were still able to collect very useful data. Once the repairs were made to the PFN, the schedule of 3 fills per day was resumed. Further progress was made on the beam line front when BLs 1-4 and 1-5 were opened on Friday, June 25. Commissioning of these lines is currently underway. Also, on June 25, first light was put through the entrance slit of the new BL5-1/5-2 SGM. This is the first step in bringing this new high-performance soft x-ray instrument on line. In the coming weeks beam will be brought through the monochromator for characterization and then the refocusing optics for two end stations, 5-1 and 5-2, will be installed. Progress was also made toward higher current running of SPEAR3 during the most recent accelerator period, during which time beam currents of up to 175 mA were stored and their properties studied (with beam lines closed at this point).
7. Emittance Measurement in SPEAR3
(contacts: Jeff Corbett,
corbett@slac.stanford.edu; Teresa Troxel, troxel@slac.stanford.edu)
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| Pinhole image of SPEAR 3 electron beam |
8. Upcoming Events at SSRL and Elsewhere
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Beam Time Requests for the first scheduling period of SSRL's FY2005 experimental run which begins Monday, October 18, are due Friday, August 13, 2004. Spokespersons with active X-ray/VUV proposals will be sent request information in the regular mail and crystallography spokespersons will be invited to apply for beam time via an email communication that will be sent out a few weeks prior to the deadline.
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SSRL Headlines is published electronically monthly to inform SSRL users, sponsors and other interested people about happenings at SSRL. SSRL is a national synchrotron user facility operated by Stanford University for the U.S. Department of Energy Office of Basic Energy Sciences. Additional support for the structural biology program is provided by the DOE Office of Biological and Environmental Research, the NIH National Center for Research Resources and the NIH Institute for General Medical Sciences. Additional information about SSRL and its operation and schedules is available from the SSRL WWW site.
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