Crystal structure of the catalytic fragment of murine poly(ADP-ribose) polymerase-2.

Poly(ADP-ribose) polymerase-1 (PARP-1) has become an important pharmacological target in the treatment of cancer due to its cellular role as a 'DNA-strand break sensor', which leads in part to resistance to some existing chemo- and radiological treatments. Inhibitors have now been developed which prevent PARP-1 from synthesizing poly(ADP-ribose) in response to DNA-breaks and potentiate the cytotoxicity of DNA damaging agents. However, with the recent discoveries of PARP-2, which has a similar DNA-damage dependent catalytic activity, and additional members containing the 'PARP catalytic' signature, the isoform selectivity and resultant pharmacological effects of existing inhibitors are brought into question. We present here the crystal structure of the catalytic fragment of murine PARP-2, at 2.8 A resolution, and compare this to the catalytic fragment of PARP-1, with an emphasis on providing a possible framework for rational drug design in order to develop future isoform-specific inhibitors

Acoustic Identification of Liquefaction Potential

The interparticle arrangement, or fabric, of sands is a key determinant of sample rigidity. This rigidity, in large part, determines the velocity and attenuation of acoustic transmissions in a test specimen, as well as its resistance to liquefaction. Utilizing high frequency small-amplitude compressional wave transmissions, different fabric arrangements of standard triaxial samples of the same sand have been reliably identified from their acoustic response. Both the compressional wave velocity and attenuation were used to determine the acoustic signature of a sample. Cyclic triaxial testing of the same laboratory-prepared samples revealed that there is direct relationship between the acoustic response of a sample prepared by a particular method and its resistance to liquefaction. The effect of stress history, induced by pre-shaking, on the resistance to liquefaction of a test sample was also detected by changes in the acoustic signature

The structure of cool accretion disc in semidetached binaries

We present the results of qualitative consideration of possible changes occurring during the transition from the hot accretion disc to the cool one. We argue the possible existence of one more type of spiral density waves in the inner part of the disc where gasdynamical perturbations are negligible. The mechanism of formation of such a wave as well as its parameters are considered. We also present the results of 3D gasdynamical simulation of cool accretion discs. These results confirm the hypothesis of possible formation of the spiral wave of a new, "precessional" type in the inner regions of the disc. Possible observational manifestations of this wave are discussed.Comment: LaTeX, 16 pages, 8 figures, to be published in Astron. Z

The impact of viscosity on the morphology of gaseous flows in semidetached binary systems

Results of 3D gas dynamical simulation of mass transfer in binaries are presented for systems with various values of viscosity. Analysis of obtained solutions shows that in the systems with low value of viscosity the flow structure is qualitatively similar to one for systems with high viscosity. Presented calculations confirm that there is no shock interaction between the stream from L1 and the forming accretion disk (`hot spot') at any value of viscosity.Comment: LaTeX, 18 pages, 15 eps-figures, Astron. Reports, in pres

Reye Syndrome Associated with Vaccination with Live Virus Vaccines

To determine whether vaccination with live virus vaccines may be etiologi cally related to Reye syndrome, we examined 404 cases reported to the Center for Disease Control. Fifteen of 269 children with Reye syndrome had been inoculated with live virus vaccines within 30 days before onset of illness. Although this temporal relationship may have occurred by chance, seasonal distribution and clustering of incubation periods suggests that live virus vaccines may occasionally serve as cofactors in the etiology of Reye syndrome through undefined mechanisms.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66647/2/10.1177_000992287901800105.pd

Radiation Testing of Electronics for the CMS Endcap Muon System

The electronics used in the data readout and triggering system for the Compact Muon Solenoid (CMS) experiment at the Large Hadron Collider (LHC) particle accelerator at CERN are exposed to high radiation levels. This radiation can cause permanent damage to the electronic circuitry, as well as temporary effects such as data corruption induced by Single Event Upsets. Once the High Luminosity LHC (HL-LHC) accelerator upgrades are completed it will have five times higher instantaneous luminosity than LHC, allowing for detection of rare physics processes, new particles and interactions. Tests have been performed to determine the effects of radiation on the electronic components to be used for the Endcap Muon electronics project currently being designed for installation in the CMS experiment in 2013. During these tests the digital components on the test boards were operating with active data readout while being irradiated with 55 MeV protons. In reactor tests, components were exposed to 30 years equivalent levels of neutron radiation expected at the HL-LHC. The highest total ionizing dose (TID) for the muon system is expected at the inner-most portion of the CMS detector, with 8900 rad over ten years. Our results show that Commercial Off-The-Shelf (COTS) components selected for the new electronics will operate reliably in the CMS radiation environment

Absence of Insect Juvenile Hormones in the American Dog Tick, Dermacentor veriabilis (Say) (Acari: Ixodidae), and in Ornithodoros parkeri Cooley (Acari: Argasidae)

Synganglia, salivary gland, midgut, ovary, fat body and muscle alone and in combination from the ixodid tick, Dermacentor variabilis (Say), or the argasid tick, Ornithodoros parkeri Cooley, were incubated in vitro in separate experiments with L-[methyl-3H]methionine and farnesoic acid or with [1-14C]acetate. Life stages examined in D. variabilis were 3 and 72 h old (after ecdysis) unfed nymphs, partially fed nymphs (18 and 72 h after attachment to the host), fully engorged nymphs (2 d after detachment from host), 3 and 72 h old (after eclosion) unfed females, partially fed unmated females (12–168 h after attachment to host) and mated replete females (2 d after detachment from the host). Those from O. parkeri were third and fourth stadium nymphs and female O. parkeri, 1–2 d after detachment. Corpora allata from Diploptera punctata, Periplaneta americana and Gromphadorina portentosa were used as positive controls in these experiments. No farnesol, methyl farnesoate, JH I, JH II, JH III, or JHIII bisepoxide was detected by radio HPLC from any tick analysis while JH III, methyl farnesoate, and farnesol were detected in the positive controls. To examine further for the presence of a tick, insect-juvenilizing agent, Galleria pupal–cuticle bioassays were conducted on lipid extracts from 10 and 15 d old eggs, unfed larvae (1–5 d after ecdysis), unfed nymphs (1–7 d after ecdysis), and partially fed, unmated female adults (completed slow feeding phase) of D. variabilis. Whole body extracts of fourth stadium D. punctata and JH III standard were used as positive controls. No juvenilizing activity in any of the tick extracts could be detected. Electron impact, gas chromatography–mass spectrometry of hemolymph extracts from fed, virgin (forcibly detached 7 d after attachment) and mated, replete (allowed to drop naturally) D. variabilis and fully engorged (1–2 d after detachment) O. parkeri females also failed to identify the common insect juvenile hormones. The same procedures were successful in the identification of JH III in hemolymph of fourth stadium D. punctata. Last stadium nymphal (female) O. parkeri implanted with synganglia from second nymphal instars underwent normal eclosion to the adult. The above studies in toto suggest that D. variabilis and O. parkeri do not have the ability to make the common insect juvenile hormones, and these juvenile hormones do not regulate tick metamorphosis or reproduction as hypothesized in the literature