625 research outputs found

    A New Literature for the Space Age

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    Technological developments, just as social changes, economic processes, or political events, make their impact on the literature of a nation, a culture or an era. The reverse, of course, is also true: man\u27s many and diverse activities are influenced and shaped by what is said about them. This paper attempts to project the trend, as well as some of the developments, of this culture-technology interaction in the forseeable future

    Structural, mechanistic and regulatory studies of serine palmitoyltransferase

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    SLs (sphingolipids) are composed of fatty acids and a polar head group derived from l-serine. SLs are essential components of all eukaryotic and many prokaryotic membranes but S1P (sphingosine 1-phosphate) is also a potent signalling molecule. Recent efforts have sought to inventory the large and chemically complex family of SLs (LIPID MAPS Consortium). Detailed understanding of SL metabolism may lead to therapeutic agents specifically directed at SL targets. We have studied the enzymes involved in SL biosynthesis; later stages are species-specific, but all core SLs are synthesized from the condensation of l-serine and a fatty acid thioester such as palmitoyl-CoA that is catalysed by SPT (serine palmitoyltransferase). SPT is a PLP (pyridoxal 5'-phosphate)-dependent enzyme that forms 3-KDS (3-ketodihydrosphingosine) through a decarboxylative Claisen-like condensation reaction. Eukaryotic SPTs are membrane-bound multi-subunit enzymes, whereas bacterial enzymes are cytoplasmic homodimers. We use bacterial SPTs (e. g. from Sphingomonas) to probe their structure and mechanism. Mutations in human SPT cause a neuropathy [HSAN1 (hereditary sensory and autonomic neuropathy type 1)], a rare SL metabolic disease. How these mutations perturb SPT activity is subtle and bacterial SPT mimics of HSAN1 mutants affect the enzyme activity and structure of the SPT dimer. We have also explored SPT inhibition using various inhibitors (e. g. cycloserine). A number of new subunits and regulatory proteins that have a direct impact on the activity of eukaryotic SPTs have recently been discovered. Knowledge gained from bacterial SPTs sheds some light on the more complex mammalian systems. In the present paper, we review historical aspects of the area and highlight recent key developments.</p

    Observation and control of hybrid spin-wave-Meissner-current transport modes

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    Superconductors are materials with zero electrical resistivity and the ability to expel magnetic fields known as the Meissner effect. Their dissipationless diamagnetic response is central to magnetic levitation and circuits such as quantum interference devices. Here, we use superconducting diamagnetism to shape the magnetic environment governing the transport of spin waves - collective spin excitations in magnets that are promising on-chip signal carriers - in a thin-film magnet. Using diamond-based magnetic imaging, we observe hybridized spin-wave-Meissner-current transport modes with strongly altered, temperature-tunable wavelengths. We extract the temperature-dependent London penetration depth from the wavelength shifts and realize local control of spin-wave refraction using a focused laser. Our results demonstrate the versatility of superconductor-manipulated spin-wave transport and have potential applications in spin-wave gratings, filters, crystals and cavities.Comment: main: 8 pages, 5 figures, supp: 15 pages, 6 figure

    Molecular cytogenetic characterization of a critical region in bands 7q35-q36 commonly deleted in malignant myeloid disorders

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    Loss of chromosome 7 (-7) or deletion of the long arm (7q-) are recurring chromosome abnormalities in myeloid leukemias. The association of - 7/7q- with myeloid leukemia suggests that these regions contain novel tumor suppressor gene(s), whose loss of function contribute to leukemic transformation or tumor progression. Based on chromosome banding analysis, two critical regions have been identified, one in band q22 and another in bands q32-q35. Presently there are no data available on the molecular delineation of the distal critical region. In this study we analyzed bone marrow and blood samples from 13 patients with myeloid leukemia (de novo myelodysplastic syndrome [MDS], n=3; de novo acute myeloid leukemia [AML], n=9; therapy-related (t-) AML, n=1) which, on chromosome banding analysis, exhibited deletions (n=12) or in one case a balanced translocation involving bands 7q31-qter using fluorescence in situ hybridization (FISH). As probes we used representative clones from a contig map of yeast artificial chromosome (YAC) clones that spans chromosome bands 7q31.1-qter. In the 12 cases with loss of 7q material, we identified a commonly deleted region of approximately 4 to 5 megabasepairs in size encompassing the distal part of 7q35 and the proximal part of 7q36. Furthermore, the breakpoint of the reciprocal translocation from the patient with t-AML was localized to a 1,300-kb sized YAC clone that maps to the proximal boundary of the commonly deleted region. Interestingly, in this case both homologs of chromosome 7 were affected: one was lost (-7) and the second exhibited the t(7q35). The identification and delineation of translocation and deletion breakpoints provides the first step toward the identification of the gene(s) involved in the pathogenesis of 7q35-q36 aberrations in myeloid disorders.link_to_OA_fulltex

    Correlated sampling in quantum Monte Carlo: a route to forces

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    In order to find the equilibrium geometries of molecules and solids and to perform ab initio molecular dynamics, it is necessary to calculate the forces on the nuclei. We present a correlated sampling method to efficiently calculate numerical forces and potential energy surfaces in diffusion Monte Carlo. It employs a novel coordinate transformation, earlier used in variational Monte Carlo, to greatly reduce the statistical error. Results are presented for first-row diatomic molecules.Comment: 5 pages, 2 postscript figure

    Niches of marine mammals in the European Arctic

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    The Arctic is warming rapidly, with concomitant sea ice losses and ecosystem changes. The animals most vulnerable to Arctic food web changes are long-lived and slow-growing such as marine mammals, which may not be able to adapt rapidly enough to respond to changes in their resource bases. To determine the current extent and sources of these resource bases, we examined isotopic and trophic niches for marine mammals in the European Arctic using skin carbon (δ13C) and nitrogen (δ 15N) stable isotope (SI) compositions from 10 species: blue, fin, humpback, minke, sperm and white whales, bearded and ringed seals, walruses and polar bears, and dietary fatty acids (FAs) in polar bears, walruses and most of the whale species listed here. SI values showed clear species separation by trophic behaviour and carbon sources. Bearded seals, walruses and white whales had the smallest isotopic niches; these species are all resident High Arctic species and are likely to be particularly vulnerable to changes in Arctic ecosystems. We found clear separation between FA groupings driven by pelagic, benthic and planktonic/algal sources: pelagic FAs in all whales, benthic FAs in walruses, and copepod/algae/dinoflagellate FAs in polar bears, with some polar bear compositions approaching those of the whales and walruses. There is strong niche partitioning between study species with minimal functional redundancy, which could impact Arctic ecosystem structure and connectivity if populations of these large nutrient vectors are reduced or lost

    Focused Ion Beam Fabrication

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    Contains summary of research program and reports on four research projects.Charles Stark Draper Laboratory (Contract DL-H-225270)Hughes Research LaboratoriesInternational Business Machines, Inc. (Contract 456614)Nippon Telegraph and Telephone, Inc.U.S. Navy - Office of Naval Research (Contract N00014-84-K-0073)U.S. Department of Defense (Contract MDA903-85-C-0215)Hitachi Central Research Laborator

    Recent translational research: Oncogene discovery by insertional mutagenesis gets a new boost

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    Knowledge of the genes and genetic pathways involved in onco-genesis is essential if we are to identify novel targets for cancer therapy. Insertional mutagenesis in mouse models is among the most efficient tools to detect novel cancer genes. Retrovirus-mediated insertional mutagenesis received a tremendous boost by the availability of the mouse genome sequence and new PCR methods. Application of such advances were limited to lympho-magenesis but are now also being applied to mammary tumourigenesis. Novel transposons that allow insertional muta-genesis studies to be conducted in tumors of any mouse tissue may give cancer gene discovery a further boost
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