We have measured the cosmic ray spectrum above 10(17.2) eV using the two air-fluorescence detectors of the High Resolution Fly's Eye observatory operating in monocular mode. We describe the detector, ...phototube, and atmospheric calibrations, as well as the analysis techniques for the two detectors. We fit the spectrum to a model consisting of galactic and extragalactic sources.
An 800-MeV proton radiography facility for dynamic experiments King, N.S.P; Ables, E; Adams, Ken ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
11/1999, Letnik:
424, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The capability has successfully been developed at the Los Alamos Nuclear Science Center (LANSCE) to utilize a spatially and temporally prepared 800
MeV proton beam to produce proton radiographs. A ...series of proton bursts are transmitted through a dynamic object and transported, via a unique magnetic lens system, to an image plane. The magnetic lens system permits correcting for the effects of multiple coulomb scattering which would otherwise completely blur the spatially transmitted information at the image plane. The proton radiographs are recorded either on a time integrating film plate or with a recently developed multi-frame electronic imaging camera system. The latter technique permits obtaining a time dependent series of proton radiographs with time intervals (modulo 358
ns) up to many microseconds and variable time intervals between images. One electronically shuttered, intensified, CCD camera is required per image. These cameras can detect single protons interacting with a scintillating fiber optic array in the image plane but also have a dynamic range which permits recording radiographs with better than 5% statistics for observation of detailed density variations in the object. A number of tests have been carried out to characterize the quality of the proton radiography system for absolute mass determination, resolution, and dynamic range. Initial dynamic experiments characterized the temporal and spatial behavior of shock propagation in a high explosive sample with up to six images per experiment. Based on experience with the prototype system, a number of upgrades are being implemented including the anticipated capability for enhanced mass discrimination through differential multiple coulomb scattering radiographs and more images with improved imaging techniques.
We have measured the spectrum of UHE cosmic rays using the Flash ADC (FADC) detector (called HiRes-II) of the High Resolution Fly’s Eye experiment running in monocular mode. We describe in detail the ...data analysis, development of the Monte Carlo simulation program, and results. We also describe the results of the HiRes-I detector. We present our measured spectra and compare them with a model incorporating galactic and extragalactic cosmic rays. Our combined spectra provide strong evidence for the existence of the spectral feature known as the “ankle.”
The bacterium Vibrio cholerae, like other human pathogens that reside in environmental reservoirs, survives predation by unicellular eukaryotes. Strains of the O1 and O139 serogroups cause cholera, ...whereas non-O1/non-O139 strains cause human infections through poorly defined mechanisms. Using Dictyostelium discoideum as a model host, we have identified a virulence mechanism in a non-O1/non-O139 V. cholerae strain that involves extracellular translocation of proteins that lack N-terminal hydrophobic leader sequences. Accordingly, we have named these genes "VAS" genes for virulence-associated secretion, and we propose that these genes encode a prototypic "type VI" secretion system. We show that vas genes are required for cytotoxicity of V. cholerae cells toward Dictyostelium amoebae and mammalian J774 macrophages by a contact-dependent mechanism. A large number of Gram-negative bacterial pathogens carry genes homologous to vas genes and potential effector proteins secreted by this pathway (i.e., hemolysin-coregulated protein and VgrG). Mutations in vas homologs in other bacterial species have been reported to attenuate virulence in animals and cultured macrophages. Thus, the genes encoding the VAS-related, type VI secretion system likely play an important conserved function in microbial pathogenesis and represent an additional class of targets for vaccine and antimicrobial drug-based therapies.
The ESX-1 locus is a region critical for full virulence in Mycobacterium tuberculosis, which encodes two secreted proteins as well as other genes involved in their secretion. The mechanism of ...secretion of the two proteins, ESAT-6 and CFP-10, and their function remain unknown. Using proteomic methods to search for additional proteins secreted by the ESX-1 locus, we discovered that a protein encoded by a chromosomally unlinked gene, espA, is also secreted by strains that contain the ESX-1 locus but not by strains with ESX-1 deletions. Mutations in individual ESX-1 genes, including those that encode ESAT-6 and CFP-10, were found to block EspA secretion. Surprisingly, mutants that lack espA reciprocally failed to secrete ESAT-6 and CFP-10 and were as attenuated as ESX-1 mutants in virulence assays. The results indicate that secretion of these proteins, which are each critical for virulence of pathogenic mycobacteria, is mutually dependent. The results further suggest that discerning the nature of the interaction and the structure of macromolecular complexes will provide insights into both an alternative mechanism of protein secretion and mycobacterial virulence.
The development of increasingly high-throughput and sensitive mass spectroscopy-based proteomic techniques provides new opportunities to examine the physiology and pathophysiology of many biologic ...fluids and tissues. The purpose of this study was to determine protein expression profiles of high-abundance synovial fluid (SF) proteins in health and in the prevalent joint disease osteoarthritis (OA). A cross-sectional study of 62 patients with early OA (n = 21), patients with late OA (n = 21), and control individuals (n = 20) was conducted. SF proteins were separated by using one-dimensional PAGE, and the in-gel digested proteins were analyzed by electrospray ionization tandem mass spectrometry. A total of 362 spots were examined and 135 high-abundance SF proteins were identified as being expressed across all three study cohorts. A total of 135 SF proteins were identified. Eighteen proteins were found to be significantly differentially expressed between control individuals and OA patients. Two subsets of OA that are not dependent on disease duration were identified using unsupervised analysis of the data. Several novel SF proteins were also identified. Our analyses demonstrate no disease duration-dependent differences in abundant protein composition of SF in OA, and we clearly identified two previously unappreciated yet distinct subsets of protein profiles in this disease cohort. Additionally, our findings reveal novel abundant protein species in healthy SF whose functional contribution to SF physiology was not previously recognized. Finally, our studies identify candidate biomarkers for OA with potential for use as highly sensitive and specific tests for diagnostic purposes or for evaluating therapeutic response.
Abstract
Whether economic growth improves the human lot is a matter of conditions. We focus on Japan, a country which shifted in the 1990s from a pattern of rampant economic growth and stagnant ...well-being, to one of modest growth and increasing well-being. We discuss concurrent policy reforms and analyse the changes in well-being. In particular, we assess whether the correlates of the increase in well-being are consistent with those expected from the reforms. We apply Blinder–Oaxaca decomposition to World Values Survey data. Results show that improved conditions for the elderly, parents and women, that is the primary groups targeted by the reforms, correlate with well-being increases. This evidence is consistent with the hypothesis that social safety nets can make economic growth compatible with sustained increases in well-being.
Parathyroid hormone (PTH) assays able to distinguish between full-length PTH (PTH1-84) and N-terminally truncated PTH (PTH7-84) are of increasing significance in the accurate diagnosis of endocrine ...and osteological diseases. We describe the discovery of new N-terminal and C-terminal PTH variants and the development of selected reaction monitoring (SRM)-based immunoassays specifically designed for the detection of full-length PTH amino acid (aa)1-84 and 2 N-terminal variants, aa7-84 and aa34-84.
Preparation of mass spectrometric immunoassay pipettor tips and MALDI-TOF mass spectrometric analysis were carried out as previously described. We used novel software to develop SRM assays on a triple-quadrupole mass spectrometer. Heavy isotope-labeled versions of target peptides were used as internal standards.
Top-down analysis of samples from healthy individuals and renal failure patients revealed numerous PTH variants, including previously unidentified aa28-84, aa48-84, aa34-77, aa37-77, and aa38-77. Quantitative SRM assays were developed for PTH1-84, PTH7-84, and variant aa34-84. Peptides exhibited linear responses (R(2) = 0.90-0.99) relative to recombinant human PTH concentration limits of detection for intact PTH of 8 ng/L and limits of quantification of 16-31 ng/L depending on the peptide. Standard error of analysis for all triplicate measurements was 3%-12% for all peptides, with <5% chromatographic drift between replicates. The CVs of integrated areas under the curve for 54 separate measurements of heavy peptides were 5%-9%.
Mass spectrometric immunoassays identified new clinical variants of PTH and provided a quantitative assay for these and previously identified forms of PTH.
PDF
