222 research outputs found

    Pendulum Mode Thermal Noise in Advanced Interferometers: A comparison of Fused Silica Fibers and Ribbons in the Presence of Surface Loss

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    The use of fused-silica ribbons as suspensions in gravitational wave interferometers can result in significant improvements in pendulum mode thermal noise. Surface loss sets a lower bound to the level of noise achievable, at what level depends on the dissipation depth and other physical parameters. For LIGO II, the high breaking strength of pristine fused silica filaments, the correct choice of ribbon aspect ratio (to minimize thermoelastic damping), and low dissipation depth combined with the other achievable parameters can reduce the pendulum mode thermal noise in a ribbon suspension well below the radiation pressure noise. Despite producing higher levels of pendulum mode thermal noise, cylindrical fiber suspensions provide an acceptable alternative for LIGO II, should unforeseen problems with ribbon suspensions arise.Comment: Submitted to Physics Letters A (Dec. 14, 1999). Resubmitted to Physics Letters A (Apr. 3, 2000) after internal (LSC) review process. PACS - 04.80.Nn, 95.55.Ym, 05.40.C

    Reduction of hexavalent chromium by fasted and fed human gastric fluid. II. Ex vivo gastric reduction modeling

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    AbstractTo extend previous models of hexavalent chromium [Cr(VI)] reduction by gastric fluid (GF), ex vivo experiments were conducted to address data gaps and limitations identified with respect to (1) GF dilution in the model; (2) reduction of Cr(VI) in fed human GF samples; (3) the number of Cr(VI) reduction pools present in human GF under fed, fasted, and proton pump inhibitor (PPI)-use conditions; and (4) an appropriate form for the pH-dependence of Cr(VI) reduction rate constants. Rates and capacities of Cr(VI) reduction were characterized in gastric contents from fed and fasted volunteers, and from fasted pre-operative patients treated with PPIs. Reduction capacities were first estimated over a 4-h reduction period. Once reduction capacity was established, a dual-spike approach was used in speciated isotope dilution mass spectrometry analyses to characterize the concentration-dependence of the 2nd order reduction rate constants. These data, when combined with previously collected data, were well described by a three-pool model (pool 1 = fast reaction with low capacity; pool 2 = slow reaction with higher capacity; pool 3 = very slow reaction with higher capacity) using pH-dependent rate constants characterized by a piecewise, log-linear relationship. These data indicate that human gastric samples, like those collected from rats and mice, contain multiple pools of reducing agents, and low concentrations of Cr(VI) (<0.7 mg/L) are reduced more rapidly than high concentrations. The data and revised modeling results herein provide improved characterization of Cr(VI) gastric reduction kinetics, critical for Cr(VI) pharmacokinetic modeling and human health risk assessment

    The Galaxy Zoo survey for giant AGN-ionized clouds: past and present black hole accretion events

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    Some active galactic nuclei (AGN) are surrounded by extended emission-line regions (EELRs), which trace both the illumination pattern of escaping radiation and its history over the light travel time from the AGN to the gas. From a new set of such EELRs, we present evidence that the AGN in many Seyfert galaxies undergo luminous episodes 0.2–2 ×105 years in duration. Motivated by the discovery of the spectacular nebula known as Hanny’s Voorwerp, ionized by a powerful AGN which has apparently faded dramatically within ≈ 105 years, Galaxy Zoo volunteers have carried out both targeted and serendipitous searches for similar emission-line clouds around low-redshift galaxies. We present the resulting list of candidates and describe spectroscopy identifying 19 galaxies with AGN-ionized regions at projected radii rproj \u3e 10 kpc. This search recovered known EELRs (such as Mrk 78, Mrk 266 and NGC 5252) and identified additional previously unknown cases, one with detected emission to r = 37 kpc. One new Sy 2 was identified. At least 14/19 are in interacting or merging systems, suggesting that tidal tails are a prime source of distant gas out of the galaxy plane to be ionized by an AGN. We see a mix of one-and two-sided structures, with observed cone angles from 23◩ to 112◩. We consider the energy balance in the ionized clouds, with lower and upper bounds on ionizing luminosity from recombination and ionization-parameter arguments, and estimate the luminosity of the core from the far-infrared data. The implied ratio of ionizing radiation seen by the clouds to that emitted by the nucleus, on the assumption of a non-variable nuclear source, ranges from 0.02 to \u3e12; 7/19 exceed unity. Small values fit well with a heavily obscured AGN in which only a small fraction of the ionizing output escapes to be traced by surrounding gas. However, large values may require that the AGN has faded over tens of thousands of years, giving us several examples of systems in which such dramatic long-period variation has occurred; this is the only current technique for addressing these time-scales in AGN history. The relative numbers of faded and non-faded objects we infer, and the projected extents of the ionized regions, give our estimate (0.2–2×105 years) for the length of individual bright phases

    The density of small tight junction pores varies among cell types and is increased by expression of claudin-2

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    Epithelial tight junctions contain size- and charge-selective pores that control the paracellular movement of charged and noncharged solutes. Claudins influence the charge selectivity and electrical resistance of junctions, but there is no direct evidence describing pore composition or whether pore size or density differs among cell types. To characterize paracellular pores independent of influences from charge selectivity, we profiled the ;apparent permeabilities' (P(app)) of a continuous series of noncharged polyethylene glycols (PEGs) across monolayers of five different epithelial cell lines and porcine ileum. We also characterized P(app) of high and low electrical resistance MDCK cell monolayers expressing heterologous claudins. P(app) profiling confirms that the paracellular barrier to noncharged solutes can be modeled as two distinct pathways: high-capacity small pores and a size-independent pathway allowing flux of larger solutes. All cell lines and ileum share a pore aperture of radius 4 A. Using P(app) of a PEG of radius 3.5 A to report the relative pore number provides the novel insight that pore density along the junction varies among cell types and is not necessarily related to electrical resistance. Expression of claudin-2 results in a selective increase in pore number but not size and has no effect on the permeability of PEGs that are larger than the pores; however, neither knockdown of claudin-2 nor overexpression of several other claudins altered either the number of small pores or their size. We speculate that permeability of all small solutes is proportional to pore number but that small electrolytes are subject to further selectivity by the profile of claudins expressed, explaining the dissociation between the P(app) for noncharged solutes and electrical resistance. Although claudins are likely to be components of the small pores, other factors might regulate pore number

    Organic Cation Transporter 1 (OCT1/mOct1) Is Localized in the Apical Membrane of Caco-2 Cell Monolayers and Enterocytes

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    ABSTRACT Organic cation transporters (OCTs) are members of the solute carrier 22 family of transporter proteins that are involved in absorption, distribution, and excretion of organic cations. OCT3 is localized in the apical (AP) membrane of enterocytes, but the literature is ambiguous about OCT1 (mOct1) localization, with some evidence suggesting a basolateral (BL) localization in human and mouse enterocytes. This is contrary to our preliminary findings showing AP localization of OCT1 in Caco-2 cell monolayers, an established model of human intestinal epithelium. Therefore, this study aims at determining the localization of OCT1 (mOct1) in Caco-2 cells, and human and mouse enterocytes. Functional studies using OCT1-specific substrate pentamidine showed transporter-mediated AP but not BL uptake in Caco-2 cells and human and mouse intestinal tissues. OCT1 inhibition decreased AP uptake of pentamidine by ∌50% in all three systems with no effect on BL uptake. A short hairpin RNA-mediated OCT1 knockdown in Caco-2 cells decreased AP uptake of pentamidine by ∌50% but did not alter BL uptake. Immunostaining and confocal microscopy in all three systems confirmed AP localization of OCT1 (mOct1). Our studies unequivocally show AP membrane localization of OCT1 (mOct1) in Caco-2 cells and human and mouse intestine. These results are highly significant as they will require reinterpretation of previous drug disposition and drug-drug interaction studies where conclusions were drawn assuming BL localization of OCT1 in enterocytes. Most importantly, these results will require revision of the regulatory guidance for industry in the United States and elsewhere because it has stated that OCT1 is basolaterally localized in enterocytes

    Locus Reference Genomic sequences: an improved basis for describing human DNA variants

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    As our knowledge of the complexity of gene architecture grows, and we increase our understanding of the subtleties of gene expression, the process of accurately describing disease-causing gene variants has become increasingly problematic. In part, this is due to current reference DNA sequence formats that do not fully meet present needs. Here we present the Locus Reference Genomic (LRG) sequence format, which has been designed for the specific purpose of gene variant reporting. The format builds on the successful National Center for Biotechnology Information (NCBI) RefSeqGene project and provides a single-file record containing a uniquely stable reference DNA sequence along with all relevant transcript and protein sequences essential to the description of gene variants. In principle, LRGs can be created for any organism, not just human. In addition, we recognize the need to respect legacy numbering systems for exons and amino acids and the LRG format takes account of these. We hope that widespread adoption of LRGs - which will be created and maintained by the NCBI and the European Bioinformatics Institute (EBI) - along with consistent use of the Human Genome Variation Society (HGVS)-approved variant nomenclature will reduce errors in the reporting of variants in the literature and improve communication about variants affecting human health. Further information can be found on the LRG web site: http://www.lrg-sequence.org

    Revising the WHO verbal autopsy instrument to facilitate routine cause-of-death monitoring.

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    OBJECTIVE: Verbal autopsy (VA) is a systematic approach for determining causes of death (CoD) in populations without routine medical certification. It has mainly been used in research contexts and involved relatively lengthy interviews. Our objective here is to describe the process used to shorten, simplify, and standardise the VA process to make it feasible for application on a larger scale such as in routine civil registration and vital statistics (CRVS) systems. METHODS: A literature review of existing VA instruments was undertaken. The World Health Organization (WHO) then facilitated an international consultation process to review experiences with existing VA instruments, including those from WHO, the Demographic Evaluation of Populations and their Health in Developing Countries (INDEPTH) Network, InterVA, and the Population Health Metrics Research Consortium (PHMRC). In an expert meeting, consideration was given to formulating a workable VA CoD list [with mapping to the International Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) CoD] and to the viability and utility of existing VA interview questions, with a view to undertaking systematic simplification. FINDINGS: A revised VA CoD list was compiled enabling mapping of all ICD-10 CoD onto 62 VA cause categories, chosen on the grounds of public health significance as well as potential for ascertainment from VA. A set of 221 indicators for inclusion in the revised VA instrument was developed on the basis of accumulated experience, with appropriate skip patterns for various population sub-groups. The duration of a VA interview was reduced by about 40% with this new approach. CONCLUSIONS: The revised VA instrument resulting from this consultation process is presented here as a means of making it available for widespread use and evaluation. It is envisaged that this will be used in conjunction with automated models for assigning CoD from VA data, rather than involving physicians
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