925 research outputs found

    Geologic considerations in underground coal mining system design

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    Geologic characteristics of coal resources which may impact new extraction technologies are identified and described to aid system designers and planners in their task of designing advanced coal extraction systems for the central Appalachian region. These geologic conditions are then organized into a matrix identified as the baseline mine concept. A sample region, eastern Kentucy is analyzed using both the developed baseline mine concept and the traditional geologic investigative approach

    Homogenization of weakly coupled systems of Hamilton--Jacobi equations with fast switching rates

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    We consider homogenization for weakly coupled systems of Hamilton--Jacobi equations with fast switching rates. The fast switching rate terms force the solutions converge to the same limit, which is a solution of the effective equation. We discover the appearance of the initial layers, which appear naturally when we consider the systems with different initial data and analyze them rigorously. In particular, we obtain matched asymptotic solutions of the systems and rate of convergence. We also investigate properties of the effective Hamiltonian of weakly coupled systems and show some examples which do not appear in the context of single equations.Comment: final version, to appear in Arch. Ration. Mech. Ana

    Field emission from two-dimensional GeAs

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    GeAs is a layered material of the IV–V groups that is attracting growing attention for possible applications in electronic and optoelectronic devices. In this study, exfoliated multilayer GeAs nanoflakes are structurally characterized and used as the channel of back-gate field-effect transistors. It is shown that their gate-modulated p-type conduction is decreased by exposure to light or electron beam. Moreover, the observation of a field emission (FE) current demonstrates the suitability of GeAs nanoflakes as cold cathodes for electron emission and opens up new perspective applications of two-dimensional GeAs in vacuum electronics. FE occurs with a turn-on field of ~80 Vum-1 and attains a current density higher than 10 Acm-2, following the general Fowler–Nordheim model with high reproducibility

    Nanopods: A New Bacterial Structure and Mechanism for Deployment of Outer Membrane Vesicles

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    Background: Bacterial outer membrane vesicles (OMV) are packets of periplasmic material that, via the proteins and other molecules they contain, project metabolic function into the environment. While OMV production is widespread in proteobacteria, they have been extensively studied only in pathogens, which inhabit fully hydrated environments. However, many (arguably most) bacterial habitats, such as soil, are only partially hydrated. In the latter, water is characteristically distributed as films on soil particles that are, on average thinner, than are typical OMV (ca. ≤10 nm water film vs. 20 to >200 nm OMV;). Methodology/Principal Findings: We have identified a new bacterial surface structure, termed a "nanopod", that is a conduit for projecting OMV significant distances (e.g., ≥6 µm) from the cell. Electron cryotomography was used to determine nanopod three-dimensional structure, which revealed chains of vesicles within an undulating, tubular element. By using immunoelectron microscopy, proteomics, heterologous expression and mutagenesis, the tubes were determined to be an assembly of a surface layer protein (NpdA), and the interior structures identified as OMV. Specific metabolic function(s) for nanopods produced by Delftia sp. Cs1-4 are not yet known. However, a connection with phenanthrene degradation is a possibility since nanopod formation was induced by growth on phenanthrene. Orthologs of NpdA were identified in three other genera of the Comamonadaceae family, and all were experimentally verified to form nanopods. Conclusions/Significance: Nanopods are new bacterial organelles, and establish a new paradigm in the mechanisms by which bacteria effect long-distance interactions with their environment. Specifically, they create a pathway through which cells can effectively deploy OMV, and the biological activity these transmit, in a diffusion-independent manner. Nanopods would thus allow environmental bacteria to expand their metabolic sphere of influence in a manner previously unknown for these organisms

    Optimal stent design for high bleeding risk patients: Evidence from a network meta-analysis

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    Objective. To determine the best stent design for high bleeding risk (HBR) patients. Background. Polymer-free (PF) drug eluting stent (DES) devices have a proven benefit over bare-metal stent (BMS) devices in previous trials. It is unknown, however, whether polymer-based (PB)-DES devices are as safe as PF-DES devices. Methods. A network meta-analysis including all randomized controlled trials (RCTs) that compared different stent technology in HBR patients with a 1-month course of dual-antiplatelet therapy (DAPT) was performed. The main efficacy outcome was major adverse cardiac event (MACE) rate, defined as the composite of all-cause mortality, myocardial infarction (MI), and target-lesion revascularization (TLR). Secondary efficacy events included all-cause and cardiac mortality, MI, stroke, TLR, and target-vessel revascularization (TVR). Safety outcomes included all bleeding, major bleeding, and stent thrombosis (ST). Results. A total of 4 RCTs with 6456 patients were included. PF-DES and PB-DES yielded a reduced rate of MACE, MI, TLR, and TVR events compared with BMS (all P<.05). ST events were reduced in PB-DES compared with BMS (P=.01). No differences were found in all-cause death, cardiac death, or stroke events in PF-DES and PB-DES compared with BMS. Furthermore, no differences were found between PF-DES and PB-DES regarding any of the outcomes. Conclusion. DES devices were associated with lower MACE and TVR rates compared with BMS, whereas there were no statistical differences in other efficacy endpoints. Also, PB-DES were associated with fewer ST events compared with BMS. There were no statistical differences between PB-DES and PF-DES with regard to any of the endpoints. t 2021 HMP Comm Personal Use Onl

    An electrostatic switch displaces phosphatidylinositol phosphate kinases from the membrane during phagocytosis

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    PIP5K is held at the membrane of forming phagosomes by a conserved, positively charged patch. During particle engulfment, the surface charge of the phagosome decreases, releasing PIP5K and enabling phagocytosis to proceed

    LRG1 destabilizes tumor vessels and restricts immunotherapeutic potency

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    BACKGROUND: A poorly functioning tumor vasculature is pro-oncogenic and may impede the delivery of therapeutics. Normalizing the vasculature, therefore, may be beneficial. We previously reported that the secreted glycoprotein leucine-rich α-2-glycoprotein 1 (LRG1) contributes to pathogenic neovascularization. Here, we investigate whether LRG1 in tumors is vasculopathic and whether its inhibition has therapeutic utility. METHODS: Tumor growth and vascular structure were analyzed in subcutaneous and genetically engineered mouse models in wild-type and Lrg1 knockout mice. The effects of LRG1 antibody blockade as monotherapy, or in combination with co-therapies, on vascular function, tumor growth, and infiltrated lymphocytes were investigated. FINDINGS: In mouse models of cancer, Lrg1 expression was induced in tumor endothelial cells, consistent with an increase in protein expression in human cancers. The expression of LRG1 affected tumor progression as Lrg1 gene deletion, or treatment with a LRG1 function-blocking antibody, inhibited tumor growth and improved survival. Inhibition of LRG1 increased endothelial cell pericyte coverage and improved vascular function, resulting in enhanced efficacy of cisplatin chemotherapy, adoptive T cell therapy, and immune checkpoint inhibition (anti-PD1) therapy. With immunotherapy, LRG1 inhibition led to a significant shift in the tumor microenvironment from being predominantly immune silent to immune active. CONCLUSIONS: LRG1 drives vascular abnormalization, and its inhibition represents a novel and effective means of improving the efficacy of cancer therapeutics

    Flow rate and source reservoir identification from airborne chemical sampling of the uncontrolled Elgin platform gas release

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    An uncontrolled gas leak from 25 March to 16 May 2012 led to evacuation of the Total Elgin wellhead and neighbouring drilling and production platforms in the UK North Sea. Initially the atmospheric flow rate of leaking gas and condensate was very poorly known, hampering environmental assessment and well control efforts. Six flights by the UK FAAM chemically instrumented BAe-146 research aircraft were used to quantify the flow rate. The flow rate was calculated by assuming the plume may be modelled by a Gaussian distribution with two different solution methods: Gaussian fitting in the vertical and fitting with a fully mixed layer. When both solution methods were used they compared within 6% of each other, which was within combined errors. Data from the first flight on 30 March 2012 showed the flow rate to be 1.3±0.2kgCH4s-1, decreasing to less than half that by the second flight on 17 April 2012. δ13CCH4 in the gas was found to be -43‰, implying that the gas source was unlikely to be from the main high pressure, high temperature Elgin gas field at 5.5km depth, but more probably from the overlying Hod Formation at 4.2km depth. This was deemed to be smaller and more manageable than the high pressure Elgin field and hence the response strategy was considerably simpler. The first flight was conducted within 5 days of the blowout and allowed a flow rate estimate within 48h of sampling, with δ13CCH4 characterization soon thereafter, demonstrating the potential for a rapid-response capability that is widely applicable to future atmospheric emissions of environmental concern. Knowledge of the Elgin flow rate helped inform subsequent decision making. This study shows that leak assessment using appropriately designed airborne plume sampling strategies is well suited for circumstances where direct access is difficult or potentially dangerous. Measurements such as this also permit unbiased regulatory assessment of potential impact, independent of the emitting party, on timescales that can inform industry decision makers and assist rapid-response planning by government

    Differences in genotype and virulence among four multidrug-resistant <i>Streptococcus pneumoniae</i> isolates belonging to the PMEN1 clone

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    We report on the comparative genomics and characterization of the virulence phenotypes of four &lt;i&gt;S. pneumoniae&lt;/i&gt; strains that belong to the multidrug resistant clone PMEN1 (Spain&lt;sup&gt;23F&lt;/sup&gt; ST81). Strains SV35-T23 and SV36-T3 were recovered in 1996 from the nasopharynx of patients at an AIDS hospice in New York. Strain SV36-T3 expressed capsule type 3 which is unusual for this clone and represents the product of an in vivo capsular switch event. A third PMEN1 isolate - PN4595-T23 - was recovered in 1996 from the nasopharynx of a child attending day care in Portugal, and a fourth strain - ATCC700669 - was originally isolated from a patient with pneumococcal disease in Spain in 1984. We compared the genomes among four PMEN1 strains and 47 previously sequenced pneumococcal isolates for gene possession differences and allelic variations within core genes. In contrast to the 47 strains - representing a variety of clonal types - the four PMEN1 strains grouped closely together, demonstrating high genomic conservation within this lineage relative to the rest of the species. In the four PMEN1 strains allelic and gene possession differences were clustered into 18 genomic regions including the capsule, the blp bacteriocins, erythromycin resistance, the MM1-2008 prophage and multiple cell wall anchored proteins. In spite of their genomic similarity, the high resolution chinchilla model was able to detect variations in virulence properties of the PMEN1 strains highlighting how small genic or allelic variation can lead to significant changes in pathogenicity and making this set of strains ideal for the identification of novel virulence determinant
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