18 research outputs found

    Toll-like receptor 4 signaling in liver injury and hepatic fibrogenesis

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    Toll-like receptors (TLRs) are a family of transmembrane pattern recognition receptors (PRR) that play a key role in innate and adaptive immunity by recognizing structural components unique to bacteria, fungi and viruses. TLR4 is the most studied of the TLRs, and its primary exogenous ligand is lipopolysaccharide, a component of Gram-negative bacterial walls. In the absence of exogenous microbes, endogenous ligands including damage-associated molecular pattern molecules from damaged matrix and injured cells can also activate TLR4 signaling. In humans, single nucleotide polymorphisms of the TLR4 gene have an effect on its signal transduction and on associated risks of specific diseases, including cirrhosis. In liver, TLR4 is expressed by all parenchymal and non-parenchymal cell types, and contributes to tissue damage caused by a variety of etiologies. Intact TLR4 signaling was identified in hepatic stellate cells (HSCs), the major fibrogenic cell type in injured liver, and mediates key responses including an inflammatory phenotype, fibrogenesis and anti-apoptotic properties. Further clarification of the function and endogenous ligands of TLR4 signaling in HSCs and other liver cells could uncover novel mechanisms of fibrogenesis and facilitate the development of therapeutic strategies

    A highly reactive precursor in the iron sulfide system

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    Iron sulfur (Fe–S) phases have been implicated in the emergence of life on early Earth due to their catalytic role in the synthesis of prebiotic molecules. Similarly, Fe–S phases are currently of high interest in the development of green catalysts and energy storage. Here we report the synthesis and structure of a nanoparticulate phase (FeSnano) that is a necessary solid-phase precursor to the conventionally assumed initial precipitate in the iron sulfide system, mackinawite. The structure of FeSnano contains tetrahedral iron, which is compensated by monosulfide and polysulfide sulfur species. These together dramatically affect the stability and enhance the reactivity of FeSnano

    Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

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    BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

    An upwind kinetic flux vector splitting method for the euler equations on unstructured grids

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    This report describes the implementation, results and experiences gained in implementing an upwind kinetic flux vector splitting (KFVS) algorithm, developed by Deshpande and Mandal (1-7) on unstructured meshes constructed using the Delaunay triangulation (8,13,15)

    The numerical simulation of invisid compressible aeronautical flows

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    In this collaborative work, an unstructured grid generation technique, based upon the Delaunay triangulation, has been combined with an upwind kinetic flux vector splitting high resolution flow algorithm to simulate inviscid compressible flows for aeronautical applications

    Investigating the influence of aquifer heterogeneity on the potential for thermal free convection in the Yarragadee Aquifer, Western Australia

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    The potential for thermal convection in aquifers is strongly influenced by permeability. Permeability is highly heterogeneous within aquifers, and spatial distributions of permeability are rarely well constrained by measurements, making it difficult to determine the potential for thermal convection in a given aquifer. In this study, this difficulty is overcome through the use of a stratigraphic forward model (SFM). The SFM simulates the processes of deposition, burial and compaction of the aquifer, yielding a geologically plausible permeability field that is conditioned through measured permeability-porosity relationships. The aim of this study is to determine the influence of aquifer heterogeneity on the potential for thermal convection in the Yarragadee Aquifer, Western Australia. Permeability distributions from the SFM of the Yarragadee Aquifer are analysed through calculation of the thermal Rayleigh number (a stability criterion) from vertically averaged permeability, and numerical hydrothermal simulations with permeability distributions taken from the SFM. Results from the numerical simulations demonstrate that thermal convection can occur with the inclusion of geologically informed heterogeneity. These findings are supported by Rayleigh number calculations that indicate that convection is most likely to occur on the eastern side of the aquifer where it is thick and has high average permeability
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