390 research outputs found

    Microstructure and crystallographic texture of silicon iron modified by torsion under quasihydrostatic pressure

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    The electron backscatter diffraction, X-ray diffraction analysis, electromotive force instantaneous measurement, microhardness and coercive force measurement techniques are used to explore the development of the microstructure, crystallographic texture and physico-mechanical properties of silicon iron (Fe-3% Si) alloy under quasi-hydrostatic pressure in a Bridgman anvil. It is found that the alloy deformation is accompanied by its significant hardenin

    Virtual Shaping on NACA 0015 by Means of a High Momentum Coefficient Synthetic Jet

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    Results concerning flow control on a NACA 0015 airfoil using high power synthetic jets are presented for low incidences and for Reynolds numbers ranging from 132000 to 425000. The forcing was operated through a spanwise slit positioned near the leading edge at x/c=1.25% or at x/c=10% on the upper surface. Static pressure distribution measurements around the airfoil, wake surveys and smoke flow visualizations were performed. Pressure distributions were significantly modified around the injection location, showing an area of intense suction which increased the lift and strongly affected the drag. Flow visualizations highlighted that the intense suction was due to a virtual shaping effect caused by the formation of a recirculation bubble capable of displacing the streamlines. Low momentum deficits in the wake velocity distributions and, in certain conditions, jet-like flow was observed for the forced cases. Finally, a scaling law relating the bubble size to the forcing intensity is propose

    Genes Involved in the Balance between Neuronal Survival and Death during Inflammation

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    Glucocorticoids are potent regulators of the innate immune response, and alteration in this inhibitory feedback has detrimental consequences for the neural tissue. This study profiled and investigated functionally candidate genes mediating this switch between cell survival and death during an acute inflammatory reaction subsequent to the absence of glucocorticoid signaling. Oligonucleotide microarray analysis revealed that following lipopolysaccharide (LPS) intracerebral administration at striatum level, more modulated genes presented transcription impairment than exacerbation upon glucocorticoid receptor blockage. Among impaired genes we identified ceruloplasmin (Cp), which plays a key role in iron metabolism and is implicated in a neurodegenative disease. Microglial and endothelial induction of Cp is a natural neuroprotective mechanism during inflammation, because Cp-deficient mice exhibited increased iron accumulation and demyelination when exposed to LPS and neurovascular reactivity to pneumococcal meningitis. This study has identified genes that can play a critical role in programming the innate immune response, helping to clarify the mechanisms leading to protection or damage during inflammatory conditions in the CNS

    Connectivity precedes function in the development of the visual word form area

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    What determines the cortical location at which a given functionally specific region will arise in development? We tested the hypothesis that functionally specific regions develop in their characteristic locations because of pre-existing differences in the extrinsic connectivity of that region to the rest of the brain. We exploited the visual word form area (VWFA) as a test case, scanning children with diffusion and functional imaging at age 5, before they learned to read, and at age 8, after they learned to read. We found the VWFA developed functionally in this interval and that its location in a particular child at age 8 could be predicted from that child's connectivity fingerprints (but not functional responses) at age 5. These results suggest that early connectivity instructs the functional development of the VWFA, possibly reflecting a general mechanism of cortical development.National Institutes of Health (U.S.) (Grant F32HD079169)Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (Grant F32HD079169)National Institutes of Health (U.S.) (Grant R01HD067312)Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (Grant R01HD067312

    The Invariance Hypothesis Implies Domain-Specific Regions in Visual Cortex

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    Is visual cortex made up of general-purpose information processing machinery, or does it consist of a collection of specialized modules? If prior knowledge, acquired from learning a set of objects is only transferable to new objects that share properties with the old, then the recognition system’s optimal organization must be one containing specialized modules for different object classes. Our analysis starts from a premise we call the invariance hypothesis: that the computational goal of the ventral stream is to compute an invariant-to-transformations and discriminative signature for recognition. The key condition enabling approximate transfer of invariance without sacrificing discriminability turns out to be that the learned and novel objects transform similarly. This implies that the optimal recognition system must contain subsystems trained only with data from similarly-transforming objects and suggests a novel interpretation of domain-specific regions like the fusiform face area (FFA). Furthermore, we can define an index of transformation-compatibility, computable from videos, that can be combined with information about the statistics of natural vision to yield predictions for which object categories ought to have domain-specific regions in agreement with the available data. The result is a unifying account linking the large literature on view-based recognition with the wealth of experimental evidence concerning domain-specific regions.National Science Foundation (U.S.). Science and Technology Center (Award CCF-1231216)National Science Foundation (U.S.) (Grant NSF-0640097)National Science Foundation (U.S.) (Grant NSF-0827427)United States. Air Force Office of Scientific Research (Grant FA8650-05-C-7262)Eugene McDermott Foundatio

    Comparative tissue transcriptomics reveal prompt inter-organ communication in response to local bacterial kidney infection

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    <p>Abstract</p> <p>Background</p> <p>Mucosal infections elicit inflammatory responses via regulated signaling pathways. Infection outcome depends strongly on early events occurring immediately when bacteria start interacting with cells in the mucosal membrane. Hitherto reported transcription profiles on host-pathogen interactions are strongly biased towards <it>in vitro </it>studies. To detail the local <it>in vivo </it>genetic response to infection, we here profiled host gene expression in a recent experimental model that assures high spatial and temporal control of uropathogenic <it>Escherichia coli </it>(UPEC) infection within the kidney of a live rat.</p> <p>Results</p> <p>Transcriptional profiling of tissue biopsies from UPEC-infected kidney tissue revealed 59 differentially expressed genes 8 h post-infection. Their relevance for the infection process was supported by a Gene Ontology (GO) analysis. Early differential expression at 3 h and 5 h post-infection was of low statistical significance, which correlated to the low degree of infection. Comparative transcriptomics analysis of the 8 h data set and online available studies of early local infection and inflammation defined a core of 80 genes constituting a "General tissue response to early local bacterial infections". Among these, 25% were annotated as interferon-γ (IFN-γ) regulated. Subsequent experimental analyses confirmed a systemic increase of IFN-γ in rats with an ongoing local kidney infection, correlating to splenic, rather than renal <it>Ifng </it>induction and suggested this inter-organ communication to be mediated by interleukin (IL)-23. The use of comparative transcriptomics allowed expansion of the statistical data handling, whereby relevant data could also be extracted from the 5 h data set. Out of the 31 differentially expressed core genes, some represented specific 5 h responses, illustrating the value of comparative transcriptomics when studying the dynamic nature of gene regulation in response to infections.</p> <p>Conclusion</p> <p>Our hypothesis-free approach identified components of infection-associated multi-cellular tissue responses and demonstrated how a comparative analysis allows retrieval of relevant information from lower-quality data sets. The data further define marked representation of IFN-γ responsive genes and a prompt inter-organ communication as a hallmark of an early local tissue response to infection.</p

    Absence of Colony Stimulation Factor-1 Receptor Results in Loss of Microglia, Disrupted Brain Development and Olfactory Deficits

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    The brain contains numerous mononuclear phagocytes called microglia. These cells express the transmembrane tyrosine kinase receptor for the macrophage growth factor colony stimulating factor-1 (CSF-1R). Using a CSF-1R-GFP reporter mouse strain combined with lineage defining antibody staining we show in the postnatal mouse brain that CSF-1R is expressed only in microglia and not neurons, astrocytes or glial cells. To study CSF-1R function we used mice homozygous for a null mutation in the Csflr gene. In these mice microglia are >99% depleted at embryonic day 16 and day 1 post-partum brain. At three weeks of age this microglial depletion continues in most regions of the brain although some contain clusters of rounded microglia. Despite the loss of microglia, embryonic brain development appears normal but during the post-natal period the brain architecture becomes perturbed with enlarged ventricles and regionally compressed parenchyma, phenotypes most prominent in the olfactory bulb and cortex. In the cortex there is increased neuronal density, elevated numbers of astrocytes but reduced numbers of oligodendrocytes. Csf1r nulls rarely survive to adulthood and therefore to study the role of CSF-1R in olfaction we used the viable null mutants in the Csf1 (Csf1op) gene that encodes one of the two known CSF-1R ligands. Food-finding experiments indicate that olfactory capacity is significantly impaired in the absence of CSF-1. CSF-1R is therefore required for the development of microglia, for a fully functional olfactory system and the maintenance of normal brain structure

    Pan-Eurasian Experiment (PEEX): Towards a holistic understanding of the feedbacks and interactions in the land-Atmosphere-ocean-society continuum in the northern Eurasian region

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    The northern Eurasian regions and Arctic Ocean will very likely undergo substantial changes during the next decades. The Arctic-boreal natural environments play a crucial role in the global climate via albedo change, carbon sources and sinks as well as atmospheric aerosol production from biogenic volatile organic compounds. Furthermore, it is expected that global trade activities, demographic movement, and use of natural resources will be increasing in the Arctic regions. There is a need for a novel research approach, which not only identifies and tackles the relevant multi-disciplinary research questions, but also is able to make a holistic system analysis of the expected feedbacks. In this paper, we introduce the research agenda of the Pan-Eurasian Experiment (PEEX), a multi-scale, multi-disciplinary and international program started in 2012 (https://www.atm.helsinki.fi/peex/). PEEX sets a research approach by which large-scale research topics are investigated from a system perspective and which aims to fill the key gaps in our understanding of the feedbacks and interactions between the land-Atmosphere-Aquatic-society continuum in the northern Eurasian region. We introduce here the state of the art for the key topics in the PEEX research agenda and present the future prospects of the research, which we see relevant in this context

    Empagliflozin in patients hospitalized for acute decompensated heart failure: an expert resolution on the discussion of the EMPULSE trial

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    An online expert meeting held on November 17, 2021 reviewed the results of the randomized, double-blind, multinational, parallel-group EMPULSE trial, evaluating the clinical benefit and safety of the sodium-glucose co-transporter-2 inhibitor (SGLT2i) empagliflozin compared with placebo in patients hospitalized with acute decompensated heart failure (ADHF). Patients were included in the study regardless of ejection fraction (EF) and the presence of diabetes and randomized during hospitalization after stabilization. In addition, the EMPULSE trial used a composite result analyzed using a stratified benefit ratio — Win Ratio analysis. There is evidence of clinical benefit of empagliflozin in hospitalized patients with preserved and reduced LVEF, as well as in patients with newly diagnosed ADHF or with acute decompensation of chronic heart failure (CHF) compared with placebo, regardless of type 2 diabetes presence. The importance of the favorable results of the EMPULSE trial and its significance for clinical practice, which implies the early administration of empagliflozin for inpatients, is noted. A number of proposals have been adopted to accelerate the introduction of empagliflozin into clinical practice for patients with ADHF
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