633 research outputs found

    The Role of Monotonicity in the Epistemic Analysis of Strategic Games

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    It is well-known that in finite strategic games true common belief (or common knowledge) of rationality implies that the players will choose only strategies that survive the iterated elimination of strictly dominated strategies. We establish a general theorem that deals with monotonic rationality notions and arbitrary strategic games and allows to strengthen the above result to arbitrary games, other rationality notions, and transfinite iterations of the elimination process. We also clarify what conclusions one can draw for the customary dominance notions that are not monotonic. The main tool is Tarski's Fixpoint Theorem.Comment: 20 page

    The role of Black churches in response to African American male well-being in the Rust Belt region : a single location case study of east side churches in Buffalo, NY

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    https://place.asburyseminary.edu/ecommonsatsdissertations/2529/thumbnail.jp

    Quality assessment and data handling methods for Affymetrix Gene 1.0 ST arrays with variable RNA integrity

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    BBackground: RNA and microarray quality assessment form an integral part of gene expression analysis and, although methods such as the RNA integrity number (RIN) algorithm reliably asses RNA integrity, the relevance of RNA integrity in gene expression analysis as well as analysis methods to accommodate the possible effects of degradation requires further investigation. We investigated the relationship between RNA integrity and array quality on the commonly used Affymetrix Gene 1.0 ST array platform using reliable within-array and between-array quality assessment measures. The possibility of a transcript specific bias in the apparent effect of RNA degradation on the measured gene expression signal was evaluated after either excluding quality-flagged arrays or compensation for RNA degradation at different steps in the analysis. Results: Using probe-level and inter-array quality metrics to assess 34 Gene 1.0 ST array datasets derived from historical, paired tumour and normal primary colorectal cancer samples, 7 arrays (20.6%), with a mean sample RIN of 3.2 (SD = 0.42), were flagged during array quality assessment while 10 arrays from samples with RINs 2), with longer and shorter than average transcripts under- and overrepresented in quality-flagged samples respectively. Applying compensatory measures for RNA degradation performed at least as well as excluding quality-flagged arrays, as judged by hierarchical clustering, gene expression analysis and Ingenuity Pathway Analysis; importantly, use of these compensatory measures had the significant benefit of enabling lower quality array data from irreplaceable clinical samples to be retained in downstream analyses. Conclusions: Here, we demonstrate an effective array-quality assessment strategy, which will allow the user to recognize lower quality arrays that can be included in the analysis once appropriate measures are applied to account for known or unknown sources of variation, such as array quality- and batch- effects, by implementing ComBat or Surrogate Variable Analysis. This approach of quality control and analysis will be especially useful for clinical samples with variable and low RNA qualities, with RIN scores ≥ 2

    Autoantibody-Based Diagnostic Biomarkers: Technological Approaches to Discovery and Validation

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    Autoantibodies produced against self-antigens, or ‘autoantigens’, result from a loss of self-tolerance triggered by genetic and/or environmental factors which induce the immune system to attack the host’s own cells, resulting in a condition referred to as autoimmunity. In classic autoimmune diseases, it is well established that the pathology relates directly to the autoantibodies. However, it is increasingly recognised that autoantibodies are also found in many other disease areas, including cancers, cardiovascular and neurodegenerative diseases, as well infectious diseases such as malaria, albeit in such diseases it is unclear whether the autoantibodies play a direct role in the pathology or whether they are merely symptomatic of disease. Irrespective of whether they are causative or symptomatic of specific diseases though, there is increasing interest globally in exploring the clinical potential of circulating autoantibodies as diagnostic biomarkers. This chapter provides an overview of the diagnostic utility of autoantibody biomarkers in a range of disease areas and discusses their potential utility in disease staging, treatment monitoring and in prediction of immune-related adverse events. It also provides an overview of traditional and contemporary technological approaches to autoantibody biomarker discovery and validation, focusing on protein microarrays that are ideally suited to this important area of research

    Killing two birds with one stone: a chemically plausible scheme for linked nucleic acid replication and coded peptide synthesis

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    AbstractTo understand how life began, we must explain the origins of nucleic acid replication and genetically coded peptide synthesis. Neither of these is easy to explain individually; here, we propose a chemically plausible scheme for the evolution of a process that simultaneously produced both polymers. Later, two separate machineries could have evolved from the linked process

    A Novel Report of Hatching Plasticity in the Phylum Echinodermata

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    Hatching plasticity occurs in response to a wide range of stimuli across many animal taxa, including annelids, arthropods, mollusks, and chordates. Despite the prominence of echinoderms in developmental biology and more than 100 years of detailed examination of their development under a variety of conditions, environmentally cued hatching plasticity has never been reported in the phylum Echinodermata. Here we report plasticity in the timing and stage of hatching of embryos of the sand dollar Echinarachnius parma in response to reductions in salinity. Embryos of E. parma increased their time to hatching more than twofold in response to ecologically relevant salinity reductions, while maintaining an otherwise normal developmental schedule. Embryos that experienced the greatest delay in hatching time emerged from the fertilization envelope as fourarm pluteus larvae rather than hatching as blastulae or early gastrulae. Salinity manipulations across multiple male-female pairs indicated high variability in hatching time both within and among clutches, suggesting significant intraspecific variation in developmental responses to salinit

    The pathophysiology of RHD and outstanding gaps

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    Rheumatic heart disease (RHD) is the major cause of cardiovascular morbidity and mortality in children and young adults in low- and middle-income countries. Acute rheumatic fever (ARF) is characterised by multiorgan inflammatory symptoms initiated through cross reaction of immune responses (IRs) to group A streptococcus (GAS) proteins to host proteins. Recurrence of these IRs targeting the heart valves may lead to permanent damage, a sequela which is termed RHD. Preliminary studies suggested genetic associations in RF reactions, but that other host factors are also involved, leaving the determinants of RHD progression incompletely understood. Previous clinical and recent epidemiological studies support differential clinical phenotypes, with varying history from different settings. This review summarises the protein-centric biomolecular changes in RHD and highlights outstanding molecular gaps where urgent focus is required to improve our understanding RHD pathophysiology. Numerous studies have confirmed alterations in the expression of structural and immune response proteins, but the modifications giving rise to neo-epitopes and their involvement in RHD have not been established. As RHD is associated with poor living conditions, identification of other factors driving inflammation to enhance RHD progression is necessary to advance our knowledge and improve patient management. Furthermore, biomarkers for early identification, disease stratification, and alternative therapeutic strategies are necessary to improve treatment and prevention strategies in order to reduce the burden of RHD. Relevance: Despite the explosion of scientific innovation over the last few decades, fundamental scientific studies to understand the pathophysiological mechanisms of RHD remain in their infancy and the determinants of RHD progression thus remain uncertain. Moreover, inconsistency in natural history and phenotypic presentations are seen between Africans and other cohorts in which preliminary studies were conducted, implying that differences in genetic complexity and environmental factors may be responsible for the differential disease progression rates. SAHeart 2022;19:38-4

    Understanding porosity formation and prevention when welding titanium alloys with 1μm wavelength laser beams

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    Keyhole laser welding is a joining technology characterised by the high focussed power density applied to the workpiece, facilitating deep penetration at high processing speeds. High aspect-ratio welds produced using this process invariably have narrow heat-affected-zones and minimal thermal distortion compared with traditional arc welding processes. Furthermore, the ability to process out of vacuum and the easy robotic manipulation of fibre optically delivered 1μm wavelength laser beams, allow keyhole laser welding to process geometrically complex components. The widespread uptake of keyhole laser welding for the production of titanium alloy components in the aerospace industry has been limited by the stringent weld quality requirements. Producing welds with levels of subsurface weld metal porosity content meeting the required weld quality criteria has been the primary obstacle. Here, three techniques for controlling the levels of weld metal porosity when welding titanium alloys with Nd:YAG rod lasers have been developed. Characterisation of the welding processes using high speed photography and optical spectroscopy, have allowed an original scientific understanding of the effects these methods have on the keyhole, melt pool and vapour plume behaviour. Combining this with a thorough assessment of the weld qualities produced, has enabled the effects of these process behaviours on the formation of weld metal porosity to be determined. It was found that with the correct process parameters a directed gas jet and a dual focus laser welding condition can both be used to reduce the occurrence of keyhole collapse during Nd:YAG laser welding. The directed gas jet prevents the formation of a beam attenuating vapour plume and interacts with the molten metal to produce a stable welding condition, whereas the dual focus laser welding condition reduces fluctuations in the process due to an enlarged keyhole. When applied, both techniques reduced the occurrence of porosity in the weld metal of full penetration butt welds produced in titanium alloys. A modulated Nd:YAG laser output, with the correct waveform and modulation frequency, also reduced the occurrence of porosity in the weld metal compared with welds produced with a continuous-wave output. This was a result of an oscillating wave being set-up in the melt pool which manipulated the keyhole geometry and prevented instabilities in the process being established. In addition, the potential for welding titanium alloys to the required weld quality criteria with state-of-the-art Yb-fibre lasers has been assessed. It was found that the high power densities of suitably focussed laser beams with excellent beam quality, were capable of producing low-porosity full penetration butt welds in titanium alloys without the techniques required for laser beams with a lower beam quality. These new techniques for keyhole laser welding of titanium alloys will encourage the uptake of keyhole laser welding for producing near-net-shape high-performance aerospace components. The advantages offered by this joining technology include high productivity, low heat input and easy robotic automation.EThOS - Electronic Theses Online ServiceTWI LtdGBUnited Kingdo
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