863 resultados para causal discovery
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A prerequisite for preventive measures is to diagnose erosive tooth wear and to evaluate the different etiological factors in order to identify persons at risk. No diagnostic device is available for the assessment of erosive defects. Thus, they can only be detected clinically. Consequently, erosion not diagnosed at an early stage may render timely preventive measures difficult. In order to assess the risk factors, patients should record their dietary intake for a distinct period of time. Then a dentist can determine the erosive potential of the diet. A table with common beverages and foodstuffs is presented for judging the erosive potential. Particularly, patients with more than 4 dietary acid intakes have a higher risk for erosion when other risk factors are present. Regurgitation of gastric acids is a further important risk factor for the development of erosion which has to be taken into account. Based on these analyses, an individually tailored preventive program may be suggested to the patients. It may comprise dietary advice, use of calcium-enriched beverages, optimization of prophylactic regimes, stimulation of salivary flow rate, use of buffering medicaments and particular motivation for nondestructive toothbrushing habits with an erosive-protecting toothpaste as well as rinsing solutions. Since erosion and abrasion often occur simultaneously, all of the causative components must be taken into consideration when planning preventive strategies but only those important and feasible for an individual should be communicated to the patient.
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Epoxyisoprostanes EI (1) and EC (2) are effective inhibitors of the secretion of proinflammatory cytokines IL-6 and IL-12. In detailed studies toward the investigation of the molecular mode of action of these structures, a highly potent lactone (3) derived from 1 was identified. The known isoprostanoids 1 and 2 are most likely precursors of 3, the product of facile intramolecular reaction between the epoxide with the carboxylic acid in 2.
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by Peter Wiernik
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High throughput discovery of ligand scaffolds for target proteins can accelerate development of leads and drug candidates enormously. Here we describe an innovative workflow for the discovery of high affinity ligands for the benzodiazepine-binding site on the so far not crystallized mammalian GABAA receptors. The procedure includes chemical biology techniques that may be generally applied to other proteins. Prerequisites are a ligand that can be chemically modified with cysteine-reactive groups, knowledge of amino acid residues contributing to the drug-binding pocket, and crystal structures either of proteins homologous to the target protein or, better, of the target itself. Part of the protocol is virtual screening that without additional rounds of optimization in many cases results only in low affinity ligands, even when a target protein has been crystallized. Here we show how the integration of functional data into structure-based screening dramatically improves the performance of the virtual screening. Thus, lead compounds with 14 different scaffolds were identified on the basis of an updated structural model of the diazepam-bound state of the GABAA receptor. Some of these compounds show considerable preference for the α3β2γ2 GABAA receptor subtype.
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Recent remarks of Pope Francis spark anew an important discussion: are we alone in the Universe? The article follows traces of the idea of extraterrestrial life throughout philosophy, evaluates the current considerations about the probability of extraterrestrial life and discusses the potential implications for the discovery of such life from a theological point of view. This “thought experiment” covers basic insights on creation, revelation and redemption.
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The next generation neutrino observatory proposed by the LBNO collaboration will address fundamental questions in particle and astroparticle physics. The experiment consists of a far detector, in its first stage a 20 kt LAr double phase TPC and a magnetised iron calorimeter, situated at 2300 km from CERN and a near detector based on a highpressure argon gas TPC. The long baseline provides a unique opportunity to study neutrino flavour oscillations over their 1st and 2nd oscillation maxima exploring the L/E behaviour, and distinguishing effects arising from δCP and matter. In this paper we have reevaluated the physics potential of this setup for determining the mass hierarchy (MH) and discovering CP-violation (CPV), using a conventional neutrino beam from the CERN SPS with a power of 750 kW. We use conservative assumptions on the knowledge of oscillation parameter priors and systematic uncertainties. The impact of each systematic error and the precision of oscillation prior is shown. We demonstrate that the first stage of LBNO can determine unambiguously the MH to > 5δ C.L. over the whole phase space. We show that the statistical treatment of the experiment is of very high importance, resulting in the conclusion that LBNO has ~ 100% probability to determine the MH in at most 4-5 years of running. Since the knowledge of MH is indispensable to extract δCP from the data, the first LBNO phase can convincingly give evidence for CPV on the 3δ C.L. using today’s knowledge on oscillation parameters and realistic assumptions on the systematic uncertainties.
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Findings on the consequences of casual sexual relationships (CSR) are inconsistent and range from positive to negative outcomes. The longitudinal association between stressful live events and CSR was investigated in a random sample of 2844 Swiss emerging adults. Cross-lagged panel models with baseline, two- and five-year follow-up data showed that life events predicted more subsequent CSR across emerging adulthood. In contrast, CSR predicted life events only from the first to the second wave. Results suggest that the link between stressful life events and CSR was mainly explained by romantic breakups as stressful life event. Environment-related life events were not substantially associated with casual sexual relationships. Thus, engaging in CSR did not seem to be a general emotion-focused coping strategy in the context of life events nor can the engagement in casual sex be seen as a result of stressful life events affecting general self-regulation.
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We discuss the topological nature of the boundary spacetime, the conformal infinity of the ambient cosmological metric. Due to the existence of a homothetic group, the bounding spacetime must be equipped not with the usual Euclidean metric topology but with the Zeeman fine topology. This then places severe constraints to the convergence of a sequence of causal curves and the extraction of a limit curve, and also to our ability to formulate conditions for singularity formation.
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Information-centric networking (ICN) enables communication in isolated islands, where fixed infrastructure is not available, but also supports seamless communication if the infrastructure is up and running again. In disaster scenarios, when a fixed infrastructure is broken, content discovery algorit hms are required to learn what content is locally available. For example, if preferred content is not available, users may also be satisfied with second best options. In this paper, we describe a new content discovery algorithm and compare it to existing Depth-first and Breadth-first traversal algorithms. Evaluations in mobile scenarios with up to 100 nodes show that it results in better performance, i.e., faster discovery time and smaller traffic overhead, than existing algorithms.