105 research outputs found
Operator pencils of the second order and linear fractional relations
The notions of a pencil of the second order and a linear fractional relation (LFR) are defined in spaces of linear bounded operators acting between Banach spaces. It is shown that these notions are closely connected with various theoretical and applied problems and have diverse applications. A number of the open problems, both for pencils and LFR, are posed in this paper. Some of the above problems are solved and applied to the study of dichotomic behavior of dynamical systems
Genetic homogenisation of two major orchid viruses through global trade‐based dispersal of their hosts
Orchid viruses are capable of causing flower deformities and death, which can se‐ verely impact the horticultural industry and wild orchid conservation. Here we show how two of these quickly evolving viruses display few genetic differences since their first emergence, across countries and host plants. This is concerning as, despite bios‐ ecurity regulations to control the movement of orchids and their related pathogens, these patterns are suggestive of rapid and regular international movement of horti‐ cultural material. Poor biosecurity practices could threaten the orchid horticultural industry and result in the accidental translocation or reintroduction of infected plant material intended to recover wild populations
The first small-molecule inhibitors of members of the ribonuclease E family
The Escherichia coli endoribonuclease RNase E is central to the processing and degradation of all types of RNA and as such is a pleotropic regulator of gene expression. It is essential for growth and was one of the first examples of an endonuclease that can recognise the 5′-monophosphorylated ends of RNA thereby increasing the efficiency of many cleavages. Homologues of RNase E can be found in many bacterial families including important pathogens, but no homologues have been identified in humans or animals. RNase E represents a potential target for the development of new antibiotics to combat the growing number of bacteria that are resistant to antibiotics in use currently. Potent small molecule inhibitors that bind the active site of essential enzymes are proving to be a source of potential drug leads and tools to dissect function through chemical genetics. Here we report the use of virtual high-throughput screening to obtain small molecules predicted to bind at sites in the N-terminal catalytic half of RNase E. We show that these compounds are able to bind with specificity and inhibit catalysis of Escherichia coli and Mycobacterium tuberculosis RNase E and also inhibit the activity of RNase G, a paralogue of RNase E
A Comprehensive Benchmark of Kernel Methods to Extract Protein–Protein Interactions from Literature
The most important way of conveying new findings in biomedical research is scientific publication. Extraction of protein–protein interactions (PPIs) reported in scientific publications is one of the core topics of text mining in the life sciences. Recently, a new class of such methods has been proposed - convolution kernels that identify PPIs using deep parses of sentences. However, comparing published results of different PPI extraction methods is impossible due to the use of different evaluation corpora, different evaluation metrics, different tuning procedures, etc. In this paper, we study whether the reported performance metrics are robust across different corpora and learning settings and whether the use of deep parsing actually leads to an increase in extraction quality. Our ultimate goal is to identify the one method that performs best in real-life scenarios, where information extraction is performed on unseen text and not on specifically prepared evaluation data. We performed a comprehensive benchmarking of nine different methods for PPI extraction that use convolution kernels on rich linguistic information. Methods were evaluated on five different public corpora using cross-validation, cross-learning, and cross-corpus evaluation. Our study confirms that kernels using dependency trees generally outperform kernels based on syntax trees. However, our study also shows that only the best kernel methods can compete with a simple rule-based approach when the evaluation prevents information leakage between training and test corpora. Our results further reveal that the F-score of many approaches drops significantly if no corpus-specific parameter optimization is applied and that methods reaching a good AUC score often perform much worse in terms of F-score. We conclude that for most kernels no sensible estimation of PPI extraction performance on new text is possible, given the current heterogeneity in evaluation data. Nevertheless, our study shows that three kernels are clearly superior to the other methods
Теорія та практика менеджменту безпеки
У збірнику подано тези доповідей та виступів учасників Міжнародної науково-практичної конференції, присвяченої питанням теорії менеджменту безпеки, безпеки особистості, прикладним аспектам забезпечення соціальної, екологічної, економічної безпеки підприємств, питанням механізму забезпечення соціоекологоекономічної безпеки регіону, проблемам забезпечення національної безпеки
Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19)
The SARS-CoV-2 virus spreading across the world has led to surges of COVID-19 illness, hospitalizations, and
death. The complex and multifaceted pathophysiology of life-threatening COVID-19 illness including viral mediated
organ damage, cytokine storm, and thrombosis warrants early interventions to address all components of the devastating
illness. In countries where therapeutic nihilism is prevalent, patients endure escalating symptoms and without
early treatment can succumb to delayed in-hospital
care and death. Prompt early initiation of sequenced multidrug
therapy (SMDT) is a widely and currently available
solution to stem the tide of hospitalizations and death. A
multipronged therapeutic approach includes 1) adjuvant
nutraceuticals, 2) combination intracellular anti-infective
therapy, 3) inhaled/oral corticosteroids, 4) antiplatelet
agents/anticoagulants, 5) supportive care including supplemental
oxygen, monitoring, and telemedicine. Randomized
trials of individual, novel oral therapies have not
delivered tools for physicians to combat the pandemic in
practice. No single therapeutic option thus far has been
entirely effective and therefore a combination is required
at this time. An urgent immediate pivot from single drug to
SMDT regimens should be employed as a critical strategy
to deal with the large numbers of acute COVID-19 patients
with the aim of reducing the intensity and duration
of symptoms and avoiding hospitalization and death
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