Solving semantic ambiguity to improve semantic web based ontology matching

A new paradigm in Semantic Web research focuses on the development of a new generation of knowledge-based problem solvers, which can exploit the massive amounts of formally specified information available on the Web, to produce novel intelligent functionalities. An important example of this paradigm can be found in the area of Ontology Matching, where new algorithms, which derive mappings from an exploration of multiple and heterogeneous online ontologies, have been proposed. While these algorithms exhibit very good performance, they rely on merely syntactical techniques to anchor the terms to be matched to those found on the Semantic Web. As a result, their precision can be affected by ambiguous words. In this paper, we aim to solve these problems by introducing techniques from Word Sense Disambiguation, which validate the mappings by exploring the semantics of the ontological terms involved in the matching process. Specifically we discuss how two techniques, which exploit the ontological context of the matched and anchor terms, and the information provided by WordNet, can be used to filter out mappings resulting from the incorrect anchoring of ambiguous terms. Our experiments show that each of the proposed disambiguation techniques, and even more their combination, can lead to an important increase in precision, without having too negative an impact on recall

Urgência e Emergência. Os conceitos frente às normas administrativas e legais e suas implicações na clínica médica.

The emergency and the urgent situation present distinct concepts for those who provide medical service, for those who receive it, for those who pay for it and for those who legislate on the matter. Conceptual distinctions found in prepaid health plan legislation and in administrative regulations require that the health professional, in his requests for exams, procedures, and hospitalizations, extensively describe the clinical situation, to prevent the situation where the patient is left with the burden of proving his need for prompt healthcare to the health care provider or in court. This is because Federal Law 9.656 restricted the concept of urgency to situations of personal accidents and gestational complications and excluded situations of intense suffering from emergencies. It expanded, however, the concept of emergencies so that the health plan has to cover cases where there is a risk of irreparable damage to the patient. It provided an extended definition for immediate treatment, which could be offered within 24 hours. The studied jurisprudence indicated the importance of medico-legal documents for characterizing the clinical condition of the patient and guaranteeing his rights with respect to his health plan contract.As situações de emergência e de urgência apresentam conceitos distintos para aqueles que prestam o serviço médico, para quem o recebe, para quem paga pelos serviços e para aqueles que legislam sobre a matéria. Distinções conceituais encontradas na legislação de planos de saúde e nas normativas administrativas demandam que o profissional da saúde, em seus pedidos de exames, procedimentos e internações, descreva a situação clínica de forma extensiva para não imputar ao paciente o ônus de comprovar a necessidade de pronto atendimento junto aos prestadores de serviço e, eventualmente, na Justiça. Isso porque a Lei no 9.656 restringiu o conceito de urgência para situações de acidentes pessoais e complicações gestacionais e excluiu das emergências as situações de sofrimento intenso. Ampliou, contudo, o conceito de emergências, que abarca cobertura de casos em que há risco de ocorrerem lesões irreparáveis para o paciente. Conferiu definição extensiva para tratamento imediato, que passou a poder ser oferecido em até 24 horas. A jurisprudência estudada indicou a importância dos documentos médico-legais na caracterização dos quadros clínicos e garantia dos direitos frente aos contratos de planos de saúde

An optogenetic gene expression system with rapid activation and deactivation kinetics

Optogenetic gene expression systems can control transcription with spatial and temporal detail unequaled with traditional inducible promoter systems. However, current eukaryotic light-gated transcription systems are limited by toxicity, dynamic range, or slow activation/deactivation. Here we present an optogenetic gene expression system that addresses these shortcomings and demonstrate its broad utility. Our approach utilizes an engineered version of EL222, a bacterial Light-Oxygen-Voltage (LOV) protein that binds DNA when illuminated with blue light. The system has a large (\u3e100-fold) dynamic range of protein expression, rapid activation (\u3c 10 s) and deactivation kinetics (\u3c 50 s), and a highly linear response to light. With this system, we achieve light-gated transcription in several mammalian cell lines and intact zebrafish embryos with minimal basal gene activation and toxicity. Our approach provides a powerful new tool for optogenetic control of gene expression in space and time

HnRNP L and L-like cooperate in multiple-exon regulation of CD45 alternative splicing

CD45 encodes a trans-membrane protein-tyrosine phosphatase expressed in diverse cells of the immune system. By combinatorial use of three variable exons 4–6, isoforms are generated that differ in their extracellular domain, thereby modulating phosphatase activity and immune response. Alternative splicing of these CD45 exons involves two heterogeneous ribonucleoproteins, hnRNP L and its cell-type specific paralog hnRNP L-like (LL). To address the complex combinatorial splicing of exons 4–6, we investigated hnRNP L/LL protein expression in human B-cells in relation to CD45 splicing patterns, applying RNA-Seq. In addition, mutational and RNA-binding analyses were carried out in HeLa cells. We conclude that hnRNP LL functions as the major CD45 splicing repressor, with two CA elements in exon 6 as its primary target. In exon 4, one element is targeted by both hnRNP L and LL. In contrast, exon 5 was never repressed on its own and only co-regulated with exons 4 and 6. Stable L/LL interaction requires CD45 RNA, specifically exons 4 and 6. We propose a novel model of combinatorial alternative splicing: HnRNP L and LL cooperate on the CD45 pre-mRNA, bridging exons 4 and 6 and looping out exon 5, thereby achieving full repression of the three variable exons

Optogenetic Control of Subcellular Protein Location and Signaling in Vertebrate Embryos.

This chapter describes the use of optogenetic heterodimerization in single cells within whole-vertebrate embryos. This method allows the use of light to reversibly bind together an "anchor" protein and a "bait" protein. Proteins can therefore be directed to specific subcellular compartments, altering biological processes such as cell polarity and signaling. I detail methods for achieving transient expression of fusion proteins encoding the phytochrome heterodimerization system in early zebrafish embryos (Buckley et al., Dev Cell 36(1):117-126, 2016) and describe the imaging parameters used to achieve subcellular light patterning

Co-regulation of alternative splicing by diverse splicing factors in Caenorhabditis elegans

Regulation of alternative splicing is controlled by pre-mRNA sequences (cis-elements) and trans-acting protein factors that bind them. The combinatorial interactions of multiple protein factors with the cis-elements surrounding a given alternative splicing event lead to an integrated splicing decision. The mechanism of multifactorial splicing regulation is poorly understood. Using a splicing-sensitive DNA microarray, we assayed 352 Caenorhabditis elegans alternative cassette exons for changes in embryonic splicing patterns between wild-type and 12 different strains carrying mutations in a splicing factor. We identified many alternative splicing events that are regulated by multiple splicing factors. Many splicing factors have the ability to behave as splicing repressors for some alternative cassette exons and as splicing activators for others. Unexpectedly, we found that the ability of a given alternative splicing factor to behave as an enhancer or repressor of a specific splicing event can change during development. Our observations that splicing factors can change their effects on a substrate during development support a model in which combinatorial effects of multiple factors, both constitutive and developmentally regulated ones, contribute to the overall splicing decision

Dual-controlled optogenetic system for the rapid down-regulation of protein levels in mammalian cells

Abstract Optogenetic switches are emerging molecular tools for studying cellular processes as they offer higher spatiotemporal and quantitative precision than classical, chemical-based switches. Light-controllable gene expression systems designed to upregulate protein expression levels meanwhile show performances superior to their chemical-based counterparts. However, systems to reduce protein levels with similar efficiency are lagging behind. Here, we present a novel two-component, blue light-responsive optogenetic OFF switch (‘Blue-OFF’), which enables a rapid and quantitative down-regulation of a protein upon illumination. Blue-OFF combines the first light responsive repressor KRAB-EL222 with the protein degradation module B-LID (blue light-inducible degradation domain) to simultaneously control gene expression and protein stability with a single wavelength. Blue-OFF thus outperforms current optogenetic systems for controlling protein levels. The system is described by a mathematical model which aids in the choice of experimental conditions such as light intensity and illumination regime to obtain the desired outcome. This approach represents an advancement of dual-controlled optogenetic systems in which multiple photosensory modules operate synergistically. As exemplified here for the control of apoptosis in mammalian cell culture, the approach opens up novel perspectives in fundamental research and applications such as tissue engineering

Long-baseline neutrino oscillation physics potential of the DUNE experiment

The sensitivity of the Deep Underground Neutrino Experiment (DUNE) to neutrino oscillation is determined, based on a full simulation, reconstruction, and event selection of the far detector and a full simulation and parameterized analysis of the near detector. Detailed uncertainties due to the flux prediction, neutrino interaction model, and detector effects are included. DUNE will resolve the neutrino mass ordering to a precision of 5σ, for all ΑCP values, after 2 years of running with the nominal detector design and beam configuration. It has the potential to observe charge-parity violation in the neutrino sector to a precision of 3σ (5σ) after an exposure of 5 (10) years, for 50% of all ΑCP values. It will also make precise measurements of other parameters governing long-baseline neutrino oscillation, and after an exposure of 15 years will achieve a similar sensitivity to sin22θ13 to current reactor experiments