119 research outputs found

    Introduction

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    Spatiotemporal integration of molecular and anatomical data in virtual reality using semantic mapping

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    We have developed a computational framework for spatiotemporal integration of molecular and anatomical datasets in a virtual reality environment. Using two case studies involving gene expression data and pharmacokinetic data, respectively, we demonstrate how existing knowledge bases for molecular data can be semantically mapped onto a standardized anatomical context of human body. Our data mapping methodology uses ontological representations of heterogeneous biomedical datasets and an ontology reasoner to create complex semantic descriptions of biomedical processes. This framework provides a means to systematically combine an increasing amount of biomedical imaging and numerical data into spatiotemporally coherent graphical representations. Our work enables medical researchers with different expertise to simulate complex phenomena visually and to develop insights through the use of shared data, thus paving the way for pathological inference, developmental pattern discovery and biomedical hypothesis testing

    Seahawk: moving beyond HTML in Web-based bioinformatics analysis

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    <p>Abstract</p> <p>Background</p> <p>Traditional HTML interfaces for input to and output from Bioinformatics analysis on the Web are highly variable in style, content and data formats. Combining multiple analyses can therfore be an onerous task for biologists. Semantic Web Services allow automated discovery of conceptual links between remote data analysis servers. A shared data ontology and service discovery/execution framework is particularly attractive in Bioinformatics, where data and services are often both disparate and distributed. Instead of biologists copying, pasting and reformatting data between various Web sites, Semantic Web Service protocols such as MOBY-S hold out the promise of seamlessly integrating multi-step analysis.</p> <p>Results</p> <p>We have developed a program (Seahawk) that allows biologists to intuitively and seamlessly chain together Web Services using a data-centric, rather than the customary service-centric approach. The approach is illustrated with a ferredoxin mutation analysis. Seahawk concentrates on lowering entry barriers for biologists: no prior knowledge of the data ontology, or relevant services is required. In stark contrast to other MOBY-S clients, in Seahawk users simply load Web pages and text files they already work with. Underlying the familiar Web-browser interaction is an XML data engine based on extensible XSLT style sheets, regular expressions, and XPath statements which import existing user data into the MOBY-S format.</p> <p>Conclusion</p> <p>As an easily accessible applet, Seahawk moves beyond standard Web browser interaction, providing mechanisms for the biologist to concentrate on the analytical task rather than on the technical details of data formats and Web forms. As the MOBY-S protocol nears a 1.0 specification, we expect more biologists to adopt these new semantic-oriented ways of doing Web-based analysis, which empower them to do more complicated, <it>ad hoc </it>analysis workflow creation without the assistance of a programmer.</p

    Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

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    Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p &lt; 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM &gt; 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM &gt; 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

    Analysis of landrace cultivation in Europe: A means to support in situ conservation of crop diversity

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    During the last century, the progressive substitution of landraces with modern, high yielding varieties, led to a dramatic reduction of in situ conserved crop diversity in Europe. Nowadays there is limited and scattered information on where landraces are cultivated. To fill this gap and lay the groundwork for a regional landrace in situ conservation strategy, information on more than 19,335 geo-referenced landrace cultivation sites were collated from 14 European countries. According to collected data, landraces of 141 herbaceous and 48 tree species are cultivated across Europe: Italy (107 species), Greece (93), Portugal (45) and Spain (44) hold the highest numbers. Common bean, onion, tomato, potato and apple are the species of main interest in the covered countries. As from collected data, about 19.8% of landrace cultivation sites are in protected areas of the Natura 2000 network. We also got evidence that 16.7% and 19.3% of conservation varieties of agricultural species and vegetables are currently cultivated, respectively. Results of the GIS analysis allowed the identification of 1261 cells (25 km × 25 km) including all the cultivation sites, distributed across all European biogeographical regions. Data of this study constitute the largest ever produced database of in situ-maintained landraces and the first attempt to create an inventory for the entire Europe. The availability of such resource will serve for better planning of actions and development of policies to protect landraces and foster their use

    How Common is Common Human Reason?:The Plurality of Moral Perspectives and Kant’s Ethics

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    In his practical philosophy, Kant aims to systematize and ground a conception of morality that every human being already in some form is supposedly committed to in virtue of her common human reason. While Kantians especially in the last few years have explicitly acknowledged the central role of common human reason for a correct understanding of Kant’s ethics, there has been very little detailed critical discussion of the very notion of a common human reason as Kant envisages it. Sticker critically discusses in what ways Kant is committed to the notion that there are certain rational insights and rational capacities that all humans share, and thus investigates critically how Kant thinks moral normativity appears to the common human being, the rational agent who did not enjoy special education or philosophical training

    Soil enzyme activities, soil physical properties, photosynthetic physical characteristics and water use of winter wheat after long-term straw mulch and organic fertilizer application

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    IntroductionInappropriate residue and nutrient management leads to soil degradation and the decline of soil quality and water storage capacity.MethodsAn ongoing field experiment has been conducted since 2011 to investigate the effects of straw mulching (SM), and straw mulching combined with organic fertilizer (SM+O), on winter wheat yield, including a control treatment (CK, no straw). We studied the effects of these treatments on soil microbial biomass nitrogen and carbon, soil enzyme activity in 2019, photosynthetic parameters, evapotranspiration (ET), water use efficiency (WUE), and yields over five consecutive years (2015-2019). We also analyzed the soil organic carbon, soil structure, field capacity, and saturated hydraulic conductivity in 2015 and 2019. ResultsResults indicate that compared with CK, SM and SM+O treatments increased the proportion of &gt;0.25mm aggregates, soil organic carbon, field capacity, and saturated hydraulic conductivity, but decreased the soil bulk density. In addition, the SM and SM+O treatments also increased soil microbial biomass nitrogen and carbon, the activity of soil enzymes, and decreased the carbon-nitrogen ratio of microbial biomass. Therefore, SM and SM+O treatments both increased the leaf water use efficiency (LWUE) and photosynthetic rate (Pn), and improved the yields and water use efficiency (WUE) of winter wheat. The combination SM (4.5 t/ha)+O (0.75 t/ha) was more effective than SM alone, and both treatments were superior to the control.ConclusionBased on the results of this study, SM+O is recommended as the most effective cultivation practice

    Identification and Functional Analysis of a Novel von Willebrand Factor Mutation in a Family with Type 2A von Willebrand Disease

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    von Willebrand factor (VWF) is essential for normal hemostasis. VWF gene mutations cause the hemorrhagic von Willebrand disease (VWD). In this study, a 9-year-old boy was diagnosed as type 2A VWD, based on a history of abnormal bleeding, low plasma VWF antigen and activity, low plasma factor VIII activity, and lack of plasma high-molecular-weight (HMW) VWF multimers. Sequencing analysis detected a 6-bp deletion in exon 28 of his VWF gene, which created a mutant lacking D1529V1530 residues in VWF A2 domain. This mutation also existed in his family members with abnormal bleedings but not in >60 normal controls. In transfected HEK293 cells, recombinant VWF ΔD1529V1530 protein had markedly reduced levels in the conditioned medium (42±4% of wild-type (WT) VWF, p<0.01). The mutant VWF in the medium had less HMW multimers. In contrast, the intracellular levels of the mutant VWF in the transfected cells were significantly higher than that of WT (174±29%, p<0.05), indicating intracellular retention of the mutant VWF. In co-transfection experiments, the mutant reduced WT VWF secretion from the cells. By immunofluorescence staining, the retention of the mutant VWF was identified within the endoplasmic reticulum (ER). Together, we identified a unique VWF mutation responsible for the bleeding phenotype in a patient family with type 2A VWD. The mutation impaired VWF trafficking through the ER, thereby preventing VWF secretion from the cells. Our results illustrate the diversity of VWF gene mutations, which contributes to the wide spectrum of VWD
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