10,059 research outputs found

    A Bayesian approach to Lagrangian data assimilation

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    Lagrangian data arise from instruments that are carried by the flow in a fluid field. Assimilation of such data into ocean models presents a challenge due to the potential complexity of Lagrangian trajectories in relatively simple flow fields. We adopt a Bayesian perspective on this problem and thereby take account of the fully non-linear features of the underlying model. In the perfect model scenario, the posterior distribution for the initial state of the system contains all the information that can be extracted from a given realization of observations and the model dynamics. We work in the smoothing context in which the posterior on the initial conditions is determined by future observations. This posterior distribution gives the optimal ensemble to be used in data assimilation. The issue then is sampling this distribution. We develop, implement, and test sampling methods, based on Markov-chain Monte Carlo (MCMC), which are particularly well suited to the low-dimensional, but highly non-linear, nature of Lagrangian data. We compare these methods to the well-established ensemble Kalman filter (EnKF) approach. It is seen that the MCMC based methods correctly sample the desired posterior distribution whereas the EnKF may fail due to infrequent observations or non-linear structures in the underlying flow

    IUPHAR-DB: An Expert-Curated, Peer-Reviewed Database of Receptors and Ion Channels

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    The International Union of Basic and Clinical Pharmacology database (IUPHAR-DB) integrates peer-reviewed pharmacological, chemical, genetic, functional and anatomical information on the 354 non-sensory G protein-coupled receptors (GPCRs), 71 ligand-gated ion channel subunits and 141 voltage-gated ion channel subunits encoded by the human, rat and mouse genomes. These genes represent the targets of about a third of currently approved drugs and are a major focus of drug discovery and development programs in the pharmaceutical industry. Individual gene pages provide a comprehensive description of the genes and their functions, with information on protein structure, ligands, expression patterns, signaling mechanisms, functional assays and biologically important receptor variants (e.g. single nucleotide polymorphisms and splice variants). The phenotypes resulting from altered gene expression (e.g. in genetically altered animals) and genetic mutations are described. Links are provided to bioinformatics resources such as NCBI RefSeq, OMIM, PubChem, human, rat and mouse genome databases. Recent developments include the addition of ligand-centered pages summarising information about unique ligand molecules in IUPHAR-DB. IUPHAR-DB represents a novel approach to biocuration because most data are provided through manual curation of published literature by a network of over 60 expert subcommittees coordinated by NC-IUPHAR. Data are referenced to the primary literature and linked to PubMed. The data are checked to ensure accuracy and consistency by the curators, added to the production server using custom-built submission tools and peer-reviewed by NC-IUPHAR, before being transferred to the public database. Data are reviewed and updated regularly (at least biennially). Other website features include comprehensive database search tools, online and downloadable gene lists and links to recent publications of interest to the field, such as reports on receptor-ligand pairings. The database is freely available at "http://www.iuphar-db.org":http://www.iuphar-db.org. Curators can be reached at curators [at] iuphar-db.org. We thank British Pharmacological Society, UNESCO (through the ICSU Grants Programme), Incyte, GlaxoSmithKline, Novartis, Servier and Wyeth for their support

    A Bayesian approach to Lagrangian data assimilation

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    Groupoid normalizers of tensor products

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    We consider an inclusion B [subset of or equal to] M of finite von Neumann algebras satisfying B′∩M [subset of or equal to] B. A partial isometry vset membership, variantM is called a groupoid normalizer if vBv*,v*Bv[subset of or equal to] B. Given two such inclusions B<sub>i</sub> [subset of or equal to] M<sub>i</sub>, i=1,2, we find approximations to the groupoid normalizers of [formula] in [formula], from which we deduce that the von Neumann algebra generated by the groupoid normalizers of the tensor product is equal to the tensor product of the von Neumann algebras generated by the groupoid normalizers. Examples are given to show that this can fail without the hypothesis [formula], i=1,2. We also prove a parallel result where the groupoid normalizers are replaced by the intertwiners, those partial isometries vset membership, variantM satisfying vBv*[subset of or equal to] B and v*v,vv*[set membership, variant] B

    Similarities and Differences in Eyewitness Testimonies of Children Who Directly Versus Vicariously Experience Stress

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    This study tested questions of ecological validity by comparing the eyewitness testimonies of children directly experiencing a painful inoculation experience with those of children in a yoked-control group who vicariously experienced the inoculation on videotape. The study involved 86 5-year-olds, divided between 2 groups: the experiential and yoked control. The experiential group was followed through a health department with a video camera as they received diphtheria, pertussis, tetanus (DFT), and oral polio inoculations. They were tested immediately, 20 min later, and I month later. Each child in the yoked-control group merely watched the videotape of his or her counterpart in the expenential group, made similar ratings of pain, and was given the same tests and suggestions. Stress and personal experience affected items congruent with the stressor to produce flashbulb-like memories, with slower rates of forgetting for some items, such as nurse identifications, and greater suggestibility for other items, such as estimates of needle size. These and the apparently conflicting results in the literature were said to make sense when personally experienced stress was viewed from S.-A. Christianson’s (1992) interactive perspective rather than as a single ubiquitous variable

    Making sense of IL-6 signalling cues in pathophysiology

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    Unravelling the molecular mechanisms that account for functional pleiotropy is a major challenge for researchers in cytokine biology. Cytokine–receptor cross-reactivity and shared signalling pathways are considered primary drivers of cytokine pleiotropy. However, reports epitomized by studies of Jak-STAT cytokine signalling identify interesting biochemical and epigenetic determinants of transcription factor regulation that affect the delivery of signal-dependent cytokine responses. Here, a regulatory interplay between STAT transcription factors and their convergence to specific genomic enhancers support the fine-tuning of cytokine responses controlling host immunity, functional identity, and tissue homeostasis and repair. In this review, we provide an overview of the signalling networks that shape the way cells sense and interpret cytokine cues. With an emphasis on the biology of interleukin-6, we highlight the importance of these mechanisms to both physiological processes and pathophysiological outcomes

    Automation of large scale transient protein expression in mammalian cells

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    Traditional mammalian expression systems rely on the time-consuming generation of stable cell lines; this is difficult to accommodate within a modern structural biology pipeline. Transient transfections are a fast, cost-effective solution, but require skilled cell culture scientists, making man-power a limiting factor in a setting where numerous samples are processed in parallel. Here we report a strategy employing a customised CompacT SelecT cell culture robot allowing the large-scale expression of multiple protein constructs in a transient format. Successful protocols have been designed for automated transient transfection of human embryonic kidney (HEK) 293T and 293S GnTI⁻ cells in various flask formats. Protein yields obtained by this method were similar to those produced manually, with the added benefit of reproducibility, regardless of user. Automation of cell maintenance and transient transfection allows the expression of high quality recombinant protein in a completely sterile environment with limited support from a cell culture scientist. The reduction in human input has the added benefit of enabling continuous cell maintenance and protein production, features of particular importance to structural biology laboratories, which typically use large quantities of pure recombinant proteins, and often require rapid characterisation of a series of modified constructs. This automated method for large scale transient transfection is now offered as a Europe-wide service via the P-cube initiative

    Orbital evolution of P\v{r}\'{i}bram and Neuschwanstein

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    The orbital evolution of the two meteorites P\v{r}\'{i}bram and Neuschwanstein on almost identical orbits and also several thousand clones were studied in the framework of the N-body problem for 5000 years into the past. The meteorites moved on very similar orbits during the whole investigated interval. We have also searched for photographic meteors and asteroids moving on similar orbits. There were 5 meteors found in the IAU MDC database and 6 NEAs with currently similar orbits to P\v{r}\'{i}bram and Neuschwanstein. However, only one meteor 161E1 and one asteroid 2002 QG46 had a similar orbital evolution over the last 2000 years.Comment: 7 pages, 2 figures, 3 table

    Global inequities and political borders challenge nature conservation under climate change

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    Underlying sociopolitical factors have emerged as important determinants of wildlife population trends and the effectiveness of conservation action. Despite mounting research into the impacts of climate change on nature, there has been little consideration of the human context in which these impacts occur, particularly at the global scale. We investigate this in two ways. First, by modeling the climatic niches of terrestrial mammals and birds globally, we show that projected species loss under climate change is greatest in countries with weaker governance and lower Gross Domestic Product, with loss of mammal species projected to be greater in countries with lower CO2 emissions. Therefore, climate change impacts on species may be disproportionately significant in countries with lower capacity for effective conservation and lower greenhouse gas emissions, raising important questions of international justice. Second, we consider the redistribution of species in the context of political boundaries since the global importance of transboundary conservation under climate change is poorly understood. Under a high-emissions scenario, we find that 35% of mammals and 29% of birds are projected to have over half of their 2070 climatic niche in countries in which they are not currently found. We map these transboundary range shifts globally, identifying borders across which international coordination might most benefit conservation and where physical border barriers, such as walls and fences, may be an overlooked obstacle to climate adaptation. Our work highlights the importance of sociopolitical context and the utility of a supranational perspective for 21st century nature conservation
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