400 research outputs found

    A study of cryogenic propellant mixing techniques. Volume 1 - Mixer design and experimental investigations Final report, Jul. 1967 - Sep. 1968

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    Mixer design and experimental tank study for cryogenic propellants, with applications for manned Mars missio

    Discovery, isolation and structural characterization of cyclotides from Viola sumatrana miq

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    Cyclotides are cyclic peptides from plants in the Violaceae, Rubiaceae, Fabaceae, Cucurbitaceae, and Solanaceae families. They are sparsely distributed in most of these families, but appear to be ubiquitous in the Violaceae, having been found in every plant so far screened from this family. However, not all geographic regions have been examined and here we report the discovery of cyclotides from a Viola species from South-East Asia. Two novel cyclotides (Visu 1 and Visu 2) and two known cyclotides (kalata S and kalata B1) were identified in V. sumatrana. NMR studies revealed that kalata S and kalata B1 had similar secondary structures. Their biological activities were determined in cytotoxicity assays; both had similar cytotoxic activity and were more toxic to U87 cells compared with other cell lines. Overall, the study strongly supports the ubiquity of cyclotides in the Violaceae and adds to our understanding of their distribution and cytotoxic activity

    From logical forms to SPARQL query with GETARUNS

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    We present a system for Question Answering which computes a prospective answer from Logical Forms produced by a full-fledged NLP for text understanding, and then maps the result onto schemata in SPARQL to be used for accessing the Semantic Web. As an intermediate step, and whenever there are complex concepts to be mapped, the system looks for a corresponding amalgam in YAGO classes. It is just by the internal structure of the Logical Form that we are able to produce a suitable and meaningful context for concept disambiguation. Logical Forms are the final output of a complex system for text understanding - GETARUNS - which can deal with different levels of syntactic and semantic ambiguity in the generation of a final structure, by accessing computational lexical equipped with sub-categorization frames and appropriate selectional restrictions applied to the attachment of complements and adjuncts. The system also produces pronominal binding and instantiates the implicit arguments, if needed, in order to complete the required Predicate Argument structure which is licensed by the semantic component

    Cell transformation assays for prediction of carcinogenic potential: State of the science and future research needs

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    Copyright @ 2011 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Cell transformation assays (CTAs) have long been proposed as in vitro methods for the identification of potential chemical carcinogens. Despite showing good correlation with rodent bioassay data, concerns over the subjective nature of using morphological criteria for identifying transformed cells and a lack of understanding of the mechanistic basis of the assays has limited their acceptance for regulatory purposes. However, recent drivers to find alternative carcinogenicity assessment methodologies, such as the Seventh Amendment to the EU Cosmetics Directive, have fuelled renewed interest in CTAs. Research is currently ongoing to improve the objectivity of the assays, reveal the underlying molecular changes leading to transformation and explore the use of novel cell types. The UK NC3Rs held an international workshop in November 2010 to review the current state of the art in this field and provide directions for future research. This paper outlines the key points highlighted at this meeting

    A short isoform of STIM1 confers frequency-dependent synaptic enhancement

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    Store-operated Ca2+-entry (SOCE) regulates basal and receptor-triggered Ca2+ signaling with STIM proteins sensing the endoplasmic reticulum (ER) Ca2+ content and triggering Ca2+ entry by gating Orai channels. Although crucial for immune cells, STIM1ā€™s role in neuronal Ca2+ homeostasis is controversial. Here, we characterize a splice variant, STIM1B, which shows exclusive neuronal expression and protein content surpassing conventional STIM1 in cerebellum and of significant abundance in other brain regions. STIM1B expression results in a truncated protein with slower kinetics of ER-plasma membrane (PM) cluster formation and ICRAC, as well as reduced inactivation. In primary wild-type neurons, STIM1B is targeted by its spliced-in domain B to presynaptic sites where it converts classic synaptic depression into Ca2+- and Orai-dependent short-term synaptic enhancement (STE) at high-frequency stimulation (HFS). In conjunction with altered STIM1 splicing in human Alzheimer disease, our findings highlight STIM1 splicing as an important regulator of neuronal calcium homeostasis and of synaptic plasticity

    A longer isoform of Stim1 is a negative SOCE regulator but increases cAMP-modulated NFAT signaling

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    Alternative splicing is a potent modifier of protein function. Stro mal interaction molecule 1 (Stim1) is the essential activator of store-operated Ca2+ entry (SOCE) triggering activation of transcrip tion factors. Here, we characterize Stim1A, a splice variant with an additional 31 amino acid domain inserted in frame within its cytosolic domain. Prominent expression of exon A is found in astro cytes, heart, kidney, and testes. Full-length Stim1A functions as a dominant-negative regulator of SOCE and ICRAC, facilitating sequence-specific fast calcium-dependent inactivation and desta bilizing gating of Orai channels. Downregulation or absence of native Stim1A results in increased SOCE. Despite reducing SOCE, Stim1A leads to increased NFAT translocation. Differential proteo mics revealed an interference of Stim1A with the cAMP-SOCE crosstalk by altered modulation of phosphodiesterase 8 (PDE8), resulting in reduced cAMP degradation and increased PIP5K activ ity, facilitating NFAT activation. Our study uncovers a hitherto unknown mechanism regulating NFAT activation and indicates that cell-type-specific splicing of Stim1 is a potent means to regu late the NFAT signalosome and cAMP-SOCE crosstalk
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