563 research outputs found

    Supporting research studies to booster flight control problems Final report

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    Asymptotic stability and response of nonlinear system

    TOC COMPLEX FORMATION: AN INVESTIGATION OF THE INTERACTIONS GOVERNING TOC COMPLEX COMPOSITION AND ASSEMBLY

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    Chloroplast-destined preproteins are translated in the cytosol, and posttranslationally targeted to and translocated across the double envelope membrane of the chloroplast by the coordinated activities of two translocon complexes: the Translocons at the Outer and Inner envelope membrane of the Chloroplast (TOC and TIC, respectively). In the model organism Arabidopsis thaliana the core TOC components include two families of GTPase receptors: TOC159 (atToc159, -132, and -120) and TOC34 (atToc33 and -34). These receptor families are hypothesized to assemble into distinct complexes and recognize transit peptides present on the N-terminus of chloroplast-destined preproteins. The GTPase domains of the TOC159 and TOC34 family members are hypothesized to interact in such a way that structurally and functionally distinct TOC complexes are formed. These distinct complexes are thought to have specificity for different subsets of preproteins. Chloroplasts must differentiate between different subsets of proteins because they are needed in different amounts during various stages of chloroplast biogenesis. This investigation examines the propensity for atToc33 and atToc34 to associate with atToc159 or atToc132, how these interactions affect TOC complex formation, as well as what protein domains are conferring this preference. In vitro competitive chloroplast targeting assays, in which the GTPase domains of atToc33 or atToc34 are used as competitors for targeting of atToc159 or atToc132 to chloroplasts, and in vitro solidphase binding assays, in which the GTPase domains of atToc33 or atToc34 are used as bait to test interactions with prey atToc159 or atToc132 are used to characterize these interactions. In order to study the influence of the highly divergent A-domain, these associations are also being investigated using A-domain deletion mutants, atToc159GM and atToc132GM as well as A-domain swapped mutants 159A132GM and 132A159GM. This investigation has revealed that the mechanisms governing TOC GTPase interactions in Arabidopsis may be dictated by the A-domain of atToc132 and the G-domain of atToc159, thereby giving insight into how key TOC components are assembled into distinct TOC complexes at the chloroplast surface. Distinct complexes are responsible for the critical identification and import of different subsets of preproteins, all of which are necessary for plant growth and development

    Proteomics: in pursuit of effective traumatic brain injury therapeutics

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    Effective traumatic brain injury (TBI) therapeutics remain stubbornly elusive. Efforts in the field have been challenged by the heterogeneity of clinical TBI, with greater complexity among underlying molecular phenotypes than initially conceived. Future research must confront the multitude of factors comprising this heterogeneity, representing a big data challenge befitting the coming informatics age. Proteomics is poised to serve a central role in prescriptive therapeutic development, as it offers an efficient endpoint within which to assess post-TBI biochemistry. We examine rationale for multifactor TBI proteomic studies and the particular importance of temporal profiling in defining biochemical sequences and guiding therapeutic development. Lastly, we offer perspective on repurposing biofluid proteomics to develop theragnostic assays with which to prescribe, monitor and assess pharmaceutics for improved translation and outcome for TBI patients

    Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts

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    BACKGROUND: The magnitude of the association between Helicobacter pylori and incidence of gastric cancer is unclear. H pylori infection and the circulating antibody response can be lost with development of cancer; thus retrospective studies are subject to bias resulting from classifi- cation of cases as H pylori negative when they were infected in the past. AIMS: To combine data from all case control studies nested within prospective cohorts to assess more reliably the relative risk of gastric cancer associated with H pylori infection.To investigate variation in relative risk by age, sex, cancer type and subsite, and interval between blood sampling and cancer diagnosis. METHODS: Studies were eligible if blood samples for H pylori serology were collected before diagnosis of gastric cancer in cases. Identified published studies and two unpublished studies were included. Individual subject data were obtained for each. Matched odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated for the association between H pylori and gastric cancer. RESULTS: Twelve studies with 1228 gastric cancer cases were considered. The association with H pylori was restricted to noncardia cancers (OR 3.0; 95% CI 2.3–3.8) and was stronger when blood samples for H pylori serology were collected 10+ years before cancer diagnosis (5.9; 3.4–10.3). H pylori infection was not associated with an altered overall risk of cardia cancer (1.0; 0.7–1.4). CONCLUSIONS: These results suggest that 5.9 is the best estimate of the relative risk of non-cardia cancer associated with H pylori infection and that H pylori does not increase the risk of cardia cancer. They also support the idea that when H pylori status is assessed close to cancer diagnosis, the magnitude of the non-cardia association may be underestimated

    Evidence that a Panel of Neurodegeneration Biomarkers Predicts Vasospasm, Infarction, and Outcome in Aneurysmal Subarachnoid Hemorrhage

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    Biomarkers for neurodegeneration could be early prognostic measures of brain damage and dysfunction in aneurysmal subarachnoid hemorrhage (aSAH) with clinical and medical applications. Recently, we developed a new panel of neurodegeneration biomarkers, and report here on their relationships with pathophysiological complications and outcomes following severe aSAH. Fourteen patients provided serial cerebrospinal fluid samples for up to 10 days and were evaluated by ultrasonography, angiography, magnetic resonance imaging, and clinical examination. Functional outcomes were assessed at hospital discharge and 6–9 months thereafter. Eight biomarkers for acute brain damage were quantified: calpain-derived α-spectrin N- and C-terminal fragments (CCSntf and CCSctf), hypophosphorylated neurofilament H

    Dose volume histogram‐based optimization of image reconstruction parameters for quantitative 90Y‐PET imaging

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147185/1/mp13269.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147185/2/mp13269_am.pd

    Calpain inhibition mediates autophagy-dependent protection against polyglutamine toxicity.

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    Over recent years, accumulated evidence suggests that autophagy induction is protective in animal models of a number of neurodegenerative diseases. Intense research in the field has elucidated different pathways through which autophagy can be upregulated and it is important to establish how modulation of these pathways impacts upon disease progression in vivo and therefore which, if any, may have further therapeutic relevance. In addition, it is important to understand how alterations in these target pathways may affect normal physiology when constitutively modulated over a long time period, as would be required for treatment of neurodegenerative diseases. Here we evaluate the potential protective effect of downregulation of calpains. We demonstrate, in Drosophila, that calpain knockdown protects against the aggregation and toxicity of proteins, like mutant huntingtin, in an autophagy-dependent fashion. Furthermore, we demonstrate that, overexpression of the calpain inhibitor, calpastatin, increases autophagosome levels and is protective in a mouse model of Huntington's disease, improving motor signs and delaying the onset of tremors. Importantly, long-term inhibition of calpains did not result in any overt deleterious phenotypes in mice. Thus, calpain inhibition, or activation of autophagy pathways downstream of calpains, may be suitable therapeutic targets for diseases like Huntington's disease.This is the published version of the manuscript. It is available online from NPG in Cell Death and Differentiaiton here: http://www.nature.com/cdd/journal/vaop/ncurrent/full/cdd2014151a.html

    Teknologi Dalam Pendidikan: Membantu Siswa Beradaptasi Dengan Revolusi Industri 4.0

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    The development of the industrial revolution demanded various changes in every activity, including in the field of education. Through technological developments in the learning process will be able to help students to face these challenges. This study aims to analyze the implementation of technology in education to help students face the challenges of the industrial revolution 4.0. This research is a descriptive qualitative research collecting data from literature study. The results of this study found that technology has a significant role in the world of education, especially in the era of the industrial revolution 4.0. Through the use of technology, students gain relevant skills and knowledge in the future. Then through the use of technology too, the creativity and innovation of students can be developed, as well as helping to establish social relations that are broader and also inclusive. Of course, in implementing this, careful planning is needed, so that the technolog
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