338 research outputs found

    Facile Route for Low-temperature Eco-friendly Solution Processed ZnSnO Thin-film Transistors

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    In this work, solution processed zinc tin oxide semiconductor films were investigated. Different from the widely reported high-temperature and toxic organic solvent-based fabrication process, a low temperature and eco-friendly aqueous solvent-based route was studied. The optimization of electrical performances on field effect mobility and reliability was proved. Moreover, a resistor-loaded inverter was constructed

    Advanced synaptic transistor device towards AI application in hardware perspective

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    For the past decades, the synaptic devices for the inmemory computing have been widely investigated due to the high-efficiency computing potential and the ability to mimic biological neurobehavior. However, the conventional twoterminal synaptic memristors show drawbacks of resistance reduction caused by large-scale paralleling and asynchronous storage-reading process, which limit its development. Recently, researchers have paid attention to the transistor-like artificial synapse. Due to the existence of insulator layer and the separation of input and read terminals, the three-terminal synaptic transistors are believed to have greater potential towards artificial intelligence (AI) application fields. In this work, a summary of recent progresses and the future challenges of synaptic transistors are discussed

    Agalsidase beta treatment is associated with improved quality of life in patients with Fabry disease: Findings from the Fabry Registry

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    Purpose: To evaluate the effect of agalsidase beta on longitudinal health-related quality of life in patients with Fabry disease. Methods: the SF-36 (R) Health Survey was used to measure health-related quality of life in Fabry Registry patients. Seventy-one men and 59 women who were treated with agalsidase beta (median dose: 1.0 mg/kg/2 weeks) and who had baseline and at least 2 yearly posttreatment health-related quality of life measurements were included in these analyses. A repeated measures model was used to analyze change in score from baseline. Results: Men improved in the physical component summary and in all eight scales of the SF-36 after 1 and 2 years and in the mental component summary after 1 year of agalsidase beta treatment (P < 0.05). Women improved in the mental component summary and in six of the eight scales after 1 and/or 2 years of treatment. Patients whose baseline SF-36 scores were below the median showed the greatest improvements. These responses were comparable with or greater than the published effects of various treatments for multiple sclerosis, rheumatoid arthritis, central neuropathic pain, and Gaucher disease. Conclusion: Long-term treatment with agalsidase beta resulted in substantial improvements in health-related quality of life in both men and women; the effect was more pronounced in men. Genet Med 2010:12(11):703 712.Genzyme CorporationGenzymeNatl Univ Hosp, Dept Endocrinol, DK-2100 Copenhagen, DenmarkSan Bassano Hosp, Dept Neurol, Bassano Del Grappa, ItalyUniv Padua, Dept Neurosci, Padua, ItalyUniv Wurzburg, Dept Med, Wurzburg, GermanyColumbia Univ, Dept Pediat, Div Clin Genet, Coll Phys & Surg, New York, NY 10027 USACincinnati Childrens Hosp, Div Human Genet, Cincinnati, OH USAUniversidade Federal de São Paulo, Inatos Metab CREIM, São Paulo, BrazilMassachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USAGenzyme Corp, Dept Biomed Data Sci & Informat, Cambridge, MA USAUniversidade Federal de São Paulo, Inatos Metab CREIM, São Paulo, BrazilWeb of Scienc

    Hypermethylation of CpG islands in the mouse asparagine synthetase gene: relationship to asparaginase sensitivity in lymphoma cells. Partial methylation in normal cells

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    We have sequenced the promoter region of the murine asparagine synthetase gene and examined its methylation profile in the CpG islands of L-asparaginase-sensitive 6C3HED cells (asparagine auxotrophs) and resistant variants (prototrophs). In the former, complete methylation of the CpG island is correlated with failure of expression of mRNA: cells of the latter possess both methylated and unmethylated alleles, as do cells of the intrinsically asparagine-independent lines L1210 and EL4. A similar phenomenon was seen in normal splenic cells of adult mice. This was age related: no methylation was found in weanlings, but up to 45% of gene copies in animals 18 weeks or older were methylated. It was also tissue related, with methylation occurring rarely in liver cells. The relationship of these changes to oncogenesis is considered. http://www.bjcancer.com © 2001 Cancer Research Campaignhttp://www.bjcancer.co

    Comparing the health of low income and less well educated groups in the United States and Canada

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    <p>Abstract</p> <p>Background</p> <p>A limited number of health status and health-related quality of life (HRQL) measures have been used for inter-country comparisons of population health. We compared the health of Canadians and Americans using a preference-based measure.</p> <p>Methods</p> <p>The Joint Canada/United States Survey of Health (JCUSH) 2002–03 conducted a comprehensive cross-sectional telephone survey on the health of community-dwelling residents in Canada and the US (n = 8688). A preference-based measure, the Health Utilities Index Mark 3 (HUI3), was included in the JCUSH. Health status was analyzed for the entire population and white population only in both countries. Mean HUI3 overall scores were compared for both countries. A linear regression determinants of health model was estimated to account for differences in health between Canada and the US. Estimation with bootstraps was used to derive variance estimates that account for the survey's complex sampling design of clustering and stratification.</p> <p>Results</p> <p>Income is associated with health in both countries. In the lowest income quintile, Canadians are healthier than Americans. At lower levels of education, again Canadians are healthier than Americans. Differences in health among subjects in the JCUSH are explained by age, gender, education, income, marital status, and country of residence.</p> <p>Conclusion</p> <p>On average, population health in Canada and the US is similar. However, health disparities between Canadians and Americans exist at lower levels of education and income with Americans worse off. The results highlight the usefulness of continuous preference-based measures of population health such as the HUI3.</p

    Replacement of α-galactosidase A in Fabry disease: effect on fibroblast cultures compared with biopsied tissues of treated patients

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    The function and intracellular delivery of enzyme therapeutics for Fabry disease were studied in cultured fibroblasts and in the biopsied tissues of two male patients to show diversity of affected cells in response to treatment. In the mutant fibroblasts cultures, the final cellular level of endocytosed recombinant α-galactosidases A (agalsidases, FabrazymeTM, and ReplagalTM) exceeded, by several fold, the amount in control fibroblasts and led to efficient direct intra-lysosomal hydrolysis of (3H)Gb3Cer. In contrast, in the samples from the heart and some other tissues biopsied after several months of enzyme replacement therapy (ERT) with FabrazymeTM, only the endothelial cells were free of storage. Persistent Gb3Cer storage was found in cardiocytes (accompanied by increase of lipopigment), smooth muscle cells, fibroblasts, sweat glands, and skeletal muscle. Immunohistochemistry of cardiocytes demonstrated, for the first time, the presence of a considerable amount of the active enzyme in intimate contact with the storage compartment. Factors responsible for the limited ERT effectiveness are discussed, namely post-mitotic status of storage cells preventing their replacement by enzyme supplied precursors, modification of the lysosomal system by longstanding storage, and possible relative lack of Sap B. These observations support the strategy of early treatment for prevention of lysosomal storage

    Computational Characterization of 3′ Splice Variants in the GFAP Isoform Family

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    Glial fibrillary acidic protein (GFAP) is an intermediate filament (IF) protein specific to central nervous system (CNS) astrocytes. It has been the subject of intense interest due to its association with neurodegenerative diseases, and because of growing evidence that IF proteins not only modulate cellular structure, but also cellular function. Moreover, GFAP has a family of splicing isoforms apparently more complex than that of other CNS IF proteins, consistent with it possessing a range of functional and structural roles. The gene consists of 9 exons, and to date all isoforms associated with 3′ end splicing have been identified from modifications within intron 7, resulting in the generation of exon 7a (GFAPδ/ε) and 7b (GFAPκ). To better understand the nature and functional significance of variation in this region, we used a Bayesian multiple change-point approach to identify conserved regions. This is the first successful application of this method to a single gene – it has previously only been used in whole-genome analyses. We identified several highly or moderately conserved regions throughout the intron 7/7a/7b regions, including untranslated regions and regulatory features, consistent with the biology of GFAP. Several putative unconfirmed features were also identified, including a possible new isoform. We then integrated multiple computational analyses on both the DNA and protein sequences from the mouse, rat and human, showing that the major isoform, GFAPα, has highly conserved structure and features across the three species, whereas the minor isoforms GFAPδ/ε and GFAPκ have low conservation of structure and features at the distal 3′ end, both relative to each other and relative to GFAPα. The overall picture suggests distinct and tightly regulated functions for the 3′ end isoforms, consistent with complex astrocyte biology. The results illustrate a computational approach for characterising splicing isoform families, using both DNA and protein sequences
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