44 research outputs found

    Integrating Research Results into a Power Engineering Curriculum

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    This paper presents summaries of the activities of six research active power engineering educators which were presented in a panel session of the same name at the IEEE Power Engineering Society Winter Meeting on February 3, 1997 in New York City, USA. Each of the panelists discusses how research results are incorporated into courses and how students benefit from this approach

    Genetic Evidence Implicates the Immune System and Cholesterol Metabolism in the Aetiology of Alzheimer's Disease

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    Background 1Late Onset Alzheimer's disease (LOAD) is the leading cause of dementia. Recent large genome-wide association studies (GWAS) identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes. Methodology We applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset. Principal Findings We found a significant overrepresentation of association signals in pathways related to cholesterol metabolism and the immune response in both of the two largest genome-wide association studies for LOAD. Significance Processes related to cholesterol metabolism and the innate immune response have previously been implicated by pathological and epidemiological studies of Alzheimer's disease, but it has been unclear whether those findings reflected primary aetiological events or consequences of the disease process. Our independent evidence from two large studies now demonstrates that these processes are aetiologically relevant, and suggests that they may be suitable targets for novel and existing therapeutic approaches

    Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

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    We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10−5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10−17; including ADGC data, meta P = 5.0 × 10−21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10−14; including ADGC data, meta P = 1.2 × 10−16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10−4; including ADGC data, meta P = 8.6 × 10−9), CD33 (GERAD+, P = 2.2 × 10−4; including ADGC data, meta P = 1.6 × 10−9) and EPHA1 (GERAD+, P = 3.4 × 10−4; including ADGC data, meta P = 6.0 × 10−10)

    Correction: genetic evidence implicates the immune system and cholesterol metabolism in the aetiology of Alzheimer's disease.

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    [This corrects the article on p. e13950 in vol. 5.]. Background: Late Onset Alzheimer's disease (LOAD) is the leading cause of dementia. Recent large genome-wide association studies (GWAS) identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes. Methodology: We applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset. Principal Findings: We found a significant overrepresentation of association signals in pathways related to cholesterol metabolism and the immune response in both of the two largest genome-wide association studies for LOAD. Significance: Processes related to cholesterol metabolism and the innate immune response have previously been implicated by pathological and epidemiological studies of Alzheimer's disease, but it has been unclear whether those findings reflected primary aetiological events or consequences of the disease process. Our independent evidence from two large studies now demonstrates that these processes are aetiologically relevant, and suggests that they may be suitable targets for novel and existing therapeutic approaches

    Green synthesis, characterization and drug-loaded iron oxide nanoparticles derived from Nerium oleander flower extract as a nanocarrier for in vitro antibacterial efficacy

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    Application of drug conjugated iron oxide hematite ( α -Fe _2 O _3 ) nanoparticles are of tremendous interest in biomedicine nowadays. Meanwhile, green production of iron oxide nanoparticles is gaining favour due to its sustainability, ease of usage, and biocompatibility. Therefore, this work reports on the use of hexahydrate ferric chloride and nerium oleander flower extract to synthesize nanoscaled hematite ( α -Fe _2 O _3 ) iron oxide particles conjugated with various drugs for antibacterial agents. Diverse morphological, physicochemical, structural, optical, and magnetic characteristics have been characterized using FESEM, EDX, XRD, UV–vis, FTIR, Raman and vibrating sample magnetometer. The synthesis of the polyshaped iron oxide nanoparticles, with average sizes ranging from 47.2 ± 20 nm, was accomplished. Furthermore, temperature-dependent variations in magnetic behavior were observed during calcination. The XRD and Raman spectra revealed hematite ( α -Fe _2 O _3 ) type formation of iron oxide nanoparticles. Only calcinated IO-NPs at high temperatures (700 °C) demonstrated low coercivity and residual magnetism, which revealed weak ferromagnetic ordering; other calcinated samples, including nascent ones, showed incredibly weak ferromagnetic ordering. Besides, the effectiveness of drug-encapsulated iron oxide nanoparticles against bacteria in vitro was examined. It was interesting to observe that gentamycin-coated IO-NPs tended to be more susceptible to S. aureus than E. coli bacteria, but streptomycin-conjugated IO-NPs showed the reverse trend. However, as compared to the nascent sample and the high temperature (700 °C) calcinated sample, both antibiotic-loaded IO-NPs displayed better inhibitory abilities

    Long-Term Lithium Therapy and Thyroid Disorders in Bipolar Disorder: A Historical Cohort Study

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    Lithium has been a cornerstone treatment for bipolar disorder (BD). Despite descriptions in the literature regarding associations between long-term lithium therapy (LTLT) and development of a thyroid disorder (overt/subclinical hypo/hyperthyroidism, thyroid nodule, and goiter) in BD, factors such as time to onset of thyroid abnormalities and impact on clinical outcomes in the course of illness have not been fully characterized. In this study we aimed to compare clinical characteristics of adult BD patients with and without thyroid disorders who were on LTLT. We aimed to identify the incidence of thyroid disorders in patients with BD on LTLT and response to lithium between patients with and without thyroid disorders in BD. The Cox proportional model was used to find the median time to the development of a thyroid disorder. Our results showed that up to 32% of patients with BD on LTLT developed a thyroid disorder, of which 79% developed hypothyroidism, which was corrected with thyroid hormone replacement. We did not find significant differences in lithium response between patients with or without thyroid disorders in BD. Findings from this study suggest that patients with BD and comorbid thyroid disorders when adequately treated have a response to lithium similar to patients with BD and no thyroid disorders

    Mouse models of neurodegenerative diseases: criteria and general methodology

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    The major symptom of Alzheimer's disease is rapidly progressing dementia, coinciding with the formation of amyloid and tau deposits in the central nervous system, and neuronal death. At present familial cases of dementias provide the most promising foundation for modelling neurodegeneration. We describe the mnemonic and other major behavioral symptoms of tauopathies, briefly outline the genetics underlying familiar cases and discuss the arising implications for modelling the disease in mostly transgenic mouse lines. We then depict to what degree the most recent mouse models replicate pathological and cognitive characteristics observed in patients.There is no universally valid behavioral test battery to evaluate mouse models. The selection of individual tests depends on the behavioral and/or memory system in focus, the type of a model and how well it replicates the pathology of a disease and the amount of control over the genetic background of the mouse model. However it is possible to provide guidelines and criteria for modelling the neurodegeneration, setting up the experiments and choosing relevant tests. One should not adopt a "one (trans)gene, one disease" interpretation, but should try to understand how the mouse genome copes with the protein expression of the transgene in question. Further, it is not possible to recommend some mouse models over others since each model is valuable within its own constraints, and the way experiments are performed often reflects the idiosyncratic reality of specific laboratories. Our purpose is to improve bridging molecular and behavioural approaches in translational research

    Genetic Predisposition to Increased Blood Cholesterol and Triglyceride Lipid Levels and Risk of Alzheimer Disease:A Mendelian Randomization Analysis

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