105 research outputs found

    An all-ZnO microbolometer for infrared imaging

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    Cataloged from PDF version of article.Microbolometers are extensively used for uncooled infrared imaging applications. These imaging units generally employ vanadium oxide or amorphous silicon as the active layer and silicon nitride as the absorber layer. However, using different materials for active and absorber layers increases the fabrication and integration complexity of the pixel structure. In order to reduce fabrication steps and therefore increase the yield and reduce the cost of the imaging arrays, a single layer can be employed both as the absorber and the active material. In this paper, we propose an all-ZnO microbolometer, where atomic layer deposition grown zinc oxide is employed both as the absorber and the active material. Optical constants of ZnO are measured and fed into finite-difference-time-domain simulations where absorption performances of microbolometers with different gap size and ZnO film thicknesses are extracted. Using the results of these optical simulations, thermal simulations are conducted using finite-element-method in order to extract the noise equivalent temperature difference (NETD) and thermal time constant values of several bolometer structures with different gap sizes, arm and film thicknesses. It is shown that the maximum performance of 171 mK can be achieved with a body thickness of 1.1 μm and arm thickness of 50 nm, while the fastest response with a time constant of 0.32 ms can be achieved with a ZnO thickness of 150 nm both in arms and body. © 2014 Elsevier B.V. All rights reserved

    The metabolic syndrome is not associated with homocysteinemia: The Persian Gulf Healthy Heart Study

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    Background: It is uncertain whether homocysteine and the metabolic syndrome or its components are related in the general population, as studies investigating the association between homocysteine levels and insulin resistance have shown conflicting results. Methods: In an ancillary study to the Persian Gulf Healthy Heart Study, a cohort study of Iranian men and women aged ≥25 yr, a random sample of 1754 subjects were evaluated for the association of plasma homocysteine levels and the metabolic syndrome using National Cholesterol Education Program (NCEP)-Adult Treatment Panel (ATP)-III criteria. Total homocysteine levels and high sensitivity C-reactive protein (CRP) were determined by enzyme-linked immunosorbent assays. Results: Subjects with lower HDL-cholesterol and higher blood pressure showed significantly higher homocysteine levels (p=0.001 and p<0.0001; respectively). There was no significant difference in serum levels of homocysteine between subjects with and without the metabolic syndrome. In multiple logistic regression analysis, the metabolic syndrome did not show a significant association with serum homocysteine levels after adjusting for sex, age, smoking, fruit and vegetable intake pattern, body mass index, and physical inactivity. Concurrent elevated CRP levels and the metabolic syndrome also did not show a significant association with serum homocysteine levels after adjusting for sex, age, and lifestyle cardiovascular risk factors. Conclusions: There was no association between the metabolic syndrome using NCEP-ATPIII criteria and homocysteinemia in this study. These data refute the hypothesis that homocysteine levels are influenced by the metabolic syndrome, at least in general healthy population

    DOGS: Reaction-Driven de novo Design of Bioactive Compounds

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    We present a computational method for the reaction-based de novo design of drug-like molecules. The software DOGS (Design of Genuine Structures) features a ligand-based strategy for automated ‘in silico’ assembly of potentially novel bioactive compounds. The quality of the designed compounds is assessed by a graph kernel method measuring their similarity to known bioactive reference ligands in terms of structural and pharmacophoric features. We implemented a deterministic compound construction procedure that explicitly considers compound synthesizability, based on a compilation of 25'144 readily available synthetic building blocks and 58 established reaction principles. This enables the software to suggest a synthesis route for each designed compound. Two prospective case studies are presented together with details on the algorithm and its implementation. De novo designed ligand candidates for the human histamine H4 receptor and γ-secretase were synthesized as suggested by the software. The computational approach proved to be suitable for scaffold-hopping from known ligands to novel chemotypes, and for generating bioactive molecules with drug-like properties

    Inhibitors of Helicobacter pylori Protease HtrA Found by ‘Virtual Ligand’ Screening Combat Bacterial Invasion of Epithelia

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    Background: The human pathogen Helicobacter pylori (H. pylori) is a main cause for gastric inflammation and cancer. Increasing bacterial resistance against antibiotics demands for innovative strategies for therapeutic intervention. Methodology/Principal Findings: We present a method for structure-based virtual screening that is based on the comprehensive prediction of ligand binding sites on a protein model and automated construction of a ligand-receptor interaction map. Pharmacophoric features of the map are clustered and transformed in a correlation vector (‘virtual ligand’) for rapid virtual screening of compound databases. This computer-based technique was validated for 18 different targets of pharmaceutical interest in a retrospective screening experiment. Prospective screening for inhibitory agents was performed for the protease HtrA from the human pathogen H. pylori using a homology model of the target protein. Among 22 tested compounds six block E-cadherin cleavage by HtrA in vitro and result in reduced scattering and wound healing of gastric epithelial cells, thereby preventing bacterial infiltration of the epithelium. Conclusions/Significance: This study demonstrates that receptor-based virtual screening with a permissive (‘fuzzy’) pharmacophore model can help identify small bioactive agents for combating bacterial infection

    Drug Discovery Using Chemical Systems Biology: Identification of the Protein-Ligand Binding Network To Explain the Side Effects of CETP Inhibitors

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    Systematic identification of protein-drug interaction networks is crucial to correlate complex modes of drug action to clinical indications. We introduce a novel computational strategy to identify protein-ligand binding profiles on a genome-wide scale and apply it to elucidating the molecular mechanisms associated with the adverse drug effects of Cholesteryl Ester Transfer Protein (CETP) inhibitors. CETP inhibitors are a new class of preventive therapies for the treatment of cardiovascular disease. However, clinical studies indicated that one CETP inhibitor, Torcetrapib, has deadly off-target effects as a result of hypertension, and hence it has been withdrawn from phase III clinical trials. We have identified a panel of off-targets for Torcetrapib and other CETP inhibitors from the human structural genome and map those targets to biological pathways via the literature. The predicted protein-ligand network is consistent with experimental results from multiple sources and reveals that the side-effect of CETP inhibitors is modulated through the combinatorial control of multiple interconnected pathways. Given that combinatorial control is a common phenomenon observed in many biological processes, our findings suggest that adverse drug effects might be minimized by fine-tuning multiple off-target interactions using single or multiple therapies. This work extends the scope of chemogenomics approaches and exemplifies the role that systems biology has in the future of drug discovery

    Light regulation of metabolic pathways in fungi

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    Light represents a major carrier of information in nature. The molecular machineries translating its electromagnetic energy (photons) into the chemical language of cells transmit vital signals for adjustment of virtually every living organism to its habitat. Fungi react to illumination in various ways, and we found that they initiate considerable adaptations in their metabolic pathways upon growth in light or after perception of a light pulse. Alterations in response to light have predominantly been observed in carotenoid metabolism, polysaccharide and carbohydrate metabolism, fatty acid metabolism, nucleotide and nucleoside metabolism, and in regulation of production of secondary metabolites. Transcription of genes is initiated within minutes, abundance and activity of metabolic enzymes are adjusted, and subsequently, levels of metabolites are altered to cope with the harmful effects of light or to prepare for reproduction, which is dependent on light in many cases. This review aims to give an overview on metabolic pathways impacted by light and to illustrate the physiological significance of light for fungi. We provide a basis for assessment whether a given metabolic pathway might be subject to regulation by light and how these properties can be exploited for improvement of biotechnological processes

    The analysis of factors affecting prognosis in fournier's gangrene and the importance of severity scores: Our results in fifty-two patients

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    Background: Fournier's gangrene (FG) is a rare, an acute, rapidly progressive, fatal necrotizing fasciitis of the genital, perianal and perineal areas. The incidence of mortality is still high, and mortality increases with age. In this study we purposed our experience in the treatment of FG and to determine risk factors affecting prognosis. Methods: Fifty-two patients operated for FG who presented at our hospital from January 2009 to December 2014 were investigated retrospectively. Patients were divided into two groups; surviving and non-surviving. Groups were compared regarding demographic features, vital signs and laboratory analysis, FG severity scores and surgical treatment requirements. Results: Mean age was 56.4 years, and female/male ratio was 20/32. The mortality rate was 9.6% (5 patients), and significantly higher in men (80%). The two most common etiological factors were soft tissue infection (63.5%) and anorectal diseases (28.8%). There was difference between groups in terms of requirements fecal diversion, respiratory rate, potassium and urea levels (p<0.05). There was significant difference between groups according to the FG severity index (FGSI) and Uludag FGSI (respectively p=0.001 and p=0.002). There were no significant difference between groups according to the duration of symptoms and hospitalization, use of antibiotic, etiology, wound culture and debridement number. Conclusions: FG is an unpredictable fulminant disease and there is need for new proposals to reduce morbidity and mortality. In our study, male gender, hypokalemia, uremia and increased respiratory rate at first presentation, and having a neurological disease were found to be the factors affecting mortality in FG patients

    The predictive value of Alvarado score, inflammatory parameters and ultrasound imaging in the diagnosis of acute appendicitis

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    Objective: Acute appendicitis (AA) is one of the most common surgical emergencies. Despite extraordinary advances in modern investigations, the accurate diagnosis of AA remains an enigmatic challenge. The aim of this study was to compare and evaluate the diagnostic accuracy of inflammatory parameters [C-reactive protein (CRP), procalcitonin (PCT), erythrocyte sedimentation rate (ESR)], ultrasound (US) and Alvarado score (AS) in reducing the rate of negative appendectomies. Material and Methods: Two hundred seventy-eight patients were included in this study. Patients were separated into two main groups as the surgery group (n=184) and non-operative group (n=94). Complete blood count, ESR and PCT levels were assessed, abdominal US was performed and AS was calculated for all patients. Results: In the surgery group, clinical predictive factors for histopathologic results such as AS ?7, AA signs on US, neutrophilia and leukocytosis were significant. Neutrophilia and leukocytosis had the highest accuracy rate among these factors. Inflammatory parameters were not predictive for histopathologic results, although higher CRP and PCT levels were significant in perforated and necrotizing appendicitis. Multifactorial regression analyses showed that AS was not of significant predictive value in the non-operative group. Conclusion: There was no superiority of AS and/or US in the diagnosis of AA. Recent findings have shown the most reliable parameters in the diagnosis of AA to be primarily 'neutrophilia' and secondarily 'leukocytosis'. Other results of this study indicated that inflammatory parameters (CRP, PCT, ESR) were not superior to other parameters but CRP and PCT levels were significantly high in complicated cases. © Copyright 2016 by Turkish Surgical Association Available

    Fuzzy virtual ligands for virtual screening

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