99 research outputs found

    Renal Function but Not Asymmetric Dimethylarginine Is Independently Associated with Retinopathy in Type 2 Diabetes

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    Background. Asymmetric dimethylarginine (ADMA) is associated with macrovascular disease and possibly with microangiopathy in type 2 diabetes (T2DM). We tested the hypothesis that ADMA is related to diabetic retinopathy (DR) independently of macrovascular disease. Methods. This cross-sectional study included 127 T2DM patients selected to achieve equal distributions of patients with and without macrovascular disease in the groups with and without DR. Results. Patients with DR had increased ADMA, longer diabetes duration, and reduced glomerular filtration rate (GFR). ADMA correlated with GFR (ρ = -0.35; P < .001), diabetes duration (ρ = 0.19; P = .048), and age (ρ = 0.19; P = .033). Logistic regression analysis revealed an association of ADMA with DR. After adjustment for macrovascular disease, this association remained significant (OR 1.48; 95% CI: 1.02–2.15; P = .039). Inclusion of GFR and T2DM duration into the model abolished this significant relationship. GFR remained the only independent predictor for DR. A 10 mL/min/1.73 m2 GFR decrease was associated with DR in a multivariate model (OR 1.30; 95% CI: 1.08–1.56; P = .006). Conclusions. These findings indicate an association between ADMA and DR in T2DM independent of macrovascular disease. This relationship is modified by GFR, the only parameter significantly related to DR in multivariate analysis

    Daten sammeln, modellieren und durchsuchen mit DARIAH - DE

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    Die sammlungsĂŒbergreifende Recherche und Nachnutzung geisteswissenschaftlicher Forschungsdaten stehen im Blickpunkt aktueller Forschung in den Digital Humanities. Obwohl das Interesse an einer ZusammenfĂŒhrung digitaler Forschungsdaten bereits kurz nach der EinfĂŒhrung erster digitaler Bibliotheken um die Jahrtausendwende entstand, bleibt die Integration von Forschungsdaten ĂŒber Sammlungsgrenzen hinweg ein aktuelles Forschungsthema. Bei einer forschungsorientierten Betrachtung von Sammlungen digitaler Daten (also z. B. digitale Texte, Digitalisate, Normdaten, Metadaten) stellt sich die Frage nach den Anforderungen und Erfolgskriterien einer ĂŒbergreifenden Föderation, Verarbeitung und Visualisierung von Forschungsdaten. Entgegen der in der Praxis ĂŒblichen Orientierung an institutionellen Anforderungen stellen die in DARIAH-DE entwickelten Konzepte und Dienste zur Verzeichnung, Korrelation und ZusammenfĂŒhrung von Forschungsdaten die BedĂŒrfnisse von WissenschaftlerInnen im Kontext ihrer Forschungsfragen in den Mittelpunkt. Dies Ă€ußert sich beispielsweise darin, dass DARIAH-DE keine strukturellen Bedingungen an Forschungsdaten stellt. Stattdessen können Daten so publiziert, modelliert und integriert werden, dass eine möglichst gute Passung an den jeweiligen geisteswissenschaftlichen Kontext erreicht wird

    Determination and optimization of material parameters of particle-based LaTiO2N photoelectrodes

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    We developed a validated numerical model capable of predicting the photocurrent-voltage characteristics of oxide and oxynitride particle-based photoelectrodes and identifying the critical parameters affecting the performance of those photoelectrodes. We used particle-based LaTiO2N photoelectrodes as the model system. Two different types of electrodes were studied: LaTiO2N photoelectrodes with TiO2 inter-particle connections and the same photoelectrodes with NiOx/CoOx/Co(OH)2 co-catalysts and a Ta2O5 passivation layer. The necessary material parameters, namely complex refractive index, permittivity, density of states of the conduction and valence bands, charge mobilities, flatband potential, doping concentration, recombination lifetimes, and interfacial hole transfer velocity, were derived by density functional theory calculations, dedicated experiments, and fitting of the numerically determined photocurrent-voltage curves to the measured ones under back-side illumination. The model was validated by comparing its prediction to front-side illumination photocurrent-voltage measurements. A parametric study was then carried out to provide an extensive set of material design guidelines and key parameters for high-performing particle-based LaTiO2N photoelectrodes. The interfacial hole transfer velocity was identified as the most significant parameter for the performance of LaTiO2N photoelectrodes

    Application of integrated transcriptomic, proteomic and metabolomic profiling for the delineation of mechanisms of drug induced cell stress

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    International audience; High content omic techniques in combination with stable human in vitro cell culture systems have the potential to improve on current pre-clinical safety regimes by providing detailed mechanistic information of altered cellular processes. Here we investigated the added benefit of integrating transcriptomics, proteomics and metabolomics together with pharmacokinetics for drug testing regimes. Cultured human renal epithelial cells (RPTEC/TERT1) were exposed to the nephrotoxin Cyclosporine A (CsA) at therapeutic and supratherapeutic concentrations for 14 days. CsA was quantified in supernatants and cellular lysates by LC-MS/MS for kinetic modeling. There was a rapid cellular uptake and accumulation of CsA, with a non-linear relationship between intracellular and applied concentrations. CsA at 15 ”M induced mitochondrial disturbances and activation of the Nrf2-oxidative-damage and the unfolded protein-response pathways. All three omic streams provided complementary information, especially pertaining to Nrf2 and ATF4 activation. No stress induction was detected with 5 ”M CsA; however, both concentrations resulted in a maximal secretion of cyclophilin B. The study demonstrates for the first time that CsA-induced stress is not directly linked to its primary pharmacology. In addition we demonstrate the power of integrated omics for the elucidation of signaling cascades brought about by compound induced cell stress
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