1,046 research outputs found

    Development of Simulators for Electrochemical Responses: Experimental and Pedagogical Applications

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    The work carried out in this CRADA addressed the development of computational algorithms to simulate the response for commonly used electrochemical techniques. The goal was the incorporation of these algorithms into DigiSimR, a generalized simulator for cyclic voltammetry (CV). CV, a ubiquitously applied electroanalytical technique used by nonelectrochemists as well as electrochemists, is sometimes referred to as "electrochemical spectroscopy". The latest version, DigiSimR 2.1, is now being sold by the industrial partner, Bioanalytical Systems, Inc. The response of the electrochemical community to this latest program (as well as its predecessors, DigiSimR 2.0 and the DOS version; versions 2.0 and 2.1 are for Windows), has been uniformly positive and numerous publications are now appearing which feature its application

    FCIC memo of staff interview with Charles Calomiris, Columbia University

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    Instability and `Sausage-String' Appearance in Blood Vessels during High Blood Pressure

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    A new Rayleigh-type instability is proposed to explain the `sausage-string' pattern of alternating constrictions and dilatations formed in blood vessels under influence of a vasoconstricting agent. Our theory involves the nonlinear elasticity characteristics of the vessel wall, and provides predictions for the conditions under which the cylindrical form of a blood vessel becomes unstable.Comment: 4 pages, 4 figures submitted to Physical Review Letter

    Importùncia da utilização de mudas sadias em hortaliças de propagação vegetativa.

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    Este artigo objetiva alertar aos tĂ©cnicos e produtores destas hortaliças sobre o risco de utilizar mudas sem procedĂȘncia e qualidade sanitĂĄria comprovada; tambĂ©m mostrar alguns exemplos de pragas e doenças que podem ser transmitidas (e ou transportadas) por mudas contaminadas.Artigo publicado tambĂ©m em Seed News, Ano 24, n. 5, p. 38-42, 2021

    The Effects of Serotonin Receptor Antagonists on Contraction and Relaxation Responses Induced by Electrical Stimulation in the Rat Small Intestine

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    Background: The main source of 5-HT in body is in enterchromafin cells of intestine, different studies mentioned different roles for endogenous 5-HT and receptors involved and it is not clearified the mechanism of action of endogenous 5-HT. Objectives: To study the role of endogenous 5-HT on modulation of contraction and relaxation responses induced by electrical field stimulation (EFS) in different regions of the rat intestine. Materials and Methods: Segments taken from the rat duodenum, jejunum, mid and terminal ileum were vertically mounted, connected to a transducer and exposed to EFS with different frequencies in the absence and presence of various inhibitors of enteric mediators i. e. specific 5-HT receptor antagonists. Results: EFS-induced responses were sensitive to TTX and partly to atropine, indicating a major neuronal involvement and a cholinergic system. Pre-treatment with WAY100635 (a 5-HT1A receptor antagonist) and granisetron up to 10.0 ”M, GR113808 (a 5-HT4 receptor antagonist), methysergide and ritanserin up to 1.0 ”M, failed to modify responses to EFS inall examined tissues. In the presence of SB258585 1.0 ”M (a 5-HT6 receptor antagonist) there was a trend to enhance contraction in the proximal part of the intestine and reduce contraction in the distal part. Pre-treatment with SB269970A 1.0 ”M (5-HT7 receptor antagonist) induced a greater contractile response to EFS at 0.4 Hz only in the duodenum. Conclusions: The application of 5-HT1A, 5-HT2, 5-HT3, 5-HT4, 5-HT6 and 5-HT7 receptor antagonists, applied at concentrations lower than 1.0 ”M did not modify the EFS-induced contraction and relaxation responses, whichsuggests the unlikely involvement of endogenous 5-HT in mediating responses to EFS in the described test conditions. Keywords: Electric Stimulation Therapy; Serotonin 5-HT1 Receptor Antagonists; Intestine, Smal

    Nintedanib targets KIT D816V neoplastic cells derived from induced pluripotent stem cells of systemic mastocytosis

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    The KIT D816V mutation is found in >80% of patients with systemic mastocytosis (SM) and is key to neoplastic mast cell (MC) expansion and accumulation in affected organs. Therefore, KIT D816V represents a prime therapeutic target for SM. Here, we generated a panel of patient-specific KIT D816V induced pluripotent stem cells (iPSCs) from patients with aggressive SM and mast cell leukemia to develop a patient-specific SM disease model for mechanistic and drug-discovery studies. KIT D816V iPSCs differentiated into neoplastic hematopoietic progenitor cells and MCs with patient-specific phenotypic features, thereby reflecting the heterogeneity of the disease. CRISPR/Cas9n-engineered KIT D816V human embryonic stem cells (ESCs), when differentiated into hematopoietic cells, recapitulated the phenotype observed for KIT D816V iPSC hematopoiesis. KIT D816V causes constitutive activation of the KIT tyrosine kinase receptor, and we exploited our iPSCs and ESCs to investigate new tyrosine kinase inhibitors targeting KIT D816V. Our study identified nintedanib, a US Food and Drug Administration-approved angiokinase inhibitor that targets vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and fibroblast growth factor receptor, as a novel KIT D816V inhibitor. Nintedanib selectively reduced the viability of iPSC-derived KIT D816V hematopoietic progenitor cells and MCs in the nanomolar range. Nintedanib was also active on primary samples of KIT D816V SM patients. Molecular docking studies show that nintedanib binds to the adenosine triphosphate binding pocket of inactive KIT D816V. Our results suggest nintedanib as a new drug candidate for KIT D816V-targeted therapy of advanced SM.Peer reviewe
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