145 research outputs found

    Equilibrum Composition of Thermal Plasma with Copper and Chromium Vapours Admixtures

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    Thermal plasma of electric arc is widely used in various technological applications: welding, cutting, lamps, spraying, protection of electrical installations, etc. Process efficiency is defined by different parameters that determine arc operation and influence the energy transfer within the medium. All energy exchanges depend on the medium, which is modified by the presence of the arc and more particularly by the appearance of new species from contact erosion. Sintered Cu-Cr composites are widely used as electrical contacts for vacuum circuit breakers. These materials take advantage of the high thermal and electrical conductivity of Cu and of the refractory and oxygen getter properties of reinforcing Cr particles. The aim of this paper is to give results of the calculation of the equilibrium composition of argon and air plasma with various admixtures of Cu and Cr

    Optimization of 3-band Mean Absorption Coefficients

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    In this paper we present a process for mean absorption coefficient optimal band selection applied to the 3-band model of radiation in an air electrical arc. For fixed temperature, the divergence of radiation flux in an infinite cylindrical plasma column is calculated using spectrally resolved absorption coefficient and serves as a reference value. Optimization process is used to properly select the bands of 3-band mean absorption approximation using both unmodified and limited Planck mean absorption coefficient. The ac-curacy of aforementioned two approximation methods is evaluated

    Estimation of the Intensively Blasted Electric Arc Model Sensitivity to Selected Variables

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    Results of measurements carried out on the fabricated experimental modular-type arc heater serve as input data for the designed simplified model of the intensively blasted electric arc burning in argon inside the cylindrical arc heater's anode channel. The axial dependence of the arc temperature and radius is expressed using the exponent, the current density on the cathode tip and the arc temperature at the end of the near-cathode boundary layer. These quantities form the vector of state variables that is sought to minimize the value of the objective function expressing the deviations between measured and computed values. On a typical example, the paper demonstrates the sensitivity of the modelling to individual state variables

    Fused 3-Hydroxy-3-trifluoromethylpyrazoles Inhibit Mutant Huntingtin Toxicity

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    [Image: see text] Here, we describe the selection and optimization of a chemical series active in both a full-length and a fragment-based Huntington’s disease (HD) assay. Twenty-four thousand small molecules were screened in a phenotypic HD assay, identifying a series of compounds bearing a 3-hydroxy-3-trifluoromethylpyrazole moiety as able to revert the toxicity induced by full-length mutant Htt by up to 50%. A chemical exploration around the series led to the identification of compound 4f, which demonstrated to be active in a Htt171–82Q rat primary striatal neuron assay and a PC12-Exon-1 based assay. This compound was selected for testing in R6/2 mice, in which it was well-tolerated and showed a positive effect on body weight and a positive trend in preventing ventricular volume enlargment. These studies provide strong rationale for further testing the potential benefits of 3-hydroxy-3-trifluoromethylpyrazoles in treating HD

    Biophysical and electrochemical studies of protein-nucleic acid interactions

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    This review is devoted to biophysical and electrochemical methods used for studying protein-nucleic acid (NA) interactions. The importance of NA structure and protein-NA recognition for essential cellular processes, such as replication or transcription, is discussed to provide background for description of a range of biophysical chemistry methods that are applied to study a wide scope of protein-DNA and protein-RNA complexes. These techniques employ different detection principles with specific advantages and limitations and are often combined as mutually complementary approaches to provide a complete description of the interactions. Electrochemical methods have proven to be of great utility in such studies because they provide sensitive measurements and can be combined with other approaches that facilitate the protein-NA interactions. Recent applications of electrochemical methods in studies of protein-NA interactions are discussed in detail

    A Comprehensive Map of Mobile Element Insertion Polymorphisms in Humans

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    As a consequence of the accumulation of insertion events over evolutionary time, mobile elements now comprise nearly half of the human genome. The Alu, L1, and SVA mobile element families are still duplicating, generating variation between individual genomes. Mobile element insertions (MEI) have been identified as causes for genetic diseases, including hemophilia, neurofibromatosis, and various cancers. Here we present a comprehensive map of 7,380 MEI polymorphisms from the 1000 Genomes Project whole-genome sequencing data of 185 samples in three major populations detected with two detection methods. This catalog enables us to systematically study mutation rates, population segregation, genomic distribution, and functional properties of MEI polymorphisms and to compare MEI to SNP variation from the same individuals. Population allele frequencies of MEI and SNPs are described, broadly, by the same neutral ancestral processes despite vastly different mutation mechanisms and rates, except in coding regions where MEI are virtually absent, presumably due to strong negative selection. A direct comparison of MEI and SNP diversity levels suggests a differential mobile element insertion rate among populations

    The impact of transposable element activity on therapeutically relevant human stem cells

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    Human stem cells harbor significant potential for basic and clinical translational research as well as regenerative medicine. Currently ~ 3000 adult and ~ 30 pluripotent stem cell-based, interventional clinical trials are ongoing worldwide, and numbers are increasing continuously. Although stem cells are promising cell sources to treat a wide range of human diseases, there are also concerns regarding potential risks associated with their clinical use, including genomic instability and tumorigenesis concerns. Thus, a deeper understanding of the factors and molecular mechanisms contributing to stem cell genome stability are a prerequisite to harnessing their therapeutic potential for degenerative diseases. Chemical and physical factors are known to influence the stability of stem cell genomes, together with random mutations and Copy Number Variants (CNVs) that accumulated in cultured human stem cells. Here we review the activity of endogenous transposable elements (TEs) in human multipotent and pluripotent stem cells, and the consequences of their mobility for genomic integrity and host gene expression. We describe transcriptional and post-transcriptional mechanisms antagonizing the spread of TEs in the human genome, and highlight those that are more prevalent in multipotent and pluripotent stem cells. Notably, TEs do not only represent a source of mutations/CNVs in genomes, but are also often harnessed as tools to engineer the stem cell genome; thus, we also describe and discuss the most widely applied transposon-based tools and highlight the most relevant areas of their biomedical applications in stem cells. Taken together, this review will contribute to the assessment of the risk that endogenous TE activity and the application of genetically engineered TEs constitute for the biosafety of stem cells to be used for substitutive and regenerative cell therapiesS.R.H. and P.T.R. are funded by the Government of Spain (MINECO, RYC-2016- 21395 and SAF2015–71589-P [S.R.H.]; PEJ-2014-A-31985 and SAF2015–71589- P [P.T.R.]). GGS is supported by a grant from the Ministry of Health of the Federal Republic of Germany (FKZ2518FSB403)
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