433 research outputs found

    αβ T cell receptor germline CDR regions moderate contact with MHC ligands and regulate peptide cross-reactivity

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    αβ T cells respond to peptide epitopes presented by major histocompatibility complex (MHC) molecules. The role of T cell receptor (TCR) germline complementarity determining regions (CDR1 and 2) in MHC restriction is not well understood. Here, we examine T cell development, MHC restriction and antigen recognition where germline CDR loop structure has been modified by multiple glycine/alanine substitutions. Surprisingly, loss of germline structure increases TCR engagement with MHC ligands leading to excessive loss of immature thymocytes. MHC restriction is, however, strictly maintained. The peripheral T cell repertoire is affected similarly, exhibiting elevated cross-reactivity to foreign peptides. Our findings are consistent with germline TCR structure optimising T cell cross-reactivity and immunity by moderating engagement with MHC ligands. This strategy may operate alongside co-receptor imposed MHC restriction, freeing germline TCR structure to adopt this novel role in the TCR-MHC interface

    Reversible oligonucleotide chain blocking enables bead capture and amplification of T-Cell receptor alpha and beta chain mRNAs

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    Next-generation sequencing (NGS) has proven to be an exceptionally powerful tool for studying genetic variation and differences in gene expression profiles between cell populations. However, these population-wide studies are limited by their inability to detect variation between individual cells within a population, inspiring the development of single-cell techniques such as Drop-seq, which add a unique barcode to the mRNA from each cell prior to sequencing. Current Drop-seq technology enables capture, amplification, and barcoding of the entire mRNA transcriptome of individual cells. NGS can then be used to sequence the 3′-end of each message to build a cell-specific transcriptional landscape. However, current technology does not allow high-throughput capture of information distant from the mRNA poly-A tail. Thus, gene profiling would have much greater utility if beads could be generated having multiple transcript-specific capture sequences. Here we report the use of a reversible chain blocking group to enable synthesis of DNA barcoded beads having capture sequences for the constant domains of the T-cell receptor α and β chain mRNAs. We demonstrate that these beads can be used to capture and pair TCRα and TCRβ sequences from total T-cell RNA, enabling reverse transcription and PCR amplification of these sequences. This is the first example of capture beads having more than one capture sequence, and we envision that this technology will be of high utility for applications such as pairing the antigen receptor chains that give rise to autoimmune diseases or measuring the ratios of mRNA splice variants in cancer stem cells

    Thermal properties of metal matrix composites with planar distribution of carbon fibres

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    High thermal conductivity (TC) and a tunable coefficient of thermal expansion are essential properties for heat management materials operating in a wide temperature range. We combine both properties in a composite with a low‐density metal matrix reinforced with pitch‐based carbon fibres. The thermal conductivity of the metal matrix was increased by 50%, the thermal expansion coefficient was reduced by a factor of five. The samples were produced by powder metallurgy and have a planar random distribution of fibres, leading to high performance in two dimensions

    High-throughput sequencing of the T-cell receptor repertoire: pitfalls and opportunities.

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    T-cell specificity is determined by the T-cell receptor, a heterodimeric protein coded for by an extremely diverse set of genes produced by imprecise somatic gene recombination. Massively parallel high-throughput sequencing allows millions of different T-cell receptor genes to be characterized from a single sample of blood or tissue. However, the extraordinary heterogeneity of the immune repertoire poses significant challenges for subsequent analysis of the data. We outline the major steps in processing of repertoire data, considering low-level processing of raw sequence files and high-level algorithms, which seek to extract biological or pathological information. The latest generation of bioinformatics tools allows millions of DNA sequences to be accurately and rapidly assigned to their respective variable V and J gene segments, and to reconstruct an almost error-free representation of the non-templated additions and deletions that occur. High-level processing can measure the diversity of the repertoire in different samples, quantify V and J usage and identify private and public T-cell receptors. Finally, we discuss the major challenge of linking T-cell receptor sequence to function, and specifically to antigen recognition. Sophisticated machine learning algorithms are being developed that can combine the paradoxical degeneracy and cross-reactivity of individual T-cell receptors with the specificity of the overall T-cell immune response. Computational analysis will provide the key to unlock the potential of the T-cell receptor repertoire to give insight into the fundamental biology of the adaptive immune system and to provide powerful biomarkers of disease

    The Impact of Risk-Based Internal Audit Approach on Improving Risk Management Processes: A Field Study in Yemeni Islamic Banks (Aden)

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    This study explores the impact of the Risk-Based Internal Audit approach on improving risk management processes in Yemeni Islamic banks in Aden. The study focuses on four core RBIA functions: early identification, risk assessment, control evaluation, and monitoring and reporting. Data from eight banks were analyzed using SPSS, linear regression, and ANOVA. In light of the study's results, there is a statistically significant impact of the risk-based internal audit approach in improving risk management processes in Islamic banks operating in Aden by 51.3%.  According to the results, the control evaluation function ranked first in influencing the improvement of risk management processes with a rate of 45.2%, followed by risk assessment at 39.9%, and early detection at 32.2%. The study suggests that the management of Yemeni Islamic banks should take into account the recommendations and reports submitted by the Internal Audit Department regarding risk management activities and processes and proposals for improvement, in addition to the need for the management of Yemeni Islamic banks to support and develop communication systems between them and the Internal Audit Department to facilitate the exchange of necessary information on time, to support the monitoring and reporting function, which had the lowest impact rate of 24.3%

    Public Relations Strategy Analysis Crisis Communications

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    Crisis communication is the exchange of information between an organization and its constituents during and after the occurrence of a crisis. This research employs a descriptive technique and a qualitative method. Techniques for data gathering include observation, interviewing, and documenting. The aim of this research is to conduct an empirical examination of the execution of strategies and supporting and inhibiting variables in crisis communication in public relations. The findings of this research suggest that a crisis communication plan should be suitable and swift in order to overcome public reaction and avoid a protracted crisis communication. Communication in Times of Crisis Pre-Crisis management is carried out by Public Relations, namely in the preparation (Planning) stage, which includes the establishment of a Public Relations team responsible for providing information, a clean-up and executive summery formation team, and Crisis-Response, namely the manufacturing stage. Press releases, clarifications, establishing stakeholder and media relations, and finally, Post-Crisis, namely the advancement of Public Relations not only to improve the company's image but also to improve performance, press conferences, and dissemination of publications are also implemented to improve things in the short and long term through program

    Study of the Effect of Irrigation Method and Spraying with Amino Acids on Some Growth Indicators and Biochemical Characteristics of Tobacco Plants (Virginia variety)

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    The experiment was implemented at the Stakhris Agricultural Research Station in Latakia during the two successive seasons of Agricultural 2021/2022, according to a split-randomized block design, with three replicates for each treatment. The research aimed to study the effect of irrigation method and spraying with amino acids on the growth and productivity of tobacco plants, the Virginia tobacco variety (Nicotiana tabacum var. Virginie vk51), where the morphological and physiological characteristics were studied (plant height (cm) and total leaf surface area (m2/plant), and the content of air-dried tobacco leaves of biochemical compounds (total protein, soluble sugars, and nicotine (%)). Using the drip irrigation method with the third level of amino acids (I1A2) gave the best results, as it was significantly superior to the rest of the treatments, as the plant height value in this treatment reached (226 cm), which was reflected positively on the total leaf surface area of ​​the plant (3.52 m²). /plant), and the qualitative characteristics of dry tobacco leaf improved, as the percentage of total protein and nicotine decreased and the percentage of total soluble sugars increased. Based on the above, it can be suggested to use the drip irrigation method with the third level of amino acids, given their significant role in stimulating growth in the Virginia variety and improving the quality of the resulting tobacco

    Characterization of Hydrogen Plasma used for Introducing Hydrogen into Semiconductors

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    This paper reports the investigation result of RF power effects on the RF hydrogen plasma parameters. The hydrogen plasma parameters are measured experimentally in the center of the deposition chamber by means of the cylindrical Langmuir probe. The measurements are done at 0.2 mbar hydrogen gas pressures. The applied discharge powers are between 50 W and 200 W. It is found that the electron and ion densities increase with the RF power. The ion density dependence of the cathode sheath voltage is fitted to Ni(cm-3)=-3.5 1010 + 9.2  107 (Vo - Vdc). The plasma and floating potentials are less sensitive to RF power.This paper reports the investigation result of RF power effects on the RF hydrogen plasma parameters. The hydrogen plasma parameters are measured experimentally in the center of the deposition chamber by means of the cylindrical Langmuir probe. The measurements are done at 0.2 mbar hydrogen gas pressures. The applied discharge powers are between 50 W and 200 W. It is found that the electron and ion densities increase with the RF power. The ion density dependence of the cathode sheath voltage is fitted to Ni(cm-3)=-3.5 1010 + 9.2  107 (Vo - Vdc). The plasma and floating potentials are less sensitive to RF power
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