348 research outputs found

    Targeted modification of major histocompatibility complex class 1 molecules via CRISPR-CAS9

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    Major Histocompatibility Complex (MHC) class I molecules present peptides derived from intracellular proteins for cytotoxic T cell recognition against virally infected cells/ tumor cells and inducing adaptive immunity. MHC-I complexes are comprised of a heavy chain, the light chain beta-2 microglobulin (B2M) and an optimized peptide. Recently, Complex of Clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated protein Cas9 has rapidly become a powerful tool for gene-editing experiments due to its high efficiency, simplicity, and versatility. This thesis proposes two approaches to apply CRISPR/Cas9-mediated knock-in methodology to modify MHC-I complexes: (i) to stably introduce specific peptides on MHC-I molecules through CRISPR-mediated insertion within the B2M locus; (ii) target single amino acid residues of the Ankylosing Spondylitis (AS)-associated HLA-B27 molecule proposed to contribute to its unusual biochemical folding characteristics. CRISPR/Cas9 was successfully employed to knock in HLA-A2 specific viral peptides, derived from SARS-CoV-2 virus, containing linker sequences at the genomic B2M locus. Immunoblotting revealed that the gene edited B2M locus facilitates the production of peptide linked β2m (PLB) protein with the expected size. Furthermore, flow cytometry analysis demonstrated gene-edited cells presented the PLB molecules together with endogenous peptide-specific HLA-A2 heavy chain at the cell surface. CRISPR/Cas9 was also harnessed to introduce point mutations into the disease-associated HLA-B*27:05 allele. The absence of Cys67 can potentially reduce the misfolding events of HLA-B27 molecules and still maintain the presence of this heavy chain at the cell surface. Additionally, HLA-B*27:05 have been transformed into HLA-B*27:09, a non-AS-associated subtype, by replacing aspartic acid (Asp)116 with a histidine (His) using CRISPR/Cas9. This is the first study exploiting gene-editing technology for modification of MHC-I complexes. While stable expression of PLB is a promising approach for development of cellular vaccines, alterations of HLA class I sequences can be considered as a potential therapeutic application for some HLA-associated diseases

    The Roles of Agricultual Cooperatives in Linking Small Farmers to Set up Large Paddy Fields in Mekong Delta

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    Agricultural cooperatives play a significant role in linking small farmers to set up large paddy fields in the Mekong Delta. Agricultural cooperatives’ association for establishment of big paddy fields allows firms to purchase secured raw materials in mass quantities, ensuring quality while reducing related costs. Farmers are able to cut down the cost of production, sell products more effectively by gaining economy of scale and have higher position and influence over the businesses. In order to enhance the role of agricultural cooperatives in linking small farmers to establish large paddy fields in the Mekong Delta, it is necessary to synchronously implement the following solutions such as (i) improving mechanisms and policies for agricultural cooperatives to promote their role in farmer linkage to set up large paddy fields; (ii) strengthening the capacity of agricultural cooperatives management staff; iii) strengthening the role of agricultural cooperatives’ representing member farmer households in carrying out the association with firms in setting up big paddy fields. Keywords: Role of agricultural cooperatives, association, large paddy field, Mekong Delta DOI: 10.7176/JESD/10-2-1

    Primary Cementless Bipolar Long Stem Hemiarthroplasty for Unstable Osteoporotic Intertrochanteric Fracture in the Elderly Patients

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    BACKGROUND: Intertrochanteric fracture (ITF) is a major part of fracture in femoral head fracture. 95% of ITF are found in elderly patients. Osteosynthese is the preferred method of choice. However, elderly patients had osteoporotic, combined with many of chronic disease conditions that increase the rate of osteosynthese failure. Hemiarthroplasty bipolar long-stem is a surgical method that helps patients relieve pain, facilitate early rehabilitation, limit long-term complications, and improve quality of life for patients. AIM: The aim of our study is to evaluate the clinical of result of primary cementless bipolar long stem hemiarthroplasty in treatment for unstable ITF in the elderly patients who have severe osteoporosis. METHODS: Between 01/2016 and 12/2017, 35 patients with ITF type A2.2 and A2.3 (AO) were included in our prospective study. These patients were over 70 years old and treatment by hemiarthroplasty cementless long stem at E hospital and Saint Paul hospital by one group surgeons. RESULTS: Mean age of studied subjects was 84.29 ± 6.17, the lowest was 71, the highest was 96; ratio male/female was 1/4. Follow-up of 35 patients for at least 6 months showed 88.6% caused by a low-energy injury; Average rehabilitation time was 4.63 ± 1.7 days. The average Harris point at the end was 90.4 ± 4.72. CONCLUSION: Primary cementless bipolar long stem hemiarthroplasty is one of good choices in treatment unstable ITF in elderly patients with severe osteoporosis helped patients improve the quality of life

    Creating Fatigue Curve for Steel Machine Elements Using Fatigue Test Method with Gradually Increasing Stress Amplitude

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    In order to create a fatigue curve, the traditional fatigue test method is applied to specimens using a cyclic stress with constant amplitude. However, this method has disadvantages such as the experimental results could not be used because of specimens broken before reaching the expected stress amplitude, or the tests may be stopped before specimen broken because of limitation of time. To overcome this hurdle of the traditional method, a new experimental method using cyclic stress with gradually increasing amplitude was proposed to build the fatigue curve for steel machine elements

    The Determinants of the Choices of Payment Methods for Goods and Services Transaction in Vietnam

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    The main objective of this study is to determine the main factors that have influences on customers’ decision to choose their payment methods. The research model applied in this study is Theory of Reasoned Action. The paper investigates 400 respondents in Vietnam to find out the determinants of their choice of payment methods. The implications from this study is expected to help financial service providers to improve the rate of using modern payment methods and improve customer satisfaction on the quality of payment services
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