40 research outputs found

    Control of Strong-Laser-Field Coupling to Electrons in Solid Targets with Wavelength-Scale Spheres

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    Irradiation of a planar solid by an intense laser pulse leads to fast electron acceleration and hard x-ray production. We have investigated whether this high field production of fast electrons can be controlled by introducing dielectric spheres of well-defined size on the target surface. We find that the presence of spheres with a diameter slightly larger than half the laser wavelength leads to Mie enhancements of the laser field which, accompanied by multipass stochastic heating of the electrons, leads to significantly enhanced hard x-ray yield and temperature

    FUNCTIONAL POLYMORPHISM OF THE PRO-INFLAMMATORY CYTOKINE GENES IN PULMONARY TUBERCULOSIS

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    In the present time, incidence of pulmonary tuberculosis (TB) becomes broader, due to spreading resistance of Mycobacterium tuberculosis (MBT) to anti-tuberculosis drugs and infection with highly virulent strains of M. tuberculosis. The MBT antigens can cause dysfunction of the receptors and modulate the cytokine secreting function of immunocompetent cells. Polymorphic genes of pro-inflammatory cytokines involved in the mechanisms of defense responses of innate immunity, determine the degree of resistance to individual mycobacterial infection, as well as severity and duration of the disease in cases of clinical manifestations. The aim of the study was to investigate the connections between allelic polymorphisms of IL2, IFNG and TNFA genes and changes in secretion of the corresponding pro-inflammatory cytokines IL-2, IFNγ, and TNFα in vitro in patients with the newly diagnosed pulmonary tuberculosis (TB), depending on the clinical form of the disease.A total of 334 patients (220 men and 114 women) aged 23 to 50 years with newly diagnosed infiltrative and disseminated TB were enrolled into the study. The control group consisted of 183 healthy donors (130 men and 53 women) of corresponding age. The material of the research included DNA extracted from the whole blood and supernatants of culture suspensions of mononuclear leukocytes isolated from venous blood in healthy volunteers and patients with TB. The evaluation of cytokines secretion was performed by measuring their concentration in the blood mononuclear cell culture supernatants. using enzyme-linked immunosorbent assay (ELISA). To study polymorphic regions of cytokine genes, a polymerase chain reaction (PCR) was applied. Analysis of the obtained data was carried out by means of the program Statistica for Windows Version 6.0 (StatSoft Inc., USA).It was found that the imbalance of secretion of pro-inflammatory cytokines in TB patients was associated with the polymorphic variants of genes of these cytokines. It was found that the hypo-secretion of IL-2 is determined by the carriage of the G allele and genotype GG (T-330G) of the IL2 gene in both the control group and in patients with TB, regardless of the clinical form. In patients with DTB carriers of the homozygous genotype TT (T-330G) of the IL2gene, increased protein secretion was established. The maximum secretion of TNFб was recorded in patients with the AA genotype (G-308A) of the TNFA gene in the control group and in ITB patients; the minimum concentration of TNFα was associated with the carrier of the homozygous GG genotype (G-308A) of the TNFA gene in all the examined groups. In patients with ITB and DTB, an increase in IFNγ secretion by mononuclear blood leukocytes is not associated with the carrier of polymorphism +874A/T of the IFNG gene.Reduced secretion of IL-2 and TNFα in TB patients is associated with polymorphisms of their genes – (T-330G) of IL2 gene and (G-308A) of TNFA gene, respectively. The polymorphism (+874A/T) of the IFNG gene does not have a modulatory effect on the secretion of IFNγ in patients with TB, regardless of clinical form of the disease

    Generation of Mie Size Microdroplet Aerosols with Applications in Laser-Driven Fusion Experiments

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    We have developed a tunable source of Mie scale microdroplet aerosols that can be used for the generation of energetic ions. To demonstrate this potential, a terawatt Ti:Al2O3 laser focused to 2×1019 W/cm2 was used to irradiate heavy water (D2O) aerosols composed of micron-scale droplets. Energetic deuterium ions, which were generated in the laser-droplet interaction, produced deuterium-deuterium fusion with approximately 2×103 fusion neutrons measured per joule of incident laser energy

    Hot Electron and X-ray Production from Intense Laser Irradiation of Wavelength-Scale Polystyrene Spheres

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    Hot electron and x-ray production from solid targets coated with polystyrene-spheres which are irradiated with high-contrast, 100 fs, 400 nm light pulses at intensity up to 2×1017 W/cm2 have been studied. The peak hard x-ray signal from uncoated fused silica targets is an order of magnitude smaller than the signal from targets coated with submicron sized spheres. The temperature of the x-rays in the case of sphere-coated targets is twice as hot as that of uncoated glass. A sphere-size scan of the x-ray yield and observation of a peak in both the x-ray production and temperature at a sphere diameter of 0.26 μm, indicate that these results are consistent with Mie enhancements of the laser field at the sphere surface and multipass stochastic heating of the hot electrons in the oscillating laser field. These results also match well with particle-in-cell simulations of the interaction

    Production of angiogenesis mediators and the structure of the vascular wall in the heart in ischemic cardiomyopathy

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    Background. In the pathogenesis of ischemic cardiomyopathy (ICMP), angiopoiesis remains unexplored.The aim. To describe the vasculature of the heart and the imbalance of angiogenesis mediators in the coronary circulation in association with the number of endothelial progenitor cells (EPC) and desquamated endothelial cells (DEC) in the blood of patients with coronary heart disease (CHD), suffering and not suffering from ICMP.Methods. Fifty-two patients with CHD (30  patients with ICMP, 22  patients without  ICMP), 15  healthy donors were examined. The content of EPC (CD14+CD34+VEGFR2+) in the blood from the cubital vein and DEC (CD45–CD146+) in the blood from the coronary sinus and the cubital vein was determined by flow cytometry. The concentrations of VEGF-A (vascular endothelial growth factor A), PDGF (platelet-derived growth factor), and SDF-1 (stromal cell-derived factor 1) in blood plasma were recorded using immunofluorescence assay; the angiopoietin-2, MMP-9 (matrix metallopeptidase 9) were recorded using enzyme immunoassay. In myocardial biopsies the specific area of vessels and the expression of αSMA (smooth muscle alpha-actin) were determined by morphometric and immunohistochemical methods.Results. In the peripheral blood of patients with CHD, regardless of the presence of ICMP, the DEC content exceeded the physiological level, and the VEGF-A, PDGF, angiopoietin-2, and MMP-9 corresponded to the norm. In CHD patients without cardiomyopathy, there was an excess of SDF-1 and EPC in the blood from the cubital vein, and in ICMP, their physiological significance was noted. In the coronary blood flow in patients with CHD without cardiomyopathy, an increase in the concentration of PDGF was found, which was not determined in patients with ICMP, who had an increased content of DEC, angiopoietin-2 and MMP-9. The specific area of the vessels in the patients of the two groups was comparable; the expression of αSMA in ICMP was 6.2 times lower than in patients with CHD without cardiomyopathy.Conclusion. The development of ICMP is accompanied by impaired maturation of vessels in the myocardium, associated with the absence of a compensatory reaction of activation of cellular and humoral factors of angiogenesis

    Expression of CD80 and HLA-DR molecules on blood monocytes in patients with pulmonary tuberculosis

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    We examined expression pattern of CD80 and HLA-DR pro-inflammatory molecules on the monocytes in patients with pulmonary tuberculosis (TB), depending on the clinical form of the disease and susceptibility of the pathogen to anti-tuberculosis drugs. The study involved forty-five patients with newly diagnosed pulmonary TB (25 men and 20 women aged 18 to 55 years, average age — 44.0±12.4 years). The control group included 15 healthy donors with similar socio-demographic characteristics as in TB patients. Venous blood was used as biomaterial for assays. Studies of the monocyte immunophenotype were carried out by flow cytometry of whole blood cells using Cytoflex flow cytometer (Beckman Coulter, USA) with specific monoclonal antibodies (eBioscience, USA). We determined the content of cells expressing surface markers of monocytes, i.e., CD14, CD45, CD80, and HLA-DR. The results of this study were evaluated using SPSS Statistics 17.0 standard software package and Microsoft Excel. In the course of the study, we have suggested a working hypothesis that the monocytes in TB patients, still being in circulation, can express activation markers during their migration to inflammation focus, especially CD80 and HLA-DR molecules. Analysis of the total CD14+ monocyte number showed its decrease in all forms and variants of clinical course of pulmonary tuberculosis compared with the control group. Assessment of pro-inflammatory markers expressed on CD14 positive monocytes, i.e., HLA-DR activation marker and CD80 co-stimulatory molecule, showed that the number of monocytes with HLA-DR expression in all TB patients was higher than in healthy donors. HLA- DR expression on CD14+ monocytes in the group of patients with infiltrative TB proved to be 15% higher than in patients with disseminated TB. The expression of CD80 on CD14+ monocytes in TB patients showed no differences between the groups and varied within the normal range. Hence, an imbalance within monocyte population in patients with pulmonary tuberculosis, regardless of its clinical form and drug sensitivity of the pathogen is developed, due to decrease in total number of CD14+ cells, along with increased relative number of monocytes expressing HLA-DR activation marker (pro-inflammatory phenotype). Meanwhile, expression of the CD80 co-stimulatory molecule on monocytes was within normal values

    Особенности иммунорегуляции у больных туберкулезом легких с эозинофилией крови

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    The aim of the investigation was to determine the characteristics of the immune response regulation for pulmonary tuberculosis (TB) and to analyze the role of regulatory T cells in the immunopathogenesis of TB with eosinophilia in the blood, depending on the clinical form of the disease and sensitivity of Micobacterium tuberculosis to anti-TB drugs.Materials and methods. 157 patients who were initially diagnosed with infiltrative and disseminated TB were examined. The material of the study was venous blood and culture of mononuclear leukocytes isolated from venous blood. The content of interleukin (IL) 4, IL-10 and transforming factor beta (TGFβ) in culture suspensions of mononuclear leukocytes in vitro and IL-5 in the blood was determined by enzyme-linked immunosorbent assay (ELISA) test. The expression of surface molecules CD4, CD20, CD25 and intracellular transcription factor Foxp3 by lymphocytes of the blood was evaluated by flow cytometry. The obtained results were analyzed by statistical methods.Results. It is shown that excessive generation of regulatory T cells in patients with TB is associated with eosinophilia of the blood and imbalance of immune response regulation mechanisms. In TB with eosinophilia, an increase in the number of Foxp3-positive regulatory T cells in the blood is combined with in vitro hypersecretion of anti-inflammatory cytokines TGFβ, IL-10, IL-4 and an increase in the content of CD20+ B lymphocytes and IL-5 in the blood. These changes are most pronounced in the disseminated form of TB in combination with drug resistance.Conclusion. Characteristics of immunoregulation at TB with blood eosinophilia are associated with activation of immunosuppression mechanisms and polarization of immune response towards Th2-dependent pathway.Цель исследования – установить особенности регуляции иммунного ответа при туберкулезе легких (ТБ) и проанализировать роль регуляторных Т-клеток в иммунопатогенезе ТБ с эозинофилией крови в зависимости от клинической формы заболевания и чувствительности Micobacterium tuberculosis к противотуберкулезным лекарственным средствам.Материалы и методы. Обследовано 157 больных с впервые выявленным инфильтративным и диссеминированным ТБ. Материалом исследования служили венозная кровь и культура мононуклеарных лейкоцитов, выделенных из венозной крови. Методом иммуноферментного анализа определяли содержание интерлейкина (IL) 4, IL-10 и трансформирующего фактора бета (TGFβ) в супернатантах культуральных суспензий мононуклеарных лейкоцитов in vitro и IL-5 в крови. Оценку экспрессии поверхностных молекул CD4, CD20, CD25 и внутриклеточного транскрипционного фактора Foxp3 в лимфоцитах крови проводили методом проточной цитометрии. Полученные результаты анализировали статистическими методами.Результаты. Показано, что у больных ТБ избыточная генерация регуляторных Т-клеток ассоциирована с эозинофилией крови и дисбалансом механизмов регуляции иммунного ответа. При ТБ с эозинофилией увеличение численности Foxp3-позитивных регуляторных Т-клеток в крови сочетается с гиперсекрецией in vitro противовоспалительных цитокинов TGFβ, IL-10, IL-4 и повышением содержания CD20+ В-лимфоцитов и IL-5 в крови. Указанные изменения являются наиболее выраженными при диссеминированной форме ТБ в сочетании с лекарственной устойчивостью возбудителя.Заключение. Особенности иммунорегуляции при ТБ с эозинофилией крови связаны с активацией механизмов иммуносупрессии и поляризацией иммунного ответа в направлении Th2-зависимого пути
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