118 research outputs found

    Disentanglement of Topological and Dynamical Fields in 3d Higher-Spin Theory within Shifted Homotopy Approach

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    The first-order correction to the one-form sector of equations of the 3d3d higher-spin theory is derived from the generating nonlinear HS system by virtue of the shifted homotopy approach. The family of solutions to the generating system that disentangles equations for dynamical and topological fields in the first order of perturbation theory is found. This family is shown to belong to the different cohomology class compared to the solution found earlier by the direct methods. The related cohomology is shown to be the same as that underlying the mass deformation in the matter sector of 3d3d higher-spin equations.Comment: 21 page

    Совмещенный процесс синтеза циклогексилциклогексанкарбоксилата из циклогексанола и CO, катализируемый системой Pd(OAc)2–PPh3–п-толуолсульфокислота

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    Objectives. To study the possibility of combining acid-catalytic cyclohexanol dehydration and alkoxycarbonylation of the formed cyclohexene with cyclohexanol and carbon(II) oxide in a single reactor in order to achieve high yields of the target cyclohexyl cyclohexanecarboxylate product under mild conditions using the Pd(OAc)2–PPh3–p-toluenesulfonic acid catalytic system.Methods. The combined process took place in a toluene medium in a periodic steel reactor designed to operate at elevated pressure, equipped with a glass insert, a magnetic stirrer, and a sampler, as well as gas input and discharge devices. The reaction mass with the components of the catalytic system was placed in a glass reactor inside a steel autoclave. The reaction mass samples obtained during the combined process were analyzed by gas–liquid chromatography with a flame ionization detector.Results. The possibility of combining cyclohexanol dehydration catalyzed by p-toluenesulfonic acid monohydrate and formed cyclohexene alkoxycarbonylation with cyclohexanol and CO during catalysis by the Pd(OAc)2–PPh3–p-toluenesulfonic acid system in a single reactor was demonstrated. Under mild conditions (temperature 110°C; CO pressure 2.1 MPa), the target product yield reached 64.8% in 5 h. However, the combined process is complicated by the formation of a cyclohexanecarboxylic acid by-product formed as a result of the cyclohexyl cyclohexanecarboxylate hydrolysis and the cyclohexene hydroxycarbonylation.Conclusions. The reactions of intramolecular acid-catalytic cyclohexanol dehydration and formed cyclohexene alkoxycarbonylation catalyzed by the Pd(OAc)2–PPh3–p-toluenesulfonic acid system can be combined in a single reactor. p-Toluenesulfonic acid can simultaneously act as a catalyst for the cyclohexanol dehydration and a co-catalyst of the palladium–phosphine system of cyclohexene alkoxycarbonylation. The involvement of cyclohexene, representing a product of reversible cyclohexanol dehydration, in the alkoxycarbonylation reaction is a factor in shifting the dehydration reaction equilibrium towards the formation of cyclohexene. Cyclohexanecarboxylic acid is a by-product of the proposed combined process. A factor in the reduction of target product yield is water formed as a result of cyclohexanol dehydration due to the involvement of the latter in the hydrolysis reaction and the course of the cyclohexene hydroxycarbonylation.Цели. Изучение возможности совмещения в одном реакторе реакций кислотнокаталитической дегидратации циклогексанола и алкоксикарбонилирования образующегося циклогексена циклогексанолом и оксидом углерода (II). Установление возможности достижения высоких выходов целевого продукта – циклогексилциклогексанкарбоксилата – в мягких условиях при катализе системой Pd(OAc)2–PPh3–п-толуолсульфокислота.Методы. Совмещенный процесс изучался в среде толуола в периодическом стальном реакторе, рассчитанном на работу при повышенном давлении, снабженном стеклянной вставкой, магнитной мешалкой, пробоотборником, устройствами ввода и сброса газов. Реакционная масса с компонентами каталитической системы помещалась в стеклянный реактор внутри стального автоклава. Отбираемые в ходе совмещенного процесса пробы реакционной массы анализировали методом газо-жидкостной хроматографии с пламенно-ионизационным детектором.Результаты. Показана возможность совмещения в одном реакторе дегидратации циклогексанола, катализируемой моногидратом п-толуолсульфокислоты, и алкоксикарбонилирования образующегося циклогексена циклогексанолом и СО при катализе системой Pd(OAc)2–PPh3–п-толуолсульфокислота. В мягких условиях (температура 110 °С, давление СО 2.1 МПа) выход целевого продукта достигал 64.8% за 5 ч. Установлено, что совмещенный процесс осложняется образованием побочного продукта – циклогексанкарбоновой кислоты – в результате гидролиза циклогексилового эфира циклогексанкарбоновой кислоты и гидроксикарбонилирования циклогексена

    Complications after BCG vaccination in a big city

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    Complications after specific prevention of tuberculosis for the last 10 years have been analyzed using the example of a big city. The frequency of severe complications (BCG-ostitis) made 0.004% and the frequency of minor complications (lymphadenitis) made 0.005% and cold abscesses made 0.01% per 100 000 vaccinated children. Often complications were caused by mistakes in the vaccine administration related to premature discharge from maternity hospital and administration of the vaccine in the polyclinic and also concurrent prenatal disorder. The issue of complications caused by anti-tuberculosis vaccination makes no grounds to review the policy of the primary BCG vaccination

    Blood and cell infiltrate neutrophilic leucocytes As inflammation markers in chronic endometritis: A prospective non-randomised controlled trial

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    Background. Inflammation declares itself with the presence of cellular tissue infiltrate, which composition reflects the inflammation type. Chronic inflammation is predominated by mononuclear cell infiltration with a certain amount of neutrophils, which role and significance are not fully understood to date.Objectives. Assessment of the infiltrated neutrophil count at various chronic endometritis severity and its dependency on the functional and metabolic activity in neutrophilic leucocytes in peripheral blood.Methods. This prospective non-randomised controlled trial estimated the CD45+ leucocyte and activated CD16b+ neutrophil counts in inflammation infiltrate using immunohistochemistry protocols. Cell counts per section 1 mm2 were measured with computer morphometry. The content of and NADPH oxidase activity in activated neutrophilic leucocytes in venous blood were estimated with a nitroblue tetrazolium reduction test.Results. The study included 40 women with a history of chronic endometritis (CE) divided in two cohorts by endometrial biopsy data, with inactive (n = 25) and active CE (n = 15). A control cohort comprised 20 women with no signs of CE. The inactive CE cohort had higher counts of CD45+ leucocytes and activated CD16b+ neutrophils in infiltrate compared to control. Higher content of activated neutrophilic leucocytes with higher NADPH oxidase activity were found in peripheral blood. Morphological exacerbation markers of EC were associated with sharper peaks of CD45+ and CD16b+ cell counts in infiltrate and an elevated functional metabolic activity in circulating neutrophilic leucocytes. A strong direct correlation was revealed between blood activated neutrophil and endometrial CD16b+ neutrophil counts, as well as NADPH oxidase activity in blood neutrophils and infiltrate CD16b+ cell counts.Conclusion. Even minor morphological markers of exacerbated endometrial inflammation are accompanied by the elevated infiltrate counts of both total CD45+ leucocytes and activated CD16b+ neutrophils. The functional metabolic activity of peripheral blood neutrophilic leucocytes is interlinked with the inflammatory infiltrate cell composition and reflects severity of chronic endometrial inflammation

    RNA polymerase gate loop guides the nontemplate DNA strand in transcription complexes

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    Upon RNA polymerase (RNAP) binding to a promoter, the s factor initiates DNA strand separation and captures the melted nontemplate DNA, whereas the core enzyme establishes interactions with the duplex DNA in front of the active site that stabilize initiation complexes and persist throughout elongation. Among many core RNAP elements that participate in these interactions, the beta' clamp domain plays the most prominent role. In this work, we investigate the role of the beta gate loop, a conserved and essential structural element that lies across the DNA channel from the clamp, in transcription regulation. The gate loop was proposed to control DNA loading during initiation and to interact with NusG-like proteins to lock RNAP in a closed, processive state during elongation. We show that the removal of the gate loop has large effects on promoter complexes, trapping an unstable intermediate in which the RNAP contacts with the nontemplate strand discriminator region and the downstream duplex DNA are not yet fully established. We find that although RNAP lacking the gate loop displays moderate defects in pausing, transcript cleavage, and termination, it is fully responsive to the transcription elongation factor NusG. Together with the structural data, our results support a model in which the gate loop, acting in concert with initiation or elongation factors, guides the nontemplate DNA in transcription complexes, thereby modulating their regulatory properties

    Transcription inactivation through local refolding of the RNA polymerase structure

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    Structural studies of antibiotics not only provide a shortcut to medicine allowing for rational structure-based drug design, but may also capture snapshots of dynamic intermediates that become 'frozen' after inhibitor binding. Myxopyronin inhibits bacterial RNA polymerase (RNAP) by an unknown mechanism. Here we report the structure of dMyx--a desmethyl derivative of myxopyronin B--complexed with a Thermus thermophilus RNAP holoenzyme. The antibiotic binds to a pocket deep inside the RNAP clamp head domain, which interacts with the DNA template in the transcription bubble. Notably, binding of dMyx stabilizes refolding of the beta'-subunit switch-2 segment, resulting in a configuration that might indirectly compromise binding to, or directly clash with, the melted template DNA strand. Consistently, footprinting data show that the antibiotic binding does not prevent nucleation of the promoter DNA melting but instead blocks its propagation towards the active site. Myxopyronins are thus, to our knowledge, a first structurally characterized class of antibiotics that target formation of the pre-catalytic transcription initiation complex-the decisive step in gene expression control. Notably, mutations designed in switch-2 mimic the dMyx effects on promoter complexes in the absence of antibiotic. Overall, our results indicate a plausible mechanism of the dMyx action and a stepwise pathway of open complex formation in which core enzyme mediates the final stage of DNA melting near the transcription start site, and that switch-2 might act as a molecular checkpoint for DNA loading in response to regulatory signals or antibiotics. The universally conserved switch-2 may have the same role in all multisubunit RNAPs

    Prognostic value of molecules of average mass in patients with chronic obstructive pulmonary disease

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    Background. Chronic obstructive pulmonary disease is a socially significant disease affecting patient’s quality of life. Assessment of endogenous intoxication in patients with chronic obstructive pulmonary disease will allow to understand pathogenetic features of different phenotypes of this disease, which can be taken into account when predicting its course.The aim of the study. To determine the prognostic value of levels of mediumand low-molecular-weight substances and oligopeptides in patients with chronic obstructive pulmonary disease.Materials and methods. One hundred and four patients with chronic obstructive pulmonary disease (COPD) and 110 somatically healthy individuals were examined. Molecular weight medium and low molecular weight substances (LMWSM) and oligopeptides (OP) were determined in blood plasma, erythrocytes and urine. Based on these indicators mathematically calculated indices of endogenous intoxication and coefficient of elimination were defined. Statistical processing of the data was performed using the SPSS 26.0 software package (IBM Corp., USA).Results. In all biological fluids, the levels of average molecules and calculated indices in the COPD patients’ group were statistically significantly different from those in the control group. The indices characterizing endotoxin accumulation were statistically significantly higher, while those characterizing toxin elimination were lower. The level of endotoxemia was correlated with the frequency of exacerbations, clinical manifestations severity, quality of life, COPD group and phenotype.Conclusions. Frequent exacerbations, groups C and D, bronchitic and mixed COPD phenotypes are characterized by more severe endotoxicosis manifested by high levels of LMWSM, OP and calculated indices
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