41 research outputs found

    Experimental study on the effect of rock pressure on sandstone permeability

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    The results of laboratory studies to determine the effect of effective stress on the permeability of sandstone are presented. During the test, the samples were subjected to a stepwise increase or decrease of the effective stress (at a constant pore pressure) in a specified step. The values of rock permeability at different values of effective stress were determined, and the influence of the grain size of the reservoir rock matrix on the character of the change in the sandstone permeability coefficient was also established. During the test, a decrease in permeability was observed with an increase in effective stress. It was found that as a result of gradual loading/unloading of the sandstone sample, the original permeability values were not restored, which indicates the beginning of the formation of residual strains in the rock. This effect should be taken into account when modeling field development because in the process of reserves extraction the effective stress acting on the reservoir rock skeleton changes, which results in a significant chang in rock permeability. The results of laboratory studies showed that the deviation of permeability in medium-grained sandstones relative to the initial value was greater than in medium- and fine-grained sandstones. The pressure sensitivity coefficient and constant of material, which are used in empirical relationships between permeability and effective stress, were numerically estimated. At the same time, the constant of material showed no such convergence, which indicates that the values of this parameter are individual for each rock

    Cytosolic Sequestration of Prep1 Influences Early Stages of T Cell Development

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    Objective: Prep1 and Pbx2 are the main homeodomain DNA-binding proteins of the TALE (three amino acid loop extension) family expressed in the thymus. We previously reported reduced Pbx2 expression and defective thymocyte maturation in Prep1 hypomorphic mice. To further investigate the role of this homeodomain DNA-binding protein in T cell development, we generated transgenic mice expressing the N-terminal fragment of Pbx1 (Pbx1NT) under the control of the Lck proximal promoter. Principal Findings: Pbx1NT causes Prep1 cytosolic sequestration, abolishes Prep1-dependent DNA-binding activity and results in reduced Pbx2 expression in developing thymocytes. Transgenic thymi reveal increased numbers of CD4 2 CD8 2 CD44 2 (DN3 and DN4) thymocytes, due to a higher frequency of DN2 and DN4 Pbx1NT thymocytes in the S phase. Transgenic thymocytes however do not accumulate at later stages, as revealed by a normal representation of CD4/CD8 double positive and single positive thymocytes, due to a higher rate of apoptotic cell death of DN4 Pbx1NT thymocytes. Conclusion: The results obtained by genetic (Prep1 hypomorphic) and functional (Pbx1NT transgenic) inactivation of Prep

    Veliparib in Combination with Carboplatin and Etoposide in Patients with Treatment-Naive Extensive-Stage Small Cell Lung Cancer:A Phase 2 Randomized Study

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    Purpose: This study investigated the efficacy and safety of oral PARP inhibitor veliparib, plus carboplatin and etoposide in patients with treatment-naive, extensive-stage small cell lung cancer (ED-SCLC). Patients and Methods: Patients were randomized 1:1:1 to veliparib [240 mg twice daily (BID) for 14 days] plus chemotherapy followed by veliparib maintenance (400 mg BID; veliparib throughout), veliparib plus chemotherapy followed by placebo (veliparib combination only), or placebo plus chemotherapy followed by placebo (control). Patients received 4-6 cycles of combination therapy, then maintenance until unacceptable toxicity/progression. The primary endpoint was progression-free survival (PFS) with veliparib throughout versus control. Results: Overall (N = 181), PFS was improved with veliparib throughout versus control [hazard ratio (HR), 0.67; 80% confidence interval (CI), 0.50-0.88; P = 0.059]; median PFS was 5.8 and 5.6 months, respectively. There was a trend toward improved PFS with veliparib throughout versus control in SLFN11-positive patients (HR, 0.6; 80% CI, 0.36-0.97). Median overall survival (OS) was 10.1 versus 12.4 months in the veliparib throughout and control arms, respectively (HR, 1.43; 80% CI, 1.09-1.88). Grade 3/4 adverse events were experienced by 82%, 88%, and 68% of patients in the veliparib throughout, veliparib combination-only and control arms, most commonly hematologic. Conclusions: Veliparib plus platinum chemotherapy followed by veliparib maintenance demonstrated improved PFS as first-line treatment for ED-SCLC with an acceptable safety profile, but there was no corresponding benefit in OS. Further investigation is warranted to define the role of biomarkers in this setting

    Cytoplasmic Prep1 Interacts with 4EHP Inhibiting Hoxb4 Translation

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    embryo development. Interestingly, Prep1 contains a putative binding motif for 4EHP, which may reflect a novel unknown function. development effect. mRNA to the 5β€² cap structure. This is the first demonstration that a mammalian homeodomain transcription factor regulates translation, and that this function can be possibly essential for the development of female germ cells and involved in mammalian zygote development

    New Nanostructured Carbon Coating Inhibits Bacterial Growth, but Does Not Influence on Animal Cells

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    An electrospark technology has been developed for obtaining a colloidal solution containing nanosized amorphous carbon. The advantages of the technology are its low cost and high performance. The colloidal solution of nanosized carbon is highly stable. The coatings on its basis are nanostructured. They are characterized by high adhesion and hydrophobicity. It was found that the propagation of microorganisms on nanosized carbon coatings is significantly hindered. At the same time, eukaryotic animal cells grow and develop on nanosized carbon coatings, as well as on the nitinol medical alloy. The use of a colloidal solution as available, cheap and non-toxic nanomaterial for the creation of antibacterial coatings to prevent biofilm formation seems to be very promising for modern medicine, pharmaceutical and food industries

    The influence of impurities on electron excitation and tunnel transfer

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    Porphyrins solutions have been studied. The work is aimed at studying of tunnel transfer of an electron in model systems in the presence of impurities, as well as the impurity effect on the form of optical spectra of molecular crystals. The influence of impurities on donor-acceptor tunnel transfer of electrons is studied. A clear criterion of resonance and non-resonance tunnelling difference is established. An expression for electron transfer process velocity with participation of impurities is obtained. Photoprocesses in frozen glassy solutions of porphyrins in triethylamine are studied. A significant increase of the tunnel electron transfer in the presence of tetrachlorated carbon and chloroform is revealedAvailable from VNTIC / VNTIC - Scientific & Technical Information Centre of RussiaSIGLERURussian Federatio

    Tn5 DNA Transposase in Multi-Omics Research

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    Tn5 transposase use in biotechnology has substantially advanced the sequencing applications of genome-wide analysis of cells. This is mainly due to the ability of Tn5 transposase to efficiently transpose DNA essentially randomly into any target DNA without the aid of other factors. This concise review is focused on the advances in Tn5 applications in multi-omics technologies, genome-wide profiling, and Tn5 hybrid molecule creation. The possibilities of other transposase uses are also discussed

    Molecular and cellular mechanisms of adipogenesis

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    The main components of metabolic syndrome include insulin resistance, hypertriglyceridemia and arterial hypertension. Obesity is the cause of metabolic syndrome, mainly as a consequence of the endocrine function of adipose tissue. The volume of adipose tissue depends on the size of individual adipocytes and on their number. The number of adipocytes increases as a result of enhanced adipocyte differentiation. The transcriptional cascade that regulates this differentiation has been well studied. The major adipogenic transcription factor peroxisome proliferator-activated receptor gamma is a ligand-activated nuclear receptor with essential roles in adipogenesis. Its ligands are used to treat metabolic syndrome and type 2 diabetes mellitus. . The present article describes the basic molecular and cellular mechanisms of adipogenesis and discusses the impact of insulin, glucocorticoids, cyclic adenosine monophosphate-activating agents, nuclear receptors and transcription factors on the process of adipogenesis. New regulatory regions of the genome that are capable of binding multiple transcription factors are described, and the most promising drug targets for the treatment of metabolic syndrome and obesity, including the homeodomain proteins Pbx1 and Prep1, are discussed.

    Reduction of Prep1 levels affects differentiation of normal and malignant B cells and accelerates Myc driven lymphomagenesis.

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    The Prep1 homeodomain transcription factor has recently been recognized as a tumor suppressor. Among other features, haploinsufficiency of Prep1 is able to strongly accelerate the B-lymphomagenesis in EΞΌMyc mice. Now we report that this occurs concomitantly with a change in the type of B-cell lymphomas generated by the Myc oncogene. Indeed, the tumors generated in the EΞΌMyc-Prep1(+/-) mice are much more immature, being mostly made up of Pro-B or Pre-B cells, while those in the EΞΌMyc-Prep1(+/+) mice are more differentiated being invariably IgM(+). Moreover, we show that Prep1 is in fact required for the differentiation of Pro-B and Pre-B cells into IgM(+) lymphocytes and/or their proliferation, thus showing also how a normal function of Prep1 affects EΞΌMyc lymphomagenesis. Finally, we show that the haploinsufficiency of Prep1 is accompanied with a major decrease of Myc-induced apoptosis and that the haploinsufficieny is sufficient for all these effects because the second allele of Prep1 is not lost even at late stages. Therefore, the tumor-suppressive activity of Prep1 is intertwined with both the interference with Myc-induced apoptosis as well as with natural developmental functions of the protein

    Mechanisms of transcriptional control of glucose metabolism in hepatocytes

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    The hepatic tissue plays a key role in the regulation and maintenance of stable blood glucose levels. The liver is the main gluconeogenesis organ of the body and is under constant hormonal control to determine the metabolic activity of hepatocytes. Hormonal signals trigger multiple post-translational regulatory mechanisms that alter the activity of key enzymes of glucose metabolism. A crucial role in the long-term control of glucose production and metabolism is played by pre-translational regulation at the level of gene expression of metabolic enzymes. There is growing evidence that this regulation, which is realised via control of the activity of transcription factors, provides constant adjustment of the body to changing environmental conditions and that its disruption leads to the development of metabolic diseases associated with insulin resistance. Therefore, the study of transcription factors that regulate glucose metabolism in the liver and the search for mechanisms to control them is of great biomedical importance in the context of metabolic disease treatment research
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