154 research outputs found

    A fine-grained silicon detector for high-energy gamma-ray astrophysics

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    We propose a silicon telescope to be placed in a satellite for the search of g-ray sources in the energy range between 25 MeV and 100 GeV. The proposed experiment will have an area of 2500 cm2, an energy resolution ranging from 7% to 8% and an angular resolution from 0.2 and 0.1 degrees between 1 GeV and 10 GeV. The telescope is based on the use of silicon strip detectors. Together with the energy measurement, a calorimeter of this type allows the determination of the particle type and its arrival direction, through the analysis of the spatial and energetic distribution of the electromagnetic shower produced. Detectors based on silicon technology have many advantages for space applications: no gas refilling system or high voltages, no need of photomultipliers (low consumption), short dead time, possibility of selftriggering. The GILDA project has been designed having in mind the weight limitation of 400 kg required by the Resource-01 satellite and it is carried out in the framework of the RIM (Russian Italian Mission) program. The launch is foreseen for the beginning of the next century

    Inferring possible magnetic field strength of accreting inflows in EXor-type objects from scaled laboratory experiments

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    Aims. EXor-type objects are protostars that display powerful UV-optical outbursts caused by intermittent and powerful events of magnetospheric accretion. These objects are not yet well investigated and are quite difficult to characterize. Several parameters, such as plasma stream velocities, characteristic densities, and temperatures, can be retrieved from present observations. As of yet, however, there is no information about the magnetic field values and the exact underlying accretion scenario is also under discussion. Methods. We use laboratory plasmas, created by a high power laser impacting a solid target or by a plasma gun injector, and make these plasmas propagate perpendicularly to a strong external magnetic field. The propagating plasmas are found to be well scaled to the presently inferred parameters of EXor-type accretion event, thus allowing us to study the behaviour of such episodic accretion processes in scaled conditions. Results. We propose a scenario of additional matter accretion in the equatorial plane, which claims to explain the increased accretion rates of the EXor objects, supported by the experimental demonstration of effective plasma propagation across the magnetic field. In particular, our laboratory investigation allows us to determine that the field strength in the accretion stream of EXor objects, in a position intermediate between the truncation radius and the stellar surface, should be of the order of 100 G. This, in turn, suggests a field strength of a few kilogausses on the stellar surface, which is similar to values inferred from observations of classical T Tauri stars

    Study of the ion plasma flow generated by a high-current vacuum arc

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    The vacuum arc discharge is intensively explored for a long time. It acts as a source of multiply charged plasma. The results of the special type plasma gun (5-10 kA, 12 μs) ion flow study with high temporal resolution and the electrode erosion dependences on the amplitude of the current pulse are presented in the research. The ion flow intensity had good reproducibility from series to series, while the values of total mass erosion differ significantly for different series of experiments under the same conditions. The ion erosion was measured to be significantly higher than that for arc sources with currents up to 1 kA. © 2019 IOP Publishing Ltd. All rights reserved.Russian Foundation for Basic Research, RFBR: 17-02-00346, 18-08-00547Russian Academy of Sciences, RAS18-2-2-16This work was supported in part by RFBR (grant Nos. 17-02-00346, 18-08-00547, 19-08-00783, 19-58-53006), by RAS Program (project No. 11) and UB RAS Program (project No. 18-2-2-16)

    Thioredoxin is involved in endothelial cell extracellular transglutaminase 2 activation mediated by celiac disease patient IgA

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    Purpose: To investigate the role of thioredoxin (TRX), a novel regulator of extracellular transglutaminase 2 (TG2), in celiac patients IgA (CD IgA) mediated TG2 enzymatic activation. Methods: TG2 enzymatic activity was evaluated in endothelial cells (HUVECs) under different experimental conditions by ELISA and Western blotting. Extracellular TG2 expression was studied by ELISA and immunofluorescence. TRX was analysed by Western blotting and ELISA. Serum immunoglobulins class A from healthy subjects (H IgA) were used as controls. Extracellular TG2 enzymatic activity was inhibited by R281. PX12, a TRX inhibitor, was also employed in the present study. Results: We have found that in HUVECs CD IgA is able to induce the activation of extracellular TG2 in a dose-dependent manner. Particularly, we noted that the extracellular modulation of TG2 activity mediated by CD IgA occurred only under reducing conditions, also needed to maintain antibody binding. Furthermore, CD IgA-treated HUVECs were characterized by a slightly augmented TG2 surface expression which was independent from extracellular TG2 activation. We also observed that HUVECs cultured in the presence of CD IgA evinced decreased TRX surface expression, coupled with increased secretion of the protein into the culture medium. Intriguingly, inhibition of TRX after CD IgA treatment was able to overcome most of the CD IgA-mediated effects including the TG2 extracellular transamidase activity. Conclusions: Altogether our findings suggest that in endothelial cells CD IgA mediate the constitutive activation of extracellular TG2 by a mechanism involving the redox sensor protein TRX

    Tissue Transglutaminase Promotes Drug Resistance and Invasion by Inducing Mesenchymal Transition in Mammary Epithelial Cells

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    Recent observations that aberrant expression of tissue transglutaminase (TG2) promotes growth, survival, and metastasis of multiple tumor types is of great significance and could yield novel therapeutic targets for improved patient outcomes. To accomplish this, a clear understanding of how TG2 contributes to these phenotypes is essential. Using mammary epithelial cell lines (MCF10A, MCF12A, MCF7 and MCF7/RT) as a model system, we determined the impact of TG2 expression on cell growth, cell survival, invasion, and differentiation. Our results show that TG2 expression promotes drug resistance and invasive functions by inducing epithelial-mesenchymal transition (EMT). Thus, TG2 expression supported anchorage-independent growth of mammary epithelial cells in soft-agar, disrupted the apical-basal polarity, and resulted in disorganized acini structures when grown in 3D-culture. At molecular level, TG2 expression resulted in loss of E-cadherin and increased the expression of various transcriptional repressors (Snail1, Zeb1, Zeb2 and Twist1). Tumor growth factor-beta (TGF-β) failed to induce EMT in cells lacking TG2 expression, suggesting that TG2 is a downstream effector of TGF-β-induced EMT. Moreover, TG2 expression induced stem cell-like phenotype in mammary epithelial cells as revealed by enrichment of CD44+/CD24-/low cell populations. Overall, our studies show that aberrant expression of TG2 is sufficient for inducing EMT in epithelial cells and establish a strong link between TG2 expression and progression of metastatic breast disease

    Extracellular Transglutaminase 2 Is Catalytically Inactive, but Is Transiently Activated upon Tissue Injury

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    Transglutaminase 2 (TG2) is a multifunctional mammalian protein with transamidase and signaling properties. Using selective TG2 inhibitors and tagged nucleophilic amine substrates, we show that the majority of extracellular TG2 is inactive under normal physiological conditions in cell culture and in vivo. However, abundant TG2 activity was detected around the wound in a standard cultured fibroblast scratch assay. To demonstrate wounding-induced activation of TG2 in vivo, the toll-like receptor 3 ligand, polyinosinic-polycytidylic acid (poly(I:C)), was injected in mice to trigger small intestinal injury. Although no TG2 activity was detected in vehicle-treated mice, acute poly(I:C) injury resulted in rapid TG2 activation in the small intestinal mucosa. Our findings provide a new basis for understanding the role of TG2 in physiology and disease

    The Redox State of Transglutaminase 2 Controls Arterial Remodeling

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    While inward remodeling of small arteries in response to low blood flow, hypertension, and chronic vasoconstriction depends on type 2 transglutaminase (TG2), the mechanisms of action have remained unresolved. We studied the regulation of TG2 activity, its (sub) cellular localization, substrates, and its specific mode of action during small artery inward remodeling. We found that inward remodeling of isolated mouse mesenteric arteries by exogenous TG2 required the presence of a reducing agent. The effect of TG2 depended on its cross-linking activity, as indicated by the lack of effect of mutant TG2. The cell-permeable reducing agent DTT, but not the cell-impermeable reducing agent TCEP, induced translocation of endogenous TG2 and high membrane-bound transglutaminase activity. This coincided with inward remodeling, characterized by a stiffening of the artery. The remodeling could be inhibited by a TG2 inhibitor and by the nitric oxide donor, SNAP. Using a pull-down assay and mass spectrometry, 21 proteins were identified as TG2 cross-linking substrates, including fibronectin, collagen and nidogen. Inward remodeling induced by low blood flow was associated with the upregulation of several anti-oxidant proteins, notably glutathione-S-transferase, and selenoprotein P. In conclusion, these results show that a reduced state induces smooth muscle membrane-bound TG2 activity. Inward remodeling results from the cross-linking of vicinal matrix proteins, causing a stiffening of the arterial wall
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