477 research outputs found

    Antenna of the space radiotelescope KRT-3

    Get PDF
    The questions of antenna design with a diameter of 3 m for space radio-interferometry are examined. The basic characteristics of the antenna are determined, on the basis of which a model of the antenna of a space radiotelescope of 3.1 m KRT-3 is developed and prepared. The technological peculiarities of the antenna preparation are examined. The results of measurement of the reflecting surfaces of the telescope are cited, which point to the fact that the antenna may operate to wave lengths in the order of 2 mm

    β-Cell failure in type 2 diabetes: a case of asking too much of too few?

    Get PDF
    The islet in type 2 diabetes (T2DM) is characterized by a deficit in β-cells, increased β-cell apoptosis, and extracellular amyloid deposits derived from islet amyloid polypeptide (IAPP). In the absence of longitudinal studies, it is unknown if the low β-cell mass in T2DM precedes diabetes onset (is a risk factor for diabetes) or develops as a consequence of the disease process. Although insulin resistance is a risk factor for T2DM, most individuals who are insulin resistant do not develop diabetes. By inference, an increased β-cell workload results in T2DM in some but not all individuals. We propose that the extent of the β-cell mass that develops during childhood may underlie subsequent successful or failed adaptation to insulin resistance in later life. We propose that a low innate β-cell mass in the face of subsequent insulin resistance may expose β-cells to a burden of insulin and IAPP biosynthetic demand that exceeds the cellular capacity for protein folding and trafficking. If this threshold is crossed, intracellular toxic IAPP membrane permeant oligomers (cylindrins) may form, compromising β-cell function and inducing β-cell apoptosis

    Identification of Bursting Water Maser Features in Orion KL

    Full text link
    In February 2011, a burst event of the H2_{2}O maser in Orion KL (Kleinmann-Low object) has started after 13-year silence. This is the third time to detect such phenomena in Orion KL, followed by those in 1979-1985 and 1998. We have carried out astrometric observations of the bursting H2_{2}O maser features in Orion KL with VERA (VLBI Exploration of Radio Astrometry), a Japanese VLBI network dedicated for astrometry. The total flux of the bursting feature at the LSR velocity of 7.58 km s1^{-1} reaches 4.4×104\times10^{4} Jy in March 2011. The intensity of the bursting feature is three orders of magnitudes larger than that of the same velocity feature in the quiescent phase in 2006. Two months later, another new feature appears at the LSR velocity of 6.95 km s1^{-1} in May 2011, separated by 12 mas north of the 7.58 km s1^{-1} feature. Thus, the current burst occurs at two spatially different features. The bursting masers are elongated along the northwest-southeast direction as reported in the previous burst in 1998. We determine the absolute positions of the bursting features for the first time ever with a submilli-arcsecond (mas) accuracy. Their positions are coincident with the shocked molecular gas called the Orion Compact Ridge. We tentatively detect the absolute proper motions of the bursting features toward southwest direction. It is most likely that the outflow from the radio source I or another young stellar object interacting with the Compact Ridge is a possible origin of the H2_{2}O maser burst.Comment: 12 pages, 3 figures, accepted for publication in ApJ

    Chronic GLP-1 receptor activation by exendin-4 induces expansion of pancreatic duct glands in rats and accelerates formation of dysplastic lesions and chronic pancreatitis in the Kras(G12D) mouse model.

    Get PDF
    Pancreatic duct glands (PDGs) have been hypothesized to give rise to pancreatic intraepithelial neoplasia (PanIN). Treatment with the glucagon-like peptide (GLP)-1 analog, exendin-4, for 12 weeks induced the expansion of PDGs with mucinous metaplasia and columnar cell atypia resembling low-grade PanIN in rats. In the pancreata of Pdx1-Cre; LSL-Kras(G12D) mice, exendin-4 led to acceleration of the disruption of exocrine architecture and chronic pancreatitis with mucinous metaplasia and increased formation of murine PanIN lesions. PDGs and PanIN lesions in rodent and human pancreata express the GLP-1 receptor. Exendin-4 induced proproliferative signaling pathways in human pancreatic duct cells, cAMP-protein kinase A and mitogen-activated protein kinase phosphorylation of cAMP-responsive element-binding protein, and increased cyclin D1 expression. These GLP-1 effects were more pronounced in the presence of an activating mutation of Kras and were inhibited by metformin. These data reveal that GLP-1 mimetic therapy may induce focal proliferation in the exocrine pancreas and, in the context of exocrine dysplasia, may accelerate formation of neoplastic PanIN lesions and exacerbate chronic pancreatitis

    LIM Protein Ajuba Participates in the Repression of the ATR-Mediated DNA Damage Response

    Get PDF
    LIM proteins constitute a superfamily characterized by the presence of a LIM domain, known to be involved in protein–protein interactions. Our previous work has implicated members of the Zyxin family of LIM proteins, namely TRIP6 and LPP, in the repression of the DNA damage response (DDR) at telomeres. Here, we describe a role for Ajuba, a closely related LIM molecule, in repressing the ATR-mediated DDR. We found that depletion of Ajuba led to apparent delays in the cell cycle, accompanied with increased Rb phosphorylation, Chk1 phosphorylation, induction of p53, and cell death. Ajuba could be found in a complex with replication protein A (RPA), and its depletion led to RPA phosphorylation, known to be an early event in ATR activation. We propose that Ajuba protects against unscheduled ATR signaling by preventing inappropriate RPA phosphorylation

    Gamma-ray Flares and VLBI Outbursts of Blazars

    Full text link
    A model is developed for the time dependent electromagnetic - radio to gamma-ray - emission of active galactic nuclei, specifically, the blazars, based on the acceleration and creation of leptons at a propagating discontinuity or {\it front} of a Poynting flux jet. The front corresponds to a discrete relativistic jet component as observed with very-long-baseline-interferometry (VLBI). Equations are derived for the number, momentum, and energy of particles in the front taking into account synchrotron, synchrotron-self-Compton (SSC), and inverse-Compton processes as well as photon-photon pair production. The apparent synchrotron, SSC, and inverse-Compton luminosities as functions of time are determined. Predictions of the model are compared with observations in the gamma, optical and radio bands. The delay between the high-energy gamma-ray flare and the onset of the radio is explained by self-absorption and/or free-free absorption by external plasma. Two types of gamma-ray flares are predicted depending on pair creation in the front.Comment: 11 pages, submitted to ApJ. 10 figures can be obtained from R. Lovelace by sending postal address to [email protected]

    β-cell dysfunctional ERAD/ubiquitin/proteasome system in type 2 diabetes mediated by islet amyloid polypeptide-induced UCH-L1 deficiency.

    Get PDF
    ObjectiveThe islet in type 2 diabetes is characterized by β-cell apoptosis, β-cell endoplasmic reticulum stress, and islet amyloid deposits derived from islet amyloid polypeptide (IAPP). Toxic oligomers of IAPP form intracellularly in β-cells in humans with type 2 diabetes, suggesting impaired clearance of misfolded proteins. In this study, we investigated whether human-IAPP (h-IAPP) disrupts the endoplasmic reticulum-associated degradation/ubiquitin/proteasome system.Research design and methodsWe used pancreatic tissue from humans with and without type 2 diabetes, isolated islets from h-IAPP transgenic rats, isolated human islets, and INS 832/13 cells transduced with adenoviruses expressing either h-IAPP or a comparable expression of rodent-IAPP. Immunofluorescence and Western blotting were used to detect polyubiquitinated proteins and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) protein levels. Proteasome activity was measured in isolated rat and human islets. UCH-L1 was knocked down by small-interfering RNA in INS 832/13 cells and apoptosis was evaluated.ResultsWe report accumulation of polyubiquinated proteins and UCH-L1 deficiency in β-cells of humans with type 2 diabetes. These findings were reproduced by expression of oligomeric h-IAPP but not soluble rat-IAPP. Downregulation of UCH-L1 expression and activity to reproduce that caused by h-IAPP in β-cells induced endoplasmic reticulum stress leading to apoptosis.ConclusionsOur results indicate that defective protein degradation in β-cells in type 2 diabetes can, at least in part, be attributed to misfolded h-IAPP leading to UCH-L1 deficiency, which in turn further compromises β-cell viability

    VLBI imaging of a flare in the Crab Nebula: More than just a spot

    Full text link
    We report on very long baseline interferometry (VLBI) observations of the radio emission from the inner region of the Crab Nebula, made at 1.6 GHz and 5 GHz after a recent high-energy flare in this object. The 5 GHz data have provided only upper limits of 0.4 milli-Jansky (mJy) on the flux density of the pulsar and 0.4 mJy/beam on the brightness of the putative flaring region. The 1.6 GHz data have enabled imaging the inner regions of the nebula on scales of up to ~40". The emission from the inner "wisps" is detected for the first time with VLBI observations. A likely radio counterpart (designated "C1") of the putative flaring region observed with Chandra and HST is detected in the radio image, with an estimated flux density of 0.5±0.30.5\pm 0.3\,mJy and a size of 0.2-0.6". Another compact feature ("C2") is also detected in the VLBI image closer to the pulsar, with an estimated flux density of 0.4 +- 0.2 mJy and a size smaller than 0{\farcs}2. Combined with the broad-band SED of the flare, the radio properties of C1 yield a lower limit of ~0.5 mG for the magnetic field and a total minimum energy of 1.2*10^41 ergs vested in the flare (corresponding to using about 0.2% of the pulsar spin-down power). The 1.6 GHz observations provide upper limits for the brightness (0.2 mJy/beam) and total flux density (0.4 mJy) of the optical Knot 1 located at 0.6" from the pulsar. The absolute position of the Crab pulsar is determined, and an estimate of the pulsar proper motion is obtained.Comment: Astronomy & Astrophysics; accepted; 10 pages, 8 figure

    Observations of Lensed Relativistic Jets as a Tool of Constraining Lens Galaxy Parameters

    Full text link
    The possibility of using lensed relativistic jets on very small angular scales to construct proper models of spiral lens galaxies and to independently determine the Hubble constant is considered. The system B0218+357 is used as an example to illustrate that there exists a great choice of model parameters adequately reproducing its observed large-scale properties but leading to a significant spread in the Hubble constant. The jet image position angle is suggested as an additional parameter that allows the range of models under consideration to be limited. It is shown that the models for which the jet image position angles differ by at least 40o40^o can be distinguished between themselves during observations on very small angular scales. The possibility of observing the geometric properties of lensed relativistic jets and measuring the superluminal velocities of knot images on time scales of several months with very long baseline space interferometers is discussed.Comment: 11 pages, 3 figures, Will be published in the Astronomy Letters, V.37, PP.483-490, 201
    corecore