Antenna of the space radiotelescope KRT-3

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

Gamma-ray Flares and VLBI Outbursts of Blazars

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]

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

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 $40^o$ 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

The brightest OH maser in the sky: a flare of emission in W75 N

A flare of maser radio emission in the OH-line 1665 MHz has been discovered in the star forming region W75 N in 2003, with the flux density of about 1000 Jy. At the time it was the strongest OH maser detected during the whole history of observations since the discovery of cosmic masers in 1965. The flare emission is linearly polarized with a degree of polarization near 100%. A weaker flare with a flux of 145 Jy was observed in this source in 2000 - 2001, which was probably a precursor of the powerful flare. Intensity of two other spectral features has decreased after beginning of the flare. Such variation of the intensity of maser condensation emission (increasing of one and decreasing of the other) can be explained by passing of the magneto hydrodynamic shock across regions of enhanced gas concentration.Comment: 9 pages with 2 figures, accepted for publication in Astronomy Letter

The Far-Infrared Spectral Energy Distributions of X-ray-selected Active Galaxies

[Abridged] We present ISO far-infrared (IR) observations of 21 hard X-ray selected AGN from the HEAO-1 A2 sample. We compare the far-IR to X-ray spectral energy distributions (SEDs) of this sample with various radio and optically selected AGN samples. The hard-X-ray selected sample shows a wider range of optical/UV shapes extending to redder near-IR colors. The bluer objects are Seyfert 1s, while the redder AGN are mostly intermediate or type 2 Seyferts. This is consistent with a modified unification model in which the amount of obscuring material increases with viewing angle and may be clumpy. Such a scenario, already suggested by differing optical/near-IR spectroscopic and X-ray AGN classifications, allows for different amounts of obscuration of the continuum emission in different wavebands and of the broad emission line region which results in a mixture of behaviors for AGN with similar optical emission line classifications. The resulting limits on the column density of obscuring material through which we are viewing the redder AGN are 100 times lower than for the standard optically thick torus models. The resulting decrease in optical depth of the obscuring material allows the AGN to heat more dust at larger radial distances. We show that an AGN-heated, flared, dusty disk with mass 10^9 solar and size of few hundred pc is able to generate optical-far-IR SEDs which reproduce the wide range of SEDs present in our sample with no need for an additional starburst component to generate the long-wavelength, cooler part of the IR continuum.Comment: 40 pages, 14 figures, accepted for publication in Astrophysical Journal, V. 590, June 10, 200

Mutant INS-Gene Induced Diabetes of Youth: Proinsulin Cysteine Residues Impose Dominant-Negative Inhibition on Wild-Type Proinsulin Transport

Recently, a syndrome of Mutant INS-gene-induced Diabetes of Youth (MIDY, derived from one of 26 distinct mutations) has been identified as a cause of insulin-deficient diabetes, resulting from expression of a misfolded mutant proinsulin protein in the endoplasmic reticulum (ER) of insulin-producing pancreatic beta cells. Genetic deletion of one, two, or even three alleles encoding insulin in mice does not necessarily lead to diabetes. Yet MIDY patients are INS-gene heterozygotes; inheritance of even one MIDY allele, causes diabetes. Although a favored explanation for the onset of diabetes is that insurmountable ER stress and ER stress response from the mutant proinsulin causes a net loss of beta cells, in this report we present three surprising and interlinked discoveries. First, in the presence of MIDY mutants, an increased fraction of wild-type proinsulin becomes recruited into nonnative disulfide-linked protein complexes. Second, regardless of whether MIDY mutations result in the loss, or creation, of an extra unpaired cysteine within proinsulin, Cys residues in the mutant protein are nevertheless essential in causing intracellular entrapment of co-expressed wild-type proinsulin, blocking insulin production. Third, while each of the MIDY mutants induces ER stress and ER stress response; ER stress and ER stress response alone appear insufficient to account for blockade of wild-type proinsulin. While there is general agreement that ultimately, as diabetes progresses, a significant loss of beta cell mass occurs, the early events described herein precede cell death and loss of beta cell mass. We conclude that the molecular pathogenesis of MIDY is initiated by perturbation of the disulfide-coupled folding pathway of wild-type proinsulin

Protein misfolding and dysregulated protein homeostasis in autoinflammatory diseases and beyond.

Cells have a number of mechanisms to maintain protein homeostasis, including proteasome-mediated degradation of ubiquitinated proteins and autophagy, a regulated process of ‘self-eating’ where the contents of entire organelles can be recycled for other uses. The unfolded protein response prevents protein overload in the secretory pathway. In the past decade, it has become clear that these fundamental cellular processes also help contain inflammation though degrading pro-inflammatory protein complexes such as the NLRP3 inflammasome. Signaling pathways such as the UPR can also be co-opted by toll-like receptor and mitochondrial reactive oxygen species signaling to induce inflammatory responses. Mutations that alter key inflammatory proteins, such as NLRP3 or TNFR1, can overcome normal protein homeostasis mechanisms, resulting in autoinflammatory diseases. Conversely, Mendelian defects in the proteasome cause protein accumulation, which can trigger interferon-dependent autoinflammatory disease. In non-Mendelian inflammatory diseases, polymorphisms in genes affecting the UPR or autophagy pathways can contribute to disease, and in diseases not formerly considered inflammatory such as neurodegenerative conditions and type 2 diabetes, there is increasing evidence that cell intrinsic or environmental alterations in protein homeostasis may contribute to pathogenesis

The pancreatic beta cell surface proteome

The pancreatic beta cell is responsible for maintaining normoglycaemia by secreting an appropriate amount of insulin according to blood glucose levels. The accurate sensing of the beta cell extracellular environment is therefore crucial to this endocrine function and is transmitted via its cell surface proteome. Various surface proteins that mediate or affect beta cell endocrine function have been identified, including growth factor and cytokine receptors, transporters, ion channels and proteases, attributing important roles to surface proteins in the adaptive behaviour of beta cells in response to acute and chronic environmental changes. However, the largely unknown composition of the beta cell surface proteome is likely to harbour yet more information about these mechanisms and provide novel points of therapeutic intervention and diagnostic tools. This article will provide an overview of the functional complexity of the beta cell surface proteome and selected surface proteins, outline the mechanisms by which their activity may be modulated, discuss the methods and challenges of comprehensively mapping and studying the beta cell surface proteome, and address the potential of this interesting subproteome for diagnostic and therapeutic applications in human disease