231 research outputs found
β-cell dysfunctional ERAD/ubiquitin/proteasome system in type 2 diabetes mediated by islet amyloid polypeptide-induced UCH-L1 deficiency.
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
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 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
VLBI imaging of a flare in the Crab Nebula: More than just a spot
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 \,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
Successful Versus Failed Adaptation to High-Fat Diet–Induced Insulin Resistance: The Role of IAPP-Induced β-Cell Endoplasmic Reticulum Stress
ObjectiveObesity is a known risk factor for type 2 diabetes. However, most obese individuals do not develop diabetes because they adapt to insulin resistance by increasing beta-cell mass and insulin secretion. Islet pathology in type 2 diabetes is characterized by beta-cell loss, islet amyloid derived from islet amyloid polypeptide (IAPP), and increased beta-cell apoptosis characterized by endoplasmic reticulum (ER) stress. We hypothesized that IAPP-induced ER stress distinguishes successful versus unsuccessful islet adaptation to insulin resistance.Research design and methodsTo address this, we fed wild-type (WT) and human IAPP transgenic (HIP) rats either 10 weeks of regular chow or a high-fat diet and prospectively examined the relations among beta-cell mass and turnover, beta-cell ER stress, insulin secretion, and insulin sensitivity.ResultsA high-fat diet led to comparable insulin resistance in WT and HIP rats. WT rats compensated with increased insulin secretion and beta-cell mass. In HIP rats, in contrast, neither beta-cell function nor mass compensated for the increased insulin demand, leading to diabetes. The failure to increase beta-cell mass in HIP rats was the result of ER stress-induced beta-cell apoptosis that increased in proportion to diet-induced insulin resistance.ConclusionsIAPP-induced ER stress distinguishes the successful versus unsuccessful islet adaptation to a high-fat diet in rats. These studies are consistent with the hypothesis that IAPP oligomers contribute to increased beta-cell apoptosis and beta-cell failure in humans with type 2 diabetes
РЕЛЯТИВИСТСКИЙ ГЕЛИТРОН
This paper formulates nonlinear equations for the microwave generator of a new type - relativistic helitron and performs analysis and optimization on this basis. It is a device with centrifugal electrostatic focusing of an axisymmetric helical relativistic electron beam interacting with the Hn1 l mode of the electromagnetic field of a coaxial resonator. On the basis of numerical simulation and optimization it's shown that its efficiency exceeds the efficiency of relativistic traveling wave tube (TWT) and back wave tube (BWT).Сформулированы нелинейные уравнения и на их основе проведен анализ и оптимизация генератора СВЧ нового типа - релятивистского гелитрона. Это прибор с центробежной электростатической фокусировкой осесимметричного винтового релятивистского электронного потока, взаимодействующего с Hn1l модой электромагнитного поля коаксиального резонатора. На основе численного моделирования и оптимизации показано, что его эффективность превосходит эффективность релятивистских лампы бегущей волны (ЛБВ) и лампы обратной волны (ЛОВ)
СЕЛЕКЦИЯ МОД H0in И E1in В ЦИЛИНДРИЧЕСКОМ РЕЗОНАТОРЕ С КРУГОВЫМ СЕЧЕНИЕМ
The cylindrical resonators at operating H0 in modes are widely used in measuring technology and gyroresonance microwave devices. However, the E1 in modes resonance coincides with the H0 in one. The article shows for detuning E1 in modes should be used ring slots at the end walls of the resonator.Цилиндрические резонаторы с рабочими модами H0in находят широкое применение в измерительной технике и гирорезонансных приборах СВЧ. Однако совпадающий с H0in резонанс имеют моды E1 in . В сообщении показано, что для отстройки E1 in следует использовать кольцевые щели у торцевых стенок резонатора
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
Movement of a relativistic electron in crossed electric and magnetic fields
Показано, что существующие в современной литературе представления о движении
электрона в скрещенных полях неверны. В случае релятивистских скоростей движение электрона нельзя
представить как наложение дрейфа со скоростью u = E0/B0 и вращения с частотой = eB0/m (e, m – заряд
и релятивистская масса электрона). В релятивистском случае эти движения не разделяются,
а мгновенная частота вращения электрона в неподвижной относительно E0, B0 системе координат
непостоянна: зависит от m, которая при вращении меняется в значительных пределах. It is shown that the ideas about the electron motion into electric and magnetic crossed fields existing
in the modern literature are incorrected. For relativistic velocity case the electron motion can't be imagined
by the superposition of the drift with velocity u = E0/B0 and the rotation with frequency = eB0/m (e, m
is charge and mass of relativistic electron). In the relativistic case these motions are not separated, moreover
the instantaneous rotation frequency of relativistic electron is unstable for fixed coordinate system (E0, B0):
depends on m, which varies considerably during rotation
БЕЗМАГНИТНЫЙ КЛИСТРОН - УДВОИТЕЛЬ ЧАСТОТЫ С ПОПЕРЕЧНОЙ МОДУЛЯЦИЕЙ
The article presents nonlinear theory and calculating efficiency of the new type electronic device - frequency non-magnetic doubler-klystron with a transverse modulation and a strip relativistic electron beam. In contrast to the known design of a frequency doubler-klystron with using transverse modulation authors apply an electrostatic lens for electronic grouping. The latter allows the use of cryogenic superconducting electrodynamic systems, which is very important for high-power devices of the terahertz range. Moreover, there isn't necessary for additional energy consumption in the present construction due to the electromagnetic lens absence.Приведены нелинейная теория и расчет КПД электронного прибора нового типа - безмагнитного клистрона - удвоителя частоты с поперечной модуляцией ленточного релятивистского электронного потока. В отличие от известной конструкции клистрона - удвоителя частоты с поперечной модуляцией в области группировки электронов используется не магнитная линза, а электростатическая. Последнее позволяет использовать криогенные сверхпроводящие электродинамические системы, что весьма важно для мощных приборов терагерцового диапазона. Кроме того, отпадает необходимость в энергозатратах на питание электромагнитов линзы в исходной конструкци
ПЕРСПЕКТИВНЫЕ МОДИФИКАЦИИ ГИРОРЕЗОНАНСНЫХ ПРИБОРОВ
The perspective gyro-resonance modifications were considered - pulsed gyro-TWT, gyro-TWT at electromagnetic super radiating mode, cascaded gyro-TWT with a corrugated waveguide, broadband gyro-amplifier with a conical waveguide, high-orbit gyrotron with a peniotron cavity, gyroklystron with conical coaxial cavities, gyroklystron with Fabry-Perot cavities, low-voltage gyroklystron and gyrotron with an inhomogeneous magnetic field.Рассмотрены перспективные модификации гирорезонансных приборов - импульсная гиро-ЛБВ, гиро-ЛБВ в режиме сверхизлучения, каскадная гиро-ЛБВ на гофрированном волноводе, широкополосный гироусилитель на коническом волноводе, высокоорбитный гиротрон на пениотронном резонаторе, гироклистрон на конических коаксиальных резонаторах, гироклистрон на резонаторах Фабри-Перо, низковольтные гироклистрон и гиротрон с неоднородным магнитным полем
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