HERPESVIRUS INFECTIONS AND CLINICAL-IMMUNOLOGIC INTERACTIONS IN PATIENTS WITH EARLY-ONSET ALZHEIMER’S DISEASE AND LATE-ONSET ALZHEIMER’S DISEASE

Alzheimer’s disease (AD) is currently the most common cause of dementia. A significant role in the pathogenesis of AD belongs to the activation of the mechanisms of neuroinflammation. There is a hypothesis that chronic infections may play a role in the maintenance of the inflammatory response in AD. The aim of this work was to study the detection rate and DNA level of herpesviruses, as well as their possible relationship with the level of the key cytokines and with clinical parameters of AD in patients with early and late onset. 30 patients with AD and 33 healthy volunteers were enrolled. The quantitative determination of DNA of CMV, EBV, HHV-6, HHV-7 was carried out by PCR. The level of cytokines and soluble IL-1β antagonist (IL-1ra) in the blood was determined by ELISA. Herpesvirus infection with increased viral load was determined if at least one of the criteria was present: 1) DNA level of EBV and/or HHV-6 > 10,000 copies/ml in saliva; 2) presence of DNA of at least one of the EBV, HHV-6, HHV-7 viruses in the blood. In the subgroup of patients with early onset and increased viral load, there was a higher increase in the levels of a number of cytokines: proinflammatory IL-8 and IL-12, a Th2-cytokine IL-4, a cytokine of the adaptive immune response IL-2. However, the level of the anti-inflammatory protein IL-1ra was lower than in the controls. These changes may indicate a dysregulation of the antiviral response, with a predominance of activation of systemic inflammation and Th2-mediated reactions. Also, in early onset AD the increased viral load was associated with lower scores on Boston naming test. The results indicate that in studies of AD mechanisms and in the search for prognostic markers of the disease, it is important to take into account the heterogeneity of AD in terms of genetic predisposition factors, risk factors, immune parameters and clinical data. Such approach is necessary for the subsequent development of personalized approaches to the prevention and treatment of AD

21cm Absorption by Compact Hydrogen Disks Around Black Holes in Radio-Loud Nuclei of Galaxies

The clumpy maser disks observed in some galactic nuclei mark the outskirts of the accretion disk that fuels the central black hole and provide a potential site of nuclear star formation. Unfortunately, most of the gas in maser disks is currently not being probed; large maser gains favor paths that are characterized by a small velocity gradient and require rare edge-on orientations of the disk. Here we propose a method for mapping the atomic hydrogen distribution in nuclear disks through its 21cm absorption against the radio continuum glow around the central black hole. In NGC 4258, the 21cm optical depth may approach unity for high angular-resolution (VLBI) imaging of coherent clumps which are dominated by thermal broadening and have the column density inferred from X-ray absorption data, ~10^{23}/cm^2. Spreading the 21cm absorption over the full rotation velocity width of the material in front of the narrow radio jets gives a mean optical depth of ~0.1. Spectroscopic searches for the 21cm absorption feature in other galaxies can be used to identify the large population of inclined gaseous disks which are not masing in our direction. Follow-up imaging of 21cm silhouettes of accelerating clumps within these disks can in turn be used to measure cosmological distances.Comment: 4 page

A combined model for the X-ray to gamma-ray emission of Cyg X-1

We use recent data obtained by three (OSSE, BATSE, and COMPTEL) of four instruments on board the Compton Gamma Ray Observatory, to construct a model of Cyg X-1 which describes its emission in a broad energy range from soft X-rays to MeV gamma-rays self-consistently. The gamma-ray emission is interpreted to be the result of Comptonization, bremsstrahlung, and positron annihilation in a hot optically thin and spatially extended region surrounding the whole accretion disk. For the X-ray emission a standard corona-disk model is applied. We show that the Cyg X-1 spectrum accumulated by the CGRO instruments during a ~4 year time period between 1991 and 1995, as well as the HEAO-3 gamma1 and gamma2 spectra can be well represented by our model. The derived parameters match the observational results obtained from X-ray measurements.Comment: 11 pages including 6 ps-figures and 2 tables, latex2e, uses emulateapj.sty (ver. of 18 Sep 96, enclosed), epsfig.sty, times.sty. To appear in July 20, 1998 issue of ApJ (v.502

THE COMBINED PROCESSES STUDY FOR MANUFACTURING AIRCRAFT PARTS

The article is devoted to research of the combined processes of forming tubular billets with various media in the process of bending-expanding, breaking-down -expanding while using thermal effects. The paper discusses the processes of forming tubular billets of hard punches, using elastic-granular materials, the peculiarities of forming tubular billets, while the breaking-down -expanding of crimp in a hard punch using elastic-granular bodies. The article presents experimental studies of the bending-expanding of tubular billets in horn-shaped blanks. The authors established the main features of billet distorting in the combined process. The article shows a diagram of the true distorting distribution in the process of stretching and compression in the horn-shaped blanks. The recommendations allow increasing the bending moment and realizing better shaping. The authors make conclusions about the prospects of the application of combined processes in air and rocket

Prognosis of Alzheimer’s Disease Using Quantitative Mass Spectrometry of Human Blood Plasma Proteins and Machine Learning

Early recognition of the risk of Alzheimer’s disease (AD) onset is a global challenge that requires the development of reliable and affordable screening methods for wide-scale application. Proteomic studies of blood plasma are of particular relevance; however, the currently proposed differentiating markers are poorly consistent. The targeted quantitative multiple reaction monitoring (MRM) assay of the reported candidate biomarkers (CBs) can contribute to the creation of a consistent marker panel. An MRM-MS analysis of 149 nondepleted EDTA–plasma samples (MHRC, Russia) of patients with AD (n = 47), mild cognitive impairment (MCI, n = 36), vascular dementia (n = 8), frontotemporal dementia (n = 15), and an elderly control group (n = 43) was performed using the BAK 125 kit (MRM Proteomics Inc., Canada). Statistical analysis revealed a significant decrease in the levels of afamin, apolipoprotein E, biotinidase, and serum paraoxonase/arylesterase 1 associated with AD. Different training algorithms for machine learning were performed to identify the protein panels and build corresponding classifiers for the AD prognosis. Machine learning revealed 31 proteins that are important for AD differentiation and mostly include reported earlier CBs. The best-performing classifiers reached 80% accuracy, 79.4% sensitivity and 83.6% specificity and were able to assess the risk of developing AD over the next 3 years for patients with MCI. Overall, this study demonstrates the high potential of the MRM approach combined with machine learning to confirm the significance of previously identified CBs and to propose consistent protein marker panels