Common Security of the Czech Republic and Slovakia Airspace by JAS-39 GRIPEN Fighter Aircrafts

Diplomová práce se zabývá problematikou ochrany vzdušného prostoru České republiky a Slovenska nadzvukovými letouny JAS-39 Gripen. První část práce je zaměřena na teoretickou rovinu obrany jako služby v obecném zájmu nehospodářské povahy a na vybrané pojmy z oblasti obrany a bezpečnosti státu. Druhá část se zabývá komparací Armády České republiky a Ozbrojených sil Slovenské republiky se zaměřením na vzdušné síly a možnosti ochrany vzdušného prostoru pomoci nadzvukových bojových letounů obou zemí. Třetí částí je zhodnocení možnosti pořízení a provozování nadzvukových letounů JAS-39 Gripen Vzdušnými silami Ozbrojených sil Slovenské republiky, které vychází z předchozího zkoumání a zároveň přibližuje možnosti zabezpečení společného vzdušného prostoru obou zemí. V poslední části jsou doporučení pro společné zabezpečení vzdušného prostoru obou zemí, vycházející z jednotlivých možností, ale i se stávající bezpečnostní a ekonomické situace.This thesis deals with the airspace protection of Czech Republic and Slovakia by JAS-39 Gripen supersonic aircrafts. The first part is focused on the theoretical level of defense as a service of general non-economic interest and certain terms of defense and national security. The second part deals with the comparsion of the Czech Army and Slovak Army with focuse on options of airspace protection by supersonic fighter aircrafts of both countries. The third part evaluates the possibility of acquisition and usage JAS-39 supersonic aircraft by the Slovak Air Force which is based on previous research and shows how to secure the common airspace of both countries. In the final chapter are recommendations for common airspace security of both countries based on each option, but also on current security and economic situation.153 - Katedra veřejné ekonomikyvelmi dobř

Salivary PYY: A Putative Bypass to Satiety

Peptide YY3-36 is a satiation hormone released postprandially into the bloodstream from L-endocrine cells in the gut epithelia. In the current report, we demonstrate PYY3-36 is also present in murine as well as in human saliva. In mice, salivary PYY3-36 derives from plasma and is also synthesized in the taste cells in taste buds of the tongue. Moreover, the cognate receptor Y2R is abundantly expressed in the basal layer of the progenitor cells of the tongue epithelia and von Ebner's gland. The acute augmentation of salivary PYY3-36 induced stronger satiation as demonstrated in feeding behavioral studies. The effect is mediated through the activation of the specific Y2 receptor expressed in the lingual epithelial cells. In a long-term study involving diet-induced obese (DIO) mice, a sustained increase in PYY3-36 was achieved using viral vector-mediated gene delivery targeting salivary glands. The chronic increase in salivary PYY3-36 resulted in a significant long-term reduction in food intake (FI) and body weight (BW). Thus this study provides evidence for new functions of the previously characterized gut peptide PYY3-36 suggesting a potential simple and efficient alternative therapeutic approach for the treatment of obesity

Engineering and In Vitro Selection of a Novel AAV3B Variant with High Hepatocyte Tropism and Reduced Seroreactivity

Limitations to successful gene therapy with adeno-associated virus (AAV) can comprise pre-existing neutralizing antibodies to the vector capsid that can block cellular entry, or inefficient transduction of target cells that can lead to sub-optimal expression of the therapeutic transgene. Recombinant serotype 3 AAV (AAV3) is an emerging candidate for liver-directed gene therapy. In this study, we integrated rational design by using a combinatorial library derived from AAV3B capsids with directed evolution by in vitro selection for liver-targeted AAV variants. The AAV3B-DE5 variant described herein was undetectable in the original viral library but gained a selective advantage upon in vitro passaging in human hepatocarcinoma spheroid cultures. AAV3B-DE5 contains 24 capsid amino acid substitutions compared with AAV3B, distributed among all five variable regions, with strong selective pressure on VR-IV, VR-V, and VR-VII. In vivo, AAV3B-DE5 demonstrated improved human hepatocyte tropism in a liver chimeric mouse model. Importantly, this variant exhibited reduced seroreactivity to human intravenous immunoglobulin (i.v. Ig), as well as individual serum samples from 100 healthy human donors. Therefore, molecular evolution using a combinatorial library platform generated a viral capsid with high hepatocyte tropism and enhanced evasion of pre-existing AAV neutralizing antibodies

Efficient Transduction of Vascular Endothelial Cells with Recombinant Adeno-Associated Virus Serotype 1 and 5 Vectors

Recombinant adeno-associated virus (rAAV) has become an attractive tool for gene therapy because of its ability to transduce both dividing and nondividing cells, elicit a limited immune response, and the capacity for imparting long-term transgene expression. Previous studies have utilized rAAV serotype 2 predominantly and found that transduction of vascular cells is relatively inefficient. The purpose of the present study was to evaluate the transduction efficiency of rAAV serotypes 1 through 5 in human and rat aortic endothelial cells (HAEC and RAEC). rAAV vectors with AAV2 inverted terminal repeats containing the human α1-antitrypsin (hAAT) gene were transcapsidated using helper plasmids to provide viral capsids for the AAV1 through 5 serotypes. True type rAAV2 and 5 vectors encoding β-galactosidase or green fluorescence protein were also studied. Infection with rAAV1 resulted in the most efficient transduction in both HAEC and RAEC compared to other serotypes (p < 0.001) at 7 days posttransduction. Interestingly, expression was increased in cells transduced with rAAV5 to levels surpassing rAAV1 by day 14 and 21. Transduction with rAAV1 was completely inhibited by removal of sialic acid with sialidase, while heparin had no effect. These studies are the first demonstration that sialic acid residues are required for rAAV1 transduction in endothelial cells. Transduction of rat aortic segments ex vivo and in vivo demonstrated significant transgene expression in endothelial and smooth muscle cells with rAAV1 and 5 serotype vectors, in comparison to rAAV2. These results suggest the unique potential of rAAV1 and rAAV5-based vectors for vascular-targeted gene-based therapeutic strategies

Aerodynamic investigations of ventilated brake discs.

The heat dissipation and performance of a ventilated brake disc strongly depends on the aerodynamic characteristics of the flow through the rotor passages. The aim of this investigation was to provide an improved understanding of ventilated brake rotor flow phenomena, with a view to improving heat dissipation, as well as providing a measurement data set for validation of computational fluid dynamics methods. The flow fields at the exit of four different brake rotor geometries, rotated in free air, were measured using a five-hole pressure probe and a hot-wire anemometry system. The principal measurements were taken using two-component hot-wire techniques and were used to determine mean and unsteady flow characteristics at the exit of the brake rotors. Using phase-locked data processing, it was possible to reveal the spatial and temporal flow variation within individual rotor passages. The effects of disc geometry and rotational speed on the mean flow, passage turbulence intensity, and mass flow were determined. The rotor exit jet and wake flow were clearly observed as characterized by the passage geometry as well as definite regions of high and low turbulence. The aerodynamic flow characteristics were found to be reasonably independent of rotational speed but highly dependent upon rotor geometry

BACTERIOPHAGES MORGANELLA MORGANII AND ITS APPLICATION WITH THE GASTROINTESTINAL DISEASES OF PIGS

For the first time, in the pig-breeding farms of the Ulyanovsky and Samarsky regions, the diagnostic investigations have been performed with a view to studying the etiological significance of the M. morganii in the infection diarrhea of the pigs-suckers. The new specific treatment-prophylaxis preparation-bacteriophage of morganells has been received; first its biological properties have been studied. The role of the M.norganii in the infection diarrhea of the pigs-suckers has been confirmed. The circulation of the morganells pathogenic strains in several pig-breeding farms of the Ulyanovsky and Samarsky regions has been established, their sensitivity to antibiotics and homologous bacteriophage has been determined. Offered has been the treatment-prophylaxis preparation - the morganellous bacteriophage; the technology of manufacture and the effective schemes of its application have been developed. For manufacture of the specific treatment-prophylaxis preparation, offered has been strain of phage M6, which has been recommended for application in the combination with the coliprotein phages with the diarrhea of the pigs-suckersAvailable from VNTIC / VNTIC - Scientific & Technical Information Centre of RussiaSIGLERURussian Federatio

On a bound of the absolute constant in the Berry–Esseen inequality for i.i.d. Bernoulli random variables

It is shown that the absolute constant in the Berry–Esseen inequality for i.i.d. Bernoulli random variables is strictly less than the Esseen constant, if 1≤n≤500000, where n is a number of summands. This result is got both with the help of a supercomputer and an interpolation theorem, which is proved in the paper as well. In addition, applying the method developed by S. Nagaev and V. Chebotarev in 2009–2011, an upper bound is obtained for the absolute constant in the Berry–Esseen inequality in the case under consideration, which differs from the Esseen constant by no more than 0.06%. As an auxiliary result, we prove a bound in the local Moivre–Laplace theorem which has a simple and explicit form. Despite the best possible result, obtained by J. Schulz in 2016, we propose our approach to the problem of finding the absolute constant in the Berry–Esseen inequality for two-point distributions since this approach, combining analytical methods and the use of computers, could be useful in solving other mathematical problems