HNF4alpha Dysfunction as a Molecular Rational for Cyclosporine Induced Hypertension

Induction of tolerance against grafted organs is achieved by the immunosuppressive agent cyclosporine, a prominent member of the calcineurin inhibitors. Unfortunately, its lifetime use is associated with hypertension and nephrotoxicity. Several mechanism for cyclosporine induced hypertension have been proposed, i.e. activation of the sympathetic nervous system, endothelin-mediated systemic vasoconstriction, impaired vasodilatation secondary to reduction in prostaglandin and nitric oxide, altered cytosolic calcium translocation, and activation of the renin-angiotensin system (RAS). In this regard the molecular basis for undue RAS activation and an increased signaling of the vasoactive oligopeptide angiotensin II (AngII) remain elusive. Notably, angiotensinogen (AGT) is the precursor of AngII and transcriptional regulation of AGT is controlled by the hepatic nuclear factor HNF4alpha. To better understand the molecular events associated with cyclosporine induced hypertension, we investigated the effect of cyclosporine on HNF4alpha expression and activity and searched for novel HNF4alpha target genes among members of the RAS cascade. Using bioinformatic algorithm and EMSA bandshift assays we identified angiotensin II receptor type 1 (AGTR1), angiotensin I converting enzyme (ACE), and angiotensin I converting enzyme 2 (ACE2) as genes targeted by HNF4alpha. Notably, cyclosporine represses HNF4alpha gene and protein expression and its DNA-binding activity at consensus sequences to AGT, AGTR1, ACE, and ACE2. Consequently, the gene expression of AGT, AGTR1, and ACE2 was significantly reduced as evidenced by quantitative real-time RT-PCR. While RAS is composed of a sophisticated interplay between multiple factors we propose a decrease of ACE2 to enforce AngII signaling via AGTR1 to ultimately result in vasoconstriction and hypertension. Taken collectively we demonstrate cyclosporine to repress HNF4alpha activity through calcineurin inhibitor mediated inhibition of nuclear factor of activation of T-cells (NFAT) which in turn represses HNF4alpha that leads to a disturbed balance of RAS

VERNAM CIPHER BASED METHOD OF PROTECTION FOR DATA TRANSFERRED BETWEEN UNMANNED AIRCRAFT AND GROUND CONTROL STATION

The paper deals with questions of protection against unauthorized access to the data transmitted between unmanned aircraft vehicle (UAV) and ground control station (GCS). This is due to the fact that standard instruments of network security sometimes provide security of not enough proper level or do not satisfy the restrictions connected with the features of UAV: limited computing resources of the UAV on-board computer and real-time operation. We have offered to use Vernam cipher (one-time pad) as an additional measure for data protection. Vernam algorithm combines such advantages as theoretically proved absolute cryptographic security, ease of implementation, high speed of encryption and low processor load. It is especially important for large volumes of data encryption (e.g. video information). Within the bounds of experimental researches the technique is used based on cryptographic gamma of block cipher GOST 28147-89 in the Cipher Feedback Mode for a one-time pad generation. Application of Vernam cipher means the deletion of used one-time pad pages. The replacement of used one-time pad pages by cipher text is proposed for assurance of the above-named requirement and for simultaneous computer memory saving. It gives additionally the opportunity not only to save key sequences but also to accumulate encrypted data in the on-board computer memory. Realization of the offered method allows increasing the data protection level without engaging large computing power and memory capacity

PERSPECTIVE DIRECTIONS OF FURTHER DEVELOPMENT OF LOCAL MICROELECTRONICS TAKING INTO ACCOUNT FOREIGN EXPERIENCE

On the basis of a comparative analysis of the development of microelectronics in Russia and leading foreign countries, the main areas for further development of local microelectronics are examined. Technical and economic aspects of transfers to new technological levels, formation of advanced transistor structures, SoC VLSI, VLSI 3D are examined