ИНСТРУМЕНТАРИЙ МИНИМИЗАЦИИ РИСКОВ ПРИ РАЗРАБОТКЕ ВЫСОКОТЕХНОЛОГИЧНОЙ ПРОДУКЦИИ

The article describes the methodological basesand the economic and mathematical tools to minimize technological risks developing high-tech products. A new, more effi cient organization of the process of developing high-techproducts, as well as tools for assessing thetechnical and economic efficiency of new technologies introduced on manufacturers of theseproducts is offered.В статье рассмотрены методологические основы и экономико-математический инструментарийминимизациитехнологических рисков разработки высокотехнологичной продукции. Предложена новая, более эффективнаяорганизацияпроцессаразработки высокотехнологичных изделий, а также инструментарий оценки технико-экономической эффективности новых технологий, внедряемыхнапредприятиях-изготовителях данной продукции

Spin dependent point potentials in one and three dimensions

We consider a system realized with one spinless quantum particle and an array of $N$ spins 1/2 in dimension one and three. We characterize all the Hamiltonians obtained as point perturbations of an assigned free dynamics in terms of some ``generalized boundary conditions''. For every boundary condition we give the explicit formula for the resolvent of the corresponding Hamiltonian. We discuss the problem of locality and give two examples of spin dependent point potentials that could be of interest as multi-component solvable models.Comment: 15 pages, some misprints corrected, one example added, some references modified or adde

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

Profile of MicroRNAs following Rat Sciatic Nerve Injury by Deep Sequencing: Implication for Mechanisms of Nerve Regeneration

Unlike the central nervous system, peripheral nerves can regenerate when damaged. MicroRNA (miRNA) is a novel class of small, non-coding RNA that regulates gene expression at the post-transcriptional level. Here, we report regular alterations of miRNA expression following rat sciatic nerve injury using deep sequencing. We harvested dorsal root ganglia tissues and the proximal stumps of the nerve, and identified 201 and 225 known miRNAs with significant expression variance at five time points in these tissues after sciatic nerve transaction, respectively. Subsequently, hierarchical clustering, miRNA expression pattern and co-expression network were performed. We screened out specific miRNAs and further obtained the intersection genes through target analysis software (Targetscan and miRanda). Moreover, GO and KEGG enrichment analyses of these intersection genes were performed. The bioinformatics analysis indicated that the potential targets for these miRNAs were involved in nerve regeneration, including neurogenesis, neuron differentiation, vesicle-mediated transport, homophilic cell adhesion and negative regulation of programmed cell death that were known to play important roles in regulating nerve repair. Finally, we combined differentially expressed mRNA with the predicted targets for selecting inverse miRNA-target pairs. Our results show that the abnormal expression of miRNA may contribute to illustrate the molecular mechanisms of nerve regeneration and that miRNAs are potential targets for therapeutic interventions and may enhance intrinsic regenerative ability