CHANGES IN THE ACTIVITY OF SOME SERUM ENZYMES IN CHRONI CLIVER DISEASES

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Structural modeling of NAD+ binding modes to PARP-1

The nuclear protein poly (ADP-ribose) polymerase-1 (PARP-1) plays an important role in the signaling and repair of DNA. PARP-1 catalyses covalent binding of poly (ADP-ribose) polymers with itself as well as with other acceptor proteins using NAD+ as a donor of ADP-ribose. Inhibitors of poly (ADP-ribose) polymerase have been shown to be effective in improvement of radiation therapy and chemotherapy of cancer in clinical testing. Development of new poly (ADP-ribose) polymerase-1 inhibitors based on derivatives of natural compounds such as NAD+ represents a novel and promising strategy. The structure of complex of human poly (ADP-ribose) polymerase-1 with NAD+ can be a starting point for rational design of small molecule inhibitors based on NAD+ derivatives. Indeed there is no crystal structure of complex poly (ADP-ribose) polymerase-1 with nicotinamide adenine dinucleotide (NAD+) available yet. In this work using molecular modeling approaches we have predicted NAD+ binding modes with PARP-1 at the donor binding site of the catalytic domain. Using structures of PARP-1 homologs in complex with NAD+ we predicted pharmacophore restraints of NAD+ binding to PARP-1. Based on clustering of PARP-1 conformations in complex with co-crystallized inhibitors and predicted pharmacophore restraints, we proposed several possible models of NAD+ binding to PARP-1 at the donor binding site of the catalytic domain. According to the predicted models, two conformations of pyrophosphate group of NAD+ in complex with PARP-1 at the donor binding site are possible. Validation of the proposed models of NAD+ binding with PARP-1 can be achieved by quantitative structure-activity analysis of NAD+ derivatives. We designed two NAD+ derivatives, which can be used for validation of predicted NAD+ binding models

Using <i>N</i>-Norms for Analyzing Symmetric Protective Electrical Circuits with Triple Modal Reservation

The redundancy of functional blocks and critical assemblies in radio-electronic equipment is among the most widely used techniques for increasing reliability. Complex redundant systems raise the problem of electromagnetic compatibility (EMC). Ignoring EMC requirements can lead to partial or complete REE failures. In this paper, the authors analyze a noise-protective electrical circuit with triple modal reservation (a promising type of cold redundancy). A multilayer stripline is investigated, the conductors of which are symmetrically arranged relative to two planes. On account of the strong electromagnetic coupling, this protective circuit can decompose dangerous ultra-wideband (UWB) interference received at the input of the primary or redundant circuits into unipolar pulses of lower amplitude. Using this approach, due to the symmetry of the conductors, equal decomposition efficiency could be achieved. However, the effect of UWB interference at the input of one of the conductors produces bipolar pulses at the output of the other conductors. In this paper, the authors evaluate the dangers of unipolar and bipolar decomposed pulses and use modal analysis to mathematically determine the polarities and amplitudes of the decomposed pulses at all output nodes for a pseudo-matched structure. By using the quasistatic approach with and without losses, the time responses to a trapezoidal pulse with a total duration of 60 ps, which simulates UWB interference, are obtained. To confirm the results of modal analysis and quasistatic simulation, an experimental study is performed. Using a stroboscopic oscilloscope DSA 8300, the authors obtained a transient response to a step excitation. Then, taking the derivative, the response to a trapezoidal pulse with a total duration of 140 ps was obtained. To analyze the criticality of the decomposed pulses, N-norms are used. In the general case, it is shown that the UWB interference is decomposed into four pulses of lower amplitude. At the same time, the value of each N-norm indicates its significant attenuation. For example, the amplitude of the UWB pulse acting on the input of the reserved conductor decreases by 10.31–8.93 times. Such results numerically demonstrate the high efficiency of the suggested approach when it comes to protecting equipment against UWB interference. It is also shown that the probability of dielectric breakdown and damage to electronic components in redundant circuits is lower than in a primary circuit. This is due to the fact that the value of N3 in the redundant circuit is 2.38 times less than in the primary circuit. However, the results demonstrate that arcing is highly probable both in primary and redundant circuits. Finally, aspects of symmetry/asymmetry in the problem under investigation are emphasized

Using N-Norms for Analyzing Symmetric Protective Electrical Circuits with Triple Modal Reservation

The redundancy of functional blocks and critical assemblies in radio-electronic equipment is among the most widely used techniques for increasing reliability. Complex redundant systems raise the problem of electromagnetic compatibility (EMC). Ignoring EMC requirements can lead to partial or complete REE failures. In this paper, the authors analyze a noise-protective electrical circuit with triple modal reservation (a promising type of cold redundancy). A multilayer stripline is investigated, the conductors of which are symmetrically arranged relative to two planes. On account of the strong electromagnetic coupling, this protective circuit can decompose dangerous ultra-wideband (UWB) interference received at the input of the primary or redundant circuits into unipolar pulses of lower amplitude. Using this approach, due to the symmetry of the conductors, equal decomposition efficiency could be achieved. However, the effect of UWB interference at the input of one of the conductors produces bipolar pulses at the output of the other conductors. In this paper, the authors evaluate the dangers of unipolar and bipolar decomposed pulses and use modal analysis to mathematically determine the polarities and amplitudes of the decomposed pulses at all output nodes for a pseudo-matched structure. By using the quasistatic approach with and without losses, the time responses to a trapezoidal pulse with a total duration of 60 ps, which simulates UWB interference, are obtained. To confirm the results of modal analysis and quasistatic simulation, an experimental study is performed. Using a stroboscopic oscilloscope DSA 8300, the authors obtained a transient response to a step excitation. Then, taking the derivative, the response to a trapezoidal pulse with a total duration of 140 ps was obtained. To analyze the criticality of the decomposed pulses, N-norms are used. In the general case, it is shown that the UWB interference is decomposed into four pulses of lower amplitude. At the same time, the value of each N-norm indicates its significant attenuation. For example, the amplitude of the UWB pulse acting on the input of the reserved conductor decreases by 10.31&ndash;8.93 times. Such results numerically demonstrate the high efficiency of the suggested approach when it comes to protecting equipment against UWB interference. It is also shown that the probability of dielectric breakdown and damage to electronic components in redundant circuits is lower than in a primary circuit. This is due to the fact that the value of N3 in the redundant circuit is 2.38 times less than in the primary circuit. However, the results demonstrate that arcing is highly probable both in primary and redundant circuits. Finally, aspects of symmetry/asymmetry in the problem under investigation are emphasized

Candidate SNP markers of reproductive potential are predicted by a significant change in the affinity of TATA-binding protein for human gene promoters

Abstract Background The progress of medicine, science, technology, education, and culture improves, year by year, quality of life and life expectancy of the populace. The modern human has a chance to further improve the quality and duration of his/her life and the lives of his/her loved ones by bringing their lifestyle in line with their sequenced individual genomes. With this in mind, one of genome-based developments at the junction of personalized medicine and bioinformatics will be considered in this work, where we used two Web services: (i) SNP_TATA_Comparator to search for alleles with a single nucleotide polymorphism (SNP) that alters the affinity of TATA-binding protein (TBP) for the TATA boxes of human gene promoters and (ii) PubMed to look for retrospective clinical reviews on changes in physiological indicators of reproductive potential in carriers of these alleles. Results A total of 126 SNP markers of female reproductive potential, capable of altering the affinity of TBP for gene promoters, were found using the two above-mentioned Web services. For example, 10 candidate SNP markers of thrombosis (e.g., rs563763767) can cause overproduction of coagulation inducers. In pregnant women, Hughes syndrome provokes thrombosis with a fatal outcome although this syndrome can be diagnosed and eliminated even at the earliest stages of its development. Thus, in women carrying any of the above SNPs, preventive treatment of this syndrome before a planned pregnancy can reduce the risk of death. Similarly, seven SNP markers predicted here (e.g., rs774688955) can elevate the risk of myocardial infarction. In line with Bowles’ lifespan theory, women carrying any of these SNPs may modify their lifestyle to improve their longevity if they can take under advisement that risks of myocardial infarction increase with age of the mother, total number of pregnancies, in multiple pregnancies, pregnancies under the age of 20, hypertension, preeclampsia, menstrual cycle irregularity, and in women smokers. Conclusions According to Bowles’ lifespan theory—which links reproductive potential, quality of life, and life expectancy—the above information was compiled for those who would like to reduce risks of diseases corresponding to alleles in own sequenced genomes. Candidate SNP markers can focus the clinical analysis of unannotated SNPs, after which they may become useful for people who would like to bring their lifestyle in line with their sequenced individual genomes