Coherent control of nuclear spin isomers of molecules: The role of molecular motion

Molecular center-of-mass motion is taken into account in the theory of coherent control of nuclear spin isomers of molecules. It is shown that infrared radiation resonant to the molecular rovibrational transition can substantially enrich nuclear spin isomers and speed up their conversion rate.Comment: REVTEX, 13 pages + 3 eps figure

The selection pressure on the neuraminidase gene of influenza viruses isolated in Ukraine from 2009 to 2015

A broad range of naturally occurring antigenic variants of the influenza virus is caused by its rapid evolutionary variability. The survival of viable influenza virus variants occurs through natural selection. The treatment of influenza infection with modern antiviral drugs – neuraminidase (NA) inhibitors – leads to the occurrence of mutations in the NA gene, which thereby result in the emergence of virus resistance to these drugs. The goal of this study was to determine the selection pressure on the NA protein of influenza viruses isolated in Ukraine from 2009 to 2015. The main method for assessing the selection pressure on proteins is to quantify the ratio of substitution rates at nonsynonymous (dN) and synonymous (dS) sites. With the help of this method, we showed that only a few codons in the NA gene were under positive selection resulting in mutations at the following sites: for influenza A viruses of the A(H1N1)pdm09 subtype – site 40, for viruses of the A(H3N2) subtype – sites 93 and 402, for Influenza B viruses of the B/Yamagata lineage – sites 74, 99, and 268, and for the viruses of the B/Victoria lineage – sites 358, 288, and 455. These sites are not associated with the NA active site, transmembrane domain, or the antigenic sites of this protein. We concluded that NA inhibitors are not a significant factor in the process of selection of the influenza viruses in Ukraine because the sites associated with the resistance of influenza viruses to NA inhibitors were not affected by positive selection. This finding could be explained by the limited use of NA inhibitors for the treatment of influenza infections in Ukraine. A broad range of naturally occurring antigenic variants of the influenza virus is caused by its rapid evolutionary variability. The survival of viable influenza virus variants occurs through natural selection. The treatment of influenza infection with modern antiviral drugs – neuraminidase (NA) inhibitors – leads to the occurrence of mutations in the NA gene, which thereby result in the emergence of virus resistance to these drugs. The goal of this study was to determine the selection pressure on the NA protein of influenza viruses isolated in Ukraine from 2009 to 2015. The main method for assessing the selection pressure on proteins is to quantify the ratio of substitution rates at nonsynonymous (dN) and synonymous (dS) sites. With the help of this method, we showed that only a few codons in the NA gene were under positive selection resulting in mutations at the following sites: for influenza A viruses of the A(H1N1)pdm09 subtype – site 40, for viruses of the A(H3N2) subtype – sites 93 and 402, for Influenza B viruses of the B/Yamagata lineage – sites 74, 99, and 268, and for the viruses of the B/Victoria lineage – sites 358, 288, and 455. These sites are not associated with the NA active site, transmembrane domain, or the antigenic sites of this protein. We concluded that NA inhibitors are not a significant factor in the process of selection of the influenza viruses in Ukraine because the sites associated with the resistance of influenza viruses to NA inhibitors were not affected by positive selection. This finding could be explained by the limited use of NA inhibitors for the treatment of influenza infections in Ukraine.

Стабилизирующее управление неустойчивой системой с гироскопическими структурами на базе нечеткой логики

Робота присвячена дослідженню системи керування двоколісним транспортним засобом на основі нечіткої логіки. Метод управління реалізовано для системи стабілізації та динамічної рівноваги на прикладі гіроскопічного монорейкового вагона. Розроблено імітаційну модель об’єкту керування у середовищі LabVIEW, що дозволило проводити дослідження в режимі on-line, змінювати параметри моделі та характеристики керування в процесі виконання експерименту. Досліджено вплив зміни параметрів системи та потужності виконуючого пристрою на процес відновлення рівноваги. Проведено порівняння динамічних характеристик транспортного засобу на основі нечіткого керування та традиційного. Показано, що введення блока нечіткої логіки в систему керування в значній мірі зменшило час перехідного процесу та спожиту енергію.The method of synthesis management system implemented for dynamic and balance stabilization the example of gyroscopic monorail car. A simulation model among LabView, which allow to conduct research in a mode on-line, modify model parameters and characteristics of the control system. Researched parameters fluctuations when changing the angular momentum, mass and power load sensor point. Researched the parameters fluctuations when changing the angular momentum, mass and power load sensor point. Lead a comparison of the characteristics vehicle vibrations and traditional fuzzy control with the help of feedback. It is shown that the introduction of block of fuzzy logic in control greatly reduce the transition process and the consume energy.Рассмотрена возможность применения метода управления на основе нечеткой логики для создания устойчивой системы двухколесного транспортного средства. Метод синтеза управления реализован для системы стабилизации и динамического равновесия на примере гироскопического монорельсового вагона. Разработана имитационная модель в среде Labview, что позволило проводить исследование в режиме on-line, изменять параметры модели и характеристики системы управления. Исследовано поведение системы при изменении ее параметров и мощности исполнительного устройства. Проведено сравнение динамических характеристик транспортного средства на основе традиционного и нечеткого управлений. Показано, что введение блока нечеткой логики в систему управления в значительной мере уменьшает время переходного процесса и потребляемую энергию

Resistance of old winter bread wheat landraces to tan spot

Background. The most effective and environmentally safe way to combat wheat diseases is to produce cultivars resistant to their pathogens. For this purpose, old landraces are often used as genetically diverse sources of traits important for breeding. In the process of wheat breeding for resistance to tan spot caused by the fungus Pyrenophora tritici-repentis (Died.) Drechs. (abbr. Ptr), selection is carried out against the dominant allele of Tsn1, the gene of sensitivity to the toxin Ptr ToxA, which induces necrosis and represents the main pathogenicity factor of Ptr controlled by the ToxA gene. The aim of the study was to characterize a set of bread wheat (Triticum aestivum L.) accessions from the VIR collection for resistance to various Ptr populations, genotype these accessions using Xfcp623 – a DNA marker of the Tsn1 gene, and identify sources of tan spot resistance.Materials and methods. Sixty-seven accessions of winter bread wheat landraces were studied. Seedling resistance to two Ptr populations was assessed using a 5-point scale adopted at VIZR. The allelic state of Tsn1 was identified by PCR.Results. Dominant alleles of Tsn1 were found for 55% of the studied accessions. Seventeen accessions were resistant or moderately resistant to two Ptr populations and an isolate from Krasnodar Territory previously used for their characterization. Nine of them had the tsn1tsn1 genotype, and 8 had Tsn1Tsn1. The accessions mainly belonged to three agroecological groups proposed by N. I. Vavilov: “steppe winter bread wheat (Banatka wheats)”, “North European forest awnless bread wheats (Sandomirka wheats)”, and “Caucasian mountain winter bread wheat”.Conclusion. The identified 17 accessions resistant to Ptr are potential breeding sources of resistance. In the studied set of accessions, no significant relationship was found between the allelic state of the Tsn1 gene in the accession and its response to the infection with pathogen populations, including isolates with the ToxA gene

Combinations of PARP Inhibitors with Temozolomide Drive PARP1 Trapping and Apoptosis in Ewing's Sarcoma.

Ewing's sarcoma is a malignant pediatric bone tumor with a poor prognosis for patients with metastatic or recurrent disease. Ewing's sarcoma cells are acutely hypersensitive to poly (ADP-ribose) polymerase (PARP) inhibition and this is being evaluated in clinical trials, although the mechanism of hypersensitivity has not been directly addressed. PARP inhibitors have efficacy in tumors with BRCA1/2 mutations, which confer deficiency in DNA double-strand break (DSB) repair by homologous recombination (HR). This drives dependence on PARP1/2 due to their function in DNA single-strand break (SSB) repair. PARP inhibitors are also cytotoxic through inhibiting PARP1/2 auto-PARylation, blocking PARP1/2 release from substrate DNA. Here, we show that PARP inhibitor sensitivity in Ewing's sarcoma cells is not through an apparent defect in DNA repair by HR, but through hypersensitivity to trapped PARP1-DNA complexes. This drives accumulation of DNA damage during replication, ultimately leading to apoptosis. We also show that the activity of PARP inhibitors is potentiated by temozolomide in Ewing's sarcoma cells and is associated with enhanced trapping of PARP1-DNA complexes. Furthermore, through mining of large-scale drug sensitivity datasets, we identify a subset of glioma, neuroblastoma and melanoma cell lines as hypersensitive to the combination of temozolomide and PARP inhibition, potentially identifying new avenues for therapeutic intervention. These data provide insights into the anti-cancer activity of PARP inhibitors with implications for the design of treatment for Ewing's sarcoma patients with PARP inhibitors.Research in the M.J.G. laboratory is supported by grants from the Wellcome Trust (086357 and 102696/Z/13/Z; http://www.wellcome.ac.uk/Funding). Research in the S.P.J. laboratory is funded by Cancer Research UK Program Grant C6/A11224 (http://www.cancerresearchuk.org/funding-for-researchers/our-funding-schemes), the European Research Council (http://erc.europa.eu/funding-and-grants)and the European Community Seventh Framework Program grant agreement no. HEALTH-F2-2010-259893 (DDResponse). Core infrastructure funding was provided by Cancer Research UK Grant C6946/A14492 and Wellcome Trust Grant WT092096. S.P.J. receives a salary from the University of Cambridge, supplemented by Cancer Research UK. J.T. was funded by the European Community Seventh Framework Program grant agreement no. HEALTH-F2-2010-259893 (DDResponse). U.M. is supported by a Cancer Research UK Clinician Scientist Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.014098

Deratization Activities in the Jewish Autonomous Region in the Post-Flooding Period

Represented is a quantitative characteristic of the objects and facilities in the Jewish Autonomous Region exposed to the flooding-2013. Justified is the necessity for implementation of preventive measures against increase in the activity of HFRS natural foci; showed are the data on disinfestation organization for the prevention of natural-focal infection during the high water and post-flooding period in 2013. Displayed are the results of deratization efficacy control in various administrative units of the entity, calculated using Abbot formula, as well as results of investigation of small rodent population density at the natural stations and substantiation of the barrier disinfestation carrying out. Specified are the areas of the continuous and barrier disinfestation, indicators of Hanta Virus contamination of the rodents caught while performing control over efficacy of deratization works

Provision for Sanitary Epidemiological Welfare of the Population of the Jewish Autonomous Region during High Water and Post-Flooding Period

Put forward was operational protocol as regards Rospotrebnadzor institutions policies in the territory of the Jewish Autonomous Region for the prevention of epidemiological implications during the post-flooding period in reference to infectious diseases. Carried out were control measures over infection morbidity rate, drinking water quality, disinfection of water supply sources, as well as sewage systems. Actions undertaken made it possible to prevent cluster cases of infectious diseases both in the flooded areas and at the temporal accommodation sites; to provide control over acute intestinal and natural-focal disease incidence, keeping it to the level of long-term average annual indexes; and to supply the population with drinking water of high quality

LKB1/KRAS mutant lung cancers constitute a genetic subset of NSCLC with increased sensitivity to MAPK and mTOR signalling inhibition

LKB1/STK11 is a multitasking tumour suppressor kinase. Germline inactivating mutations of the gene are responsible for the Peutz-Jeghers hereditary cancer syndrome. It is also somatically inactivated in approximately 30% of non-small-cell lung cancer (NSCLC). Here, we report that LKB1/KRAS mutant NSCLC cell lines are sensitive to the MEK inhibitor CI-1040 shown by a dose-dependent reduction in proliferation rate, whereas LKB1 and KRAS mutations alone do not confer similar sensitivity. We show that this subset of NSCLC is also sensitised to the mTOR inhibitor rapamycin. Importantly, the data suggest that LKB1/KRAS mutant NSCLCs are a genetically and functionally distinct subset and further suggest that this subset of lung cancers might afford an opportunity for exploitation of anti-MAPK/mTOR-targeted therapies