Genome-wide co-expression analysis in multiple tissues

Expression quantitative trait loci (eQTLs) represent genetic control points of gene expression, and can be categorized as cis- and trans-acting, reflecting local and distant regulation of gene expression respectively. Although there is evidence of co-regulation within clusters of trans-eQTLs, the extent of co-expression patterns and their relationship with the genotypes at eQTLs are not fully understood. We have mapped thousands of cis- and trans-eQTLs in four tissues (fat, kidney, adrenal and left ventricle) in a large panel of rat recombinant inbred (RI) strains. Here we investigate the genome-wide correlation structure in expression levels of eQTL transcripts and underlying genotypes to elucidate the nature of co-regulation within cis- and trans-eQTL datasets. Across the four tissues, we consistently found statistically significant correlations of cis-regulated gene expression to be rare (<0.9% of all pairs tested). Most (>80%) of the observed significant correlations of cis-regulated gene expression are explained by correlation of the underlying genotypes. In comparison, co-expression of trans-regulated gene expression is more common, with significant correlation ranging from 2.9%-14.9% of all pairs of trans-eQTL transcripts. We observed a total of 81 trans-eQTL clusters (hot-spots), defined as consisting of > or =10 eQTLs linked to a common region, with very high levels of correlation between trans-regulated transcripts (77.2-90.2%). Moreover, functional analysis of large trans-eQTL clusters (> or =30 eQTLs) revealed significant functional enrichment among genes comprising 80% of the large clusters. The results of this genome-wide co-expression study show the effects of the eQTL genotypes on the observed patterns of correlation, and suggest that functional relatedness between genes underlying trans-eQTLs is reflected in the degree of co-expression observed in trans-eQTL clusters. Our results demonstrate the power of an integrative, systematic approach to the analysis of a large gene expression dataset to uncover underlying structure, and inform future eQTL studies

Glycosidase-catalyzed synthesis of glycosylated nutraceutical ingredients

Hydroxyphenyl propenoic acids (hydroxycinnamic acids) and their alcohol derivatives are common components of the human diet which often occur in plants in the form of various glycosides. As the diets rich in polyphenols have repeatedly been related to low incidence of cardiovascular, neurodegenerative, and oncological diseases, various food supplements containing these compounds are becoming increasingly popular among the general population. In quest of a biocatalytic route to structurally complex phenolic glycosides, we built a sustainable and convenient, one-pot two-enzyme method for the glucosylation of arylalkyl alcohols based on the synthetic exploitation of a fungal rutinosidase from A. niger and rhamnosidase from A. terreus. Both these enzymes were available to us as heterologous proteins produced by a recombinant strain of P. pastoris. As an example, the -glucoside salidroside, a compound endowed with various pharmacological effects and commercialized in Rhodiola rosea nutraceutical formulations, was obtained in high isolated yield and purity from tyrosol thanks to our one-pot enzymatic process. Furthermore, during the course of our investigation, we found that the rutinosidase from A. niger not only efficiently converted hydroxylated aromatic acids (e.g. coumaric and ferulic acids) into the respective phenolic rutinosides, but surprisingly could also catalyze the formation of the respective glycosyl esters. Here the results of our systematic study about the glycosidase-based biocatalytic preparation of lycosylated nutraceutical ingredients, which lead us to the discovery of a unique enzymatic entry to naturally occurring glycosyl esters, are reported

A Novel Multi-parameter Family of Quantum Systems with Partially Broken N-fold Supersymmetry

We develop a systematic algorithm for constructing an N-fold supersymmetric system from a given vector space invariant under one of the supercharges. Applying this algorithm to spaces of monomials, we construct a new multi-parameter family of N-fold supersymmetric models, which shall be referred to as "type C". We investigate various aspects of these type C models in detail. It turns out that in certain cases these systems exhibit a novel phenomenon, namely, partial breaking of N-fold supersymmetry.Comment: RevTeX 4, 28 pages, no figure

The reaction of chlorotetrafluorophosphorane with trimethylamine

The reaction of chlorotetrafluorophosphorane with trimethylamine affords a 1:1 Lewis acid-base complex of composition ClF4P[middle dot]NMe3. It has been established by 1H and 19F NMR spectroscopy that the Cl and Me3N ligands occupy mutually trans positions in a locally octahedral geometry around phosphorus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23385/1/0000330.pd

Оценка точности измерения магнитоотрывного усилия датчиками прибора НТ-800 для раннего выявления дефектов их изготовления

Сontrol of mechanical stresses formed with the deposition of nickel coatings plays an important role in the diagnosis of coatings’ technical condition. Large internal stresses can lead to cracking or flaking of coatings which is completely unacceptable for critical parts and assembly units used, for example, in space technology for which reliability is of paramount importance. An important aspect of internal stresses monitoring is the measurement error of the instruments used. The purpose of this work was to determine the characteristics of the device sensors, which make the assessment of their manufacturing possible at the preliminary stage of the measuring equipment assembling in order to maintain the required accuracy of subsequent measurements.In most cases the measurement error assessment is possible only after the equipment manufacture and calibration. In this paper it is proposed to evaluate the accuracy characteristics of device sensors based on the precision (repeatability and reproducibility) of the primary informative parameter recording. In the case of the NT-800 device that was developed at the Institute of Applied Physics of the National Academy of Sciences of Belarus the effect of precision characteristics deterioration on the eventual measurement error is demonstrated. Determining the precision parameters before establishing correlation dependences between the primary informative parameter and the measured characteristic is proposed in order to reject poorly manufactured sensors and reduce labor costs.In particular, measurements of the magnitude proportional to the magnetic breakaway force were carried out using the NT-800 device with nickel specimens simulating coatings with a thickness of 200 to 700 μm and a rolling value from 0 to 40 %. It was established that in the case of well-made sensors the variation coefficient calculated from the dispersion of repeatability is in the range 0.2–0.6 %, and the variation coefficient calculated from the dispersion of reproducibility does not exceed 0.9 %. In the case of a sensor with the sensitive element parameters worsened, the variation coefficient of repeatability and reproducibility were up by one and a half times. Deterioration of the precision characteristics resulted in significant changes in the readings of the calibrated instrument. Thus the absolute measurement error for a sensor with a poorly made sensitive element turned out to be approximately 3 times higher in the range of 200– 300 MPa than that for a sensor with good precision parameters.Контроль механических напряжений, возникающих при нанесении никелевых покрытий, играет важную роль при диагностике их технического состояния. Большие внутренние напряжения могут приводить к растрескиванию или отслаиванию покрытий, что совершенно недопустимо для ответственных деталей и сборочных единиц, использующихся, например, в космической технике, для которых надёжность имеет первостепенное значение. Важным аспектом контроля внутренних напряжений является погрешность измерений используемых приборов. Целью настоящей работы являлось определение характеристик датчиков приборов, позволяющих оценить качество их изготовления на предварительной стадии сборки измерительной техники, для соблюдения необходимой точности последующих измерений.В большинстве случаев оценка погрешности измерений возможна только после изготовления оборудования и проведения градуировки. В настоящей работе предложено оценивать точностные характеристики датчиков приборов исходя из прецизионности (повторяемости и воспроизводимости) регистрации первичного информативного параметра. На примере прибора «НТ-800», разработанного в Институте прикладной физики Национальной академии наук Беларуси, показано влияние ухудшения характеристик прецизионности датчиков на итоговую погрешность измерений. Предложено определять параметры прецизионности до установления корреляционных зависимостей между первичным информативным параметром и измеряемой характеристикой с целью отбраковки некачественно изготовленных датчиков и снижения трудозатрат. В частности, проведены измерения величины, пропорциональной магнитоотрывному усилию (имеющей корреляционную связь с остаточными напряжениями), прибором НТ-800 на никелевых образцах, имитирующих покрытия, толщиной от 200 до 700 мкм и величиной прокатки от 0 до 40 %. Установлено, что в случае качественно изготовленного первичного преобразователя коэффициент вариации дисперсии повторяемости находится в диапазоне 0,2–0,6 %, а коэффициент вариации, рассчитанный по значениям дисперсии воспроизводимости, не превышает 0,9 %. В случае датчика с ухудшенными параметрами чувствительного элемента коэффициенты вариации повторяемости и воспроизводимости были в 1,5 раза выше. Ухудшение характеристик прецизионности привело к значительному увеличению погрешности измерения остаточных напряжений. Так, абсолютная погрешность измерений напряжений у некачественно изготовленного датчика в диапазоне 200–300 МПа была приблизительно в 3 раза выше, чем у датчика с высокими показателями прецизионности.

Chiral perturbation theory calculation for pn -> dpipi at threshold

We investigate the reaction pn -> dpipi in the framework of Chiral Perturbation Theory. For the first time a complete calculation of the leading order contributions is presented. We identify various diagrams that are of equal importance as compared to those recognized in earlier works. The diagrams at leading order behave as expected by the power counting. Also for the first time the nucleon-nucleon interaction in the initial, intermediate and final state is included consistently and found to be very important. This study provides a theoretical basis for a controlled evaluation of the non-resonant contributions in two-pion production reactions in nucleon-nucleon collisions.Comment: 24 pages, 3 figures, 3 table

МОДЕЛИРОВАНИЕ УДАРНОГО КОНТАКТА ИНДЕНТОРА С НЕЖЕСТКИМИ СТАЛЬНЫМИ КОНСТРУКЦИЯМИ ПРИ ИЗМЕРЕНИИ ТВЕРДОСТИ

The problems of measuring hardness of constructions with insufficient rigidity by the dynamic indentation are discussed. The disadvantages of the existing dynamic hardness testers are described, the operation of which consists in impact indentation and determination of the hardness, depending on the restitution coefficient. Finite-element models of the contact of the indenter and the pipes samples with various wall thicknesses and diameters and cantilevered plates of various thicknesses are developed. Indentation diagrams for the investigated samples of pipes and plates in the coordinate plane of force-displacement are obtained. The results of the simulation have good convergence with the experimental data. With the help of the finite element models the separation of local penetration and deflection of construction is made. It is shown the influence of steel construction deflection on the process of indenter impression into the material tested and the change of indentation parameters as restitution coefficient, contact force, penetration depth and time of the active part of the impact. The limits of possible application of dynamic hardness testers have been determined. The ways of the increasing of the hardness measurement accuracy on the base of the data obtained during impact interaction are shown. It is established that the use of dependences between hardness and the time of the active stage of impact, as well as the ratio of the contact force to the depth of penetration at the loading stage, makes it possible to evaluate the hardness for pipes with the wall thickness exceeding 5 mm and cantilevered plates at the distance from the fixed support up to 100 mm. Рассматриваются вопросы измерения твердости конструкций недостаточной жесткости методом ударного вдавливания индентора. Описываются недостатки существующих динамических твердомеров, принцип действия которых заключается в нанесении удара по испытуемому образцу и регистрации коэффициента восстановления скорости, зависящего от твердости. Построены конечно-элементные модели ударного взаимодействия индентора с образцами труб с различной толщиной стенки и диаметром, а также консольно закрепленных пластин разной толщины. Получены диаграммы вдавливания индентора в исследуемые образцы труб и пластин в координатах контактное усилие – перемещение. Показана достаточно хорошая сходимость между результатами моделирования и экспериментальными данными, полученными на твердомере, позволяющем регистрировать кривую нагружения в процессе ударного взаимодействия. С помощью построенных конечно-элементных моделей выделен вклад локальной деформации и прогиба в общий отклик конструкции при индентировании. Установлено влияние прогиба конструкций на процесс внедрения индентора в материал, а также на такие параметры индентирования, как коэффициент восстановления скорости, контактное усилие, перемещение и время активного этапа удара. Определены границы допустимого использования твердомеров ударного действия. Показаны пути повышения точности измерения твердости на основе данных, получаемых на этапе внедрения индентора. Установлено, что использование градуировочных зависимостей между твердостью и временем активного этапа удара, а также отношением контактного усилия к глубине внедрения на этапе нагружения позволяет провести оценку твердости для труб с толщиной стенки свыше 5 мм и консольно закрепленных пластин на расстоянии от места закрепления вплоть до 100 мм.