The genomic basis of rapid adaptation to antibiotic combination therapy in Pseudomonas aeruginosa

Combination therapy is a common antibiotic treatment strategy that aims at minimizing the risk of resistance evolution in several infectious diseases. Nonetheless, evidence supporting its efficacy against the nosocomial opportunistic pathogen Pseudomonas aeruginosa remains elusive. Identification of the possible evolutionary paths to resistance in multidrug environments can help to explain treatment outcome. For this purpose, we here performed whole-genome sequencing of 127 previously evolved populations of P. aeruginosa adapted to sublethal doses of distinct antibiotic combinations and corresponding single-drug treatments, and experimentally characterized several of the identified variants. We found that alterations in the regulation of efflux pumps are the most favored mechanism of resistance, regardless of the environment. Unexpectedly, we repeatedly identified intergenic variants in the adapted populations, often with no additional mutations and usually associated with genes involved in efflux pump expression, possibly indicating a regulatory function of the intergenic regions. The experimental analysis of these variants demonstrated that the intergenic changes caused similar increases in resistance against single and multidrug treatments as those seen for efflux regulatory gene mutants. Surprisingly, we could find no substantial fitness costs for a majority of these variants, most likely enhancing their competitiveness toward sensitive cells, even in antibiotic-free environments. We conclude that the regulation of efflux is a central target of antibiotic-mediated selection in P. aeruginosa and that, importantly, changes in intergenic regions may represent a usually neglected alternative process underlying bacterial resistance evolution, which clearly deserves further attention in the future

Revisiting the Local Scaling Hypothesis in Stably Stratified Atmospheric Boundary Layer Turbulence: an Integration of Field and Laboratory Measurements with Large-eddy Simulations

The `local scaling' hypothesis, first introduced by Nieuwstadt two decades ago, describes the turbulence structure of stable boundary layers in a very succinct way and is an integral part of numerous local closure-based numerical weather prediction models. However, the validity of this hypothesis under very stable conditions is a subject of on-going debate. In this work, we attempt to address this controversial issue by performing extensive analyses of turbulence data from several field campaigns, wind-tunnel experiments and large-eddy simulations. Wide range of stabilities, diverse field conditions and a comprehensive set of turbulence statistics make this study distinct

Interactions between downslope flows and a developing cold-air pool

A numerical model has been used to characterize the development of a region of enhanced cooling in an alpine valley with a width of order (Formula presented.) km, under decoupled stable conditions. The region of enhanced cooling develops largely as a region of relatively dry air which partitions the valley atmosphere dynamics into two volumes, with airflow partially trapped within the valley by a developing elevated inversion. Complex interactions between the region of enhanced cooling and the downslope flows are quantified. The cooling within the region of enhanced cooling and the elevated inversion is almost equally partitioned between radiative and dynamic effects. By the end of the simulation, the different valley atmospheric regions approach a state of thermal equilibrium with one another, though this cannot be said of the valley atmosphere and its external environment.Peer reviewe

Pollutant dispersion in a developing valley cold-air pool

Pollutants are trapped and accumulate within cold-air pools, thereby affecting air quality. A numerical model is used to quantify the role of cold-air-pooling processes in the dispersion of air pollution in a developing cold-air pool within an alpine valley under decoupled stable conditions. Results indicate that the negatively buoyant downslope flows transport and mix pollutants into the valley to depths that depend on the temperature deficit of the flow and the ambient temperature structure inside the valley. Along the slopes, pollutants are generally entrained above the cold-air pool and detrained within the cold-air pool, largely above the ground-based inversion layer. The ability of the cold-air pool to dilute pollutants is quantified. The analysis shows that the downslope flows fill the valley with air from above, which is then largely trapped within the cold-air pool, and that dilution depends on where the pollutants are emitted with respect to the positions of the top of the ground-based inversion layer and cold-air pool, and on the slope wind speeds. Over the lower part of the slopes, the cold-air-pool-averaged concentrations are proportional to the slope wind speeds where the pollutants are emitted, and diminish as the cold-air pool deepens. Pollutants emitted within the ground-based inversion layer are largely trapped there. Pollutants emitted farther up the slopes detrain within the cold-air pool above the ground-based inversion layer, although some fraction, increasing with distance from the top of the slopes, penetrates into the ground-based inversion layer.Peer reviewe

Анализ современных технологий заводнения при разработке нефтяных месторождений

Объектом исследования являются системы заводнения применяемые на месторождениях России Цель работы – анализ современных технологий заводнения при разработке нефтяных месторождений, а также обоснование применения технологий заводнения с целью увеличения темпов отбора, коэффициента нефтеизвлечения, технико-экономических показателей. В выпускной квалификационной работе приведены сведения о современных технологиях заводнения, применяемых на месторождениях России. Проведены расчеты экономической эффективности при внедрении нестационарного метода заводнения. Проанализирован процесс работы методов заводнения в условиях месторождений России. Бакалаврская работа выполнена в текстовом редакторе Microsoft Word, и Microsoft Excel.The object of the study are the waterflooding systems used in the fields of Russia The aim of the work is the analysis of modern flooding technologies in the development of oil fields, as well as the rationale for using flooding technologies to increase the rate of selection, the oil recovery factor, and the technical and economic indicators. In the final qualification work information on modern water flooding technologies used in the fields of Russia is given. Calculations of economic efficiency are implemented in the introduction of the non-stationary flooding method. The process of work of flooding methods in the conditions of Russian deposits is analyzed. Bachelor's work is executed in the text editor Microsoft Word, and Microsoft Excel

Evelopment of the model of diagnosis of the risk of bankruptcy

The article presents an overview of foreign and domestic models for the diagnosis of bankruptcy risk, and gives a brief description of them. Also considered the development of our own model of bankruptcy risk diagnostics for Russian enterprise

Исследование датчиков рН и удельной электрической проводимости фирмы WTW в системе автоматизированного контроля качества очистки сточных вод

We demonstrate the suitability of microcavities based on circular grating resonators (CGRs) as fast switches. This type of optical resonator is characterized by a high quality factor and very small mode volume. The waveguide-coupled CGRs are fabricated with silicon-on-insulator technology compatible with standard complementary metal-oxide semiconductor (CMOS) processing. The linear optical properties of the CGRs are investigated by transmission spectroscopy. From 3D finite-difference time-domain simulations of isolated CGRs, we identify the measured resonances. We probe the spatial distribution and the parasitic losses of a resonant optical mode with scanning near-field optical microscopy. We observe fast all-optical switching within a few picoseconds by optically generating free charge carriers within the cavity. (C) 2009 Optical Society of Americ

Photophysical properties of thin films and solid phase of switchable supermolecular anthracene-based rotaxanes

Polycrystalline powders and thin films of a novel rotaxane, methyl-exopyridine-anthracene rotaxane (EPAR-Me), and of the related thread and stoppers 10-[3,5-di (ter butyl)phenoxy]decyl-2-({2-[(9-anthrylcarbonyl) amino] acetyl}amino) acetate (ANTPEP), have been characterised by photoluminescence, absorption and photoluminescence excitation spectroscopy. A rather unusual, i.e. unstructured and largely red-shifted, photoluminescence spectral behaviour of the rotaxane has been found. Preliminary time resolved measurements indicate a fast energy transfer from the anthracene unit to different species the nature of which is still not assigned.

DNA deaminases: AIDing hormones in immunity and cancer

It is well established that hormones can cause cancer, much less known is how they induce this change in our somatic cells. This review highlights the recent finding that estrogen can exert its DNA-damaging potential by directly activating DNA deaminases. This recently discovered class of proteins deaminate cytosine to uracil in DNA, and are essential enzymes in the immune system. The enhanced production of a given DNA deaminase, induced by estrogen, can lead not only to a more active immune response, but also to an increase in mutations and oncogenic translocations. Identifying the direct molecular link between estrogen and a mutation event provides us with new targets for studying and possibly inhibiting the pathological side-effects of estrogen