Protein and DNA sequence determinants of thermophilic adaptation

Prokaryotes living at extreme environmental temperatures exhibit pronounced signatures in the amino acid composition of their proteins and nucleotide compositions of their genomes reflective of adaptation to their thermal environments. However, despite significant efforts, the definitive answer of what are the genomic and proteomic compositional determinants of Optimal Growth Temperature of prokaryotic organisms remained elusive. Here the authors performed a comprehensive analysis of amino acid and nucleotide compositional signatures of thermophylic adaptation by exhaustively evaluating all combinations of amino acids and nucleotides as possible determinants of Optimal Growth Temperature for all prokaryotic organisms with fully sequences genomes.. The authors discovered that total concentration of seven amino acids in proteomes, IVYWREL, serves as a universal proteomic predictor of Optimal Growth Temperature in prokaryotes. Resolving the old-standing controversy the authors determined that the variation in nucleotide composition (increase of purine load, or A+G content with temperature) is largely a consequence of thermal adaptation of proteins. However, the frequency with which A and G nucleotides appear as nearest neighbors in genome sequences is strongly and independently correlated with Optimal Growth Temperature. as a result of codon bias in corresponding genomes. Together these results provide a complete picture of proteomic and genomic determinants of thermophilic adaptation.Comment: in press PLoS Computational Biology; revised versio

Positive and Negative Design in Stability and Thermal Adaptation of Natural Proteins

The aim of this work is to elucidate how physical principles of protein design are reflected in natural sequences that evolved in response to the thermal conditions of the environment. Using an exactly solvable lattice model, we design sequences with selected thermal properties. Compositional analysis of designed model sequences and natural proteomes reveals a specific trend in amino acid compositions in response to the requirement of stability at elevated environmental temperature: the increase of fractions of hydrophobic and charged amino acid residues at the expense of polar ones. We show that this “from both ends of the hydrophobicity scale” trend is due to positive (to stabilize the native state) and negative (to destabilize misfolded states) components of protein design. Negative design strengthens specific repulsive non-native interactions that appear in misfolded structures. A pressure to preserve specific repulsive interactions in non-native conformations may result in correlated mutations between amino acids that are far apart in the native state but may be in contact in misfolded conformations. Such correlated mutations are indeed found in TIM barrel and other proteins

Strong extinction of a far-field laser beam by a single quantum dot

Through the utilization of index-matched GaAs immersion lens techniques we demonstrate a record extinction (12%) of a far-field focused laser by a single InAs/GaAs quantum dot. This contrast level enables us to report for the first time resonant laser transmission spectroscopy on a single InAs/GaAs quantum dot without the need for phase-sensitive lock-in detection

Observation of Faraday rotation from a single confined spin

Ability to read-out the state of a single confined spin lies at the heart of solid-state quantum information processing. While all-optical spin measurements using Faraday rotation has been successfully implemented in ensembles of semiconductor spins, read-out of a single semiconductor spin has only been achieved using transport measurements based on spin-charge conversion. Here, we demonstrate an all-optical dispersive measurement of the spin-state of a single electron trapped in a semiconductor quantum dot. We obtain information on the spin state through conditional Faraday rotation of a spectrally detuned optical field, induced by the polarization- and spin-selective trion (charged quantum dot) transitions. To assess the sensitivity of the technique, we use an independent resonant laser for spin-state preparation. An all-optical dispersive measurement on single spins has the important advantage of channeling the measurement back-action onto a conjugate observable, thereby allowing for repetitive or continuous quantum nondemolition (QND) read-out of the spin-state. We infer from our results that there are of order unity back-action induced spin-flip Raman scattering events within our measurement timescale. Therefore, straightforward improvements such as the use of a solid-immersion lens and higher efficiency detectors would allow for back-action evading spin measurements, without the need for a cavity

Quantum computing with defects

Identifying and designing physical systems for use as qubits, the basic units of quantum information, are critical steps in the development of a quantum computer. Among the possibilities in the solid state, a defect in diamond known as the nitrogen-vacancy (NV-1) center stands out for its robustness - its quantum state can be initialized, manipulated, and measured with high fidelity at room temperature. Here we describe how to systematically identify other deep center defects with similar quantum-mechanical properties. We present a list of physical criteria that these centers and their hosts should meet and explain how these requirements can be used in conjunction with electronic structure theory to intelligently sort through candidate defect systems. To illustrate these points in detail, we compare electronic structure calculations of the NV-1 center in diamond with those of several deep centers in 4H silicon carbide (SiC). We then discuss the proposed criteria for similar defects in other tetrahedrally-coordinated semiconductors.Comment: 31 pages, 7 figures, 2 table

Фармако-токсикологічні властивості препарату “Цифлур” як профілактичного засобу за нодулярного дерматиту

The article presents data study of acute toxicity of the drug “Ciflur”. Nodular dermatitis causes significant economic losses due to a temporary decrease in milk productivity, temporary or permanent sterility of breeding bulls, skin lesions, and death of sick animals due to secondary infections. Specific treatments have not been developed. Preventive disinsection of livestock premises is effective for prevention. For this purpose, a new drug “Сiflur” was developed. 1 ml of the drug contains the active substance: cyfluthrin – 10.0 mg. Toxicity studies of the drug and evaluation of the results were performed in accordance with standard methods. The study of acute toxicity of the drug “Сiflur” when applied to the skin was performed on 18 white rats weighing 170–190 g. The animals were divided into 3 groups of 6 heads. Rats were kept in the vivarium in accordance with sanitary rules and on a standard diet adopted in the vivarium with the use of compound feed. The first group of rats on the skin was applied the drug “Сiflur” at a dose of 1250 mg/kg, the second  – 2500 mg/kg body weight. The third group of rats was a control – these animals on the skin was applied Solveso 200 solvent in the amount of 2500 mg/kg body weight. Acute toxicity of the drug was studied when applying the drug to a pre-cut area of skin on the back, which was at least 10 % of the total surface area of the animal. In order to prevent excessive spreading on the skin, the drug was applied slowly, drying with warm air with a hair dryer. For 14 days after cutaneous application of the drug was recorded daily its effect on the survival of rats, the appearance of rats and manifestations of physiological disorders of animals. Rats were weighed before application, as well as 3, 7 and 14 days after the start of the study. After 14 days, an autopsy was performed and the condition of the internal organs was examined for possible impressions, and the internal organs were weighed and their relative weight coefficients were calculated. Therefore, a single skin application of “Ciflur” at doses of 1250 and 2500 mg/kg body weight did not result in the death of experimental rats. The acute LD50 of the drug “Сiflur”when applied to the skin exceeds 2500 mg/kg body weight, which allows it to be classified as hazard class 4 according to the International Standard GOST 12.1.007-76, or category 5 according to the International Global Classification of Harmonized System (GHS). Only the application of “Ciflur” at the highest dose (2500 mg/kg body weight) caused a slight short-term reddening of the skin in some experimental rats, which disappeared without intervention for 4–8 hours.У статті наведені дані щодо вивчення фармако-токсикологічних властивостей препарату “Цифлур” як профілактичного засобу за нодулярного дерматиту. Нодулярний дерматит спричиняє значні економічні втрати через те, що викликає тимчасове зниження молочної продуктивності, тимчасову або постійну стерильність биків-плідників, ураження шкіри, а також загибель хворих тварин унаслідок секундарних інфекцій. Специфічні методи лікування не розроблені. Для профілактики ефективним є дезінсекція тваринницьких приміщень. З цією метою було розроблено новий препарат “Цифлур”. 1 мл препарату містить діючу речовину: цифлутрин – 10,0 мг. Дослідження токсичності препарату та оцінку отриманих результатів проводили відповідно до стандартних методів. Вивчення гострої токсичності препарату “Цифлур” при нашкірному нанесенні проводили на 18 білих щурах масою тіла 170–190 г. Тварин розділяли на 3 групи по 6 голів. Щурів утримували у віварії згідно з санітарними правилами та на стандартному раціоні, прийнятими у віварії з використанням комбікорму. Першій групі щурів на шкіру наносили препарат “Цифлур” в дозі 1250 мг/кг, другій – 2500 мг/кг маси тіла. Третя група щурів була контрольною – цим тваринам на шкіру наносили розчинник Сольвессо 200 в кількості 2500 мг/кг маси тіла. Гостру токсичність препарату вивчали при нанесенні препарату на попередньо вистрижену ділянку шкіри на спині, яка становила не менше ніж 10 % від загальної площі поверхні тварини. З метою запобігання надмірному розтіканню по шкірі препарат наносили повільно, підсушуючи теплим повітрям за допомогою фена. Впродовж 14 діб після нашкірного нанесення препарату щоденно реєстрували його вплив на виживання щурів, на зовнішній вигляд щурів і прояви порушень фізіологічного стану тварин. Щурів зважували до нанесення препарату, а також через 3, 7 та 14 діб від початку досліджень. Через 14 діб проводили розтин та обстеження внутрішніх органів на наявність можливих уражень, внутрішні органи зважували та розраховували коефіцієнтів їх відносної маси. Отже, одноразове нашкірне нанесення препарату “Цифлур” в дозах 1250 та 2500 мг/кг маси тіла не спричиняло загибелі піддослідних щурів. LD50 препарату “Цифлур” при нашкірному нанесенні перевищує 2500 мг/кг маси тіла, що дозволяє віднести його до 4 класу небезпеки згідно з Міжнародним стандартом ГОСТ 12.1.007-76 або до категорії 5 за Міжнародною глобальною класифікацією Global Harmonized System, (GHS). Лише нанесення препарату “Цифлур” в найбільшій дозі (2500 мг/кг маси тіла) спричиняло незначне короткострокове почервоніння шкіри у частини піддослідних щурів, яке зникало саме без стороннього втручання впродовж 4–8 годин

Comparative analysis of thermophilic and mesophilic proteins using Protein Energy Networks

<p>Abstract</p> <p>Background</p> <p>Thermophilic proteins sustain themselves and function at higher temperatures. Despite their structural and functional similarities with their mesophilic homologues, they show enhanced stability. Various comparative studies at genomic, protein sequence and structure levels, and experimental works highlight the different factors and dominant interacting forces contributing to this increased stability.</p> <p>Methods</p> <p>In this comparative structure based study, we have used interaction energies between amino acids, to generate structure networks called as Protein Energy Networks (PENs). These PENs are used to compute network, sub-graph, and node specific parameters. These parameters are then compared between the thermophile-mesophile homologues.</p> <p>Results</p> <p>The results show an increased number of clusters and low energy cliques in thermophiles as the main contributing factors for their enhanced stability. Further more, we see an increase in the number of hubs in thermophiles. We also observe no community of electrostatic cliques forming in PENs.</p> <p>Conclusion</p> <p>In this study we were able to take an energy based network approach, to identify the factors responsible for enhanced stability of thermophiles, by comparative analysis. We were able to point out that the sub-graph parameters are the prominent contributing factors. The thermophiles have a better-packed hydrophobic core. We have also discussed how thermophiles, although increasing stability through higher connectivity retains conformational flexibility, from a cliques and communities perspective.</p

Abendland und Wirtschaftswunder. Zur kulturkritischen Physiognomie der westdeutschen Romanprosa zwischen 1945 und 1959

This study in the field of literature deals with seven novels of early Western German postwar-literature: Hermann Kasack, Die Stadt hinter dem Strom (1946); Ernst Kreuder, Die Unauffindbaren (1048); Hans Werner Richter, Die Geschlagenen (1949); Arno Schmidt, Schwarze Spiegel (1951); Wolfgang Koeppen, Tauben im Gras (1951), Das Treibhaus (1953); Heinrich Böll, Billard um halb zehn (1959). The general thesis says that in these representative texts the intellectual Gestalt of holds a key position. Despite of the rhetorics of the (1945) and the self-understandig of the authors as left-wing progressives the novels cling to an intellectual tradition of pre-war Germany that is linked to the anti-dmocratic right-wing opponents of the so-called . The critique of the and the complimentary emphasis of the wirter / intellectual as a leading figure in society are anti-Western issues which are continually re-installed through the authors' concepts of history and their claim of intellectual superiority. Developing a broad concept of analysis combining tools from hermeneutics and the social sciences (), the study points out in neat interpretations how this persistent scheme from the tradition of cultural criticism is working in various layers of the texts. There are detailed readings of the modelling of society, space and characters (esp. female ones); the study takes an additional look on essayistic and poetological passages as well as on Gnostic aspects of the involved cultural criticism

Interplay between pleiotropy and secondary selection determines rise and fall of mutators in stress response

Dramatic rise of mutators has been found to accompany adaptation of bacteria in response to many kinds of stress. Two views on the evolutionary origin of this phenomenon emerged: the pleiotropic hypothesis positing that it is a byproduct of environmental stress or other specific stress response mechanisms and the second order selection which states that mutators hitchhike to fixation with unrelated beneficial alleles. Conventional population genetics models could not fully resolve this controversy because they are based on certain assumptions about fitness landscape. Here we address this problem using a microscopic multiscale model, which couples physically realistic molecular descriptions of proteins and their interactions with population genetics of carrier organisms without assuming any a priori fitness landscape. We found that both pleiotropy and second order selection play a crucial role at different stages of adaptation: the supply of mutators is provided through destabilization of error correction complexes or fluctuations of production levels of prototypic mismatch repair proteins (pleiotropic effects), while rise and fixation of mutators occur when there is a sufficient supply of beneficial mutations in replication-controlling genes. This general mechanism assures a robust and reliable adaptation of organisms to unforeseen challenges. This study highlights physical principles underlying physical biological mechanisms of stress response and adaptation

РАЗРАБОТКА ИМПОРТОЗАМЕЩАЮЩИХ ТЕХНОЛОГИЙ ПРИ ПРОИЗВОДСТВЕ СТРОИТЕЛЬНЫХ МАТЕРИАЛОВ

The paper presents results of investigations on rational usage of mineral resources. In particular, it has shown the possibility to increase a period of raw material serviceability and its application for production of building products depending on chemical and mineralogical composition of the waste. Analysis of the executed investigations shows that import substitution of anthracite, lignite and black coal for local fuels (milled peat and its sub-standard product) is possible in the production technology of porous building materials.A mathematical model for drying process has been developed in the paper. Technology for thermal performance of a sintering machine with calculation of its length at the given pallet speed has been proposed on the basis of the developed model. Once-through circulation of flue gases and heated materials is the main specific feature of belt sintering machines being used in production. In such a case the whole drying process can be divided into two periods: a period of constant drying rate and a period of falling drying rate. Calculations have shown that the drying rate depends on moisture content but it does not depend on heat exchange Bio-criteria, however, heating rate is a function of temperature and Biq. A mechanism of moisture transfer using various drying methods is the same as in an environment with constant temperature and so in an environment with variable temperature. Application of the mathematical model provides the possibility to save significantly power resources expended for drying process.The paper gives description of methodology for calculation of technologically important optimum parameters for sintering processes of agglomeration while using milled peat.Представлены результаты исследований по проблеме рационального использования минеральных ресурсов, в частности показана возможность расширения интервала пригодности сырья и его использования для получения строительных продуктов в зависимости от химического и минералогического состава отходов. Анализ проведенных исследований показывает, что в технологии производства пористых строительных материалов возможно импортозамещение антрацита, бурого и каменного угля на местные виды топлива - фрезерный торф и его некондиционный продукт.Разработана математическая модель процесса сушки и на основе ее решения предложена технология тепловой работы агломерационной машины с расчетом ее длины при заданных скоростях движения палет. Прямоточное движение дымовых газов и нагреваемых материалов является основной особенностью применяемых в производстве ленточных агломерационных машин. При этом весь процесс сушки можно разделить на два периода: постоянной и падающей скорости сушки. Результаты вычислений показали, что скорость сушки зависит от влагосодержания, но не зависит от теплообменного критерия Био. Однако скорость нагревания является функцией и температуры, и Biq. Механизм переноса влаги при различных методах сушки один и тот же в среде как с постоянной, так и с переменной температурами. Применение данной математической модели дает возможность значительной экономии энергоресурсов, затрачиваемых на сушку.Приведены методики расчета технологически важных оптимальных параметров процессов агломерации с применением фрезерного торфа