A conformational analysis of walker motif A [GXXXXGKT (S)] in nucleotide-binding and other proteins

The sequence GXXXXGKT/S, popularly known as Walker motif A, is widely believed to be the site for binding nucleotides in many proteins. Examination of the crystal structures in the Protein Data Bank showed that about half of the examples having these sequences do not bind or use nucleotides. Data analyses showed 92 different Walker sequences of the variable quartet (XXXX). Ramachandran angles in this segment revealed conformational similarity in the group of 45 proteins, known to bind or utilize nucleotides. The conformations of this segment in other proteins differ widely and it is not known whether they play any role in their functions. A flip of a peptide unit at different locations, with little change in the backbone conformation was noted in nine pairs of these proteins having same Walker sequence. An examination of the immediate neighborhood of the Walker sequence indicates that this region is preceded by a β -strand and followed by an α-helix, resulting in the motif β–W–α, an invariant feature amongst nucleotide-binding proteins

Click-based porous cationic polymers for enhanced carbon dioxide capture

Imidazolium based porous cationic polymers were synthesized using an innovative and facile approach, which takes advantage of the Debus Radziszewski reaction to obtain meso- and microporous polymers following click chemistry principles. In the obtained set of materials, click based porous cationic polymers have the same cationic backbone, whereas they bear the commonly used anions of imidazolium poly(ionic liquid)s. These materials show hierarchical porosity and a good specific surface area. Furthermore, their chemical structure was extensively characterized using ATR FTIR and SS NMR spectroscopies, and HR MS. These polymers show good performance towards carbon dioxide sorption, especially those possessing the acetate anion. This polymer has an uptake of 2 mmol per g of CO2 at 1 bar and 273 K, a value which is among the highest recorded for imidazolium poly(ionic liquid)s. These polymers were also modified in order to introduce N-heterocyclic carbenes along the backbone. Carbon dioxide loading in the carbene-containing polymer is in the same range as that of the non-modified versions, but the nature of the interaction is substantially different. The combined use of in situ FTIR spectroscopy and microcalorimetry evidenced a chemisorption phenomenon that brings about the formation of an imidazolium carboxylate zwitterion.Comment: 29 page, 33 figure

The Computational Power of Optimization in Online Learning

We consider the fundamental problem of prediction with expert advice where the experts are "optimizable": there is a black-box optimization oracle that can be used to compute, in constant time, the leading expert in retrospect at any point in time. In this setting, we give a novel online algorithm that attains vanishing regret with respect to $N$ experts in total $\widetilde{O}(\sqrt{N})$ computation time. We also give a lower bound showing that this running time cannot be improved (up to log factors) in the oracle model, thereby exhibiting a quadratic speedup as compared to the standard, oracle-free setting where the required time for vanishing regret is $\widetilde{\Theta}(N)$. These results demonstrate an exponential gap between the power of optimization in online learning and its power in statistical learning: in the latter, an optimization oracle---i.e., an efficient empirical risk minimizer---allows to learn a finite hypothesis class of size $N$ in time $O(\log{N})$. We also study the implications of our results to learning in repeated zero-sum games, in a setting where the players have access to oracles that compute, in constant time, their best-response to any mixed strategy of their opponent. We show that the runtime required for approximating the minimax value of the game in this setting is $\widetilde{\Theta}(\sqrt{N})$, yielding again a quadratic improvement upon the oracle-free setting, where $\widetilde{\Theta}(N)$ is known to be tight

Discovering Valuable Items from Massive Data

Suppose there is a large collection of items, each with an associated cost and an inherent utility that is revealed only once we commit to selecting it. Given a budget on the cumulative cost of the selected items, how can we pick a subset of maximal value? This task generalizes several important problems such as multi-arm bandits, active search and the knapsack problem. We present an algorithm, GP-Select, which utilizes prior knowledge about similarity be- tween items, expressed as a kernel function. GP-Select uses Gaussian process prediction to balance exploration (estimating the unknown value of items) and exploitation (selecting items of high value). We extend GP-Select to be able to discover sets that simultaneously have high utility and are diverse. Our preference for diversity can be specified as an arbitrary monotone submodular function that quantifies the diminishing returns obtained when selecting similar items. Furthermore, we exploit the structure of the model updates to achieve an order of magnitude (up to 40X) speedup in our experiments without resorting to approximations. We provide strong guarantees on the performance of GP-Select and apply it to three real-world case studies of industrial relevance: (1) Refreshing a repository of prices in a Global Distribution System for the travel industry, (2) Identifying diverse, binding-affine peptides in a vaccine de- sign task and (3) Maximizing clicks in a web-scale recommender system by recommending items to users

Efficacy and safety of pharmacological treatments for patent ductus arteriosus closure: A systematic review and network meta-analysis of clinical trials and observational studies

Efficacy and safety profiles of different pharmacological interventions used to treat patent ductus arteriosus (PDA) are relatively unexplored. Integrating the findings of randomized clinical trials (RCTs) with those from observational studies may provide key evidence on this important issue. We aimed at estimating the relative likelihood of failure to close the PDA, need for surgical closure, and occurrence of adverse events among preterm and full-term infants treated with indomethacin, ibuprofen, or acetaminophen, placebo, or no treatment including both RCTs and observational studies. We searched PubMed, Embase, and the Register of Controlled Trials from inception to October 30, 2018. We first estimated proportions of subjects with failure to close the PDA, subjects in whom surgical closure was performed after pharmacological treatment, death, and subjects with selected adverse events (AEs). These estimates were obtained using frequentist random-effect meta-analysis of arm-specific proportions. We then compared active drugs with each other and with control (either placebo or no treatment) by summarizing results at the end of treatment reported in the papers, regardless of number of administration(s), dose, route and type of administration, and study design and quality. We also summarized primary outcome results separately at first, second and third cycles of treatment. These estimates were obtained using Bayesian random-effects network meta-analysis for mixed comparisons, and frequentist random-effect pairwise meta-analysis for direct comparisons. We included 64 RCTs and 24 observational studies including 14,568 subjects (5339 in RCTs and 9229 in observational studies, 8292 subjects received indomethacin, 4761 ibuprofen, 574 acetaminophen, and 941 control (including placebo or no intervention).The proportion of subjects with failure to close the PDA was 0.24 (95% Confidence Interval, CI: 0.20, 0.29) for indomethacin, 0.18 (0.14, 0.22) for ibuprofen, 0.19 (0.09, 0.30) for acetaminophen, and 0.59 (0.48, 0.69) for control. At end of treatment, compared to control, we found inverse associations between all active drugs and failure to close PDA (for indomethacin Odds Ratio, OR, was 0.17 [95% Credible Interval, CrI: 0.11-0.24], ibuprofen 0.19 [0.12-0.28], and acetaminophen 0.15 [0.09-0.26]), without differences among active drugs. We showed inverse associations between effective drugs and need for surgical closure, as compared to control (for indomethacin OR was 0.28 [0.15-0.50], ibuprofen 0.30 [0.16-0.54], and acetaminophen 0.19 [0.07-0.46]), without differences among drugs. Indomethacin was directly associated with intraventricular hemorrhage (IVH) (1.27; 1.00, 1.62) compared to ibuprofen, and to oliguria as compared to ibuprofen (3.92; 1.69, 9.82) or acetaminophen (10.8; 1.86, 93.1). In conclusion, active pharmacological treatment, with indomethacin, ibuprofen, or acetaminophen, is inversely associated with failure to close the PDA compared to non-treatment. Ibuprofen should be preferred to indomethacin to avoid occurrence of IVH or oliguria, acetaminophen should be preferred to indomethacin to avoid oliguria

Development of Al-Mg Alloy for the protection of steel structure in 3.5% Nacl

Aluminium (Al) is thoroughly used as a sacrificial metal for the protection of steel in seawater. Aluminium is rarely used as a sacrificial anode without being alloyed due to its built-in properties to get passivates and form a passive layer and the continuity of its layer depends on the chemical composition and microstructure. In this paper, Aluminium-Magnesium(5xxx) system is considered because magnesium remarkably affects the chemical properties by changing the microstructure of Aluminium from a homogeneous solid solution to a complex structure with multiple intermetallic phases. In this research work developing Aluminium-Magnesium alloys containing 2.5 and 4.5 weight percent magnesium. The microstructures of pure aluminium and developed alloys were studied and the effect of the distribution of magnesium whether as a second phase particle, intermetallic compound or precipitates on the performance of aluminium sacrificial anode was discussed. Standard weight loss method and potentiodynamic tests are used to evaluate the performance of alloy sacrificial anode. The result shows that as the magnesium content increases corrosion rate of developed alloy increases and corrosion potential shifts in more negative directions. Corrosion potential is increased by 250 mV at 4.5% magnesium because of the formation of an intermetallic compound of aluminium& Magnesium (β phase - Al3Mg2) at the grain boundary. Magnesium improves the corrosion rate of developed alloy, it acts as a depassivators for the passive film of Aluminium by forming intermetallic compound and this compound has different electrochemicalproperties that leads to corrosion of aluminium and improves the performance of aluminium sacrificial anode

Ultrametric Logarithm Laws, II

We prove positive characteristic versions of the logarithm laws of Sullivan and Kleinbock-Margulis and obtain related results in Metric Diophantine Approximation.Comment: submitted to Montasefte Fur Mathemati

The Cloud Aerosol Interaction and Precipitation Enhancement Experiment (CAIPEEX): overview and preliminary results

While the demand for enhancing rainfall through cloud seeding is strong and persistent in the country, considerable uncertainty exists on the success of such an endeavour at a given location. To understand the pathways of aerosol-cloud interaction through which this might be achieved, a national experiment named Cloud Aerosol Interaction and Precipitation Enhancement EXperiment (CAIPEEX) in two phases, was carried out. The rationale of CAIPEEX, the strategy for conducting the experiment, data quality and potential for path-breaking science are described in this article. Pending completion of quality control and calibration of the CAIPEEX phase-II data, here we present some initial results of CAIPEEX phase-I aimed at documenting the prevailing microphysical characteristics of aerosols and clouds and associated environmental conditions over different regions of the country and under different monsoon conditions with the help of an instrumented research aircraft. First-time simultaneous observations of aerosol, cloud condensation nuclei (CCN) and cloud droplet number concentration (CDNC) over the Ganges Valley during monsoon season show very high concentrations (> 1000 cm-3) of CCN at elevated layers. Observations of elevated layers with high aerosol concentration over the Gangetic valley extending up to 6 km and relatively less aerosol concentration in the boundary layer are also documented. We also present evidence of strong cloud- aerosol interaction in the moist environments with an increase in the cloud droplet effective radius. Our observations also show that pollution increases CDNC and the warm rain depth, and delays its initiation. The critical effective radius for warm rain initiation is found to be between 10 and 12 µm in the polluted clouds and it is between 12 and 14 µm in cleaner monsoon clouds

Сучасний погляд на соціокультурний підхід у вихованні особистості майбутніх фахівців медичної галузі

The article describes the main approaches that address the issues of socio-cultural approach to training of future specialists. In the analysis of existing approaches to training of specialists in higher educational institutions the importance of reforming the existing system from a position of socio-cultural approach because of the consideration and implementation of socio-cultural components in the training future professionals can develop the skills of self-organization and self-development of future specialists. The authors emphasized that this problem must be solved in line with the comprehensive (systemic) approach to the forming of personality of specialist.У статті розглянуті основні підходи, які зачіпають проблематику соціокультурного підходу до підготовки майбутніх фахівців. При аналізі існуючих підходів до професійної підготовки фахівців у вищих навчальних закладах підкреслено важливість реформування існуючої системи з позиції соціокультурного підходу, оскільки урахування та впровадження соціокультурних компонентів у професійну підготовку майбутніх професіоналів дозволяє формувати навички самоорганізації та самовдосконалення у майбутніх спеціалістів. Авторами підкреслено, що дана проблема повинна вирішуватись в руслі комплексного (системного) підходу до формування особистості фахівця