Professional Education and Ethics.

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Breaking the paradigm: Dr Insight empowers signature-free, enhanced drug repurposing

Motivation: Transcriptome-based computational drug repurposing has attracted considerable interest by bringing about faster and more cost-effective drug discovery. Nevertheless, key limitations of the current drug connectivity-mapping paradigm have been long overlooked, including the lack of effective means to determine optimal query gene signatures. Results: The novel approach Dr Insight implements a frame-breaking statistical model for the ‘hand-shake’ between disease and drug data. The genome-wide screening of concordantly expressed genes (CEGs) eliminates the need for subjective selection of query signatures, added to eliciting better proxy for potential disease-specific drug targets. Extensive comparisons on simulated and real cancer datasets have validated the superior performance of Dr Insight over several popular drug-repurposing methods to detect known cancer drugs and drug–target interactions. A proof-of-concept trial using the TCGA breast cancer dataset demonstrates the application of Dr Insight for a comprehensive analysis, from redirection of drug therapies, to a systematic construction of disease-specific drug-target networks

Mixing effectiveness in the Apollo oxygen tanks of spin-up and rotation-reversal maneuvers

Two-dimensional simulations of stratified flows in the Apollo oxygen tanks have been used to estimate the mixing effectiveness of spin-up and rotation-reversal maneuvers. Calculations have been made for square and circular cylindrical tank geometries. Differences arising from heater position on the tank wall or near the center of the tank have been investigated. In the event of a prolonged period without normal maneuvers, the potential pressure decay (drop in pressure that would result from adiabatic mixing) can be suppressed by more than a factor of two through the use of spin-up and rotation-reversal maneuvers. Changes in rotation rate of order three revolutions per hour or greater are sufficient for this purpose

The Most Severe Test for Hydrophobicity Scales: Two Proteins with 88% Sequence Identity but Different Structure and Function

Protein-protein interactions (protein functionalities) are mediated by water, which compacts individual proteins and promotes close and temporarily stable large-area protein-protein interfaces. In their classic paper Kyte and Doolittle (KD) concluded that the "simplicity and graphic nature of hydrophobicity scales make them very useful tools for the evaluation of protein structures". In practice, however, attempts to develop hydrophobicity scales (for example, compatible with classical force fields (CFF) in calculating the energetics of protein folding) have encountered many difficulties. Here we suggest an entirely different approach, based on the idea that proteins are self-organized networks, subject to finite-scale criticality (like some network glasses). We test this proposal against two small proteins that are delicately balanced between alpha and alpha/beta structures, with different functions encoded with only 12% of their amino acids. This example explains why protein structure prediction is so challenging, and it provides a severe test for the accuracy and content of hydrophobicity scales. The new method confirms KD's evaluation, and at the same time suggests that protein structure, dynamics and function can be best discussed without using CFF

Phase transition in the globalization of trade

Globalization processes interweave economic structures at a worldwide scale, trade playing a central role as one of the elemental channels of interaction among countries. Despite the significance of such phenomena, measuring economic globalization still remains an open problem. More quantitative treatments could improve the understanding of globalization at the same time that help a formal basis for comparative economic history. In this letter, we investigate the time evolution of the statistical properties of bilateral trade imbalances between countries in the trade system. We measure their cumulative probability distribution at different moments in time to discover a sudden transition circa 1960 from a regime where the distribution was always represented by a steady characteristic function to a new state where the distribution dilates as time goes on. This suggests that the rule that was governing the statistical behavior of bilateral trade imbalances until the 60's abruptly changed to a new form persistent in the last decades. In the new regime, the figures for the different years collapse into a universal master curve when rescaled by the corresponding global gross domestic product value. This coupling points to an increased interdependence of world economies and its onset corresponds in time with the starting of the last globalization wave.Comment: Final versio

Spectrophotometry of 2 complete samples of flat radio spectrum quasars

Spectrophotometry of two complete samples of flat-spectrum radio quasars show that for these objects there is a strong correlation between the equivalent width of the CIV wavelength 1550 emission line and the luminosity of the underlying continuum. Assuming Friedmann cosmologies, the scatter in this correlation is a minimum for q (sub o) is approximately 1. Alternatively, luminosity evolution can be invoked to give compact distributions for q (sub o) is approximately 0 models. A sample of Seyfert galaxies observed with IUE shows that despite some dispersion the average equivalent width of CIV wavelength 1550 in Seyfert galaxies is independent of the underlying continuum luminosity. New redshifts for 4 quasars are given

Rose Of Pyramid Land

https://digitalcommons.library.umaine.edu/mmb-vp/6686/thumbnail.jp

Theres a Girl in Havana

https://digitalcommons.library.umaine.edu/mmb-vp/6324/thumbnail.jp

Beta Secondary Deuterium Kinetic Isotope Effects on the Thermal Stereomutations of 1,2-Diphenylcyclopropanes

(+)-(1S,2S)-trans-1,2-Diphenylcyclopropane and (-)-(1R,2R)-trans- l,2-diphenyl-3,3-t2-cyclopropane at 234 °C interconvert reversibly with the corresponding enantiomers and css-1,2-diphenyl cyclopropanes. For the unlabeled trans isomer, the ratio of rate constants for one-center epimerization (k) and two-center turnover (&12) was found to be 1.1. A small normal k^Jk-Q effect, 3% per deuterium, was observed for the rate constant for one-center epimerization (k1); a substantial normal k-^lk-Q effect, 17% per deuterium, was observed for the rate constant for two-center turnover (k^). Thus different transition structures, presumably EF and EE 1,3-diphenyltrimethylene diradicals, dominate the two sorts of stereomutations

Molecular interactions between the specialist herbivore Manduca sexta (Lepidoptera, Sphigidae) and its natural host Nicotiana attenuata. VIII. An unbiased GCxGC-ToFMS analysis of the plant´s elicited volatile emissions

Treating wounds in Nicotiana attenuata leaves with Manduca sexta oral secretions (W+OS) mimics most changes elicited by M. sexta herbivory, but an unbiased analysis of the effect of the different OS constituents on volatile emissions is lacking. We used two-dimensional gas chromatography/time-of-flight (GCxGC-ToF) mass spectrometry combined with multivariate statistics to parse volatiles into regulatory patterns. Volatiles released by wounding alone and by the alkalinity of OS were assessed by applying a buffer known to mimic the pH-mediated changes of OS elicitation (pectin methyl esterase activation and methanol release). The activities of fatty acid amino acid conjugates, well-known elicitors of antiherbivore defenses, and of 2-hydroxyoctadecatrienoic acid, a newly discovered signal in OS, were determined. Approximately 400 analytes were detected after deconvolution and alignment of GCxGC data; 35 volatiles were significantly regulated upon W+OS. Two-thirds of these were specifically regulated by OS, being either amplified (most terpenoids and certain hexenylesters) or strongly repressed (many short-chain alcohols and some aromatic and hexenylester derivatives). Fatty acid amino acid conjugates played a central role in this pattern of regulation, since they induced the emission of half of OS-elicited volatiles and inhibited the production of almost all OS-repressed volatiles; 2-hydroxyoctadecatrienoic acid influenced emission of trans-α-bergamotene, while other unknown OS constituents amplified hexenylester production. We conclude that the complex bouquet of herbivory-elicited volatiles results from the complex modulations of the wound response by diverse cues found in OS. This work also underscores the value of ultra-high-resolution GCxGC-ToF analysis combined with the nontargeted mining of the resulting data