185 research outputs found
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Preliminary Definition of Geophysical Regions in Western Eurasia
The authors present a regionalized crustal model of Western Eurasia, WEA. The model is constructed using results from published studies and maps of geological and geophysical parameters in this region, and was developed in conjunction with the updated regionalization of Middle East and North Africa by Walter et al.[2000]. As this is the first realization of the Eurasian modeling effort, they have limited themselves to only twelve broad regions. Particular attention has been given to identifying the boundaries for each region. The main use of this model will be to assist in monitoring the Comprehensive Nuclear Test Ban Treaty (CTBT). Specifically, this model will help them to calibrate and predict the travel time and amplitudes of various regional seismic phases and to locate events accurately. The model based approach allows them to readily calibrate both the seismic and the aseismic parts of western Eurasia. Each region is specified by an one-dimensional model of compressional and shear velocities, densities and layer thicknesses. Further improvements to this model will involve, but not be limited to, increasing the spatial coverage toward the east and west of Eurasia, identify sub-regions based on their distinct physical properties and the use of new and improved body wave and surface wave datasets. In the future, they expect to use this model and its successors to be the baseline model for calibration techniques, e.g., kriging, to improve their capability to detect, locate and discriminate different seismic events in Eurasia
Iterative Compilation in a Non-linear Optimisation Space
This paper investigates the applicability of iterative search techniques in program optimisation. Iterative compilation is usually considered too expensive for general purpose computing but is applicable to embedded applications where the cost is easily amortised over the number of embedded systems produced. This paper presents a case study, where an iterative search algorithm is used to investigate a nonlinear transformation space and find the fastest execution time within a fixed number of evaluations. By using execution time as feedback, it searches a large but restricted transformation space and shows performance improvement over existing approaches. We show that in the case of large transformation spaces, we can achieve within 0.3% of the best possible time by visiting less then 0.25% of the space using a simple algorithm and find the minimum after visiting less than 1% of the space
MACiE (Mechanism, Annotation and Classification in Enzymes): novel tools for searching catalytic mechanisms
MACiE (Mechanism, Annotation and Classification in Enzymes) is a database of enzyme reaction mechanisms, and is publicly available as a web-based data resource. This paper presents the first release of a web-based search tool to explore enzyme reaction mechanisms in MACiE. We also present Version 2 of MACiE, which doubles the dataset available (from Version 1). MACiE can be accessed fro
Mathematically Gifted Adolescents Have Deficiencies in Social Valuation and Mentalization
Many mathematically gifted adolescents are characterized as being indolent, underachieving and unsuccessful despite their high cognitive ability. This is often due to difficulties with social and emotional development. However, research on social and emotional interactions in gifted adolescents has been limited. The purpose of this study was to observe differences in complex social strategic behaviors between gifted and average adolescents of the same age using the repeated Ultimatum Game. Twenty-two gifted adolescents and 24 average adolescents participated in the Ultimatum Game. Two adolescents participate in the game, one as a proposer and the other as a responder. Because of its simplicity, the Ultimatum Game is an apt tool for investigating complex human emotional and cognitive decision-making in an empirical setting. We observed strategic but socially impaired offers from gifted proposers and lower acceptance rates from gifted responders, resulting in lower total earnings in the Ultimatum Game. Thus, our results indicate that mathematically gifted adolescents have deficiencies in social valuation and mentalization
Confab - Systematic generation of diverse low-energy conformers
<p>Abstract</p> <p>Background</p> <p>Many computational chemistry analyses require the generation of conformers, either on-the-fly, or in advance. We present Confab, an open source command-line application for the systematic generation of low-energy conformers according to a diversity criterion.</p> <p>Results</p> <p>Confab generates conformations using the 'torsion driving approach' which involves iterating systematically through a set of allowed torsion angles for each rotatable bond. Energy is assessed using the MMFF94 forcefield. Diversity is measured using the heavy-atom root-mean-square deviation (RMSD) relative to conformers already stored. We investigated the recovery of crystal structures for a dataset of 1000 ligands from the Protein Data Bank with fewer than 1 million conformations. Confab can recover 97% of the molecules to within 1.5 Å at a diversity level of 1.5 Å and an energy cutoff of 50 kcal/mol.</p> <p>Conclusions</p> <p>Confab is available from <url>http://confab.googlecode.com</url>.</p
Incorporation of a chiral gem-disubstituted nitrogen heterocycle yields an oxazolidinone antibiotic with reduced mitochondrial toxicity
gem-Disubstituted N-heterocycles are rarely found in drugs, despite their potential to improve the drug-like properties of small molecule pharmaceuticals. Linezolid, a morpholine heterocycle-containing oxazolidinone antibiotic, exhibits significant side effects associated with human mitochondrial protein synthesis inhibition. We synthesized a gem-disubstituted linezolid analogue that when compared to linezolid, maintains comparable (albeit slightly diminished) activity against bacteria, comparable in vitro physicochemical properties, and a decrease in undesired mitochondrial protein synthesis (MPS) inhibition. This research contributes to the structure-activity-relationship data surrounding oxazolidinone MPS inhibition, and may inspire investigations into the utility of gem-disubstituted N-heterocycles in medicinal chemistry
A basic theory of inheritance: How bad practice prevails
This paper develops an inheritance theory explaining the diffusion and persistence of detrimental management practice. Received wisdom, in both management theory and practice, would suggest that a practice that lowers the life expectancy of adopting firms, over time, will vanish because it puts those firms at a competitive disadvantage. In this paper, I challenge this view. I develop a conceptual model that details how a practice that lowers the survival chances of adopting organizations may still spread and continue to exist across a population of firms. I propose that a combination of three basic conditions is sufficient to bring about this phenomenon: if the practice is somehow associated with success, if there exists causal ambiguity, and if the rate of its diffusion is high compared with the rate at which it accelerates firms’ demise, the practice may continue to thrive and become a widespread and persistent feature in an industry. A pivotal conceptual insight is that the endurance of particular management practices and strategies is not merely a corollary of the competitiveness of the
organizations that use them but that they have fitness levels of their own
‘When Birds of a Feather Flock Together’: Synesthetic Correspondences Modulate Audiovisual Integration in Non-Synesthetes
Parise C, Spence C. ‘When Birds of a Feather Flock Together’: Synesthetic Correspondences Modulate Audiovisual Integration in Non-Synesthetes. Presented at the 10th International Multisensory Research Forum (IMRF 2009), New York, NY
Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy
High risk of recurrence/progression bladder tumours is treated with Bacillus Calmette-Guérin (BCG) immunotherapy after complete resection of the tumour. Approximately 75% of these tumours express the uncommon carbohydrate antigen sialyl-Tn (Tn), a surrogate biomarker of tumour aggressiveness. Such changes in the glycosylation of cell-surface proteins influence tumour microenvironment and immune responses that may modulate treatment outcome and the course of disease. The aim of this work is to determine the efficiency of BCG immunotherapy against tumours expressing sTn and sTn-related antigen sialyl-6-T (s6T).
METHODS:
In a retrospective design, 94 tumours from patients treated with BCG were screened for sTn and s6T expression. In vitro studies were conducted to determine the interaction of BCG with high-grade bladder cancer cell line overexpressing sTn.
RESULTS:
From the 94 cases evaluated, 36 had recurrence after BCG treatment (38.3%). Treatment outcome was influenced by age over 65 years (HR=2.668; (1.344-5.254); P=0.005), maintenance schedule (HR=0.480; (0.246-0.936); P=0.031) and multifocality (HR=2.065; (1.033-4.126); P=0.040). sTn or s6T expression was associated with BCG response (P=0.024; P<0.0001) and with increased recurrence-free survival (P=0.001). Multivariate analyses showed that sTn and/or s6T were independent predictive markers of recurrence after BCG immunotherapy (HR=0.296; (0.148-0.594); P=0.001). In vitro studies demonstrated higher adhesion and internalisation of the bacillus to cells expressing sTn, promoting cell death.
CONCLUSION:
s6T is described for the first time in bladder tumours. Our data strongly suggest that BCG immunotherapy is efficient against sTn- and s6T-positive tumours. Furthermore, sTn and s6T expression are independent predictive markers of BCG treatment response and may be useful in the identification of patients who could benefit more from this immunotherapy
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