177 research outputs found

    An analysis of the Research Fellowship Scheme of the Royal College of Surgeons of England.

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    BACKGROUND: The Research Fellowship Scheme of the Royal College of Surgeons of England commenced in 1993 with the aim of exposing selected surgical trainees to research techniques and methodology, with the hope of having an impact on surgical research and increasing the cadre of young surgeons who might decide to pursue an academic career in surgery. Over 11 million pounds sterling (approximately US 20 million dollars) has been invested in 264 fellowships. The College wished to evaluate the impact of the Scheme on the careers of research fellows, surgical research, and patient care. As the 10th anniversary of the Scheme approached. STUDY DESIGN: Two-hundred and sixty research fellows whose current addresses were available were sent a questionnaire. Two-hundred and thirty-eight (91.5%) responded. RESULTS: Three-quarters of the research fellows conducted laboratory-based research, with most of the remainder conducting patient-based clinical research. One-third of the fellows who have reached consultant status have an academic component to their post. The total number of publications based on fellowship projects was 531, with a median impact factor of 3.5. Almost all fellows had been awarded a higher degree or were working toward this. Half of the fellows received subsequent funding for research, mostly awarded by national or international funding bodies. CONCLUSIONS: The Research Fellowship Scheme of the Royal College of Surgeons of England has successfully supported many trainee surgeons in the initial phase of their research career. It has helped surgical research by increasing the pool of surgeons willing to embark on an academic career. Indirectly, patient care has benefited by promoting an evidence-based culture among young surgeons. Such schemes are relevant to surgical training programs elsewhere if more young surgeons are to be attracted into academic surgery

    The Role of Northeast Ohio Central Cities in the Regional Economy, 2000-2007

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    This report examines the four central cities in Northeast Ohio – Akron, Canton, Cleveland, and Youngstown — in the context of their metropolitan areas. A central city is the largest or most important city of a metropolitan area. A metropolitan area combines a large city with adjacent urbanized areas and peripheral areas that are closely bound to the center with strong ties to commuting, commerce, and a common labor market

    The First Direct Detection of Kirkwood Transitions in Concentrated Aqueous Electrolytes using Small Angle X-ray Scattering

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    Ion-ion correlations, screening, and equilibrium bulk structure in various concentrated electrolytes are investigated using synchrotron small angle X-ray scattering (SAXS), theory, and molecular simulation. Utilizing SAXS measurements we provide estimates of the Kirkwood Transition (KT) for a variety of aqueous electrolytes (NaCl, CaCl2_2, SrCl2_2, and ErCl3_3). The KT may be defined as the concentration above which the ion-ion correlations cease to decay exponentially with a single length scale given by the Debye length λD\lambda_{\rm D} and develop an additional length scale, d=2π/Q0d=2\pi/Q_0 that reflects the formation of local domains of charge. Theoretical models of the KT have been known for decades for highly idealized models of electrolytes, but experimental verification of KT in real electrolytes has yet to be confirmed. Herein, we provide consistent theoretical and experimental estimates of both the inverse screening lengths a0a_0 and inverse domain size, Q0Q_0 for the aforementioned electrolyte systems. Taken together, a0a_0 and Q0Q_0 are known descriptors of the KT and provide a view into the complexity of ion-ion interaction beyond the well-accepted Debye-H\"{u}ckel limit. Our findings suggest a picture of interaction for real electrolytes that is more general than that found in idealized models that is manifest in the precise form of the non-local response function that we estimate through the interpretation of the experimental SAXS signal. Importantly, the additional complexity of describing ion-ion interaction of real electrolytes will implicate the short-range ion-ion interactions that can only be computed via molecular simulation and provide a quantitative approach to describe electrolyte phenomena beyond Debye-H\"{u}ckel theory.Comment: 3

    Spiral Density Waves in a Young Protoplanetary Disk

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    Gravitational forces are expected to excite spiral density waves in protoplanetary disks, disks of gas and dust orbiting young stars. However, previous observations that showed spiral structure were not able to probe disk midplanes, where most of the mass is concentrated and where planet formation takes place. Using the Atacama Large Millimeter/submillimeter Array we detected a pair of trailing symmetric spiral arms in the protoplanetary disk surrounding the young star Elias 2-27. The arms extend to the disk outer regions and can be traced down to the midplane. These millimeter-wave observations also reveal an emission gap closer to the star than the spiral arms. We argue that the observed spirals trace shocks of spiral density waves in the midplane of this young disk.Comment: This is our own version of the manuscript, the definitive version was published in Science (DOI: 10.1126/science.aaf8296) on September 30, 2016. Posted to the arxiv for non-commercial us

    \u3ci\u3eArabidopsis\u3c/i\u3e Accelerated Cell Death 11, ACD11, Is a Ceramide-1-Phosphate Transfer Protein and Intermediary Regulator of Phytoceramide Levels

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    The accelerated cell death 11 (acd11) mutant of Arabidopsis provides a genetic model for studying immune response activation and localized cellular suicide that halt pathogen spread during infection in plants. Here, we elucidate ACD11 structure and function and show that acd11 disruption dramatically alters the in vivo balance of sphingolipid mediators that regulate eukaryotic-programmed cell death. In acd11 mutants, normally low ceramide-1- phosphate (C1P) levels become elevated, but the relatively abundant cell death inducer phytoceramide rises acutely. ACD11 exhibits selective intermembrane transfer of C1P and phyto-C1P. Crystal structures establish C1P binding via a surface-localized, phosphate headgroup recognition center connected to an interior hydrophobic pocket that adaptively ensheaths lipid chains via a cleft-like gating mechanism. Point mutation mapping confirms functional involvement of binding site residues. A π helix (π bulge) near the lipid binding cleft distinguishes apo-ACD11 from other GLTP folds. The global two-layer, α-helically dominated, ‘‘sandwich’’ topology displaying C1P-selective binding identifies ACD11 as the plant prototype of a GLTP fold subfamily

    Amino acid sequence of the ligand-binding domain of the aryl hydrocarbon receptor 1 predicts sensitivity of wild birds to effects of dioxin-like compounds

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    Author Posting. © The Author(s), 2012. This is the author's version of the work. It is posted here by permission of Oxford University Press for personal use, not for redistribution. The definitive version was published in Toxicological Sciences 131 (2013): 139-152, doi:10.1093/toxsci/kfs259.The sensitivity of avian species to the toxic effects of dioxin-like compounds (DLCs) varies up to 1000-fold among species and this variability has been associated with inter-species differences in aryl hydrocarbon receptor 1 ligand binding domain (AHR1 LBD) sequence. We previously showed that LD50 values, based on in ovo exposures to DLCs, were significantly correlated with in vitro EC50 values obtained with a luciferase reporter gene (LRG) assay that measures AHR1-mediated induction of cytochrome P4501A in COS-7 cells transfected with avian AHR1 constructs. Those findings suggest that the AHR1 LBD sequence and the LRG assay can be used to predict avian species sensitivity to DLCs. In the present study, the AHR1 LBD sequences of 86 avian species were studied and differences at amino acid sites 256, 257, 297, 324, 337 and 380 were identified. Site-directed mutagenesis, the LRG assay and homology modeling highlighted the importance of each amino acid site in AHR1 sensitivity to 2,3,8,8-tetrachlorodibenzo-p-dioxin and other DLCs. The results of the study revealed that: (1) only amino acids at sites 324 and 380 affect the sensitivity of AHR1 expression constructs of 86 avian species to DLCs and (2) in vitro luciferase activity in AHR1 constructs containing only the LBD of the species of interest is significantly correlated (r2 = 0.93, p<0.0001) with in ovo toxicity data for those species. These results indicate promise for the use of AHR1 LBD amino acid sequences independently, or combined with the LRG assay, to predict avian species sensitivity to DLCs.This research was supported by unrestricted grants from the Dow Chemical Company and Georgia-Pacific LLC to the University of Ottawa, Environment Canada’s STAGE program and, in part, by a Discovery Grant from the National Science and Engineering Research Council of Canada (Project # 326415-07). The authors wish to acknowledge the support of an instrumentation grant from the Canada Foundation for Infrastructure. Professor Giesy was supported by the Canada Research Chair program and an at large Chair Professorship at the Department of Biology and Chemistry and State Key Laboratory in Marine Pollution, City University of Hong Kong, the Einstein Professor Program of the Chinese Academy of Sciences and the Visiting Professor Program of King Saud University. M. Hahn and S. Karchner were supported by NOAA Sea Grant (grant number NA06OAR4170021 (R/B-179)), and by the Walter A. and Hope Noyes Smith endowed chair.2013-08-2
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