Two acyclic imides: 3-bromo-N-(3-bromobenzoyl)-N-(pyridin-2-yl)benzamide and 3-bromo-N-(3-bromobenzoyl)-N-(pyrimidin-2-yl)benzamide

The title compounds, C19H12Br2N2O2 and C18H11Br2N3O2, were synthesized in good yields from condensation reactions of 3-bromobenzoyl chloride with 2-aminopyridine or 2-aminopyrimidine using standard condensation reaction conditions and subsequent column chromatography

Fluorine substitutions in an antigenic peptide selectively modulate T cell receptor binding in a minimally perturbing manner

T cell receptor (TCR) recognition of antigenic peptides bound and presented by major histocompatibility complex (MHC) molecules forms the basis of the cellular immune response to pathogens and cancer. TCRs bind peptide/MHC molecules weakly and with fast kinetics, features which have hindered detailed biophysical studies of these interactions. Modified peptides resulting in enhanced TCR binding could help overcome these challenges. Further, there is considerable interest in using modified peptides with enhanced TCR binding as the basis for clinical vaccines. Here, we studied how fluorine substitutions in an antigenic peptide can selectively impact TCR recognition. Using a structure-guided design approach, we found that fluorination of the HTLV-1 Tax11-19 peptide (Tax) enhanced binding by the Tax-specific TCR A6, yet weakened binding by the Tax-specific TCR B7. The changes in affinity were consistent with crystallographic structures and fluorine chemistry, and with A6, independent of other substitutions in the interface. Peptide fluorination thus provides a means to selectively modulate TCR binding affinity without significantly perturbing peptide composition or structure. Lastly, in probing the mechanism of fluorine’s effect on TCR binding, our data were most consistent with fluorine’s unique “polar hydrophobicity,” a finding which should impact other attempts to alter molecular recognition with fluorine

Neptunism and transformism:Robert Jameson and other evolutionary theorists in early nineteenth-century Scotland

This paper sheds new light on the prevalence of evolutionary ideas in Scotland in the early nineteenth century and establish what connections existed between the espousal of evolutionary theories and adherence to the directional history of the earth proposed by Abraham Gottlob Werner and his Scottish disciples. A possible connection between Wernerian geology and theories of the transmutation of species in Edinburgh in the period when Charles Darwin was a medical student in the city was suggested in an important 1991 paper by James Secord. This study aims to deepen our knowledge of this important episode in the history of evolutionary ideas and explore the relationship between these geological and evolutionary discourses. To do this it focuses on the circle of natural historians around Robert Jameson, Wernerian geologist and professor of natural history at the University of Edinburgh from 1804 to 1854. From the evidence gathered here there emerges a clear confirmation that the Wernerian model of geohistory facilitated the acceptance of evolutionary explanations of the history of life in early nineteenth-century Scotland. As Edinburgh was at this time the most important center of medical education in the English-speaking world, this almost certainly influenced the reception and development of evolutionary ideas in the decades that followed.</p

Tide and wind coupling in a semienclosed bay driven by coastal upwelling

The Ría de Vigo is a semi-enclosed bay in which tidal residual currents are associated with coastal upwelling events. Both upwelling and downwelling favourable winds generate a bidirectional exchange flow with the shelf – a two-layer circulation with surface waters leaving (entering) the ria and a compensating inflow (outflow) through the bottom layer under upwelling (downwelling) conditions. This vertical circulation changes the vertical density structure inside the ria. In the ria, the tide is mainly semidiurnal (M2, S2 and K2), with some energy in the diurnal band (K1). Our velocity observations show that the vertical structure of the tidal currents in the ria do not exhibit a classic barotropic profile with a bottom boundary layer beneath uniform “free-stream” flow as the tidal bottom boundary layer is affected by stratification. This links tidal circulation to the wind-driven residual circulation, since the latter also greatly helps to control the stratification. We quantify this effect by fitting tidal ellipses to observed velocities through the water column. In addition to this indirect coupling through stratification, there is a direct interaction in which velocities in the upper and bottom layers are best correlated with winds while the mid-water velocities are best correlated with tides. These wind-tide interactions are expected to play a key role in the resuspension and transport of nutrients and phytoplankton in the Ria.CTM2012-3515

Establishing the Scope and Methodological Approach to Out-of-hospital Outcomes and Effectiveness Research

: Outcomes research offers out-of-hospital medicine a valuable methodology for studying the effectiveness of services provided in the out-of hospital setting. A clear understanding of the history and constructs of outcomes research is necessary for its integration into emergency medical services research. This report describes the conceptual framework of outcomes research and key methodological considerations for the successful implementation of out-of-hospital outcomes research. Illustrations of the specific applications of outcomes research and implications to existing methodologies are given, as well as suggestions for improved interdisciplinary research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75033/1/j.aem.2004.04.014.pd

Risk Adjustment and Outcome Measures for Out-of-hospital Respiratory Distress

: The purpose of the Emergency Medical Services Outcomes Project (EMSOP) is to develop a foundation and framework for out-of-hospital outcomes research. In prior work, this group delineated the priority conditions, described conceptual models, suggested core and risk adjustment measures potentially useful to emergency medical services research, and summarized out-of-hospital pain measurement. In this fifth article in the EMSOP series, the authors recommend specific risk-adjustment measures and outcome measures for use in out-of-hospital research on patients presenting with respiratory distress. The methodology included systematic literature searches and a structured review by an expert panel. The EMSOP group recommends use of pulse oximetry, peak expiratory flow rate, and the visual analog dyspnea scale as potential risk-adjustment measures and outcome measures for out-of-hospital research in patients with respiratory distress. Furthermore, using mortality as an outcome measure is also recommended. Future research is needed to alleviate the paucity of validated tools for out-of-hospital outcomes research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73779/1/j.aem.2004.03.010.pd