1,621 research outputs found

    The magnetomechanical effect in electrolytic iron

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    The effect of stress on the magnetization of high purity iron has been studied systematically at different locations on the M,H plane corresponding to a variety of magnetic states of the material. The results confirm earlier studies that show the sign of the derivative dM/dσ changes at different locations on the M,H plane, and can even change as a result of a monotonic increase of stress either in compression or tension. The observed behavior can be explained on the basis of a recent theory which predicts that the irreversible changes in magnetization resulting from changes in applied stress cause the magnetization to approach the anhysteretic magnetization curve at the given applied field strength

    Role of Peptide Backbone Conformation on Biological Activity of Chemotactic Peptides

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    To investigate the role of peptide backbone conformation on the biological activity of chemotactic peptides, we synthesized a unique analog of N-formyl-Met-Leu-Phe-OH incorporating the C α,α disubstituted residue, dipropylglycine (Dpg) in place of Leu. The conformation of the stereochemically constrained Dpg analog was examined in the crystalline state by x-ray diffraction and in solution using NMR, IR, and CD methods. The secretagogue activity of the peptide on human neutrophils was determined and compared with that of a stereochemically constrained, folded type II β-turn analog incorporating 1-aminocyclohexanecarboxylic acid (Ac6c) at position 2 (f-Met- Ac6c -Phe-OMe), the parent peptide (f-Met-Leu-Phe-OH) and its methyl ester derivative (f-Met-Leu-Phe-OMe). In the solid state, the Dpg analog adopts an extended β-sheet-like structure with an intramolecular hydrogen bond between the NH and CO groups of the Dpg residue, thereby forming a fully extended (C5) conformation at position 2. The ϕ and ψ values for Met and Phe residues are significantly lower than the values expected for an ideal antiparallel beta conformation causing a twist in the extended backbone both at the N and C termini. Nuclear magnetic resonance studies suggest the presence of a significant population of the peptide molecules in an extended antiparallel β conformation and the involvement of Dpg NH in a C5 intramolecular hydrogen bond in solutions of deuterated chloroform and deuterated dimethyl sulfoxide. IR studies provide evidence for the presence of an intramolecular hydrogen bond in the molecule and the antiparallel extended conformation in chloroform solution. CD spectra in methanol, trifluoroethanol, and trimethyl phosphate indicate that the Dpg peptide shows slight conformational flexibility, whereas the folded Ac6c analog is quite rigid. The extended Dpg peptide consistently shows the highest activity in human peripheral blood neutrophils, being approximately 8 and 16 times more active than the parent peptide and the folded Ac6c analog, respectively. However, the finding that all four peptides have ED50 (the molar concentration of peptide to induce half-maximal enzyme release) values in the 10(-8)-10(-9) M range suggests that an induced fit mechanism may indeed be important in this ligand-receptor interaction. Moreover, it is also possible that alterations in the backbone conformation at the tripeptide level may not significantly alter the side chain topography and/or the accessibility of key functional groups important for interaction with the receptor

    Heart enhancers with deeply conserved regulatory activity are established early in zebrafish development.

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    During the phylotypic period, embryos from different genera show similar gene expression patterns, implying common regulatory mechanisms. Here we set out to identify enhancers involved in the initial events of cardiogenesis, which occurs during the phylotypic period. We isolate early cardiac progenitor cells from zebrafish embryos and characterize 3838 open chromatin regions specific to this cell population. Of these regions, 162 overlap with conserved non-coding elements (CNEs) that also map to open chromatin regions in human. Most of the zebrafish conserved open chromatin elements tested drive gene expression in the developing heart. Despite modest sequence identity, human orthologous open chromatin regions recapitulate the spatial temporal expression patterns of the zebrafish sequence, potentially providing a basis for phylotypic gene expression patterns. Genome-wide, we discover 5598 zebrafish-human conserved open chromatin regions, suggesting that a diverse repertoire of ancient enhancers is established prior to organogenesis and the phylotypic period

    National Survey of Introductory Pharmacy Practice Experience Programs

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    Objective: The objective of this study was to identify commonalities and provide a descriptive overview of key program elements and oversight of U.S. introductory pharmacy practice experience (IPPE) programs. Methods: A Web-based questionnaire, consisting of 40 questions, was sent to 91 schools of pharmacy. The questionnaire addressed the following IPPE program topics, in addition to school demographics: program oversight, experience site selection, program structure, relationship to didactic curriculum, and quality assurance issues. Results: Forty-six schools of pharmacy responded resulting in a response rate of 50.5%. Results identified commonalities in each of the key areas, as well as identifying multiple discrepancies in interpretation of the 2007 Accreditation Council for Pharmacy Education (ACPE) Standards and Guidelines (Standards 2007) for IPPEs. Only 21 of 42 respondents indicated they believed their IPPE program was currently in compliance with Standards 2007. Conclusion: The survey results demonstrate a need for clarification by ACPE stakeholders in several areas addressed within the Standards 2007. No other previous research surveys were found addressing the key issues identified in this survey, revealing the need for additional research on IPPE programs within pharmacy school curricula

    Structure of turbulence and sediment stratification in wave-supported mud layers

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    We present results from laboratory experiments in a wave flume with and without a sediment bed to investigate the turbulent structure and sediment dynamics of wave-supported mud layers. The presence of sediment on the bed significantly alters the structure of the wave boundary layer relative to that observed in the absence of sediment, increasing the TKE by more than a factor of 3 at low wave orbital velocities and suppressing it at the highest velocities. The transition between the low and high-velocity regimes occurs when ReΔ ≃ 450, where ReΔ is the Stokes Reynolds number. In the low-velocity regime (ReΔ 450) the ripples are significantly smaller, the near-bed sediment concentrations are significantly higher and density stratification due to sediment becomes important. In this regime the TKE and Reynolds stress are lower in the sediment bed runs than in comparable runs with no sediment. The regime transition at ReΔ = 450 appears to result from washout of the ripples and increased concentrations of fine sand suspended in the boundary layer, which increases the settling flux and the stratification near the bed. The increased stratification damps turbulence, especially near the top of the high-concentration layer, reducing the layer thickness. We anticipate that these effects will influence the transport capacity of wave-supported gravity currents on the continental shelf

    Oxo-aglaiastatin-mediated inhibition of translation initiation

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    We thank Dr. Elias George (McGill University) for the kind gift of Pgp-1-expressing HeLa cells. RIM was supported by a doctoral fellowship from the Cole Foundation. This research was supported by a grant from the Canadian Institutes of Health Research (FDN-148366) to JP. J.A.P., Jr. is supported by NIH Grant R35 GM118173. Work at the Boston University Center for Molecular Discovery is supported by Grant R24 GM111625. (Cole Foundation; FDN-148366 - Canadian Institutes of Health Research; R35 GM118173 - NIH; R24 GM111625)Published versionSupporting documentatio

    Nine years of comparative effectiveness research education and training: initiative supported by the PhRMA Foundation

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    The term comparative effectiveness research (CER) took center stage with passage of the American Recovery and Reinvestment Act (2009). The companion US$1.1 billion in funding prompted the launch of initiatives to train the scientific workforce capable of conducting and using CER. Passage of the Patient Protection and Affordable Care Act (2010) focused these initiatives on patients, coining the term ‘patient-centered outcomes research’ (PCOR). Educational and training initiatives were soon launched. This report describes the initiative of the Pharmaceutical Research and Manufacturers Association of America (PhRMA) Foundation. Through provision of grant funding to six academic Centers of Excellence, to spearheading and sponsoring three national conferences, the PhRMA Foundation has made significant contributions to creation of the scientific workforce that conducts and uses CER/PCOR

    Risk Assessment and Scaling for the SLS LH2 ET

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    In this report the main physics processes in LH2 tank during prepress and rocket flight are studied. The goal of this investigation is to analyze possible hazards and to make risk assessment in proposed LH2 tank designs for SLS with 5 engines (the situation with 4 engines is less critical). For analysis we use the multinode model (MNM) developed by us and presented in a separate report and also 3D ANSYS simulations. We carry out simulation and theoretical analysis the physics processes such as (i) accumulation of bubbles in LH2 during replenish stage and their collapsing in the liquid during the prepress; (ii) condensation-evaporation at the liquid-vapor interface and tank wall, (iv) heating the liquid near the interface and wall due to condensation and environment heat, (v) injection of hot He during prepress and of hot GH2 during flight, (vi) mixing and cooling of the injected gases due to heat transfer between the gases, liquid and the tank wall. We analyze the effects of these physical processes on the thermo- and fluid gas dynamics in the ullage and on the stratification of temperature in the liquid and assess the associated hazards. A special emphasize is put on the scaling predictions for the larger SLS LH2 tank

    A conceptual framework for understanding the social acceptance of energy infrastructure: insights from energy storage

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    Although social acceptance research has blossomed over the last decade, interdisciplinary studies combining market, socio-political and community aspects are scarce. We propose a novel integration of social science theory in which the belief systems or social representations held by key actors play a crucial role in fostering acceptance of novel technologies, and where a polycentric perspective places particular emphasis on ways that middle actors mediate processes of change between scales. We advance a methodological approach that combines qualitative and quantitative research methods and exemplify the framework by focusing on acceptance of renewable energy storage solutions to accommodate high levels of renewable energy deployment. A research agenda for the social acceptance of energy storage is proposed that sets out key research questions relating international, national and local levels. The outcome of such studies would not only lead to enhanced understanding of processes of social acceptance, but deliver important insights for policy and practice
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