143 research outputs found

    A Role for IRAK-M IN PGE2-Induced Immunosuppression Post-Bone Marrow Transplant

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    Assessment of an All-Particle Hybrid Method for Hypersonic Rarefied Flow

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106450/1/AIAA2013-1203.pd

    Pharmacogenomic testing in paediatrics: clinical implementation strategies

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    Pharmacogenomics (PGx) relates to the study of genetic factors determining variability in drug response. Implementing PGx testing in paediatric patients can enhance drug safety, helping to improve drug efficacy or reduce the risk of toxicity. Despite its clinical relevance, the implementation of PGx testing in paediatric practice to date has been variable and limited. As with most paediatric pharmacological studies, there are well-recognised barriers to obtaining high-quality PGx evidence, particularly when patient numbers may be small, and off-label or unlicensed prescribing remains widespread. Furthermore, trials enrolling small numbers of children can rarely, in isolation, provide sufficient PGx evidence to change clinical practice, so extrapolation from larger PGx studies in adult patients, where scientifically sound, is essential. This review paper discusses the relevance of PGx to paediatrics and considers implementation strategies from a child health perspective. Examples are provided from Canada, the Netherlands and the UK, with consideration of the different healthcare systems and their distinct approaches to implementation, followed by future recommendations based on these cumulative experiences. Improving the evidence base demonstrating the clinical utility and cost-effectiveness of paediatric PGx testing will be critical to drive implementation forwards. International, interdisciplinary collaborations will enhance paediatric data collation, interpretation and evidence curation, while also supporting dedicated paediatric PGx educational initiatives. PGx consortia and paediatric clinical research networks will continue to play a central role in the streamlined development of effective PGx implementation strategies to help optimise paediatric pharmacotherapy.Personalised Therapeutic

    Electronic structure of the quasi-one-dimensional organic conductor TTF-TCNQ

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    We study the electronic structure of the quasi-one-dimensional organic conductor TTF-TCNQ by means of density-functional band theory, Hubbard model calculations, and angle-resolved photoelectron spectroscopy (ARPES). The experimental spectra reveal significant quantitative and qualitative discrepancies to band theory. We demonstrate that the dispersive behavior as well as the temperature-dependence of the spectra can be consistently explained by the finite-energy physics of the one-dimensional Hubbard model at metallic doping. The model description can even be made quantitative, if one accounts for an enhanced hopping integral at the surface, most likely caused by a relaxation of the topmost molecular layer. Within this interpretation the ARPES data provide spectroscopic evidence for the existence of spin-charge separation on an energy scale of the conduction band width. The failure of the one-dimensional Hubbard model for the {\it low-energy} spectral behavior is attributed to interchain coupling and the additional effect of electron-phonon interaction.Comment: 18 pages, 9 figure

    Scenario analysis report with policy recommendations: An assessment of sustainability, resilience, efficiency and fairness and effective chain relationships in VALUMICS case studies : Deliverable 8.4

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    This is an open access article distributed under the Creative Commons Attribution License, to view a copy of the license, see: https://creativecommons.org/licenses/by/4.0/. The final version of this report is available at https://doi.org/10.5281/zenodo.6534011The functioning of food value chains entails a complex organisation from farm to fork which is characterised by various governance forms and externalities which have shaped the overall food system. VALUMICS food value chain case studies: wheat to bread, dairy cows to milk, beef cattle to steak, farmed salmon to fillets and tomato to processed tomato were selected to enable explorative and empirical analysis to better understand the functioning of the food system and, to identify the main challenges that need to be addressed to improve sustainability, integrity, resilience, and fairness of European food chains. The VALUMICS system analysis was executed through four operational phases starting with Groundwork & analysis including mapping specific attributes and impacts of food value chains and their externalities. This was followed by Case study baseline analysis, which provided input to the third phase on Modelling and exploration of future scenarios and finally Policy and synthesis of the overall work. This report is an overall synthesis of the VALUMICS results as follows: • Key findings from the VALUMICS project on the functioning of European food value chains and their impacts on more sustainable, resilient, fairer, and transparent food system are summarised through a compilation of 25 Research Findings and Policy Briefs. • By highlighting the major contributions from the research activities throughout the four phases of the VALUMICS project, this report delivers an assessment of various factors influencing sustainability, resilience, efficiency and fairness and effective chain relationships of different food value chains, and their determinants. • The synthesis of the outcome allows the identification of opportunities and challenges characterising the functioning of food supply chains, and thus, the prospects and potentials for strengthening the EU food sector

    Statistical Theory of Spin Relaxation and Diffusion in Solids

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    A comprehensive theoretical description is given for the spin relaxation and diffusion in solids. The formulation is made in a general statistical-mechanical way. The method of the nonequilibrium statistical operator (NSO) developed by D. N. Zubarev is employed to analyze a relaxation dynamics of a spin subsystem. Perturbation of this subsystem in solids may produce a nonequilibrium state which is then relaxed to an equilibrium state due to the interaction between the particles or with a thermal bath (lattice). The generalized kinetic equations were derived previously for a system weakly coupled to a thermal bath to elucidate the nature of transport and relaxation processes. In this paper, these results are used to describe the relaxation and diffusion of nuclear spins in solids. The aim is to formulate a successive and coherent microscopic description of the nuclear magnetic relaxation and diffusion in solids. The nuclear spin-lattice relaxation is considered and the Gorter relation is derived. As an example, a theory of spin diffusion of the nuclear magnetic moment in dilute alloys (like Cu-Mn) is developed. It is shown that due to the dipolar interaction between host nuclear spins and impurity spins, a nonuniform distribution in the host nuclear spin system will occur and consequently the macroscopic relaxation time will be strongly determined by the spin diffusion. The explicit expressions for the relaxation time in certain physically relevant cases are given.Comment: 41 pages, 119 Refs. Corrected typos, added reference

    Observation of hard scattering in photoproduction events with a large rapidity gap at HERA

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    Events with a large rapidity gap and total transverse energy greater than 5 GeV have been observed in quasi-real photoproduction at HERA with the ZEUS detector. The distribution of these events as a function of the Îłp\gamma p centre of mass energy is consistent with diffractive scattering. For total transverse energies above 12 GeV, the hadronic final states show predominantly a two-jet structure with each jet having a transverse energy greater than 4 GeV. For the two-jet events, little energy flow is found outside the jets. This observation is consistent with the hard scattering of a quasi-real photon with a colourless object in the proton.Comment: 19 pages, latex, 4 figures appended as uuencoded fil

    Comprehensive lung injury pathology induced by mTOR inhibitors

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    Molecular Targets in Oncology[Abstract] Interstitial lung disease is a rare side effect of temsirolimus treatment in renal cancer patients. Pulmonary fibrosis is characterised by the accumulation of extracellular matrix collagen, fibroblast proliferation and migration, and loss of alveolar gas exchange units. Previous studies of pulmonary fibrosis have mainly focused on the fibro-proliferative process in the lungs. However, the molecular mechanism by which sirolimus promotes lung fibrosis remains elusive. Here, we propose an overall cascade hypothesis of interstitial lung diseases that represents a common, partly underlying synergism among them as well as the lung pathogenesis side effects of mammalian target of rapamycin inhibitors
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