4,768 research outputs found

    High-throughput in-situ characterization and modelling of precipitation kinetics in compositionally graded alloys

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    The development of new engineering alloy chemistries is a time consuming and iterative process. A necessary step is characterization of the nano/microstructure to provide a link between the processing and properties of each alloy chemistry considered. One approach to accelerate the identification of optimal chemistries is to use samples containing a gradient in composition, ie. combinatorial samples, and to investigate many different chemistries at the same time. However, for engineering alloys, the final properties depend not only on chemistry but also on the path of microstructure development which necessitates characterization of microstructure evolution for each chemistry. In this contribution we demonstrate an approach that allows for the in-situ, nanoscale characterization of the precipitate structures in alloys, as a function of aging time, in combinatorial samples containing a composition gradient. The approach uses small angle x-ray scattering (SAXS) at a synchrotron beamline. The Cu-Co system is used for the proof-of-concept and the combinatorial samples prepared contain a gradient in Co from 0% to 2%. These samples are aged at temperatures between 450{\textdegree}C and 550{\textdegree}C and the precipitate structures (precipitate size, volume fraction and number density) all along the composition gradient are simultaneously monitored as a function of time. This large dataset is used to test the applicability and robustness of a conventional class model for precipitation that considers concurrent nucleation, growth and coarsening and the ability of the model to describe such a large dataset.Comment: Published in Acta Materiali

    Long term time-lapse microgravity and geotechnical monitoring of relict salt-mines, Marston, Cheshire, UK.

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    The area around the town of Northwich in Cheshire, U. K., has a long history of catastrophic ground subsidence caused by a combination of natural dissolution and collapsing abandoned mine workings within the underlying Triassic halite bedrock geology. In the village of Marston, the Trent and Mersey Canal crosses several abandoned salt mine workings and previously subsiding areas, the canal being breached by a catastrophic subsidence event in 1953. This canal section is the focus of a long-term monitoring study by conventional geotechnical topographic and microgravity surveys. Results of 20 years of topographic time-lapse surveys indicate specific areas of local subsidence that could not be predicted by available site and mine abandonment plan and shaft data. Subsidence has subsequently necessitated four phases of temporary canal bank remediation. Ten years of microgravity time-lapse data have recorded major deepening negative anomalies in specific sections that correlate with topographic data. Gravity 2D modeling using available site data found upwardly propagating voids, and associated collapse material produced a good match with observed microgravity data. Intrusive investigations have confirmed a void at the major anomaly. The advantages of undertaking such long-term studies for near-surface geophysicists, geotechnical engineers, and researchers working in other application areas are discussed

    Finite element approximation of a phase field model for void electromigration

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    We consider a fully practical finite element approximation of the nonlinear degenerate parabolic syste

    Spherical solid-propellant rocket motor Patent

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    Spherical solid propellant rocket engine desig

    The cooperative functions of the EBNA3 Proteins are central to EBV persistence and latency

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    The Epstein–Barr nuclear antigen 3 (EBNA3) family of proteins, comprising EBNA3A, EBNA3B, and EBNA3C, play pivotal roles in the asymptomatic persistence and life-long latency of Epstein–Barr virus (EBV) in the worldwide human population. EBNA3-mediated transcriptional reprogramming of numerous host cell genes promotes in vitro B cell transformation and EBV persistence in vivo. Despite structural and sequence similarities, and evidence of substantial cooperative activity between the EBNA3 proteins, they perform quite different, often opposing functions. Both EBNA3A and EBNA3C are involved in the repression of important tumour suppressive pathways and are considered oncogenic. In contrast, EBNA3B exhibits tumour suppressive functions. This review focuses on how the EBNA3 proteins achieve the delicate balance required to support EBV persistence and latency, with emphasis on the contribution of the Allday laboratory to the field of EBNA3 biology

    Epstein-Barr virus nuclear protein EBNA3C directly induces expression of AID and somatic mutations in B cells

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    Activation-induced cytidine deaminase (AID), the enzyme responsible for induction of sequence variation in immunoglobulins (Igs) during the process of somatic hypermutation (SHM) and also Ig class switching, can have a potent mutator phenotype in the development of lymphoma. Using various Epstein-Barr virus (EBV) recombinants, we provide definitive evidence that the viral nuclear protein EBNA3C is essential in EBV-infected primary B cells for the induction of AID mRNA and protein. Using lymphoblastoid cell lines (LCLs) established with EBV recombinants conditional for EBNA3C function, this was confirmed, and it was shown that transactivation of the AID gene (AICDA) is associated with EBNA3C binding to highly conserved regulatory elements located proximal to and upstream of the AICDA transcription start site. EBNA3C binding initiated epigenetic changes to chromatin at specific sites across the AICDA locus. Deep sequencing of cDNA corresponding to the IgH V-D-J region from the conditional LCL was used to formally show that SHM is activated by functional EBNA3C and induction of AID. These data, showing the direct targeting and induction of functional AID by EBNA3C, suggest a novel role for EBV in the etiology of B cell cancers, including endemic Burkitt lymphoma

    UK export performance research - review and implications

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    Previous research on export performance has been criticized for being a mosaic of autonomous endeavours and for a lack of theoretical development. Building upon extant models of export performance, and a review and analysis of research on export performance in the UK for the period 1990-2005, an integrated model of export performance is developed and theoretical explanations of export performance are put forward. It is suggested that a multi-theory approach to explaining export performance is viable. Management and policy implications for the UK emerging from the review and synthesis of the literature and the integrated model are discussed

    Prescription Drugs and the Duty to Warn: An Argument for Patient Package Inserts

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    It has been more than ten years since the Food and Drug Administration proposed regulations which would have required detailed patient information for all prescription drugs. The proposed regulations, intended to promote the safe and effective use of prescription drugs, would have required a manufacturer to supply non-technical, non-promotional information, referred to as patient package inserts, directly to the patient. This note will analyze the need for patient information in satisfying the tort objectives of informed consent and public safety. The note will then analyze the practical effect of the learned intermediary and informed consent doctrines upon the manufacturer\u27s and physician\u27s duty to supply patient information. The note will then analyze the FDA regulations leading to the proposed patient package insert (PPI) program, the program itself, the rationale for the program and the reasons for its revocation. Finally, the note will present rationale for re-enacting the FDA regulations
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