5,735 research outputs found

    The Leucoplakic Vulva: Premalignant Determinants

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    Scalable design of tailored soft pulses for coherent control

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    We present a scalable scheme to design optimized soft pulses and pulse sequences for coherent control of interacting quantum many-body systems. The scheme is based on the cluster expansion and the time dependent perturbation theory implemented numerically. This approach offers a dramatic advantage in numerical efficiency, and it is also more convenient than the commonly used Magnus expansion, especially when dealing with higher order terms. We illustrate the scheme by designing 2nd-order pi-pulses and a 6th-order 8-pulse refocusing sequence for a chain of qubits with nearest-neighbor couplings. We also discuss the performance of soft-pulse refocusing sequences in suppressing decoherence due to low-frequency environment.Comment: 4 pages, 2 tables. (modified first table, references added, minor text changes

    Blending of nanoscale and microscale in uniform large-area sculptured thin-film architectures

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    The combination of large thickness (>3>3 μ\mum), large--area uniformity (75 mm diameter), high growth rate (up to 0.4 μ\mum/min) in assemblies of complex--shaped nanowires on lithographically defined patterns has been achieved for the first time. The nanoscale and the microscale have thus been blended together in sculptured thin films with transverse architectures. SiOx_x (x2x\approx 2) nanowires were grown by electron--beam evaporation onto silicon substrates both with and without photoresist lines (1--D arrays) and checkerboard (2--D arrays) patterns. Atomic self--shadowing due to oblique--angle deposition enables the nanowires to grow continuously, to change direction abruptly, and to maintain constant cross--sectional diameter. The selective growth of nanowire assemblies on the top surfaces of both 1--D and 2--D arrays can be understood and predicted using simple geometrical shadowing equations.Comment: 17 pages, 9 figure

    A caspase-3 'death-switch' in colorectal cancer cells for induced and synchronous tumor apoptosis in vitro and in vivo facilitates the development of minimally invasive cell death biomarkers

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    Novel anticancer drugs targeting key apoptosis regulators have been developed and are undergoing clinical trials. Pharmacodynamic biomarkers to define the optimum dose of drug that provokes tumor apoptosis are in demand; acquisition of longitudinal tumor biopsies is a significant challenge and minimally invasive biomarkers are required. Considering this, we have developed and validated a preclinical 'death-switch' model for the discovery of secreted biomarkers of tumour apoptosis using in vitro proteomics and in vivo evaluation of the novel imaging probe [ 18 F]ML-10 for non-invasive detection of apoptosis using positron emission tomography (PET). The 'death-switch' is a constitutively active mutant caspase-3 that is robustly induced by doxycycline to drive synchronous apoptosis in human colorectal cancer cells in vitro or grown as tumor xenografts. Deathswitch induction caused caspase-dependent apoptosis between 3 and 24 hours in vitro and regression of 'death-switched' xenografts occurred within 24 h correlating with the percentage of apoptotic cells in tumor and levels of an established cell death biomarker (cleaved cytokeratin-18) in the blood. We sought to define secreted biomarkers of tumor apoptosis from cultured cells using Discovery Isobaric Tag proteomics, which may provide candidates to validate in blood. Early after caspase-3 activation, levels of normally secreted proteins were decreased (e.g. Gelsolin and Midkine) and proteins including CD44 and High Mobility Group protein B1 (HMGB1) that were released into cell culture media in vitro were also identified in the bloodstream of mice bearing death-switched tumors. We also exemplify the utility of the death-switch model for the validation of apoptotic imaging probes using [ 18 F]ML-10, a PET tracer currently in clinical trials. Results showed increased tracer uptake of [ 18 F]ML-10 in tumours undergoing apoptosis, compared with matched tumour controls imaged in the same animal. Overall, the death-switch model represents a robust and versatile tool for the discovery and validation of apoptosis biomarkers. © 2013 Macmillan Publishers Limited. All rights reserved

    A systematic evidence map of intervention evaluations to reduce gang-related violence

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    Objective: To identify and map evaluations of interventions on gang violence using innovative systematic review methods to inform future research needs. Methods: A previous iteration of this map (Hodgkinson et al., (2009). “Reducing gang-related crime: A systematic review of ‘comprehensive’ interventions.”) was updated in 2021/22 with inclusion of evaluations since the original searches in 2006. Innovative automatic searching and screening was used concurrently with a ‘conventional’ strategy that utilised 58 databases and other online resources. Data were presented in an online interactive evidence gap map. Results: Two hundred and forty-eight evaluations were described, including 114 controlled studies, characterised as comprehensive interventions, encompassing more than one distinct type of intervention. Conclusion: This suggests a substantial body of previously unidentified robust evidence on interventions that could be synthesised to inform policy and practice decision-making. Further research is needed to investigate the extent to which using automated methodologies can improve the efficiency and quality of systematic reviews

    The Mersey Estuary : sediment geochemistry

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    This report describes a study of the geochemistry of the Mersey estuary carried out between April 2000 and December 2002. The study was the first in a new programme of surveys of the geochemistry of major British estuaries aimed at enhancing our knowledge and understanding of the distribution of contaminants in estuarine sediments. The report first summarises the physical setting, historical development, geology, hydrography and bathymetry of the Mersey estuary and its catchment. Details of the sampling and analytical programmes are then given followed by a discussion of the sedimentology and geochemistry. The chemistry of the water column and suspended particulate matter have not been studied, the chief concern being with the geochemistry of the surface and near-surface sediments of the Mersey estuary and an examination of their likely sources and present state of contamination
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