5,340 research outputs found

    How often does the Unruh-DeWitt detector click beyond four dimensions?

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    We analyse the response of an arbitrarily-accelerated Unruh-DeWitt detector coupled to a massless scalar field in Minkowski spacetimes of dimensions up to six, working within first-order perturbation theory and assuming a smooth switch-on and switch-off. We express the total transition probability as a manifestly finite and regulator-free integral formula. In the sharp switching limit, the transition probability diverges in dimensions greater than three but the transition rate remains finite up to dimension five. In dimension six, the transition rate remains finite in the sharp switching limit for trajectories of constant scalar proper acceleration, including all stationary trajectories, but it diverges for generic trajectories. The divergence of the transition rate in six dimensions suggests that global embedding spacetime (GEMS) methods for investigating detector response in curved spacetime may have limited validity for generic trajectories when the embedding spacetime has dimension higher than five.Comment: 30 pages. v3: presentational improvement. Published versio

    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

    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

    The Leucoplakic Vulva: Premalignant Determinants

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    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).¬†‚ÄúReducing gang-related crime: A systematic review of ‚Äėcomprehensive‚Äô interventions.‚ÄĚ) 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 ‚Äėconventional‚Äô 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

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

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    The combination of large thickness (>3>3 őľ\mum), large--area uniformity (75 mm diameter), high growth rate (up to 0.4 őľ\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 (x‚Čą2x\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

    Recent developments in research into the Cyathostominae and Anoplocephala perfoliata

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    Intestinal helminths are an important cause of equine disease. Of these parasites, the Cyathostominae are the commonest group that infect horses. These nematodes consist of a complex tribe of 51 species, although individual horses tend to harbour 10 or so common species, in addition to a few rarer species. The Cyathostominae can be extremely pathogenic, and high levels of infection result in clinical symptoms ranging from chronic weight loss to colic, diarrhoea and death. As part of their life cycle, immature cyathostomins penetrate the large intestinal wall, where they can enter a state of inhibited larval development. These larvae can exist in this state for months to years, after which they subsequently re-emerge. If larvae re-emerge in large numbers (i.e. several million), severe pathological consequences ensue. The inhibited larvae are also relatively refractory to several of the currently available anthelmintics, so that horses treated previously with anthelmintics can still carry life-threatening burdens of these parasitic stages. Little is known about the cyathostomin larvae during their mucosal phase, and current research efforts are focused on investigating the biology of these stages. Much of the research described here highlights this area of research and details studies aimed at investigating the host immune responses that the mucosal larvae invoke. As part of this research effort, molecular tools have been developed to facilitate the identification of larval and egg stages of cyathostomins. These molecular tools are now proving very useful in the investigation of the relative contributions that individual, common cyathostomin species make to the pathology and epidemiology of mixed helminth infections. At the more applied level, research is also in progress to develop an immunodiagnostic test that will allow numbers of mucosal larvae to be estimated. This test utilises antigen-specific IgG(T) serum antibody responses as markers of infection. As anthelmintic resistance will be the major constraint on the future control of the Cyathostominae, researchers are now actively investigating this area and studies aimed at elucidating the molecular mechanisms of drug resistance are described. Another parasite which has assumed a clinically important role in horses is the tapeworm, Anoplocephala perfoliata. This parasite is prevalent world-wide and has been shown to be a significant cause of equine colic. Because previous methods of estimating the infection intensity of tapeworm were inaccurate, recent research has been directed at developing an immunodiagnostic ELISA for these cestodes. Specific IgG(T) responses to antigens secreted by adult tapeworms have been shown to provide a reasonable indication of infection intensity. An ELISA based on these responses is now commercially available. The steps involved in the development of this ELISA are described here. In addition to these recent advances in research, this review also outlines the principle areas for future research into these important equine parasites
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