5,168 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

    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

    Impact of nutritional supplements and monosaccharides on growth, oxalate accumulation, and culture pH by Sclerotinia sclerotiorum

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    Sclerotinia sclerotiorum D-E7 was studied to determine the impact of nutritional supplements and monosaccharides on growth, oxalate accumulation, and culture pH in broth media (initial pH c. 5). Cultures with 0.1% nutritional supplement (tryptone, yeast extract, or soytone) yielded minimal growth, 2–3 mM oxalate, and a final culture pH of 4.2–4.8. In contrast, cultures with 0.1% nutritional supplement and 25 mM glucose yielded significant growth, minimal oxalate (\u3c1 mM), and a final culture pH of 2.8–3.7. Similar trends were observed when glucose in 0.1% soytone cultures was replaced with 25 mM d-mannose, l-arabinose, or d-xylose. With 1% soytone-25 mM glucose cultures, growth and oxalate accumulation (∼21 mM) occurred with little change in initial pH. This was not the case with 1% soytone-250 mM glucose cultures; increased glucose levels resulted in a decrease in oxalate accumulation (∼7 mM) and in final culture pH (3.4). Time-course studies with these cultures revealed that oxalate accumulation was suppressed during growth when the culture pH dropped to \u3c4. Overall, these results indicate that (1) the decrease in external pH (i.e. acidification) was independent of oxalate accumulation and (2) acidification coupled to glucose-dependent growth regulated oxalate accumulation by Sclerotinia sclerotiorum

    Wearable sensors can reliably quantify gait alterations associated with disability in people with progressive multiple sclerosis in a clinical setting

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    Gait disability in people with progressive multiple sclerosis (MS) is difficult to quantify using existing clinical tools. This study aims to identify reliable and objective gait-based biomarkers to monitor progressive multiple sclerosis (MS) in clinical settings. During routine clinical visits, 57 people with secondary progressive MS and 24 healthy controls walked for 6 minutes wearing three inertial motion sensors. Fifteen gait measures were computed from the sensor data and tested for between-session reliability, for differences between controls and people with moderate and severe MS disability, and for correlation with Expanded Disability Status Scale (EDSS) scores. The majority of gait measures showed good to excellent between-session reliability when assessed in a subgroup of 23 healthy controls and 25 people with MS. These measures showed that people with MS walked with significantly longer step and stride durations, reduced step and stride regularity, and experienced difficulties in controlling and maintaining a stable walk when compared to controls. These abnormalities significantly increased in people with a higher level of disability and correlated with their EDSS scores. Reliable and objective gait-based biomarkers using wearable sensors have been identified. These biomarkers may allow clinicians to quantify clinically relevant alterations in gait in people with progressive MS within the context of regular clinical visits

    Dispelling the myths of online education: learning via the information superhighway

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    There continues to be a perception that online education is inferior to traditional education. In the U.S. online learning is more developed than in the U.K. This paper provides insights into a U.S. provision and takes a close look at what are perceived as weaknesses of on line learning and argues that these are not necessarily inherent weaknesses of this form of educational delivery. Then, results of two major studies, undertaken in the U.S. are provided comparing the effectiveness of online education to traditional education as perceived by current MBA students and past graduates. Results of these studies suggest that students of MBA modules and MBA graduates perceive the quality and effectiveness of online education to be similar to, if not higher than, the quality and effectiveness of traditional modules and programmes

    The Generalized Jacobi Equation

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    The Jacobi equation in pseudo-Riemannian geometry determines the linearized geodesic flow. The linearization ignores the relative velocity of the geodesics. The generalized Jacobi equation takes the relative velocity into account; that is, when the geodesics are neighboring but their relative velocity is arbitrary the corresponding geodesic deviation equation is the generalized Jacobi equation. The Hamiltonian structure of this nonlinear equation is analyzed in this paper. The tidal accelerations for test particles in the field of a plane gravitational wave and the exterior field of a rotating mass are investigated. In the latter case, the existence of an attractor of uniform relative radial motion with speed 2−1/2c≈0.7c2^{-1/2}c\approx 0.7 c is pointed out. The astrophysical implications of this result for the terminal speed of a relativistic jet is briefly explored.Comment: LaTeX file, 4 PS figures, 28 pages, revised version, accepted for publication in Classical and Quantum Gravit

    Is self monitoring of blood pressure in pregnancy safe and effective?

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    Guidelines encourage the use of self-monitoring of blood pressure in pregnancy, and research suggests that women prefer it. But the blood pressure monitoring in pregnancy group (BUMP) explain that our enthusiasm may run ahead of the evidence. They outline what is known and call for better understanding before self-monitoring is implemented

    Contraceptive practices, preferences and barriers among abortion clients in North Carolina.

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    Objectives: Abortion clinics provide an ideal setting for women to receive contraceptive care because the women served may not have other contacts with the health system and are at risk for unintended pregnancies. The objective of this study was to understand practices, preferences, and barriers to use of contraception for women obtaining abortions at clinics in North Carolina. Methods: We conducted a cross-sectional survey of abortion clients and facilities at 10 abortion clinics in North Carolina. We collected data on contraceptive availability at each clinic. We collected individual responses on women’s experiences obtaining contraception before the current pregnancy and their intentions for future use of contraception. Results: From October 2015 to February 2016, 376 client surveys were completed at 9 clinics, and 10 clinic surveys were completed. Almost one-third of women (29%) reported that they had wanted to use contraception in the last year but were unable. Approximately three-fourths of respondents (76%) stated that they intend to use contraception after this pregnancy. Approximately one-fifth of women stated that would like to use long-acting reversible contraception (LARC) after this abortion. Only the clinics that accepted insurance for abortion and other services provided LARC at the time of the abortion (40%). Conclusions: This study provides a unique, statewide view into the contraceptive barriers for women seeking abortion in North Carolina. Addressing the relatively high demand for LARC after abortion could help significantly reduce unintended pregnancy and recourse to abortion in North Carolina
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