2,646 research outputs found

    Coupling of Two Motor Proteins: a New Motor Can Move Faster

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    We study the effect of a coupling between two motor domains in highly-processive motor protein complexes. A simple stochastic discrete model, in which the two parts of the protein molecule interact through some energy potential, is presented. The exact analytical solutions for the dynamic properties of the combined motor species, such as the velocity and dispersion, are derived in terms of the properties of free individual motor domains and the interaction potential. It is shown that the coupling between the motor domains can create a more efficient motor protein that can move faster than individual particles. The results are applied to analyze the motion of helicase RecBCD molecules

    Methodological and economic evaluations of seven survey modes applied to health service research

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    Objective: To evaluate methodological outcomes and cost-effectiveness of seven survey modes, using a study of general public views towards pharmacy public health services. Methods: A cross-sectional survey was conducted in North West England among people aged =?18 years, using two approaches. Three interviewer-assisted modes were street, door-to-door and telephone. Four self-completion modes were single-and double-mailing to residential addresses, surveys sent to public/private business by post (postal-business), and questionnaires dropped-off at venues (drop-off). The study compared response rates, demographics and two domains ((a) actual use of and (b) willingness to use pharmacy public health services) between modes. Incremental cost-effectiveness ratios of different modes were assessed against the single-mailing. Key findings: Response rate varied between 5.1% (postal-business) and 34.5% (street). Respondent age, education, employment, socioeconomic and deprivation status varied between different modes. Results for domain (a) were similar for all modes. Interviewer-assisted modes resulted in more positive views on willingness to use advisory services (P < 0.05). The drop-off mode saved ?45.92 (US$72.55) per 1% increase in response rate compared to single mailing, while interviewer-assisted and double-mailing were more costly. At higher response rates, cost-savings by the drop-off mode diminished, but for other survey modes, additional costs decreased. Conclusion: Drop-off mode is cost-effective compared to the standard single mailing, but selection bias is possible. Street surveys are also an efficient method, but may carry a higher risk of social desirability bias. Mixed-modes surveys may reach wider sectors of the population. The similarity in use of services suggests all survey modes reach members of the public relevant to pharmacy researchers

    Discovery of novel reductive elimination pathway for 10-hydroxywarfarin

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    Coumadin (R/S-warfarin) anticoagulant therapy is highly efficacious in preventing the formation of blood clots; however, significant inter-individual variations in response risks over or under dosing resulting in adverse bleeding events or ineffective therapy, respectively. Levels of pharmacologically active forms of the drug and metabolites depend on a diversity of metabolic pathways. Cytochromes P450 play a major role in oxidizing R- and S-warfarin to 6-, 7-, 8-, 10-, and 4\u27-hydroxywarfarin, and warfarin alcohols form through a minor metabolic pathway involving reduction at the C11 position. We hypothesized that due to structural similarities with warfarin, hydroxywarfarins undergo reduction, possibly impacting their pharmacological activity and elimination. We modeled reduction reactions and carried out experimental steady-state reactions with human liver cytosol for conversion o

    The Changing Epidemiology of Malaria in Ifakara Town, Southern Tanzania.

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    Between 1995 and 2000 there were marked changes in the epidemiology of malaria in Ifakara, southern Tanzania. We documented these changes using parasitological and clinical data from a series of community- and hospital-based studies involving children up to the age of 5 years. There was a right shift and lowering in the age-specific parasite prevalence in the community-based cohort studies. The incidence of clinical malaria in placebo-receiving infants in additional study cohorts dropped from 0.8 in 1995 to 0.43 episodes per infant per year in 2000, an incidence rate ratio of 0.53 (95% confidence interval: 0.404, 0.70, P<0.0001). At the same time, there was an increase in the total number of malaria admissions and a marked right shift in the age pattern of these admissions (median age in 1995 1.55 years vs. 2.33 in 2000, P<0.0001). However, the burden of malaria deaths remained in infants. We discuss how these dramatic changes in the epidemiology of malaria may have arisen from the use of currently available malaria control tools. Caution is required in the interpretation of hospital-based data as it is likely to underestimate the impact of anaemia on mortality in the community, where most paediatric deaths occur. Even in low/moderate malaria transmission settings, where older children suffer most malaria episodes, targeting effective malaria control at infants may produce important reductions in infant mortality caused by malaria

    Fluctuations of an evaporating black hole from back reaction of its Hawking radiation: Questioning a premise in earlier work

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    This paper delineates the first steps in a systematic quantitative study of the spacetime fluctuations induced by quantum fields in an evaporating black hole. We explain how the stochastic gravity formalism can be a useful tool for that purpose within a low-energy effective field theory approach to quantum gravity. As an explicit example we apply it to the study of the spherically-symmetric sector of metric perturbations around an evaporating black hole background geometry. For macroscopic black holes we find that those fluctuations grow and eventually become important when considering sufficiently long periods of time (of the order of the evaporation time), but well before the Planckian regime is reached. In addition, the assumption of a simple correlation between the fluctuations of the energy flux crossing the horizon and far from it, which was made in earlier work on spherically-symmetric induced fluctuations, is carefully analyzed and found to be invalid. Our analysis suggests the existence of an infinite amplitude for the fluctuations of the horizon as a three-dimensional hypersurface. We emphasize the need for understanding and designing operational ways of probing quantum metric fluctuations near the horizon and extracting physically meaningful information.Comment: 10 pages, REVTeX; minor changes, a few references added and a brief discussion of their relevance included. To appear in the proceedings of the 10th Peyresq meeting. Dedicated to Rafael Sorkin on the occasion of his 60th birthda

    Evaluating the impact of DREAMS on HIV incidence among adolescent girls and young women: A population-based cohort study in Kenya and South Africa

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    Background: Through a multisectoral approach, the DREAMS Partnership aimed to reduce HIV incidence among adolescent girls and young women (AGYW) by 40% over 2 years in high-burden districts across sub-Saharan Africa. DREAMS promotes a combination package of evidence-based interventions to reduce individual, family, partner, and community-based drivers of young women’s heightened HIV risk. We evaluated the impact of DREAMS on HIV incidence among AGYW and young men in 2 settings. // Methods and findings: We directly estimated HIV incidence rates among open population-based cohorts participating in demographic and HIV serological surveys from 2006 to 2018 annually in uMkhanyakude (KwaZulu-Natal, South Africa) and over 6 rounds from 2010 to 2019 in Gem (Siaya, Kenya). We compared HIV incidence among AGYW aged 15 to 24 years before DREAMS and up to 3 years after DREAMS implementation began in 2016. We investigated the timing of any change in HIV incidence and whether the rate of any change accelerated during DREAMS implementation. Comparable analyses were also conducted for young men (20 to 29/34 years). In uMkhanyakude, between 5,000 and 6,000 AGYW were eligible for the serological survey each year, an average of 85% were contacted, and consent rates varied from 37% to 67%. During 26,395 person-years (py), HIV incidence was lower during DREAMS implementation (2016 to 2018) than in the previous 5-year period among 15- to 19-year-old females (4.5 new infections per 100 py as compared with 2.8; age-adjusted rate ratio (aRR) = 0.62, 95% confidence interval [CI] 0.48 to 0.82), and lower among 20- to 24-year-olds (7.1/100 py as compared with 5.8; aRR = 0.82, 95% CI 0.65 to 1.04). Declines preceded DREAMS introduction, beginning from 2012 to 2013 among the younger and 2014 for the older women, with no evidence of more rapid decline during DREAMS implementation. In Gem, between 8,515 and 11,428 AGYW were eligible each survey round, an average of 34% were contacted and offered an HIV test, and consent rates ranged from 84% to 99%. During 10,382 py, declines in HIV incidence among 15- to 19-year-olds began before DREAMS and did not change after DREAMS introduction. Among 20- to 24-year-olds in Gem, HIV incidence estimates were lower during DREAMS implementation (0.64/100 py) compared with the pre-DREAMS period (0.94/100 py), with no statistical evidence of a decline (aRR = 0.69, 95% CI 0.53 to 2.18). Among young men, declines in HIV incidence were greater than those observed among AGYW and also began prior to DREAMS investments. Study limitations include low study power in Kenya and the introduction of other interventions such as universal treatment for HIV during the study period. // Conclusions: Substantial declines in HIV incidence among AGYW were observed, but most began before DREAMS introduction and did not accelerate in the first 3 years of DREAMS implementation. Like the declines observed among young men, they are likely driven by earlier and ongoing investments in HIV testing and treatment. Longer-term implementation and evaluation are needed to assess the impact of such a complex HIV prevention intervention and to help accelerate reductions in HIV incidence among young women

    ROSAT observations of X-ray emission from planetary nebulae

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    We have searched the entire ROSAT archive for useful observations to study X-ray emission from Galactic planetary nebulae (PNs). The search yields a sample of 63 PNs, which we call the ROSAT PN sample. About 20-25% of this sample show X-ray emission; these include 13 definite detections and three possible detections (at a 2-sigma level). All X-ray sources in these PNs are concentrated near the central stars. Only A 30, BD+30 3639, and NGC 6543 are marginally resolved by the ROSAT instruments. Three types of X-ray spectra are seen in PNs. Type 1 consists of only soft X-ray emission (<0.5 keV), peaks at 0.1-0.2 keV, and can be fitted by blackbody models at temperatures 1-2 10^5 K. Type 2 consists of harder X-ray emission, peaks at >0.5 keV, and can be fitted by thin plasma emission models at temperatures of a few 10^6 K. Type 3 is a composite of a bright Type 1 component and a fainter Type 2 component. Unresolved soft sources with Type 1 spectra or the soft component of Type 3 spectra are most likely photospheric emission from the hot central stars. Absorption cross sections are large for these soft-energy photons; therefore, only large, tenuous, evolved PNs with hot central stars and small absorption column densities have been detected. The origin of hard X-ray emission from PNs is uncertain. PNs with Type 2 spectra are small, dense, young nebulae with relatively cool (<<10^5 K) central stars, while PNs with Type 3 X-ray spectra are large, tenuous, evolved nebulae with hot central stars. The hard X-ray luminosities are also different between these two types of PNs, indicating perhaps different origins of their hard X-ray emission. Future Chandra and XMM observations with high spatial and spectral resolution will help to understand the origin of hard X-ray emission from PNs.Comment: To be published in The Astrophysical Journal Supplement Series. 21 pages, 7 figures, 5 table
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