138 research outputs found

    Tracked Vehicle Physics-based Energy Modelling and Series Hybrid System Optimisation for the Bradley Fighting Vehicle

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    A hybrid electric tracked ground vehicle (HETGV) can reduce military fuel usage, however a review of current tools determined they are not suitable to estimate HEGTV performance. Based on topographic data and vehicle attributes, this research developed an estimation tool by creating a model to determine tracked vehicle energy and fuel requirements, and using these requirements, created a HEGTV cost and performance optimisation for the Bradley fighting vehicle energy system. The optimised design reduced fuel consumption by 15%, and met the vehicle\u27s peak power requirement of 365 kW, with a recommended configuration of a 135 kW generator and 100 kWh battery, and an estimated drivetrain and fuel cost of $155,000. This analysis concludes by articulating the operational and tactical impacts of increased fuel efficiency

    Prospecting environmental mycobacteria: combined molecular approaches reveal unprecedented diversity

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    Background: Environmental mycobacteria (EM) include species commonly found in various terrestrial and aquatic environments, encompassing animal and human pathogens in addition to saprophytes. Approximately 150 EM species can be separated into fast and slow growers based on sequence and copy number differences of their 16S rRNA genes. Cultivation methods are not appropriate for diversity studies; few studies have investigated EM diversity in soil despite their importance as potential reservoirs of pathogens and their hypothesized role in masking or blocking M. bovis BCG vaccine. Methods: We report here the development, optimization and validation of molecular assays targeting the 16S rRNA gene to assess diversity and prevalence of fast and slow growing EM in representative soils from semi tropical and temperate areas. New primer sets were designed also to target uniquely slow growing mycobacteria and used with PCR-DGGE, tag-encoded Titanium amplicon pyrosequencing and quantitative PCR. Results: PCR-DGGE and pyrosequencing provided a consensus of EM diversity; for example, a high abundance of pyrosequencing reads and DGGE bands corresponded to M. moriokaense, M. colombiense and M. riyadhense. As expected pyrosequencing provided more comprehensive information; additional prevalent species included M. chlorophenolicum, M. neglectum, M. gordonae, M. aemonae. Prevalence of the total Mycobacterium genus in the soil samples ranged from 2.3×107 to 2.7×108 gene targets g−1; slow growers prevalence from 2.9×105 to 1.2×107 cells g−1. Conclusions: This combined molecular approach enabled an unprecedented qualitative and quantitative assessment of EM across soil samples. Good concordance was found between methods and the bioinformatics analysis was validated by random resampling. Sequences from most pathogenic groups associated with slow growth were identified in extenso in all soils tested with a specific assay, allowing to unmask them from the Mycobacterium whole genus, in which, as minority members, they would have remained undetected

    Estrogen and progesterone induce persistent increases in p53-dependent apoptosis and suppress mammary tumors in BALB/c-Trp53+/- mice

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    Introduction Treatment with estrogen and progesterone (E+P) mimics the protective effect of parity on mammary tumors in rodents and depends upon the activity of p53. The following experiments tested whether exogenous E+P primes p53 to be more responsive to DNA damage and whether these pathways confer resistance to mammary tumors in a mouse model of Li-Fraumeni syndrome. Methods Mice that differ in p53 status (Trp53+/+, Trp53+/-, Trp53-/-) were treated with E+P for 14 days and then were tested for p53-dependent responses to ionizing radiation. Responses were also examined in parous and age-matched virgins. The effects of hormonal exposures on tumor incidence were examined in BALB/c-Trp53+/- mammary tissues. Results Nuclear accumulation of p53 and apoptotic responses were increased similarly in the mammary epithelium from E+P-treated and parous mice compared with placebo and age-matched virgins. This effect was sustained for at least 7 weeks after E+P treatment and did not depend on the continued presence of ovarian hormones. Hormone stimulation also enhanced apoptotic responses to ionizing radiation in BALB/c-Trp53+/- mice but these responses were intermediate compared with Trp53+/+ and Trp-/- tissues, indicating haploinsufficiency. The appearance of spontaneous mammary tumors was delayed by parity in BALB/c-Trp53+/- mice. The majority of tumors lacked estrogen receptor (ER), but ER+ tumors were observed in both nulliparous and parous mice. However, apoptotic responses to ionizing radiation and tumor incidence did not differ among outgrowths of epithelial transplants from E+P-treated donors and nulliparous donors

    Connecting Land–Atmosphere Interactions to Surface Heterogeneity in CHEESEHEAD19

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    The Chequamegon Heterogeneous Ecosystem Energy-Balance Study Enabled by a High-Density Extensive Array of Detectors 2019 (CHEESEHEAD19) is an ongoing National Science Foundation project based on an intensive field campaign that occurred from June to October 2019. The purpose of the study is to examine how the atmospheric boundary layer (ABL) responds to spatial heterogeneity in surface energy fluxes. One of the main objectives is to test whether lack of energy balance closure measured by eddy covariance (EC) towers is related to mesoscale atmospheric processes. Finally, the project evaluates data-driven methods for scaling surface energy fluxes, with the aim to improve model–data comparison and integration. To address these questions, an extensive suite of ground, tower, profiling, and airborne instrumentation was deployed over a 10 km × 10 km domain of a heterogeneous forest ecosystem in the Chequamegon–Nicolet National Forest in northern Wisconsin, United States, centered on an existing 447-m tower that anchors an AmeriFlux/NOAA supersite (US-PFa/WLEF). The project deployed one of the world’s highest-density networks of above-canopy EC measurements of surface energy fluxes. This tower EC network was coupled with spatial measurements of EC fluxes from aircraft; maps of leaf and canopy properties derived from airborne spectroscopy, ground-based measurements of plant productivity, phenology, and physiology; and atmospheric profiles of wind, water vapor, and temperature using radar, sodar, lidar, microwave radiometers, infrared interferometers, and radiosondes. These observations are being used with large-eddy simulation and scaling experiments to better understand submesoscale processes and improve formulations of subgrid-scale processes in numerical weather and climate models

    Common Gene Therapy Viral Vectors Do Not Efficiently Penetrate Sputum from Cystic Fibrosis Patients

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    Norwalk virus and human papilloma virus, two viruses that infect humans at mucosal surfaces, have been found capable of rapidly penetrating human mucus secretions. Viral vectors for gene therapy of Cystic Fibrosis (CF) must similarly penetrate purulent lung airway mucus (sputum) to deliver DNA to airway epithelial cells. However, surprisingly little is known about the rates at which gene delivery vehicles penetrate sputum, including viral vectors used in clinical trials for CF gene therapy. We find that sputum spontaneously expectorated by CF patients efficiently traps two viral vectors commonly used in CF gene therapy trials, adenovirus (d∼80 nm) and adeno-associated virus (AAV serotype 5; d∼20 nm), leading to average effective diffusivities that are ∼3,000-fold and 12,000-fold slower than their theoretical speeds in water, respectively. Both viral vectors are slowed by adhesion, as engineered muco-inert nanoparticles with diameters as large as 200 nm penetrate the same sputum samples at rates only ∼40-fold reduced compared to in pure water. A limited fraction of AAV exhibit sufficiently fast mobility to penetrate physiologically thick sputum layers, likely because of the lower viscous drag and smaller surface area for adhesion to sputum constituents. Nevertheless, poor penetration of CF sputum is likely a major contributor to the ineffectiveness of viral vector based gene therapy in the lungs of CF patients observed to date

    A proposed systems approach to the evaluation of integrated palliative care

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    <p>Abstract</p> <p>Background</p> <p>There is increasing global interest in regional palliative care networks (PCN) to integrate care, creating systems that are more cost-effective and responsive in multi-agency settings. Networks are particularly relevant where different professional skill sets are required to serve the broad spectrum of end-of-life needs. We propose a comprehensive framework for evaluating PCNs, focusing on the nature and extent of inter-professional collaboration, community readiness, and client-centred care.</p> <p>Methods</p> <p>In the absence of an overarching structure for examining PCNs, a framework was developed based on previous models of health system evaluation, explicit theory, and the research literature relevant to PCN functioning. This research evidence was used to substantiate the choice of model factors.</p> <p>Results</p> <p>The proposed framework takes a systems approach with system structure, process of care, and patient outcomes levels of consideration. Each factor represented makes an independent contribution to the description and assessment of the network.</p> <p>Conclusions</p> <p>Realizing palliative patients' needs for complex packages of treatment and social support, in a seamless, cost-effective manner, are major drivers of the impetus for network-integrated care. The framework proposed is a first step to guide evaluation to inform the development of appropriate strategies to further promote collaboration within the PCN and, ultimately, optimal palliative care that meets patients' needs and expectations.</p

    Applying Definitions of “Asbestos” to Environmental and “Low-Dose” Exposure Levels and Health Effects, Particularly Malignant Mesothelioma

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    Although asbestos research has been ongoing for decades, this increased knowledge has not led to consensus in many areas of the field. Two such areas of controversy include the specific definitions of asbestos, and limitations in understanding exposure-response relationships for various asbestos types and exposure levels and disease. This document reviews the current regulatory and mineralogical definitions and how variability in these definitions has led to difficulties in the discussion and comparison of both experimental laboratory and human epidemiological studies for asbestos. This review also examines the issues of exposure measurement in both animal and human studies, and discusses the impact of these issues on determination of cause for asbestos-related diseases. Limitations include the lack of detailed characterization and limited quantification of the fibers in most studies. Associated data gaps and research needs are also enumerated in this review

    A community-based geological reconstruction of Antarctic Ice Sheet deglaciation since the Last Glacial Maximum

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    A robust understanding of Antarctic Ice Sheet deglacial history since the Last Glacial Maximum is important in order to constrain ice sheet and glacial-isostatic adjustment models, and to explore the forcing mechanisms responsible for ice sheet retreat. Such understanding can be derived from a broad range of geological and glaciological datasets and recent decades have seen an upsurge in such data gathering around the continent and Sub-Antarctic islands. Here, we report a new synthesis of those datasets, based on an accompanying series of reviews of the geological data, organised by sector. We present a series of timeslice maps for 20ka, 15ka, 10ka and 5ka, including grounding line position and ice sheet thickness changes, along with a clear assessment of levels of confidence. The reconstruction shows that the Antarctic Ice sheet did not everywhere reach the continental shelf edge at its maximum, that initial retreat was asynchronous, and that the spatial pattern of deglaciation was highly variable, particularly on the inner shelf. The deglacial reconstruction is consistent with a moderate overall excess ice volume and with a relatively small Antarctic contribution to meltwater pulse 1a. We discuss key areas of uncertainty both around the continent and by time interval, and we highlight potential priorit. © 2014 The Authors

    A Glial Variant of the Vesicular Monoamine Transporter Is Required To Store Histamine in the Drosophila Visual System

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    Unlike other monoamine neurotransmitters, the mechanism by which the brain's histamine content is regulated remains unclear. In mammals, vesicular monoamine transporters (VMATs) are expressed exclusively in neurons and mediate the storage of histamine and other monoamines. We have studied the visual system of Drosophila melanogaster in which histamine is the primary neurotransmitter released from photoreceptor cells. We report here that a novel mRNA splice variant of Drosophila VMAT (DVMAT-B) is expressed not in neurons but rather in a small subset of glia in the lamina of the fly's optic lobe. Histamine contents are reduced by mutation of dVMAT, but can be partially restored by specifically expressing DVMAT-B in glia. Our results suggest a novel role for a monoamine transporter in glia that may be relevant to histamine homeostasis in other systems
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