4,094 research outputs found

    Language Variation and Change in Hawai’i English: KIT, DRESS, and TRAP

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    Using an apparent time approach and acoustic phonetic analysis, this study provides the first description of sociolinguistic variation in the realizations of the short-front vowels in Hawaiʻi English. We demonstrate that the realizations of the short-front vowels in Hawaiʻi are conditioned by speaker sex and age, and whether an individual self-identifies as a speaker of Pidgin. We argue that the differences between the vowel realizations of Pidgin and non-Pidgin speakers are likely to be at least partially socially-motivated

    Comparison of rule- and ordinary differential equation-based dynamic model of DARPP-32 signalling network

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    Dynamic modelling has considerably improved our understanding of complex molecular mechanisms. Ordinary differential equations (ODEs) are the most detailed and popular approach to modelling the dynamics of molecular systems. However, their application in signalling networks, characterised by multi-state molecular complexes, can be prohibitive. Contemporary modelling methods, such as rule- based (RB) modelling, have addressed these issues. The advantages of RB modelling over ODEs have been presented and discussed in numerous reviews. In this study, we conduct a direct comparison of the time courses of a molecular system founded on the same reaction network but encoded in the two frameworks. To make such a comparison, a set of reactions that underlie an ODE model was manually encoded in the Kappa language, one of the RB implementations. A comparison of the models was performed at the level of model specification and dynamics, acquired through model simulations. In line with previous reports, we confirm that the Kappa model recapitulates the general dynamics of its ODE counterpart with minor differences. These occur when molecules have multiple sites binding the same interactor. Furthermore, activation of these molecules in the RB model is slower than in the ODE one. As reported for other molecular systems, we find that, also for the DARPP-32 reaction network, the RB representation offers a more expressive and flexible syntax that facilitates access to fine details of the model, easing model reuse. In parallel with these analyses, we report a refactored model of the DARPP-32 interaction network that can serve as a canvas for the development of more complex dynamic models to study this important molecular system

    Space-Based Range Safety and Future Space Range Applications

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    The National Aeronautics and Space Administration (NASA) Space-Based Telemetry and Range Safety (STARS) study is a multiphase project to demonstrate the performance, flexibility and cost savings that can be realized by using space-based assets for the Range Safety [global positioning system (GPS) metric tracking data, flight termination command and range safety data relay] and Range User (telemetry) functions during vehicle launches and landings. Phase 1 included flight testing S-band Range Safety and Range User hardware in 2003 onboard a high-dynamic aircraft platform at Dryden Flight Research Center (Edwards, California, USA) using the NASA Tracking and Data Relay Satellite System (TDRSS) as the communications link. The current effort, Phase 2, includes hardware and packaging upgrades to the S-band Range Safety system and development of a high data rate Ku-band Range User system. The enhanced Phase 2 Range Safety Unit (RSU) provided real-time video for three days during the historic Global Flyer (Scaled Composites, Mojave, California, USA) flight in March, 2005. Additional Phase 2 testing will include a sounding rocket test of the Range Safety system and aircraft flight testing of both systems. Future testing will include a flight test on a launch vehicle platform. This paper discusses both Range Safety and Range User developments and testing with emphasis on the Range Safety system. The operational concept of a future space-based range is also discussed

    Adjustment with aphasia after stroke: study protocol for a pilot feasibility randomised controlled trial for SUpporting wellbeing through PEeR Befriending (SUPERB)

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    Background: Despite the high prevalence of mood problems after stroke, evidence on effective interventions particularly for those with aphasia is limited. There is a pressing need to systematically evaluate interventions aiming to improve wellbeing for people with stroke and aphasia. This study aims to evaluate the feasibility of a peer-befriending intervention. Methods/design: SUPERB is a single blind, parallel group feasibility trial of peer befriending for people with aphasia post-stroke and low levels of psychological distress. The trial includes a nested qualitative study and pilot economic evaluation and it compares usual care (n = 30) with usual care + peer befriending (n = 30). Feasibility outcomes include proportion screened who meet criteria, proportion who consent, rate of consent, number of missing/incomplete data on outcome measures, attrition rate at follow-up, potential value of conducting main trial using value of information analysis (economic evaluation), description of usual care, and treatment fidelity of peer befriending. Assessments and outcome measures (mood, wellbeing, communication, and social participation) for participants and significant others will be administered at baseline, with outcome measures re-administered at 4 and 10 months post-randomisation. Peer befrienders will complete outcome measures before training and after they have completed two cycles of befriending. The qualitative study will use semi-structured interviews of purposively sampled participants (n = 20) and significant others (n = 10) from both arms of the trial, and all peer befrienders to explore the acceptability of procedures and experiences of care. The pilot economic evaluation will utilise the European Quality of life measure (EQ-5D-5 L) and a stroke-adapted version of the Client Service Receipt Inventory (CSRI). Discussion: This study will provide information on feasibility outcomes and an initial indication of whether peer befriending is a suitable intervention to explore further in a definitive phase III randomised controlled trial. Trial registration: ClinicalTrials.gov identifier NCT02947776, registered 28th October 2016

    Antibodies to normal and Alzheimer human brain structures from non-immunised mice of various ages

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    AbstractSupernatants from mouse spleen hybridoma lines established without previous immunisation were screened immunohistochemically against cryostat sections of human temporal cortex and found to stain a variety of brain structures, including Alzheimer plaques and tangles. The age of the mice had no effect on antibody production

    Analysis of Congestion Control

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    Agents must work. Given the trends in elec- tronic models, programmers particularly note the construction of the lookaside buffer, which embodies the theoretical principles of dis- tributed systems. In order to overcome this chal- lenge, we consider how the Turing machine can be applied to the simulation of the UNIVAC computer

    Solution-Phase Synthesis of Heteroatom-Substituted Carbon Scaffolds for Hydrogen Storage

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    This paper reports a bottom-up solution-phase process for the preparation of pristine and heteroatom (boron, phosphorus, or nitrogen)-substituted carbon scaffolds that show good surface areas and enhanced hydrogen adsorption capacities and binding energies. The synthesis method involves heating chlorine-containing small organic molecules with metallic sodium at reflux in high-boiling solvents. For heteroatom incorporation, heteroatomic electrophiles are added to the reaction mixture. Under the reaction conditions, micrometer-sized graphitic sheets assembled by 3−5 nm-sized domains of graphene nanoflakes are formed, and when they are heteroatom-substituted, the heteroatoms are uniformly distributed. The substituted carbon scaffolds enriched with heteroatoms (boron ~7.3%, phosphorus ~8.1%, and nitrogen ~28.1%) had surface areas as high as 900 m^2 g^(−1) and enhanced reversible hydrogen physisorption capacities relative to pristine carbon scaffolds or common carbonaceous materials. In addition, the binding energies of the substituted carbon scaffolds, as measured by adsorption isotherms, were 8.6, 8.3, and 5.6 kJ mol^(−1) for the boron-, phosphorus-, and nitrogen-enriched carbon scaffolds, respectively

    Acute exercise enhances the expansion of cytotoxic T-cells specific to leukemia and melanoma antigens: implications for adoptive transfer immunotherapy?

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    INTRODUCTION: The ex vivo expansion of tumor-associated-antigen (TAA)-specific cytotoxic T-cells from healthy donors for adoptive transfer in cancer patients has been used successfully to prevent relapse after hematopoietic stem cell transplantation (HSCT). However, this therapy is limited by the difficulty in priming and expanding sufficient numbers of functional TAA-specific T-cells, as T-cells recognizing TAA are usually low in frequency and avidity in healthy donors. Furthermore, monocyte-derived dendritic cells (Mo-DC) are used for TAA-presentation, but their manufacture is limited by low blood monocyte numbers. Therefore, large and impractical numbers of blood cells are required to successfully expand TAA-specific T-cells. Acute exercise is well-known to transiently activate and increase the numbers of T-cells and monocytes in peripheral blood. We therefore hypothesized that the immune-enhancing effects of exercise could be harnessed to enhance the ex vivo expansion of TAA-specific T-cells for adoptive transfer immunotherapy. AIMS: To examine the effects of acute exercise on (1) the number and function of TAA-specific T-cells expanded ex vivo, and 2) the generation and function of mo-DC. METHODS: 12 healthy adults (mean ± SD: Age 27±2.6yrs) completed an acute bout of stair-running exercise (time: 104±17sec). Mo-DC generated from pre and post exercise blood samples were pulsed with the melanoma-associated-antigens MAGE-A4 and PRAME, the common tumor-antigen survivin, and the leukemia-associated-antigen WT-1. Autologous DC were used to expand TAA-specific T-cells obtained before and after exercise over 14-days. T-cells were enumerated and phenotyped by flow cytometry and function was assessed by ELISPOT and antigen-specific cytotoxicity. RESULTS: A greater number of mo-DC were generated from post-exercise blood samples (pre: 2.0±1.0 X106cells, post: 5.2±2.6 X106cells). This was due to the 1.7 fold increase in blood monocytes post-exercise, as the number of mo-DC generated per input CD14+cell did not differ (pre: 0.40±0.25, post: 0.59±0.36). Total T-cell expansion was increased post-exercise (fold-increase: pre: 2.48±0.75, post: 2.90±0.74). ELISPOT revealed that the majority of donors had enrichment in TAA-specific T-cells post-exercise, as T-cell lines expanded from post-exercise samples exhibited an increased interferon-gamma response to TAA compared to T-cell lines expanded from pre-exercise samples. Exercise had no effect on T-cell phenotype or antigen-specific cytotoxicity in the expanded cells. CONCLUSION: These data indicate that a single bout of exercise enhances mo-DC generation and the expansion of TAA-specific T-cells ex vivo. Exercise may therefore serve as an adjuvant to enhance the expansion of TAA-specific T-cells in healthy donors and improve the efficacy of adoptive transfer therapy in cancer patients

    Feeding of soy protein isolate to rats during pregnancy and lactation suppresses formation of aberrant crypt foci in their progeny's colons: interaction of diet with fetal alcohol exposure

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    Soy protein isolate (SPI) in the diet may inhibit colon tumorigenesis. We examined azoxymethane (AOM)-induced aberrant crypt foci (ACF) in male rats in relation to lifetime, pre-weaning, or post-weaning dietary exposure to SPI and also within the context of fetal alcohol exposure. Pregnant Sprague Dawley rats were fed AIN-93G diets containing casein (20%, the control diet) or SPI (20%) as the sole protein source starting on gestation day 4 (GD 4). Progeny were weaned on postnatal day (PND) 21 to the same diet as their dams and were fed this diet until termination of the experiment at PND 138. Rats received AOM on PND 89 and 96. Lifetime (GD 4 to PND 138) feeding of SPI led to reduced frequency of ACF with 4 or more crypts in the distal colon. Progeny of dams fed SPI only during pregnancy and lactation or progeny fed SPI only after weaning exhibited similarly reduced frequency of large ACF in distal colon. Number of epithelial cells, in the distal colon, undergoing apoptosis was unaffected by diet. SPI reduced weight gain and adiposity, but these were not correlated with fewer numbers of large ACF. Lifetime SPI exposure similarly inhibited development of large ACF in Sprague Dawley rats whose dams were exposed to ethanol during pregnancy. In summary, feeding of SPI to rat dams during pregnancy and lactation suppresses numbers of large ACF in their progeny, implying a long-term or permanent change elicited by the maternal diet. Moreover, results support the use of ACF as an intermediate endpoint for elucidating effects of SPI and its biochemical constituents in colon cancer prevention in rats
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