275 research outputs found

    Corticosterone Regulates Both Naturally Occurring and Cocaine‐Induced Dopamine Signaling by Selectively Decreasing Dopamine Uptake

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    Stressful and aversive events promote maladaptive reward‐seeking behaviors such as drug addiction by acting, in part, on the mesolimbic dopamine system. Using animal models, data from our laboratory and others show that stress and cocaine can interact to produce a synergistic effect on reward circuitry. This effect is also observed when the stress hormone corticosterone is administered directly into the nucleus accumbens (NAc), indicating that glucocorticoids act locally in dopamine terminal regions to enhance cocaine\u27s effects on dopamine signaling. However, prior studies in behaving animals have not provided mechanistic insight. Using fast‐scan cyclic voltammetry, we examined the effect of systemic corticosterone on spontaneous dopamine release events (transients) in the NAc core and shell in behaving rats. A physiologically relevant systemic injection of corticosterone (2 mg/kg i.p.) induced an increase in dopamine transient amplitude and duration (both voltammetric measures sensitive to decreases in dopamine clearance), but had no effect on the frequency of transient release events. This effect was compounded by cocaine (2.5 mg/kg i.p.). However, a second experiment indicated that the same injection of corticosterone had no detectable effect on the dopaminergic encoding of a palatable natural reward (saccharin). Taken together, these results suggest that corticosterone interferes with naturally occurring dopamine uptake locally, and this effect is a critical determinant of dopamine concentration specifically in situations in which the dopamine transporter is pharmacologically blocked by cocaine

    Causal Factors and Adverse Events of Aviation Accidents and Incidents Related to Integrated Vehicle Health Management

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    Causal factors in aviation accidents and incidents related to system/component failure/malfunction (SCFM) were examined for Federal Aviation Regulation Parts 121 and 135 operations to establish future requirements for the NASA Aviation Safety Program s Integrated Vehicle Health Management (IVHM) Project. Data analyzed includes National Transportation Safety Board (NSTB) accident data (1988 to 2003), Federal Aviation Administration (FAA) incident data (1988 to 2003), and Aviation Safety Reporting System (ASRS) incident data (1993 to 2008). Failure modes and effects analyses were examined to identify possible modes of SCFM. A table of potential adverse conditions was developed to help evaluate IVHM research technologies. Tables present details of specific SCFM for the incidents and accidents. Of the 370 NTSB accidents affected by SCFM, 48 percent involved the engine or fuel system, and 31 percent involved landing gear or hydraulic failure and malfunctions. A total of 35 percent of all SCFM accidents were caused by improper maintenance. Of the 7732 FAA database incidents affected by SCFM, 33 percent involved landing gear or hydraulics, and 33 percent involved the engine and fuel system. The most frequent SCFM found in ASRS were turbine engine, pressurization system, hydraulic main system, flight management system/flight management computer, and engine. Because the IVHM Project does not address maintenance issues, and landing gear and hydraulic systems accidents are usually not fatal, the focus of research should be those SCFMs that occur in the engine/fuel and flight control/structures systems as well as power systems

    Commercial Aircraft Integrated Vehicle Health Management Study

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    Statistical data and literature from academia, industry, and other government agencies were reviewed and analyzed to establish requirements for fixture work in detection, diagnosis, prognosis, and mitigation for IVHM related hardware and software. Around 15 to 20 percent of commercial aircraft accidents between 1988 and 2003 involved inalftfnctions or failures of some aircraft system or component. Engine and landing gear failures/malfunctions dominate both accidents and incidents. The IVI vl Project research technologies were found to map to the Joint Planning and Development Office's National Research and Development Plan (RDP) as well as the Safety Working Group's National Aviation Safety Strategic. Plan (NASSP). Future directions in Aviation Technology as related to IVHlvl were identified by reviewing papers from three conferences across a five year time span. A total of twenty-one trend groups in propulsion, aeronautics and aircraft categories were compiled. Current and ftiture directions of IVHM related technologies were gathered and classified according to eight categories: measurement and inspection, sensors, sensor management, detection, component and subsystem monitoring, diagnosis, prognosis, and mitigation

    Corticosterone Potentiation of Cocaine-Induced Reinstatement of Conditioned Place Preference in Mice is Mediated by Blockade of the Organic Cation Transporter 3

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    The mechanisms by which stressful life events increase the risk of relapse in recovering cocaine addicts are not well understood. We previously reported that stress, via elevated corticosterone, potentiates cocaine-primed reinstatement of cocaine seeking following self-administration in rats and that this potentiation appears to involve corticosterone-induced blockade of dopamine clearance via the organic cation transporter 3 (OCT3). In the present study, we use a conditioned place preference/reinstatement paradigm in mice to directly test the hypothesis that corticosterone potentiates cocaine-primed reinstatement by blockade of OCT3. Consistent with our findings following self-administration in rats, pretreatment of male C57/BL6 mice with corticosterone (using a dose that reproduced stress-level plasma concentrations) potentiated cocaine-primed reinstatement of extinguished cocaine-induced conditioned place preference. Corticosterone failed to re-establish extinguished preference alone but produced a leftward shift in the dose–response curve for cocaine-primed reinstatement. A similar potentiating effect was observed upon pretreatment of mice with the non-glucocorticoid OCT3 blocker, normetanephrine. To determine the role of OCT3 blockade in these effects, we examined the abilities of corticosterone and normetanephrine to potentiate cocaine-primed reinstatement in OCT3-deficient and wild-type mice. Conditioned place preference, extinction and reinstatement of extinguished preference in response to low-dose cocaine administration did not differ between genotypes. However, corticosterone and normetanephrine failed to potentiate cocaine-primed reinstatement in OCT3-deficient mice. Together, these data provide the first direct evidence that the interaction of corticosterone with OCT3 mediates corticosterone effects on drug-seeking behavior and establish OCT3 function as an important determinant of susceptibility to cocaine use

    Unique and conserved MicroRNAs in wheat chromosome 5D revealed by next-generation sequencing

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    MicroRNAs are a class of short, non-coding, single-stranded RNAs that act as post-transcriptional regulators in gene expression. miRNA analysis of Triticum aestivum chromosome 5D was performed on 454 GS FLX Titanium sequences of flow sorted chromosome 5D with a total of 3,208,630 good quality reads representing 1.34x and 1.61x coverage of the short (5DS) and long (5DL) arms of the chromosome respectively. In silico and structural analyses revealed a total of 55 miRNAs; 48 and 42 miRNAs were found to be present on 5DL and 5DS respectively, of which 35 were common to both chromosome arms, while 13 miRNAs were specific to 5DL and 7 miRNAs were specific to 5DS. In total, 14 of the predicted miRNAs were identified in wheat for the first time. Representation (the copy number of each miRNA) was also found to be higher in 5DL (1,949) compared to 5DS (1,191). Targets were predicted for each miRNA, while expression analysis gave evidence of expression for 6 out of 55 miRNAs. Occurrences of the same miRNAs were also found in Brachypodium distachyon and Oryza sativa genome sequences to identify syntenic miRNA coding sequences. Based on this analysis, two other miRNAs: miR1133 and miR167 were detected in B. distachyon syntenic region of wheat 5DS. Five of the predicted miRNA coding regions (miR6220, miR5070, miR169, miR5085, miR2118) were experimentally verified to be located to the 5D chromosome and three of them : miR2118, miR169 and miR5085, were shown to be 5D specific. Furthermore miR2118 was shown to be expressed in Chinese Spring adult leaves. miRNA genes identified in this study will expand our understanding of gene regulation in bread wheat

    Comparison of atomic scale dynamics for the middle and late transition metal nanocatalysts

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    Catalysis of chemical reactions by nanosized clusters of transition metals holds the key to the provision of sustainable energy and materials. However, the atomistic behaviour of nanocatalysts still remains largely unknown due to uncertainties associated with the highly labile metal nanoclusters changing their structure during the reaction. In this study, we reveal and explore reactions of nm-sized clusters of 14 technologically important metals in carbon nano test tubes using time-series imaging by atomically-resolved transmission electron microscopy (TEM), employing the electron beam simultaneously as an imaging tool and stimulus of the reactions. Defect formation in nanotubes and growth of new structures promoted by metal nanoclusters enable the ranking of the different metals both in order of their bonding with carbon and their catalytic activity, showing significant variation across the Periodic Table of Elements. Metal nanoclusters exhibit complex dynamics shedding light on atomistic workings of nanocatalysts, with key features mirroring heterogeneous catalysis

    Thermal error modelling for real-time error compensation

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    A modelling strategy for the prediction of both the scalar and the position-dependent thermal error components is presented. Two types of empirical modelling method based on the multiple regression analysis (MRA) and the artificial neural network (ANN) have been proposed for the real-time prediction of thermal errors with multiple temperature measurements. Both approaches have a systematic and computerised algorithm to search automatically for the nonlinear and interaction terms between different temperature variables. The experimental results on a machining centre show that both the MRA and the ANN can accurately predict the time-variant thermal error components under different spindle speeds and temperature fields. The accuracy of a horizontal machining centre can be improved through experiment by a factor of ten and the errors of a cut aluminium workpiece owing to thermal distortion have been reduced from 92.4 µm to 7.2 µm in the lateral direction. The depth difference due to the spindle thermal growth has been reduced from 196 µm to 8 µm.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45884/1/170_2005_Article_BF01239613.pd

    Cardiometabolic risk factors and quality of life in severely obese children and adolescents in the Netherlands

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    BACKGROUND: The prevalence of severe obesity in children and adolescents is increasing. However, little is known about cardiometabolic risk factors and quality of life of children with severe obesity.Therefore, the aim of this study was to assess the demographic characteristics and the prevalence of cardiometabolic risk factors and quality of life in severely obese children and adolescents undergoing intensive inpatient treatment for obesity. METHODS: Data were collected between August 2009 and April 2011 on 16 children (8-13y) and 64 adolescents (13-19y) with severe obesity (SDS-BMI >= 3.0 or SDS-BMI >= 2.3 and comorbidity) participating in an RCT evaluating two intensive inpatient treatment programs for obesity. Demographic, anthropometric, clinical characteristics and two components of the EuroQol for the assessment of quality of life are described. RESULTS: Eighty percent of participants in this study had at least one cardiometabolic risk factor in addition to severe obesity. Low HDL-cholesterol and hypertension were most prevalent (65.0% respectively 31.2%). The highest significant correlations were found between SDS-BMI and SDS-waist circumference, fasting plasma insulin and HOMA-IR (correlation coefficients respectively 0.80, 0.49, and 0.48). With regard to quality of life, the mean utility score of the participants was 0.79 on a scale of 0.0 to 1.0 on the EuroQol questionnaire and their mean individual valuation was 69.1 on a scale of 0 to100. CONCLUSION: Cardiometabolic risk factors are already highly prevalent in this group of severely obese children and adolescents. The score of 69.1 found for quality of life in this study suggests that participants experience important limitations in their quality of life. However, quality of life is not associated with the prevalence of cardiometabolic risk factors. TRIAL REGISTRATION: Netherlands Trial Register (NTR1678, registered 20-Feb-2009)
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