2,633 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

    Corticosterone Acts in the Nucleus Accumbens to Enhance Dopamine Signaling and Potentiate Reinstatement of Cocaine Seeking

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    Stressful life events are important contributors to relapse in recovering cocaine addicts, but the mechanisms by which they influence motivational systems are poorly understood. Studies suggest that stress may “set the stage” for relapse by increasing the sensitivity of brain reward circuits to drug-associated stimuli. We examined the effects of stress and corticosterone on behavioral and neurochemical responses of rats to a cocaine prime after cocaine self-administration and extinction. Exposure of rats to acute electric footshock stress did not by itself reinstate drug-seeking behavior but potentiated reinstatement in response to a subthreshold dose of cocaine. This effect of stress was not observed in adrenalectomized animals, and was reproduced in nonstressed animals by administration of corticosterone at a dose that reproduced stress-induced plasma levels. Pretreatment with the glucocorticoid receptor antagonist RU38486 did not block the corticosterone effect. Corticosterone potentiated cocaine-induced increases in extracellular dopamine in the nucleus accumbens (NAc), and pharmacological blockade of NAc dopamine receptors blocked corticosterone-induced potentiation of reinstatement. Intra-accumbens administration of corticosterone reproduced the behavioral effects of stress and systemic corticosterone. Corticosterone treatment acutely decreased NAc dopamine clearance measured by fast-scan cyclic voltammetry, suggesting that inhibition of uptake2-mediated dopamine clearance may underlie corticosterone effects. Consistent with this hypothesis, intra-accumbens administration of the uptake2 inhibitor normetanephrine potentiated cocaine-induced reinstatement. Expression of organic cation transporter 3, a corticosterone-sensitive uptake2 transporter, was detected on NAc neurons. These findings reveal a novel mechanism by which stress hormones can rapidly regulate dopamine signaling and contribute to the impact of stress on drug intake

    RSA/Legacy Wind Sensor Comparison

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    This report describes a comparison of data from ultrasonic and cup-and-vane anemometers on 5 wind towers at Vandenberg AFB. The ultrasonic sensors are scheduled to replace the Legacy cup-and-vane sensors under the Range Standardization and Automation (RSA) program. Because previous studies have noted differences between peak wind speeds reported by mechanical and ultrasonic wind sensors, the latter having no moving parts, the 30th and 45th Weather Squadrons wanted to understand possible differences between the two sensor types. The period-of-record was 13-30 May 2005. A total of 153,961 readings of I-minute average and peak wind speed/direction from each sensor type were used. Statistics of differences in speed and direction were used to identify 18 out of 34 RSA sensors having the most consistent performance, with respect to the Legacy sensors. Data from these 18 were used to form a composite comparison. A small positive bias in the composite RSA average wind speed increased from +0.5 kts at 15 kts, to +1 kt at 25 kts. A slightly larger positive bias in the RSA peak wind speed increased from +1 kt at 15 kts, to +2 kts at 30 kts

    Aquifer Depletion and the Cost of Water Conservation: The Southern High Plains of Texas Case

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    Irrigated agriculture has played a vital role in the development and growth of the Great Plains Region of the United States. The primary source of water for irrigation in this region is the Ogallala Aquifer. The Southern portion of the Ogallala Aquifer is considered exhaustible due to the low level of recharge relative to the quantities of water pumped. Analysis and evaluation of water conservation policies which could extend the economic life of the Ogallala Aquifer in the Southern High Plains of Texas and Eastern New Mexico, and which could contribute to maintaining the viability of the regional economy is important. This study evaluates the impacts of water conservation policies which limit drawdown of the Ogallala Aquifer. County level dynamic optimization models maximizing net present value of net returns to land, management, groundwater, and irrigation systems over a sixty year planning horizon were formulated to evaluate three aquifer drawdown restrictions. The results of this study indicate that because of the differences in hydrologic characteristics and current irrigation levels across counties in the study area, blanket water conservation policies for the region as a whole are likely to be inefficient. This study concludes that for this region, water conservation policies that focus on counties that would deplete the aquifer to less than 30 ft. of saturated thickness possess the lowest implicit cost of conserving saturated thickness.water conservation, water policy evaluation, aquifer management, dynamic optimization, Resource /Energy Economics and Policy,

    Policy Alternatives for the Southern Ogallala Aquifer

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    Due to declining water levels in the Ogallala Aquifer, policy alternatives for extending the life of the aquifer for irrigation and other purposes are evaluated. The study concludes that blanket water conservation policies for the region are likely to be inefficient because of economic and hydrologic differences in the region.Resource /Energy Economics and Policy,

    Countering Trusting Trust through Diverse Double-Compiling

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    An Air Force evaluation of Multics, and Ken Thompson's famous Turing award lecture "Reflections on Trusting Trust," showed that compilers can be subverted to insert malicious Trojan horses into critical software, including themselves. If this attack goes undetected, even complete analysis of a system's source code will not find the malicious code that is running, and methods for detecting this particular attack are not widely known. This paper describes a practical technique, termed diverse double-compiling (DDC), that detects this attack and some compiler defects as well. Simply recompile the source code twice: once with a second (trusted) compiler, and again using the result of the first compilation. If the result is bit-for-bit identical with the untrusted binary, then the source code accurately represents the binary. This technique has been mentioned informally, but its issues and ramifications have not been identified or discussed in a peer-reviewed work, nor has a public demonstration been made. This paper describes the technique, justifies it, describes how to overcome practical challenges, and demonstrates it.Comment: 13 pages

    Perceptions of Preparedness Among New Graduate Nurses: Traditional Curriculum Versus Concept-Based Curriculum

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    Concept-based curriculum (CBC) is a newer trend in nursing education curriculum aimed at preparing new graduates to enter the workforce as generalist nurses better suited to care for a more medically complex population. Using CBC, students are introduced to concepts in order to build conceptual understandings as they engage in knowledge and skill learning, as opposed to a traditional nursing curriculum that is taught in sections grouped by patient population and medical complexity. At a nursing school housed within a private university in the southeast, the traditional nursing curriculum was replaced with CBC in 2016. To better understand the preparedness of new graduate nurses, students graduating from both traditional curriculum and CBC curricular designs were asked about their perception of preparedness in five specific areas during their first three months of clinical practice. The results of the explanatory mixed-methods survey, which consisted of Likert scale responses and qualitative data, showed no statistically significant difference in perception of preparedness between the two groups. The outcomes of each individual curricula were not dramatically different, but the actionable data reinforces the importance of clinical learning

    Visualizing Spacetime Curvature via Frame-Drag Vortexes and Tidal Tendexes I. General Theory and Weak-Gravity Applications

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    When one splits spacetime into space plus time, the Weyl curvature tensor (vacuum Riemann tensor) gets split into two spatial, symmetric, and trace-free (STF) tensors: (i) the Weyl tensor's so-called "electric" part or tidal field, and (ii) the Weyl tensor's so-called "magnetic" part or frame-drag field. Being STF, the tidal field and frame-drag field each have three orthogonal eigenvector fields which can be depicted by their integral curves. We call the integral curves of the tidal field's eigenvectors tendex lines, we call each tendex line's eigenvalue its tendicity, and we give the name tendex to a collection of tendex lines with large tendicity. The analogous quantities for the frame-drag field are vortex lines, their vorticities, and vortexes. We build up physical intuition into these concepts by applying them to a variety of weak-gravity phenomena: a spinning, gravitating point particle, two such particles side by side, a plane gravitational wave, a point particle with a dynamical current-quadrupole moment or dynamical mass-quadrupole moment, and a slow-motion binary system made of nonspinning point particles. [Abstract is abbreviated; full abstract also mentions additional results.]Comment: 25 pages, 20 figures, matches the published versio

    Wave Function of a Brane-like Universe

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    Within the mini-superspace model, brane-like cosmology means performing the variation with respect to the embedding (Minkowski) time τ\tau before fixing the cosmic (Einstein) time tt. The departure from Einstein limit is parameterized by the 'energy' conjugate to τ\tau, and characterized by a classically disconnected Embryonic epoch. In contrast with canonical quantum gravity, the wave-function of the brane-like Universe is (i) τ\tau-dependent, and (ii) vanishes at the Big Bang. Hartle-Hawking and Linde proposals dictate discrete 'energy' levels, whereas Vilenkin proposal resembles α\alpha-particle disintegration.Comment: Revtex, 4 twocolumn pages, 3 eps figures (accepted for publication in Class. Quan. Grav.

    GenBank

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    GenBank (R) is a comprehensive database that contains publicly available nucleotide sequences for more than 240 000 named organisms, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the web-based BankIt or standalone Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the EMBL Data Library in Europe and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through NCBI's retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, begin at the NCBI Homepage ()
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