EFFECTS OF AN OPIOID AGONIST (U50,488H) AND ANTAGONIST (NALTREXONE) ON THE SEEKING AND INTAKE OF SUCROSE AND ETHANOL IN SELECTED AND NONSELECTED RATS

poster abstractNaltrexone (NTX) is clinically efficacious at attenuating alcohol intake in non-abstinent alcoholics and, to a lesser extent, craving, independent of intake. While generally regarded as a nonselective opioid antagonist, NTX has been shown to have concentration dependent selectivity with lower doses (< 1.0 mg/kg) selective for the mu receptor and doses exceeding 1.0 mg/kg capable of binding to kappa receptors. While the mu system has been implicated in mediating the reinforcing effects of EtOH, the role of the kappa system is less clear. Recent evidence suggests that kappa activation may mediate EtOH aversion. Thus, the present study sought to evaluate the effects of the kappa agonist U50,488H (U50) in a paradigm that procedurally separates the motivation to seek vs. consume a reinforcer to assess whether U50 differentially affects these behaviors in both selected (alcohol-preferring P rats) and nonselected (Long Evans) rats, and whether these effects are specific to EtOH. The effects of a low (mu specific) and high (nonspecific) dose range of NTX were also assessed. Rats were trained to complete a single response requirement that resulted in access to either 2% sucrose or 10% EtOH for a 20-min drinking session. In three separate experiments, rats were injected (using a balanced design) with either saline or 1 of 3 doses of drug: U50 (IP; 2.5, 5.0, or 10.0mg/kg), low NTX (SC; 0.1, 0.3, or 1.0 mg/kg) or high NTX (SC; 1.0, 3.0, or 10.0 mg/kg) on both consummatory and appetitive treatment days. Following either a 15 (U50) or 30 minute (NTX) pretreatment, rats were placed into an operant chamber and intake (consummatory) or lever responses (appetitive) and response latencies were recorded. The results showed that overall, U50 and NTX attenuated intake and responding for sucrose and EtOH. Independent of reinforcer, LE rats were more sensitive to U50’s effects on intake while P rats were more sensitive to the effects on seeking. P rats were more sensitive overall to lower doses of NTX than LE rats and lower doses of NTX were more selective in attenuating EtOH responding vs. sucrose. Higher doses of NTX suppressed intake and responding across both lines and reinforcers. These results demonstrate that craving and intake may be differentially regulated by the kappa and mu opioid receptor systems as a function of “family history” and suggest that different mechanisms of the same (opioid) system may differentially affect craving and intake. Supported by T32-AA00746

Assessing the mechanisms of common Pb incorporation into titanite

Common Pb, the portion of non-radiogenic Pb within a U bearing mineral, needs to be accurately accounted for in order to subtract its effect on U-Pb isotopic ratios so that meaningful ages can be calculated. The propensity to accommodate common Pb during crystallization, or later, is different across the range of U bearing minerals used for geochronology. Titanite frequently accommodates significant amounts of common Pb. However, the most appropriate method to correct for this requires knowledge on the mechanism and timing of common Pb incorporation; information that is commonly difficult to extract. In this study, the spatial and compositional distribution of trace elements (including Pb) in metamorphic titanites from a Greenland amphibolite is investigated on the grain- to nano-scale. Titanites have an isotopically similar signature for both common and radiogenic-Pb in all grains but significantly different quantities of the non-radiogenic component. Microstructural and compositional examination of these grains reveals undeformed, but high common Pb (F207%) titanites have homogeneous element distributions on the atomic scale suggesting common Pb is incorporated into titanite during its growth and not during later processes. In contrast, deformed titanite comprising low-angle boundaries, formed by subgrain rotation recrystallization, comprise networks of dislocations that are enriched in Mg, Al, K and Fe. Smaller cations may migrate due to elastic strain in the vicinity of the dislocation network, yet the larger K cations more likely reflect the mobility of externally-derived K along the orien tation interface. The absence of Pb enrichment along the boundary indicates that either Pb was too large to fit into migrating lattice dislocations or static low-angle boundaries and/or that there was no external Pb available to diffuse along the grain boundary. As the common Pb composition is distinctly different to regional Pb models, the metamorphic titanite grew in a homogeneous Pb reservoir dominated by the break-down of precursor U-bearing phases. The different quantity of common Pb in the titanite grains indicates a mineral-driven element partitioning in an isotopically homogeneous metamorphic reservoir, consistent with low U, low total REE and flat LREE signatures in high F207% analyses. These results have implications for the selection of appropriate common Pb corrections in titanite and other accessory phases

Amplitude measurements of Faraday waves

A light reflection technique is used to measure quantitatively the surface elevation of Faraday waves. The performed measurements cover a wide parameter range of driving frequencies and sample viscosities. In the capillary wave regime the bifurcation diagrams exhibit a frequency independent scaling proportional to the wavelength. We also provide numerical simulations of the full Navier-Stokes equations, which are in quantitative agreement up to supercritical drive amplitudes of 20%. The validity of an existing perturbation analysis is found to be limited to 2.5% overcriticaly.Comment: 7 figure

John Latham’s cosmos and mid-century representation

The conceptual artist John Latham (1921 – 2006) is sometimes cast as disconnected to the currents of British visual culture. Latham’s idiosyncratic cosmology based upon time and events and incorporating human creativity rather than matter and energy is used to distinguish this disconnection. However, this paper argues that his work can be seen as closely related to that of other mid-century cultural producers who were engaged with alternative cosmic speculations, and part of a broader shift in the register of representation. Papers from the Latham digital archive help make this case

Unexpected Behavior of Heavy-Ion Fusion Cross Sections at Extreme Sub-Barrier Energies

The excitation function for fusion evaporation in the system was measured over a range in cross section covering 6 orders of magnitude. The cross section exhibits an abrupt decrease at extreme sub-barrier energies. This behavior, which is also present in a few other systems found in the literature, cannot be reproduced with present models, including those based on a coupled-channels approach. Possible causes are discussed, including a dependence on the intrinsic structure of the participants

The Pitt Bacteremia Score Predicts Mortality in Nonbacteremic Infections

Background. Predicting mortality risk in patients is important in research settings. The Pitt bacteremia score (PBS) is commonly used as a predictor of early mortality risk in patients with bloodstream infections (BSIs). We determined whether the PBS predicts 14-day inpatient mortality in nonbacteremia carbapenem-resistant Enterobacteriaceae (CRE) infections. Methods. Patients were selected from the Consortium on Resistance Against Carbapenems in Klebsiella and Other Enterobacteriaceae, a prospective, multicenter, observational study. We estimated risk ratios to analyze the predictive ability of the PBS overall and each of its components individually. We analyzed each component of the PBS in the prediction of mortality, assessed the appropriate cutoff value for the dichotomized score, and compared the predictive ability of the qPitt score to that of the PBS. Results. In a cohort of 475 patients with CRE infections, a PBS 4 was associated with mortality in patients with nonbacteremia infections (risk ratio [RR], 21.9 95% confidence interval [CI], 7.0, 68.8) and with BSIs (RR, 6.0 95% CI, 2.5, 14.4). In multivariable analysis, the hypotension, mechanical ventilation, mental status, and cardiac arrest parameters of the PBS were independent risk factors for 14-day all-cause inpatient mortality. The temperature parameter as originally calculated for the PBS was not independently associated with mortality. However, a temperature < 36.0° C vs 36° C was independently associated with mortality. A qPitt score 2 had similar discrimination as a PBS 4 in nonbacteremia infections. Conclusions. Here, we validated that the PBS and qPitt score can be used as reliable predictors of mortality in nonbacteremia CRE infections

Significant out-of-sample classification from methylation profile scoring for amyotrophic lateral sclerosis

We conducted DNA methylation association analyses using Illumina 450K data from whole blood for an Australian amyotrophic lateral sclerosis (ALS) case–control cohort (782 cases and 613 controls). Analyses used mixed linear models as implemented in the OSCA software. We found a significantly higher proportion of neutrophils in cases compared to controls which replicated in an independent cohort from the Netherlands (1159 cases and 637 controls). The OSCA MOMENT linear mixed model has been shown in simulations to best account for confounders. When combined in a methylation profile score, the 25 most-associated probes identified by MOMENT significantly classified case–control status in the Netherlands sample (area under the curve, AUC = 0.65, CI95% = [0.62–0.68], p = 8.3 × 10−22). The maximum AUC achieved was 0.69 (CI95% = [0.66–0.71], p = 4.3 × 10−34) when cell-type proportion was included in the predictor

Energy Flow in the Hadronic Final State of Diffractive and Non-Diffractive Deep-Inelastic Scattering at HERA

An investigation of the hadronic final state in diffractive and non--diffractive deep--inelastic electron--proton scattering at HERA is presented, where diffractive data are selected experimentally by demanding a large gap in pseudo --rapidity around the proton remnant direction. The transverse energy flow in the hadronic final state is evaluated using a set of estimators which quantify topological properties. Using available Monte Carlo QCD calculations, it is demonstrated that the final state in diffractive DIS exhibits the features expected if the interaction is interpreted as the scattering of an electron off a current quark with associated effects of perturbative QCD. A model in which deep--inelastic diffraction is taken to be the exchange of a pomeron with partonic structure is found to reproduce the measurements well. Models for deep--inelastic $ep$ scattering, in which a sizeable diffractive contribution is present because of non--perturbative effects in the production of the hadronic final state, reproduce the general tendencies of the data but in all give a worse description.Comment: 22 pages, latex, 6 Figures appended as uuencoded fil

A Search for Selectrons and Squarks at HERA

Data from electron-proton collisions at a center-of-mass energy of 300 GeV are used for a search for selectrons and squarks within the framework of the minimal supersymmetric model. The decays of selectrons and squarks into the lightest supersymmetric particle lead to final states with an electron and hadrons accompanied by large missing energy and transverse momentum. No signal is found and new bounds on the existence of these particles are derived. At 95% confidence level the excluded region extends to 65 GeV for selectron and squark masses, and to 40 GeV for the mass of the lightest supersymmetric particle.Comment: 13 pages, latex, 6 Figure