mGluR5 antagonism inhibits cocaine reinforcement and relapse by elevation of extracellular glutamate in the nucleus accumbens via a CB1 receptor mechanism.

Metabotropic glutamate receptor 5 (mGluR5) antagonism inhibits cocaine self-administration and reinstatement of drug-seeking behavior. However, the cellular and molecular mechanisms underlying this action are poorly understood. Here we report a presynaptic glutamate/cannabinoid mechanism that may underlie this action. Systemic or intra-nucleus accumbens (NAc) administration of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) dose-dependently reduced cocaine (and sucrose) self-administration and cocaine-induced reinstatement of drug-seeking behavior. The reduction in cocaine-taking and cocaine-seeking was associated with a reduction in cocaine-enhanced extracellular glutamate, but not cocaine-enhanced extracellular dopamine (DA) in the NAc. MPEP alone, when administered systemically or locally into the NAc, elevated extracellular glutamate, but not DA. Similarly, the cannabinoid CB1 receptor antagonist, rimonabant, elevated NAc glutamate, not DA. mGluR5s were found mainly in striatal medium-spiny neurons, not in astrocytes, and MPEP-enhanced extracellular glutamate was blocked by a NAc CB1 receptor antagonist or N-type Ca++ channel blocker, suggesting that a retrograde endocannabinoid-signaling mechanism underlies MPEP-induced glutamate release. This interpretation was further supported by our findings that genetic deletion of CB1 receptors in CB1-knockout mice blocked both MPEP-enhanced extracellular glutamate and MPEP-induced reductions in cocaine self-administration. Together, these results indicate that the therapeutic anti-cocaine effects of mGluR5 antagonists are mediated by elevation of extracellular glutamate in the NAc via an endocannabinoid-CB1 receptor disinhibition mechanism

Trace the Accretion Geometry of H 1743--322 with Type C Quasi-periodic Oscillations in Multiple Outbursts

We present a systematic analysis of type C quasi-periodic oscillation (QPO) observations of H 1743--322 throughout the Rossi X-ray Timing Explorer (RXTE) era. We find that, while different outbursts have significant flux differences, they show consistent positive correlations between the QPO fractional root-mean-square (rms) amplitude and non-thermal fraction of the emission, which indicate an independence of the intrinsic QPO rms on individual outburst brightness in H 1743--322. However, the dependence of the QPO rms on frequency is different between the outburst rise and decay phases, where QPO fractional rms of the decay phase is significantly lower than that of the rise phase at low frequencies. The spectral analysis also reveals different ranges of coronal temperature between the two outburst stages. A semi-quantitative analysis shows that the Lense-Thirring precession model could be responsible for the QPO rms differences, requiring a variable coronal geometric shape. However, the variable-Comptonization model could also account for the findings. The fact that the rms differences and the hysteresis traces in the hardness-intensity diagram (HID) accompany each other indicates a connection between the two phenomena. By correlating the findings with QPO phase lags and the quasi-simultaneous radio flux previously published, we propose there could be corona-jet transitions in H 1743--322 similar to those that have been recently reported in GRS 1915+105.Comment: 21 pages, 12 figure

Elaboration and characterization of Fe1–xO thin films sputter deposited from magnetite target

Majority of the authors report elaboration of iron oxide thin films by reactive magnetron sputtering from an iron target with Ar–O2 gas mixture. Instead of using the reactive sputtering of a metallic target we report here the preparation of Fe1–xOthin films, directly sputtered froma magnetite target in a pure argon gas flow with a bias power applied. This oxide is generally obtained at very low partial oxygen pressure and high temperature.We showed that bias sputtering which can be controlled very easily can lead to reducing conditions during deposition of oxide thin film on simple glass substrates. The proportion of wustite was directly adjusted bymodifying the power of the substrate polarization. Atomic force microscopy was used to observe these nanostructured layers. Mössbauer measurements and electrical properties versus bias polarization and annealing temperature are also reported

IDBA-tran: a more robust de novo de Bruijn graph assembler for transcriptomes with uneven expression levels

published_or_final_versio

Efficacy of multidomain interventions to improve physical frailty, depression and cognition: data from cluster- randomized controlled trials

BackgroundFrailty is the pre- eminent exigency of aging. Although frailty- related impairments are preventable, and multidomain interventions appear more effective than unimodal ones, the optimal components remain uncertain.MethodsWe devised multidomain interventions against physical and cognitive decline among prefrail/frail community- dwelling - ¥65- year- olds and evaluated these in complementary cluster- randomized trials of efficacy and participant empowerment. The Efficacy Study compared ~3- monthly telephone consultations vs. 16, 2 h sessions/year comprising communally partaken physical and cognitive training plus nutrition and disease education; the Empowerment Study compared the standard Efficacy Study multidomain intervention (Sessions 1- 10) vs. an enhanced version redesigned to empower and motivate individual participants. Changes from baseline in physical, functional, and cognitive performance were measured after 6 and 12 months in the Efficacy Study and after 6 months in the Empowerment Study, with post- intervention follow- up at 9 months. Primary outcomes are as follows: Cardiovascular Health Study frailty score; gait speed; handgrip strength; and Montreal Cognitive Assessment (MoCA). Secondary outcomes are as follows: instrumental activities of daily living; metabolic equivalent of task (MET); depressed mood (Geriatric Depression Scale- 5 - ¥2); and malnutrition (Mini- Nutritional Assessment short- form - ¤11). Intervention effects were analyzed using a generalized linear mixed model.ResultsEfficacy Study participants (n = 1082, 40 clusters) were 75.1 ± 6.3 years old, 68.7% women, and 64.7% prefrail/frail; analytic clusters: 19 intervention (410/549 completed) vs. 21 control (375/533 completed). Empowerment Study participants (n = 440, 14 clusters) were 75.9 ± 7.1 years old, 83.6% women, and 56.7% prefrail/frail; analytic clusters: seven intervention (209/230 completed) vs. seven control (189/210 completed). The standard and enhanced multidomain interventions both reduced frailty and significantly improved aspects of physical, functional, and cognitive performance, especially among - ¥75- year- olds. Standard multidomain intervention decreased depression [odds ratio 0.56, 95% confidence interval (CI) 0.32, 0.99] and malnutrition (odds ratio 0.45, 95% CI 0.26, 0.78) by 12 months and improved concentration at Months 6 (0.23, 95% CI 0.04, 0.42) and 12 (0.46, 95% CI 0.22, 0.70). Participant empowerment augmented activity (4.67 MET/h, 95% CI 1.64, 7.69) and gait speed (0.06 m/s, 95% CI 0.00, 0.11) at 6 months, with sustained improvements in delayed recall (0.63, 95% CI 0.20, 1.06) and MoCA performance (1.29, 95% CI 0.54, 2.03), and less prevalent malnutrition (odds ratio 0.39, 95% CI 0.18, 0.84), 3 months after the intervention ceased.ConclusionsPragmatic multidomain intervention can diminish physical frailty, malnutrition, and depression and enhance cognitive performance among community- dwelling elders, especially - ¥75- year- olds; this might supplement healthy aging policies, probably more effectively if participants are empowered.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/1/jcsm12534.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/2/10.1002_jcsm.12534_Fig_S4.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/3/jcsm12534_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/4/10.1002_jcsm.12534_Fig_S2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/5/10.1002_jcsm.12534_Table_S3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/6/10.1002_jcsm.12534_Fig_S3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/7/10.1002_jcsm.12534_Appendix_S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/8/10.1002_jcsm.12534_Table_S2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/9/10.1002_jcsm.12534_Table_S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/10/10.1002_jcsm.12534_Fig_S1.pd

Gravitational-wave Detection With Matter-wave Interferometers Based On Standing Light Waves

We study the possibility of detecting gravitational-waves with matter-wave interferometers, where atom beams are split, deflected and recombined totally by standing light waves. Our calculation shows that the phase shift is dominated by terms proportional to the time derivative of the gravitational wave amplitude. Taking into account future improvements on current technologies, it is promising to build a matter-wave interferometer detector with desired sensitivity.Comment: 7 pages, 3 figures. To be published in General Relativity and Gravitatio

Obliquity pacing of the western Pacific Intertropical Convergence Zone over the past 282,000 years

The Intertropical Convergence Zone (ITCZ) encompasses the heaviest rain belt on the Earth. Few direct long-term records, especially in the Pacific, limit our understanding of long-term natural variability for predicting future ITCZ migration. Here we present a tropical precipitation record from the Southern Hemisphere covering the past 282,000 years, inferred from a marine sedimentary sequence collected off the eastern coast of Papua New Guinea. Unlike the precession paradigm expressed in its East Asian counterpart, our record shows that the western Pacific ITCZ migration was influenced by combined precession and obliquity changes. The obliquity forcing could be primarily delivered by a cross-hemispherical thermal/pressure contrast, resulting from the asymmetric continental configuration between Asia and Australia in a coupled East Asian-Australian circulation system. Our finding suggests that the obliquity forcing may play a more important role in global hydroclimate cycles than previously thought

Analysis of Oscillations and Defect Measures for the Quasineutral Limit in Plasma Physics

We perform a rigorous analysis of the quasineutral limit for a hydrodynamical model of a viscous plasma represented by the Navier Stokes Poisson system in $3-D$. We show that as $\lambda\to 0$ the velocity field $u^{\lambda}$ strongly converges towards an incompressible velocity vector field $u$ and the density fluctuation $\rho^{\lambda}-1$ weakly converges to zero. In general the limit velocity field cannot be expected to satisfy the incompressible Navier Stokes equation, indeed the presence of high frequency oscillations strongly affects the quadratic nonlinearities and we have to take care of self interacting wave packets. We shall provide a detailed mathematical description of the convergence process by using microlocal defect measures and by developing an explicit correctors analysis. Moreover we will be able to identify an explicit pseudo parabolic pde satisfied by the leading correctors terms. Our results include all the previous results in literature, in particular we show that the formal limit holds rigorously in the case of well prepared data.Comment: Submitted pape

Absence of Morphotropic Phase Boundary Effects in BiFeO3-PbTiO3 Thin Films Grown via a Chemical Multilayer Deposition Method

Here, we report the unusual behaviour shown by the (BiFeO3)1-x-(PbTiO3)x (BF-xPT) films prepared using a multilayer deposition approach by chemical solution deposition method. Thin film samples of various compositions were prepared by depositing several bilayers of BF and PT precursors by varying the BF or PT layer thicknesses. X-ray diffraction showed that final samples of all compositions show mixing of the two compounds resulting in a single phase mixture, also confirmed by transmission electron microscopy. In contrast to bulk equilibrium compositions, our samples show a monoclinic (MA type) structure suggesting disappearance of morphotropic phase boundary (MPB) about x = 0.30 as observed in the bulk. This is accompanied by the lack of any enhancement of remnant polarization at MPB as shown by the ferroelectric measurements. Magnetic measurements show that the magnetization of the samples increases with increasing BF content. Significant magnetization of the samples indicates melting of spin spirals in the BF-xPT arising from random distribution of iron atoms across the film. Absence of Fe2+ ions in the films was corroborated by X-ray photoelectron spectroscopy measurements. The results illustrate that used thin film processing methodology significantly changes the structural evolution in contrast to predictions from the equilibrium phase diagram as well as modify the functional characteristics of BP-xPT system dramatically.Comment: 15 pages, 6 figure

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13