Quantum versus Semiclassical Description of Selftrapping: Anharmonic Effects

Selftrapping has been traditionally studied on the assumption that quasiparticles interact with harmonic phonons and that this interaction is linear in the displacement of the phonon. To complement recent semiclassical studies of anharmonicity and nonlinearity in this context, we present below a fully quantum mechanical analysis of a two-site system, where the oscillator is described by a tunably anharmonic potential, with a square well with infinite walls and the harmonic potential as its extreme limits, and wherein the interaction is nonlinear in the oscillator displacement. We find that even highly anharmonic polarons behave similar to their harmonic counterparts in that selftrapping is preserved for long times in the limit of strong coupling, and that the polaronic tunneling time scale depends exponentially on the polaron binding energy. Further, in agreement, with earlier results related to harmonic polarons, the semiclassical approximation agrees with the full quantum result in the massive oscillator limit of small oscillator frequency and strong quasiparticle-oscillator coupling.Comment: 10 pages, 6 figures, to appear in Phys. Rev.

Spin and Conductance-Peak-Spacing Distributions in Large Quantum Dots: A Density Functional Theory Study

We use spin-density-functional theory to study the spacing between conductance peaks and the ground-state spin of 2D model quantum dots with up to 200 electrons. Distributions for different ranges of electron number are obtained in both symmetric and asymmetric potentials. The even/odd effect is pronounced for small symmetric dots but vanishes for large asymmetric ones, suggesting substantially stronger interaction effects than expected. The fraction of high-spin ground states is remarkably large.Comment: 4 pages, 3 figure

Hepatic Steatosis and Thyroid Function Tests in Overweight and Obese Children

Objectives. Associations between thyroid function and nonalcoholic fatty liver disease (NAFLD) are unknown in childhood. Thus, the aim of the present study was to investigate in 402 consecutive overweight/obese children the association between thyroid function tests and hepatic steatosis as well as metabolic variables. Methods. Hepatic steatosis was diagnosed by ultrasound after exclusion of infectious and metabolic disorders. Fasting serum samples were taken for determination of thyroid function (TSH, FT4, and FT3), along with alanine aminotransferase (ALT), lipid profile, glucose, insulin, and insulin resistance (IR). Results. Eighty-eight children (21.9%) had TSH above the normal range (>4.0 mIU/L). FT3 and FT4 were within the reference intervals in all subjects. Elevated TSH was associated with increased odds of having hepatic steatosis (OR 2.10 (95% CI, 1.22–3.60)), hepatic steatosis with elevated ALT (2.42 (95% CI, 1.29–4.51)), hypertriglyceridemia, elevated total cholesterol, and IR as well as metabolic syndrome (considered as a single clinical entity), after adjustment for age, gender, pubertal status, and body mass index-SD score (or waist circumference). Conclusions. In overweight/obese children, elevated TSH concentration is a significant predictor of hepatic steatosis and lipid and glucose dysmetabolism, independently of the degree of total and visceral obesity

Long-Term Outcome of Repetitive Transcranial Magnetic Stimulation in a Large Cohort of Patients With Cocaine-Use Disorder: An Observational Study

Background: Cocaine is a psychostimulant drug used as performance enhancer throughout history. The prolonged use of cocaine is associated with addiction and a broad range of cognitive deficits. Currently, there are no medications proven to be effective for cocaine-use disorder (CocUD). Previous preliminary clinical work suggests some benefit from repetitive transcranial magnetic stimulation (rTMS) stimulating the prefrontal cortex (PFC), involved in inhibitory cognitive control, decision-making and attention. All published studies to date have been limited by small sample sizes and short follow-up times. Methods: This is a retrospective observational study of 284 outpatients (of whom 268 were men) meeting DSM-5 criteria for CocUD. At treatment entry, most were using cocaine every day or several times per week. All patients underwent 3 months of rTMS and were followed for up to 2 years, 8 months. Self-report, reports by family or significant others and regular urine screens were used to assess drug use. Results: Median time to the first lapse (resumption of cocaine use) since the beginning of treatment was 91 days. For most patients, TMS was re-administered weekly, then monthly, throughout follow-up. The decrease in frequency of rTMS sessions was not accompanied by an increase in lapses to cocaine use. Mean frequency of cocaine use was <1·0 day/month (median 0), while serious rTMS-related adverse events were infrequent, consistent with published reports from smaller studies. Conclusions: This is the first follow-up study to show that rTMS treatment is accompanied by long-lasting reductions in cocaine use in a large cohort

Identification of a Brainstem Circuit Regulating Visual Cortical State in Parallel with Locomotion

SummarySensory processing is dependent upon behavioral state. In mice, locomotion is accompanied by changes in cortical state and enhanced visual responses. Although recent studies have begun to elucidate intrinsic cortical mechanisms underlying this effect, the neural circuits that initially couple locomotion to cortical processing are unknown. The mesencephalic locomotor region (MLR) has been shown to be capable of initiating running and is associated with the ascending reticular activating system. Here, we find that optogenetic stimulation of the MLR in awake, head-fixed mice can induce both locomotion and increases in the gain of cortical responses. MLR stimulation below the threshold for overt movement similarly changed cortical processing, revealing that MLR’s effects on cortex are dissociable from locomotion. Likewise, stimulation of MLR projections to the basal forebrain also enhanced cortical responses, suggesting a pathway linking the MLR to cortex. These studies demonstrate that the MLR regulates cortical state in parallel with locomotion

Mobility recorded by wearable devices and gold standards: the Mobilise-D procedure for data standardization

Wearable devices are used in movement analysis and physical activity research to extract clinically relevant information about an individual’s mobility. Still, heterogeneity in protocols, sensor characteristics, data formats, and gold standards represent a barrier for data sharing, reproducibility, and external validation. In this study, we aim at providing an example of how movement data (from the real-world and the laboratory) recorded from different wearables and gold standard technologies can be organized, integrated, and stored. We leveraged on our experience from a large multi-centric study (Mobilise-D) to provide guidelines that can prove useful to access, understand, and re-use the data that will be made available from the study. These guidelines highlight the encountered challenges and the adopted solutions with the final aim of supporting standardization and integration of data in other studies and, in turn, to increase and facilitate comparison of data recorded in the scientific community. We also provide samples of standardized data, so that both the structure of the data and the procedure can be easily understood and reproduced

Streamlined design of a self-inactivating feline immunodeficiency virus vector for transducing ex vivo dendritic cells and T lymphocytes.

BACKGROUND: Safe and efficient vector systems for delivering antigens or immunomodulatory molecules to dendritic cells (DCs), T lymphocytes or both are considered effective means of eliciting adaptive immune responses and modulating their type, extent, and duration. As a possible tool toward this end, we have developed a self-inactivating vector derived from feline immunodeficiency virus (FIV) showing performance characteristics similar to human immunodeficiency virus-derived vectors but devoid of the safety concerns these vectors have raised. METHODS: The pseudotyped FIV particles were generated with a three-plasmid system consisting of: the packaging construct, providing Gag, Pol and the accessory proteins; the vector(s), basically containing FIV packaging signal (psi), Rev responsive element, R-U5 region at both ends, and the green fluorescent protein as reporter gene; and the Env plasmid, encoding the G protein of vesicular stomatitis virus (VSV-G) or the chimeric RD114 protein. Both packaging and vector constructs were derived from p34TF10, a replication competent molecular clone of FIV. The pseudotyped particles were produced by transient transfection in the Crandell feline fibroblast kidney (CrFK) or the human epithelial (293T) cell line. RESULTS: To broaden its species tropism, the final vector construct was achieved through a series of intermediate constructs bearing a longer psi, the FIV central polypurin tract sequence (cPPT), or the woodchuck hepatitis post-regulatory element (WPRE). These constructs were compared for efficiency and duration of transduction in CrFK or 293T cells and in the murine fibroblast cell line NIH-3T3. Whereas psi elongation and cPPT addition did not bring any obvious benefit, insertion of WPRE downstream GFP greatly improved vector performances. To maximize the efficiency of transduction for ex-vivo murine DCs and T-lymphocytes, this construct was tested with VSV-G or RD114 and using different transduction protocols. The results indicated that the FIV construct derived herein stably transduced both cell types, provided that appropriate vector makeup and transduction protocol were used. Further, transduced DCs underwent changes suggestive of an induced maturation. CONCLUSION: In contrast to previously described FIV vectors that were poorly efficient in delivering genetic material to DCs and T lymphocytes, the vector developed herein has potential for use in experimental immunization strategies

Active crustal extension and strain accumulation from GPS data in the Molise region (central-southern Apennines, Italy)

In this paper, we report new GPS measurements which indicate active NE-SW extension and strain accumulation in the Molise region (Apennines, Italy). The GPS observations were collected during campaigns on benchmarks of the dense IGM95 network (average distance 20 km), spanning a maximum observation interval of 13 years, and have been integrated with measurements from the available permanent GPS sites. Considering the differential motion of the GPS sites, located on the Tyrrhenian and Adriatic coasts, we can evaluate a 4-5 mm/yr extension accommodated across this part of the Apennines. The velocity field exhibits clusters of sites with homogeneous velocity vectors, outlining two main divergence areas, both characterized by the largest velocity gradients: one near Venafro and the other near Isernia where two primary active faults and several historical earthquakes have been documented. These results suggest that an active extension in this part of the Apennines can be currently distributed between the two faults systems associated with the largest earthquakes of this region

Loss of D2 Dopamine Receptor Function Modulates Cocaine-Induced Glutamatergic Synaptic Potentiation in the Ventral Tegmental Area

Potentiation of glutamate responses is a critical synaptic response to cocaine exposure in ventral tegmental area (VTA) neurons. However, the mechanism by which cocaine exposure promotes potentiation of NMDA receptors (NMDARs) and subsequently AMPA receptors (AMPARs) is not fully understood. In this study we demonstrate that repeated cocaine treatment causes loss of D2 dopamine receptor functional responses via interaction with lysosome-targeting G-protein-associated sorting protein1 (GASP1). We also show that the absence of D2 downregulation in GASP1-KO mice prevents cocaine-induced potentiation of NMDAR currents, elevation of the AMPA/NMDA ratio, and redistribution of NMDAR and AMPAR subunits to the membrane. As a pharmacological parallel, coadministration of the high-affinity D2 agonist, aripiprazole, reduces not only functional downregulation of D2s in response to cocaine but also potentiation of NMDAR and AMPAR responses in wild-type mice. Together these data suggest that functional loss of D2 receptors is a critical mechanism mediating cocaine-induced glutamate plasticity in VTA neurons

Development of Feline Immunodeficiency Virus ORF-A (tat) Mutants: In Vitro and in Vivo Characterization

AbstractA functional ORF-A is essential for efficient feline immunodeficiency virus replication in lymphocytes. We have characterized a series of mutants of the Petaluma strain, derived from p34TF10 and having different combinations of stop codons and increasingly long deletions in ORF-A. Six clones proved fully replicative in fibroblastoid Crandell feline kidney cells and monocyte-derived macrophage cultures but failed to replicate in T cell lines and primary lymphoblasts. Cats inoculated with three selected mutants had considerably milder infections than controls given intact ORF-A virus. In vivo, the mutants maintained growth properties similar to those in vitro for at least 7 months, except that replication in lymphoid cells was strongly reduced but not ablated. One mutant underwent extensive ORF-A changes without, however, reverting to wild-type. Antiviral immune responses were feeble in all cats, suggesting that viral loads were too low to represent a sufficiently powerful antigenic stimulus