Effects of cocaethylene on dopamine and serotonin synthesis in Long–Evans and Sprague–Dawley brains

We examined the behavioral and neurochemical effects of cocaethylene treatment in Long–Evans (�LE). and Sprague–Dawley� (SD) rats. Cocaethylene-induced behaviors were significantly less in LE rats. Cocaethylene caused an inhibition of dopamine synthesis in the caudate nucleus and nucleus accumbens that was equivalent in both rat lines. Serotonin synthesis was also suppressed by cocaethylene treatment, however this phenomenon was less pronounced when compared with the effects on dopamine synthesis

Health, safety and environmental issues in thin film manufacturing

An investigation is made of Health, Safety and Environmental (HSE) aspects for the manufacturing, use and decommissioning of CdTe, CIS and a-Si modules. Issues regarding energy requirements, resource availability, emissions of toxic materials, occupational health and safety and module waste treatment are reviewed. Waste streams in thin film module manufacturing are analyzed in detail and treatment methods are discussed. Finally the technological options for thin film module recycling are investigated. It is concluded that there are no serious HSE bottlenecks for upscaling to production levels of 500 MWp/yr and that adequate methods are available for treatment of the manufacturing wastes. However, on the longer term issues regarding CdTe and CIS module waste treatment, In and Te resource availability and module recycling need to adressed. Appropriate recycling methods for CdTe and CIS modules do not exist at present but the problem is being adressed by the PV industry

Pharmacological characterization of novel synthetic opioids (NSO) found in the recreational drug marketplace

Novel synthetic opioids (NSO) are increasingly encountered in illicit heroin and counterfeit pain pills. Many NSO are resurrected from older biomedical literature or patent applications, so limited information is available about their biological effects. Here we examined the pharmacology of three structurally-distinct NSO found in the recreational drug market: N-(1-(2-phenylethyl)-4-piperidinyl)-N-phenylbutyramide (butyrylfentanyl), 3,4-dichloro-N-[(1R,2R)-2-(dimethylamino)cyclohexyl]-N-methylbenzamide (U-47700) and 1-cyclohexyl-4-(1,2-diphenylethyl)piperazine (MT-45). Radioligand binding and GTPγS functional assays were carried out in cells transfected with murine mu- (MOR-1), delta- (DOR-1) or kappa-opioid receptors (KOR-1). Antinociceptive effects were determined using the radiant heat tail flick technique in mice, and opioid specificity was assessed with the mu-opioid antagonist naloxone. Butyrylfentanyl, U-47700 and MT-45 displayed nM affinities at MOR-1, but were less potent than morphine, and had much weaker effects at DOR-1 and KOR-1. All NSO exhibited agonist actions at MOR-1 in the GTPγS assay. Butyrylfentanyl and U-47700 were 31- and 12-fold more potent than morphine in the tail flick assay, whereas MT-45 was equipotent with morphine. Analgesic effects were reversed by naloxone and absent in genetically-engineered mice lacking MOR-1. Our findings confirm that butyrylfentanyl, U-47700 and MT-45 are selective MOR-1 agonists with in vitro affinities less than morphine. However, analgesic potencies vary more than 30-fold across the compounds, and in vitro binding affinity does not predict in vivo potency. Taken together, our findings highlight the risks to humans who may unknowingly be exposed to these and other NSO when taking adulterated heroin or counterfeit pain medications. This article is part of the Special Issue entitled ‘Designer Drugs and Legal Highs.’ © 201

Fentanyl-related designer drugs W-18 and W-15 lack appreciable opioid activity in vitro and in vivo

W-18 (4-chloro-N-[1-[2-(4-nitrophenyl)ethyl]-2-piperidinylidene]-benzenesulfonamide) and W-15 (4-chloro-N-[1-(2-phenylethyl)-2-piperidinylidene]-benzenesulfonamide) represent two emerging drugs of abuse chemically related to the potent opioid agonist fentanyl (N-(1-(2-phenylethyl)-4-piperidinyl)-N-phenylpropanamide). Here, we describe the comprehensive pharmacological profiles of W-18 and W-15, as examination of their structural features predicted that they might lack opioid activity. We found W-18 and W-15 to be without detectible activity at μ, δ, κ, and nociception opioid receptors in a variety of assays. We also tested W-18 and W-15 for activity as allosteric modulators at opioid receptors and found them devoid of significant positive or negative allosteric modulatory activity. Comprehensive profiling at essentially all the druggable GPCRs in the human genome using the PRESTO-Tango platform revealed no significant activity. Weak activity at the sigma receptors and the peripheral benzodiazepine receptor was found for W-18 (Ki = 271 nM). W-18 showed no activity in either the radiant heat tail-flick or the writhing assays and also did not induce classical opioid behaviors. W-18 is extensively metabolized, but its metabolites also lack opioid activity. Thus, although W-18 and W-15 have been suggested to be potent opioid agonists, our results reveal no significant activity at these or other known targets for psychoactive drugs

Modeling the Longitudinal Asymmetry in Sunspot Emergence -- the Role of the Wilson Depression

The distributions of sunspot longitude at first appearance and at disappearance display an east-west asymmetry that results from a reduction in visibility as one moves from disk centre to the limb. To first order, this is explicable in terms of simple geometrical foreshortening. However, the centre-to-limb visibility variation is much larger than that predicted by foreshortening. Sunspot visibility is also known to be affected by the Wilson effect: the apparent dish shape of the sunspot photosphere caused by the temperature-dependent variation of the geometrical position of the tau=1 layer. In this article we investigate the role of the Wilson effect on the sunspot appearance distributions, deducing a mean depth for the umbral tau=1 layer of 500 to 1500 km. This is based on the comparison of observations of sunspot longitude distribution and Monte Carlo simulations of sunspot appearance using different models for spot growth rate, growth time and depth of Wilson depression.Comment: 18 pages, 10 figures, in press (Solar Physics

Modeling the Subsurface Structure of Sunspots

While sunspots are easily observed at the solar surface, determining their subsurface structure is not trivial. There are two main hypotheses for the subsurface structure of sunspots: the monolithic model and the cluster model. Local helioseismology is the only means by which we can investigate subphotospheric structure. However, as current linear inversion techniques do not yet allow helioseismology to probe the internal structure with sufficient confidence to distinguish between the monolith and cluster models, the development of physically realistic sunspot models are a priority for helioseismologists. This is because they are not only important indicators of the variety of physical effects that may influence helioseismic inferences in active regions, but they also enable detailed assessments of the validity of helioseismic interpretations through numerical forward modeling. In this paper, we provide a critical review of the existing sunspot models and an overview of numerical methods employed to model wave propagation through model sunspots. We then carry out an helioseismic analysis of the sunspot in Active Region 9787 and address the serious inconsistencies uncovered by \citeauthor{gizonetal2009}~(\citeyear{gizonetal2009,gizonetal2009a}). We find that this sunspot is most probably associated with a shallow, positive wave-speed perturbation (unlike the traditional two-layer model) and that travel-time measurements are consistent with a horizontal outflow in the surrounding moat.Comment: 73 pages, 19 figures, accepted by Solar Physic

Squeezed tensor non-Gaussianity in non-attractor inflation

We investigate primordial tensor non-Gaussianity in single field inflation, during a phase of non-attractor evolution when the spectrum of primordial tensor modes can be enhanced to a level detectable at interferometer scales. Making use of a tensor duality we introduced in arXiv:1808.10475, we analytically compute the full bispectrum of primordial tensor fluctuations during the non-attractor era. During this epoch the shape of the tensor bispectrum is enhanced in the squeezed limit, its amplitude can be amplified with respect to slow-roll models, and tensor non-Gaussianity can exhibit a scale dependence distinctive of our set-up. We prove that our results do not depend on the frame used for the calculations. Squeezed tensor non-Gaussianity induces a characteristic quadrupolar anisotropy on the power spectrum of the stochastic background of primordial tensor perturbations. As a step to make contact with gravitational wave experiments, we discuss the response function of a ground based Michelson interferometer to a gravitational wave background with such a feature.Comment: 34 pages, 4 figure

An open-access database and analysis tool for perovskite solar cells based on the FAIR data principles

Large datasets are now ubiquitous as technology enables higher-throughput experiments, but rarely can a research field truly benefit from the research data generated due to inconsistent formatting, undocumented storage or improper dissemination. Here we extract all the meaningful device data from peer-reviewed papers on metal-halide perovskite solar cells published so far and make them available in a database. We collect data from over 42, 400 photovoltaic devices with up to 100 parameters per device. We then develop open-source and accessible procedures to analyse the data, providing examples of insights that can be gleaned from the analysis of a large dataset. The database, graphics and analysis tools are made available to the community and will continue to evolve as an open-source initiative. This approach of extensively capturing the progress of an entire field, including sorting, interactive exploration and graphical representation of the data, will be applicable to many fields in materials science, engineering and biosciences. © 2021, The Author(s)

2D characterization of near-surface V P/V S: surface-wave dispersion inversion versus refraction tomography

International audienceThe joint study of pressure (P-) and shear (S-) wave velocities (Vp and Vs ), as well as their ratio (Vp /Vs), has been used for many years at large scales but remains marginal in near-surface applications. For these applications, and are generally retrieved with seismic refraction tomography combining P and SH (shear-horizontal) waves, thus requiring two separate acquisitions. Surface-wave prospecting methods are proposed here as an alternative to SH-wave tomography in order to retrieve pseudo-2D Vs sections from typical P-wave shot gathers and assess the applicability of combined P-wave refraction tomography and surface-wave dispersion analysis to estimate Vp/Vs ratio. We carried out a simultaneous P- and surface-wave survey on a well-characterized granite-micaschists contact at Ploemeur hydrological observatory (France), supplemented with an SH-wave acquisition along the same line in order to compare Vs results obtained from SH-wave refraction tomography and surface-wave profiling. Travel-time tomography was performed with P- and SH- wave first arrivals observed along the line to retrieve Vtomo p and Vtomo s models. Windowing and stacking techniques were then used to extract evenly spaced dispersion data from P-wave shot gathers along the line. Successive 1D Monte Carlo inversions of these dispersion data were performed using fixed Vp values extracted from Vtomo p the model and no lateral constraints between two adjacent 1D inversions. The resulting 1D Vsw s models were then assembled to create a pseudo-2D Vsw s section, which appears to be correctly matching the general features observed on the section. If the pseudo-section is characterized by strong velocity incertainties in the deepest layers, it provides a more detailed description of the lateral variations in the shallow layers. Theoretical dispersion curves were also computed along the line with both and models. While the dispersion curves computed from models provide results consistent with the coherent maxima observed on dispersion images, dispersion curves computed from models are generally not fitting the observed propagation modes at low frequency. Surface-wave analysis could therefore improve models both in terms of reliability and ability to describe lateral variations. Finally, we were able to compute / sections from both and models. The two sections present similar features, but the section obtained from shows a higher lateral resolution and is consistent with the features observed on electrical resistivity tomography, thus validating our approach for retrieving Vp/Vs ratio from combined P-wave tomography and surface-wave profiling

Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000–17 : analysis for the Global Burden of Disease Study 2017

Background Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood diarrhoea. Methods We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor estimates. Findings The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54·0% (95% uncertainty interval [UI] 38·1–65·8), 17·4% (7·7–28·4), and 59·5% (34·2–86·9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy coverage. Interpretation By co-analysing geospatial trends in diarrhoeal burden and its key risk factors, we could assess candidate drivers of subnational death reduction. Further, by doing a counterfactual analysis of the remaining disease burden using key risk factors, we identified potential intervention strategies for vulnerable populations. In view of the demands for limited resources in LMICs, accurately quantifying the burden of diarrhoea and its drivers is important for precision public health