Prenatal THC Does Not Affect Female Mesolimbic Dopaminergic System in Preadolescent Rats

Cannabis use among pregnant women is increasing worldwide along with permissive sociocultural attitudes toward it. Prenatal cannabis exposure (PCE), however, is associated with adverse outcome among offspring, ranging from reduced birth weight to child psychopathology. We have previously shown that male rat offspring prenatally exposed to Δ9-tetrahydrocannabinol (THC), a rat model of PCE, exhibit extensive molecular, cellular, and synaptic changes in dopamine neurons of the ventral tegmental area (VTA), resulting in a susceptible mesolimbic dopamine system associated with a psychotic-like endophenotype. This phenotype only reveals itself upon a single exposure to THC in males but not females. Here, we characterized the impact of PCE on female behaviors and mesolimbic dopamine system function by combining in vivo single-unit extracellular recordings in anesthetized animals and ex vivo patch clamp recordings, along with neurochemical and behavioral analyses. We find that PCE female offspring do not show any spontaneous or THC-induced behavioral disease-relevant phenotypes. The THC-induced increase in dopamine levels in nucleus accumbens was reduced in PCE female offspring, even when VTA dopamine activity in vivo and ex vivo did not differ compared to control. These findings indicate that PCE impacts mesolimbic dopamine function and its related behavioral domains in a sex-dependent manner and warrant further investigations to decipher the mechanisms determining this sex-related protective effect from intrauterine THC exposure.     

Influence of Organic Carbon Sources on Metal Removal from Mine Impacted Water Using Sulfate-Reducing Bacteria Bioreactors in Cold Climates

Mine Water and the Environment - Acid mine drainage (AMD) is a major environmental challenge for the mining industry in northern climates. Laboratory-scale experiments were conducted to test...     

From Oxadiazole to Triazole Analogues: Optimization toward a Dual Orexin Receptor Antagonist with Improved in vivo Efficacy in Dogs

The orexin system is responsible for regulating the sleep-wake cycle. Suvorexant, a dual orexin receptor antagonist (DORA) is approved by the FDA for the treatment of insomnia disorders. Herein, we report the optimization efforts toward a DORA, where our starting point was (5-methoxy-4-methyl-2-[1,2,3]triazol-2-yl-phenyl)-{(S)-2-[5-(2-trifluoromethoxy-phenyl)-[1,2,4]oxadiazol-3-yl]-pyrrolidin-1-yl}methanone ( 6 ), a compound which emerged from our in-house research program. Compound 6 was shown to be a potent, brain-penetrating DORA with in vivo efficacy similar to suvorexant in rats. However, shortcomings from low metabolic stability, high plasma protein binding (PPB), low brain free fraction (f_u brain), and low aqueous solubility, were identified and hence, compound 6 was not an ideal candidate for further development. Our optimization efforts addressing the above-mentioned shortcomings resulted in the identification of (4-chloro-2-[1,2,3]triazol-2-yl-phenyl)-{(S)-2-methyl-2-[5-(2-trifluoromethoxy-phenyl)-4H-[1,2,4]triazol-3-yl]-pyrrolidin-1-yl}l-methanone ( 42 ), a DORA with improved in vivo efficacy compared to 6 .     

Co-doping effects of (Al,Ti, Mg) on the microstructure and electrical behavior of ZnO-based ceramics

Co-doped ZnO-based ceramics using Al, Ti, and Mg ions in different ratios were synthesized with the objective to investigate the doping effects on the crystalline features, microstructure and the electrical behavior. For Al and Ti doping, a coexistence of crystalline phases was shown with a major wurtzite ZnO structure and secondary spinel phases (ZnAl₂O₄, Zn₂TiO₄, or Zn_aTi_bAl_cO_d), while Mg doping did not alter significantly the structural features of the wurtzite ZnO phase. The electrical behavior induced by Al, Ti, and Mg co-doping in different ratios was investigated using Raman, electron paramagnetic resonance (EPR) and ²⁷Al and ⁶⁷Zn solid-state nuclear magnetic resonance (NMR). Al doping induces a high electrical conductivity compared to other doping elements. In particular, shallow donors from Zn_i-Al_Zn defect structures are inferred from the characteristic NMR signal at about 185 ppm; that is, quite far from the usual oxygen coordinated Al. The Knight shift effect emanating from a highly conducting Al-doped ZnO ceramics was considered as the origin of this observation. Oppositely, as Ti doping leads to the formation of secondary spinel phases, EPR analysis shows a high concentration of Ti³⁺ ions which limit the electrical conductivity. The correlation between the structural features at the local order, the involved defects and the electrical behavior as function of the doping process are discussed.     

Fast Measurements of the Gas‐Liquid Diffusion Coefficient in the Gaussian Wake of a Spherical Bubble

A fast method is proposed for determining the oxygen gas‐liquid diffusion coefficient from measurements of the fluorescence quenching behind a bubble. The approach consists of capturing pictures of the concentration field at micro‐scale in the laminar bubble wake. The Gaussian concentration profiles measured in the wake are demonstrated to be systematically equivalent to an instantaneous plane diffusion case. The approach permits to accurately evaluate the gas‐liquid diffusivity in a very short time of around one second.     

Learning from the extreme River Tyne flood in January 2005

Extreme floods often demonstrate unanticipated characteristics that pose problems for management and response. The floods on the Tyne and Eden in January 2005 provided numerous examples of such unexpected response. This paper describes characteristics of storm rainfall and runoff generation on the River Tyne catchment, flood effects and damage. Unusual aspects of hydrological behaviour are highlighted as a basis for assessing what lessons can be learned for flood risk management. These include problems associated with coincidence of extreme wind speeds and rainfall, the retarding influence of floodplain storage on flood wave travel time in extreme flows, the influence of critical storm duration on the severity of the resulting flood on headwaters and main river, and the variety of mechanisms of flood occurrence. The occurrence of such an extreme flood provides the opportunity to validate and enhance the review process of the Environment Agency's flood zone maps.     

Fate of N-nitrosodimethylamine, trihalomethane and haloacetic acid precursors in tertiary treatment including biofiltration

The presence of disinfection by-products (DBPs) such as trihalomethanes (THMs), haloacetic acids (HAAs) and N-nitrosamines in water is of great concern due to their adverse effects on human health. In this work, the removal of N-nitrosodimethylamine (NDMA), total THM and five HAA precursors from secondary effluent by biological activated carbon (BAC) is investigated at full and pilot scale. In the pilot plant two filter media, sand and granular activated carbon, are tested. In addition, we evaluate the influence of ozonation prior to BAC filtration on its performance. Among the bulk of NDMA precursors, the fate of four pharmaceuticals containing a dimethylamino moiety in the chemical structure are individually investigated. Both NDMA formation potential and each of the studied pharmaceuticals are dramatically reduced by the BAC even in the absence of main ozonation prior to the filtration. The low removal of NDMA precursors at the sand filtration in comparison to the removal of NDMA precursors at the BAC suggests that adsorption may play an important role on the removal of NDMA precursors by BAC. Contrary, the precursors for THM and HAA formation are reduced in both sand filtration and BAC indicating that the precursors for the formation of these DBPs are to some extent biodegradable.     

Toward Demystifying the Mohs Hardness Scale

Today, the Mohs scale is used profusely throughout educational systems without any persuasive understanding of the fundamental principles. Why one mineral has a scratch hardness over the next culminating in a scale of 1 (chalk) to 10 (diamond) has no atomistic or structure‐sensitive basis that explains this outcome. With modern computationally based atomistic and multiscale models, there is increasing promise of defining the pressure and rate‐dependent parameters that will allow a fundamental understanding of the Mohs scale. This study principally addresses the combined fracture and plasticity parameters that qualitatively affect fracture at the nanoscale. A physical model wherein the crack tip under a scratch is shielded by dislocations is supported by molecular dynamics (MD) simulations in both ductile aluminum and brittle silicon carbide. Next, this model is applied to nanoindentation data from the literature to produce a ranking of Mohs minerals based on their fundamental properties. As such, what is presented here is a first step to address the flow and fracture parameters ultimately required to provide a figure of merit for scratch hardness and thus the Mohs scale.     

Carbon–polymer composites with extreme electrical conductivity

The aim of this study was to develop Carbon–polymer composites with extreme electrical conductivity (100 S/cm) combined with good flexural strength. Despite the many optimization methods described in the literature, no comprehensive optimization procedure was to be found because the formulation did not control by itself the final properties. This study showed the major influence of the processing conditions with these peculiar materials. A detailed study of the influence of the processing conditions on the microstructural and macroscopic properties was performed. We, thereby, proposed a comprehensive way to optimize the properties of the final product. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42274.