Etude Critique de Deux Rejets Méthodologiques Chez B. F. Skinner.

Acritical discussion of Skinner's rejection of hypothetico-deductive methods, which he considers as inadequate, and of psychophysical explanations, interesting in his view, but only as a parallel to the study of behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Design of monomode quadruple-clad fibres

The design of quadruple-clad profiles, leading to (truly) monomode fibres is described: an explicit set of parameters is proposed. Experimental results are presented, concerning a fibre with a dispersion smaller than ±0.5 ps/km nm and an attenuation around 0.3 dB/km, over the 1.5?1.65 ?m wavelength interval.     

Aluminum Fluidity in Casting

The understanding and control of fluidity is, and has been, a major aspect of foundry technology development. This paper reviews the progress made in this area over the years as it applies to aluminum castings. As a result of this development, thin-wall, high-integrity aluminum castings which were previously not thought possible have been produced. Further work in this area is expected to allow metal-matrix composites to fulfill their technical and economic promise.     

Exposure of biological preparations to radiofrequency electromagnetic fields under low gravity

There is interest as to whether the electromagnetic fields used in mobile radiotelephony might affect biological processes. Other weak fields such as gravity intervene in a number of physical and biological processes. Under appropriate in vitro conditions, the macroscopic self-organization of microtubules, a major cellular component, is triggered by gravity. We wished to investigate whether self-organization might also be affected by radiotelephone electromagnetic fields. Detecting a possible effect requires removing the obscuring effects triggered by gravity. A simple manner of doing this is by rotating the sample about the horizontal. However, if the external field does not also rotate with the sample, its possible effect might also be averaged down by rotation. Here, we describe an apparatus in which both the sample and an applied radiofrequency electromagnetic field (1.8 GHz) are stationary with respect to one another while undergoing horizontal rotation. The electromagnetic field profile within the apparatus has been measured and the apparatus tested by reproducing the in vitro behavior of microtubule preparations under conditions of weightlessness. Specific adsorption rates of electromagnetic energy within a sample are measured from the initial temperature rise the incident field causes. The apparatus can be readily adapted to expose samples to various other external fields and factors under conditions of weightlessness.     

Anforderungen an Stahl‐ und Verbundknoten bei Stützenausfall in einem Rahmentragwerk

Eine lokale Schädigung innerhalb der Tragstruktur (z. B. Stützenausfall durch Anprall oder Explosion) kann zu einem Versagen der Gesamtstruktur und damit zum Einsturz des Gebäudes führen. Um solch ein globales Versagen durch lokale Schädigung zu vermeiden, muss innerhalb der Tragstruktur eine Umlagerung der Schnittgrößen ermöglicht werden, d. h., es müssen sich alternative Lastpfade ausbilden können. Solch eine Umlagerung, z. B. von einem reinen Biegezustand in einen gemischten Biege‐/Membranspannungszustand, bedingt unter Umständen sehr große Verformungen, die zu großen Deformationen der Anschlüsse führen. Im Rahmen eines europäischen RFCS‐Forschungsprojektes wurde versucht, mit Hilfe sehr duktiler Anschlussausbildungen die Robustheit von Stahl‐ und Verbundrahmentragwerken zu verbessern. Hauptaugenmerk bei der Konzeption der Anschlüsse war dabei, den Material‐ und Fertigungsaufwand der Anschlüsse so gering wie möglich zu halten und die Umlagerungsmöglichkeiten für außergewöhnliche Bemessungssituationen vornehmlich über das Vorhalten hoher Verformungskapazitäten der Anschlüsse zu aktivieren. Aus diesem Grund wurden hier nachgiebige teiltragfähige Anschlüsse gewählt. Als außergewöhnliche Bemessungssituation wurde in diesem Projekt schwerpunktmäßig der Stützenausfall in einem Rahmentragwerk betrachtet. (RFCS Research Fund for Coal and Steel) Requirements on steel‐ and composite joints for the load case column removal. Local failure in a structure (e. g. sudden column loss due to impact or explosion) may lead to progressive collapse propagation of the global structural system resulting in a total collapse. To avoid progressive collapse initiated by local damage a redistribution of force from the damaged part of the structure has to be enabled by alternate load paths. Activation of alternate load paths by change of the bearing mechanism from pure bending state to more or less pure membrane state is a measure that is only possible by allowing large deformations resulting in high deformation requirements for the joints. In the course of an European RFCS research project ductile joint solutions have been developed to improve the robustness as characteristic of the structure. Main focus of the joint design was to obtain the required deformation capacity for accidental design situations mainly from ductile joint and cause at the same time only few additional material and fabrication costs for the joints. As a result semi‐rigid and partial‐strength joint solutions have been chosen. Objectives within the project were to determine requirements of the joints concerning deformation capacity as well as M‐N‐resistance to enable the activation of catenary action for the load case notional column removal.     

Oxadiazole Derivatives as Dual Orexin Receptor Antagonists: Synthesis,Structure–Activity Relationships,and Sleep-Promoting Properties in Rats

The orexin system plays an important role in the regulation of wakefulness. Suvorexant, a dual orexin receptor antagonist (DORA) is approved for the treatment of primary insomnia. Herein, we outline our optimization efforts toward a novel DORA. We started our investigation with rac-[3-(5-chloro-benzooxazol-2-ylamino)piperidin-1-yl]-(5-methyl-2-[1,2,3]triazol-2-ylphenyl)methanone ( 3 ), a structural hybrid of suvorexant and a piperidine-containing DORA. During the optimization, we resolved liabilities such as chemical instability, CYP3A4 inhibition, and low brain penetration potential. Furthermore, structural modification of the piperidine scaffold was essential to improve potency at the orexin 2 receptor. This work led to the identification of (5-methoxy-4-methyl-2-[1,2,3]triazol-2-ylphenyl)-{(S)-2-[5-(2-trifluoromethoxyphenyl)-[1,2,4]oxadiazol-3-yl]pyrrolidin-1-yl}methanone ( 51 ), a potent, brain-penetrating DORA with in vivo efficacy similar to that of suvorexant in rats.     

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 .     

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...     

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.