Comparative autoradiographic distribution of central omega (benzodiazepine) modulatory site subtypes with high, intermediate and low affinity for zolpidem and alpidem

Pharmacological characterization of [3H]benzodiazepine binding to membrane preparations of adult rat hippocampus and neonatal rat brain have demonstrated, in addition to the omega 1 and omega 2 populations of central omega benzodiazepine binding sites associated with GABAA receptors, the existence of binding sites with microM affinity for the imidazopyridines zolpidem and alpidem. In the present study we have investigated their comparative autoradiographic distribution using [3H]flumazenil as a ligand. In the neonatal rat CNS, the imidazopyridine derivatives zolpidem and alpidem were found to discriminate two [3H]flumazenil binding site populations with an IC50 value ratio of more than 200-fold. In the different regions investigated (spinal cord, striatum, neocortex and inferior colliculus) the low affinity component had IC50 values of 20-40 microM (zolpidem) and 5-15 microM (alpidem) and accounted for ca. 50% of the total binding site population. In the adult rat, these imidazopyridine derivatives displayed a greater displacing potency in the cerebellum (IC50 = 6 and 36 nM, respectively) than in the hippocampus (IC50 = 37 and 403 nM, respectively). In the cerebellum, [3H]flumazenil binding was fully displaced by 1 microM of either compound and Hill coefficients of displacement curves were close to unity. In the hippocampus, 25% of [3H]flumazenil binding were resistant to 3 microM zolpidem or 1 microM alpidem, but were displaced by 100 microM of either compound. CL 218,872 also displayed a greater displacing potency in the cerebellum (IC50 = 83 nM) than in the hippocampus (IC50 = 711 nM) but [3H]flumazenil binding in the hippocampus was fully displaced by 10 microM of this compound. In adult rat hippocampus, zolpidem and alpidem were found to discriminate between three central omega site subtypes which display high (IC50 = 31 and 6.1 nM, for these imidazopyridine derivatives. In contrast, CL 218,872 discriminated between omega 1 and omega 2 sites but not between two omega 2 receptor subpopulations. omega 1 sites were mainly localized in layer IV of the sensorimotor cortex, cerebellum, substantia nigra, olfactory bulb and inferior colliculus. omega 2I sites were present in the cortical mantle (with higher levels in the cingulate and olfactory than in the sensorimotor cortex) and in subcortical (hippocampus, hypothalamus and nucleus accumbens) limbic structures. In the hippocampus, hypothalamus, spinal cord and nucleus accumbens, omega 2L sites accounted for more than 25% of the specific [3H]flumazenil binding; the density of these sites was minor in the cortex and in most pyramidal and extrapyramidal system structures.(ABSTRACT TRUNCATED AT 400 WORDS)     

Simulation of the Forming Behaviour of a Boron Modified P91 Ferritic Steel

The forming behaviour at high temperature of a modified 9%Cr‐1%Mo (P91) ferritic steel containing B and Ti for elevated temperature service was investigated. The microstructure of the as‐received material is mainly martensite at room temperature, but special etching revealed prior austenite grains of about 25 μm in size. Torsion tests were conducted at temperatures in the range 850 to 1250 °C to simulate the hot rolling process under comparable conditions of temperature, strain rate and strain. The deformation data obtained from these tests were correlated with the Garofalo equation with a stress exponent of 4.6 and an activation energy of 315 kJ/mol. This equation was used to predict the formability behaviour for the rolling process and also to determine the maximum forming efficiency and stability of the steel. A temperature of 1200 °C is recommended to conduct the forming process.     

Design and implementation of efficient QCA full-adders using fault-tolerant majority gates

The Journal of Supercomputing - CMOS technology is facing physical limitations in scaling the manufacturing process. Therefore, to deepen the development of better designs in a smaller area, it is...     

Using new scheduling heuristics based on resource consumption information for increasing throughput on rule‐based spam filtering systems

The large increase of spam deliveries since the first half of 2013 entailed hard to solve troubles in spam filters. In order to adequately fight spam, the throughput of spam filtering platforms should be necessarily increased. In this context, and taking into consideration the widespread utilization of rule‐based filtering frameworks in the spam filtering domain, this work proposes three novel scheduling strategies for optimizing the time needed to classify new incoming e‐mails through an intelligent management of computational resources depending on the Central Processing Unit (CPU) usage and Input/Output (I/O) delays. In order to demonstrate the suitability of our approaches, we include in our experiments a comparative study in contrast to other successful heuristics previously published in the scientific literature. Results achieved demonstrated that one of our alternative heuristics allows time savings of up to 10% in message filtering, while keeping the same classification accuracy. Copyright © 2015 John Wiley & Sons, Ltd.     

Influence of the final ethanol concentration on the acetification and production rate in the wine vinegar process

BACKGROUND: The acetification process needs an overall study of the variables influencing it in order to establish their optimum values. Based on industrial experience and available literature, including a recently proposed model by the authors, among the variables most strongly influencing the acetification process are the ethanol concentration at the time the reactor is unloaded, the unloaded volume and the loading rate. To ensure economically efficient industrial production of vinegar, and to check the predictions of the aforementioned model, the influence of the final ethanol concentration at unloading time on the mean acetification rate and on productivity has been studied in this work. RESULTS: An increase in the final ethanol concentration from 0.5 to 3.5% (v/v) increased the mean overall acetification rate and acetic acid production by 38 and 26%, respectively. The increase was established mainly during the loading phase. CONCLUSIONS: The final ethanol concentration is a key variable for process optimization. If a high rate is desired then a product containing much unused substrate will be obtained, which may be industrially unacceptable. These results suggest the necessity to investigate other possibilities when high values for yield and productivity must to be achieved. Copyright © 2010 Society of Chemical Industry     

Microstructure and mechanical properties of rapidly solidified Fe-25%Cr-5%Al ribbons produced by planar flow casting

Catalyst substrate foils of the highly oxidation resistant Fe-25Cr-5Al alloy (mass contents in %) with a thickness ranging from 40 to 180 μm have been produced by planar flow casting. The rapidly solidified ribbons showed a monophase ferritic microstructure of columnar grains. The grain size determined over a section parallel to the ribbon wheel side ranged from 5 μm for the thin ribbons (40 μm) to 18 μm for the thicker ones {180 μm). This anisotropic columnar solidification microstructure exhibits a strong <100> fiber texture, with the fiber axis nearly perpendicular to the plane of the ribbon. The position of the maximum in the pole figure was tilted from the center point toward the casting direction. Results of uniaxial tensile tests showed that only the yield stress data of the ribbons in the as-cast condition are reproducible, whereas the ultimate tensile strength and the elongation to failure data show a wide scatter band. The fracture mode exhibits ductile features such as glide bands and dimples.     

A soft-computing methodology for noninvasive time-spatial temperature estimation.

The safe and effective application of thermal therapies is restricted due to lack of reliable noninvasive temperature estimators. In this paper, the temporal echo-shifts of backscattered ultrasound signals, collected from a gel-based phantom, were tracked and assigned with the past temperature values as radial basis functions neural networks input information. The phantom was heated using a piston-like therapeutic ultrasound transducer. The neural models were assigned to estimate the temperature at different intensities and points arranged across the therapeutic transducer radial line (60 mm apart from the transducer face). Model inputs, as well as the number of neurons were selected using the multiobjective genetic algorithm (MOGA). The best attained models present, in average, a maximum absolute error less than 0.5 degrees C, which is pointed as the borderline between a reliable and an unreliable estimator in hyperthermia/diathermia. In order to test the spatial generalization capacity, the best models were tested using spatial points not yet assessed, and some of them presented a maximum absolute error inferior to 0.5 degrees C, being "elected" as the best models. It should be also stressed that these best models present implementational low-complexity, as desired for real-time applications.     

Influence of the thermomechanical processing on the fracture mechanisms of high strength aluminium/pure aluminium multilayer laminate materials

The microstructure and mechanical properties, with emphasis in the impact fracture toughness behaviour, of two multilayer laminate materials have been investigated. The multilayer materials are constituted by alternated sheets of pure aluminium (Al 1200 or Al 1050) and high strength Al 7075 alloy. Stacked layers of these alloys have been successfully joined using two processing routes with different total hot rolling strains. Both laminates have been tested at room temperature under impact Charpy tests, three-point bend tests and shear tests on the interfaces. Both laminates exhibited more than eight times improvement in impact fracture toughness over the monolithic Al 7075-T6. The toughness increase in the higher rolling strained laminate is almost entirely due to crack blunting mechanism, while in the lower strained laminate, crack deflection by delamination and crack renucleation processes were active.