Lorazepam-valproate interaction: studies in normal subjects and isolated perfused rat liver

Valproate (VPA) has been shown to interact with all the major antiepileptic drugs (AEDs) through two mechanisms of action: displacement from albumin binding sites and inhibition of drug metabolism. More recently, evidence showed that VPA inhibits the elimination of drugs metabolized by glucuronide conjugation. Lorazepam (LZP), which is primarily eliminated by conjugation with glucuronic acid, is administered concurrently with VPA both in treatment of epilepsy and in patients treated with VPA for psychiatric disorders. Therefore, a significant drug interaction is likely. We investigated such interaction both in in vitro isolated perfused rat liver (IPRL) and in normal subjects. LZP [2 mg, intravenous (i.v.) bolus] was administered to 8 normal volunteers before and after chronic dosing with VPA. In 6 of 8 subjects, VPA significantly decreased LZP plasma clearance by an average of 40% (p < 0.05) and increased LZP concentrations by decreasing formation clearance of the LZP glucuronide. In the IPRL studies, VPA also significantly decreased formation of LZP glucuronide (from 0.72 +/- 0.14 to 0.22 +/- 0.15 ml/h/kg, p < 0.05), indicating that IPRL is a useful tool for evaluation of the effect of VPA on drugs eliminated by glucuronide conjugation.     

The role of occlusion in the perception of depth, lightness, and opacity.

A theory is presented that explains how the visual system infers the lightness, opacity, and depth of surfaces from stereoscopic images. It is shown that the polarity and magnitude of image contrast play distinct roles in surface perception, which can be captured by 2 principles of perceptual inference. First, a contrast depth asymmetry principle articulates how the visual system computes the ordinal depth and lightness relationships from the polarity of local, binocularly matched image contrast. Second, a global transmittance anchoring principle expresses how variations in contrast magnitudes are used to infer the presence of transparent surfaces. It is argued that these principles provide a unified explanation of how the visual system computes the 3-D surface structure of opaque and transparent surfaces. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A new adaptation of mapping method to study mixing of multiphase flows in mixers with complex geometries

The main objective of the present work is to modify the traditional mapping method for the simulation of distributive mixing of multiphase flows in geometries involving moving parts such as, internal mixers or twin-screw extruders without a limitation on their geometrical periodicity. The periodicity condition, limits the results of traditional mapping method to tracking mapping mesh between specific discrete time intervals or distances for that geometry is repeated, hence, result is only for fixed orientation of rotors. Imaginary domain method is introduced to track mapping mesh from one state to the next free of geometrical periodicity limitations. In this work the method is introduced and its applicability and accuracy is discussed in details. A two-dimensional (2D) simulation of mixing of two Newtonian fluids with different viscosities in an intermeshing internal mixer is used as a test case study. In this example the key issues of ability to predict mixing state in details for all orientations of rotors is presented. To reduce diffusion errors of mapping method in the boundaries of the rotors, mapping mesh refinement technique that relies upon one single reference mesh is also presented.     

Alpha 2 mRNA of Na+K+ ATPase is increased in astroctyes of rat hippocampus after treatment with kainic acid

The Na+K+ ATPase (Na+ pump) plays a central role in regulating cation homeostasis and is thought to have an important role in cell proliferation. The multitude of subunit isoforms comprising the functional Na+K+ ATPase has raised the possibility that specific subunit isoform combinations may be involved in different cellular processes. We have investigated the involvement of the specific isoforms in neurons and glia at the site of a CNS lesion. Intracerebroventricular injection of kainic acid was used to induce neuronal cell loss and reactive gliosis in rat hippocampus and levels of Na+K+ ATPase subunit isoform mRNA levels were determined in cells of rat hippocampus using in situ hybridization. alpha 2 mRNA levels increased 35-40% in CA1 and CA3 astrocytes between 1-3 weeks after KA injection with no significant change in other subunit isoform mRNA levels. In addition alpha 3 mRNA levels in CA1 pyramidal neurons were decreased by approx. 35%. Small neurons in the CA1 and CA3 region showed no changes in mRNA levels for any of the Na+K+ ATPase subunit isoforms. These results may indicate a possible role for alpha 2 subunit isoform in the conversion of glial cells from a normal phenotype to the reactive phenotype characteristic in this model of CNS injury.     

Food aversion conditioned in anesthetized sheep

We discovered that a food aversion could be conditioned in anesthetized sheep. Sheep were allowed to eat a familiar food (alfalfa-grain pellets) for 30 min, and 90 min later they were given either an intraruminal (IR) injection of water (C), an IR injection of LiCl (L), anesthesia followed by an IR injection of water (A), or anesthesia followed by an IR injection of LiCl (A+L). Induction of anesthesia was by an intravenous injection of pentobarbitone sodium, and maintenance of deep anesthesia was by halothane. Sheep were maintained in deep anesthesia for 2 h to ensure that the effects of LiCl on the acquisition of a food aversion, which occur within about 1 h, were completed before they awakened. When tested 5 days later, sheep that received LiCl (treatments L and A+L) consumed less alfalfa-grain pellets than sheep that did not receive LiCl (treatments C and A) (241 g vs. 306 g; p = 0.057). Intake of sheep that were anesthetized (treatments A and A+L) did not differ from that of sheep that were not anesthetized (treatments C and L) (295 g vs. 252 g; p = 0.183). Nor was there an interaction between LiCl and anesthesia (p = 0.423). Thus, we conclude that changes in preferences for foods caused by postingestive feedback occur automatically every time food is ingested (i.e., they are noncognitive), and the kind and amount of feedback is a function of the match between the food's chemical characteristics and its ability to meet the animal's current demands for nutrients.     

The domain composition method applied to Poisson's equation in two dimensions

Domain composition, a recently described method for formulating continuum field problems, removes certain restrictions on the construction of finite element models such that it is possible to solve a finite element problem without using a global compatible mesh. The domain composition method couples or otherwise constrains meshes in local regions to obtain a solution equivalent to that produced by conventional finite element methods. In particular, the domain composition method enables finite element models to be formulated with overlapping elements. Several advantages come from this, including an ability to automatically generate a finite element model from a solid geometric model, an ability to use a variety of element types in a single finite element model and an ability to exactly match element boundaries to the local geometry. This paper shows in detail a finite element formulation of Poisson's equation using domain composition and presents certain key algorithms that incorporate the domain composition method into well-established finite element procedures.     

The formalization and analysis of a communications protocol

The MSMIE protocol [SBC89] allows processors in a distributed system to communicate via shared memory. It was designed to meet the reliability and efficiency needs of applications such as nuclear safety systems. We present a formal model of the MSMIE protocol expressed in the notation CCS. Desirable properties of the protocol are expressed in the modal mu-calculus, an expressive modal logic. We show that the protocol lacks an important liveness property. In actual operation, additional operating constraints are checked to avoid potential problems. We present a modified protocol and show that it possesses the liveness property even without checking operating constraints. We also show how parts of the analysis were automated with the Concurrency Workbench.     

The role of examples and rules in the acquisition of a cognitive skill

In 3 experiments, participants memorized 8 examples, each exemplifying a different rule. Participants were asked to extend these rules to new examples. They practiced applications of the rules to examples over a period of 4 days (Experiment 1) or 5 days (Experiments 2 and 3). Although these rules were bidirectional, an asymmetry gradually built up such that participants became more facile in using the rules in the practiced direction. Participants also showed an advantage when the initial study example was repeated or when test examples were repeated. It is argued that skill acquisition involves development of a complex set of strategies based on use of rules and retrieval of examples. Four overlapping stages of skill acquisition are described.     

Impact and penetration by L/D ≤ 1 projectiles

Calculations of steel target penetration by L/D ≤ 1 tungsten and tungsten alloy projectiles have been extended to L/D = 1/32 over the velocity range 1.5 to 5 km/s. The ratio of crater to projectile diameter tends to 1 as L/D decreases over this entire velocity range. For impact velocities of 1.5 and 3 km/s, penetration depth normalized by projectile length, P/L, increases with decreasing projectile L/D up to a maximum value and then decreases for still lower L/D. Experiments at impact velocities of 2 and 3 km/s confirm these results. For 5 km/s impact velocity, the calculations show P/L increasing with decreasing projectile L/D over the entire range 1/32 ≤ L/D ≤ 1. The projectile L/D for which the maximum P/L occurs appears to depend on the impact velocity. P/L generally scales with impact velocity as P/L v^f(L/D) where f(L/D) ranges from 0 for a long rod to, we believe, 2 in the limit as projectile L/D approaches zero. The calculations show for 1/8 ≤ L/D ≤ 1/2, P/L v^0.9; for L/D = 1/16, P/L v^1.5; and for L/D = 1/32, the new results give P/L v^1.9.     

Guest Editors' Introduction: Machine Ethics

Machine ethics is concerned with how machines behave toward human users and other machines. It aims to create a machine that's guided by an acceptable ethical principle or set of principles in the decisions it makes about possible courses of action it could take. As ethics experts continue to progress toward consensus concerning the right way to behave in ethical dilemmas, the task for those working in machine ethics is to codify these insights. Eight articles in this special issue address the issues.This article is part of a special issue on Machine Ethics.