Comparing Abstraction Refinement Algorithms

We present a generic algorithm that provides a unifying scheme for the comparison of abstraction refinement algorithms. It is centered around the notion of refinement cue which generalizes counterexamples. It is demonstrated how the essential features of several refinement algorithms can be captured as instances.We argue that the generic algorithm does not limit the completeness of instances, and show that the proposed generalization of counterexamples is necessary for completeness — thus addressing a shortcoming of more limited notions of counterexample-guided refinement.     

Oil Spill Dispersant Effectiveness Protocol. I: Impact of Operational Variables

The current U.S. Environmental Protection Agency protocol for testing the effectiveness of dispersants, the swirling flask test, has been found to give widely varying results in the hands of different testing laboratories. The sources of the ambiguities in the test were determined by considering several options in a rigorous systematic fashion. Options considered were variability among three operators and the variability and limitations of three analytical instruments in establishing a calibration curve for oil/dispersant mixtures. Other options included flask type, impact of operational variables (rotational speed, mixing time, settling time, and oil:dispersant ratio), development of a revised procedure for dispersant effectiveness, reproducibility and repeatability of the revised procedure, and development of selection criteria for screening of dispersants. A redesign of the test flask, which is characterized by having baffles with a stopcock at the bottom for sample collection, was deemed necessary to accomplish reproducibility within operator and between operators. The results indicated that the baffled flask provided a total coefficient of variation (variations within operator and between operators) less than 11% compared to above 100% in some cases for the swirling flask.     

Oil Spill Dispersant Effectiveness Protocol. II: Performance of Revised Protocol

The current U.S. Environmental Protection Agency (EPA) protocol for testing the effectiveness of dispersants for use in treating oil spills on the open water, the swirling flask test (SFT), has been found to give widely varying results in the hands of different testing laboratories. Part I addressed the sources of the ambiguities in the EPA SFT and the development of a new test referred to as the baffled flask test (BFT). In this part of the series, further experiments were conducted for estimating the repeatability of three operators in determining the effectiveness of 18 dispersants by both the EPA SFT and the BFT methods. Overall statistical analysis of the results indicated that the coefficient of variation by the BFT was only 7.8% compared to 21.9% for the EPA SFT. The mean percent effectiveness of the EPA SFT was only 19.7% as compared to 64.6% for the BFT. Proposed selection criteria for screening of dispersants for listing on the National Contingency Plan Product Schedule have been developed.     

Twelve-Week Outcomes From an Investigation of High-Dose Nicotine Patch Therapy for Heavy Smokers With a Past History of Alcohol Dependence.

This study reports findings from an investigation of the efficacy of high-dose nicotine patch (NP) therapy for heavy smokers with a past history of alcohol dependence. One hundred thirty participants were randomly assigned to 42 mg or 21 mg of transdermal nicotine for 4 weeks, followed by an 8-week dose titration. Follow-up assessments were conducted at 4 and 12 weeks. Differences between dose conditions were nonsignificant, although unexpectedly, outcomes favored participants in the 21-mg NP condition. Nicotine abstinence at follow-up was related to longer length of alcohol abstinence at time of enrollment. Future research should investigate ways to improve smoking quit rates in this population, including more frequent counseling sessions and/or other pharmacotherapies. These investigations should focus primarily on smokers in early alcohol recovery. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Labelled-replica techniques: post-shadow labelling of intramembrane particles in freeze-fracture replicas

Three methods are described for direct post-fracture, post-shadow labelling of individual classes of intramembrane particles (IMPs) in freeze-fracture replicas of biological membranes. The P-face IMPs corresponding to the acetylcholine receptor complexes (AChRs) of vertebrate neuroeffector junctions are identified by post-replication labelling with ferritin-antibody complexes and with neurotoxin-biotin-avidin-colloidal gold affinity ligands. (The freeze-etch nomenclature of Branton et al., 1975, is used in this report.) These post-shadow labelling techniques resemble conventional en bloc labelling techniques except that the labelling reagents must penetrate a thin but discontinuous layer of platinum superimposed on the molecules of interest. In the ‘sectioned labelled-replica technique’, the replicated and labelled tissues are stained, embedded in plastic and sectioned parallel to the replica-tissue interfaces. In the direct ‘labelled-replica techniques’, the replicated and labelled samples are freeze-dried or critical point dried, the labelled surfaces are stabilized by carbon coating, and the underlying tissues are dissolved, allowing the labelled-replicas to be examined as conventional freeze-fracture replicas. The unshadowed side of each AChR IMP is shown to retain sufficient biochemical information to permit both immunospecific and neurotoxin specific labelling despite formaldehyde fixation, freezing, fracturing, platinum shadowing, and thawing in aqueous media. A new mixed ferricyanide-osmium staining method reveals electron opaque structures spanning the membrane bilayer in the same size, number and distribution as the labelled IMPs. These experiments demonstrate the feasibility of identifying individual IMPs in freeze-fracture replicas and may allow the identification of specific membrane lesions in human disease.     

Junctional complexes and cell polarity in the urinary tubule

In this review, we demonstrate how differentiated membrane domains can be detected in epithelial cells using conventional light and electron microscopy, freeze-fracture electron microscopy and the immunoand cytochemical detection of membrane components. Using specific examples from the kidney, we show how the polarized insertion of these components into either apical or basolateral plasma membrane regions on either side of the tight junction barrier is related to specific functions of principal and intercalated cells in the collecting duct. In addition, distinct basal and lateral membrane domains have been revealed in some cells that are maintained in the absence of a tight junctional barrier in the plane of the membrane. This suggests that other factors, possibly related to cytoskeletal elements, may be involved in the functional segregation of these membrane areas. We propose that epithelial cell plasma membranes should be subdivided into apical, lateral and basal regions, and that the term “basolateral” may be an oversimplification.     

Quorum sensing in Escherichia coli, Salmonella typhimurium, and Vibrio harveyi: a new family of genes responsible for autoinducer production

In bacteria, the regulation of gene expression in response to changes in cell density is called quorum sensing. Quorum-sensing bacteria produce, release, and respond to hormone-like molecules (autoinducers) that accumulate in the external environment as the cell population grows. In the marine bacterium Vibrio harveyi two parallel quorum-sensing systems exist, and each is composed of a sensor-autoinducer pair. V. harveyi reporter strains capable of detecting only autoinducer 1 (AI-1) or autoinducer 2 (AI-2) have been constructed and used to show that many species of bacteria, including Escherichia coli MG1655, E. coli O157:H7, Salmonella typhimurium 14028, and S. typhimurium LT2 produce autoinducers similar or identical to the V. harveyi system 2 autoinducer AI-2. However, the domesticated laboratory strain E. coli DH5alpha does not produce this signal molecule. Here we report the identification and analysis of the gene responsible for AI-2 production in V. harveyi, S. typhimurium, and E. coli. The genes, which we have named luxSV.h., luxSS.t., and luxSE.c. respectively, are highly homologous to one another but not to any other identified gene. E. coli DH5alpha can be complemented to AI-2 production by the introduction of the luxS gene from V. harveyi or E. coli O157:H7. Analysis of the E. coli DH5alpha luxSE.c. gene shows that it contains a frameshift mutation resulting in premature truncation of the LuxSE.c. protein. Our results indicate that the luxS genes define a new family of autoinducer-production genes.     

Supplemental methionine and time of supplementation effects on ruminal fermentation, digesta kinetics, and in situ dry matter and neutral detergent fiber disappearance in cattle

Two experiments were conducted to study the effects of methionine supplementation on ruminal fermentation and digesta kinetics. In Exp. 1, nine ruminally cannulated beef heifers (average initial BW = 527 kg) in a crossover design were fed low-quality grass hay and cottonseed meal with or without 11.4 g of supplemental methionine (polysaccharide-coated). Particulate and fluid kinetics, rate of DM and NDF disappearance, ruminal VFA and NH3 N concentrations, and pH were not altered (P > .10) by supplemental methionine; however, ruminal purine concentration was greater (P < .05) in methionine-supplemented heifers than in unsupplemented heifers. In Exp. 2, 12 ruminally cannulated Holstein steers (average initial BW = 622 kg) grazing a fescue pasture were allotted to one of three groups: no supplemental methionine (CON) or 11.4 g of supplemental methionine fed at 0700 (AM) or at 1200 (PM). Forage intake, particulate kinetics, ruminal fluid kinetics, pH, VFA, and NH3 N concentrations were not altered (P > .10) by supplemental methionine or supplementation time. In situ rate of DM and NDF disappearance was greater (P < .05) in supplemented steers than in CON steers; AM steers exhibited faster (P < .05) rates than PM steers. Overall, methionine supplementation of low-quality forage increased ruminal purine concentration but did not alter in situ fermentation or digesta passage, whereas supplementation at 0700, but not at 1200, of steers grazing fescue forage increased rate of NDF fermentation.     

The perceived effect of breakdown and repair on the performance of multiprocessor systems

It is argued that classical measures of computer system performance, for example mean response time, are inadequate in the context of fault-tolerant system design. Alternative, perception-based measures are proposed and theorems established describing their properties. Focus is directed upon the homogeneous M/M/m system in which total processor power is constrained by budget and processors are subject to failure and repair. A numerical technique for extracting both classical and perception-based measures from the associated two-dimensional Markov process is offered, along with bounds on time and space required for its execution. It is seen that the perception-based approach to system design can call for twice as many processors as the classical approach.     

Evidence for Oxidative Pathways in the Pathogenesis of PD: Are Antioxidants Candidate Drugs to Ameliorate Disease Progression?

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that arises due to a complex and variable interplay between elements including age, genetic, and environmental risk factors that manifest as the loss of dopaminergic neurons. Contemporary treatments for PD do not prevent or reverse the extent of neurodegeneration that is characteristic of this disorder and accordingly, there is a strong need to develop new approaches which address the underlying disease process and provide benefit to patients with this debilitating disorder. Mitochondrial dysfunction, oxidative damage, and inflammation have been implicated as pathophysiological mechanisms underlying the selective loss of dopaminergic neurons seen in PD. However, results of studies aiming to inhibit these pathways have shown variable success, and outcomes from large-scale clinical trials are not available or report varying success for the interventions studied. Overall, the available data suggest that further development and testing of novel therapies are required to identify new potential therapies for combating PD. Herein, this review reports on the most recent development of antioxidant and anti-inflammatory approaches that have shown positive benefit in cell and animal models of disease with a focus on supplementation with natural product therapies and selected synthetic drugs.