On the Complexity of Verifying Concurrent Transition Systems

In implementation verification, we check that an implementation is correct with respect to a specification by checking whether the behaviors of a transition system that models the program's implementation correlate with the behaviors of a transition system that models its specification. In this paper, we investigate the effect of concurrency on the complexity of implementation verification. We consider trace-based and tree-based approaches to the verification of concurrent transition systems, with and without fairness. Our results show that in almost all cases the complexity of the problem is exponentially harder than that of the sequential case. Thus, as in the model-checking verification methodology, the state-explosion problem cannot be avoided.     

Correction of birefringence and thermal lensing in nonreciprocal resonators by use of a dynamic imaging mirror

Enhanced correction of thermally induced birefringence in the presence of strong single-pass, azimuthally dependent bipolar focusing was achieved in single-rod laser oscillators by use of an adaptive optic rear mirror with image relay and aberration correction capabilities. Together with a Faraday rotator, the imaging variable radius mirror was successfully tested in stable and unstable Nd:Cr:GSGG power oscillators under variable pump power conditions from 0 to 800 W. Birefringence correction in the absence of ray retracing was achieved.     

Functional analysis of a rickettsial OmpA homology domain of Shigella flexneri icsA

Shigella flexneri is a gram-negative bacterium that causes diarrhea and dysentery by invasion and spread through the colonic epithelium. Bacteria spread by assembling actin and other cytoskeletal proteins of the host into "actin tails" at the bacterial pole; actin tail assembly provides the force required to move bacteria through the cell cytoplasm and into adjacent cells. The 120-kDa S. flexneri outer membrane protein IcsA is essential for actin assembly. IcsA is anchored in the outer membrane by a carboxy-terminal domain (the beta domain), such that the amino-terminal 706 amino acid residues (the alpha domain) are exposed on the exterior of the bacillus. The alpha domain is therefore likely to contain the domains that are important to interactions with host factors. We identify and characterize a domain of IcsA within the alpha domain that bears significant sequence similarity to two repeated domains of rickettsial OmpA, which has been implicated in rickettsial actin tail formation. Strains of S. flexneri and Escherichia coli that carry derivatives of IcsA containing deletions within this domain display loss of actin recruitment and increased accessibility to IcsA-specific antibody on the surface of intracytoplasmic bacteria. However, site-directed mutagenesis of charged residues within this domain results in actin assembly that is indistinguishable from that of the wild type, and in vitro competition of a polypeptide of this domain fused to glutathione S-transferase did not alter the motility of the wild-type construct. Taken together, our data suggest that the rickettsial homology domain of IcsA is required for the proper conformation of IcsA and that its disruption leads to loss of interactions of other IcsA domains within the amino terminus with host cytoskeletal proteins.     

The influence of nonremembered affective associations on preference.

An important influence on our preference toward a specific object is its associations with affective information. Here, the authors concentrate on the role of memory on shaping such preferences. Specifically, the authors used a multistage behavioral paradigm that fostered associations between neutral shapes and affective images. Participants that explicitly remembered these affective associations preferred neutral shapes associated with positive images. Counterintuitively, participants who could not explicitly remember the associations preferred neutral shapes that were associated with negative images. Generally, the difference in preference between participants who could and could not remember the affective associations demonstrates a critical link between memory and preference formation. The authors propose that the preference for negatively associated items is a manifestation of a mechanism that produces an inherent incentive for rapidly assessing potentially threatening aspects in the environment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Attenuation of cocaine-induced locomotor activity by butyrylcholinesterase.

A primary enzyme for the metabolism of cocaine is butyrylcholinesterase (BChE). To determine whether the systemic administration of BChE can increase the metabolism of cocaine sufficiently to alter a behavioral effect, rats were tested in a locomotor activity chamber after receiving 17 mg of cocaine per kg intraperitoneally. In rats pretreated intravenously with 5,000 IU of horse serum-derived BChE, the locomotor activity effect was significantly attenuated. BChE pretreatment increased plasma BChE levels approximately 400-fold. When added to rat plasma, this amount of BChE reduced the cocaine half-life from over 5 hr to less than 5 min. BChE altered the cocaine metabolic pattern such that the relatively nontoxic metabolite ecgonine methyl ester was produced, rather than benzoylecgonine. These results suggest that systemic administration of BChE can increase the metabolism of cocaine sufficiently to alter a behavioral effect of cocaine and thus should be investigated as a potential treatment for cocaine abuse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prevention of type 2 diabetes

Type 2 diabetes is a major cause of morbidity and mortality resulting from its microangiopathic and macroangiopathic complications. Current approaches to its management and to the prevention of diabetic complications are difficult to implement effectively, and there is little evidence to date that these approaches are reducing the impact of this disease. The recognition that type 2 diabetes usually has a prolonged prediabetic phase raises the possibility that the emergence of hyperglycemia and the atherosclerotic complications associated with diabetes may be preventable by the institution of early treatment modalities. Sufficient data suggest that life-style modification or pharmacotherapy directed at improving insulin sensitivity or insulin secretion in subjects with impaired glucose tolerance may reduce progression to diabetes. Two long-term prospective, controlled trials have been initiated to test this hypothesis.     

Laser-induced chorioretinal venous anastomosis for nonischemic central or branch retinal vein occlusion

Sea urchin embryos have provided excellent material for experimental and molecular analyses of the processes of cell and axis specification during embryogenesis. These studies revealed the tremendous developmental plasticity of cells in early embryos and the roles that cell-cell interactions play in determining cell fates. Details concerning sea urchin development can be found in a number of excellent reviews. This review summarizes experimental and molecular studies relating to axis determination and cell fate specification in echinoid embryos. Correlations are drawn from research carried out on the development of axial systems in other organisms.     

Value of the pretransplant evaluation in predicting toxic day-100 mortality among blood stem-cell and bone marrow transplant recipients

PURPOSE: To determine the value of pretransplant studies in predicting day 100 nonrelapse toxic mortality following high-dose therapy. PATIENTS AND METHODS: A retrospective review of 383 consecutive hematopoietic stem-cell transplants was performed with attention to toxic mortality and pretransplant factors. Univariate log-rank analysis was used to yield the most significant cut-off values for individual factors. Multivariate analysis using Cox proportional hazards regression determined factors independently predictive of early toxic death. RESULTS: Nonrelapse toxic mortality before day 100 occurred in 23 of 383 (6.0%) transplant recipients. Factors associated with an increased risk of toxic death by univariate analysis included forced expiratory volume in 1 second (FEV1) less than 78% of predicted (P = .0002), allogeneic versus autologous transplant (P = .0003), diffusion capacity of carbon monoxide less than 52% of predicted (P = .002), serum creatinine concentration greater than 1.1 mg/dL (P = .003), Eastern Cooperative Oncology Group performance status greater than 0 (P = .006), preparative regimen containing total-body irradiation versus chemotherapy alone (P = .006), marrow versus blood stem cell (P = .01), serum ALT greater than 50 IU/L (P = .02), diagnosis of hematologic disorder versus solid tumor (P = .06), serum bilirubin level greater than 1.1 mg/dL (P = .08), left ventricular ejection fraction (P = .09), and growth factor use (P = .09). In the multivariate model, transplant type (relative risk, 4.2), FEV1 (relative risk, 4.5), performance status (relative risk, 3.7), serum creatinine (relative risk, 3.8), and serum bilirubin (relative risk, 3.7) were found to be independent predictors of early toxic mortality. CONCLUSION: The pretransplant evaluation is a useful tool to identify patients at risk for early toxic mortality following high-dose therapy.     

Antinociceptive analogs of orphanin FQ/nociceptin(1-11)

The presence of pairs of basic amino acids within the sequence of orphanin FQ/nociceptin (OFQ/N) peptide, the endogenous ligand for the ORL1/KOR-3 receptor, has raised the possibility that processing might generate pharmacologically important truncated peptides, including OFQ/N(1-11). OFQ/N(1-11) is pharmacologically active in vivo with a potency comparable to OFQ/N. Several tyrosine-containing analogs of OFQ/N(1-11) have been synthesized and examined for antinociceptive activity. Like OFQ/N(1-11), [Tyr1]OFQ/N(1-11), [Tyr10]OFQ/N(1-11) and [IodoTyr10]OFQ/N(1-11) given supraspinally in mice were antinociceptive in the tailflick assay in mice. The tyrosine analogs showed similar potencies as OFQ/N(1-11) but longer durations of action. This response was readily reversed by the opioid antagonist naloxone despite poor affinities for these analogs at opioid receptors. Another compound, [Tyr11]OFQ/N(1-11) was highly epileptogenic, inducing naloxone-sensitive seizures in greater than 50% of the mice tested at doses comparable to those examined with the other analogs. These results indicate that it is possible to make analgesic OFQ/N(1-11) analogs. The activity of [IodoTyr10]OFQ/N(1-11) suggests that it may prove useful as a radioligand in exploring potential OFQ/N(1-11) binding sites.