Assume,guarantee or repair: a regular framework for non regular properties

We present Assume-Guarantee-Repair (AGR)—a novel framework which verifies that a program satisfies a set of properties and also repairs the program in case the verification fails. We consider communicating programs—these are simple C-like programs, extended with synchronous actions over communication channels. Our method, which consists of a learning-based approach to assume–guarantee reasoning, performs verification and repair simultaneously: in every iteration, AGR either makes another step towards proving that the (current) system satisfies the required properties, or alters the system in a way that brings it closer to satisfying the properties. To handle infinite-state systems we build finite abstractions, for which we check the satisfaction of complex properties that contain first-order constraints, using both syntactic and semantic-aware methods. We implemented AGR and evaluated it on various communication protocols. Our experiments present compact proofs of correctness and quick repairs.

     

Technical Validation and Clinical Implications of Ultrasensitive PCR Approaches for EGFR-Thr790Met Mutation Detection in Pretreatment FFPE Samples and in Liquid Biopsies from Non-Small Cell Lung Cancer Patients

In pretreatment tumor samples of EGFR-mutated non-small cell lung cancer (NSCLC) patients, EGFR-Thr790Met mutation has been detected in a variable prevalence by different ultrasensitive assays with controversial prognostic value. Furthermore, its detection in liquid biopsy (LB) samples remains challenging, being hampered by the shortage of circulating tumor DNA (ctDNA). Here, we describe the technical validation and clinical implications of a real-time PCR with peptide nucleic acid (PNA-Clamp) and digital droplet PCR (ddPCR) for EGFR-Thr790Met detection in diagnosis FFPE samples and in LB. Limit of blank (LOB) and limit of detection (LOD) were established by analyzing negative and low variant allele frequency (VAF) FFPE and LB specimens. In a cohort of 78 FFPE samples, both techniques showed an overall agreement (OA) of 94.20%. EGFR-Thr790Met was detected in 26.47% of cases and was associated with better progression-free survival (PFS) (16.83 ± 7.76 vs. 11.47 ± 1.83 months; p = 0.047). In LB, ddPCR was implemented in routine diagnostics under UNE-EN ISO 15189:2013 accreditation, increasing the detection rate of 32.43% by conventional methods up to 45.95%. During follow-up, ddPCR detected EGFR-Thr790Met up to 7 months before radiological progression. Extensively validated ultrasensitive assays might decipher the utility of pretreatment EGFR-Thr790Met and improve its detection rate in LB studies, even anticipating radiological progression.     

Volatile-Mediated Interactions between Cabbage Plants in the Field and the Impact of Ozone Pollution

Plants constitutively release volatile organic compounds (VOCs), but qualitatively and quantitatively alter their emission of VOCs in response to biotic and abiotic stresses. The blend of VOCs emitted reflects the physiological status of the plant. Plants may be exposed to the VOC blend emitted by their near neighbors and gain information that allows them to adjust their own defenses. These plant-plant interactions may potentially be exploited to protect crops from pests, but they can be disturbed by abiotic factors making the process sensitive to environmental perturbation. Despite numerous studies describing plant-plant interactions, relatively few have been conducted with agriculturally significant cultivated plant varieties under field conditions. Here we studied plant-plant interactions in a conspecific association of Brassica oleracea var. capitata (cabbage) and show that undamaged plants exposed to neighbors damaged by the herbivore Pieris brassicae are primed for stronger volatile emissions upon subsequent herbivore attack. We conducted a field study in an ozone free-air concentration enrichment (FACE) facility with ambient and elevated ozone levels and found that elevated tropospheric ozone significantly alters the priming of VOCs in receiver plants. We conclude that plant-plant interactions may prime defensive attributes of receiver plants under field conditions, but are impaired by ozone pollution. Therefore, when planning the manipulation of plant-plant interactions for agricultural purposes, the potential effects of atmospheric pollutants should be considered.     

Calibration via Multi-period State Estimation in Water Distribution Systems

Calibration of model parameters is of utmost importance to ensure the good performance of hydraulic simulation models. In this work, calibration is conceived within a joint multi-period parameter and state estimation approach, where model parameters (i.e. roughness coefficients) and hydraulic variables should be computed from available measurements at different times. The aim of this paper is twofold: (1) to present a novel methodology for the calibration of water networks via multi-period state estimation, and (2) to adapt observability analysis to this approach. The novelty of this work is that such a large-scale non-linear optimisation problem is here solved using mathematical programming decomposition techniques. On the other hand, observability analysis requires the construction of the multi-period measurement and parameter Jacobian matrix of the problem. The proposed approach enables computation of the observable roughness coefficients from available readings over time, making possible the periodic reassessment of roughness values based on recent online measurements. The potential of the method is illustrated by means of a case study, which shows how such a methodology would contribute to make the most of telemetry data for calibration purposes.     

Modelling Cl- homeostasis and volume regulation of the cardiac cell

We aim at introducing a Cl- homeostasis to the cardiac ventricular cell model (Kyoto model), which includes the sarcomere shortening and the mitochondria oxidative phosphorylation. First, we examined mechanisms underlying the cell volume regulation in a simple model consisting of Na+/K+ pump, Na+-K+-2Cl- cotransporter 1 (NKCC1), cystic fibrosis transmembrane conductance regulator, volume-regulated Cl- channel and background Na+, K+ and Cl- currents. The high intracellular Cl- concentration of approximately 30 mM was achieved by the balance between the secondary active transport via NKCC1 and passive currents. Simulating responses to Na+/K+ pump inhibition revealed the essential role of Na+/K+ pump in maintaining the cellular osmolarity through creating the negative membrane potential, which extrudes Cl- from a cell, confirming the previous model study in the skeletal muscle. In addition, this model well reproduced the experimental data such as the responses to hypotonic shock in the presence or absence of beta-adrenergic stimulation. Finally, the volume regulation via Cl- homeostasis was successfully incorporated to the Kyoto model. The steady state was well established in the comprehensive cell model in respect to both the intracellular ion concentrations and the shape of the action potential, which are all in the physiological range. The source code of the model, which can reproduce every result, is available from http://www.sim-bio.org/.     

Prejudice reduction in white students: Comparing three conceptual approaches.

Schools and businesses increasingly use prejudice-reduction interventions, which typically emphasize 1 of 3 concepts: cooperation, political tolerance, or respect. This study serves as an initial laboratory investigation of the relative effectiveness of these 3 concepts, as compared with a control concept (intelligence), for reducing prejudice. Participants read a paragraph designed to prime 1 of the 3 prejudice reduction concepts or the control. Two self-report inventories (Social Dominance Orientation Scale and the Modern Racism Scale) and 2 implicit measures (a budget survey and the Race Implicit Association Test) were used to assess levels of racism and in-group preference. Participants in the cooperation condition scored significantly lower on the Race Implicit Association Test than those in the control condition, suggesting that control participants had a relatively stronger automatic preference for Whites. A significant effect of prime was also found on the Modern Racism Scale; participants in the respect condition had the lowest scores, indicative of relatively lower levels of prejudice toward African Americans. Males emerged as more biased than females on 3 of the 4 dependent measures. Implications for designing multicultural education programs are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of chemical modification of oligohomopyrimidine on triplex formation: thermodynamic and kinetic studies

To investigate the effect of chemical modification of the third strand on the stability of triplex DNA, we have examined the thermodynamic properties of the triplex formation between a 23-mer double-stranded homopurine-homopyrimidine and each of five kinds of 15-mer chemically modified single-stranded homopyrimidines by isothermal titration calorimetry, and the kinetic properties by interaction analysis system. The modifications of the third strand included two base modifications, two sugar moiety modifications, and one phosphate backbone modification. The thermodynamic and kinetic parameters for the triplex formation were similar in magnitude among the two base-modified and two sugar-modified single strands. By contrast, the binding constant for the triplex formation with the single strand with phosphorothioate backbone was more than ten times as small as that for the other triplex formation. On the basis of the kinetic analyses, the single strand with phosphorothioate backbone was more difficult to associate with and easier to dissociate from the target double strand than the other single strands, which resulted in the much smaller binding constant.     

Normoxic cardiopulmonary bypass reduces oxidative myocardial damage and nitric oxide during cardiac operations in the adult

The purpose of this study was to explain smoking habits amongst middle-aged men in Finland by describing their experiences of smoking and their attitudes towards smoking. As a pilot survey for a major health campaign targeted at 40-year-old men, the data for this study were collected using two questionnaires in connection with voluntary medical examinations. The first questionnaire was based on Prochaska's theory of stages of change in health behaviour. The second instrument was an attitude scale developed specifically for this study on the basis of Green and Kreuter's theory of factors influencing health behaviour. According to the results 31% of males aged 40 were regular smokers. Men with a lower level of education and out of work smoked more often than others. Non-smokers reported a better self-perceived health than smokers. Smoking cessation is a process in which men gradually proceed from one step to the next. In this study 12% of the men were in the contemplation stage and 11% in the preparation stage. One-quarter of the men had recently given up the habit and were in the action stage, while 2% had quit smoking over 6 months ago and were in the maintenance stage. One-quarter of the men regarded smoking as an integral part of their way of life and felt that public opinion towards smoking is hostile.     

A simple method for assessing the mutational effect on the protein-DNA interaction: application to amino acid substitutions

We have developed a simple method to assess the effect of mutationson the binding affinity change in the protein-DNA interaction.In this method, we evaluate the contribution of the local geometriceffect in protein-DNA recognition by calculating the changein interaction energy caused by mutations, and assess the bindingactivity by introducing the binding affinity index. We appliedthis method to the interaction between repressor and DNA. Inspite of the simplicity of the present method, the calculatedresults qualitatively agree with experimental results for alimited number of mutants of repressor. The mutational effectsare mostly attributed to the complementary interactions in theprotein-DNA complex. Although the method is still preliminaryand should be the subject of further experimental verification,it may be used effectively at the planning stage of mutagenesisexperiments to narrow down the selection of mutation by excludingunreasonable mutations.     

State Variable Implications on Hydraulic State Estimation

Hydraulic State Estimation allows to estimate the most likely state of a water supply network considering multiple sources of information and their associated uncertainty. It is set out as an optimization problem, often addressed according to the Weighted Least Squares criterion. It can be formulated differently depending on the selected set of state variables. This choice is not straightforward and leads to different problem dimensions, time complexities and convergence behavior. All possible essential approaches are gathered in this work and two are identified as the most suitable according to the resulting problem dimensions: a head-based approach and a demand-based approach. The particularities and the formulation according to both sets of state variables are discussed, seeking for efficient implementation. Their time complexity and convergence behavior are compared to draw conclusions that help to identify the most suitable approach for real practice applications.