Ilinva: Using Abduction to Generate Loop Invariants

International audienceWe describe a system to prove properties of programs. The key feature of this approach is a method to automatically synthesize in-ductive invariants of the loops contained in the program. The method is generic, i.e., it applies to a large set of programming languages and application domains; and lazy, in the sense that it only generates invariants that allow one to derive the required properties. It relies on an existing system called GPiD for abductive reasoning modulo theories [14], and on the platform for program verification Why3 [16]. Experiments show evidence of the practical relevance of our approach

Lipid productivity and cell wall ultrastructure of six strains of Nannochloropsis: Implications for biofuel production and downstream processing

Microalgae are generating considerable interest for third generation biodiesel production. However, appropriate strain selection is proving challenging due to the significant variation in cellular physiology, metabolic potential and genetics observed even amongst strains deemed morphologically similar. Six strains of Nannochloropsis from the CCAP culture collection were assessed for their lipid productivity and cellular structure, as proxies for oil production and harvesting ease, to assess their suitability as biodiesel production platforms. Differences in growth rate and lipid accumulation across the strains were observed. Nannochloropsis oculata strain 849/7 showed significantly reduced doubling time compared to Nannochloropsis salina strain 849/3, whilst Nannochloropsis oceanica 849/10 produced the highest lipid content. In addition the six strains could be differentiated into 3 distinct classes based on their cell wall thickness, which varied across the strains from 63 to 119 nm and which is independent of both species and geographical isolation location. The importance of these variations in ultrastructure and physiology for biodiesel production is discussed

Polynomial Method for PLL Controller Optimization†

The Phase-Locked Loop (PLL) is a key component of modern electronic communication and control systems. PLL is designed to extract signals from transmission channels. It plays an important role in systems where it is required to estimate the phase of a received signal, such as carrier tracking from global positioning system satellites. In order to robustly provide centimeter-level accuracy, it is crucial for the PLL to estimate the instantaneous phase of an incoming signal which is usually buried in random noise or some type of interference. This paper presents an approach that utilizes the recent development in the semi-definite programming and sum-of-squares field. A Lyapunov function will be searched as the certificate of the pull-in range of the PLL system. Moreover, a polynomial design procedure is proposed to further refine the controller parameters for system response away from the equilibrium point. Several simulation results as well as an experiment result are provided to show the effectiveness of this approach

Elevation and cholera: an epidemiological spatial analysis of the cholera epidemic in Harare, Zimbabwe, 2008-2009

BACKGROUND: In highly populated African urban areas where access to clean water is a challenge, water source contamination is one of the most cited risk factors in a cholera epidemic. During the rainy season, where there is either no sewage disposal or working sewer system, runoff of rains follows the slopes and gets into the lower parts of towns where shallow wells could easily become contaminated by excretes. In cholera endemic areas, spatial information about topographical elevation could help to guide preventive interventions. This study aims to analyze the association between topographic elevation and the distribution of cholera cases in Harare during the cholera epidemic in 2008 and 2009. METHODS: We developed an ecological study using secondary data. First, we described attack rates by suburb and then calculated rate ratios using whole Harare as reference. We illustrated the average elevation and cholera cases by suburbs using geographical information. Finally, we estimated a generalized linear mixed model (under the assumption of a Poisson distribution) with an Empirical Bayesian approach to model the relation between the risk of cholera and the elevation in meters in Harare. We used a random intercept to allow for spatial correlation of neighboring suburbs. RESULTS: This study identifies a spatial pattern of the distribution of cholera cases in the Harare epidemic, characterized by a lower cholera risk in the highest elevation suburbs of Harare. The generalized linear mixed model showed that for each 100 meters of increase in the topographical elevation, the cholera risk was 30% lower with a rate ratio of 0.70 (95% confidence interval=0.66-0.76). Sensitivity analysis confirmed the risk reduction with an overall estimate of the rate ratio between 20% and 40%. CONCLUSION: This study highlights the importance of considering topographical elevation as a geographical and environmental risk factor in order to plan cholera preventive activities linked with water and sanitation in endemic areas. Furthermore, elevation information, among other risk factors, could help to spatially orientate cholera control interventions during an epidemic

The emotional movie database (EMDB): a self-report and psychophysiological study

Film clips are an important tool for evoking emotional responses in the laboratory. When compared with other emotionally potent visual stimuli (e.g., pictures), film clips seem to be more effective in eliciting emotions for longer periods of time at both the subjective and physiological levels. The main objective of the present study was to develop a new database of affective film clips without auditory content, based on a dimensional approach to emotional stimuli (valence, arousal and dominance). The study had three different phases: (1) the pre-selection and editing of 52 film clips (2) the self-report rating of these film clips by a sample of 113 participants and (3) psychophysiological assessment [skin conductance level (SCL) and the heart rate (HR)] on 32 volunteers. Film clips from different categories were selected to elicit emotional states from different quadrants of affective space. The results also showed that sustained exposure to the affective film clips resulted in a pattern of a SCL increase and HR deceleration in high arousal conditions (i.e., horror and erotic conditions). The resulting emotional movie database can reliably be used in research requiring the presentation of non-auditory film clips with different ratings of valence, arousal and dominance.Portuguese Foundation for Science and Technology with individual grants (SFRH/BD/41484/2007 and SFRH/BD/64355/2009

Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications.

Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylated DNA binding domain sequencing (MBD-seq). We applied all four methods to biological replicates of human embryonic stem cells to assess their genome-wide CpG coverage, resolution, cost, concordance and the influence of CpG density and genomic context. The methylation levels assessed by the two bisulfite methods were concordant (their difference did not exceed a given threshold) for 82% for CpGs and 99% of the non-CpG cytosines. Using binary methylation calls, the two enrichment methods were 99% concordant and regions assessed by all four methods were 97% concordant. We combined MeDIP-seq with methylation-sensitive restriction enzyme (MRE-seq) sequencing for comprehensive methylome coverage at lower cost. This, along with RNA-seq and ChIP-seq of the ES cells enabled us to detect regions with allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression

Whole-genome sequencing for prediction of Mycobacterium tuberculosis drug susceptibility and resistance: a retrospective cohort study

Background Diagnosing drug-resistance remains an obstacle to the elimination of tuberculosis. Phenotypic drug-susceptibility testing is slow and expensive, and commercial genotypic assays screen only common resistance-determining mutations. We used whole-genome sequencing to characterise common and rare mutations predicting drug resistance, or consistency with susceptibility, for all first-line and second-line drugs for tuberculosis. Methods Between Sept 1, 2010, and Dec 1, 2013, we sequenced a training set of 2099 Mycobacterium tuberculosis genomes. For 23 candidate genes identified from the drug-resistance scientific literature, we algorithmically characterised genetic mutations as not conferring resistance (benign), resistance determinants, or uncharacterised. We then assessed the ability of these characterisations to predict phenotypic drug-susceptibility testing for an independent validation set of 1552 genomes. We sought mutations under similar selection pressure to those characterised as resistance determinants outside candidate genes to account for residual phenotypic resistance. Findings We characterised 120 training-set mutations as resistance determining, and 772 as benign. With these mutations, we could predict 89·2% of the validation-set phenotypes with a mean 92·3% sensitivity (95% CI 90·7–93·7) and 98·4% specificity (98·1–98·7). 10·8% of validation-set phenotypes could not be predicted because uncharacterised mutations were present. With an in-silico comparison, characterised resistance determinants had higher sensitivity than the mutations from three line-probe assays (85·1% vs 81·6%). No additional resistance determinants were identified among mutations under selection pressure in non-candidate genes. Interpretation A broad catalogue of genetic mutations enable data from whole-genome sequencing to be used clinically to predict drug resistance, drug susceptibility, or to identify drug phenotypes that cannot yet be genetically predicted. This approach could be integrated into routine diagnostic workflows, phasing out phenotypic drug-susceptibility testing while reporting drug resistance early

Predictors of Hospitalization for Injection Drug Users Seeking Care for Soft Tissue Infections

BACKGROUND: Soft tissue infections (STIs) from injection drug use are a common cause of Emergency Department visits, hospitalizations, and operating room procedures, yet little is known about factors that may predict the need for these costly medical services. OBJECTIVE: To describe a cohort of injection drug users seeking Emergency Department care for STIs and to identify risk factors associated with hospitalization. We hypothesized that participants who delayed seeking care would be hospitalized more often than those who did not. DESIGN: Cohort study using in-person structured interviews and medical record review. Logistic regression assessed the association between hospital admission and delay in seeking care as well as other demographic, clinical, and psychosocial factors. PARTICIPANTS: Injection drug users who sought Emergency Department care for STIs from May 2001 to March 2002. RESULTS: Of the 136 participants, 55 (40%) were admitted to the hospital. Delay in seeking care was not associated with hospital admission. Participants admitted for their infection were significantly more likely to be living in a shelter (P = .01) and to report being hospitalized 2 or more times in the past year (P < .01). CONCLUSIONS: We identified a subpopulation of injection drug users, mostly living in shelters, who were hospitalized frequently in the past year and who were more likely to be hospitalized for their current infections compared to others. As members of this subpopulation can be easily identified and located, they may benefit from interventions to reduce the health care utilization resulting from these infections