Acceptance Criteria for Critical Software Based on Testability Estimates and Test Results

Testability is defined as the probability that a program will fail a test, conditional on the program containing some fault. In this paper, we show that statements about the testability of a program can be more simply described in terms of assumptions on the probability distribution of the failure intensity of the program. We can thus state general acceptance conditions in clear mathematical terms using Bayesian inference. We develop two scenarios, one for software for which the reliability requirements are that the software must be completely fault-free, and another for requirements stated as an upper bound on the acceptable failure probability

Dioxin Toxicity In Vivo Results from an Increase in the Dioxin-Independent Transcriptional Activity of the Aryl Hydrocarbon Receptor

The Aryl hydrocarbon receptor (Ahr) is the nuclear receptor mediating the toxicity of dioxins -widespread and persistent pollutants whose toxic effects include tumor promotion, teratogenesis, wasting syndrome and chloracne. Elimination of Ahr in mice eliminates dioxin toxicity but also produces adverse effects, some seemingly unrelated to dioxin. Thus the relationship between the toxic and dioxin-independent functions of Ahr is not clear, which hampers understanding and treatment of dioxin toxicity. Here we develop a Drosophila model to show that dioxin actually increases the in vivo dioxin-independent activity of Ahr. This hyperactivation resembles the effects caused by an increase in the amount of its dimerisation partner Ahr nuclear translocator (Arnt) and entails an increased transcriptional potency of Ahr, in addition to the previously described effect on nuclear translocation. Thus the two apparently different functions of Ahr, dioxin-mediated and dioxin-independent, are in fact two different levels (hyperactivated and basal, respectively) of a single function

Chirped pulse Raman amplification in warm plasma: towards controlling saturation

Stimulated Raman backscattering in plasma is potentially an efficient method of amplifying laser pulses to reach exawatt powers because plasma is fully broken down and withstands extremely high electric fields. Plasma also has unique nonlinear optical properties that allow simultaneous compression of optical pulses to ultra-short durations. However, current measured efficiencies are limited to several percent. Here we investigate Raman amplification of short duration seed pulses with different chirp rates using a chirped pump pulse in a preformed plasma waveguide. We identify electron trapping and wavebreaking as the main saturation mechanisms, which lead to spectral broadening and gain saturation when the seed reaches several millijoules for durations of 10's - 100's fs for 250 ps, 800 nm chirped pump pulses. We show that this prevents access to the nonlinear regime and limits the efficiency, and interpret the experimental results using slowly-varying-amplitude, current-averaged particle-in-cell simulations. We also propose methods for achieving higher efficiencies.close0

Reviewing, indicating, and counting books for modern research evaluation systems

In this chapter, we focus on the specialists who have helped to improve the conditions for book assessments in research evaluation exercises, with empirically based data and insights supporting their greater integration. Our review highlights the research carried out by four types of expert communities, referred to as the monitors, the subject classifiers, the indexers and the indicator constructionists. Many challenges lie ahead for scholars affiliated with these communities, particularly the latter three. By acknowledging their unique, yet interrelated roles, we show where the greatest potential is for both quantitative and qualitative indicator advancements in book-inclusive evaluation systems.Comment: Forthcoming in Glanzel, W., Moed, H.F., Schmoch U., Thelwall, M. (2018). Springer Handbook of Science and Technology Indicators. Springer Some corrections made in subsection 'Publisher prestige or quality

Change in diet, physical activity, and body weight among young-adults during the transition from high school to college

<p>Abstract</p> <p>Background</p> <p>The freshmen year of college is likely a critical period for risk of weight gain among young-adults.</p> <p>Methods</p> <p>A longitudinal observational study was conducted to examine changes in weight, dietary intake, and other health-related behaviors among first-year college students (n = 186) attending a public University in the western United States. Weight was measured at the beginning and end of fall semester (August – December 2005). Participants completed surveys about dietary intake, physical activity and other health-related behaviors during the last six months of high school (January – June 2005) in August 2005 and during their first semester of college (August – December 2005) in December 2005.</p> <p>Results</p> <p>159 students (n = 102 women, 57 men) completed both assessments. The average BMI at the baseline assessment was 23.0 (standard deviation (SD) 3.8). Although the average amount of weight gained during the 15-week study was modest (1.5 kg), 23% of participants gained ≥ 5% of their baseline body weight. Average weight gain among those who gained ≥ 5% of baseline body weight was 4.5 kg. Those who gained ≥ 5% of body weight reported less physical activity during college than high school, were more likely to eat breakfast, and slept more than were those who did not gain ≥ 5% of body weight.</p> <p>Conclusion</p> <p>Almost one quarter of students gained a significant amount of weight during their first semester of college. This research provides further support for the implementation of education or other strategies aimed at helping young-adults entering college to achieve or maintain a healthy body weight.</p

Metal–organic complexation in the marine environment

We discuss the voltammetric methods that are used to assess metal–organic complexation in seawater. These consist of titration methods using anodic stripping voltammetry (ASV) and cathodic stripping voltammetry competitive ligand experiments (CSV-CLE). These approaches and a kinetic approach using CSV-CLE give similar information on the amount of excess ligand to metal in a sample and the conditional metal ligand stability constant for the excess ligand bound to the metal. CSV-CLE data using different ligands to measure Fe(III) organic complexes are similar. All these methods give conditional stability constants for which the side reaction coefficient for the metal can be corrected but not that for the ligand. Another approach, pseudovoltammetry, provides information on the actual metal–ligand complex(es) in a sample by doing ASV experiments where the deposition potential is varied more negatively in order to destroy the metal–ligand complex. This latter approach gives concentration information on each actual ligand bound to the metal as well as the thermodynamic stability constant of each complex in solution when compared to known metal–ligand complexes. In this case the side reaction coefficients for the metal and ligand are corrected. Thus, this method may not give identical information to the titration methods because the excess ligand in the sample may not be identical to some of the actual ligands binding the metal in the sample

Circulating levels of dickkopf-1, osteoprotegerin and sclerostin are higher in old compared with young men and women and positively associated with whole-body bone mineral density in older adults

Summary: Bone mineral density declines with increasing older age. We examined the levels of circulating factors known to regulate bone metabolism in healthy young and older adults. The circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin were positively associated with WBMD in older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young. Purpose: To investigate the relationship between whole-body bone mineral density (WBMD) and levels of circulating factors with known roles in bone remodelling during 'healthy' ageing. Methods: WBMD and fasting plasma concentrations of dickkopf-1, fibroblast growth factor-23, osteocalcin, osteoprotegerin, osteopontin and sclerostin were measured in 272 older subjects (69 to 81 years; 52% female) and 171 younger subjects (18-30 years; 53% female). Results: WBMD was lower in old than young. Circulating osteocalcin was lower in old compared with young, while dickkopf-1, osteoprotegerin and sclerostin were higher in old compared with young. These circulating factors were each positively associated with WBMD in the older adults and the relationships remained after adjustment for covariates (r-values ranging from 0.174 to 0.254, all p<0.01). In multivariate regression, the body mass index, circulating sclerostin and whole-body lean mass together accounted for 13.8% of the variation with WBMD in the older adults. In young adults, dickkopf-1 and body mass index together accounted for 7.7% of variation in WBMD. Conclusion: Circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin are positively associated with WBMD in community-dwelling older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young

Fibronectin matrix-mediated cohesion suppresses invasion of prostate cancer cells

<p>Abstract</p> <p>Background</p> <p>Invasion is an important early step in the metastatic cascade and is the primary cause of death of prostate cancer patients. In order to invade, cells must detach from the primary tumor. Cell-cell and cell-ECM interactions are important regulators of cohesion - a property previously demonstrated to mediate cell detachment and invasion. The studies reported here propose a novel role for α5β1 integrin - the principle mediator of fibronectin matrix assembly (FNMA) - as an invasion suppressor of prostate cancer cells.</p> <p>Methods</p> <p>Using a combination of biophysical and cell biological methods, and well-characterized prostate cancer cell lines of varying invasiveness, we explore the relationship between cohesion, invasiveness, and FNMA.</p> <p>Results</p> <p>We show that cohesion is inversely proportional to invasive capacity. We also show that more invasive cells express lower levels of α5β1 integrin and lack the capacity for FNMA. Cells were generated to over-express either wild-type α5 integrin or an integrin in which the cytoplasmic domain of α5 was replaced with that of α2. The α2 construct does not promote FNMA. We show that only wild-type α5 integrin promotes aggregate compaction, increases cohesion, and reduces invasion of the more aggressive cells, and that these effects can be blocked by the 70-kDa fibronectin fragment.</p> <p>Conclusions</p> <p>We propose that restoring capacity for FNMA in deficient cells can increase tumor intercellular cohesion to a point that significantly reduces cell detachment and subsequent invasion. In prostate cancer, this could be of therapeutic benefit by blocking an early key step in the metastatic cascade.</p

Characteristic Evolution and Matching

I review the development of numerical evolution codes for general relativity based upon the characteristic initial value problem. Progress in characteristic evolution is traced from the early stage of 1D feasibility studies to 2D axisymmetric codes that accurately simulate the oscillations and gravitational collapse of relativistic stars and to current 3D codes that provide pieces of a binary black hole spacetime. Cauchy codes have now been successful at simulating all aspects of the binary black hole problem inside an artificially constructed outer boundary. A prime application of characteristic evolution is to extend such simulations to null infinity where the waveform from the binary inspiral and merger can be unambiguously computed. This has now been accomplished by Cauchy-characteristic extraction, where data for the characteristic evolution is supplied by Cauchy data on an extraction worldtube inside the artificial outer boundary. The ultimate application of characteristic evolution is to eliminate the role of this outer boundary by constructing a global solution via Cauchy-characteristic matching. Progress in this direction is discussed.Comment: New version to appear in Living Reviews 2012. arXiv admin note: updated version of arXiv:gr-qc/050809