Stepwise refinement of interrupt-driven real-time programs

Embedded real-time programs rely on external interrupts to respond to events in their physical environment in a timely fashion. Formal program verification theories, such as the refinement calculus, are intended for development of sequential, block-structured code and do not allow for asynchronous control constructs such as interrupt service routines. In this article we extend the refinement calculus to support formal development of interrupt-dependent programs. To do this we: use a timed semantics, to support reasoning about the occurrence of interrupts within bounded time intervals; introduce a restricted form of concurrency, to model composition of interrupt service routines with the main program they may preempt; introduce a semantics for shared variables, to model contention for variables accessed by both interrupt service routines and the main program; and use real-time scheduling theory to discharge timing requirements on interruptible program code.

A semi-local method for iterative depth-map refinement

We present an iterative hierarchical algorithm for multi-view stereo. The algorithm attempts to utilise as much contextual information as is available to compute highly accurate and robust depth maps. There are three novel aspects to the approach: 1) firstly we incrementally improve the depth fidelity as the algorithm progresses through the image pyramid; 2) secondly we show how to incorporate visual hull information (when available) to constrain depth searches; and 3) we show how to simultaneously enforce the consistency of the depth-map by continual comparison with neighbouring depth-maps. We show that this approach produces highly accurate depth-maps and, since it is essentially a local method, is both extremely fast and simple to implement.

An examination of the factorial invariance and refinement of the multidimensional school anger inventory for five Pacific Rim countries

The validity of the Multidimensional School Anger Inventory (MSAI) was examined with adolescents from 5 Pacific Rim countries (N ¼ 3,181 adolescents; age, M ¼ 14.8 years; 52% females). Confirmatory factor analyses examined configural invariance for the MSAI’s anger experience, hostility, destructive expression, and anger coping subscales. The model did not converge for Peruvian students. Using the top 4 loaded items for anger experience, hostility, and destructive expression configural invariance and partial metric and scalar invariances were found. Latent means analysis compared mean responses on each subscale to the U.S. sample. Students from other countries showed higher mean responses on the anger experience subscale (ds ¼ .37–.73). Australian (d ¼ .40) and Japanese students (d ¼ .21) had significantly higher mean hostility subscale scores. Australian students had higher mean scores on the destructive expression subscale (d ¼ .30), whereas Japanese students had lower mean scores (d ¼ 2.17). The largest latent mean gender differences (females lower than males) were for destructive expression among Australian (d ¼ 2.67), Guatemalan (d ¼ 2.42), and U.S. (d ¼ 2.66) students. This study supported an abbreviated, 12-item MSAI with partial invariance. Implications for the use of the MSAI in comparative research are discussed.

Selective involvement of TIMP-2 in the second activational cleavage of pro-MMP-2 : refinement of the pro-MMP-2 activation mechanism

A tissue inhibitor of metalloproteinases-2 (TIMP-2)-independent mechanism for generating the first activational cleavage of pro-matrix metalloproteinase-2 (MMP-2) was identified in membrane type-1 MMP (MT1-MMP)-transfected MCF-7 cells and confirmed in TIMP-2-deficient fibroblasts. In contrast, the second MMP-2-activational step was found to be TIMP-2 dependent in both systems. MMP-2 hemopexin C-terminal domain was found to be critical for the first step processing, confirming a need for membrane tethering. We propose that the intermediate species of MMP-2 forms the well-established trimolecular complex (MT1-MMP/TIMP-2/MMP-2) for further TIMP-2-dependent autocatalytic cleavage to the fully active species. This alternate mechanism may supplement the traditional TIMP-2-mediated first step mechanism.

Model refinement through high-performance computing: an agent-based HIV example

Background Recent advances in Immunology highlighted the importance of local properties on the overall progression of HIV infection. In particular, the gastrointestinal tract is seen as a key area during early infection, and the massive cell depletion associated with it may influence subsequent disease progression. This motivated the development of a large-scale agent-based model. Results Lymph nodes are explicitly implemented, and considerations on parallel computing permit large simulations and the inclusion of local features. The results obtained show that GI tract inclusion in the model leads to an accelerated disease progression, during both the early stages and the long-term evolution, compared to a theoretical, uniform model. Conclusions These results confirm the potential of treatment policies currently under investigation, which focus on this region. They also highlight the potential of this modelling framework, incorporating both agent-based and network-based components, in the context of complex systems where scaling-up alone does not result in models providing additional insights.

The development and refinement of the practice domain framework as a conceptual tool for understanding and guiding social care practice

This study identified the common factors that influence social care practice across disciplines (such as social work and psychology), practice fields, and geographical contexts and further developed the Practice Domain Framework as an empirically-based conceptual framework to assist practitioners in understanding practice complexities. The framework has application in critical reflection, professional supervision, interdisciplinary understanding, teamwork, management, teaching and research. A mixed-methods design was used to identify the components and structure of the refined framework. Eighteen influential factors were identified and organised into eight domains: the Societal, Structural, Organisational, Practice Field, Professional Practice, Accountable Practice, Community of Place, and Personal.

Bayesian refinement of association signals for 14 loci in 3 common diseases

To further investigate susceptibility loci identified by genome-wide association studies, we genotyped 5,500 SNPs across 14 associated regions in 8,000 samples from a control group and 3 diseases: type 2 diabetes (T2D), coronary artery disease (CAD) and Graves' disease. We defined, using Bayes theorem, credible sets of SNPs that were 95% likely, based on posterior probability, to contain the causal disease-associated SNPs. In 3 of the 14 regions, TCF7L2 (T2D), CTLA4 (Graves' disease) and CDKN2A-CDKN2B (T2D), much of the posterior probability rested on a single SNP, and, in 4 other regions (CDKN2A-CDKN2B (CAD) and CDKAL1, FTO and HHEX (T2D)), the 95% sets were small, thereby excluding most SNPs as potentially causal. Very few SNPs in our credible sets had annotated functions, illustrating the limitations in understanding the mechanisms underlying susceptibility to common diseases. Our results also show the value of more detailed mapping to target sequences for functional studies. © 2012 Nature America, Inc. All rights reserved.

High-resolution refinement of orthorhombic bovine pancreatic phospholipase A2

The X-ray structure of recombinant bovine pancreatic phospholipase A(2) (PLA2), which specifically catalyzes the cleavage of the sn-2 acylester bond of phospholipids, has been refined at 1.5 Angstrom resolution. The crystal belongs to the space group P2(1)2(1)2(1) with unit-cell parameters a = 47.12, b = 64.59 and c = 38.14 Angstrom similar to the native enzyme reported previously by Dijkstra et nl. [J. Mel. Biol. (1981), 147, 97-123]. The refinement converged to an R value of 18.4% (R-free = 22.8%) for 16 374 reflections between 10.0 and 1.5 Angstrom resolution. The surface-loop residues (60-70) art: ordered in the present orthorhombic recombinant enzyme, but disordered in the trigonal recombinant enzyme. The active-site residues, His48, Asp99, and the catalytic water superimpose well with the trigonal form. Besides the catalytic water which is hydrogen bonded to His48, it is often seen that there is a second water attached to the same N atom of His48 and simultaneously hydrogen bonded to the O atom of Asp49. It is thought that the second water facilitates the tautomerism of His48 for enzyme catalysis, The catalytic water is also hydrogen bonded to the equatorial water coordinated to the calcium ion, In addition to the equatorial water, there is also an axial calcium water and the additional structural water. These five common water molecules are hydrogen bonded to the additional 16 water molecules in the present orthorhombic structure which may further enhance the structural integrity of the active site. Besides the protein and one calcium ion, a total of 134 water molecules were located in the present high-resolution refinement.

Refinement of defection strategies stabilizes cooperation

Cooperation among unrelated individuals is an enduring evolutionary riddle and a number of possible solutions have been suggested. Most of these suggestions attempt to refine cooperative strategies, while little attention is given to the fact that novel defection strategies can also evolve in the population. Especially in the presence of punishment to the defectors and public knowledge of strategies employed by the players, a defecting strategy that avoids getting punished by selectively cooperating only with the punishers can get a selective benefit over non-conditional defectors. Furthermore, if punishment ensures cooperation from such discriminating defectors, defectors who punish other defectors can evolve as well. We show that such discriminating and punishing defectors can evolve in the population by natural selection in a Prisoner’s Dilemma game scenario, even if discrimination is a costly act. These refined defection strategies destabilize unconditional defectors. They themselves are, however, unstable in the population. Discriminating defectors give selective benefit to the punishers in the presence of non-punishers by cooperating with them and defecting with others. However, since these players also defect with other discriminators they suffer fitness loss in the pure population. Among the punishers, punishing cooperators always benefit in contrast to the punishing defectors, as the latter not only defect with other punishing defectors but also punish them and get punished. As a consequence of both these scenarios, punishing cooperators get stabilized in the population. We thus show ironically that refined defection strategies stabilize cooperation. Furthermore, cooperation stabilized by such defectors can work under a wide range of initial conditions and is robust to mistakes.