Steps in modular specifications for concurrent modules

© 2015 Published by Elsevier B.V.The specification of a concurrent program module is a difficult problem. The specifications must be strong enough to enable reasoning about the intended clients without reference to the underlying module implementation. We survey a range of verification techniques for specifying concurrent modules, in particular highlighting four key concepts: auxiliary state, interference abstraction, resource ownership and atomicity. We show how these concepts combine to provide powerful approaches to specifying concurrent modules

The Neuroscience Information Framework: A Data and Knowledge Environment for Neuroscience

With support from the Institutes and Centers forming the NIH Blueprint for Neuroscience Research, we have designed and implemented a new initiative for integrating access to and use of Web-based neuroscience resources: the Neuroscience Information Framework. The Framework arises from the expressed need of the neuroscience community for neuroinformatic tools and resources to aid scientific inquiry, builds upon prior development of neuroinformatics by the Human Brain Project and others, and directly derives from the Society for Neuroscience’s Neuroscience Database Gateway. Partnered with the Society, its Neuroinformatics Committee, and volunteer consultant-collaborators, our multi-site consortium has developed: (1) a comprehensive, dynamic, inventory of Web-accessible neuroscience resources, (2) an extended and integrated terminology describing resources and contents, and (3) a framework accepting and aiding concept-based queries. Evolving instantiations of the Framework may be viewed at http://nif.nih.gov, http://neurogateway.org, and other sites as they come on line

Large-Scale Structures Behind the Milky Way from Near-IR Surveys

About 25% of the optical extragalactic sky is obscured by the dust and stars of our Milky Way. Dynamically important structures might still lie hidden in this zone. Various approaches are presently being employed to uncover the galaxy distribution in the Zone of Avoidance (ZOA) but all suffer from (different) limitations and selection effects. We investigated the potential of using the DENIS NIR survey for studies of galaxies behind the obscuration layer of our Milky Way and for mapping the Galactic extinction. As a pilot study, we recovered DENIS I, J and K band images of heavily obscured but optically still visible galaxies. We determined the I, J and K band luminosity functions of galaxies on three DENIS strips that cross the center of the nearby, low-latitude, rich cluster Abell 3627. The extinction-corrected I-J and J-K colours of these cluster galaxies compare well with that of an unobscured cluster. We searched for and identified galaxies at latitudes where the Milky Way remains fully opaque (|b| 4-5mag) - in a systematic search as well as around positions of galaxies detected with the blind HI survey of the ZOA currently conducted with the Multibeam Receiver of the Parkes Radiotelescope.Comment: 12 pages, including 5 PS figures, LaTeX, uses crckapb.sty and epsf.tex. Better resolved figures available upon request. To appear in proceedings of the 3rd Euroconference (Meudon, France, June 1997) on ``The Impact of Near IR Surveys'', Kluwer 199

A risk profile for identifying community-dwelling elderly with a highrisk of recurrent falling: results of a 3-year prospective study

Introduction: The aim of the prospective study reported here was to develop a risk profile that can be used to identify community-dwelling elderly at a high risk of recurrent falling. Materials and methods: The study was designed as a 3-year prospective cohort study. A total of 1365 community-dwelling persons, aged 65 years and older, of the population-based Longitudinal Aging Study Amsterdam participated in the study. During an interview in 1995/1996, physical, cognitive, emotional and social aspects of functioning were assessed. A follow-up on the number of falls and fractures was conducted during a 3-year period using fall calendars that participants filled out weekly. Recurrent fallers were identified as those who fell at least twice within a 6-month period during the 3-year follow-up. Results: The incidence of recurrent falls at the 3-year follow-up point was 24.9% in women and 24.4% in men. Of the respondents, 5.5% reported a total of 87 fractures that resulted from a fall, including 20 hip fractures, 21 wrist fractures and seven humerus fractures. Recurrent fallers were more prone to have a fall-related fracture than those who were not defined as recurrent fallers (11.9% vs. 3.4%; OR: 3.8; 95% CI: 2.3-6.1). Backward logistic regression analysis identified the following predictors in the risk profile for recurrent falling: two or more previous falls, dizziness, functional limitations, weak grip strength, low body weight, fear of falling, the presence of dogs/cats in the household, a high educational level, drinking 18 or more alcoholic consumptions per week and two interaction terms (high educationx18 or more alcohol consumptions per week and two or more previous falls x fear of falling) (AUC=0.71). Discussion: At a cut-off point of 5 on the total risk score (range 0-30), the model predicted recurrent falling with a sensitivity of 59% and a specificity of 71%. At a cut-off point of 10, the sensitivity and specificity were 31% and 92%, respectively. A risk profile including nine predictors that can easily be assessed seems to be a useful tool for the identification of community-dwelling elderly with a high risk of recurrent falling. © International Osteoporosis Foundation and National Osteoporosis Foundation 2006

JaVerT: JavaScript verification toolchain

The dynamic nature of JavaScript and its complex semantics make it a difficult target for logic-based verification. We introduce JaVerT, a semi-automatic JavaScript Verification Toolchain, based on separation logic and aimed at the specialist developer wanting rich, mechanically verified specifications of critical JavaScript code. To specify JavaScript programs, we design abstractions that capture its key heap structures (for example, prototype chains and function closures), allowing the developer to write clear and succinct specifications with minimal knowledge of the JavaScript internals. To verify JavaScript programs, we develop JaVerT, a verification pipeline consisting of: JS-2-JSIL, a well-tested compiler from JavaScript to JSIL, an intermediate goto language capturing the fundamental dynamic features of JavaScript; JSIL Verify, a semi-automatic verification tool based on a sound JSIL separation logic; and verified axiomatic specifications of the JavaScript internal functions. Using JaVerT, we verify functional correctness properties of: data-structure libraries (key-value map, priority queue) written in an object-oriented style; operations on data structures such as binary search trees (BSTs) and lists; examples illustrating function closures; and test cases from the official ECMAScript test suite. The verification times suggest that reasoning about larger, more complex code using JaVerT is feasible

Functional claudication distance: a reliable and valid measurement to assess functional limitation in patients with intermittent claudication

BACKGROUND: Disease severity and functional impairment in patients with intermittent claudication is usually quantified by the measurement of pain-free walking distance (intermittent claudication distance, ICD) and maximal walking distance (absolute claudication distance, ACD). However, the distance at which a patient would prefer to stop because of claudication pain seems a definition that is more correspondent with the actual daily life walking distance. We conducted a study in which the distance a patient prefers to stop was defined as the functional claudication distance (FCD), and estimated the reliability and validity of this measurement. METHODS: In this clinical validity study we included patients with intermittent claudication, following a supervised exercise therapy program. The first study part consisted of two standardised treadmill tests. During each test ICD, FCD and ACD were determined. Primary endpoint was the reliability as represented by the calculated intra-class correlation coefficients. In the second study part patients performed a standardised treadmill test and filled out the Rand-36 questionnaire. Spearman's rho was calculated to assess validity. RESULTS: The intra-class correlation coefficients of ICD, FCD and ACD were 0.940, 0.959, and 0.975 respectively. FCD correlated significantly with five out of nine domains, namely physical function (rho = 0.571), physical role (rho = 0.532), vitality (rho = 0.416), pain (rho = 0.416) and health change (rho = 0.414). CONCLUSION: FCD is a reliable and valid measurement for determining functional capacity in trained patients with intermittent claudication. Furthermore it seems that FCD better reflects the actual functional impairment. In future studies, FCD could be used alongside ICD and ACD

Long-Time Asymptotics for the Korteweg-de Vries Equation via Nonlinear Steepest Descent

We apply the method of nonlinear steepest descent to compute the long-time asymptotics of the Korteweg-de Vries equation for decaying initial data in the soliton and similarity region. This paper can be viewed as an expository introduction to this method.Comment: 31 page

Structural Determinants of the Dictyostatin Chemotype for Tubulin Binding Affinity and Antitumor Activity Against Taxane- and Epothilone-Resistant Cancer Cells

A combined biochemical, structural, and cell biology characterization of dictyostatin is described, which enables an improved understanding of the structural determinants responsible for the high-affinity binding of this anticancer agent to the taxane site in microtubules (MTs). The study reveals that this macrolide is highly optimized for MT binding and that only a few of the structural modifications featured in a library of synthetic analogues resulted in small gains in binding affinity. The high efficiency of the dictyostatin chemotype in overcoming various kinds of clinically relevant resistance mechanisms highlights its potential for therapeutic development for the treatment of drug-resistant tumors. A structural explanation is advanced to account for the synergy observed between dictyostatin and taxanes on the basis of their differential effects on the MT lattice. The X-ray crystal structure of a tubulin−dictyostatin complex and additional molecular modeling have allowed the rationalization of the structure−activity relationships for a set of synthetic dictyostatin analogues, including the highly active hybrid 12 with discodermolide. Altogether, the work reported here is anticipated to facilitate the improved design and synthesis of more efficacious dictyostatin analogues and hybrids with other MT-stabilizing agents.We thank Peter T. Northcote for peloruside A, W.-S. Fang for Flutax-2, K. H. Altmann for epothilone D, Dr. Paraskevi Giannakakou (Weill Cornell Medical Center, New York) for the 1A9, PTX10, PTX22, and A8 cell lines, and Prof. Richard Ludueñ a (University of Texas) for the HeLa βIII-transfected cells. We thank Matadero INCOVA (Segovia) for the calf brains for tubulin purification. This work was supported in part by grants BIO2013-42984-R (J.F.D.) and SAF2012-39760-C02-02 (F.G.) from Ministerio de Economia y Competitividad, grant S2010/ ́ BMD-2457 BIPEDD2 from Comunidad Autonoma de Madrid ́ (F.G. and J.F.D.), and the Swiss National Science Foundation grants 310030B_138659 and 31003A_166608 (M.O.S.). The authors acknowledge networking contribution by the COST Action CM1407 “Challenging organic syntheses inspired by naturefrom natural products chemistry to drug discovery” and the COST action CM1470. I.P. thanks the EPSRC and AstraZeneca for funding, Dr. John Leonard (AstraZeneca) for useful discussions, Dr. Stuart Mickel (Novartis) for the provision of chemicals, and the EPSRC UK National Mass Spectrometry Facility at Swansea University for mass spectra

On the Transfer of Damage Detectors Between Structures: An Experimental Case Study

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordIncomplete data – which fail to represent environmental effects or damage – are a significant challenge for structural health monitoring (SHM). Population-based frameworks offer one solution by considering that information might be shared, in some sense, between similar structures. In this work, the data from a group of aircraft tailplanes are considered collectively, in a shared (more consistent) latent space. As a result, the measurements from one tailplane enable damage detection in another, utilising various pair-wise comparisons within the population. Specifically, Transfer Component Analysis (TCA) is applied to match the normal condition data from different population members. The resulting nonlinear projection leads to a general representation for the normal condition across the population, which informs damage detection via measures of discordancy. The method is applied to a experimental dataset, based on vibration-based laser vibrometer measurements from three tailplanes. By considering the partial datasets together, consistent damage-sensitive features can be defined, leading to an 87% increase in the true positive rate, compared to conventional SHM.Engineering and Physical Sciences Research Council (EPSRC

Structural Determinants of the Dictyostatin Chemotype for Tubulin Binding Affinity and Antitumor Activity Against Taxane- and Epothilone-Resistant Cancer Cells

A combined biochemical, structural, and cell biology characterization of dictyostatin is described, which enables an improved understanding of the structural determinants responsible for the high-affinity binding of this anticancer agent to the taxane site in microtubules (MTs). The study reveals that this macrolide is highly optimized for MT binding and that only a few of the structural modifications featured in a library of synthetic analogues resulted in small gains in binding affinity. The high efficiency of the dictyostatin chemotype in overcoming various kinds of clinically relevant resistance mechanisms highlights its potential for therapeutic development for the treatment of drug-resistant tumors. A structural explanation is advanced to account for the synergy observed between dictyostatin and taxanes on the basis of their differential effects on the MT lattice. The X-ray crystal structure of a tubulin−dictyostatin complex and additional molecular modeling have allowed the rationalization of the structure−activity relationships for a set of synthetic dictyostatin analogues, including the highly active hybrid 12 with discodermolide. Altogether, the work reported here is anticipated to facilitate the improved design and synthesis of more efficacious dictyostatin analogues and hybrids with other MT-stabilizing agents.We thank Peter T. Northcote for peloruside A, W.-S. Fang for Flutax-2, K. H. Altmann for epothilone D, Dr. Paraskevi Giannakakou (Weill Cornell Medical Center, New York) for the 1A9, PTX10, PTX22, and A8 cell lines, and Prof. Richard Ludueñ a (University of Texas) for the HeLa βIII-transfected cells. We thank Matadero INCOVA (Segovia) for the calf brains for tubulin purification. This work was supported in part by grants BIO2013-42984-R (J.F.D.) and SAF2012-39760-C02-02 (F.G.) from Ministerio de Economia y Competitividad, grant S2010/ ́ BMD-2457 BIPEDD2 from Comunidad Autonoma de Madrid ́ (F.G. and J.F.D.), and the Swiss National Science Foundation grants 310030B_138659 and 31003A_166608 (M.O.S.). The authors acknowledge networking contribution by the COST Action CM1407 “Challenging organic syntheses inspired by naturefrom natural products chemistry to drug discovery” and the COST action CM1470. I.P. thanks the EPSRC and AstraZeneca for funding, Dr. John Leonard (AstraZeneca) for useful discussions, Dr. Stuart Mickel (Novartis) for the provision of chemicals, and the EPSRC UK National Mass Spectrometry Facility at Swansea University for mass spectra