Stateful Testing: Finding More Errors in Code and Contracts

Automated random testing has shown to be an effective approach to finding faults but still faces a major unsolved issue: how to generate test inputs diverse enough to find many faults and find them quickly. Stateful testing, the automated testing technique introduced in this article, generates new test cases that improve an existing test suite. The generated test cases are designed to violate the dynamically inferred contracts (invariants) characterizing the existing test suite. As a consequence, they are in a good position to detect new errors, and also to improve the accuracy of the inferred contracts by discovering those that are unsound. Experiments on 13 data structure classes totalling over 28,000 lines of code demonstrate the effectiveness of stateful testing in improving over the results of long sessions of random testing: stateful testing found 68.4% new errors and improved the accuracy of automatically inferred contracts to over 99%, with just a 7% time overhead.Comment: 11 pages, 3 figure

Agrin isoforms and their role in synaptogenesis

Agrin is thought to mediate the motor neuron-induced aggregation of synaptic proteins on the surface of muscle fibers at neuromuscular junctions. Recent experiments provide direct evidence in support of this hypothesis, reveal the nature of agrin immunoreactivity at sites other than neuromuscular junctions, and have resulted in findings that are consistent with the possibility that agrin plays a role in synaptogenesis throughout the nervous system

Mechanical Properties of Collagen Fibrils

AbstractThe formation of collagen fibers from staggered subfibrils still lacks a universally accepted model. Determining the mechanical properties of single collagen fibrils (diameter 50–200nm) provides new insights into collagen structure. In this work, the reduced modulus of collagen was measured by nanoindentation using atomic force microscopy. For individual type 1 collagen fibrils from rat tail, the modulus was found to be in the range from 5 GPa to 11.5GPa (in air and at room temperature). The hypothesis that collagen anisotropy is due to the subfibrils being aligned along the fibril axis is supported by nonuniform surface imprints performed by high load nanoindentation

Single live-cell imaging for systems biology

Understanding how mammalian cells function requires a dynamic perspective. However, due to the complexity of signalling networks these non-linear systems can easily elude human intuition. The central aim of systems biology is to improve our understanding of the temporal complexity of cell signalling pathways, using a combination of experimental and computational approaches. Live cell imaging and computational modelling are compatible techniques which allow quantitative analysis of cell signalling pathway dynamics. Non-invasive imaging techniques, based on the use of various luciferases and fluorescent proteins, trace cellular events such as gene expression, protein-protein interactions and protein localisation in cells. By employing a number of markers in a single assay, multiple parameters can be measured simultaneously in the same cell. Following acquisition using specialised microscopy, analysis of multi-parameter time-lapse images facilitates the identification of important qualitative and quantitative relationships – linking intracellular signalling, gene expression and cell fate. Improvements in reporter genes coupled with significant advances in detector technologies, are now allowing us to image gene expression non-invasively in individual living cells. These methods are providing remarkable insights into the dynamics of gene expression during complex processes, such as the cell cycle and the responses of cells to hormones, growth factors and nutrients. On a larger scale, dynamics of gene expression may also be monitored in living organisms. This new technology will greatly assist attempts to decipher the complex behaviours exhibited by biological signalling networks, for instance the ability to integrate multiple input signals over time, and generate specific outputs

Adalimumab in Juvenile Idiopathic Arthritis–Associated Uveitis:5-Year Follow-up of the Bristol Participants of the SYCAMORE Trial

PURPOSE:To determine longer-term outcomes of participants enrolled from a single center in the SYCAMORE trial, a randomized placebo-controlled trial of adalimumab versus placebo in children with juvenile idiopathic arthritis-associated uveitis (JIA-U) uncontrolled on methotrexate. DESIGN:Retrospective interventional case series. METHODS:Medical records of all 28 SYCAMORE participants recruited at the Bristol Eye Hospital were reviewed at approximately 3-monthly intervals up to 5 years from the trial randomization date. Uveitis activity, treatment course, visual outcomes, ocular complications and adverse events were recorded. Data are presented using summary statistics. RESULTS:Following withdrawal of the investigational medicinal product (IMP), 25 of the 28 participants were started on adalimumab for active juvenile idiopathic arthritis-associated uveitis (JIA-U). Of the 12 participants in the active treatment arm of the SYCAMORE study, 11 (92%) were restarted on adalimumab after withdrawal of the IMP for active JIA-U (median time to flare 188 days (range 42-413)). Two participants stopped adalimumab for uncontrolled JIA-U. One participant had a reduction in vision to 0.3 due to cataract. Mean visual acuity for the remaining 27 participants was -0.04 (right eye) and -0.05 (left eye). CONCLUSIONS:Drug-induced remission of JIA-U did not persist when adalimumab was withdrawn after 1-2 years treatment. Adalimumab was well tolerated and visual acuity outcomes were excellent

Bis(triphenyl­phospho­ranyl­idene)ammonium iodide

The title compound, C36H30NP2 +·I−, was obtained accidently from crystallization of a reaction mixture containing [(Ph3P)2N]OH and B(OH)3, which was contaminated with MeI. There are two independent [(Ph3P)2N]+ cations and two I− anions within the asymmetric unit. The central PNP angles are non-linear [137.6 (2) and 134.4 (2)°] and the phenyl substituents on P centres adopt different conformations within these two cations

Increased threat of tropical cyclones and coastal flooding to New York City during the anthropogenic era

Author Posting. © The Author(s), 2015. This is the author's version of the work. It is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences of the United States of America 112 (2015): 12610-12615, doi:10.1073/pnas.1513127112.In a changing climate, future inundation of the United States’ Atlantic coast will depend on both storm surges during tropical cyclones and the rising relative sea-levels on which those surges occur. However, the observational record of tropical cyclones in the North Atlantic basin is too short (AD 1851-present) to accurately assess long-term trends in storm activity. To overcome this limitation, we use proxy sealevel records, and downscale three CMIP5 models to generate large synthetic tropical cyclone data sets for the North Atlantic basin; driving climate conditions span from AD 850 to AD 2005. We compare preanthropogenic era (AD 850 – AD 1800) and anthropogenic era (AD 1970 – AD 2005) storm-surge model results for New York City, exposing links between increased rates of sea-level rise and storm flood heights. We find that mean flood heights increased by ~1.24 m (due mainly to sea level rise) from ~AD 850 to the anthropogenic era, a result that is significant at the 99% confidence level. Additionally, changes in tropical cyclone characteristics have led to increases in the extremes of the types of storms that create the largest storm surges for New York City. As a result, flood risk has greatly increased for the region; for example, the 500 year return period for a ~2.25 m flood height during the preanthropogenic era has decreased to ~24.4 years in the anthropogenic era. Our results indicate the impacts of climate change on coastal inundation, and call for advanced risk management strategies.The authors acknowledge funding for this study from NOAA Grants # 424-18 45GZ and # NA11OAR4310101 and National Science Foundation award OCE 1458904.2016-03-2