Automatic Verification of Message-Based Device Drivers

We develop a practical solution to the problem of automatic verification of the interface between device drivers and the OS. Our solution relies on a combination of improved driver architecture and verification tools. It supports drivers written in C and can be implemented in any existing OS, which sets it apart from previous proposals for verification-friendly drivers. Our Linux-based evaluation shows that this methodology amplifies the power of existing verification tools in detecting driver bugs, making it possible to verify properties beyond the reach of traditional techniques.Comment: In Proceedings SSV 2012, arXiv:1211.587

A Gadamerian approach to interpreting pain: model-making metaphors through embodied cognitive theory

This paper will discuss how the conceptualization of embodied, abstract notions such as pain, which is multi-modal, non-visual and subjective, has the potential to be communicated visually using model making, as it is traditionally understood in the fields of architecture and design. We propose a new methodological approach to research where Gadamer’s understanding of intersubjective interpretation (2004) used in conjunction with Simulation theory (Gallese and Goldman 1998) in embodied cognitive science, provides a strong framework in which to formulate a palette of materials and forms to visualize subjective experience. This novel approach to design research is currently being undertaken within the field of Health Sciences to produce metaphorically provocative, descriptive models of the lived experience of people with Rheumatoid Arthritis (RA) to help bridge the gap in understanding between the sufferer and the public. This paper seeks to engage briefly with two questions integral to the research being undertaken; how does one understand another’s pain, and how can one conceptualize and communicate abstract notions such as pain visually using material and form as language

Analyses of single marker and pairwise effects of candidate loci for rheumatoid arthritis using logistic regression and random forests

Using parametric and nonparametric techniques, our study investigated the presence of single locus and pairwise effects between 20 markers of the Genetic Analysis Workshop 15 (GAW15) North American Rheumatoid Arthritis Consortium (NARAC) candidate gene data set (Problem 2), analyzing 463 independent patients and 855 controls. Specifically, our work examined the correspondence between logistic regression (LR) analysis of single-locus and pairwise interaction effects, and random forest (RF) single and joint importance measures. For this comparison, we selected small but stable RFs (500 trees), which showed strong correlations (r~0.98) between their importance measures and those by RFs grown on 5000 trees. Both RF importance measures captured most of the LR single-locus and pairwise interaction effects, while joint importance measures also corresponded to full LR models containing main and interaction effects. We furthermore showed that RF measures were particularly sensitive to data imputation. The most consistent pairwise effect on rheumatoid arthritis was found between two markers within MAP3K7IP2/SUMO4 on 6q25.1, although LR and RFs assigned different significance levels

Pre-Virtualization: Slashing the cost of virtualization

Despite its current popularity, para-virtualization has an enormous cost. Its diversion from the platform architecture abandons many of the benefits that come with pure virtualization (the faithful emulation of the platform API): stable and well-defined platform interfaces, single binaries for kernel and device drivers (and thus lower testing, maintenance, and support cost), and vendor independence. These limitations are accepted as inevitable for significantly better performance and the ability to provide virtualization-like behavior on non-virtualizable hardware, such as x86. We argue that the above limitations are not inevitable, and present pre- virtualization, which preserves the benefits of full virtualization without sacrificing the performance benefits of para-virtualization. In a semi-automatic step an OS is prepared for virtualization. The required modifications are orders of magnitudes smaller than for para-virtualization. A virtualization module, that is collocated with the guest OS, transforms the standard platform API into the respective hypervisor API. The guest OS is still programmed against a common architecture, and the binary remains fully functional on bare hardware. The support of a new hypervisor or updated interface only requires the implementation of a single interface mapping. We validated our approach for a variety of hypervisors, on two very different hardware platforms (x86 and Itanium), with multiple generations of Linux as guests. We found that pre-virtualization achieves essentially the same performance as para-virtualization, at a fraction of the engineering cost

Entropy-driven genome organization

DNA and RNA polymerases active on bacterial and human genomes in the crowded environment of a cell are modeled as beads spaced along a string. Aggregation of the large polymerizing complexes increases the entropy of the system through an increase in entropy of the many small crowding molecules; this occurs despite the entropic costs of looping the intervening DNA. Results of a quantitative cost/benefit analysis are consistent with observations that active polymerases cluster into replication and transcription “factories” in both pro- and eukaryotes. We conclude that the second law of thermodynamics acts through nonspecific entropic forces between engaged polymerases to drive the self-organization of genomes into loops containing several thousands (and sometimes millions) of basepairs

A dynamical model reveals gene co-localizations in nucleus

Co-localization of networks of genes in the nucleus is thought to play an important role in determining gene expression patterns. Based upon experimental data, we built a dynamical model to test whether pure diffusion could account for the observed co-localization of genes within a defined subnuclear region. A simple standard Brownian motion model in two and three dimensions shows that preferential co-localization is possible for co-regulated genes without any direct interaction, and suggests the occurrence may be due to a limitation in the number of available transcription factors. Experimental data of chromatin movements demonstrates that fractional rather than standard Brownian motion is more appropriate to model gene mobilizations, and we tested our dynamical model against recent static experimental data, using a sub-diffusion process by which the genes tend to colocalize more easily. Moreover, in order to compare our model with recently obtained experimental data, we studied the association level between genes and factors, and presented data supporting the validation of this dynamic model. As further applications of our model, we applied it to test against more biological observations. We found that increasing transcription factor number, rather than factory number and nucleus size, might be the reason for decreasing gene co-localization. In the scenario of frequency-or amplitude-modulation of transcription factors, our model predicted that frequency-modulation may increase the co-localization between its targeted genes

Validation of Recently Proposed Colorectal Cancer Susceptibility Gene Variants in an Analysis of Families and Patients-a Systematic Review

High-throughput sequencing analysis has accelerated searches for genes associated with risk for colorectal cancer (CRC); germline mutations in NTHL1, RPS20, FANCM, FAN1, TP53, BUB1, BUB3, LRP6, and PTPN12 have been recently proposed to increase CRC risk. We attempted to validate the association between variants in these genes and development of CRC in a systematic review of 11 publications, using sequence data from 863 familial CRC cases and 1604 individuals without CRC (controls). All cases were diagnosed at an age of 55 years or younger and did not carry mutations in an established CRC predisposition gene. We found sufficient evidence for NTHL1 to be considered a CRC predisposition gene-members of 3 unrelated Dutch families were homozygous for inactivating p.Gln90Ter mutations; a Canadian woman with polyposis, CRC, and multiple tumors was reported to be heterozygous for the inactivating NTHL1 p.Gln90Ter/c.709+1G>A mutations; and a man with polyposis was reported to carry p.Gln90Ter/p.Gln287Ter; whereas no inactivating homozygous or compound heterozygous mutations were detected in controls. Variants that disrupted RPS20 were detected in a Finnish family with early-onset CRC (p.Val50SerfsTer23), a 39-year old individual with metachronous CRC (p.Leu61GlufsTer11 mutation), and a 41-year-old individual with CRC (missense p.Val54Leu), but not in controls. We therefore found published evidence to support the association between variants in NTHL1 and RPS20 with CRC, but not of other recently reported CRC susceptibility variants. We urge the research community to adopt rigorous statistical and biological approaches coupled with independent replication before making claims of pathogenicity

Free Schools in England: ‘Not Unlike other Schools’?

The aim of this article is to investigate the argument that choice and competition will unleash entrepreneurial innovation in free schools. Free schools were introduced as a subset of the Academies by the Conservative–Liberal Democrat Coalition government, following the general election in 2010. The government made it possible for non-state providers to set up their own independent, state-funded schools in order to create more choice, competition and innovation. We conclude that a higher level of substantive innovation is taking place in regards to management practices than in respect of curriculum and pedagogical practices. Innovation in curriculum and pedagogical practices is very limited. Creating a free school offer that seems to differ from other schools appears to be done through marketing and branding rather than innovation. We argue that parents, OFSTED, and the relative isolation of free schools constrain innovation from taking place