Declarative Specification

Deriving formal specifications from informal requirements is extremely difficult since one has to overcome the conceptual gap between an application domain and the domain of formal specification methods. To reduce this gap we introduce application-specific specification languages, i.e., graphical and textual notations that can be unambiguously mapped to formal specifications in a logic language. We describe a number of realised approaches based on this idea, and evaluate them with respect to their domain specificity vs. generalit

On the origins of Mendelian disease genes in man: the impact of gene duplication

Over 3,000 human diseases are known to be linked to heritable genetic variation, mapping to over 1,700 unique genes. Dating of the evolutionary age of these disease-associated genes has suggested that they have a tendency to be ancient, specifically coming into existence with early metazoa. The approach taken by past studies, however, assumes that the age of a disease is the same as the age of its common ancestor, ignoring the fundamental contribution of duplication events in the evolution of new genes and function. Here, we date both the common ancestor and the duplication history of known human disease-associated genes. We find that the majority of disease genes (80%) are genes that have been duplicated in their evolutionary history. Periods for which there are more disease-associated genes, for example, at the origins of bony vertebrates, are explained by the emergence of more genes at that time, and the majority of these are duplicates inferred to have arisen by whole-genome duplication. These relationships are similar for different disease types and the disease-associated gene's cellular function. This indicates that the emergence of duplication-associated diseases has been ongoing and approximately constant (relative to the retention of duplicate genes) throughout the evolution of life. This continued until approximately 390 Ma from which time relatively fewer novel genes came into existence on the human lineage, let alone disease genes. For single-copy genes associated with disease, we find that the numbers of disease genes decreases with recency. For the majority of duplicates, the disease-associated mutation is associated with just one of the duplicate copies. A universal explanation for heritable disease is, thus, that it is merely a by-product of the evolutionary process; the evolution of new genes (de novo or by duplication) results in the potential for new diseases to emerge

Declarative specifications

Deriving formal specifications from informal requirements is extremely difficult since one has to overcome the conceptual gap between an application domain and the domain of formal specification methods. To reduce this gap we introduce application-specific specification languages, i.e., graphical and textual notations that can be unambiguously mapped to formal specifications in a logic language. We describe a number of realised approaches based on this idea, and evaluate them with respect to their domain specificity vs. generalit

The relationship between self-reported sensory experiences and autistic traits in the general population:a mixed methods analysis

There have been few examples of inductive research in sensory reactivity, particularly in relation to autistic traits among the general population. This study used a mixed methods approach to explore the nature of sensory experiences among people with different levels of autistic traits. Participants completed the Glasgow Sensory Questionnaire and the Autism Spectrum Quotient. Both quantitative and qualitative analyses were performed on the data. Responses to the open questions were analyzed as part of this study, and the closed questionnaire data have been reported elsewhere. Data were coded and responses quantitatively compared by group. In addition, data were qualitatively analyzed using a general inductive approach, which resulted in two themes: “problematic sensory experiences” and “calming sensory experiences.” Results show that coping mechanisms and certain aspects of the sensory experience vary according to autistic trait level, and provide insight into the nature of sensory reactivity across the general population

The biological context of HIV-1 host interactions reveals subtle insights into a system hijack

<p>Abstract</p> <p>Background</p> <p>In order to replicate, HIV, like all viruses, needs to invade a host cell and hijack it for its own use, a process that involves multiple protein interactions between virus and host. The HIV-1, Human Protein Interaction Database available at NCBI's website captures this information from the primary literature, containing over 2,500 unique interactions. We investigate the general properties and biological context of these interactions and, thus, explore the molecular specificity of the HIV-host perturbation. In particular, we investigate (i) whether HIV preferentially interacts with highly connected and 'central' proteins, (ii) known phenotypic properties of host proteins inferred from essentiality and disease-association data, and (iii) biological context (molecular function, processes and location) of the host proteins to identify attributes most strongly associated with specific HIV interactions.</p> <p>Results</p> <p>After correcting for ascertainment bias in the literature, we demonstrate a significantly greater propensity for HIV to interact with highly connected and central host proteins. Unexpectedly, we find there are no associations between HIV interaction and inferred essentiality. Similarly, we find a tendency for HIV not to interact with proteins encoded by genes associated with disease. Crucially, we find that functional categories over-represented in HIV-host interactions are innately enriched for highly connected and central proteins in the host system.</p> <p>Conclusions</p> <p>Our results imply that HIV's propensity to interact with highly connected and central proteins is a consequence of interactions with particular cellular functions, rather than being a direct effect of network topological properties. The lack of a propensity for interactions with phenotypically essential proteins suggests a selective pressure to minimise virulence in retroviral evolution. Thus, the specificity of HIV-host interactions is complex, and only superficially explained by network properties.</p

Crowdworker Economics in the Gig Economy

The nature of work is changing. As labor increasingly trends to casual work in the emerging gig economy, understanding the broader economic context is crucial to effective engage- ment with a contingent workforce. Crowdsourcing represents an early manifestation of this fluid, laisser-faire, on-demand workforce. This work analyzes the results of four large-scale surveys of US-based Amazon Mechanical Turk workers recorded over a six-year period, providing compa- rable measures to national statistics. Our results show that despite unemployment far higher than national levels, crowd- workers are seeing positive shifts in employment status and household income. Our most recent surveys indicate a trend away from full-time-equivalent crowdwork, coupled with a reduction in estimated poverty levels to below national figures. These trends are indicative of an increasingly flexible workforce, able to maximize their opportunities in a rapidly changing national labor market, which may have material impacts on existing models of crowdworker behavior.This work was supported by an EPSRC studentship and EPSRC grants EP/N010558/1 and EP/R004471/1

An integrated CFD/experimental analysis of aerodynamic forces and moments

Aerodynamic analysis using computational fluid dynamics (CFD) is most fruitful when it is combined with a thorough program of wind tunnel testing. The understanding of aerodynamic phenomena is enhanced by the synergistic use of both analysis methods. A technique is described for an integrated approach to determining the forces and moments acting on a wind tunnel model by using a combination of experimentally measured pressures and CFD predictions. The CFD code used was FLO57 (an Euler solver) and the wind tunnel model was a heavily instrumented delta wing with 62.5 deg of leading-edge sweep. A thorough comparison of the CFD results and the experimental data is presented for surface pressure distributions and longitudinal forces and moments. The experimental pressures were also integrated over the surface of the model and the resulting forces and moments are compared to the CFD and wind tunnel results. The accurate determination of various drag increments via the combined use of the CFD and experimental pressures is presented in detail

Successful management of elderly breast cancer patients treated without radiotherapy

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background Breast cancer in the elderly may follow a less aggressive course. There are data suggesting that radiotherapy (RT) following breast conserving surgery (BCS) for invasive carcinoma may not be necessary in some elderly patients. The addition of RT to surgery might constitute an imposition to such patients due to age-related factors. The aim of this study was to assess the efficacy of BCS without adjuvant RT in this group of patients. Patients and methods A retrospective review of 92 elderly (median age 75 years; range: 70 – 87 years) patients (analysed as 93 'patients' due to one patient having bilateral cancers) managed in a dedicated breast clinic and who underwent BCS for invasive carcinoma was carried out. Eighty-three patients did not receive postoperative RT to the breast (no-RT group) whereas the remaining 10 had RT (RT-group). Results The median age in this group was 75 (range 70 – 87) years. The mean tumour size was 18 mm with a median follow-up of 37 (range 6 – 142) months. In the no RT group, adjuvant endocrine therapy with tamoxifen was given to 40/53 patients. No patients in the oestrogen receptor (ER) negative group received tamoxifen. The local recurrence (LR) rate in this group was 8.4% (2.4% per year, n = 7/83), with median time to LR of 17 months. In this no-RT group LR was correlated to ER status (2/53 ER+, 5/26ER-, p = 0.024) and margins of excision (n = 1/54 >5 mm, 2/17 1–5 mm, 4/12 <1 mm, p = 0.001). Within the ER positive group the LR rate was 0.92% per annum (0.62% per annum in patients treated with adjuvant tamoxifen, regardless of margin status). Breast cancer specific survival was correlated to histological grade (p < 0.05) and ER status (p < 0.05). Conclusion It would appear that omission of RT following successful BCS in elderly patients with ER positive tumours receiving adjuvant tamoxifen may be acceptable. The LR rate as shown in this retrospective study is highly comparable to that of younger patients treated by conventional therapy. This concept is now being evaluated prospectively following a change in treatment practice.Published versio

The effect of fiber orientation on the toughening of short fiber-reinforced polymers

The effect of fiber orientation on the toughening of polymers by short glass fibers generally below their critical length was investigated using specimens with either well-aligned or randomly oriented fibers. The fibers were aligned by an electric field in a photopolymerizable monomer, which was polymerized while the field was still being applied. These materials were fractured with the aligned fibers in three orientations with respect to the crack plane and propagation direction. Specimens with fibers aligned normal to the fracture plane were the most tough, those with randomly oriented fibers were less tough, and those with fibers aligned within the fracture plane were the least tough. The fracture behaviors compared favorably with predictions based on observed processes accounting for fiber orientation. The processes considered were fiber pull-out (including snubbing), fiber breakage, fiber–matrix debonding, and localized matrix-yielding adjacent to fibers bridging the fracture plane. Fibers not quite perpendicular to the fracture plane provided the greatest toughening; these fibers pulled out completely and gave a significant contribution from snubbing. Fibers at higher angles provided less toughening, involving nearly equal contributions from pull-out, breakage, and debonding. Fibers within the fracture plane provided the least toughening, involving debonding alone. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 2740–2751, 2003Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34402/1/12913_ftp.pd