The design-by-adaptation approach to universal access: learning from videogame technology

This paper proposes an alternative approach to the design of universally accessible interfaces to that provided by formal design frameworks applied ab initio to the development of new software. This approach, design-byadaptation, involves the transfer of interface technology and/or design principles from one application domain to another, in situations where the recipient domain is similar to the host domain in terms of modelled systems, tasks and users. Using the example of interaction in 3D virtual environments, the paper explores how principles underlying the design of videogame interfaces may be applied to a broad family of visualization and analysis software which handles geographical data (virtual geographic environments, or VGEs). One of the motivations behind the current study is that VGE technology lags some way behind videogame technology in the modelling of 3D environments, and has a less-developed track record in providing the variety of interaction methods needed to undertake varied tasks in 3D virtual worlds by users with varied levels of experience. The current analysis extracted a set of interaction principles from videogames which were used to devise a set of 3D task interfaces that have been implemented in a prototype VGE for formal evaluation

PubChem3D: Diversity of shape

<p>Abstract</p> <p>Background</p> <p>The shape diversity of 16.4 million biologically relevant molecules from the PubChem Compound database and their 1.46 billion diverse conformers was explored as a function of molecular volume.</p> <p>Results</p> <p>The diversity of shape space was investigated by determining the shape similarity threshold to achieve a maximum on the count of reference shapes per unit of conformer volume. The rate of growth in shape space, as represented by a decreasing shape similarity threshold, was found to be remarkably smooth as a function of volume. There was no apparent correlation between the count of conformers per unit volume and their diversity, meaning that a single reference shape can describe the shape space of many chemical structures. The ability of a volume to describe the shape space of lesser volumes was also examined. It was shown that a given volume was able to describe 40-70% of the shape diversity of lesser volumes, for the majority of the volume range considered in this study.</p> <p>Conclusion</p> <p>The relative growth of shape diversity as a function of volume and shape similarity is surprisingly uniform. Given the distribution of chemicals in PubChem versus what is theoretically synthetically possible, the results from this analysis should be considered a conservative estimate to the true diversity of shape space.</p

An ontology for major histocompatibility restriction

BACKGROUND: MHC molecules are a highly diverse family of proteins that play a key role in cellular immune recognition. Over time, different techniques and terminologies have been developed to identify the specific type(s) of MHC molecule involved in a specific immune recognition context. No consistent nomenclature exists across different vertebrate species. PURPOSE: To correctly represent MHC related data in The Immune Epitope Database (IEDB), we built upon a previously established MHC ontology and created an ontology to represent MHC molecules as they relate to immunological experiments. DESCRIPTION: This ontology models MHC protein chains from 16 species, deals with different approaches used to identify MHC, such as direct sequencing verses serotyping, relates engineered MHC molecules to naturally occurring ones, connects genetic loci, alleles, protein chains and multi-chain proteins, and establishes evidence codes for MHC restriction. Where available, this work is based on existing ontologies from the OBO foundry. CONCLUSIONS: Overall, representing MHC molecules provides a challenging and practically important test case for ontology building, and could serve as an example of how to integrate other ontology building efforts into web resources. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13326-016-0045-5) contains supplementary material, which is available to authorized users

The role of ALOX5AP, LTA4H and LTB4R polymorphisms in determining baseline lung function and COPD susceptibility in UK smokers

<p>Abstract</p> <p>Background</p> <p>We have previously shown evidence that polymorphisms within genes controlling leukotriene B₄(LTB₄) production (<it>ALOX5AP </it>and <it>LTA4H</it>) are associated with asthma susceptibility in children. Evidence also suggests a potential role of LTB₄in COPD disease mechanisms including recruitment of neutrophils to the lung. The aim of the current study was to see if these SNPs and those spanning the receptor genes for LTB₄(<it>LTB4R1 </it>and <it>LTB4R2</it>) influence baseline lung function and COPD susceptibility/severity in smokers.</p> <p>Methods</p> <p>Eight <it>ALOX5AP</it>, six <it>LTA4H </it>and six <it>LTB4R </it>single nucleotide polymorphisms (SNPs) were genotyped in a UK Smoking Cohort (n = 992). Association with baseline lung function (FEV₁and FEV₁/FVC ratio) was determined by linear regression. Logistic regression was used to compare smoking controls (n = 176) with spirometry-defined COPD cases (n = 599) and to more severe COPD cases (GOLD stage 3 and 4, n = 389).</p> <p>Results</p> <p>No association with <it>ALOX5AP</it>, <it>LTA4H </it>or <it>LTB4R </it>survived correction for multiple testing. However, we showed modest association with <it>LTA4H </it>rs1978331C (intron 11) with increased FEV₁(p = 0.029) and with increased FEV₁/FVC ratio (p = 0.020).</p> <p>Conclusions</p> <p>These data suggest that polymorphisms spanning <it>ALOX5AP</it>, <it>LTA4H </it>and the <it>LTB4R </it>locus are not major determinants of baseline lung function in smokers, but provide tentative evidence for <it>LTA4H </it>rs1978331C (intron 11) in determining baseline FEV₁and FEV₁/FVC ratio in Caucasian Smokers in addition to our previously identified role in asthma susceptibility.</p

PubChem3D: Similar conformers

<p>Abstract</p> <p>Background</p> <p>PubChem is a free and open public resource for the biological activities of small molecules. With many tens of millions of both chemical structures and biological test results, PubChem is a sizeable system with an uneven degree of available information. Some chemical structures in PubChem include a great deal of biological annotation, while others have little to none. To help users, PubChem pre-computes "neighboring" relationships to relate similar chemical structures, which may have similar biological function. In this work, we introduce a "Similar Conformers" neighboring relationship to identify compounds with similar 3-D shape and similar 3-D orientation of functional groups typically used to define pharmacophore features.</p> <p>Results</p> <p>The first two diverse 3-D conformers of 26.1 million PubChem Compound records were compared to each other, using a shape Tanimoto (ST) of 0.8 or greater and a color Tanimoto (CT) of 0.5 or greater, yielding 8.16 billion conformer neighbor pairs and 6.62 billion compound neighbor pairs, with an average of 253 "Similar Conformers" compound neighbors per compound. Comparing the 3-D neighboring relationship to the corresponding 2-D neighboring relationship ("Similar Compounds") for molecules such as caffeine, aspirin, and morphine, one finds unique sets of related chemical structures, providing additional significant biological annotation. The PubChem 3-D neighboring relationship is also shown to be able to group a set of non-steroidal anti-inflammatory drugs (NSAIDs), despite limited PubChem 2-D similarity.</p> <p>In a study of 4,218 chemical structures of biomedical interest, consisting of many known drugs, using more diverse conformers per compound results in more 3-D compound neighbors per compound; however, the overlap of the compound neighbor lists per conformer also increasingly resemble each other, being 38% identical at three conformers and 68% at ten conformers. Perhaps surprising is that the average count of conformer neighbors per conformer increases rather slowly as a function of diverse conformers considered, with only a 70% increase for a ten times growth in conformers per compound (a 68-fold increase in the conformer pairs considered).</p> <p>Neighboring 3-D conformers on the scale performed, if implemented naively, is an intractable problem using a modest sized compute cluster. Methodology developed in this work relies on a series of filters to prevent performing 3-D superposition optimization, when it can be determined that two conformers cannot possibly be a neighbor. Most filters are based on Tanimoto equation volume constraints, avoiding incompatible conformers; however, others consider preliminary superposition between conformers using reference shapes.</p> <p>Conclusion</p> <p>The "Similar Conformers" 3-D neighboring relationship locates similar small molecules of biological interest that may go unnoticed when using traditional 2-D chemical structure graph-based methods, making it complementary to such methodologies. The computational cost of 3-D similarity methodology on a wide scale, such as PubChem contents, is a considerable issue to overcome. Using a series of efficient filters, an effective throughput rate of more than 150,000 conformers per second per processor core was achieved, more than two orders of magnitude faster than without filtering.</p

Clinical essentialising: a qualitative study of doctors’ medical and moral practice

While certain substantial moral dilemmas in health care have been given much attention, like abortion, euthanasia or gene testing, doctors rarely reflect on the moral implications of their daily clinical work. Yet, with its aim to help patients and relieve suffering, medicine is replete with moral decisions. In this qualitative study we analyse how doctors handle the moral aspects of everyday clinical practice. About one hundred consultations were observed, and interviews conducted with fifteen clinical doctors from different practices. It turned out that the doctors’ approach to clinical cases followed a rather strict pattern across specialities, which implied transforming patients’ diverse concerns into specific medical questions through a process of ‘essentialising’: Doctors broke the patient’s story down, concretised the patient’s complaints and categorised the symptoms into a medical sense. Patients’ existential meanings were removed, and the focus placed on the patients’ functioning. By essentialising, doctors were able to handle a complex and ambiguous reality, and establish a medically relevant problem. However, the process involved a moral as well as a practical simplification. Overlooking existential meanings and focusing on purely functional aspects of patients was an integral part of clinical practice and not an individual flaw. The study thus questions the value of addressing doctors’ conscious moral evaluations. Yet doctors should be aware that their daily clinical work systematically emphasises beneficence at the expense of others—that might be more important to the patient

Ovine pedomics : the first study of the ovine foot 16S rRNA-based microbiome

We report the first study of the bacterial microbiome of ovine interdigital skin based on 16S rRNA by pyrosequencing and conventional cloning with Sanger-sequencing. Three flocks were selected, one a flock with no signs of footrot or interdigital dermatitis, a second flock with interdigital dermatitis alone and a third flock with both interdigital dermatitis and footrot. The sheep were classified as having either healthy interdigital skin (H), interdigital dermatitis (ID) or virulent footrot (VFR). The ovine interdigital skin bacterial community varied significantly by flock and clinical condition. The diversity and richness of operational taxonomic units was greater in tissue from sheep with ID than H or VFR affected sheep. Actinobacteria, Bacteriodetes, Firmicutes and Proteobacteria were the most abundant phyla comprising 25 genera. Peptostreptococcus, Corynebacterium and Staphylococcus were associated with H, ID and VFR respectively. Sequences of Dichelobacter nodosus, the causal agent of ovine footrot, were not amplified due to mismatches in the 16S rRNA universal forward primer (27F). A specific real time PCR assay was used to demonstrate the presence of D. nodosus which was detected in all samples including the flock with no signs of ID or VFR. Sheep with ID had significantly higher numbers of D. nodosus (104-109 cells/g tissue) than those with H or VFR feet

Erosion consequences on beach functions along the Maresme coast (NW Mediterranean, Spain)

A methodology to analyse the influence of erosion on beach functions at a regional scale is presented. The method considers erosion hazards at different timescales and assesses consequences by evaluating impacts on recreation and protection functions. To provide useful information to decision makers for managing these functions, hazard and consequences are integrated at the municipal level within a risk matrix. This methodology is applied at the Maresme, a 45-km sandy coast situated northward of Barcelona, which supports a strong urban and infrastructure development as well as an intensive beach recreational use. Obtained results indicate differentiated erosion implications along the region, depending on the management target considered. Thus, southern municipalities are more prone to erosion affecting the protection function of the beach and leisure use by the local population, whereas erosion will have a greater effect on foreign tourism in the northern municipalities. These results highlight the necessity to employ an articulated erosion risk assessment focusing on specific targets depending on the site in question. This methodology can help coastal managers to adopt tailored measures to manage erosion impacts towards specific goals, in a more efficient and sustainable manner

Shakespearean allusion and the detective fiction of Georgette Heyer

This essay argues that Shakespearean allusion is a recurrent and important factor in the detective novels of Georgette Heyer. Though the master text for Heyer is Hamlet, a variety of Shakespeare plays are referred to, and mention of them functions in multiple ways. Quotations from Shakespeare reveal truths about the characters and comment on their situations and personalities. They also afford points of entry for people previously unacquainted to talk to each other, and finally they have effects in terms of genre, since their presence can, with equal facility, tend towards comic relief (in line with a tradition in Golden Age crime fiction of using Macbeth in particular to comic effect) or work to add gravitas and resonance. The use of Shakespearean allusion is thus central to Heyer’s technique. This article is published as part of a collection to commemorate the 400th anniversary of William Shakespeare’s death