Disciplining Innovations

The editors of the 'Disciplining Innovations' issue introduce the theme

The Impact of Accretion Disk Winds on the Optical Spectra of Cataclysmic Variables

Many high-state non-magnetic cataclysmic variables (CVs) exhibit blue-shifted absorption or P-Cygni profiles associated with ultraviolet (UV) resonance lines. These features imply the existence of powerful accretion disk winds in CVs. Here, we use our Monte Carlo ionization and radiative transfer code to investigate whether disk wind models that produce realistic UV line profiles are also likely to generate observationally significant recombination line and continuum emission in the optical waveband. We also test whether outflows may be responsible for the single-peaked emission line profiles often seen in high-state CVs and for the weakness of the Balmer absorption edge (relative to simple models of optically thick accretion disks). We find that a standard disk wind model that is successful in reproducing the UV spectra of CVs also leaves a noticeable imprint on the optical spectrum, particularly for systems viewed at high inclination. The strongest optical wind-formed recombination lines are H$\alpha$ and He II $\lambda4686$. We demonstrate that a higher-density outflow model produces all the expected H and He lines and produces a recombination continuum that can fill in the Balmer jump at high inclinations. This model displays reasonable verisimilitude with the optical spectrum of RW Trianguli. No single-peaked emission is seen, although we observe a narrowing of the double-peaked emission lines from the base of the wind. Finally, we show that even denser models can produce a single-peaked H$\alpha$ line. On the basis of our results, we suggest that winds can modify, and perhaps even dominate, the line and continuum emission from CVs.Comment: 15 pages, 13 figures. Accepted to MNRA

Line-driven Disk Winds in Active Galactic Nuclei: The Critical Importance of Ionization and Radiative Transfer

Accretion disk winds are thought to produce many of the characteristic features seen in the spectra of active galactic nuclei (AGN) and quasi-stellar objects (QSOs). These outflows also represent a natural form of feedback between the central supermassive black hole and its host galaxy. The mechanism for driving this mass loss remains unknown, although radiation pressure mediated by spectral lines is a leading candidate. Here, we calculate the ionization state of, and emergent spectra for, the hydrodynamic simulation of a line-driven disk wind previously presented by Proga & Kallman (2004). To achieve this, we carry out a comprehensive Monte Carlo simulation of the radiative transfer through, and energy exchange within, the predicted outflow. We find that the wind is much more ionized than originally estimated. This is in part because it is much more difficult to shield any wind regions effectively when the outflow itself is allowed to reprocess and redirect ionizing photons. As a result, the calculated spectrum that would be observed from this particular outflow solution would not contain the ultraviolet spectral lines that are observed in many AGN/QSOs. Furthermore, the wind is so highly ionized that line-driving would not actually be efficient. This does not necessarily mean that line-driven winds are not viable. However, our work does illustrate that in order to arrive at a self-consistent model of line-driven disk winds in AGN/QSO, it will be critical to include a more detailed treatment of radiative transfer and ionization in the next generation of hydrodynamic simulations.Comment: 13 pages, 10 figures - Accepted for publication in Ap

High quality rendering of protein dynamics in space filling mode

Producing high quality depictions of molecular structures has been an area of academic interest for years, with visualisation tools such as UCSF Chimera, Yasara and PyMol providing a huge number of different rendering modes and lighting effects. However, no visualisation program supports per-pixel lighting effects with shadows whilst rendering a molecular trajectory in space filling mode. In this paper, a new approach to rendering high quality visualisations of molecular trajectories is presented. To enhance depth, ambient occlusion is included within the render. Shadows are also included to help the user perceive relative motions of parts of the protein as they move based on their trajectories. Our approach requires a regular grid to be constructed every time the molecular structure deforms allowing per-pixel lighting effects and ambient occlusion to be rendered every frame, at interactive refresh rates. Two different regular grids are investigated, a fixed grid and a memory efficient compact grid. The algorithms used allow trajectories of proteins comprising of up to 300,000 atoms in size to be rendered at ninety frames per second on a desktop computer using the GPU for general purpose computations. Regular grid construction was found to only take up a small proportion of the total time to render a frame. It was found that despite being slower to construct, the memory efficient compact grid outperformed the theoretically faster fixed grid when the protein being rendered is large, owing to its more efficient memory access patterns. The techniques described could be implemented in other molecular rendering software

Automatic categorization of diverse experimental information in the bioscience literature

Background: Curation of information from bioscience literature into biological knowledge databases is a crucial way of capturing experimental information in a computable form. During the biocuration process, a critical first step is to identify from all published literature the papers that contain results for a specific data type the curator is interested in annotating. This step normally requires curators to manually examine many papers to ascertain which few contain information of interest and thus, is usually time consuming. We developed an automatic method for identifying papers containing these curation data types among a large pool of published scientific papers based on the machine learning method Support Vector Machine (SVM). This classification system is completely automatic and can be readily applied to diverse experimental data types. It has been in use in production for automatic categorization of 10 different experimental datatypes in the biocuration process at WormBase for the past two years and it is in the process of being adopted in the biocuration process at FlyBase and the Saccharomyces Genome Database (SGD). We anticipate that this method can be readily adopted by various databases in the biocuration community and thereby greatly reducing time spent on an otherwise laborious and demanding task. We also developed a simple, readily automated procedure to utilize training papers of similar data types from different bodies of literature such as C. elegans and D. melanogaster to identify papers with any of these data types for a single database. This approach has great significance because for some data types, especially those of low occurrence, a single corpus often does not have enough training papers to achieve satisfactory performance. Results: We successfully tested the method on ten data types from WormBase, fifteen data types from FlyBase and three data types from Mouse Genomics Informatics (MGI). It is being used in the curation work flow at WormBase for automatic association of newly published papers with ten data types including RNAi, antibody, phenotype, gene regulation, mutant allele sequence, gene expression, gene product interaction, overexpression phenotype, gene interaction, and gene structure correction. Conclusions: Our methods are applicable to a variety of data types with training set containing several hundreds to a few thousand documents. It is completely automatic and, thus can be readily incorporated to different workflow at different literature-based databases. We believe that the work presented here can contribute greatly to the tremendous task of automating the important yet labor-intensive biocuration effort

Cognitive function in a general population of men and women: a cross sectional study in the European Investigation of Cancer-Norfolk cohort (EPIC-Norfolk).

BACKGROUND: Although ageing is strongly associated with cognitive decline, a wide range of cognitive ability is observed in older populations with varying rates of change across different cognitive domains. METHODS: Cognitive function was measured as part of the third health examination of the European Prospective Investigation of Cancer in Norfolk (EPIC-Norfolk 3) between 2006 and 2011 (including measures from the pilot phase from 2004 to 2006). This was done using a battery consisting of seven previously validated cognitive function tests assessing both global function and specific domains. The battery included a shortened version of the Extended Mental State Exam (SF-EMSE); letter cancellation task; Hopkins Verbal Learning Test (HVLT); Cambridge Neuropsychological Test Automated Battery Paired Associates Learning Test (CANTAB-PAL); Visual Sensitivity Test (VST); Shortened version of the National Adult Reading Test (Short-NART) and a task to test for prospective memory. We report the distribution of cognitive function in different cognitive domains by age and sex and compare the utility of a number of assessment tests in a general population of older men and women. RESULTS: Cognitive test data were available for 8585 men and women taking part in EPIC-Norfolk 3. Increasing age was generally associated with declining mean cognitive function, but there was a wide range observed within each age group as well as variability across different cognitive domains. Some sex differences were also observed. CONCLUSION: Descriptive data are presented for this general population sample of older men and women. There is a wide range of cognitive performance seen in this population. Though average performance declines with age, there is large individual variability across different cognitive domains. These variations may provide insights into the determinants of cognitive function in later life.The infrastructure for this study was supported by the Medical Research Council, UK (G0401527) and Cancer Research UK (CRUK, C864/A8257). The clinic for EPIC-Norfolk 3 was funded by Research into Ageing (262). The pilot phase was supported by MRC (G9502233) and CRUK (C864/A2883).This is the final published version. It first appeared at http://www.biomedcentral.com/1471-2318/14/142

E-cadherin can limit the transforming properties of activating β-catenin mutations

Wnt pathway deregulation is a common characteristic of many cancers. But only Colorectal Cancer predominantly harbours mutations in APC, whereas other cancer types (hepatocellular carcinoma, solid pseudopapillary tumours of pancreas) have activating mutations in β-catenin (CTNNB1). We have compared the dynamics and the potency of β-catenin mutations in vivo. Within the murine small intestine (SI), an activating mutation of β-catenin took much longer to achieve a Wnt deregulation and acquire a crypt-progenitor-cell (CPC) phenotype than Apc or Gsk3 loss. Within the colon, a single activating mutation of β-catenin was unable to drive Wnt deregulation or induce the CPC phenotype. This ability of β-catenin mutation to differentially transform the SI versus the colon correlated with significantly higher expression of the β-catenin binding partner E-cadherin. This increased expression is associated with a higher number of E-cadherin:β-catenin complexes at the membrane. Reduction of E-cadherin synergised with an activating mutation of β-catenin so there was now a rapid CPC phenotype within the colon and SI. Thus there is a threshold of β-catenin that is required to drive transformation and E-cadherin can act as a buffer to prevent β-catenin accumulation

Through a glass, brightly: Sawyer’s Science Fiction as a Foundation for Ethics

The novels of Robert J. Sawyer have contained dinosaurs, aliens, Neanderthals and artificial intelligences. While including these science fiction tropes, his novels have always been about the human condition. These scientific nova are used as a mirror for the reader to examine humanity, with an eye to ethical behavior. Sawyer once suggested that his novels “fight the good fight about the value of rationalism over superstition, of openmindedness but not credulousness over dogma” (SF Site July 2002). As part of this scientific rationalism, Sawyer’s works show continued interest in ethics as an ultimate good. While his early novels take place in far-future environments, Sawyer’s recent novels are in the near future, with relatively few SF tropes. Darko Suvin once defined science fiction as “a literary genre whose necessary and sufficient conditions are the presence and interaction of estrangement and cognition, and whose main formal device is an imaginative framework alternative to the author’s empirical environment” (Suvin 1979: 7-8). According to Suvin’s definition, Sawyer’s novels are weighted in favour of a world very much recognizable as our own, with specific elements which form the imaginative frameworks. In novels like the Neanderthal Parallax trilogy, or Wake Watch Wonder, Sawyer presents the reader with reasoned arguments towards an alternative ethical framework, by substituting our human experiences with those of Neanderthals or AI. Through eyes not unlike our own, Sawyer’s readers look at society until the light of a new world, illuminating the darkness of our past

The effectiveness of the Inspiring Futures parenting programme in improving behavioural and emotional outcomes in primary school children with behavioural or emotional difficulties: study protocol for a randomised controlled trial.

textabstractBackground: There is a need to build the evidence base of early interventions promoting children's health and development in the UK. Malachi Specialist Family Support Services ('Malachi') is a voluntary sector organisation based in the UK that delivers a therapeutic parenting group programme called Inspiring Futures to parents of children identified as having behavioural and emotional difficulties. The programme comprises two parts, delivered sequentially: (1) a group-based programme for all parents for 10-12 weeks, and (2) one-to-one sessions with selected parents from the group-based element for up to 12 weeks. Methods/design: A randomised controlled trial will be conducted to evaluate Malachi's Inspiring Futures parenting programme. Participants will be allocated to one of two possible arms, with follow-up measures at 16 weeks (post-parent group programme) and at 32 weeks (post-one-to-one sessions with selected parents). The sample size is 248 participants with a randomisation allocation ratio of 1:1. The intervention arm will be offered the Inspiring Futures programme. The control group will receive services as usual. The aim is to determine the effectiveness of the Inspiring Futures programme on the primary outcome of behavioural and emotional difficulties of primary school children identified as having behavioural or emotional difficulties. Discussion: This study will further enhance the evidence for early intervention parenting programmes for child behavioural and emotional problems in the UK