Phrasing Bimanual Interaction for Visual Design

Architects and other visual thinkers create external representations of their ideas to support early-stage design. They compose visual imagery with sketching to form abstract diagrams as representations. When working with digital media, they apply various visual operations to transform representations, often engaging in complex sequences. This research investigates how to build interactive capabilities to support designers in putting together, that is phrasing, sequences of operations using both hands. In particular, we examine how phrasing interactions with pen and multi-touch input can support modal switching among different visual operations that in many commercial design tools require using menus and tool palettes—techniques originally designed for the mouse, not pen and touch. We develop an interactive bimanual pen+touch diagramming environment and study its use in landscape architecture design studio education. We observe interesting forms of interaction that emerge, and how our bimanual interaction techniques support visual design processes. Based on the needs of architects, we develop LayerFish, a new bimanual technique for layering overlapping content. We conduct a controlled experiment to evaluate its efficacy. We explore the use of wearables to identify which user, and distinguish what hand, is touching to support phrasing together direct-touch interactions on large displays. From design and development of the environment and both field and controlled studies, we derive a set methods, based upon human bimanual specialization theory, for phrasing modal operations through bimanual interactions without menus or tool palettes

The ATPase cycle of PcrA helicase and its coupling to translocation on DNA.

The superfamily 1 bacterial helicase PcrA has a role in the replication of certain plasmids, acting with the initiator protein (RepD) that binds to and nicks the double-stranded origin of replication. PcrA also translocates single-stranded DNA with discrete steps of one base per ATP hydrolyzed. Individual rate constants have been determined for the DNA helicase PcrA ATPase cycle when bound to either single-stranded DNA or a double-stranded DNA junction that also has RepD bound. The fluorescent ATP analogue 2'(3')-O-(N-methylanthraniloyl)ATP was used throughout all experiments to provide a complete ATPase cycle for a single nucleotide species. Fluorescence intensity and anisotropy stopped-flow measurements were used to determine rate constants for binding and release. Quenched-flow measurements provided the kinetics of the hydrolytic cleavage step. The fluorescent phosphate sensor MDCC-PBP was used to measure phosphate release kinetics. The chemical cleavage step is the rate-limiting step in the cycle and is essentially irreversible and would result in the bound ATP complex being a major component at steady state. This cleavage step is greatly accelerated by bound DNA, producing the high activation of this protein compared to the protein alone. The data suggest the possibility that ADP is released in two steps, which would result in bound ADP also being a major intermediate, with bound ADP.P(i) being a very small component. It therefore seems likely that the major transition in structure occurs during the cleavage step, rather than P(i) release. ATP rebinding could then cause reversal of this structural transition. The kinetic mechanism of the PcrA ATPase cycle is very little changed by potential binding to RepD, supporting the idea that RepD increases the processivity of PcrA by increasing affinity to DNA rather than affecting the enzymatic properties per se

Genomic and physiological variability within Group II (non-proteolytic) Clostridium botulinum

BACKGROUND: Clostridium botulinum is a group of four physiologically and phylogenetically distinct bacteria that produce botulinum neurotoxin. While studies have characterised variability between strains of Group I (proteolytic) C. botulinum, the genetic and physiological variability and relationships between strains within Group II (non-proteolytic) C. botulinum are not well understood. In this study the genome of Group II strain C. botulinum Eklund 17B (NRP) was sequenced and used to construct a whole genome DNA microarray. This was used in a comparative genomic indexing study to compare the relatedness of 43 strains of Group II C. botulinum (14 type B, 24 type E and 5 type F). These results were compared with characteristics determined from physiological tests. RESULTS: Whole genome indexing showed that strains of Group II C. botulinum isolated from a wide variety of environments over more than 75 years clustered together indicating the genetic background of Group II C. botulinum is stable. Further analysis showed that strains forming type B or type F toxin are closely related with only toxin cluster genes targets being unique to either type. Strains producing type E toxin formed a separate subset. Carbohydrate fermentation tests supported the observation that type B and F strains form a separate subset to type E strains. All the type F strains and most of type B strains produced acid from amylopectin, amylose and glycogen whereas type E strains did not. However, these two subsets did not differ strongly in minimum growth temperature or maximum NaCl concentration for growth. No relationship was found between tellurite resistance and toxin type despite all the tested type B and type F strains carrying tehB, while the sequence was absent or diverged in all type E strains. CONCLUSIONS: Although Group II C. botulinum form a tight genetic group, genomic and physiological analysis indicates there are two distinct subsets within this group. All type B strains and type F strains are in one subset and all type E strains in the other

Not just a migration problem: Metapopulations, habitat shifts and gene flow are also important for fishway science and management

Worldwide, fishways are increasingly criticized for failing to meet conservation goals. We argue that this is largely due to the dominance of diadromous species of the Northern Hemisphere (e.g., Salmonidae) in the research that underpins the concepts and methods of fishway science and management. With highly diverse life histories, swimming abilities and spatial ecologies, most freshwater fish species do not conform to the stereotype imposed by this framework. This is leading to a global proliferation of fishways that are often unsuitable for native species. The vast majority of fish populations do not undertake extensive migrations between clearly separated critical habitats, yet the movement of individuals and the genetic information they carry is critically important for population viability. We briefly review some of the latest advances in spatial ecological modelling for dendritic networks to better define what it means to achieve effective fish passage at a barrier. Through a combination of critical habitat assessment and the modelling of metapopulations, climate change�driven habitat shifts, and adaptive gene flow, we recommend a conceptual and methodological framework for fishway target�setting and monitoring suitable for a wide range of species. In the process, we raise a number of issues that should contribute to the ongoing debate about fish passage research and the design and monitoring of fishways

Understanding the Changing Cultural Value of the BBC World Service and the British Council

This project investigated the changing cultural value of the BBC World Service (WS) and the British Council (BC) and how their cultural value can be assessed and measured. For eight decades, these organisations have been the face and voice of Britain overseas. Our research found that their attraction and influence abroad remains strong, but is on the wane, reflecting the UK’s declining economic and political significance on the world stage. Among the key findings of our historical and contemporary research: Cultural value is the catalyst of all aspects of value at WS and BC, founded on their capacity to act as transcultural intermediaries, fostering international understanding, and setting benchmarks in global standards for journalism and cultural relations work. Cultural value is relational, never independent of political and economic value. It is perspectival: audiences trust the quality and credibility of outputs; high professional standards and prestige benefit staff; funders appreciate the diplomatic and soft power assets. Cultural value accrues slowly over time but can be quickly lost. Social media afford new ways of connecting, informing and engaging citizens at home and abroad. Our case studies analysing the uses of Twitter and Facebook by BC and WS around global media events underscore the so far limited role of social media in democratising participation and promoting intercultural dialogue. We developed an innovative, theoretically grounded and empirically informed Cultural Value Model (CVM). This is an innovative device for conceptualising, analysing and assessing value in a multidimensional, composite, visual way. The CVM is designed for planning, monitoring and evaluating projects and organisations over time, alongside existing performance indicators and impact measures. It is currently being tested and developed on further projects at WS and BC as well as at the Swedish Institute

Self-control, plan quality and digital delivery of action planning for condom and contraceptive pill use of 14-24 year olds: Findings from a clinic-based online pilot randomised controlled trial

© 2018 The International Association of Applied Psychology. This is the peer reviewed version of the following article: Self‐Control, Plan Quality, and Digital Delivery of Action Planning for Condom and Contraceptive Pill Use of 14–24‐Year‐Olds: Findings from a Clinic‐Based Online Pilot Randomised Controlled Trial in Health & Wellbeing, Vol 10, Issue 3, Nov 2018, which has been published in final form at https://doi.org/10.1111/aphw.12138. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Background: Inconsistent use of the contraceptive pill and condoms contributes significantly to poor sexual health outcomes for young people. There is evidence that action planning interventions may improve pill and condom use, but this approach is not systematically used in sexual healthcare. This study is the first to assess acceptability and feasibility of evaluating a digital intervention to support action plan formation for three sexual health behaviours with clinic attendees. It also considered the role of trait self-control and whether the intervention supported production of quality plans. Methods: Eighty-eight integrated sexual health clinic attendees aged 14–24 years (M = 20.27 years) were recruited to a pilot randomised controlled trial (RCT). Of these, 67 also completed three-month follow-up. Measures included self-reported contraceptive or condom “mishaps”, theory of planned behaviour variables, and a measure of self-control. Results: Descriptive analyses supported study acceptability and feasibility. The intervention supported pill and condom users to produce quality plans, though potential improvements were identified. Bivariate correlations suggested that high levels of trait self-control may negatively influence plan quality. Data suggest that the intervention may reduce pill or condom “mishaps”. Conclusions: A future full RCT is likely feasible and brief digital action planning interventions may usefully be incorporated within sexual healthcare.Peer reviewedFinal Accepted Versio

RNA:DNA hybrids are a novel molecular pattern sensed by TLR9.

The sensing of nucleic acids by receptors of the innate immune system is a key component of antimicrobial immunity. RNA:DNA hybrids, as essential intracellular replication intermediates generated during infection, could therefore represent a class of previously uncharacterised pathogen-associated molecular patterns sensed by pattern recognition receptors. Here we establish that RNA:DNA hybrids containing viral-derived sequences efficiently induce pro-inflammatory cytokine and antiviral type I interferon production in dendritic cells. We demonstrate that MyD88-dependent signalling is essential for this cytokine response and identify TLR9 as a specific sensor of RNA:DNA hybrids. Hybrids therefore represent a novel molecular pattern sensed by the innate immune system and so could play an important role in host response to viruses and the pathogenesis of autoimmune disease

Porcine endogenous retroviruses PERV A and A/C recombinant are insensitive to a range of divergent mammalian TRIM5 proteins including human TRIM5

The potential risk of cross-species transmission of porcine endogenous retroviruses (PERV) to humans has slowed the development of xenotransplantation, using pigs as organ donors. Here, we show that PERVs are insensitive to restriction by divergent TRIM5{alpha} molecules despite the fact that they strongly restrict a variety of divergent lentiviruses. We also show that the human PERV A/C recombinant clone 14/220 reverse transcribes with increased efficiency in human cells, leading to significantly higher infectivity. We conclude that xenotransplantation studies should consider the danger of highly infectious TRIM5{alpha}-insensitive human-tropic PERV recombinants

Quantitative MRI brain in congenital adrenal hyperplasia: in vivo assessment of the cognitive and structural impact of steroid hormones

Abstract Context Brain white matter hyper-intensities are seen on routine clinical imaging in 46% of adults with congenital adrenal hyperplasia (CAH). The extent and functional relevance of these abnormalities have not been studied using quantitative MRI analysis. Objective To examine white matter microstructure, neural volumes and CNS metabolites in CAH due to 21-hydroxylase deficiency (21OHD) and to determine whether identified abnormalities are associated with cognition, glucocorticoid and androgen exposure. Design, setting and participants A cross-sectional study at a tertiary hospital including 19 females (18-50 years) with 21OHD and 19 age-matched healthy females. Main outcome measure Recruits underwent cognitive assessment and brain imaging including; diffusion weighted imaging of white matter, T1-weighted volumetry and magnetic resonance spectroscopy for neural metabolites. We evaluated white matter microstructure using tract-based spatial statistics. We compared cognitive scores, neural volumes and metabolites between groups and relationships between glucocorticoid exposure, MRI and neurologic outcomes. Results Patients with 21OHD had widespread reductions in white matter structural integrity, reduced volumes of right hippocampus, bilateral thalami, cerebellum and brainstem, and reduced mesial temporal lobe total choline content. Working memory, processing speed, and digit span and matrix reasoning scores were reduced in patients with 21OHD, despite similar education and intelligence to controls. 21OHD individuals exposed to higher glucocorticoid doses had greater abnormalities in white matter microstructure and cognitive performance. Conclusion For the first time we demonstrate that 21OHD and current glucocorticoid replacement regimens have a profound impact on brain morphology and function. If reversible, these CNS markers represent a potential target for treatment