Phylogeographic diversity and mosaicism of the Helicobacter pylori tfs integrative and conjugative elements.

Background: The genome of the gastric pathogen Helicobacter pylori is characterised by considerable variation of both gene sequence and content, much of which is contained within three large genomic islands comprising the cag pathogenicity island (cagPAI) and two mobile integrative and conjugative elements (ICEs) termed tfs3 and tfs4. All three islands are implicated as virulence factors, although whereas the cagPAI is well characterised, understanding of how the tfs elements influence H. pylori interactions with different human hosts is significantly confounded by limited definition of their distribution, diversity and structural representation in the global H. pylori population. Results: To gain a global perspective of tfs ICE population dynamics we established a bioinformatics workflow to extract and precisely define the full tfs pan-gene content contained within a global collection of 221 draft and complete H. pylori genome sequences. Complete (ca. 35-55kbp) and remnant tfs ICE clusters were reconstructed from a dataset comprising >12,000 genes, from which orthologous gene complements and distinct alleles descriptive of different tfs ICE types were defined and classified in comparative analyses. The genetic variation within defined ICE modular segments was subsequently used to provide a complete description of tfs ICE diversity and a comprehensive assessment of their phylogeographic context. Our further examination of the apparent ICE modular types identified an ancient and complex history of ICE residence, mobility and interaction within particular H. pylori phylogeographic lineages and further, provided evidence of both contemporary inter-lineage and inter-species ICE transfer and displacement. Conclusions: Our collective results establish a clear view of tfs ICE diversity and phylogeographic representation in the global H. pylori population, and provide a robust contextual framework for elucidating the functional role of the tfs ICEs particularly as it relates to the risk of gastric disease associated with different tfs ICE genotypes

Adaptive Grey-Box Fuzz-Testing with Thompson Sampling

Fuzz testing, or "fuzzing," refers to a widely deployed class of techniques for testing programs by generating a set of inputs for the express purpose of finding bugs and identifying security flaws. Grey-box fuzzing, the most popular fuzzing strategy, combines light program instrumentation with a data driven process to generate new program inputs. In this work, we present a machine learning approach that builds on AFL, the preeminent grey-box fuzzer, by adaptively learning a probability distribution over its mutation operators on a program-specific basis. These operators, which are selected uniformly at random in AFL and mutational fuzzers in general, dictate how new inputs are generated, a core part of the fuzzer's efficacy. Our main contributions are two-fold: First, we show that a sampling distribution over mutation operators estimated from training programs can significantly improve performance of AFL. Second, we introduce a Thompson Sampling, bandit-based optimization approach that fine-tunes the mutator distribution adaptively, during the course of fuzzing an individual program. A set of experiments across complex programs demonstrates that tuning the mutational operator distribution generates sets of inputs that yield significantly higher code coverage and finds more crashes faster and more reliably than both baseline versions of AFL as well as other AFL-based learning approaches.Comment: Published as a workshop paper in the 11th ACM Workshop on Artificial Intelligence and Security (AISec '18) with the 25th ACM Conference on Computer and Communications Security (CCS '18

How tidal processes impact the transfer of sediment from source to sink : Mekong River collaborative studies

Author Posting. © Oceanography Society, 2017. This article is posted here by permission of Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 30, no. 3 (2017): 22–33, doi:10.5670/oceanog.2017.311.Significant sediment transformation and trapping occur along the tidal and estuarine reaches of large rivers, complicating sediment source signals transmitted to the coastal ocean. The collaborative Mekong Tropical Delta Study explored the tidally influenced portion of the Mekong River to investigate processes that impact mud- and sand-sized sediment transport and deposition associated with varying fluvial and marine influences. Researchers participating in this 2014–2015 project found that as sand and mud progress down the tidal portion of the river, sands in suspension can settle during reduced or slack flows as river discharge becomes progressively more affected by tides in the seaward direction. Consequently, deposits on the tidal river bed are connected to sand transport in the channel. In contrast, fine mud particles remain in suspension until they reach an interface zone where waters are still fresh, but the downstream saline estuary nonetheless impacts the flows. In this interface zone, as within the estuary, fine particles tend to settle, draping the sand beds with mud and limiting the connection between the bed and suspended sand. In the Mekong system, the interface and estuarine zones migrate along the distributary channels seasonally, resulting in variable trapping dynamics and channel bed texture. Therefore, the signature of fluvial-sediment discharge is altered on its path to the coastal ocean, and the disconnected mud and sand supply functions at the river mouth should result in distinct offshore depositional signatures.This research was funded by the US Office of Naval Research (grant numbers: N00014-15-1-2011, N00014- 13-1-0127, N00014-13-1-0781, N00014-14-1-0145)

Speech intelligibility in higher education teaching facilities

This paper expands upon the initial work conducted by Rutherford, Wilson and Hickman4 and explores the relationship between the Speech Transmission Index (STI) and its application within the context of higher education teaching and learning facilities. As is well known, the modern learning environment comprises a diverse student population of both native [L1] and non-native [L2] listeners & speakers and, as has been evidenced in research and recognized within BS EN 60268-16:201116, such [L2] listeners provide a significant challenge when predicting STI performance in any given space.The purpose of the research presented here is to delve deeper into the relationship between STI and both native and non-native listening groups. Data is presented that extends the findings from the original study, particularly with respect to the relationship between the STI value and [L2] listener performance. The paper concludes that whilst STI over predicts [L2] listener performance, the level of over-prediction itself is fundamentally dependent upon the STI value. For high STI values (>0.8), a relatively small over prediction was observed during intelligibility experiments (approx. 6%) however at low STI values

The costs of treating vaginal and vulval cancer in England (2009-2015).

Funder: Merck Sharp and Dohme; doi: http://dx.doi.org/10.13039/100009947BACKGROUND: Human papillomavirus (HPV) infection is a pre-requisite for cervical cancer, which represents the third most common cancer among women worldwide. A causal relationship also exists between HPV and cancer in other areas of the female reproductive system including the vagina and vulva. Whilst the incidence of vaginal cancer in the UK has remained relatively stable over the past 25 years, vulval cancer rates are increasing. A body of literature exists on the epidemiology and aetiology of vaginal and vulval cancer, but little is known about the economic burden. The objective of this study was to quantify the costs of treating these cancers on the National Health Service (NHS) in England. METHODS: Inpatient and outpatient episodes were derived from Hospital Episode Statistics (HES). Health Resource Group (HRG) tariffs and National Reference Costs were used to estimate the cost of treating pre-cancerous and invasive vaginal and vulval lesions in England. RESULTS: The study showed that for the 5 years from 2009/2010 to 2014/2015 the total cost associated with pre-cancerous and invasive vaginal and vulval lesions was over £14 million per year on average (95% of which was attributed to inpatient costs). Vulval cancer accounted for the largest proportion; an estimated 60% of the total cost (£8.82 million). On average 4316 patients per year in England were admitted to hospital and 912 patients attended outpatient settings for pre-cancerous and invasive disease of the vagina and vulva. CONCLUSION: The results indicate that vaginal and vulval cancer cost the English health care system over £14 million per year. Given the causal role of HPV in a proportion of these cancers, preventative measures such as the national HPV immunisation programme have the potential to reduce the economic burden. To ensure optimal use of NHS resources, it is important that future economic evaluations of such preventative measures consider the full burden of HPV related disease

In B cells, phosphatidylinositol 5-phosphate 4-kinase-α synthesizes PI(4,5)P2 to impact mTORC2 and Akt signaling.

Phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are enigmatic lipid kinases with physiological functions that are incompletely understood, not the least because genetic deletion and cell transfection have led to contradictory data. Here, we used the genetic tractability of DT40 cells to create cell lines in which endogenous PI5P4Kα was removed, either stably by genetic deletion or transiently (within 1 h) by tagging the endogenous protein genomically with the auxin degron. In both cases, removal impacted Akt phosphorylation, and by leaving one PI5P4Kα allele present but mutating it to be kinase-dead or have PI4P 5-kinase activity, we show that all of the effects on Akt phosphorylation were dependent on the ability of PI5P4Kα to synthesize phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] rather than to remove PI5P. Although stable removal of PI5P4Kα resulted in a pronounced decrease in Akt phosphorylation at Thr308 and Ser473, in part because of reduced plasma membrane PIP3, its acute removal led to an increase in Akt phosphorylation only at Ser473. This process invokes activation primarily of mammalian target of rapamycin complex 2 (mTORC2), which was confirmed by increased phosphorylation of other mTORC2 substrates. These findings establish PI5P4Kα as a kinase that synthesizes a physiologically relevant pool of PI(4,5)P2 and as a regulator of mTORC2, and show a phenomenon similar to the "butterfly effect" described for phosphatidylinositol 3-kinase Iα [Hart JR, et al. (2015) Proc Natl Acad Sci USA 112(4):1131-1136], whereby through apparently the same underlying mechanism, the removal of a protein's activity from a cell can have widely divergent effects depending on the time course of that removal.S.J.B. was supported by an A.J. Clark Studentship from the British Pharmacological Society, A.D. by Sidney Sussex College, the Cambridge Overseas Trust and the Säid Foundation, and J.H.C by the MRC (Grant RG64071).This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Proceedings of the National Academy of Sciences (PNAS)

InGAME international pathway to collaboration: Collaboration in Games UK-China

In 2019 the Arts &amp; Humanities Research Council (AHRC) funded a series of projects as part of its UK-China Creative Partnerships Programme. Led by Abertay University in partnership with academic and industry partners across the UK and China, InGAME International was funded through this AHRC programme with the aim of studying the potential for UK-China cooperation and collaboration in the computer games sector. The project is linked to the AHRC Creative Industries Cluster, InGAME: Innovation for Games and Media Enterprise, which is also led by Abertay University in partnership with the University of Dundee and University of St Andrews. The games industry is one of the largest and fastest growing sectors in both the UK and the Chinese creative economies. In 2023, China was the largest gaming market globally with revenue forecast at $82.064 billion compared with$7.94 billion in the UK (Statista, 2023). The growth in China’s market has long been the source of appeal for UK game developers and publishers seeking new routes to market. However, the divergence between the UK and China in terms of market profile, consumption patterns, leading companies, technologies, regulation, licensing, management, and business culture has presented ongoing difficulties for any UK based developer interested in engagement in- or with- China. It is from this basis that the current study sought to consolidate industry, legal, and regulatory knowhow with a view to providing a valuable resource to games professionals and researchers who have interests in UK-China collaboration. This Pathway to Collaboration report curates the cumulative knowledge and insight generated during the InGAME International programme, with an intended audience of games industry professionals and researchers interested in UK-China collaboration. At the heart of the research is an unprecedented qualitative study that involved in-depth interviews with 47 leading experts from the UK, China and other territories and with knowledge of games development, business, publishing, marketing, localisation, IP, copyright, regulation, markets, and sales. This report is the first comprehensive qualitative study to investigate the intersection between the UK and China games industries and markets at this scale and depth, providing readers with an invaluable, interactive resource that will support professionals and researchers to initiate new collaborations between the two nations.</p

InGAME international pathway to collaboration: Collaboration in Games UK-China

In 2019 the Arts &amp; Humanities Research Council (AHRC) funded a series of projects as part of its UK-China Creative Partnerships Programme. Led by Abertay University in partnership with academic and industry partners across the UK and China, InGAME International was funded through this AHRC programme with the aim of studying the potential for UK-China cooperation and collaboration in the computer games sector. The project is linked to the AHRC Creative Industries Cluster, InGAME: Innovation for Games and Media Enterprise, which is also led by Abertay University in partnership with the University of Dundee and University of St Andrews. The games industry is one of the largest and fastest growing sectors in both the UK and the Chinese creative economies. In 2023, China was the largest gaming market globally with revenue forecast at $82.064 billion compared with$7.94 billion in the UK (Statista, 2023). The growth in China’s market has long been the source of appeal for UK game developers and publishers seeking new routes to market. However, the divergence between the UK and China in terms of market profile, consumption patterns, leading companies, technologies, regulation, licensing, management, and business culture has presented ongoing difficulties for any UK based developer interested in engagement in- or with- China. It is from this basis that the current study sought to consolidate industry, legal, and regulatory knowhow with a view to providing a valuable resource to games professionals and researchers who have interests in UK-China collaboration. This Pathway to Collaboration report curates the cumulative knowledge and insight generated during the InGAME International programme, with an intended audience of games industry professionals and researchers interested in UK-China collaboration. At the heart of the research is an unprecedented qualitative study that involved in-depth interviews with 47 leading experts from the UK, China and other territories and with knowledge of games development, business, publishing, marketing, localisation, IP, copyright, regulation, markets, and sales. This report is the first comprehensive qualitative study to investigate the intersection between the UK and China games industries and markets at this scale and depth, providing readers with an invaluable, interactive resource that will support professionals and researchers to initiate new collaborations between the two nations.</p

On the Efficacy and Mediation of a One-on-One HIV Risk-Reduction Intervention for African American Men Who Have Sex With Men: A Randomized Controlled Trial

We examined the efficacy and mediation of Being Responsible for Ourselves (BRO), an HIV/STI risk reduction intervention for African American men who have sex with men (MSM), the population with the highest HIV diagnosis rate in the US. We randomized African American MSM to one of two interventions: BRO HIV/STI risk reduction, targeting condom use; or attention-matched control, targeting physical activity and healthy diet. The interventions were based on social cognitive theory, the reasoned-action approach, and qualitative research. Men reporting anal intercourse with other men in the past 90 days were eligible and completed pre-intervention