CD44v8-10 Is a Cancer-Specific Marker for Gastric Cancer Stem Cells

The surface marker CD44 has been identified as one of several markers associated with cancer stem cells (CSC) in solid tumors, but its ubiquitous expression in many cell types, including hematopoietic cells, has hindered its use in targeting CSCs. In this study, 28 paired primary tumor and adjacent nontumor gastric tissue samples were analyzed for cell surface protein expression. Cells that expressed pan-CD44 were found to occur at significantly higher frequency in gastric tumor tissues. We identified CD44v8-10 as the predominant CD44 variant expressed in gastric cancer cells and verified its role as a gastric CSC marker by limiting dilution and serial transplantation assays. Parallel experiments using CD133 failed to enrich for gastric CSCs. Analyses of another 26 primary samples showed significant CD44v8-10 upregulation in gastric tumor sites. Exogenous expression of CD44v8-10 but not CD44 standard (CD44s) increased the frequency of tumor initiation in immunocompromised mice. Reciprocal silencing of total CD44 resulted in reduced tumor-initiating potential of gastric cancer cells that could be rescued by CD44v8-10 but not CD44s expression. Our findings provide important functional evidence that CD44v8-10 marks human gastric CSCs and contributes to tumor initiation, possibly through enhancing oxidative stress defense. In addition, we showed that CD44v8-10 expression is low in normal tissues. Because CD44 also marks CSCs of numerous human cancers, many of which may also overexpress CD44v8-10, CD44v8-10 may provide an avenue to target CSCs in other human cancers.

In situ, high-resolution imaging of labile phosphorus in sediments of a large eutrophic lake

Understanding the labile status of phosphorus (P) in sediments is crucial for managing a eutrophic lake, but it is hindered by lacking in situ data particularly on a catchment scale. In this study, we for the first time characterized in situ labile P in sediments with the Zr-oxide diffusive gradients in thin films (Zr-oxide DGT) technique at a two-dimensional (2D), submillimeter resolution in a large eutrophic lake (Lake Taihu, China, with an area of 2338km²). The concentration of DGT-labile P in the sediment profiles showed strong variation mostly ranging from 0.01 to 0.35mgL^-1 with a considerable number of hotspots. The horizontal heterogeneity index of labile P varied from 0.04 to 4.5. High values appeared at the depths of 0-30mm, likely reflecting an active layer of labile P under the sediment-water interface (SWI). Concentration gradients of labile P were observed from the high-resolution 1D DGT profiles in both the sediment and overlying water layers close to the SWI. The apparent diffusion flux of P across the SWI was calculated between -21 and 65ngcm^-2d^-1, which showed that the sediments tended to be a source and sink of overlying water P in the algal- and macrophyte-dominated regions, respectively. The DGT-labile P in the 0-30mm active layer showed a better correlation with overlying water P than the labile P measured by ex situ chemical extraction methods. It implies that in situ, high-resolution profiling of labile P with DGT is a more reliable approach and will significantly extend our ability in in situ monitoring of the labile status of P in sediments in the field.

Combined effect of high pressure processing and antimicrobial packaging to control the growth of Listeria monocytogenes on ready-to-eat chicken breast

In the European Union, food is considered safe with regard to Listeria monocytogenes if its numbers do not exceed 100 cfu/g throughout the shelf-life of the food. Therefore, it is important to determine if a food supports growth of L. monocytogenes. Challenge tests are laboratory-based studies that measure the growth of L. monocytogenes on artificially contaminated food stored under foreseeable conditions of transportation, distribution and storage. The aim of this study was to elaborate and optimize a user-friendly protocol to perform challenge tests on food and to apply it to determine whether growth of L. monocytogenes is supported during the production and distribution of a potentially risky food i.e. mushrooms. A three-strain mixture of L. monocytogenes was inoculated onto three independent batches of whole mushrooms, sliced mushrooms, mushroom casing and mushroom substrate at a concentration of about 100 -1000 cfu/g. The batches were incubated at potential abuse temperatures, as a worst case scenario, and at intervals during storage L. monocytogenes numbers, % moisture and pH were determined. The results showed that the sliced and whole mushrooms supported growth of L. monocytogenes while mushroom casing allowed survival but did not support growth. Mushroom substrate showed a rich background microflora able of growing in Listeria selective media which hindered enumeration of L. monocytogenes. Combase predictions were not always accurate, indicating that challenge tests are a necessary part of growth determination of L. monocytogenes.

Computational scheduling methods for integrating plug-in electric vehicles with power systems: a review

Traditional internal combustion engine vehicles are a major contributor to global greenhouse gas emissions and other air pollutants, such as particulate matter and nitrogen oxides. If the tail pipe point emissions could be managed centrally without reducing the commercial and personal user functionalities, then one of the most attractive solutions for achieving a significant reduction of emissions in the transport sector would be the mass deployment of electric vehicles. Though electric vehicle sales are still hindered by battery performance, cost and a few other technological bottlenecks, focused commercialisation and support from government policies are encouraging large scale electric vehicle adoptions. The mass proliferation of plug-in electric vehicles is likely to bring a significant additional electric load onto the grid creating a highly complex operational problem for power system operators. Electric vehicle batteries also have the ability to act as energy storage points on the distribution system. This double charge and storage impact of many uncontrollable small kW loads, as consumers will want maximum flexibility, on a distribution system which was originally not designed for such operations has the potential to be detrimental to grid balancing. Intelligent scheduling methods if established correctly could smoothly integrate electric vehicles onto the grid. Intelligent scheduling methods will help to avoid cycling of large combustion plants, using expensive fossil fuel peaking plant, match renewable generation to electric vehicle charging and not overload the distribution system causing a reduction in power quality. In this paper, a state-of-the-art review of scheduling methods to integrate plug-in electric vehicles are reviewed, examined and categorised based on their computational techniques. Thus, in addition to various existing approaches covering analytical scheduling, conventional optimisation methods (e.g. linear, non-linear mixed integer programming and dynamic programming), and game theory, meta-heuristic algorithms including genetic algorithm and particle swarm optimisation, are all comprehensively surveyed, offering a systematic reference for grid scheduling considering intelligent electric vehicle integration.

UK medical graduates’ preparedness for practice (P4P): A multi-site qualitative study

Introduction Previous research has demonstrated mixed findings in terms of graduates’ P4P in terms of their knowledge and skills, and interpersonal, systemic and technological aspects (Monrouxe et al. 2014). Few studies have included diverse stakeholders from multiple sites and employing longitudinal methods. We therefore aimed to understand the extent to which UK medical graduates are prepared for practice as Foundation doctors. Methods Cross-sectional qualitative narrative interview and longitudinal audio-diary (LAD) studies with participants from England, Scotland, Wales and Northern Ireland. Study 1 comprised 27 group and 84 individual interviews (n=185) with participants representing different stakeholders (F1s, fully registered trainees, clinical educators, undergraduate/postgraduate deans/foundation programme directors, other healthcare professionals, employers, policy makers, government representatives, and patient/public representatives). Study 2 comprised LADs with 26 F1s over 4-months. Results Participants found it hard initially to conceptualise the term ‘preparedness for practice’. We identified 2187 personal incident narratives (i.e. stories of P4P experiences) across our data: 506 (23%) were classed as ‘prepared’, 730 (33%) as ‘unprepared’ and 951 (44%) as ‘unspecified’. We identified factors that facilitated (e.g. supportive supervisors/colleagues, opportunities for shadowing) and hindered (e.g. unsupportive or disrespectful colleagues, poor organization, understaffing) transitions into and through the Foundation programme. The LADs suggested that trainees felt more confident and competent over time, but that such development was not always linear as challenging circumstances (e.g. new rotations) sometimes made trainees feel unprepared for situations where they had previously indicated preparedness. Conclusion Our findings add to the existing evidence on medical graduates’ P4P in the UK (e.g. Goldacre et al. 2008; Illing et al. 2013). Our findings support the role of assistantships and supportive supervisors for smoothing transitions from student to F1. Further longitudinal and action research studies are now needed to follow students through their final-year assistantships and into their F2 year.

Catholicism and Fascism in Interwar Ireland

The interwar era saw the collapse of liberal democracy and the rise of anti-democratic authoritarian movements and states throughout much of Europe. Parliamentary or liberal democracy proved especially vulnerable in countries with large Catholic populations and ‘successor states’ – those states that achieved independence following the Great War. Despite meeting both criteria, the democratic structures of the Irish Free State – established in 1922 following a revolutionary struggle against British rule – proved remarkably resilient: indeed, it was arguably the only successor state to remain fully democratic by 1939 This outcome appears all the more striking given the formation of the state amidst a civil war, a form of conflict that frequently prevented the successful emergence of democracy. This is an article about the dog that didn’t bark: why did the kind of authoritarian political movements that flourished in many other parts of interwar Europe attract negligible support in the Irish Free State, and what does this have to tell us about the relationship between Catholicism and authoritarian politics? It begins by surveying the Irish Catholic Church’s attitudes to far-right politics in Continental Europe, and assessing how ‘official’ Catholic attitudes shaped popular perceptions of fascism and clerical authoritarianism within Ireland. It then explores the extent to which Ireland’s only significant fascistic movement – the Blueshirts – was influenced by, and sought to exploit, Catholicism. It concludes by questioning whether the immense influence of the Catholic Church and Catholic values within Irish political culture and society facilitated or hindered the cause of authoritarian politics in Ireland.

Machine learning for transient discovery in Pan-STARRS1 difference imaging

Efficient identification and follow-up of astronomical transients is hindered by the need for humans to manually select promising candidates from data streams that contain many false positives. These artefacts arise in the difference images that are produced by most major ground-based time-domain surveys with large format CCD cameras. This dependence on humans to reject bogus detections is unsustainable for next generation all-sky surveys and significant effort is now being invested to solve the problem computationally. In this paper, we explore a simple machine learning approach to real-bogus classification by constructing a training set from the image data of similar to 32 000 real astrophysical transients and bogus detections from the Pan-STARRS1 Medium Deep Survey. We derive our feature representation from the pixel intensity values of a 20 x 20 pixel stamp around the centre of the candidates. This differs from previous work in that it works directly on the pixels rather than catalogued domain knowledge for feature design or selection. Three machine learning algorithms are trained (artificial neural networks, support vector machines and random forests) and their performances are tested on a held-out subset of 25 per cent of the training data. We find the best results from the random forest classifier and demonstrate that by accepting a false positive rate of 1 per cent, the classifier initially suggests a missed detection rate of around 10 per cent. However, we also find that a combination of bright star variability, nuclear transients and uncertainty in human labelling means that our best estimate of the missed detection rate is approximately 6 per cent.

The impact of organisational factors and government policy on psychiatric nurses family focused practice with parents who have mental illness, their dependent children and families in Ireland

Government policy and organizational factors influence family focused practice in adult mental health services. However, how these aspects shape psychiatric nurses’ practice with parents who have mental illness, their dependent children and families is less well understood. Drawing on the findings of a qualitative study, this article explores the way in which Irish policy and organizational factors might influence psychiatric nurses’ family focused practice, and whether (and how) family focused practice might be further promoted. A purposive sample of 14 psychiatric nurses from eight mental health services completed semi-structured interviews in 2013. The analysis was inductive and presented as thematic networks. Both groups described how policies and organizational culture enabled and/or hindered family focused practice, with differences between community and acute participants seen. The need to develop national and international policies along with practices to embed information and support regarding parenting into ongoing care is implicated in this study.

A practical taxonomy of methods and literature for managing uncertain spatial data in geographic information systems

Perfect information is seldom available to man or machines due to uncertainties inherent in real world problems. Uncertainties in geographic information systems (GIS) stem from either vague/ambiguous or imprecise/inaccurate/incomplete information and it is necessary for GIS to develop tools and techniques to manage these uncertainties. There is a widespread agreement in the GIS community that although GIS has the potential to support a wide range of spatial data analysis problems, this potential is often hindered by the lack of consistency and uniformity. Uncertainties come in many shapes and forms, and processing uncertain spatial data requires a practical taxonomy to aid decision makers in choosing the most suitable data modeling and analysis method. In this paper, we: (1) review important developments in handling uncertainties when working with spatial data and GIS applications; (2) propose a taxonomy of models for dealing with uncertainties in GIS; and (3) identify current challenges and future research directions in spatial data analysis and GIS for managing uncertainties.

An in vitro model of nociceptors in human trigeminal nerves

Background: The oro-facial region is densely innervated by the trigeminal nerve, which when stimulated can induce noxious pain sensation and contribute to neurogenic inflammation in local tissues. Recent research on the expression of specialised ion channels on the trigeminal nerve has highlighted the need to undertake more extensive studies on ion channel expression/functionality with the aim of elucidating their role in pain sensations. A major family of such ion channels is the transient receptor potential (TRP) channels which are activated by a wide variety of thermal, mechanical or chemical stimuli and merit investigation as possible druggable targets for future analgesics.
Objective: Study of TRP channel expression and regulation in oro-facial tissues is hindered by the fact that the cell bodies of neurons innervating these tissues are located in the trigeminal ganglion. Using dental pulp stem cells differentiated towards peripheral neuronal equivalents (PNEs), we sought to determine TRP channel expression, functionality and potential modulation by cytokines in this novel model.
Method: Dental pulp stem cells (DPSCs) were grown on substrate-coated tissue culture plates and differentiated towards a neuronal phenotype using neuronal induction media. Quantitative polymerase chain reaction (qPCR) was performed on PNEs +/-cytokine treatment. Ion channel functionality was investigated using whole cell patch clamping.
Result: qPCR analysis showed that PNEs expressed the TRP channels TRPA1, TRPV1, TRPV4 and TRPM8. TRPA1 was the most abundantly expressed TRP channel studied whereas TRPM8 was lowly expressed. TRP channel expression was shown to be regulated by treatment with inflammatory cytokines. Patch clamp studies using specific agonists and antagonists for TRPA1 and TRPV1 showed these channels were functional.
Conclusion: PNEs differentiated from DPSCs provide a suitable model for TRP channel expression, regulation, and sensistisation in oro-facial tissues. This human neuronal model has potential for use in pre-clinical studies of novel analgesics.

The value of tests in the diagnosis and management of glaucoma.

PURPOSE:

To assess the noneconomic value of tests used in the diagnosis and management of glaucoma, and explore the contexts and factors that determine such value.

DESIGN:

Perspective.

METHODS:

Selected articles from primary and secondary sources were reviewed and interpreted in the context of the authors' clinical and research experience, influenced by our perspectives on the tasks of reducing the global problem of irreversible blindness caused by glaucoma. The value of any test used in glaucoma is addressed by 3 questions regarding: its contexts, its kind of value, and its implicit or explicit benefits.

RESULTS:

Tonometry, slit-lamp gonioscopy, and optic disc evaluation remain the foundation of clinic-based case finding, whether in areas of more or less abundant resources. In resource-poor areas, there is urgency in identifying patients at risk for severe functional loss of vision; screening strategies have proven ineffective, and efforts are hindered by the inadequate allocation of support. In resource-abundant areas, the wider spectrum of glaucoma is addressed, with emphasis on early detection of structural changes of little functional consequence; these are increasingly the focus of new and expensive technologies whose clinical value has not been established in longitudinal and population-based studies. These contrasting realities in part reflect differences among the value ascribed, often implicitly, to the tests used in glaucoma.

CONCLUSIONS:

The value of any test is determined by 3 aspects: its context of usage; its comparative worth and to whom its benefit accrues; and how we define historically what we are testing. These multiple factors

Molecular phylogenetic analysis of a known and a new hydrothermal vent octopod:Their relationships with the genus Benthoctopus (Cephalopoda: Octopodidae)

The resolution of evolutionary relationships among deep-sea incirrate octopuses has been hindered by the paucity of individuals available for morphological studies and by the lack of tissue samples preserved using fixatives compatible with simple DNA extraction techniques. Evolutionary relationships from 11 species of deep-sea incirrate octopuses were investigated using 2392 base pairs (bp) of DNA from four mitochondrial genes (12S rDNA, 16S rDNA, cytochrome c oxidase subunit III, and cytochrome b) and the nuclear gene, rhodopsin. Morphological examination of these species was also undertaken. Molecular analyses distinguish a species of octopus from hydrothermal vents at Manus Basin from the vent octopodid Vulcanoctopus hydrothermalis known from vents on the East Pacific Rise. Both are herein considered members of the clade currently assigned the name Benthoctopus, although taxonomic implications preclude formally naming Vulcanoctopus as a junior synonym. Morphological investigations led to the conclusion that Benthoctopus macrophallus is a junior synonym of Benthoctopus yaquinae. An amended diagnosis of Benthoctopus is provided with additional information on male reproductive characteristics. Copyright © 2009 · Magnolia Press.

Northern Ireland

Northern Ireland has been considered a conflict-resolution success story. The 1998 Belfast/Good Friday Agreement provided a framework for managing a long-standing ethnonational conflict, and has ushered in relative political stability. The consociational features of the Northern Ireland Assembly can be seen either as necessary for managing conflict or as institutionalizing sectarianism so that politics along left–right lines cannot emerge. Although there is evidence for the development of a “Northern Irish” identity to counter competing British and Irish identities, Northern Ireland is a long way from transcending the sectarian structures that shape almost all aspects of social and political life. Northern Ireland remains segregated along religious lines and is also prone to tensions around the anniversaries of atrocities and the public use of symbols and rituals. The failure to systematically “deal with the past” through public information recovery and truth-telling mechanisms also seems to have hindered progress toward reconciliation.

Beneficial Effects of Berberine on Oxidized LDL-induced Cytotoxicity in Human Retinal Müller Cells

PURPOSE. Limited mechanistic understanding of diabetic retinopathy (DR) has hindered therapeutic advances. Berberine, an isoquinolone alkaloid, has shown favorable effects on glucose and lipid metabolism in animal and human studies, but effects on DR are unknown. We previously demonstrated intraretinal extravasation and modification of LDL in human diabetes, and toxicity of modified LDL to human retinal M¨uller cells. We now explore pathogenic effects of modified LDL on M¨uller cells, and the efficacy of berberine in mitigating this cytotoxicity. METHODS. Confluent human M¨uller cells were exposed to in vitro–modified ‘highly oxidized, glycated (HOG-) LDL versus native-LDL (N-LDL; 200 mg protein/L) for 6 or 24 hours, with/ without pretreatment with berberine (5 lM, 1 hour) and/or the adenosine monophosphate (AMP)-activated protein kinase (AMPK) inhibitor, Compound C (5 lM, 1 hour). Using techniques including Western blots, reactive oxygen species (ROS) detection assay, and quantitative real-time PCR, the following outcomes were assessed: cell viability (CCK-8 assay), autophagy (LC3, Beclin-1, ATG-5), apoptosis (cleaved caspase 3, cleaved poly-ADP ribose polymerase), oxidative stress (ROS, nuclear factor erythroid 2-related factor 2, glutathione peroxidase 1, NADPH oxidase 4), angiogenesis (VEGF, pigment epithelium-derived factor), inflammation (inducible nitric oxide synthase, intercellular adhesion molecule 1, IL-6, IL-8, TNF-a), and glial cell activation (glial fibrillary acidic protein). RESULTS. Native-LDL had no effect on cultured human M¨uller cells, but HOG-LDL exhibited marked toxicity, significantly decreasing viability and inducing autophagy, apoptosis, oxidative stress, expression of angiogenic factors, inflammation, and glial cell activation. Berberine attenuated all the effects of HOG-LDL (all P < 0.05), and its effects were mitigated by AMPK inhibition (P < 0.05). CONCLUSIONS. Berberine inhibits modified LDL-induced M¨uller cell injury by activating the AMPK pathway, and merits further study as an agent for preventing and/or treating DR.