Epigenetic therapy in lung cancer and mesothelioma

Thoracic malignancies present a considerable global health burden with the incidence and mortality of both lung cancer and malignant pleural mesothelioma (MPM) increasing year on year. Survival rates are poor and treatment options are limited in these cancers. Several epigenetic modifications have been associated with the development of both of these diseases with alterations discriminating between MPM and adenocarcinoma (AC) of the lung. In addition, studies have suggested that epigenetic agents are effective in altering the cellular characteristics of lung and MPM cells in terms of proliferation and migration. Furthermore, it has been demonstrated that epigenetic therapy can alter a pathologically relevant gene expression profile, with one that is more associated with comparative normal tissue. Therefore agents, which target the epi-genomes of lung cancer and MPM, may provide a substantial therapeutic improvement when used in combination with current therapy or indeed benefit when used as a single treatment modality.

Gender and National Identity Constructions in the Cross-Border Merger Context

In this article we explore ways in which vertical gender inequality is accomplished in discourse in the context of a recent chain of cross-border mergers and acquisitions that resulted in the formation of a multinational Nordic company. We analyse social interactions of ‘doing’ gender in interviews with male senior executives from Denmark, Finland and Sweden. We argue that their explanations for the absence of women in the top echelons of the company serve to distance vertical gender inequality. The main contribution of the article is an analysis of how national identities are discursively (re)constructed in such distancing. New insights are offered to studying gender in multinationals with a cross-cultural team of researchers. Our study sheds light on how gender intersects with nationality in shaping the multinational organization and the identities of male executives in globalizing business.

Measurement of acceleration while walking as an automated method for gait assessment in dairy cattle

The aims were to determine whether measures of acceleration of the legs and back of dairy cows while they walk could help detect changes in gait or locomotion associated with lameness and differences in the walking surface. In 2 experiments, 12 or 24 multiparous dairy cows were fitted with five 3-dimensional accelerometers, 1 attached to each leg and 1 to the back, and acceleration data were collected while cows walked in a straight line on concrete (experiment 1) or on both concrete and rubber (experiment 2). Cows were video-recorded while walking to assess overall gait, asymmetry of the steps, and walking speed. In experiment 1, cows were selected to maximize the range of gait scores, whereas no clinically lame cows were enrolled in experiment 2. For each accelerometer location, overall acceleration was calculated as the magnitude of the 3-dimensional acceleration vector and the variance of overall acceleration, as well as the asymmetry of variance of acceleration within the front and rear pair of legs. In experiment 1, the asymmetry of variance of acceleration in the front and rear legs was positively correlated with overall gait and the visually assessed asymmetry of the steps (r ≥0.6). Walking speed was negatively correlated with the asymmetry of variance of the rear legs (r=−0.8) and positively correlated with the acceleration and the variance of acceleration of each leg and back (r ≥0.7). In experiment 2, cows had lower gait scores [2.3 vs. 2.6; standard error of the difference (SED)=0.1, measured on a 5-point scale] and lower scores for asymmetry of the steps (18.0 vs. 23.1; SED=2.2, measured on a continuous 100-unit scale) when they walked on rubber compared with concrete, and their walking speed increased (1.28 vs. 1.22m/s; SED=0.02). The acceleration of the front (1.67 vs. 1.72g; SED=0.02) and rear (1.62 vs. 1.67g; SED=0.02) legs and the variance of acceleration of the rear legs (0.88 vs. 0.94g; SED=0.03) were lower when cows walked on rubber compared with concrete. Despite the improvements in gait score that occurred when cows walked on rubber, the asymmetry of variance of acceleration of the front leg was higher (15.2 vs. 10.4%; SED=2.0). The difference in walking speed between concrete and rubber correlated with the difference in the mean acceleration and the difference in the variance of acceleration of the legs and back (r ≥0.6). Three-dimensional accelerometers seem to be a promising tool for lameness detection on farm and to study walking surfaces, especially when attached to a leg.

The top 100 questions of importance to the future of global agriculture

Despite a significant growth in food production over the past half-century, one of the most important challenges facing society today is how to feed an expected population of some nine billion by the middle of the 20th century. To meet the expected demand for food without significant increases in prices, it has been estimated that we need to produce 70-100 per cent more food, in light of the growing impacts of climate change, concerns over energy security, regional dietary shifts and the Millennium Development target of halving world poverty and hunger by 2015. The goal for the agricultural sector is no longer simply to maximize productivity, but to optimize across a far more complex landscape of production, rural development, environmental, social justice and food consumption outcomes. However, there remain significant challenges to developing national and international policies that support the wide emergence of more sustainable forms of land use and efficient agricultural production. The lack of information flow between scientists, practitioners and policy makers is known to exacerbate the difficulties, despite increased emphasis upon evidence-based policy. In this paper, we seek to improve dialogue and understanding between agricultural research and policy by identifying the 100 most important questions for global agriculture. These have been compiled using a horizon-scanning approach with leading experts and representatives of major agricultural organizations worldwide. The aim is to use sound scientific evidence to inform decision making and guide policy makers in the future direction of agricultural research priorities and policy support. If addressed, we anticipate that these questions will have a significant impact on global agricultural practices worldwide, while improving the synergy between agricultural policy, practice and research. This research forms part of the UK Government's Foresight Global Food and Farming Futures project.

The Escherichia coli Phosphotyrosine Proteome Relates to Core Pathways and Virulence

While phosphotyrosine modification is an established regulatory mechanism in eukaryotes, it is less well characterized in bacteria due to low prevalence. To gain insight into the extent and biological importance of tyrosine phosphorylation in Escherichia coli, we used immunoaffinity-based phosphotyrosine peptide enrichment combined with high resolution mass spectrometry analysis to comprehensively identify tyrosine phosphorylated proteins and accurately map phosphotyrosine sites. We identified a total of 512 unique phosphotyrosine sites on 342 proteins in E. coli K12 and the human pathogen enterohemorrhagic E. coli (EHEC) O157:H7, representing the largest phosphotyrosine proteome reported to date in bacteria. This large number of tyrosine phosphorylation sites allowed us to define five phosphotyrosine site motifs. Tyrosine phosphorylated proteins belong to various functional classes such as metabolism, gene expression and virulence. We demonstrate for the first time that proteins of a type III secretion system (T3SS), required for the attaching and effacing (A/E) lesion phenotype characteristic for intestinal colonization by certain EHEC strains, are tyrosine phosphorylated by bacterial kinases. Yet, A/E lesion and metabolic phenotypes were unaffected by the mutation of the two currently known tyrosine kinases, Etk and Wzc. Substantial residual tyrosine phosphorylation present in an etk wzc double mutant strongly indicated the presence of hitherto unknown tyrosine kinases in E. coli. We assess the functional importance of tyrosine phosphorylation and demonstrate that the phosphorylated tyrosine residue of the regulator SspA positively affects expression and secretion of T3SS proteins and formation of A/E lesions. Altogether, our study reveals that tyrosine phosphorylation in bacteria is more prevalent than previously recognized, and suggests the involvement of phosphotyrosine-mediated signaling in a broad range of cellular functions and virulence.

Acoustic signatures of the seafloor: Tools for predicting grouper habitat

Groupers are important components of commercial and recreational fisheries. Current methods of diver-based grouper census surveys could potentially benefit from development of remotely sensed methods of seabed classification. The goal of the present study was to determine if areas of high grouper abundance have characteristic acoustic signatures. A commercial acoustic seabed mapping system, QTC View Series V, was used to survey an area near Carysfort Reef, Florida Keys. Acoustic data were clustered using QTC IMPACT software, resulting in three main acoustic classes covering 94% of the area surveyed. Diver-based data indicate that one of the acoustic classes corresponded to hard substrate and the other two represented sediment. A new measurement of seabed heterogeneity, designated acoustic variability, was also computed from the acoustic survey data in order to more fully characterize the acoustic response (i.e., the signature) of the seafloor. When compared with diver-based grouper census data, both acoustic classification and acoustic variability were significantly different at sites with and without groupers. Sites with groupers were characterized by hard bottom substrate and high acoustic variability. Thus, the acoustic signature of a site, as measured by acoustic classification or acoustic variability, is a potentially useful tool for stratifying diver sampling effort for grouper census.

Synopsis of biological data on the Nassau grouper, Epinephelus striatus (Bloch, 1792), and the jewfish, E. itajara (Lichenstein, 1822)

Information on the biology, fishery resources, explotiation patterns, management, and conservation status of two species of grouper-the Nassau grouper, Epinephelus striatus, and the jewfish, Epinephelus itajara-is compiled, reviewed, and analyzed. (PDF file contains 68 pages.)

A catch-free stock assessment model with application to goliath grouper (Epinephelus itajara) off southern Florida

Many modern stock assessment methods provide the machinery for determining the status of a stock in relation to certain reference points and for estimating how quickly a stock can be rebuilt. However, these methods typically require catch data, which are not always available. We introduce a model-based framework for estimating reference points, stock status, and recovery times in situations where catch data and other measures of absolute abundance are unavailable. The specif ic estimator developed is essentially an age-structured production model recast in terms relative to pre-exploitation levels. A Bayesian estimation scheme is adopted to allow the incorporation of pertinent auxiliary information such as might be obtained from meta-analyses of similar stocks or anecdotal observations. The approach is applied to the population of goliath grouper (Epinephelus itajara) off southern Florida, for which there are three indices of relative abundance but no reliable catch data. The results confirm anecdotal accounts of a marked decline in abundance during the 1980s followed by a substantial increase after the harvest of goliath grouper was banned in 1990. The ban appears to have reduced fishing pressure to between 10% and 50% of the levels observed during the 1980s. Nevertheless, the predicted fishing mortality rate under the ban appears to remain substantial, perhaps owing to illegal harvest and depth-related release mortality. As a result, the base model predicts that there is less than a 40% chance that the spawning biomass will recover to a level that would produce a 50% spawning potential ratio.

As novas faces da dualidade educacional na contemporaneidade e o ideário educacional anarquista

A presente tese nasce da hipótese da existência da dualidade educacional (DE) nas políticas contemporâneas e que se confirma nesse trabalho. Por sua vez, a DE (uma escola para elite e outra para a classe popular) existe para que a classe hegemônica possa conservar a estratificação social e a divisão do trabalho a seu favor. Tem conivência do Estado, mesmo ele se expressando enquanto uma disputa de classe em movimento. Como metodologia de trabalho, utiliza-se o materialismo histórico-dialético no intuito de abranger o conflito de interesses entre classes sociais e poder caracterizar a materialidade e a dialeticidade nas subjetivações elucidadas. O trabalho de combate à DE é feito com mediações do ideário educacional anarquista e que se aproxima do marxismo através do nascedouro iluminista, comum às duas correntes. É um trabalho de cunho humanista e vai além da lógica iluminista. Pois é possível perceber o avanço em que o anarquismo trata as categorias igualdade, liberdade e solidariedade. No intuito de abranger melhor as relações do fenômeno da DE, é considerada a conjuntura política e econômica globalizada nas novas configurações entre Estado e sociedade civil no Brasil sob a vigência do capitalismo financeiro; além de ser levado em consideração o pensamento de Florestan Fernandes no que diz respeito ao Brasil ser um país de capitalismo dependente. Em relação às parcerias público-privadas na contemporaneidade, que promovem educação financiada pelo Estado, mas controlada pela sociedade civil; na prática, esse controle é feito por grupos empresariais, tendo em vista a falta de organização da população para esse fim. Desse modo, as estratégias hegemônicas de formatação e implantação das políticas educacionais neoliberais contribuem para a identificação do próprio fenômeno da dualidade educacional, no seio de estruturas organizativas bem planejadas. As novas faces da DE nas contradições de uma educação mercantilizada e alinhada aos ditames internacionais influenciam as políticas públicas educacionais locais. Por exemplo, a Gestão Integrada da Escola (GIDE), implantada desde 2011 na rede pública fluminense, é um projeto de caráter neoliberal, mas que tem uma lógica taylorista-fordista em seu funcionalismo gerencial administrativo-pedagógico. Nesse sistema fica patente a previsibilidade do processo fabril para a construção de um conhecimento sob a chancela de uma nova versão do tecnicismo que subtrai a criatividade e autonomia profissional e escolar, elege uma grade curricular fragmentada e mínima, prioriza o caráter quantitativo dos resultados nas estatísticas que, para tal, burocratiza o trabalho do professor e da própria escola. Na contramão desse ensino instrumental e padronizado desenvolvido pela GIDE, é conveniente rever o significado do que é o ensino libertário, que é aquele que consagra a liberdade e sacrifica progressivamente a autoridade numa educação que tem como objetivo final formar homens livres e respeitadores da liberdade alheia. Essa pesquisa no campo da educação apontou como uma forte pista a federalização das unidades escolares públicas. O chão da escola precisa assumir a sua autonomia possível frente ao sistema centralizador de ensino em um processo dialético de recriação de identidade e reafirmação da escola enquanto força organizativa local junto à comunidade

The impact of interconnectedness in a triadic relationship between a financial services provider, IFAs, and customers.

The aim of this study is to investigate the impact of interconnectedness between a long-term savings and investments provider, Independent Financial Advisers (IFAs) and customers. Ritter’s (2000) framework of the effect of interconnectedness was used to analyse this triadic relationship. Conceptual studies of triadic business relationships are scarce in marketing and organisational research (Blakenburg & Johanson, 1992; Havila, Johnson & Thilenius, 2004; Ritter, 2000). However, the applicability of a triadic relationship has been tested in a number of case studies (Andersson & Mattsson, 2004; Cunningham & Pyatt, 1989; Jaaskelainen, Kuivalainen & Saarenketo, 2000; Narayandas, 2002; Odorici & Corrado, 2004; Pardo & Salle, 1994; Trimachi, 2002). This study was conducted in collaboration with one of the UK’s largest long-term savings and investments providers. A substantial proportion of the provider’s business is conducted through IFAs and thus their significance as a major stakeholder. Indeed, the majority of sales in the long-term savings and investments industry in the UK are realised through IFAs. Academic studies (Gough, 2005; Gough & Nurullah, 2009) have indicated that IFAs are the strongest distribution channel in the industry. Thus, by analysing the impact of the interconnectedness in this relationship, a strategy that can increase the relationship performance can be proposed. However, to the best of the authors’ knowledge, a study that investigates the effect of the interconnectedness in this triadic relationship has not been established. In addition, the regulatory environment which continues to face change such as the recent implementation of Retail Distribution Review (RDR) on 1st January 2013 will make the relationship more rather than less complex.

Relationship development in international retail franchising: Case study evidence from the UK fashion sector

Doherty, A. M. and Alexander, N. (2004). Relationship development in international retail franchising: Case study evidence from the UK fashion sector. European Journal of Marketing. 38(9-10), pp.1215-1235 RAE2008

Internationalization motives and facilitating factors: Qualitative evidence from smaller specialist retailers

Hutchison, K.; Alexander, N.; Quinn, B.; and Doherty, A. M. (2007). Internationalization motives and facilitating factors: Qualitative evidence from smaller specialist retailers. Journal of International Marketing. 15(3), pp.96-122 RAE2008

Power and control in international retail franchising

Alexander, Nicholas, Doherty, Anne Marie, 'Power and control in international retail franchising', European Journal of Marketing (2006) 40(11-12) pp.1292-1316 RAE2008

The impact of learning context on the acquisition of sociopragmatic variation patterns in non-native speaker teachers of English

The study is a cross-linguistic, cross-sectional investigation of the impact of learning contexts on the acquisition of sociopragmatic variation patterns and the subsequent enactment of compound identities. The informants are 20 non-native speaker teachers of English from a range of 10 European countries. They are all primarily mono-contextual foreign language learners/users of English: however, they differ with respect to the length of time accumulated in a target language environment. This allows for three groups to be established – those who have accumulated 60 days or less; those with between 90 days and one year and the final group, all of whom have accumulated in excess of one year. In order to foster the dismantling of the monolith of learning context, both learning contexts under consideration – i.e. the foreign language context and submersion context are broken down into micro-contexts which I refer to as loci of learning. For the purpose of this study, two loci are considered: the institutional and the conversational locus. In order to make a correlation between the impact of learning contexts and loci of learning on the acquisition of sociopragmatic variation patterns, a two-fold study is conducted. The first stage is the completion of a highly detailed language contact profile (LCP) questionnaire. This provides extensive biographical information regarding language learning history and is a powerful tool in illuminating the intensity of contact with the L2 that learners experience in both contexts as well as shedding light on the loci of learning to which learners are exposed in both contexts. Following the completion of the LCP, the informants take part in two role plays which require the enactment of differential identities when engaged in a speech event of asking for advice. The enactment of identities then undergoes a strategic and linguistic analysis in order to investigate if and how differences in the enactment of compound identities are indexed in language. Results indicate that learning context has a considerable impact not only on how identity is indexed in language, but also on the nature of identities enacted. Informants with very low levels of crosscontextuality index identity through strategic means – i.e. levels of directness and conventionality; however greater degrees of cross-contextuality give rise to the indexing of differential identities linguistically by means of speaker/hearer orientation and (non-) solidary moves. When it comes to the nature of identity enacted, it seems that more time spent in intense contact with native speakers in a range of loci of learning allows learners to enact their core identity; whereas low levels of contact with over-exposure to the institutional locus of learning fosters the enactment of generic identities.

Living with acquired brain injury

This study found that natural community supports were comprised of two distinct groupings; firstly immediate families, friends and peer support groups; secondly neighbours and local community groups such as sporting and activity- based organisations and groups. The findings of this study indicate that living with acquired brain injury involves a process where the person moves from acute high intensity health services onto rehabilitative services and then onto re-establishing independent lives. It is evident that smooth transitions and interconnectivity of services are essential in facilitating this recovery process. Instrumental to the recovery is the support of immediate family and close friends, who form people’s immediate natural support network and go a long way towards facilitating individuals in rebuilding their lives. A key finding of this study is that broader natural community supports do not appear to play as central a role in supporting individuals to live independent lives when compared to the role of family and friends. The lack of involvement of broader community groups, in many ways, prompted individuals to contact formal support services. For the majority of participants, independence is facilitated through the combination of immediate natural community supports and formal services. The role of formal support services is key to developing broader community support networks. This study found a blurred division between formal services and broader community support networks. The authors recommended that the role of formal supports services in acting as a bridge between the needs of the individual and the development of meaningful community networks, be formally recognised and further developed. Additionally, they argued that the importance of the role of broader natural community, supports such as those provided by community and sporting groups must be enhanced. Greater awareness of the issues faced by people living with acquired brain injury and its often invisible nature is necessary in this endeavour. The authors stated it is important to recognise that there are multiple issues impacting on independent living and these issues intersect, for instance with age, gender, employment, qualifications and so on. A lack of public awareness of acquired brain injury was found to be a key barrier to independent living, along with issues relating to socialising, access to employment and finances. The findings of this study reflect the complexities of living with acquired brain injury and the need for holistic support that is cognisant of the factors which impact on integration. It is vital that flexible, personalised services are developed which are fit for purpose and meet the needs of not only people with acquired brain injury but also their immediate natural community support network. Recognition of the intersection between immediate/ broader natural community supports and formal services is also key to developing the comprehensive and practical supports required to achieve an independent life. This was a qualitative study and all participants were sourced through Headway, a community based service provider for people with ABI. Data collection was divided into two stages: firstly focus groups, followed by individual interviews. Four focus groups were convened in Cork (2), Dublin (1) and Limerick (1). Each focus group was facilitated by at least two members of the research team and a total of twenty-six individuals participated in the focus groups. Thematic analysis of the data was undertaken to guide and inform the second stage of the study; the individual interviews. Ten interviews were undertaken with individuals who presented with ABI in the Cork and Limerick regions.