155 research outputs found

    The victorious English language: hegemonic practices in the management academy

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    This study explores hegemonic linguistic processes, that is, the dominant and unreflective use of the English language in the production of textual knowledge accounts. The authors see the production of management knowledge as situated in central or peripheral locations, which they examine from an English language perspective. Their inquiry is based on an empirical study based on the perspectives of 33 management academics (not English language speakers) in (semi) peripheral locations, who have to generate and disseminate knowledge in and through the English language. Although the hegemony of the center in the knowledge production process has long been acknowledged, the specific contribution of this study is to explore how the English language operates as part of the “ideological complex” that produces and maintains this hegemony, as well as how this hegemony is manifested at the local level of publication practices in peripherally located business and management schools

    Cerebellar ataxia with sensory ganglionopathy; does autoimmunity have a role to play?

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    Background and purpose: Cerebellar ataxia with sensory ganglionopathy (SG) is a disabling combination of neurological dysfunction usually seen as part of some hereditary ataxias. However, patients may present with this combination without a genetic cause. Methods: We reviewed records of all patients that have been referred to the Sheffield Ataxia Centre who had neurophysiological and imaging data suggestive of SG and cerebellar ataxia respectively. We excluded patients with Friedreich's ataxia, a common cause of this combination. All patients were screened for genetic causes and underwent extensive investigations. Results: We identified 40 patients (45% males, mean age at symptom onset 53.7 ± 14.7 years) with combined cerebellar ataxia and SG. The majority of patients (40%) were initially diagnosed with cerebellar dysfunction and 30% were initially diagnosed with SG. For 30% the two diagnoses were made at the same time. The mean latency between the two diagnoses was 6.5 ± 8.9 years (range 0-44). The commonest initial manifestation was unsteadiness (77.5%) followed by patchy sensory loss (17.5%) and peripheral neuropathic pain (5%).Nineteen patients (47.5%) had gluten sensitivity, of whom 3 patients (7.5%) had biopsy proven coeliac disease. Other abnormal immunological tests were present in another 15 patients. Six patients had malignancy, which was diagnosed within 5 years of the neurological symptoms. Only 3 patients (7.5%) were classified as having a truly idiopathic combination of cerebellar ataxia with SG. Conclusion: Our case series highlights that amongst patients with the unusual combination of cerebellar ataxia and SG, immune pathogenesis plays a significant role

    The S enantiomer of 2-hydroxyglutarate increases central memory CD8 populations and improves CAR-T therapy outcome

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    Cancer immunotherapy is advancing rapidly and gene-modified T cells expressing chimeric antigen receptors (CARs) show particular promise. A challenge of CAR-T cell therapy is that the ex vivo-generated CAR-T cells become exhausted during expansion in culture, and do not persist when transferred back to patients. It has become clear that naive and memory CD8 T cells perform better than the total CD8 T-cell populations in CAR-T immunotherapy because of better expansion, antitumor activity, and persistence, which are necessary features for therapeutic success and prevention of disease relapse. However, memory CAR-T cells are rarely used in the clinic due to generation challenges. We previously reported that mouse CD8 T cells cultured with the S enantiomer of the immunometabolite 2-hydroxyglutarate (S-2HG) exhibit enhanced antitumor activity. Here, we show that clinical-grade human donor CAR-T cells can be generated from naive precursors after culture with S-2HG. S-2HG-treated CAR-T cells establish long-term memory cells in vivo and show superior antitumor responses when compared with CAR-T cells generated with standard clinical protocols. This study provides the basis for a phase 1 clinical trial evaluating the activity of S-2HG-treated CD19-CAR-T cells in patients with B-cell malignancies

    Metaproteomics and metabolomics analyses of chronically petroleum-polluted sites reveal the importance of general anaerobic processes uncoupled with degradation

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    Crude oil is one of the most important natural assets for humankind, yet it is a major environmental pollutant, notably in marine environments. One of the largest crude oil polluted areas in the word is the semi-enclosed Mediterranean Sea, in which the metabolic potential of indigenous microbial populations towards the large-scale chronic pollution is yet to be defined, particularly in anaerobic and micro-aerophilic sites. Here, we provide an insight into the microbial metabolism in sediments from three chronically polluted marine sites along the coastline of Italy: the Priolo oil terminal/refinery site (near Siracuse, Sicily), harbour of Messina (Sicily) and shipwreck of MT Haven (near Genoa). Using shotgun metaproteomics and community metabolomics approaches, the presence of 651 microbial proteins and 4776 metabolite mass features have been detected in these three environments, revealing a high metabolic heterogeneity between the investigated sites. The proteomes displayed the prevalence of anaerobic metabolisms that were not directly related with petroleum biodegradation, indicating that in the absence of oxygen, biodegradation is significantly suppressed. This suppression was also suggested by examining the metabolome patterns. The proteome analysis further highlighted the metabolic coupling between methylotrophs and sulphate reducers in oxygen-depleted petroleum-polluted sediments

    Conversion of Uric Acid into Ammonium in Oil-Degrading Marine Microbial Communities: a Possible Role of Halomonads

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    Uric acid is a promising hydrophobic nitrogen source for biostimulation of microbial activities in oil-impacted marine environments. This study investigated metabolic processes and microbial community changes in a series of microcosms using sediment from the Mediterranean and the Red Sea amended with ammonium and uric acid. Respiration, emulsification, ammonium and protein concentration measurements suggested a rapid production of ammonium from uric acid accompanied by the development of microbial communities containing hydrocarbonoclastic bacteria after 3 weeks of incubation. About 80 % of uric acid was converted to ammonium within the first few days of the experiment. Microbial population dynamics were investigated by Ribosomal Intergenic Spacer Analysis and Illumina sequencing as well as by culture-based techniques. Resulting data indicated that strains related to Halomonas spp. converted uric acid into ammonium, which stimulated growth of microbial consortia dominated by Alcanivorax spp. and Pseudomonas spp. Several strains of Halomonas spp. were isolated on uric acid as the sole carbon source showed location specificity. These results point towards a possible role of halomonads in the conversion of uric acid to ammonium utilized by hydrocarbonoclastic bacteria

    Understanding the antimicrobial mechanism of TiO2-based nanocomposite films in a pathogenic bacterium

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    Titania (TiO2)-based nanocomposites subjected to light excitation are remarkably effective in eliciting microbial death. However, the mechanism by which these materials induce microbial death and the effects that they have on microbes are poorly understood. Here, we assess the low dose radical-mediated TiO2 photocatalytic action of such nanocomposites and evaluate the genome/proteome-wide expression profiles of Pseudomonas aeruginosa PAO1 cells after two minutes of intervention. The results indicate that the impact on the gene-wide flux distribution and metabolism is moderate in the analysed time span. Rather, the photocatalytic action triggers the decreased expression of a large array of genes/proteins specific for regulatory, signalling and growth functions in parallel with subsequent selective effects on ion homeostasis, coenzyme-independent respiration and cell wall structure. The present work provides the first solid foundation for the biocidal action of titania and may have an impact on the design of highly active photobiocidal nanomaterial

    Research and Client-Based Projects

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    This chapter will:; ; ; Show how to develop a needs analysis based on sound research principles;; ; ; Examine a number of different client-based projects that have taken a business discourse approach to teaching;; ; ; Discuss different ways in which business discourse research can be used in the classroom;; ; ; Present a case study that illustrates how business discourse projects can be incorporated into teaching practices together with a set of tasks related to the use of business discourse research in the classroom and a set of further readings

    Fuzzy min-max neural networks for categorical data: application to missing data imputation

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    The fuzzy min–max neural network classifier is a supervised learning method. This classifier takes the hybrid neural networks and fuzzy systems approach. All input variables in the network are required to correspond to continuously valued variables, and this can be a significant constraint in many real-world situations where there are not only quantitative but also categorical data. The usual way of dealing with this type of variables is to replace the categorical by numerical values and treat them as if they were continuously valued. But this method, implicitly defines a possibly unsuitable metric for the categories. A number of different procedures have been proposed to tackle the problem. In this article, we present a new method. The procedure extends the fuzzy min–max neural network input to categorical variables by introducing new fuzzy sets, a new operation, and a new architecture. This provides for greater flexibility and wider application. The proposed method is then applied to missing data imputation in voting intention polls. The micro data—the set of the respondents’ individual answers to the questions—of this type of poll are especially suited for evaluating the method since they include a large number of numerical and categorical attributes

    The two enantiomers of 2-hydroxyglutarate differentially regulate cytotoxic T cell function

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    2-Hydroxyglutarate (2HG) is a byproduct of the tricarboxylic acid (TCA) cycle and is readily detected in the tissues of healthy individuals. 2HG is found in two enantiomeric forms: S-2HG and R-2HG. Here, we investigate the differential roles of these two enantiomers in cluster of differentiation (CD)8+ T cell biology, where we find they have highly divergent effects on proliferation, differentiation, and T cell function. We show here an analysis of structural determinants that likely underlie these differential effects on specific α-ketoglutarate (αKG)-dependent enzymes. Treatment of CD8+ T cells with exogenous S-2HG, but not R-2HG, increased CD8+ T cell fitness in vivo and enhanced anti-tumor activity. These data show that S-2HG and R-2HG should be considered as two distinct and important actors in the regulation of T cell function. Proteomic
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