168 resultados para Botterill, Jason


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Purpose: The purpose of this paper is to investigate the relationship between the facets of cultural intelligence (CQ) (cognitive, meta-cognitive, motivational and behavioural) and the dimensions of cross-cultural adjustment (interaction, general and work adjustment).

Design/methodology/approach: Interviews and questionnaire survey were carried out with British expatriates from the architectural, engineering and construction sector. A total of 191 respondents, with experience from 29 different countries, actively participated in this research. Structural equation model was subsequently developed to investigate the relationship between elements of CQ and cross-cultural adjustment.

Findings: Results of structural equation modelling revealed that collectively all the four aspects of CQ have significant influence on general, interaction and work adjustment, particularly motivational and cognitive CQ. Cognitive CQ which empowers the expatriates with in-depth knowledge about different cultures was a significant predictor of interaction and work adjustment, whereas, motivational CQ is a significant predictor for general and work adjustment. However, no support was gathered for meta-cognitive and behavioural aspects of CQ.

Practical implications: Globally, construction companies and projects are entering an era of increased internationalisation which has prompted the migration/promotion of British construction professionals to different parts of the world for their specialised capabilities and skills. Thus, it is of utmost importance that these professionals adjust to their new world of varied culture and still be productive in their work.

Originality/value: An understanding of these essential factors can actually help British construction organisations to select and mentor individuals and to provide necessary training for successful international assignments.

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Rationale: Mesenchymal stem cells secrete paracrine factors that can regulate lung permeability and decrease inflammation, making it a potentially attractive therapy for acute lung injury. However, concerns exist whether mesenchymal stem cells' immunomodulatory properties may have detrimental effects if targeted toward infectious causes of lung injury. Objectives: Therefore, we tested the effect of mesenchymal stem cells on lung fluid balance, acute inflammation, and bacterial clearance. Methods: We developed an Escherichia coli pneumonia model in our ex vivo perfused human lung to test the therapeutic effects of mesenchymal stem cells on bacterial-induced acute lung injury. Measurements and Main Results: Clinical-grade human mesenchymal stem cells restored alveolar fluid clearance to a normal level, decreased inflammation, and were associated with increased bacterial killing and reduced bacteremia, in part through increased alveolar macrophage phagocytosis and secretion of antimicrobial factors. Keratinocyte growth factor, a soluble factor secreted by mesenchymal stem cells, duplicated most of the antimicrobial effects. In subsequent in vitro studies, we discovered that human monocytes expressed the keratinocyte growth factor receptor, and that keratinocyte growth factor decreased apoptosis of human monocytes through AKT phosphorylation, an effect that increased bacterial clearance. Inhibition of keratinocyte growth factor by a neutralizing antibody reduced the antimicrobial effects of mesenchymal stem cells in the ex vivo perfused human lung and monocytes grown in vitro injured with E. coli bacteria. Conclusions: In E. coli-injured human lungs, mesenchymal stem cells restored alveolar fluid clearance, reduced inflammation, and exerted antimicrobial activity, in part through keratinocyte growth factor secretion.

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The flexibility of the metal-organic framework Cu-2(OH)(C8H3O7S)(H2O)center dot 2H(2)O (Cu-SIP-3) toward reversible single-crystal to single-crystal transformations is demonstrated using in situ diffraction methods at variable temperature. At temperatures below a dehydration-induced phase transition (T < 370 K) the structure is confirmed as being hydrated. In the temperature range where the transition takes place (370 K < T < 405 K) no discrete, sharp Bragg peaks can be seen in the single-crystal X-ray diffraction pattern, indicating significant loss of long-range order. At temperatures higher than 405 K, the Bragg peaks return and the structure can be refined as dehydrated Cu-SIP-3. The loss of guest water molecules can be followed at temperatures below the phase transition giving insight into the mechanism of the dehydration. Addition of nitric oxide gas to the material above the gating opening pressure of 275 mbar also leads to loss of Bragg scattering in the diffraction pattern.

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High power femtosecond laser pulses have unique properties that could lead to their application as ionization or activation sources in mass spectrometry. By concentrating many photons into pulse lengths approaching the timescales associated with atomic motion, very strong electric field strengths are generated, which can efficiently ionize and fragment molecules without the need for resonant absorption. However, the complex interaction between these pulses and biomolecular species is not well understood. To address this issue, we have studied the interaction of intense, femtosecond pulses with a number of amino acids and small peptides. Unlike previous studies, we have used neutral forms of these molecular targets, which allowed us to investigate dissociation of radical cations without the spectra being complicated by the action of mobile protons. We found fragmentation was dominated by fast, radical-initiated dissociation close to the charge site generated by the initial ionization or from subsequent ultrafast migration of this charge. Fragments with lower yields, which are useful for structural determinations, were also observed and attributed to radical migration caused by hydrogen atom transfer within the molecule.

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A boronic acid moiety was found to be a critical pharmacophore for enhanced in vitro potency against wild type hepatitis C replicons and known clinical polymorphic and resistant HCV mutant replicons. The synthesis, optimization, and structure-activity relationships associated with inhibition of HCV replication in a sub-genomic replication system for a series of non-nucleoside boron-containing HCV RNA-Dependent RNA Polymerase (NS5B) inhibitors are described. A summary of the discovery of GSK5852 (3), a molecule which entered clinical trials in subjects infected with HCV in 2011, is included.

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The degree of gene hypermethylation in non-neoplastic colonic mucosa (NNCM) is a potentially important event in the development of colorectal cancer (CRC), particularly for the subgroup with a CpG island methylator phenotype (CIMP). In this study, we aimed to use an unbiased and high-throughput approach to evaluate the topography of DNA methylation in the non-neoplastic colonic mucosa (NNCM) surrounding colorectal cancer (CRC). A total of 61 tissue samples comprising 53 NNCM and 8 tumor samples were obtained from hemicolectomy specimens of two CRC patients (Cases 1 and 2). NNCM was stripped from the underlying colonic wall and samples taken at varying distances from the tumor. The level of DNA methylation in NNCM and tumor tissues was assessed at 1,505 CpG sites in 807 cancer-related genes using Illumina GoldenGate® methylation arrays. Case 1 tumor showed significantly higher levels of methylation compared to surrounding NNCM samples (P?

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A downstream target of the Wnt pathway, neurone glial-related cell adhesion molecule (Nr-CAM) has recently been implicated in human cancer development. However, its role in colorectal cancer (CRC) pathobiology and clinical relevance remains unknown. In this study, we examined the clinical significance of Nr-CAM protein expression in a retrospective series of 428 CRCs using immunohistochemistry and tissue microarrays. Cox proportional hazards regression was used to calculate hazard ratios (HR) of mortality according to various clinicopathological features and molecular markers. All CRC samples were immunoreactive for Nr-CAM protein expression, compared to 10 / 245 (4%) matched normal tissue (P <0.0001). Of 428 CRC samples, 97 (23%) showed Nr-CAM overexpression, which was significantly associated with nodal (P = 0.012) and distant (P = 0.039) metastasis, but not with extent of local invasion or tumor size. Additionally, Nr-CAM overexpression was associated with vascular invasion (P = 0.0029), p53 expression (P = 0.036), and peritoneal metastasis at diagnosis (P = 0.013). In a multivariate model adjusted for other clinicopathological predictors of survival, Nr-CAM overexpression correlated with a significant increase in disease-specific (HR 1.66; 95% confidence interval 1.11-2.47; P = 0.014) and overall mortality (HR 1.57; 95% confidence interval 1.07-2.30; P = 0.023) in advanced but not early stage disease. Notably, 5-fluorouracil-based chemotherapy conferred significant survival benefit to patients with tumors negative for Nr-CAM overexpression but not to those with Nr-CAM overexpressed tumors. In conclusion, Nr-CAM protein expression is upregulated in CRC tissues. Nr-CAM overexpression is an independent marker of poor prognosis among advanced CRC patients, and is a possible predictive marker for non-beneficence to 5-fluorouracil- based chemotherapy.

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The development of accurate structural/thermal numerical models of complex systems, such as aircraft fuselage barrels, is often limited and determined by the smallest scales that need to be modelled. The development of reduced order models of the smallest scales and consequently their integration with higher level models can be a way to minimise the bottle neck present, while still having efficient, robust and accurate numerical models. In this paper a methodology on how to develop compact thermal fluid models (CTFMs) for compartments where mixed convection regimes are present is demonstrated. Detailed numerical simulations (CFD) have been developed for an aircraft crown compartment and validated against experimental data obtained from a 1:1 scale compartment rig. The crown compartment is defined as the confined area between the upper fuselage and the passenger cabin in a single aisle commercial aircraft. CFD results were utilised to extract average quantities (temperature and heat fluxes) and characteristic parameters (heat transfer coefficients) to generate CTFMs. The CTFMs have then been compared with the results obtained from the detailed models showing average errors for temperature predictions lower than 5%. This error can be deemed acceptable when compared to the nominal experimental error associated with the thermocouple measurements.

The CTFMs methodology developed allows to generate accurate reduced order models where accuracy is restricted to the region of Boundary Conditions applied. This limitation arises from the sensitivity of the internal flow structures to the applied boundary condition set. CTFMs thus generated can be then integrated in complex numerical modelling of whole fuselage sections.

Further steps in the development of an exhaustive methodology would be the implementation of a logic ruled based approach to extract directly from the CFD simulations numbers and positions of the nodes for the CTFM.

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We present the first direct measurement of ultrafast charge migration in a biomolecular building block the amino acid phenylalanine. Using an extreme ultraviolet pulse of 1.5 fs duration to ionize molecules isolated in the gas phase, the location of the resulting hole was probed by a 6 fs visible/near-infrared pulse. By measuring the yield of a doubly charged ion as a function of the delay between the two pulses, the positive hole was observed to migrate to one end of the cation within 30 fs. This process is likely to originate from even faster coherent charge oscillations in the molecule being dephased by bond stretching which eventually localizes the final position of the charge. This demonstration offers a clear template for observing and controlling this phenomenon in the future.

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Pigmented paravenous chorioretinal atrophy (PPCRA) is an unusual retinal degeneration characterized by accumulation of pigmentation along retinal veins. The purpose of this study was to describe the phenotype of a family with PPCRA, determine the mode of inheritance, and identify the causal mutation.

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With the increase in construction in dense urban environments, the delays associated with managing the material supply chain to site is called into question. Purpose: The aim of this investigation is to gain the perspective of construction contractors operating in a dense urban environment and the resulting strategies adopted to reduce delays in the delivery of materials to site. Methodology: This is achieved through incorporating a comprehensive literature review on the subject in conjunction with industry interviews with construction professionals in the identification of various management issues and corresponding strategies in the reduction of delays in the delivery of materials to site. Findings: The key issue which emerges is the lack of space for unloading bays while the corresponding key strategy is to schedule deliveries outside peak congestion times. Practical Implication: With confined site construction evident throughout the industry and the noted importance of an effective supply chain, the findings here in further assist on-site management in the daily task of ensuring the effective delivery and off-loading of materials in a complex and hazardous environment. Originality/Value: This research aids on-site management of confined site environments in the coordination of the material supply chain to site.

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The Construction Design and Management (CDM) Regulations (2007) is one of the most important set of health and safety regulations in the construction industry today. The aim of this research is to examine critical success factors for CDM compliance in small to medium size contractors in the UK construction industry. The objectives of the research include the identification of critical barriers in doing so along with the identification of success factors where CDM is incorporated. A mixed method approach is adopted in the identification and categorisation of the various factors encompassing a literature review, interviews and questionnaire survey. The key finding which emerge is the lack of knowledge and understanding with regards the CDM regulations with the recommendation to encourage small and medium contractor compliance through illustrating the benefits attainable. The practicality of the research is evident based on the significant uptake in the CDM by larger contractors, yet the research indicates that further insight and guidance is required to educate and inform those working within small to medium sized contractors in the UK. Where such acknowledgement and compliance is adopted, it is envisaged that this sector will benefit from reduced incidents and accidents, increased productivity while ultimately leading to a safer and more productive industry as a whole.