98 resultados para excision determinants


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Previous research shows that approximately half of the coagulase-negative staphylococci (CNS) isolated from patients in the intensive care unit (ICU) at Belfast City Hospital were resistant to methicillin. The presence of this relatively high proportion of methicillin-resistance genetic material gives rise to speculation that these organisms may act as potential reservoirs of methicillinresistance genetic material to methicillin-sensitive Staphylococcus aureus (MSSA). Mechanisms of horizontal gene transfer from PBP2a-positive CNS to MSSA, potentially transforming MSSA to MRSA, aided by electroporation-type activities such as transcutaneous electrical nerve stimulation (TENS), should be considered. Methicillin-resistant CNS (MR-CNS) isolates are collected over a two-month period from a variety of clinical specimen types, particularly wound swabs. The species of all isolates are confirmed, as well as their resistance to oxacillin by standard disc diffusion assays. In addition, MSSA isolates are collected over the same period and confirmed as PBP2a-negative. Electroporation experiments are designed to mimic the time/voltage combinations used commonly in the clinical application of TENS. No transformed MRSA were isolated and all viable S. aureus cells remained susceptible to oxacillin and PBP2a-negative. Experiments using MSSA pre-exposed to sublethal concentrations of oxacillin (0.25 µg/mL) showed no evidence of methicillin gene transfer and the generation of an MRSA. The study showed no evidence of horizontal transfer of methicillin resistance genetic material from MR-CNS to MSSA. These data support the belief that TENS and the associated time/voltage combinations used do not increase conjugational transposons or facilitate horizontal gene transfer from MR-CNS to MSSA.

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The business angel market is usually identified as a local market, and the proximity of an investment has been shown to be key in the angel's investment preferences and an important filter at the screening stage of the investment decision. This is generally explained by the personal and localized networks used to identify potential investments, the hands-on involvement of the investor and the desire to minimize risk. However, a significant minority of investments are long distance. This paper is based on data from 373 investments made by 109 UK business angels. We classify the location of investments into three groups: local investments ( those made within the same county or in adjacent counties); intermediate investments ( those made in counties adjacent to the 'local' counties); and long-distance investments ( those made beyond this range). Using ordered logit analysis the paper develops and tests a number of hypotheses that relate long-distance investment to investment characteristics and investor characteristics. The paper concludes by drawing out the implications for entrepreneurs seeking business angel finance in investment-deficient regions, business angel networks seeking to match investors to entrepreneurs and firms ( which are normally their primary clients), and for policy-makers responsible for local and regional economic development.

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Purpose – This paper explores the factors which determine the degree of knowledge transfer in inter-firm new product development projects. We test a theoretical model exploring how inter-firm knowledge transfer is enabled or hindered by a buyer’s learning intent, the degree of supplier protectiveness, inter-firm knowledge ambiguity, and absorptive capacity. Design/methodology/approach – A sample of 153 R&D intensive manufacturing firms in the UK automotive, aerospace, pharmaceutical, electrical, chemical, and general manufacturing industries were used to test the framework. Two-step structural equation modeling in AMOS 7.0 was used to analyse the data. Findings – Our results indicate that a buyer’s learning intent increases inter-firm knowledge transfer, but also acts as an incentive for suppliers to protect their knowledge. Such defensive measures increase the degree of inter-firm knowledge ambiguity, encouraging buyer firms to invest in absorptive capacity as a means to interpret supplier knowledge, but also increase the degree of knowledge transfer. Practical implications – Our paper illustrates the effects of focusing on acquisition, rather than accessing, supplier technological knowledge. We show that an overt learning strategy can be detrimental to knowledge transfer between buyer-supplier, as supplier’s react by restricting the flow of information. Organisations are encouraged to consider this dynamic when engaging in multi-organisational new product development projects. Originality/value – This paper examines the dynamics of knowledge transfer within inter-firm NPD projects, showing how transfer is influenced by the buyer firm’s learning intention, supplier’s response, characteristics of the relationship and knowledge to be transferred.

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Using cross-country data, we investigate the determinants of reservation wages and their course over the jobless spell. Higher unemployment benefits lead to higher reservation wages. Further, again consistent with the basic search model, repeated observations on the same individual provide scant evidence of declining reservation wages.

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This article offers a replication for Britain of Brown and Heywood's analysis of the determinants of performance appraisal in Australia. Although there are some important limiting differences between our two datasets - the Australia Workplace Industrial Relations Survey (AWIRS) and the Workplace Employment Relations Survey (WERS) - we reach one central point of agreement and one intriguing shared insight. First, performance appraisal is negatively associated with tenure: where employers cannot rely on the carrot of deferred pay or the stick of dismissal to motivate workers, they will tend to rely more on monitoring, ceteris paribus. Second, employer monitoring and performance pay may be complementary. However, consonant with the disparate results from the wider literature, there is more modest agreement on the contribution of specific human resource management practices, and still less on the role of job control.

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A significant proportion of human cancers overexpress DNA polymerase beta (Pol beta), the major DNA polymerase involved in base excision repair. The underlying mechanism and biological consequences of overexpression of this protein are unknown. We examined whether Pol beta, expressed at levels found in tumor cells, is involved in the repair of DNA damage induced by oxaliplatin treatment and whether the expression status of this protein alters the sensitivity of cells to oxaliplatin. DNA damage induced by oxaliplatin treatment of HCT116 and HT29 colon cancer cells was observed to be associated with the stabilization of Pol beta protein on chromatin. In comparison with HCT116 colon cancer cells, isogenic oxaliplatin-resistant (HCT-OR) cells were found to have higher constitutive levels of Pol beta protein, faster in vitro repair of a DNA substrate containing a single nucleotide gap and faster repair of 1,2-GG oxaliplatin adduct levels in cells. In HCT-OR cells, small interfering RNA knockdown of Pol beta delayed the repair of oxaliplatin-induced DNA damage. In a different model system, Pol beta-deficient fibroblasts were less able to repair 1,2-GG oxaliplatin adducts and were hypersensitive to oxaliplatin treatment compared with isogenic Pol beta-expressing cells. Consistent with previous studies, Pol beta-deficient mouse fibroblasts were not hypersensitive to cisplatin treatment. These data provide the first link between oxaliplatin sensitivity and DNA repair involving Pol beta. They demonstrate that Pol beta modulates the sensitivity of cells to oxaliplatin treatment. Oncogene (2010) 29, 463-468; doi:10.1038/onc.2009.327; published online 19 October 2009

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This study examined the previously unexplored occupational grade-specific relationships of domestic responsibilities, the age of children, and work-family spillover, with registered sickness absence (>3 days' sick leave episodes, a mean follow-up of 17 months; n = 18,366 municipal employees; 76% women). The results showed that negative spillover from work into family life predicted a heightened rate of sickness absence spells among both women and men in all occupational categories (except upper white-collar men), but especially among blue-collar and lower white-collar employees. Furthermore, among all white-collar employees (except upper white-collar men), having young children (

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Steroids form a structurally closely related group. As a result, antibodies produced for use in immunoassays regularly show unwanted cross-reactivities, These may be reduced by altering hapten-protein coupling procedures, thereby reducing the exposure of the determinants giving rise to the undesirable cross-reaction. However, these procedures carl prove to be complex, expensive and nor totally predictable in outcome. Exploitation of the clonal selection theory is an attractive alternative approach. The host is primed with the interfering cross-reactant coupled to a non-immunogenic amino acid copolymer to inactivate the B-lymphocyte clones specific for this steroid, producing a specific immunotolerance. Then, 3 days Inter, the host is immunized with the steroid against which nn antibody is required. The clones producing antibody to this immunogen are unaffected and the cross-reactivity is significantly reduced or deleted The technique has been applied to the reduction of endogenous sex steroid cross-reactivity from antibodies prepared against synthetic and semi-synthetic androgens (17 alpha-methyltestosterone, 19-nor-beta-testosterone) and the progestogen medroxyprogesterone. Antibodies prepared against the synthetic oestrogen zeranol using this technique have significantly reduced its undesirable cross-reactivity with the fungal metabolite 7 alpha-zearalenol. Highly specific antisera have been generated in all cases, the only adverse effect being a reduction in the titres achieved in comparison with rabbits receiving the conventional immunizing regime.