827 resultados para novel resistance strategies


Relevância:

30.00% 30.00%

Publicador:

Resumo:

Purpose - Managers at the company attempt to implement a knowledge management information system in an attempt to avoid loss of expertise while improving control and efficiency. The paper seeks to explore the implications of the technological solution to employees within the company. Design/methodology/approach - The paper reports qualitative research conducted in a single organization. Evidence is presented in the form of interview extracts. Findings - The case section of the paper presents the accounts of organizational participants. The accounts reveal the workers' reactions to the technology-based system and something of their strategies of resistance to the system. These accounts also provide glimpses of the identity construction engaged in by these knowledge workers. The setting for the research is in a knowledge-intensive primary industry. Research was conducted through observation and interviews. Research limitations/implications - The issues identified are explored in a single case-study setting. Future research could look at the relevance of the findings to other settings. Practical implications - The case evidence presented indicates some of the complexity of implementation of information systems in organizations. This could certainly be seen as more evidence of the uncertainty associated with organizational change and of the need for managers not to expect an easy adoption of intrusive IT solutions. Originality/value - This paper adds empirical insight to a largely conceptual literature. © Emerald Group Publishing Limited.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Proper maintenance of plant items is crucial for the safe and profitable operation of process plants, The relevant maintenance policies fall into the following four categories: (i) preventivejopportunistic/breakdown replacement policies, (ii) inspection/inspection-repair-replacernent policies, (iii) restorative maintenance policies, and (iv) condition based maintenance policies, For correlating failure times of component equipnent and complete systems, the Weibull failure distribution has been used, A new powerful method, SEQLIM, has been proposed for the estimation of the Weibull parameters; particularly, when maintenance records contain very few failures and many successful operation times. When a system consists of a number of replaceable, ageing components, an opporturistic replacernent policy has been found to be cost-effective, A simple opportunistic rrodel has been developed. Inspection models with various objective functions have been investigated, It was found that, on the assumption of a negative exponential failure distribution, all models converge to the same optimal inspection interval; provided the safety components are very reliable and the demand rate is low, When deterioration becomes a contributory factor to same failures, periodic inspections, calculated from above models, are too frequent, A case of safety trip systems has been studied, A highly effective restorative maintenance policy can be developed if the performance of the equipment under this category can be related to some predictive modelling. A novel fouling model has been proposed to determine cleaning strategies of condensers, Condition-based maintenance policies have been investigated. A simple gauge has been designed for condition monitoring of relief valve springs. A typical case of an exothermic inert gas generation plant has been studied, to demonstrate how various policies can be applied to devise overall maintenance actions.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

The concept of mobility, related to technology in particular, has evolved dramatically over the last two decades including: (i) hardware ranging from walkmans to Ipods, laptops to netbooks, PDAs to 3G mobile phone; (ii) software supporting multiple audio and video formats driven by ubiquitous mobile wireless access, WiMax, automations such as radio frequency ID tracking and location aware services. Against the background of increasing budget deficit, along with the imperative for efficiency gains, leveraging ICT and mobility promises for work related tasks, in a public administration context, in emerging markets, point to multiple possible paths. M-government transition involve both technological changes and adoption to deliver government services differently (e.g. 24/7, error free, anywhere to the same standards) but also the design of digital strategies including possibly competing m-government models, the re-shaping of cultural practices, the creation of m-policies and legislations, the structuring of m-services architecture, and progress regarding m-governance. While many emerging countries are already offering e-government services and are gearing-up for further m-government activities, little is actually known about the resistance that is encountered, as a reflection of civil servants' current standing, before any further macro-strategies are deployed. Drawing on the resistance and mobility literature, this chapter investigates how civil servants' behaviors, in an emerging country technological environment, through their everyday practice, react and resist the influence of m-government transition. The findings points to four main type of resistance namely: i) functional resistance; ii) ideological resistance; iii) market driven resistance and iv) geographical resistance. Policy implication are discussed in the specific context of emerging markets. © 2011, IGI Global.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

AIMS: To investigate the influence of chemical and physical factors on the rate and extent of germination of Clostridium difficile spores. METHODS AND RESULTS: Germination of C. difficile spores following exposure to chemical and physical germinants was measured by loss of either heat or ethanol resistance. Sodium taurocholate and chenodeoxycholate initiated germination together with thioglycollate medium at concentrations of 0.1-100 mmol l(-1) and 10-100 mmol l(-1) respectively. Glycine (0.2% w/v) was a co-factor required for germination with sodium taurocholate. There was no significant difference in the rate of germination of C. difficile spores in aerobic and anaerobic conditions (P > 0.05) however, the initial rate of germination was significantly increased at 37 degrees C compared to 20 degrees C (P < 0.05). The optimum pH range for germination was 6.5-7.5, with a decreased rate and extent of germination occurring at pH 5.5 and 8.5. CONCLUSIONS: This study demonstrates that sodium taurocholate and chenodeoxycholate initiate germination of C. difficile spores and is concentration dependant. Temperature and pH influence the rate and extent of germination. SIGNIFICANCE AND IMPACT OF THE STUDY: This manuscript enhances the knowledge of the factors influencing the germination of C. difficile spores. This may be applied to the development of potential novel strategies for the prevention of C. difficile infection.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Reproducible preparation of a number of modified clay and clay~like materials by both conventional and microwave-assisted chemistry, and their subsequent characterisation, has been achieved, These materials are designed as hydrocracking catalysts for the upgrading of liquids obtained by the processing of coal. Contact with both coal derived liquids and heavy petroleum resids has demonstrated that these catalysts are superior to established proprietary catalysts in terms of both initial activity and deactivation resistance, Of particular activity were a chromium-pillared montmorillonite and a tin intercalated laponite, Layered Double Hydroxides (LDH's) have exhibited encouraging thermal stability. Development of novel methods for hydrocracking coal derived liquids, using a commercial microwave oven, modified reaction vessels and coal model compounds has been attempted. Whilst safe and reliable operation of a high pressure microwave "bomb" apparatus employing hydrogen, has been achieved, no hydrotreatment reactions occurred,

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Type 2 diabetes is an insidious disorder, with micro and/or macrovascular and nervous damage occurring in many patients before diagnosis. This damage is caused by hyperglycaemia and the diverse effects of insulin resistance. Obesity, in particular central obesity, is a strong pre-disposing factor for type 2 diabetes. Skeletal muscle is the main site of insulin-stimulated glucose disposal and appears to be the first organ that becomes insulin resistant in the diabetic state, with later involvement of adipose tissue and the liver. This study has investigated the use of novel agents to ameliorate insulin-resistance in skeletal muscle as a means of identifying intervention sites against insulin resistance and of improving glucose uptake and metabolism by skeletal muscle. Glucose uptake was measured in vitro by cultured L6 myocytes and isolated muscles from normal and obese diabetic ob/ob mice, using either the tritiated non-metabolised glucose analogue 2-deoxy-D-glucose or by glucose disposal. Agents studied included lipoic acid, isoferulic acid, bradykinin, lipid mobilising factor (provisionally synonymous with Zinca2 glycoprotein) and the trace elements lithium, selenium and chromium. The putative role of TNFa in insulin resistance was also investigated. Lipoic acid improved insulin-stimulated glucose uptake in normal and insulin resistance murine muscles, as well as cultured myocytes. Isoferulic acid, bradykinin and LMF also produced a transient increase in glucose uptake in cultured myocytes. Physiological concentrations of TNFa were found to cause insulin resistance in cultured, but no in excised murine muscles. The effect of the M2 metabolite of the satiety-inducing agent sibutramine on lipolysis in excised murine and human adipocytes was also investigated. M2 increased lipolysis from normal lean and obese ob/ob mouse adipocytes. Arguably the most important observation was that M2 also increased the lipolytic rate in adipocytes from catecholamine resistant obese subjects. The studies reported in this thesis indicate that a diversity of agents can improve glucose uptake and ameliorate insulin resistance. It is likely that these agents are acting via different pathways. This thesis has also shown that M2 can induce lipolysis in both rodent and human adipocytes. M2 hence has potential to directly reduce adiposity, in addition to well documented effects via the central nervous system.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

The aim of this thesis was to investigate antibacterial agents for use in disinfectant formulation in conjunction with benzalkonium chloride (BKC), and if possible, to synthesise novel agents based upon successful structures. Development of resistance to antibacterial agents following long-term exposure of P. aeruginosa to BKC was also investigated, examining cross-resistance to clinically relevant antibiotics and determining mechanisms of resistance. In this study over 50 compounds were examined for antibacterial action against P. aeruginosa, both alone and in conjunction with BKC. Successful compounds were used to design novel agents, based upon the acridine ring structure, some of which showed synergy with BKC. In 15 of the 16 strains exposed to increasing concentrations of BKC, resistance to the disinfectant arose. Strains PAO1 and OO14 were examined further, each showing stable BKC resistance and a slightly varying profile of cross-resistance. In strain PAO1 alterations in the fatty acids of the cytoplasmic membrane, increase in expression of OprG, decrease in susceptibility to EDTA as an outer membrane permeabilising agent and an increase in negativity of the cell surface charge were observed as cells became more resistant to BKC. In strain OO14 a decrease in whole cell phosphatidylcholine content, a decrease in binding/uptake of BKC and an increase in cell surface hydrophobicity were observed as cells became more resistant to BKC. Resistance to tobramycin in strain OO14 was initially high, but fell as cells were adapted to BKC, this coincided with a quantitative reduction of plasmid DNA in the cells.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

The microbial demand for iron is often met by the elaboration of siderophores into the surrounding medium and expression of cognate outer membrane receptors for the ferric siderophore complexes. Conditions of iron limitation, such as those encountered in vivo, cause Pseudomonas aeruginosa to express two high-affinity iron-uptake systems based on pyoverdin and pyochelin. These systems will operate both in the organism's natural habitat, soil and water, where the solubility of iron at neutral pH is extremely low, and in the human host where the availability of free iron is too low to sustain bacterial growth due to the iron-binding glycoproteins transferrin and lactoferrin. Cross-feeding and radiolabelled iron uptake experiments demonstrated that pyoverdin biosynthesis and uptake were highly heterogeneous amongst P.aeruginosa strains, that growth either in the presence of pyoverdin or pyochelin resulted in induction of specific IROMPs, and that induction of iron uptake is siderophore-specific. The P.aeruginosa Tn5 mutant PH1 is deficient in ferripyoverdin uptake and resistant to pyocin Sa, suggesting that the site of interaction of pyocin Sa is a ferripyoverdin receptor. Additional Tn5 mutants appeared to exploit different strategies to achieve pyocin Sa-resistance, involving modifications in expression of pyoverdin-mediated iron uptake, indicating that complex regulatory systems exist to enable these organisms to compete effectively for iron. Modulation of expression of IROMPs prompted a study of the mechanism of uptake of a semi-synthetic C(7) α-formamido substituted cephalosporin BRL 41897A. Sensitivity to this agent correlated with expression of the 75 kDa ferri-pyochelin receptor and demonstrated the potential of high-affinity iron uptake systems for targeting of novel antibiotics. Studies with ferri-pyoverdin uptake-deficient mutant PH1 indicated that expression of outer membrane protein G (OprG), which is usually expressed under iron-rich conditions and repressed under iron-deficient conditions, was perturbed. Attempts were made to clone the oprG gene using a degenerate probe based on the N-terminal amino acid sequence. A strongly hybridising HindIll restriction fragment was cloned and sequenced, but failed to reveal an open reading frame correspondmg to OprG. However, there appears to be good evidence that a part of the gene codmg for the hydrophilic membrane-associated ATP-binding component of a hitherto uncharacterised periplasmic- binding-protein-dependent transport system has been isolated. The full organisation and sequence of the operon, and substrate for this putative transport system, are yet: to be elucidated,

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Survival studies were conducted on Legionella pneumophila cells that had been grown intracellulary in Acanthamoeba polyphaga and then exposed to polyhexamethylene biguanide (PHMB), benzisothiazolone (BIT), 5-chloro-N-methylisothiazolone (CMIT) and tetradecyltrimethyl ammonium bromide (TTAB). Susceptibilities were also determined for L.pneumophila grown under nutrient sufficient and iron-, nitrogen- and phosphate-depleted conditions, in a chemically defined medium. BIT was relatively ineffective against cells grown under iron-depletion; in contrast iron-depleted conditions increased the susceptibilities of cells to PHMB, TTAB and CMIT. Cells grown under phosphate-depletion showed a marked increase in sensitivity towards all the biocides. Conversely, the activities of all four biocides were greatly reduced against L.pneumophila grown in amoebae. To study the physiological basis for the increased resistance of intra-amoebal grown legionella, the surface properties of the cells were examined by studying outer membrane proteins (OMs), lipopolysaccharides and cellular fatty acids. Intra-amoebal grown legionella were found to differ in several respects compared to cells grown in vitro; they contained a novel 15-kDal OM protein and a monosaturated straight-chain fatty acid (18:19). These compounds were also found in abundant quantities in the host amoeba. Intra-amoebal grown legionella contained more LPS bands than did in vitro grown organisms and were less susceptible to protease K digestion. Cells grown under phosphate depletion were markedly sensitive to protease K digestion and contained lower levels of LPS. Immunoblot analysis of intra-amoebal grown legionella with anti-acanthamoebal serum revealed that both the surface of the bacteria and sarkosyl extracted OMs contained amoebal proteins. These findings suggest that the 15-kDal OM protein is likely to be of amoebal origin and binds tightly to the OM of the bacterium. It is proposed that disruption of amoebal membranes, as a result of intra-amoebal infection liberates macromolecules, including a 15-kDal polypeptide, a major constituent of the membrane, which associates closely with the surface of the legionellae. Thus L.pneumophila which have extraneous membrane material bound to their surface may respond differently to biocide inactivation, as these macromolecules may act as a penetration barrier to such agents. This phenomenon could contribute to the recalcitrance of legionellae in water systems.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Introduction: Orally disintegrating tablets (ODTs) have emerged as one of the novel solid oral dosage forms with a potential to deliver a wide range of drug candidates to both paediatric and geriatric patient populations. Of the plethora of available technologies, compression of excipients offers a cost-effective and translatable methodology for the manufacture of ODTs. Areas covered: The review is a modest endeavour from the authors to assemble literature published over the last couple of decades on formulation development of compressed ODT. It describes the main ODT excipients used since the introduction of this dosage form in the 1990s and explores the switch from cellulose-based excipients towards sugar/polyols. Furthermore, it unfolds the key properties of ODT fillers, binders and disintegrants with an emphasis on their advantages and drawbacks. The review also provides a critical assessment of the various strategies employed for performance enhancement of compressed ODT with a focus on the underlying mechanisms for fast disintegration and acceptable mechanical strength. Expert opinion: Recent increase in the total number of compression-based technologies for ODT development promises to reduce the manufacturing cost of this dosage form in the future. However, some of the developed methods may affect the stability of tablets due to susceptibility to moisture, collapse of pores or the generation of less stable polymorphs which require rigorous testing prior to commercialization. © 2013 Informa UK, Ltd.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Developing the premise that strategies are forged through an ongoing mutual process of developing motives and responses to multiple degrees of resistance, this paper examines the motives underpinning the adoption of joint venture strategies using empirical details from four British retail firms. The findings point to multiple motives forming from multiple paths of resistance in the foreign market, but also among individuals within the firm as well as across the whole international programme. Moreover, this study reveals a paradoxical tension between management's operational impatience to immediately ground the retail format and an overall wariness or gloomy perceptions associated with adopting an international retail joint venture. The paper therefore concludes that the motives and barriers are manifestations of the struggles involved in internationalising retail operations.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Cardiovascular diseases (CVD) contributed to almost 30% of worldwide mortality; with heart failure being one class of CVD. One popular and widely available treatment for heart failure is the intra-aortic balloon pump (IABP). This heart assist device is used in counterpulsation to improve myocardial function by increasing coronary perfusion, and decreasing aortic end-diastolic pressure (i.e. the resistance to blood ejection from the heart). However, this device can only be used acutely, and patients are bedridden. The subject of this research is a novel heart assist treatment called the Chronic Intermittent Mechanical Support (CIMS) which was conceived to offer advantages of the IABP device chronically, whilst overcoming its disadvantages. The CIMS device comprises an implantable balloon pump, a percutaneous drive line, and a wearable driver console. The research here aims to determine the haemodynamic effect of balloon pump activation under in vitro conditions. A human mock circulatory loop (MCL) with systemic and coronary perfusion was constructed, capable of simulating various degrees of heart failure. Two prototypes of the CIMS balloon pump were made with varying stiffness. Several experimental factors (balloon inflation/deflation timing, Helium gas volume, arterial compliance, balloon pump stiffness and heart valve type) form the factorial design experiments. A simple modification to the MCL allowed flow visualisation experiments using video recording. Suitable statistical tests were used to analyse the data obtained from all experiments. Balloon inflation and deflation in the ascending aorta of the MCL yielded favourable results. The sudden balloon deflation caused the heart valve to open earlier, thus causing longer valve opening duration in a cardiac cycle. It was also found that pressure augmentation in diastole was significantly correlated with increased cardiac output and coronary flowrate. With an optimum combination (low arterial compliance and low balloon pump stiffness), systemic and coronary perfusions were increased by 18% and 21% respectively, while the aortic end-diastolic pressure (forward flow resistance) decreased by 17%. Consequently, the ratio of oxygen supply and demand to myocardium (endocardial viability ratio, EVR) increased between 33% and 75%. The increase was mostly attributed to diastolic augmentation rather than systolic unloading.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Solid tumours display a complex drug resistance phenotype that involves inherent and acquired mechanisms. Multicellular resistance is an inherent feature of solid tumours and is known to present significant barriers to drug permeation in tumours. Given this barrier, do acquired resistance mechanisms such as P-glycoprotein (P-gp) contribute significantly to resistance? To address this question, the multicellular tumour spheroid (MCTS) model was used to examine the influence of P-gp on drug distribution in solid tissue. Tumour spheroids (TS) were generated from either drug-sensitive MCF7WT cells or a drug-resistant, P-gp-expressing derivative MCF7Adr. Confocal microscopy was used to measure time courses and distribution patterns of three fluorescent compounds; calcein-AM, rhodamine123 and BODIPY-taxol. These compounds were chosen because they are all substrates for P-gp-mediated transport, exhibit high fluorescence and are chemically dissimilar. For example, BODIPY-taxol and rhodamine 123 showed high accumulation and distributed extensively throughout the TSWT, whereas calcein-AM accumulation was restricted to the outermost layers. The presence of P-gp in TSAdr resulted in negligible accumulation, regardless of the compound. Moreover, the inhibition of P-gp by nicardipine restored intracellular accumulation and distribution patterns to levels observed in TSWT. The results demonstrate the effectiveness of P-gp in modulating drug distribution in solid tumour models. However, the penetration of agents throughout the tissue is strongly determined by the physico-chemical properties of the individual compounds.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Research in the present thesis is focused on the norms, strategies,and approaches which translators employ when translating humour in Children's Literature from English into Greek. It is based on process-oriented descriptive translation studies, since the focus is on investigating the process of translation. Viewing translation as a cognitive process and a problem soling activity, this thesis Think-aloud protocols (TAPs) in order to investigate translator's minds. As it is not possible to directly observe the human mind at work, an attempt is made to ask the translators themselves to reveal their mental processes in real time by verbalising their thoughts while carrying out a translation task involving humour. In this study, thirty participants at three different levels of expertise in translation competence, i.e. tn beginner, ten competent, and ten experts translators, were requested to translate two humourous extracts from the fictional diary novel The Secret Diary of Adrian Mole, Aged 13 ¾ by Sue Townsend (1982) from English into Greek. As they translated, they were asked to verbalise their thoughts and reason them, whenever possible, so that their strategies and approaches could be detected, and that subsequently, the norms that govern these strategies and approaches could be revealed. The thesis consists of four parts: the introduction, the literature review, the study, and the conclusion, and is developed in eleven chapters. the introduction contextualises the study within translation studies (TS) and presents its rationale, research questions, aims, and significance. Chapters 1 to 7 present an extensive and inclusive literature review identifying the principles axioms that guide and inform the study. In these seven chapters the following areas are critically introduced: Children's literature (Chapter 1), Children's Literature Translation (Chapter 2), Norms in Children's Literature (Chapter 3), Strategies in Children's Literature (Chapter 4), Humour in Children's Literature Translation (Chapter 5), Development of Translation Competence (Chapter 6), and Translation Process Research (Chapter 7). In Chapters 8 - 11 the fieldwork is described in detail. the piolot and the man study are described with a reference to he environments and setting, the participants, the research -observer, the data and its analysis, and limitations of the study. The findings of the study are presented and analysed in Chapter 9. Three models are then suggested for systematising translators' norms, strategies, and approaches, thus, filling the existing gap in the field. Pedagogical norms (e.g. appropriateness/correctness, famililarity, simplicity, comprehensibility, and toning down), literary norms (e.g. sound of language and fluency). and source-text norms (e.g. equivalence) were revealed to b the most prominent general and specific norms governing the translators'  strategies and approaches in the process of translating humour in ChL. The data also revealed that monitoring and communication strategies (e.g. additions, omissions, and exoticism) were the prevalent strategies employed by translators. In Chapter 10 the main findings and outcomes of a potential secondary benefit (beneficial outcomes) are discussed on the basis of the research questions and aims of the study, and implications of the study are tackled in Chapter 11. In the conclusion, suggestions for future directions are given and final remarks noted.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

This study examines the actions of the novel enzyme-resistant, NH 2-terminally modified GIP analog (Hyp3)GIP and its fatty acid-derivatized analog (Hyp3)GIPLys16PAL. Acute effects are compared with the established GIP receptor antagonist (Pro3)GIP. All three peptides exhibited DPP IV resistance, and significantly inhibited GIP stimulated cAMP formation and insulin secretion in GIP receptor-transfected fibroblasts and in clonal pancreatic BRIN-BD11 cells, respectively. Likewise, in obese diabetic ob/ob mice, intraperitoneal administration of GIP analogs significantly inhibited the acute antihyperglycemic and insulin-releasing effects of native GIP. Administration of once daily injections of (Hyp 3)GIP or (Hyp3)GIPLys16PAL for 14 days resulted in significantly lower plasma glucose levels (P < 0.05) after (Hyp 3)GIP on days 12 and 14 and enhanced glucose tolerance (P < 0.05) and insulin sensitivity (P < 0.05 to P < 0.001) in both groups by day 14. Both (Hyp3)GIP and (Hyp3)GIPLys16PAL treatment also reduced pancreatic insulin (P < 0.05 to P < 0.01) without affecting islet number. These data indicate that (Hyp3)GIP and (Hyp 3)GIPLys16PAL function as GIP receptor antagonists with potential for ameliorating obesity-related diabetes. Acylation of (Hyp 3)GIP to extend bioactivity does not appear to be of any additional benefit. Copyright © 2007 the American Physiological Society.