928 resultados para Freedom of choice


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This paper uses a feminist post-structuralist approach to examine the gendered identities of a sample of British business leaders in Britain. While recent national surveys offer many material reasons why women are acutely under-represented as business leaders, the role of language is rarely addressed. This paper explores the ways in which ten senior women and men construct their sense of leadership identities through the medium of interview narratives. Drawing upon two poststructuralist models of analysis (Derrida’s 1987 theory of deconstruction and Bakhtin’s 1927/1981 concept of double-voiced discourse), the paper shows how both females and males are able to shift pragmatically between interwoven corporate discourses, which demand competing cultural allegiances from one moment to the next, allegiances constantly tested by the rapid change and uncertainty that characterise global business. While male leaders experience a relative freedom of movement between different cultural discourses, female leaders are circumscribed by negative and reductive representations of female speech and behaviour. In sum, senior women are required constantly to observe, review, police and repair their use of leadership language, which potentially undermines their confidence and authority as leaders.

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This work attempts to create a systemic design framework for man-machine interfaces which is self consistent, compatible with other concepts, and applicable to real situations. This is tackled by examining the current architecture of computer applications packages. The treatment in the main is philosophical and theoretical and analyses the origins, assumptions and current practice of the design of applications packages. It proposes that the present form of packages is fundamentally contradictory to the notion of packaging itself. This is because as an indivisible ready-to-implement solution, current package architecture displays the following major disadvantages. First, it creates problems as a result of user-package interactions, in which the designer tries to mould all potential individual users, no matter how diverse they are, into one model. This is worsened by the minute provision, if any, of important properties such as flexibility, independence and impartiality. Second, it displays rigid structure that reduces the variety and/or multi-use of the component parts of such a package. Third, it dictates specific hardware and software configurations which probably results in reducing the number of degrees of freedom of its user. Fourth, it increases the dependence of its user upon its supplier through inadequate documentation and understanding of the package. Fifth, it tends to cause a degeneration of the expertise of design of the data processing practitioners. In view of this understanding an alternative methodological design framework which is both consistent with systems approach and the role of a package in its likely context is proposed. The proposition is based upon an extension of the identified concept of the hierarchy of holons* which facilitates the examination of the complex relationships of a package with its two principal environments. First, the user characteristics and his decision making practice and procedures; implying an examination of the user's M.I.S. network. Second, the software environment and its influence upon a package regarding support, control and operation of the package. The framework is built gradually as discussion advances around the central theme of a compatible M.I.S., software and model design. This leads to the formation of the alternative package architecture that is based upon the design of a number of independent, self-contained small parts. Such is believed to constitute the nucleus around which not only packages can be more effectively designed, but is also applicable to many man-machine systems design.

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The pneumonia caused by Pneumocystis carinii is ultimately responsible for the death of many acquired immunodeficiency syndrome (AIDS) patients. Large doses of trimethoprim and pyrimethamine in combination with a sulphonamide and/or pentamidine suppress the infection but produce serious side-effects and seldom prevent recurrence after treatment withdrawal. However, the partial success of the aforementioned antifolates, and also trimetrexate used alone, does suggest dihydrofolate reductase (DHFR) as a target for the development of antipneumocystis agents. From the DHFR inhibitory activities of 3'-substituted pyrimethamine analogues it was suggested that the 3'-(3'',3''-dimethyltriazen-1''-yl) substituent may be responsible for the greater activity for the P.carinii over the mammalian enzyme. Crystallographic and molecular modeling studies revealed considerable geometrical and electronic differences between the triazene and the chemically related formamidine functions that may account for the differences in DHFR inhibitory profiles. Structural and electronic parameters calculated for a series of 3'-(3'',3''-disubstitutedtriazen-1''-yl) pyrimethamine analogues did not correlate with the DHFR inhibitory activities. However, the in vitro screening against P.carinii DHFR revealed that the 3''-hydroxyethyl-3''-benzyl analogue was the most active and selective. Models of the active sites of human and P.carinii DHFRs were constructed using DHFR sequence and structural homology data which had identified key residues involved in substrate and cofactor binding. Low energy conformations of the 3'',3''-dimethyl and 3''-hydroxyethyl-3''-benzyle analogues, determined from nuclear magnetic resonance studies and theoretical calculations, were docked by superimposing the diaminopyrimidine fragment onto a previously docked pyrimethamine analogue. Enzyme kinetic data supported the 3''-hydroxyethyl-3''-benzyl moiety being located in the NADPH binding groove. The 3''-benzyl substituent was able to locate to within 3 AA of a valine residue in the active site of P.carinii DHFR thereby producing a hydrophobic contact. The equivalent residue in human DHFR is threonine, more hydrophilic and less likely to be involved in such a contact. This difference may account for the greater inhibitory activity this analogue has for P.carinii DHFR and provide a basis for future drug design. From an in vivo model of PCP in immunosuppressed rats it was established that the 3"-hydroxyethyl-3"-benzyl analogue was able to reduce the.P.carinii burden more effectively with increasing doses, without causmg any visible signs of toxicity. However, equivalent doses were not as effective as pentamidine, a current treatment of choice for Pneumocystis carinii pneumonia.

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Currently available treatments for insulin-dependent diabetes mellitus are often inadequate in terms of both efficacy and patient compliance. Gene therapy offers the possibility of a novel and improved method by which exogenous insulin can be delivered to a patient. This was approached in the present study by constructing a novel insulin-secreting cell line. For the purposes of this work immortalized cell lines were used. Fibroblasts and pituitary cells were transfected with the human preproisinulin gene to create stable lines of proinsulin- and insulin-secreting cells. The effect of known β-cell secretagogues on these cells were investigated, and found mostly to have no stimulatory effect, although IBMX, arginine and ZnSO4 each increased the rate of secretion. Cyclosporin (CyA) is currently the immunosuppresant of choice for transplant recipients; the effect of this treatment on endogenous β-cell function was assessed both in vivo and in vitro. Therapeutic doses of CyA were found to reduce plasma insulin concentrations and to impair glucose tolerance. The effect of immunoisolation on insulin release by HIT T15 cells was also investigated. The presence of an alginate membrane was found to severely impair insulin release. For the first implantation of the insulin-secreting cells, the animal model selected was the athymic nude mouse. This animal is immunoincompetent, and hence the use of an immunosuppressive regimen is circumvented. Graft function was assessed by measurement of plasma human C peptide concentrations, using a highly specific assay. Intraperitoneal implantation of genetically manipulated insulin-secreting pituitary cells into nude mice subsequently treated with a large dose of streptozotocin (STZ) resulted in a significantly delayed onset of hyperglycaemia when compared to control animals. Consumption of a ZnSO4 solution was shown to increase human C peptide release by the implant. Ensuing studies in nude mice examined the efficacy of different implantation sites, and included histochemical examination of the tumours. Aldehyde fuchsin staining and immunocytochemical processing demonstrated the presence of insulin containing cells within the excised tissue. Following initial investigations in nude mice, implantation studies were performed in CyA-immunosuppressed normal and STZ-diabetic mice. Graft function was found to be less efficacious, possibly due to the subcutaneous implantation site, or to the immunosuppresive regimen. Histochemical and transmission electron microscopic analysis of the tumour-like cell clusters found at autopsy revealed necrosis of cells at the core, but essentially normal cell morphology, with dense secretory granules in peripheral cells. The thesis provides evidence that gene therapy offers a feasibly new approach to insulin delivery.

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The present thesis investigates targeted (locally and systemically) delivery of a novel group of inhibitors of enzyme transglutaminases (TGs). TGs are a widely distributed group of enzymes that catalyse the formation of isopeptide bonds between the y-carboxamide group of protein-bound glutamines and the a-amino group of protein-bound lysines or polyamines. The first group of the novel inhibitors tested were the tluorescently labelled inhibitors of Factor XIIIa (FXIIIa). These small, non-toxic inhibitors have the potential to prevent stabilisation of thrombi by FXIIIa and consequently increase the natural rate of thrombolysis, in addition it reduces staphylococcal colonisation of catheters by inhibiting their FXIIIa¬mediated cross-linking to blood clot proteins on the central venous catheter (CVCs) surface. The aim of this work was to incorporate the FXIIIa inhibitor either within coating of polyurethane (PU) catheters or to integrate it into silicone catheters, so as to reduce the incidence of thrombotic occlusion and associated bacterial infection in CVCs. The initial work focused on the incorporation of FXIIIa inhibitors within polymeric coatings of PU catheters. After defining the key characteristics desired for an effective polymeric-coating, polyvinylpyrrolidone (PVP), poly(lactic-co-glycolic acid) (PLGA) or their combination were studies as polymers of choice for coating of the catheters_ The coating was conducted by dip-coating method in a polymer solution containing the inhibitor. Upon incubation of the inhibitor-and polymer-coated strips in buffer, PVP was dissolved instantly, generating fast and significant drug release, whilst PLGA did not dissolve, yielding a slow and an insufficient amount of drug release. Nevertheless, the drug release profile was enhanced upon employing a blend solution of PVP and PLGA. The second part of the study was to incorporate the FXIIIa inhibitor into a silicone elastomer; results demonstrated that FXIIIa inhibitor can be incorporated and released from silicone by using citric acid (CA) and sodium bicarbonate (SB) as additives and the drug release rate can be controlled by the amount of incorporated additives in the silicone matrix. Furthermore, it was deemed that the inhibitor was still biologically active subsequent to being released from the silicone elastomer strips. Morphological analysis confirmed the formation of channels and cracks inside the specimens upon the addition of CA and SB. Nevertheless, the tensile strength, in addition to Young's modulus of silicone elastomer strips, decreased constantly with an increasing amount of amalgamated CA/ SB in the formulations. According to our results, incorporation of FXIIIa inhibitor into catheters and other medical implant devices could offer new perspectives in preventing bio-material associated infections and thrombosis. The use of tissue transglutaminase (T02) inhibitor for treating of liver fibrosis was also investigated. Liver fibrosis is characterized by increased synthesis and decreased degradation of the extracellular matrix (ECM). Transglutaminase-mediated covalent cross-linking is involved in the stabilization of ECM in human liver fibrosis. Thus, TG2 inhibitors may be used to counteract the decreased degradation of the ECM. The potential of a liposome based drug delivery system for site specific delivery of the fluorescent TG2 inhibitor into the liver was investigated; results indicated that the TG2 inhibitor can be successfully integrated into liposomes and delivered to the liver, therefore demonstrating that liposomes can be employed for site-specific delivery of TG2 inhibitors into the liver and TG2 inhibitor incorporating liposomes could offer a new approach in treating liver fibrosis and its end stage disease cirrhosis.

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Progressive addition spectacle lenses (PALs) have now become the method of choice for many presbyopic individuals to alleviate the visual problems of middle-age. Such lenses are difficult to assess and characterise because of their lack of discrete geographical locators of their key features. A review of the literature (mostly patents) describing the different designs of these lenses indicates the range of approaches to solving the visual problem of presbyopia. However, very little is published about the comparative optical performance of these lenses. A method is described here based on interferometry for the assessment of PALs, with a comparison of measurements made on an automatic focimeter. The relative merits of these techniques are discussed. Although the measurements are comparable, it is considered that the interferometry method is more readily automated, and would be ultimately capable of producing a more rapid result.

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The two elcctrophysiological tests currently favoured in the clinical measurement of hearing threshold arc the brainstorm evoked potential (BAEP) and the slow vertex response (SVR). However, both tests possess disadvantages. The BAEP is the test of choice in younger patients as it is stable at all levels of arousal, but little information has been obtained to date at a range of frequencies. The SVR is frequency specific but is unreliable in certain adult subjects and is unstable during sleep or in young children. These deficiencies have prompted research into a third group of potentials, the middle latency response (MLR) and the 40HZ responses. This research has compared the SVR and 40HZ response in waking adults and reports that the 40HZ test can provide a viable alternative to the SVR provided that a high degree of subject relaxation is ensured. A second study examined the morphology of the MLR and 40HZ during sleep. This work suggested that these potentials arc markedly different during sleep and that methodological factors have been responsible for masking these changes in previous studies. The clinical possibilities of tone pip BAEPs were then examined as these components were proved to be the only stable responses present in sleep. It was found that threshold estimates to 5OOHz, lOOOHz and 4000Hz stimuli could be made to within 15dBSL in most cases. A final study looked more closely at methods of obtaining frequency specific information in sleeping subjects. Threshold estimates were made using established BAEP parameters and this was compared to a 40HZ procedure which recorded a series of BAEPs over a 100msec. time sweep. Results indicated that the 40mHz procedure was superior to existing techniques in estimating threshold to low frequency stimuli. This research has confirmed a role for the MLR and 40Hz response as alternative measures of hearing capability in waking subjects and proposes that the 40Hz technique is useful in measuring frequency specific thresholds although the responses recorded derive primarily from the brainstem.

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The study examines factors influencing language planning decisions in contemporary France. It focuses upon the period 1992-1994, which witnessed the introduction of two major language policy measures, the first an amendment to the French Constitution, in 1992, proclaiming the language of the Republic as French, the second, in 1994, legislation to extend the ambit of the loi Bas-Lauriol, governing the use of the French language in France. The thesis posits a significant role for the pro-reform movement led by the French language association Avenir de la Langue Francaise (ALF) in the introduction and formulation of the policy measures concerned. The movement is depicted as continuing the traditional pattern of intellectual involvement in language planning, whilst also marking the beginning of a highly proactive, and increasingly political approach. Detailed examination of the movement's activities reveals that contextual factors and strategic strength combined to facilitate access to the levers of power, and enabled those involved to exert an impact on policy initiation, formulation, and ultimately implementation. However, ALF's decision to pursue the legislative route led to the expansion of the network of actors involved in language policymaking, and the development of counter-pressure from sectoral groups. It is suggested that this more interventionist approach destabilised the traditionally consensual language policy community, and called into question the quasi-monopoly of the intelligentsia in respect of language policymaking. It raised broader questions relating to freedom of expression and the permissible limits of language regulation in a democracy such as France. It also exposed ongoing ambiguities and inconsistencies in the interpretation of the tenets of language planning.

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This thesis reviews the main methodological developments in public sector investment appraisal and finds growing evidence that appraisal techniques are not fulfilling their earlier promise. It is suggested that an important reason for this failure lies in the inability of these techniques to handle uncertainty except in a highly circumscribed fashion. It is argued that a more fruitful approach is to strive for flexibility. Investment projects should be formulated with a view to making them responsive to a wide range of possible future events, rather than embodying a solution which is optimal for one configuration of circumstances only. The distinction drawn in economics between the short and the long run is used to examine the nature of flexibility. The concept of long run flexibility is applied to the pre-investment range of choice open to the decisionmaker. It is demonstrated that flexibility is reduced at a very early stage of decisionmaking by the conventional system of appraisal which evaluates only a small number of options. The pre-appraisal filtering process is considered further in relation to decisionmaking models. It is argued that for public sector projects the narrowing down of options is best understood in relation to an amended mixed scanning model which places importance on the process by which the 'national interest ' is determined. Short run flexibility deals with operational characteristics, the degree to which particular projects may respond to changing demands when the basic investment is already in place. The tension between flexibility and cost is noted. A short case study on the choice of electricity generating plant is presented. The thesis concludes with a brief examination of the approaches used by successive British governments to public sector investment, particularly in relation to the nationalised industries

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To exploit the popularity of TCP as still the dominant sender and protocol of choice for transporting data reliably across the heterogeneous Internet, this thesis explores end-to-end performance issues and behaviours of TCP senders when transferring data to wireless end-users. The theme throughout is on end-users located specifically within 802.11 WLANs at the edges of the Internet, a largely untapped area of work. To exploit the interests of researchers wanting to study the performance of TCP accurately over heterogeneous conditions, this thesis proposes a flexible wired-to-wireless experimental testbed that better reflects conditions in the real-world. To exploit the transparent functionalities between TCP in the wired domain and the IEEE 802.11 WLAN protocols, this thesis proposes a more accurate methodology for gauging the transmission and error characteristics of real-world 802.11 WLANs. It also aims to correlate any findings with the functionality of fixed TCP senders. To exploit the popularity of Linux as a popular operating system for many of the Internet’s data servers, this thesis studies and evaluates various sender-side TCP congestion control implementations within the recent Linux v2.6. A selection of the implementations are put under systematic testing using real-world wired-to-wireless conditions in order to screen and present a viable candidate/s for further development and usage in the modern-day heterogeneous Internet. Overall, this thesis comprises a set of systematic evaluations of TCP senders over 802.11 WLANs, incorporating measurements in the form of simulations, emulations, and through the use of a real-world-like experimental testbed. The goal of the work is to ensure that all aspects concerned are comprehensively investigated in order to establish rules that can help to decide under which circumstances the deployment of TCP is optimal i.e. a set of paradigms for advancing the state-of-the-art in data transport across the Internet.

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The oxidation of lipids has long been a topic of interest in biological and food sciences, and the fundamental principles of non-enzymatic free radical attack on phospholipids are well established, although questions about detail of the mechanisms remain. The number of end products that are formed following the initiation of phospholipid peroxidation is large, and is continually growing as new structures of oxidized phospholipids are elucidated. Common products are phospholipids with esterified isoprostane-like structures and chain-shortened products containing hydroxy, carbonyl or carboxylic acid groups; the carbonyl-containing compounds are reactive and readily form adducts with proteins and other biomolecules. Phospholipids can also be attacked by reactive nitrogen and chlorine species, further expanding the range of products to nitrated and chlorinated phospholipids. Key to understanding the mechanisms of oxidation is the development of advanced and sensitive technologies that enable structural elucidation. Tandem mass spectrometry has proved invaluable in this respect and is generally the method of choice for structural work. A number of studies have investigated whether individual oxidized phospholipid products occur in vivo, and mass spectrometry techniques have been instrumental in detecting a variety of oxidation products in biological samples such as atherosclerotic plaque material, brain tissue, intestinal tissue and plasma, although relatively few have achieved an absolute quantitative analysis. The levels of oxidized phospholipids in vivo is a critical question, as there is now substantial evidence that many of these compounds are bioactive and could contribute to pathology. The challenges for the future will be to adopt lipidomic approaches to map the profile of oxidized phospholipid formation in different biological conditions, and relate this to their effects in vivo. This article is part of a Special Issue entitled: Oxidized phospholipids-their properties and interactions with proteins.

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The purpose of the present study is to make a comparative evaluation of the legislative controls on unfairness in the context of B2B, B2C and small businesses contracts in England and Brazil. This work will focus on the examination of statutes and relevant case law which regulate exemption clauses and terms on the basis of their ‘unfairness’. The approach adopted by legislation and courts towards the above controls may vary according to the type of contract. Business contracts are more in line with the classical model of contract law according to which parties are presumably equals and able to negotiate terms. As a consequence interventions should be avoided for the sake of freedom of contract even if harmful terms were included. Such assumption of equality however is not applicable to small businesses contracts because SMEs are often in a disadvantageous position in relation to their larger counterparties. Consumer contracts in their turn are more closely regulated by the English and Brazilian legal systems which recognised that vulnerable parties are more exposed to unfair terms imposed by the stronger party as a result of the inequality of bargaining power. For this reason those jurisdictions adopted a more interventionist approach to provide special protection to consumers which is in line with the modern law of contract. The contribution of this work therefore consists of comparing how the law of England and Brazil tackles the problem of ‘unfairness’ in the above types of contracts. This study will examine the differences and similarities between rules and concepts of both jurisdictions with references to the law of their respective regional trade agreements (EU and the Mercosul). Moreover it will identify existing issues in the English and Brazilian legislation and recommend lessons that one system can learn from the other.

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Mergers and acquisitions (M&) are increasingly becoming a strategy of choice for companies attempting to achieve and sustain competitive advantage. However, not all M&As are a success. In this paper, we examine the three main reasons highlighted in the literature as major causes of M&A failure (clashing corporate cultures, absence of clear communication, and employee involvement) in three Indian pharmaceutical companies, and we analyze the role played by the HR function in addressing them. Also, we discuss the importance of gaining the commitment and focus of the workforce during the acquisition process through employee involvement.

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Mechanical physiological pulsations are movements of a body surface incited by the movements of muscles in organs inside the body. Here we demonstrate the use of long-period grating sensors in the detection of cardio-vascular pulsations (CVP), in particular apex and carotid pulsations. To calibrate the sensors, we use a mechanical tool designed specifically to measure the sensor response to a localized perturbation at different grating curvatures as working points. From the data we infer the amplitude of the CVP. Together with the electrophysiological signals, the CVP signals obtained from the sensors can provide significant information on heart function which is inaccessible to the electrocardiogram. The low cost and easy handling of the fibre sensors increase their prospects to become the sensors of choice for novel diagnostic devices. © 2013 The Royal Swedish Academy of Sciences.

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This thesis presents a two-dimensional water model investigation and development of a multiscale method for the modelling of large systems, such as virus in water or peptide immersed in the solvent. We have implemented a two-dimensional ‘Mercedes Benz’ (MB) or BN2D water model using Molecular Dynamics. We have studied its dynamical and structural properties dependence on the model’s parameters. For the first time we derived formulas to calculate thermodynamic properties of the MB model in the microcanonical (NVE) ensemble. We also derived equations of motion in the isothermal–isobaric (NPT) ensemble. We have analysed the rotational degree of freedom of the model in both ensembles. We have developed and implemented a self-consistent multiscale method, which is able to communicate micro- and macro- scales. This multiscale method assumes, that matter consists of the two phases. One phase is related to micro- and the other to macroscale. We simulate the macro scale using Landau Lifshitz-Fluctuating Hydrodynamics, while we describe the microscale using Molecular Dynamics. We have demonstrated that the communication between the disparate scales is possible without introduction of fictitious interface or approximations which reduce the accuracy of the information exchange between the scales. We have investigated control parameters, which were introduced to control the contribution of each phases to the matter behaviour. We have shown, that microscales inherit dynamical properties of the macroscales and vice versa, depending on the concentration of each phase. We have shown, that Radial Distribution Function is not altered and velocity autocorrelation functions are gradually transformed, from Molecular Dynamics to Fluctuating Hydrodynamics description, when phase balance is changed. In this work we test our multiscale method for the liquid argon, BN2D and SPC/E water models. For the SPC/E water model we investigate microscale fluctuations which are computed using advanced mapping technique of the small scales to the large scales, which was developed by Voulgarakisand et. al.