918 resultados para Gene Doping, Performance-Enhancement, Pragmatic Ethics


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While environmental legislation in Australia regulates tourism development, it is less effective in operational areas because of the dependency of tourism on environmental resources that are not managed by operators, and the small but incremental nature of operational impacts. The absence of functional environmental standards for tourism means that little guidance exists: a problem compounded by variability in the diversity of operation types and receiving environments, as well as the accessibility of information by a non-technical audience. While legislation and economic considerations may provide impetus to adopt environmental practices, it is proposed that an environmental philosophy is necessary for tourism businesses to seek out and maintain alternative sustainable modes of operation. Review of the environmental audit process used by a Queensland resort suggests commitment to continual improvement in environmental performance is attributable to individual and corporate ethics. While the case is an ecotourism operation, the literature indicates that these factors have relevance to tourism generally. Although client satisfaction and return on investment objectives are constraints, environmental auditing can provide impetus for practical expression of environmental objectives. Facilitation of ethically-motivated voluntary action may be more effective in achieving tourism's environmental objectives than codifying standards in static legislation.

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In the present study, NaSi-l sulphate transporter knock-out (Nas1-/-) mice, an animal model of hyposulphataernia, were examined for spatial memory and learning in a Morris water maze, and for olfactory function in a cookie test. The Nas1-/- mice displayed significantly (P < 0.05) increased latencies to find an escape platform in the reversal teaming trials at 2 days but not 1 day after the last acquisition trial in a Morris water maze test. suggesting that Nas1-/- mice may have proactive memory interference. While the wild-type (Ncis1+/+) mice showed a significant (P < 0.02) decrease in time to locate a hidden food reward over four trials after overnight fasting, Nas1-/- mice did not change their performance, resulting in significantly (P < 0.05) higher latencies when compared to their Nas1+/+ littermates. There were no significant differences between Nas1-/- and Nas1+/+ mice in the cookie test after moderate food deprivation. In addition, both Nas1-/- and Nas1+/+ mice displayed similar escape latencies in the acquisition phase of the Morris water maze test, suggesting that learning, motivation, vision and motor skills required for the task may not be affected in Nas1-/- mice. This is the first study to demonstrate an impairment in memory and olfactory performance in the hyposulphataemic Nas1-/- mouse. (c) 2004 Elsevier B.V. All rights reserved.

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Objectives: The aim of this study was to assess the consistency and performance of radiologists interpreting breast magnetic resonance imaging (MRI) examinations. Materials and Methods: Two test sets of eight cases comprising cancers, benign disease, technical problems and parenchymal enhancement were prepared from two manufacturers' equipment (X and Y) and reported by 15 radiologists using the recording form and scoring system of the UK MRI breast screening study [(MAgnetic Resonance Imaging in Breast Screening (MARIBS)]. Variations in assessments of morphology, kinetic scores and diagnosis were measured by assessing intraobserver and interobserver variability and agreement. The sensitivity and specificity of reporting performances was determined using receiver operating characteristic (ROC) curve analysis. Results: Intraobserver variation was seen in 13 (27.7%) of 47 of the radiologists' conclusions (four technical and seven pathological differences). Substantial interobserver variation was observed in the scores recorded for morphology, pattern of enhancement, quantification of enhancement and washout pattern. The overall sensitivity of breast MRI was high [88.6%, 95% confidence interval (CI) 77.4-94.7%], combined with a specificity of 69.2% (95% CI 60.5-76.7%). The sensitivities were similar for the two test sets (P=.3), but the specificity was significantly higher for the Manufacturer X dataset (P

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The demand for palliative care is increasing, yet there are few data on the best models of care nor well-validated interventions that translate current evidence into clinical practice. Supporting multidisciplinary patient-centered palliative care while successfully conducting a large clinical trial is a challenge. The Palliative Care Trial (PCT) is a pragmatic 2 x 2 x 2 factorial cluster randomized controlled trial that tests the ability of educational outreach visiting and case conferencing to improve patient-based outcomes such as performance status and pain intensity. Four hundred sixty-one consenting patients and their general practitioners (GPs) were randomized to the following: (1) GP educational outreach visiting versus usual care, (2) Structured patient and caregiver educational outreach visiting versus usual care and (3) A coordinated palliative care model of case conferencing versus the standard model of palliative care in Adelaide, South Australia (3:1 randomization). Main outcome measures included patient functional status over time, pain intensity, and resource utilization. Participants were followed longitudinally until death or November 30, 2004. The interventions are aimed at translating current evidence into clinical practice and there was particular attention in the trial's design to addressing common pitfalls for clinical studies in palliative care. Given the need for evidence about optimal interventions and service delivery models that improve the care of people with life-limiting illness, the results of this rigorous, high quality clinical trial will inform practice. Initial results are expected in mid 2005. (c) 2005 Elsevier Inc. All rights reserved.

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A significant enhancement in glass formation in a newly developed Zr51Cu20.7Ni12Al16.3 alloy has been achieved by yttrium doping. With just 0.5 at.% yttrium doping, the critical diameter of the as-cast alloys for glass formation has been increased from 3 mm to at least 10 mm. In the undoped, large-sized alloys, massive oxygen stabilized crystalline phases are observed but disappear in yttrium doped alloys. Very small amounts of stable alpha-Y2O3 phases found in the yttrium doped alloys, and their negligible effect on the metallic glasses' properties, provide a superior solution to achieve metallic glasses with a high glass formability. (c) 2006 Elsevier B.V. All rights reserved.

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It is well known that resistance training improves muscle strength in older adults and may enhance or preserve functional performance. However, it is unclear if the volume of work undertaken in the elderly alters the response in functional performance. PURPOSE: To investigate the effect of a high- versus low-volume resistance training program on functional performance in older adults. METHODS: Thirty-two healthy men and women aged 65-78 years were randomly assigned to either a single-set (SS, n = 16) or 3-set (MS, n = 16) progressive resistance training program for 20 weeks. Groups trained 2 days per week using machine weights at 8 repetitions maximum (8-RM) for 7 upper and lower body exercises. Muscle strength was assessed by the 1-RM and functional performance by a battery of tests (repeated chair rise, usual and fast 6-m walk, 6-m backwards walk, floor rise to standing, stair climb, and 400-m walk time). RESULTS: Twenty-eight subjects completed the study. There was no difference between groups at baseline in muscle strength or functional performance. Whole body muscle strength significantly increased in both groups with greater gains in the 3-set group (MS 32.9 ± 3.1%; SS 18.6 ± 2.7%, mean ± SE; P < 0.01). Significant improvement (time effect, P < 0.01) occurred for both groups in the chair rise (MS 13.6 ± 3.2%; SS 10.2 ± 3.0%), 6-m backwards walk (MS 14.9 ± 3.3%; SS 14.3 ± 4.2%), stair climb (MS 6.4 ± 2.8%; SS 7.7 ± 3.1%) and 400-m walk (MS 7.4 ± 1.4%; SS 3.9 ± 1.2%). There were no interaction (group × time) effects for functional performance and no differences by sex. CONCLUSION: Resistance training that utilizes either a singleset or 3-set regimen may significantly and similarly improve functional performance in community-dwelling older adults. Enhancement of functional performance may prolong independence and improve quality of life. ©2004The American College of Sports Medicine

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Fast Classification (FC) networks were inspired by a biologically plausible mechanism for short term memory where learning occurs instantaneously. Both weights and the topology for an FC network are mapped directly from the training samples by using a prescriptive training scheme. Only two presentations of the training data are required to train an FC network. Compared with iterative learning algorithms such as Back-propagation (which may require many hundreds of presentations of the training data), the training of FC networks is extremely fast and learning convergence is always guaranteed. Thus FC networks may be suitable for applications where real-time classification is needed. In this paper, the FC networks are applied for the real-time extraction of gene expressions for Chlamydia microarray data. Both the classification performance and learning time of the FC networks are compared with the Multi-Layer Proceptron (MLP) networks and support-vector-machines (SVM) in the same classification task. The FC networks are shown to have extremely fast learning time and comparable classification accuracy.

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The majority of previous research into service quality and services marketing has concentrated upon the measurement of service quality outcomes, rather than the enhancement of the process by which service is delivered. In this study a conceptual model of the service acculturation process is proposed, modelling the input of service managers and employees in the delivery of service quality to customers. The conceptualisation is then empirically tested utilising a dyadic study of the New Zealand hotel industry. Results indicate that 1) a strong commitment to service is important for both managers and employees; and 2) that employees’ teamwork may have an adverse effect on perceived quality of customer service. Implications of the results and future research directions are subsequently discussed.

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There is controversy over whether integrated manufacturing (IM), comprising advanced manufacturing technology, just-in-time inventory control and total quality management, empowers or deskills shop floor work. Moreover, both IM and empowerment are promoted on the assumption that they enhance competitiveness. We examine these issues in a study of 80 manufacturing companies. The extent of use of IM was positively associated with empowerment (i.e., job enrichment and employee skill enhancement), but, with the minor exception of AMT, bore little relationship with subsequent company performance. In contrast, the extent of empowerment within companies predicted the subsequent level of company performance controlling for prior performance, with the effect on productivity mediating that on profit. Copyright © 2004 John Wiley & Sons, Ltd.

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Background Pulmonary delivery of gene therapy offers the potential for the treatment of a range of lung conditions, including cystic fibrosis, asthma and lung cancer. Spray-drying may be used to prepare dry powders for inhalation; however, aerosolisation of such powders is limited, resulting in poor lung deposition and biological functionality. In this study, we examine the use of amino acids (arginine, aspartic acid, threonine, phenylalanine) to enhance the aerosolisation of spray-dried powders containing model non-viral gene vectors. Methods Lipid/polycation/pDNA (LPD) vectors, in the presence or absence of amino acids, were dispersed in lactose solutions, and spray-dried to produce appropriately sized dry powders. Scanning electron microscopy and laser diffraction were used to determine particle morphology and diameter, respectively. Gel electrophoresis was used to examine the influence of amino acids on the structural integrity of the LPD complex. In vitro cell (A.549) transfection was used to determine the biological functionality of the dry powders, and the in vitro aerosolisation performance was assessed using a multistage liquid impinger (MSLI). Results Both gel electrophoresis and in vitro cell transfection indicated that certain amino acids (aspartic acid, threonine) can adversely affect the integrity and biological functionality of the LPD complex. All amino acids significantly increased the aerosolisation of the powder, with the arginine and phenylalanine powders showing optimal deposition in the lower stages of the MSLI. Conclusions Amino acids can be used to enhance the aerosolisation of spray-dried powders for respiratory gene delivery, allowing the development of stable and viable formulations for pulmonary gene therapy.

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Two key issues defined the focus of this research in manufacturing plasmid DNA for use In human gene therapy. First, the processing of E.coli bacterial cells to effect the separation of therapeutic plasmid DNA from cellular debris and adventitious material. Second, the affinity purification of the plasmid DNA in a Simple one-stage process. The need arises when considering the concerns that have been recently voiced by the FDA concerning the scalability and reproducibility of the current manufacturing processes in meeting the quality criteria of purity, potency, efficacy, and safety for a recombinant drug substance for use in humans. To develop a preliminary purification procedure, an EFD cross-flow micro-filtration module was assessed for its ability to effect the 20-fold concentration, 6-time diafiltration, and final clarification of the plasmid DNA from the subsequent cell lysate that is derived from a 1 liter E.coli bacterial cell culture. Historically, the employment of cross-flow filtration modules within procedures for harvesting cells from bacterial cultures have failed to reach the required standards dictated by existing continuous centrifuge technologies, frequently resulting in the rapid blinding of the membrane with bacterial cells that substantially reduces the permeate flux. By challenging the EFD module, containing six helical wound tubular membranes promoting centrifugal instabilities known as Dean vortices, with distilled water between the Dean number's of 187Dn and 818Dn,and the transmembrane pressures (TMP) of 0 to 5 psi. The data demonstrated that the fluid dynamics significantly influenced the permeation rate, displaying a maximum at 227Dn (312 Imh) and minimum at 818Dn (130 Imh) for a transmembrane pressure of 1 psi. Numerical studies indicated that the initial increase and subsequent decrease resulted from a competition between the centrifugal and viscous forces that create the Dean vortices. At Dean numbers between 187Dn and 227Dn , the forces combine constructively to increase the apparent strength and influence of the Dean vortices. However, as the Dean number in increases above 227 On the centrifugal force dominates the viscous forces, compressing the Dean vortices into the membrane walls and reducing their influence on the radial transmembrane pressure i.e. the permeate flux reduced. When investigating the action of the Dean vortices in controlling tile fouling rate of E.coli bacterial cells, it was demonstrated that the optimum cross-flow rate at which to effect the concentration of a bacterial cell culture was 579Dn and 3 psi TMP, processing in excess of 400 Imh for 20 minutes (i.e., concentrating a 1L culture to 50 ml in 10 minutes at an average of 450 Imh). The data demonstrated that there was a conflict between the Dean number at which the shear rate could control the cell fouling, and the Dean number at which tile optimum flux enhancement was found. Hence, the internal geometry of the EFD module was shown to sub-optimal for this application. At 579Dn and 3 psi TMP, the 6-fold diafiltration was shown to occupy 3.6 minutes of process time, processing at an average flux of 400 Imh. Again, at 579Dn and 3 psi TMP the clarification of the plasmid from tile resulting freeze-thaw cell lysate was achieved at 120 Iml1, passing 83% (2,5 mg) of the plasmid DNA (6,3 ng μ-1 10.8 mg of genomic DNA (∼23,00 Obp, 36 ng μ-1 ), and 7.2 mg of cellular proteins (5-100 kDa, 21.4 ngμ-1 ) into the post-EFD process stream. Hence the EFD module was shown to be effective, achieving the desired objectives in approximately 25 minutes. On the basis of its ability to intercalate into low molecular weight dsDNA present in dilute cell lysates, and be electrophoresed through agarose, the fluorophore PicoGreen was selected for the development of a suitable dsDNA assay. It was assesseel for its accuracy, and reliability, In determining the concentration and identity of DNA present in samples that were eleclrophoresed through agarose gels. The signal emitted by intercalated PicoGreen was shown to be constant and linear, and that the mobility of the PicaGreen-DNA complex was not affected by the intercalation. Concerning the secondary purification procedure, various anion-exchange membranes were assessed for their ability to capture plasmid DNA from the post-EFD process stream. For a commercially available Sartorius Sartobind Q15 membrane, the reduction in the equilibriumbinding capacity for  ctDNA in buffer of increasing ionic demonstrated that DNA was being.adsorbed by electrostatic  interactions only. However, the problems associated with fluid distribution across the membrane demonstrated that the membrane housing was the predominant cause of the .erratic breakthrough curves. Consequently, this would need to be rectified before such a membrane could be integrated into the current system, or indeed be scaled beyond laboratory scale. However, when challenged with the process material, the data showed that considerable quantities of protein (1150 μg) were adsorbed preferentially to the plasmid DNA (44 μg). This was also shown for derived Pall Gelman UltraBind US450 membranes that had been functionalised by varying molecular weight poly-L~lysine and polyethyleneimine ligands. Hence the anion-exchange membranes were shown to be ineffective in capturing plasmid DNA from the process stream. Finally, work was performed to integrate a sequence-specific DNA·binding protein into a single-stage DNA chromatography, isolating plasmid DNA from E.coli cells whilst minimising the contamination from genomic DNA and cellular protein. Preliminary work demonstrated that the fusion protein was capable of isolating pUC19 DNA into which the recognition sequence for the fusion-protein had been inserted (pTS DNA) when in the presence of the conditioned process material. Althougth the pTS recognition sequence differs from native pUC19 sequences by only 2 bp, the fusion protein was shown to act as a highly selective affinity ligand for pTS DNA alone. Subsequently, the scale of the process was scaled 25-fold and positioned directly following the EFD system. In conclusion, the integration of the EFD micro-filtration system and zinc-finger affinity purification technique resulted in the capture of approximately 1 mg of plasmid DNA was purified from 1L of E.coli  culture in a simple two stage process, resulting in the complete removal of genomic DNA and 96.7% of cellular protein in less than 1 hour of process time.

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The ERS-1 Satellite was launched in July 1991 by the European Space Agency into a polar orbit at about 800 km, carrying a C-band scatterometer. A scatterometer measures the amount of backscatter microwave radiation reflected by small ripples on the ocean surface induced by sea-surface winds, and so provides instantaneous snap-shots of wind flow over large areas of the ocean surface, known as wind fields. Inherent in the physics of the observation process is an ambiguity in wind direction; the scatterometer cannot distinguish if the wind is blowing toward or away from the sensor device. This ambiguity implies that there is a one-to-many mapping between scatterometer data and wind direction. Current operational methods for wind field retrieval are based on the retrieval of wind vectors from satellite scatterometer data, followed by a disambiguation and filtering process that is reliant on numerical weather prediction models. The wind vectors are retrieved by the local inversion of a forward model, mapping scatterometer observations to wind vectors, and minimising a cost function in scatterometer measurement space. This thesis applies a pragmatic Bayesian solution to the problem. The likelihood is a combination of conditional probability distributions for the local wind vectors given the scatterometer data. The prior distribution is a vector Gaussian process that provides the geophysical consistency for the wind field. The wind vectors are retrieved directly from the scatterometer data by using mixture density networks, a principled method to model multi-modal conditional probability density functions. The complexity of the mapping and the structure of the conditional probability density function are investigated. A hybrid mixture density network, that incorporates the knowledge that the conditional probability distribution of the observation process is predominantly bi-modal, is developed. The optimal model, which generalises across a swathe of scatterometer readings, is better on key performance measures than the current operational model. Wind field retrieval is approached from three perspectives. The first is a non-autonomous method that confirms the validity of the model by retrieving the correct wind field 99% of the time from a test set of 575 wind fields. The second technique takes the maximum a posteriori probability wind field retrieved from the posterior distribution as the prediction. For the third technique, Markov Chain Monte Carlo (MCMC) techniques were employed to estimate the mass associated with significant modes of the posterior distribution, and make predictions based on the mode with the greatest mass associated with it. General methods for sampling from multi-modal distributions were benchmarked against a specific MCMC transition kernel designed for this problem. It was shown that the general methods were unsuitable for this application due to computational expense. On a test set of 100 wind fields the MAP estimate correctly retrieved 72 wind fields, whilst the sampling method correctly retrieved 73 wind fields.

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Optically multiplexed multi-carrier systems with channel spacing reduced to the symbol rate per carrier are highly susceptible to inter-channel crosstalk, which places stringent requirements for the specifications of system components and hinders the use of high-level formats. In this paper, we investigate the performance benefits of using offset 4-, 16-, and 64-quadrature amplitude modulation (QAM) in coherent wavelength division multiplexing (CoWDM). We compare this system with recently reported Nyquist WDM and no-guard-interval optical coherent orthogonal frequency division multiplexing, and show that the presented system greatly relaxes the requirements for device specifications and enhances the spectral efficiency by enabling the use of high-level QAM. The achieved performance can approach the theoretical limits using practical components.