972 resultados para Preparation phase
Resumo:
Research on firm exit has grown considerably in volume and sophistication in recent years, leading to new insights and strengthened research-based evidence. However, no framework explicitly explains nascent disengagement, i.e., termination of start-up efforts before the firm has reached an operational stage. Further, prior research has had limited success at explaining nascent entrepreneurial behaviour using theories based on logics of resource availability and economic rationality. In response, this chapter approaches nascent stage disengagement unconventionally by proposing to analogously apply Sternberg’s (1986) Triangular Theory of Love, arguing that founders are less likely to give up the start-up effort if they create strong, almost loving relations to their businesses. Nascent entrepreneurs who terminate the start-up process are proposed to lack one or more of the components – intimacy, passion, and commitment – which are essential according to Sternberg’s theory.
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Background A novel ultrasonic atomization approach for the formulation of biodegradable poly(lactic-co-glycolic acid) (PLGA) microparticles of a malaria DNA vaccine is presented. A 40 kHz ultrasonic atomization device was used to create the microparticles from a feedstock containing 5 volumes of 0.5% w/v PLGA in acetone and 1 volume of condensed DNA which was fed at a flow rate of 18ml h-1. The plasmid DNA vectors encoding a malaria protein were condensed with a cationic polymer before atomization. Results High levels of gene expression in vitro were observed in COS-7 cells transfected with condensed DNA at a nitrogen to phosphate (N/P) ratio of 10. At this N/P ratio, the condensed DNA exhibited a monodispersed nanoparticle size (Z-average diameter of 60.8 nm) and a highly positive zeta potential of 38.8mV. The microparticle formulations of malaria DNA vaccine were quality assessed and it was shown that themicroparticles displayed high encapsulation efficiencies between 82-96% and a narrow size distribution in the range of 0.8-1.9 μm. In vitro release profile revealed that approximately 82% of the DNA was released within 30 days via a predominantly diffusion controlledmass transfer system. Conclusions This ultrasonic atomization technique showed excellent particle size reproducibility and displayed potential as an industrially viable approach for the formulation of controlled release particles.
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Numerous efforts have been dedicated to the synthesis of large-volume methacrylate monoliths for large-scale biomolecules purification but most were obstructed by the enormous release of exotherms during preparation, thereby introducing structural heterogeneity in the monolith pore system. A significant radial temperature gradient develops along the monolith thickness, reaching a terminal temperature that supersedes the maximum temperature required for structurally homogenous monoliths preparation. The enormous heat build-up is perceived to encompass the heat associated with initiator decomposition and the heat released from free radical-monomer and monomer-monomer interactions. The heat resulting from the initiator decomposition was expelled along with some gaseous fumes before commencing polymerization in a gradual addition fashion. Characteristics of 80 mL monolith prepared using this technique was compared with that of a similar monolith synthesized in a bulk polymerization mode. An extra similarity in the radial temperature profiles was observed for the monolith synthesized via the heat expulsion technique. A maximum radial temperature gradient of only 4.3°C was recorded at the center and 2.1°C at the monolith peripheral for the combined heat expulsion and gradual addition technique. The comparable radial temperature distributions obtained birthed identical pore size distributions at different radial points along the monolith thickness.
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The creation of a commercially viable and a large-scale purification process for plasmid DNA (pDNA) production requires a whole-systems continuous or semi-continuous purification strategy employing optimised stationary adsorption phase(s) without the use of expensive and toxic chemicals, avian/bovine-derived enzymes and several built-in unit processes, thus affecting overall plasmid recovery, processing time and economics. Continuous stationary phases are known to offer fast separation due to their large pore diameter making large molecule pDNA easily accessible with limited mass transfer resistance even at high flow rates. A monolithic stationary sorbent was synthesised via free radical liquid porogenic polymerisation of ethylene glycol dimethacrylate (EDMA) and glycidyl methacrylate (GMA) with surface and pore characteristics tailored specifically for plasmid binding, retention and elution. The polymer was functionalised with an amine active group for anion-exchange purification of pDNA from cleared lysate obtained from E. coli DH5α-pUC19 pellets in RNase/protease-free process. Characterization of the resin showed a unique porous material with 70% of the pores sizes above 300 nm. The final product isolated from anion-exchange purification in only 5 min was pure and homogenous supercoiled pDNA with no gDNA, RNA and protein contamination as confirmed with DNA electrophoresis, restriction analysis and SDS page. The resin showed a maximum binding capacity of 15.2 mg/mL and this capacity persisted after several applications of the resin. This technique is cGMP compatible and commercially viable for rapid isolation of pDNA.
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A monolithic stationary phase was prepared via free radical co-polymerization of ethylene glycol dimethacrylate (EDMA) and glycidyl methacrylate (GMA) with pore diameter tailored specifically for plasmid binding, retention and elution. The polymer was functionalized. with 2-chloro-N,N-diethylethylamine hydrochloride (DEAE-Cl) for anion-exchange purification of plasmid DNA (pDNA) from clarified lysate obtained from E. coli DH5α-pUC19 culture in a ribonuclease/ protease-free environment. Characterization of the monolithic resin showed a porous material, with 68% of the pores existing in the matrix having diameters above 300 nm. The final product isolated from a single-stage 5 min anion-exchange purification was a pure and homogeneous supercoiled (SC) pDNA with no gDNA, RNA and protein contamination as confirmed by ethidium bromide agarose gel electrophoresis (EtBr-AGE), enzyme restriction analysis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This non-toxic technique is cGMP compatible and highly scalable for production of pDNA on a commercial level.
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Mechanically interlocked molecules, such as catenanes and rotaxanes, are fascinating due to their unique sensing and catalytic properties and their potential to act as molecular motors or switches. Traditionally their synthesis has been laborious and expensive, however this research project endeavoured to overcome this challenge by exploring novel ways of preparing mechanically interlocked molecules both in solution and on surfaces. A series of disulfide-linked macrocycles, [2]catenanes and [2]rotaxanes were synthesised in solution using reversible dynamic covalent chemistry. Subsequently, the interlocked architectures were adapted into solid-tethered systems via attachment to swelling polystyrene resins.
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This thesis consists of three studies on investment strategies for Australian retirees. Specifically, it investigates retirees' preference between alternative drawdown strategies in the presence of government pensions, appropriate management of longevity risk through the use of deferred annuities and asset allocation in retirement. It finds drawdown strategies linked to life expectancy to be the best performers. Deferred annuities are found to improve retirement incomes for risk averse retirees. For retirees who want to meet certain wealth thresholds in retirement, equity dominated portfolios provide superior outcomes for higher threshold levels.
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Road infrastructure is a major contributor of greenhouse gas (GHG) around the world. Once constructed, a road becomes a part of a road network and is subjected to recurrent maintenance/rehabilitation activities. Studies to date are mostly aimed at the development of sustainability indicators that deal with the material and construction phases of a road when it is constructed. The operation phase is infrequently studied and there is a need for sustainability indicators to be developed relating to this phase to better understand the GHG emissions as a proper response to the climate change phenomena. During the operation phase, maintenance/rehabilitation activities are undertaken based on certain agreed intervention criteria that do not include environmental implications relating to the climate change aspect properly. Availability of appropriate indicators may, therefore, assist in sustainable road asset maintenance management. This paper presents the findings of a literature based study and has proposed a way forward to develop a key “road operation phase” environmental indicator, which can contribute to road operation phase carbon footprint management based on a comprehensive road life cycle system boundary model. The proposed indicator can address multiple aspects of high impact road operation life environmental components such as: pavement rolling resistance, albedo, material, traffic congestion and lighting, based on availability of relevant scientific knowledge. Development of the indicator to appropriate level would offset the impacts of these components significantly and contribute to sustainable road operation management.
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PURPOSE Brivanib, an oral, multi-targeted tyrosine kinase inhibitor with activity against vascular endothelial growth factor (VEGF) and fibroblast growth factor receptor (FGFR) was investigated as a single agent in a phase II trial to assess the activity and tolerability in recurrent or persistent endometrial cancer (EMC). PATIENTS AND METHODS Eligible patients had persistent or recurrent EMC after receiving one to two prior cytotoxic regimens, measurable disease, and performance status of ≤2. Treatment consisted of brivanib 800 mg orally every day until disease progression or prohibitive toxicity. Primary endpoints were progression-free survival (PFS) at six months and objective tumor response. Expression of multiple angiogenic proteins and FGFR2 mutation status was assessed. RESULTS Forty-five patients were enrolled. Forty-three patients were eligible and evaluable. Median age was 64 years. Twenty-four patients (55.8%) received prior radiation. Median number of cycles was two (range 1-24). No GI perforations but one rectal fistula were seen. Nine patients had grade 3 hypertension, with one experiencing grade 4 confusion. Eight patients (18.6%; 90% CI 9.6%-31.7%) had responses (one CR and seven PRs), and 13 patients (30.2%; 90% CI 18.9%-43.9%) were PFS at six months. Median PFS and overall survival (OS) were 3.3 and 10.7 months, respectively. When modeled jointly, VEGF and angiopoietin-2 expression may diametrically predict PFS. Estrogen receptor-α (ER) expression was positively correlated with OS. CONCLUSION Brivanib is reasonably well tolerated and worthy of further investigation based on PFS at six months in recurrent or persistent EMC.
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It has long been known that disasters can have mental health consequences such as increased rates of PTSD, depression and anxiety. While some research has shown that secondary stressors during the aftermath of a disaster can influence psychological outcomes, this aspect of the disaster experience has not been widely studied. This paper reports on two studies that investigated which aspects of the experience of being flooded were most predictive of mental health outcomes. The first study was a qualitative study of adults whose homes had been inundated in the Mackay flood of 2008 (n=16). Thematic analysis of interviews conducted 18-20 months post-flood found that stressors during the flood aftermath such as difficulties and delays during the rebuilding process and a difficult experience with an insurance company were nominated as the most stressful aspect of the flood by the majority of participants. The second study surveyed Mackay flood survivors three and a half years post-flood, and Brisbane 2011 flood survivors 7-9 months post-flood (n=158). Findings indicated aftermath stress contributed to mental health outcomes over and above the contribution of perceived trauma, objective flood severity, prior mental health, self-efficacy and demographic factors. The implications of these results for the provision of community recovery services following natural disasters are discussed, including the need to provide effective targeting of support services throughout the lengthy rebuilding phase; a possible role for co-ordinating tradespeople; and training for insurance company staff aimed at minimising the incidence of insurance company staff inadvertently adding to disaster victims’ stress.
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Purpose of this paper One way in which the tendering process can be further improved is by reviewing and clarifying the high costs that participants face during the course of the tendering phase. The study aims to provide project teams working in construction tender preparation a clear picture of what to expect when tendering for infrastructure projects. Design/methodology/approach Firstly, a review of current literature on tendering in infrastructure projects is conducted to identify the associated costs affecting traditional and PPP procurements as well as the potential measures contributing to tendering cost-reduction. A theoretical framework and its corresponding research hypotheses, which are based on the literature reviewed, are then proposed. An industry-wide questionnaire survey is currently under design to solicit industry practitioners’ views on tendering costs and the associated tendering cost-reduction measures. The data collected in the survey will subject to statistical analysis to test the proposed research hypotheses, which will be reported in a forthcoming paper. Findings and value The direct and indirect costs in public-private procurement have been identified and have been categorised into internal and external costs arising from working on tender submissions. A theoretical framework, mainly composed of five mechanisms of cost reduction, has been proposed and will be tested in a forthcoming industry-wide questionnaire survey. Originality/value of paper The findings are expected to lead to a transparent tendering process in infrastructure procurement, in which there is increased engagement from the private sector as well as an increase in competitive tendering.
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One of the objectives of this study was to evaluate soil testing equipment based on its capability of measuring in-place stiffness or modulus values. As design criteria transition from empirical to mechanistic-empirical, soil test methods and equipment that measure properties such as stiffness and modulus and how they relate to Florida materials are needed. Requirements for the selected equipment are that they be portable, cost effective, reliable, a ccurate, and repeatable. A second objective is that the selected equipment measures soil properties without the use of nuclear materials.The current device used to measure soil compaction is the nuclear density gauge (NDG). Equipment evaluated in this research included lightweight deflectometers (LWD) from different manufacturers, a dynamic cone penetrometer (DCP), a GeoGauge, a Clegg impact soil tester (CIST), a Briaud compaction device (BCD), and a seismic pavement analyzer (SPA). Evaluations were conducted over ranges of measured densities and moistures.Testing (Phases I and II) was conducted in a test box and test pits. Phase III testing was conducted on materials found on five construction projects located in the Jacksonville, Florida, area. Phase I analyses determined that the GeoGauge had the lowest overall coefficient of variance (COV). In ascending order of COV were the accelerometer-type LWD, the geophone-type LWD, the DCP, the BCD, and the SPA which had the highest overall COV. As a result, the BCD and the SPA were excluded from Phase II testing.In Phase II, measurements obtained from the selected equipment were compared to the modulus values obtained by the static plate load test (PLT), the resilient modulus (MR) from laboratory testing, and the NDG measurements. To minimize soil and moisture content variability, the single spot testing sequence was developed. At each location, test results obtained from the portable equipment under evaluation were compared to the values from adjacent NDG, PLT, and laboratory MR measurements. Correlations were developed through statistical analysis. Target values were developed for various soils for verification on similar soils that were field tested in Phase III. The single spot testing sequence also was employed in Phase III, field testing performed on A-3 and A-2-4 embankments, limerock-stabilized subgrade, limerock base, and graded aggregate base found on Florida Department of Transportation construction projects. The Phase II and Phase III results provided potential trend information for future research—specifically, data collection for in-depth statistical analysis for correlations with the laboratory MR for specific soil types under specific moisture conditions. With the collection of enough data, stronger relationships could be expected between measurements from the portable equipment and the MR values. Based on the statistical analyses and the experience gained from extensive use of the equipment, the combination of the DCP and the LWD was selected for in-place soil testing for compaction control acceptance. Test methods and developmental specifications were written for the DCP and the LWD. The developmental specifications include target values for the compaction control of embankment, subgrade, and base materials.