963 resultados para Quantitative systems pharmacology


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Destruction of cancer cells by genetically modified viral and nonviral vectors has been the aim of many research programs. The ability to target cytotoxic gene therapies to the cells of interest is an essential prerequisite, and the treatment has always had the potential to provide better and more long-lasting therapy than existing chemotherapies. However, the potency of these infectious agents requires effective testing systems, in which hypotheses can be explored both in vitro and in vivo before the establishment of clinical trials in humans. The real prospect of off-target effects should be eliminated in the preclinical stage, if current prejudices against such therapies are to be overcome. In this review we have set out, using adenoviral vectors as a commonly used example, to discuss some of the key parameters required to develop more effective testing, and to critically assess the current cellular models for the development and testing of prostate cancer biotherapy. Only by developing models that more closely mirror human tissues will we be able to translate literature publications into clinical trials and hence into acceptable alternative treatments for the most commonly diagnosed cancer in humans.

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In this paper, we present the outcomes of a project on the exploration of the use of Field Programmable Gate Arrays (FPGAs) as co-processors for scientific computation. We designed a custom circuit for the pipelined solving of multiple tri-diagonal linear systems. The design is well suited for applications that require many independent tri-diagonal system solves, such as finite difference methods for solving PDEs or applications utilising cubic spline interpolation. The selected solver algorithm was the Tri-Diagonal Matrix Algorithm (TDMA or Thomas Algorithm). Our solver supports user specified precision thought the use of a custom floating point VHDL library supporting addition, subtraction, multiplication and division. The variable precision TDMA solver was tested for correctness in simulation mode. The TDMA pipeline was tested successfully in hardware using a simplified solver model. The details of implementation, the limitations, and future work are also discussed.

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Abstract: LiteSteel beam (LSB) is a new cold-formed steel hollow flange channel section produced using a simultaneous cold-forming and dual electric resistance welding process. It is commonly used as floor joists and bearers with web openings in residential, industrial and commercial buildings. Their shear strengths are considerably reduced when web openings are included for the purpose of locating building services. A cost effective method of eliminating the detrimental effects of a large web opening is to attach suitable stiffeners around the web openings of LSBs. Experimental and numerical studies were undertaken to investigate the shear behaviour and strength of LSBs with circular web openings reinforced using plate, stud, transverse and sleeve stiffeners with varying sizes and thicknesses. Both welding and varying screw-fastening arrangements were used to attach these stiffeners to the web of LSBs. Finite element models of LSBs with stiffened web openings in shear were developed to simulate their shear behaviour and strength of LSBs. They were then validated by comparing the results with experimental test results and used in a detailed parametric study. These studies have shown that plate stiffeners were the most suitable, however, their use based on the current American standards was found to be inadequate. Suitable screw-fastened plate stiffener arrangements with optimum thicknesses have been proposed for LSBs with web openings to restore their original shear capacity. This paper presents the details of the numerical study and the results.

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We examined the variation in association between high temperatures and elderly mortality (age ≥ 75 years) from year to year in 83 US cities between 1987 and 2000. We used a Poisson regression model and decomposed the mortality risk for high temperatures into: a “main effect” due to high temperatures using lagged non-linear function, and an “added effect” due to consecutive high temperature days. We pooled yearly effects across both regional and national levels. The high temperature effects (both main and added effects) on elderly mortality varied greatly from year to year. In every city there was at least one year where higher temperatures were associated with lower mortality. Years with relatively high heat-related mortality were often followed by years with relatively low mortality. These year to year changes have important consequences for heat-warning systems and for predictions of heat-related mortality due to climate change.

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This paper presents an approach to developing indicators for expressing resilience of a generic water supply system. The system is contextualised as a meta-system consisting of three subsystems to represent the water catchment and reservoir, treatment plant and the distribution system supplying the end-users. The level of final service delivery to end-users is considered as a surrogate measure of systemic resilience. A set of modelled relationships are used to explore relationships between system components when placed under simulated stress. Conceptual system behaviour of specific types of simulated pressure is created for illustration of parameters for indicator development. The approach is based on the hypothesis that an in-depth knowledge of resilience would enable development of decision support system capability which in turn will contribute towards enhanced management of a water supply system. In contrast to conventional water supply system management approaches, a resilience approach facilitates improvement in system efficiency by emphasising awareness of points-of-intervention where system managers can adjust operational control measures across the meta-system (and within subsystems) rather than expansion of the system in entirety in the form of new infrastructure development.

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Optimisation of Organic Rankine Cycle (ORCs) for binary-cycle geothermal applications could play a major role in determining the competitiveness of low to moderate temperature geothermal resources. Part of this optimisation process is matching cycles to a given resource such that power output can be maximised. Two major and largely interrelated components of the cycle are the working fluid and the turbine. Both components need careful consideration: the selection of working fluid and appropriate operating conditions as well as optimisation of the turbine design for those conditions will determine the amount of power that can be extracted from a resource. In this paper, we present the rationale for the use of radial-inflow turbines for ORC applications and the preliminary design of several radial-inflow machines based on a number of promising ORC systems that use five different working fluids: R134a, R143a, R236fa, R245fa and n-Pentane. Preliminary meanline analysis lead to the generation of turbine designs for the various cycles with similar efficiencies (77%) but large differences in dimensions (139–289 mm rotor diameter). The highest performing cycle, based on R134a, was found to produce 33% more net power from a 150 °C resource flowing at 10 kg/s than the lowest performing cycle, based on n-Pentane.

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Optimisation of Organic Rankine Cycles (ORCs) for binary-cycle geothermal applications could play a major role in the competitiveness of low to moderate temperature geothermal resources. Part of this optimisation process is matching cycles to a given resource such that power output can be maximised. Two major and largely interrelated components of the cycle are the working fluid and the turbine. Both components need careful consideration. Due to the temperature differences in geothermal resources a one-size-fits-all approach to surface power infrastructure is not appropriate. Furthermore, the traditional use of steam as a working fluid does not seem practical due to the low temperatures of many resources. A variety of organic fluids with low boiling points may be utilised as ORC working fluids in binary power cycle loops. Due to differences in thermodynamic properties, certain fluids are able to extract more heat from a given resource than others over certain temperature and pressure ranges. This enables the tailoring of power cycle infrastructure to best match the geothermal resource through careful selection of the working fluid and turbine design optimisation to yield the optimum overall cycle performance. This paper presents the rationale for the use of radial-inflow turbines for ORC applications and the preliminary design of several radial-inflow turbines based on a selection of promising ORC cycles using five different high-density working fluids: R134a, R143a, R236fa, R245fa and n-Pentane at sub- or trans-critical conditions. Numerous studies published compare a variety of working fluids for various ORC configurations. However, there is little information specifically pertaining to the design and implementation of ORCs using realistic radial turbine designs in terms of pressure ratios, inlet pressure, rotor size and rotational speed. Preliminary 1D analysis leads to the generation of turbine designs for the various cycles with similar efficiencies (77%) but large differences in dimensions (139289 mm rotor diameter). The highest performing cycle (R134a) was found to produce 33% more net power from a 150°C resource flowing at 10 kg/s than the lowest performing cycle (n-Pentane).

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The knowledge economy relies on the diffusion and use of knowledge as well as its creation (Houghton and Sheenan, 2000). The future success of economic activity will depend on the capacity of organisations to transform by increasing their flexibility. In particular, this transformation is dependant on a decentralised, networked and multi-skilled workforce. To help organisations transition, new strategies and structures for education are required. Education systems need to concentrate less on specialist skills and more on the development of people with broad-based problem solving skills that are adaptable, with social and inter-personal communication skills necessary for networking and communication. This paper presents the findings of a ‘Knowledge Economy Market Development Mapping Study’ conducted to identify the value of design education programs from primary through to tertiary level in Queensland, Australia. The relationship of these programs to the development of the capacities mentioned above is explored. The study includes the collection of qualitative and quantitative data consisting of a literature review, focus groups and survey. Recommendations for the future development of design education programs in Queensland, Australia are proposed, and future research opportunities are presented and discussed.

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The knowledge economy relies on the diffusion and use of knowledge as well as its creation (Houghton and Sheenan, 2000). The future success of economic activity will depend on the capacity of organisations to transform by increasing their flexibility. In particular, this transformation is dependant on a decentralised, networked and multi-skilled workforce. To help organisations transition, new strategies and structures for education are required. Education systems need to concentrate less on specialist skills and more on the development of people with broad-based problem solving skills that are adaptable, with social and inter-personal communication skills necessary for networking and communication. This paper presents the findings of a ‘Knowledge Economy Market Development Mapping Study’ conducted to identify the value of design education programs from primary through to tertiary level in Queensland, Australia. The relationship of these programs to the development of the capacities mentioned above is explored. The study includes the collection of qualitative and quantitative data consisting of a literature review, focus groups and survey. Recommendations for the future development of design education programs in Queensland, Australia are proposed, and future research opportunities are presented and discussed.

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The Cross-Entropy (CE) is an efficient method for the estimation of rare-event probabilities and combinatorial optimization. This work presents a novel approach of the CE for optimization of a Soft-Computing controller. A Fuzzy controller was designed to command an unmanned aerial system (UAS) for avoiding collision task. The only sensor used to accomplish this task was a forward camera. The CE is used to reach a near-optimal controller by modifying the scaling factors of the controller inputs. The optimization was realized using the ROS-Gazebo simulation system. In order to evaluate the optimization a big amount of tests were carried out with a real quadcopter.

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Substantial research efforts have been expended to deal with the complexity of concurrent systems that is inherent to their analysis, e.g., works that tackle the well-known state space explosion problem. Approaches differ in the classes of properties that they are able to suitably check and this is largely a result of the way they balance the trade-off between analysis time and space employed to describe a concurrent system. One interesting class of properties is concerned with behavioral characteristics. These properties are conveniently expressed in terms of computations, or runs, in concurrent systems. This article introduces the theory of untanglings that exploits a particular representation of a collection of runs in a concurrent system. It is shown that a representative untangling of a bounded concurrent system can be constructed that captures all and only the behavior of the system. Representative untanglings strike a unique balance between time and space, yet provide a single model for the convenient extraction of various behavioral properties. Performance measurements in terms of construction time and size of representative untanglings with respect to the original specifications of concurrent systems, conducted on a collection of models from practice, confirm the scalability of the approach. Finally, this article demonstrates practical benefits of using representative untanglings when checking various behavioral properties of concurrent systems.

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A multicausal model of adolescent homelessness is proposed, based upon the notion that homeless youth suffer from emotional, social, and cultural deprivation. The model was tested in a sample of homeless adolescents (n = 54) and a similar, but not homeless, control group (n = 58). Emotional deprivation was assessed on the Parental Bonding Inventory (Parker, Tupling,&Brown, 1979), whereas social and cultural deprivation were assessed on the Family Environment Scale (Moos&Moos, 1981). The homeless adolescents were found to be significantly more deprived emotionally, socially, and culturally than the controls. The results indicate support for a deprivation model of adolescent homelessness with implications for public policy and intervention planning.

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Linear adaptive channel equalization using the least mean square (LMS) algorithm and the recursive least-squares(RLS) algorithm for an innovative multi-user (MU) MIMOOFDM wireless broadband communications system is proposed. The proposed equalization method adaptively compensates the channel impairments caused by frequency selectivity in the propagation environment. Simulations for the proposed adaptive equalizer are conducted using a training sequence method to determine optimal performance through a comparative analysis. Results show an improvement of 0.15 in BER (at a SNR of 16 dB) when using Adaptive Equalization and RLS algorithm compared to the case in which no equalization is employed. In general, adaptive equalization using LMS and RLS algorithms showed to be significantly beneficial for MU-MIMO-OFDM systems.

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The gold standard method for detecting chlamydial infection in domestic and wild animals is PCR, but the technique is not suited to testing animals in the field when a rapid diagnosis is frequently required. The objective of this study was to compare the results of a commercially available enzyme immunoassay test for Chlamydia against a quantitative Chlamydia pecorum-specific PCR performed on swabs collected from the conjunctival sac, nasal cavity and urogenital sinuses of naturally infected koalas (Phascolarctos cinereus). The level of agreement for positive results between the two assays was low (43.2%). The immunoassay detection cut-off was determined as approximately 400 C. pecorum copies, indicating that the test was sufficiently sensitive to be used for the rapid diagnosis of active chlamydial infections.

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The relationship between Heritage Language and ethnic identity has gained significant research ground in North America. However, there is a dearth of similar research conducted in other regions of the world. There seems to be little if any work investigating the link between Chinese Australians’ ethnic identity and their Chinese Heritage Language. This sociological quantitative study interpreted Chinese Australians’ “Chineseness” as their ethnic identity, linked this “Chineseness” to their Chinese Heritage Language, and did so by virtue of Bourdieu’s key concept ‘habitus’. 227 cases were analyzed by Structural Equation Modelling. The result demonstrated a statistically significant strong positive relationship between Chinese Australian urban young adults’ “Chineseness” and their self-perceptions of their Chinese Heritage Language proficiency (r=.73). This paper explained the findings in light of Bourdieu’s (1991) contention that people make choices about languages according to the habitus they have.