Modeling prostate cancer: a perspective on transgenic mouse models

Despite considerable success in treatment of early stage localized prostate cancer (PC), acute inadequacy of late stage PC treatment and its inherent heterogeneity poses a formidable challenge. Clearly, an improved understanding of PC genesis and progression along with the development of new targeted therapies are warranted. Animal models, especially, transgenic immunocompetent mouse models, have proven to be the best ally in this respect. A series of models have been developed by modulation of expression of genes implicated in cancer-genesis and progression; mainly, modulation of expression of oncogenes, steroid hormone receptors, growth factors and their receptors, cell cycle and apoptosis regulators, and tumor suppressor genes have been used. Such models have contributed significantly to our understanding of the molecular and pathological aspects of PC initiation and progression. In particular, the transgenic mouse models based on multiple genetic alterations can more accurately address the inherent complexity of PC, not only in revealing the mechanisms of tumorigenesis and progression but also for clinically relevant evaluation of new therapies. Further, with advances in conditional knockout technologies, otherwise embryonically lethal gene changes can be incorporated leading to the development of new generation transgenics, thus adding significantly to our existing knowledge base. Different models and their relevance to PC research are discussed.

Semantic modeling method for configurable enterprise information systems

Business practices vary from one company to another and business practices often need to be changed due to changes of business environments. To satisfy different business practices, enterprise systems need to be customized. To keep up with ongoing business practice changes, enterprise systems need to be adapted. Because of rigidity and complexity, the customization and adaption of enterprise systems often takes excessive time with potential failures and budget shortfall. Moreover, enterprise systems often drag business behind because they cannot be rapidly adapted to support business practice changes. Extensive literature has addressed this issue by identifying success or failure factors, implementation approaches, and project management strategies. Those efforts were aimed at learning lessons from post implementation experiences to help future projects. This research looks into this issue from a different angle. It attempts to address this issue by delivering a systematic method for developing flexible enterprise systems which can be easily tailored for different business practices or rapidly adapted when business practices change. First, this research examines the role of system models in the context of enterprise system development; and the relationship of system models with software programs in the contexts of computer aided software engineering (CASE), model driven architecture (MDA) and workflow management system (WfMS). Then, by applying the analogical reasoning method, this research initiates a concept of model driven enterprise systems. The novelty of model driven enterprise systems is that it extracts system models from software programs and makes system models able to stay independent of software programs. In the paradigm of model driven enterprise systems, system models act as instructors to guide and control the behavior of software programs. Software programs function by interpreting instructions in system models. This mechanism exposes the opportunity to tailor such a system by changing system models. To make this true, system models should be represented in a language which can be easily understood by human beings and can also be effectively interpreted by computers. In this research, various semantic representations are investigated to support model driven enterprise systems. The significance of this research is 1) the transplantation of the successful structure for flexibility in modern machines and WfMS to enterprise systems; and 2) the advancement of MDA by extending the role of system models from guiding system development to controlling system behaviors. This research contributes to the area relevant to enterprise systems from three perspectives: 1) a new paradigm of enterprise systems, in which enterprise systems consist of two essential elements: system models and software programs. These two elements are loosely coupled and can exist independently; 2) semantic representations, which can effectively represent business entities, entity relationships, business logic and information processing logic in a semantic manner. Semantic representations are the key enabling techniques of model driven enterprise systems; and 3) a brand new role of system models; traditionally the role of system models is to guide developers to write system source code. This research promotes the role of system models to control the behaviors of enterprise.

Relationships between rainfall intensity, duration and suspended particle washoff from an urban road surface

A basic understanding of the relationships between rainfall intensity, duration of rainfall and the amount of suspended particles in stormwater runoff generated from road surfaces has been gained mainly from past washoff experiments using rainfall simulators. Simulated rainfall was generally applied at constant intensities, whereas rainfall temporal patterns during actual storms are typically highly variable. This paper discusses a rationale for the application of the constant-intensity washoff concepts to actual storm event runoff. The rationale is tested using suspended particle load data collected at a road site located in Toowoomba, Australia. Agreement between the washoff concepts and measured data is most consistent for intermediate-duration storms (duration <5 h and >1 h). Particle loads resulting from these storm events increase linearly with average rainfall intensity. Above a threshold intensity, there is evidence to suggest a constant or plateau particle load is reached. The inclusion of a peak discharge factor (maximum 6 min rainfall intensity) enhances the ability to predict particle loads.

Heat strain, hydration status, and symptoms of heat illness in surface mine workers

The aim of the research program was to evaluate the heat strain, hydration status, and heat illness symptoms experienced by surface mine workers. An initial investigation involved 91 surface miners completing a heat stress questionnaire; assessing the work environment, hydration practices, and heat illness symptom experience. The key findings included 1) more than 80 % of workers experienced at least one symptom of heat illness over a 12 month period; and 2) the risk of moderate symptoms of heat illness increased with the severity of dehydration. These findings highlight a health and safety concern for surface miners, as experiencing symptoms of heat illness is an indication that the physiological systems of the body may be struggling to meet the demands of thermoregulation. To illuminate these findings a field investigation to monitor the heat strain and hydration status of surface miners was proposed. Two preliminary studies were conducted to ensure accurate and reliable data collection techniques. Firstly, a study was undertaken to determine a calibration procedure to ensure the accuracy of core body temperature measurement via an ingestible sensor. A water bath was heated to several temperatures between 23 . 51 ¢ªC, allowing for comparison of the temperature recorded by the sensors and a traceable thermometer. A positive systematic bias was observed and indicated a need for calibration. It was concluded that a linear regression should be developed for each sensor prior to ingestion, allowing for a correction to be applied to the raw data. Secondly, hydration status was to be assessed through urine specific gravity measurement. It was foreseeable that practical limitations on mine sites would delay the time between urine collection and analysis. A study was undertaken to assess the reliability of urine analysis over time. Measurement of urine specific gravity was found to be reliable up to 24 hours post urine collection and was suitable to be used in the field study. Twenty-nine surface miners (14 drillers [winter] and 15 blast crew [summer]) were monitored during a normal work shift. Core body temperature was recorded continuously. Average mean core body temperature was 37.5 and 37.4 ¢ªC for blast crew and drillers, with average maximum body temperatures of 38.0 and 37.9 ¢ªC respectively. The highest body temperature recorded was 38.4 ¢ªC. Urine samples were collected at each void for specific gravity measurement. The average mean urine specific gravity was 1.024 and 1.021 for blast crew and drillers respectively. The Heat Illness Symptoms Index was used to evaluate the experience of heat illness symptoms on shift. Over 70 % of drillers and over 80 % of blast crew reported at least one symptom. It was concluded that 1) heat strain remained within the recommended limits for acclimatised workers; and 2) the majority of workers were dehydrated before commencing their shift, and tend to remain dehydrated for the duration. Dehydration was identified as the primary issue for surface miners working in the heat. Therefore continued study focused on investigating a novel approach to monitoring hydration status. The final aim of this research program was to investigate the influence dehydration has on intraocular pressure (IOP); and subsequently, whether IOP could provide a novel indicator of hydration status. Seven males completed 90 minutes of walking in both a cool and hot climate with fluid restriction. Hydration variables and intraocular pressure were measured at baseline and at 30 minute intervals. Participants became dehydrated during the trial in the heat but maintained hydration status in the cool. Intraocular pressure progressively declined in the trial in the heat but remained relatively stable when hydration was maintained. A significant relationship was observed between intraocular pressure and both body mass loss and plasma osmolality. This evidence suggests that intraocular pressure is influenced by changes in hydration status. Further research is required to determine if intraocular pressure could be utilised as an indirect indicator of hydration status.

Radiation effect on free convection laminar flow along a vertical flat plate with streamwise sinusoidal surface temperature

The effect of thermal radiation on a steady two-dimensional natural convection laminar flow of viscous incompressible optically thick fluid along a vertical flat plate with streamwise sinusoidal surface temperature has been investigated in this study. Using the appropriate variables; the basic governing equations are transformed to convenient form and then solved numerically employing two efficient methods, namely, Implicit finite difference method (IFD) together with Keller box scheme and Straight forward finite difference (SFFD) method. Effects of the variation of the physical parameters, for example, conduction-radiation parameter (Planck number), surface temperature parameter, and the amplitude of the surface temperature, are shown on the skin friction and heat transfer rate quantitatively are shown numerically. Velocity and temperature profiles as well as streamlines and isotherms are also presented and discussed for the variation of conduction-radiation parameter. It is found that both skin-friction and rate of heat transfer are enhanced considerably by increasing the values of conduction radiation parameter, Rd.

Viscous dissipation effects on natural convection from a vertical plate with uniform surface heat flux placed in a thermally stratified media

In the present study we investigate the effect of viscous dissipation on natural convection from a vertical plate placed in a thermally stratified environment. The reduced equations are integrated by employing the implicit finite difference scheme of Keller box method and obtained the effect of heat due to viscous dissipation on the local skin friction and local Nusselt number at various stratification levels, for fluids having Prandtl numbers of 10, 50, and 100. Solutions are also obtained using the perturbation technique for small values of viscous dissipation parameters $\xi$ and compared to the finite difference solutions for 0 · $\xi$ · 1. Effect of viscous dissipation and temperature stratification are also shown on the velocity and temperature distributions in the boundary layer region.

Natural convection from a plane vertical porous surface in non-isothermal surroundings

In this paper, laminar natural convection flow from a permeable and isothermal vertical surface placed in non-isothermal surroundings is considered. Introducing appropriate transformations into the boundary layer equations governing the flow derives non-similar boundary layer equations. Results of both the analytical and numerical solutions are then presented in the form of skin-friction and Nusselt number. Numerical solutions of the transformed non-similar boundary layer equations are obtained by three distinct solution methods, (i) the perturbation solutions for small � (ii) the asymptotic solution for large � (iii) the implicit finite difference method for all � where � is the transpiration parameter. Perturbation solutions for small and large values of � are compared with the finite difference solutions for different values of pertinent parameters, namely, the Prandtl number Pr, and the ambient temperature gradient n.

The influence of climate variability on hydrological processes and surface and groundwater hydrochemistry : the tropical upper roper river catchment, Northern Territory, Australia

The Upper Roper River is one of the Australia’s unique tropical rivers which have been largely untouched by development. The Upper Roper River catchment comprises the sub-catchments of the Waterhouse River and Roper Creek, the two tributaries of the Roper River. There is a complex geological setting with different aquifer types. In this seasonal system, close interaction between surface water and groundwater contributes to both streamflow and sustaining ecosystems. The interaction is highly variable between seasons. A conceptual hydrogeological model was developed to investigate the different hydrological processes and geochemical parameters, and determine the baseline characteristics of water resources of this pristine catchment. In the catchment, long term average rainfall is around 850 mm and is summer dominant which significantly influences the total hydrological system. The difference between seasons is pronounced, with high rainfall up to 600 mm/month in the wet season, and negligible rainfall in the dry season. Canopy interception significantly reduces the amount of effective rainfall because of the native vegetation cover in the pristine catchment. Evaporation exceeds rainfall the majority of the year. Due to elevated evaporation and high temperature in the tropics, at least 600 mm of annual rainfall is required to generate potential recharge. Analysis of 120 years of rainfall data trend helped define “wet” and “dry periods”: decreasing trend corresponds to dry periods, and increasing trend to wet periods. The period from 1900 to 1970 was considered as Dry period 1, when there were years with no effective rainfall, and if there was, the intensity of rainfall was around 300 mm. The period 1970 – 1985 was identified as the Wet period 2, when positive effective rainfall occurred in almost every year, and the intensity reached up to 700 mm. The period 1985 – 1995 was the Dry period 2, with similar characteristics as Dry period 1. Finally, the last decade was the Wet period 2, with effective rainfall intensity up to 800 mm. This variability in rainfall over decades increased/decreased recharge and discharge, improving/reducing surface water and groundwater quantity and quality in different wet and dry periods. The stream discharge follows the rainfall pattern. In the wet season, the aquifer is replenished, groundwater levels and groundwater discharge are high, and surface runoff is the dominant component of streamflow. Waterhouse River contributes two thirds and Roper Creek one third to Roper River flow. As the dry season progresses, surface runoff depletes, and groundwater becomes the main component of stream flow. Flow in Waterhouse River is negligible, the Roper Creek dries up, but the Roper River maintains its flow throughout the year. This is due to the groundwater and spring discharge from the highly permeable Tindall Limestone and tufa aquifers. Rainfall seasonality and lithology of both the catchment and aquifers are shown to influence water chemistry. In the wet season, dilution of water bodies by rainwater is the main process. In the dry season, when groundwater provides baseflow to the streams, their chemical composition reflects lithology of the aquifers, in particular the karstic areas. Water chemistry distinguishes four types of aquifer materials described as alluvium, sandstone, limestone and tufa. Surface water in the headwaters of the Waterhouse River, the Roper Creek and their tributaries are freshwater, and reflect the alluvium and sandstone aquifers. At and downstream of the confluence of the Roper River, river water chemistry indicates the influence of rainfall dilution in the wet season, and the signature of the Tindall Limestone and tufa aquifers in the dry. Rainbow Spring on the Waterhouse River and Bitter Spring on the Little Roper River (known as Roper Creek at the headwaters) discharge from the Tindall Limestone. Botanic Walk Spring and Fig Tree Spring discharge into the Roper River from tufa. The source of water was defined based on water chemical composition of the springs, surface and groundwater. The mechanisms controlling surface water chemistry were examined to define the dominance of precipitation, evaporation or rock weathering on the water chemical composition. Simple water balance models for the catchment have been developed. The important aspects to be considered in water resource planning of this total system are the naturally high salinity in the region, especially the downstream sections, and how unpredictable climate variation may impact on the natural seasonal variability of water volumes and surface-subsurface interaction.