Assessment of gene expression of intracellular calcium channels, pumps and exchangers with epidermal growth factor-induced epithelial-mesenchymal transition in a breast cancer cell line

Background Epithelial-mesenchymal transition (EMT) is a process implicated in cancer metastasis that involves the conversion of epithelial cells to a more mesenchymal and invasive cell phenotype. In breast cancer cells EMT is associated with altered store-operated calcium influx and changes in calcium signalling mediated by activation of cell surface purinergic receptors. In this study, we investigated whether MDA-MB-468 breast cancer cells induced to undergo EMT exhibit changes in mRNA levels of calcium channels, pumps and exchangers located on intracellular calcium storing organelles, including the Golgi, mitochondria and endoplasmic reticulum (ER). Methods Epidermal growth factor (EGF) was used to induce EMT in MDA-MB-468 breast cancer cells. Serum-deprived cells were treated with EGF (50 ng/mL) for 12 h and gene expression was assessed using quantitative RT-PCR. Results and conclusions These data reveal no significant alterations in mRNA levels of the Golgi calcium pump secretory pathway calcium ATPases (SPCA1 and SPCA2), or the mitochondrial calcium uniporter (MCU) or Na+/Ca2+ exchanger (NCLX). However, EGF-induced EMT was associated with significant alterations in mRNA levels of specific ER calcium channels and pumps, including (sarco)-endoplasmic reticulum calcium ATPases (SERCAs), and inositol 1,4,5-trisphosphate receptor (IP3R) and ryanodine receptor (RYR) calcium channel isoforms. The most prominent change in gene expression between the epithelial and mesenchymal-like states was RYR2, which was enriched 45-fold in EGF-treated MDA-MB-468 cells. These findings indicate that EGF-induced EMT in breast cancer cells may be associated with major alterations in ER calcium homeostasis.

Washout hole for bi-ventricular assist device (BVAD) centrifugal blood pump

The shortage of donor hearts for patients with end stage heart failure has accelerated the development of ventricular assist devices (VAD) that act as a replacement heart. Mechanical devices involving pulsatile, axial and centrifugal devices have been proposed. Recent clinical developments indicate that centrifugal devices are not only beneficial for bridge to transplantation applications, but may also aid myocardial recovery. The results of a recent study have shown that patients who received a VAD have extended lives and improved quality of life compared to recipients of drug therapy. Unfortunately 25% of these patients develop right heart failure syndrome, sepsis and multi-organ failure. It was reported that 17% of patients initially receiving an LVAD later required a right ventricular assist device (RVAD). Hence, current research focus is in the development of a bi-ventricular assist device (BVAD). Current BVAD technology is either too bulky or necessitates having to implant two pumps working independently. The latter requires two different controllers for each pump leading to the potential complication of uneven flow dynamics and the requirements for a large amount of body space. This paper illustrates the combination of the LVAD and RVAD as one complete device to augment the function of both the left and right cardiac chambers with double impellers. The proposed device has two impellers rotating in counter directions, hence eliminating the necessity of the body muscles and tubing/heart connection to restrain the pump. The device will also have two separate chambers with independent rotating impeller for the left and right chambers. A problem with centrifugal impellers is the fluid stagnation underneath the impeller. This leads to thrombosis and blood clots.This paper presents the design, construction and location of washout hole to prevent thrombus for a Bi-VAD centrifugal pump. Results using CFD will be used to illustrate the superiority of our design concept in terms of preventing thrombus formation and hemolysis.

Passive control of a bi-ventricular assist device : an experimental and numerical investigation

For the last two decades heart disease has been the highest single cause of death for the human population. With an alarming number of patients requiring heart transplant, and donations not able to satisfy the demand, treatment looks to mechanical alternatives. Rotary Ventricular Assist Devices, VADs, are miniature pumps which can be implanted alongside the heart to assist its pumping function. These constant flow devices are smaller, more efficient and promise a longer operational life than more traditional pulsatile VADs. The development of rotary VADs has focused on single pumps assisting the left ventricle only to supply blood for the body. In many patients however, failure of both ventricles demands that an additional pulsatile device be used to support the failing right ventricle. This condition renders them hospital bound while they wait for an unlikely heart donation. Reported attempts to use two rotary pumps to support both ventricles concurrently have warned of inherent haemodynamic instability. Poor balancing of the pumps’ flow rates quickly leads to vascular congestion increasing the risk of oedema and ventricular ‘suckdown’ occluding the inlet to the pump. This thesis introduces a novel Bi-Ventricular Assist Device (BiVAD) configuration where the pump outputs are passively balanced by vascular pressure. The BiVAD consists of two rotary pumps straddling the mechanical passive controller. Fluctuations in vascular pressure induce small deflections within both pumps adjusting their outputs allowing them to maintain arterial pressure. To optimise the passive controller’s interaction with the circulation, the controller’s dynamic response is optimised with a spring, mass, damper arrangement. This two part study presents a comprehensive assessment of the prototype’s ‘viability’ as a support device. Its ‘viability’ was considered based on its sensitivity to pathogenic haemodynamics and the ability of the passive response to maintain healthy circulation. The first part of the study is an experimental investigation where a prototype device was designed and built, and then tested in a pulsatile mock circulation loop. The BiVAD was subjected to a range of haemodynamic imbalances as well as a dynamic analysis to assess the functionality of the mechanical damper. The second part introduces the development of a numerical program to simulate human circulation supported by the passively controlled BiVAD. Both investigations showed that the prototype was able to mimic the native baroreceptor response. Simulating hypertension, poor flow balancing and subsequent ventricular failure during BiVAD support allowed the passive controller’s response to be assessed. Triggered by the resulting pressure imbalance, the controller responded by passively adjusting the VAD outputs in order to maintain healthy arterial pressures. This baroreceptor-like response demonstrated the inherent stability of the auto regulating BiVAD prototype. Simulating pulmonary hypertension in the more observable numerical model, however, revealed a serious issue with the passive response. The subsequent decrease in venous return into the left heart went unnoticed by the passive controller. Meanwhile the coupled nature of the passive response not only decreased RVAD output to reduce pulmonary arterial pressure, but it also increased LVAD output. Consequently, the LVAD increased fluid evacuation from the left ventricle, LV, and so actually accelerated the onset of LV collapse. It was concluded that despite the inherently stable baroreceptor-like response of the passive controller, its lack of sensitivity to venous return made it unviable in its present configuration. The study revealed a number of other important findings. Perhaps the most significant was that the reduced pulse experienced during constant flow support unbalanced the ratio of effective resistances of both vascular circuits. Even during steady rotary support therefore, the resulting ventricle volume imbalance increased the likelihood of suckdown. Additionally, mechanical damping of the passive controller’s response successfully filtered out pressure fluctuations from residual ventricular function. Finally, the importance of recognising inertial contributions to blood flow in the atria and ventricles in a numerical simulation were highlighted. This thesis documents the first attempt to create a fully auto regulated rotary cardiac assist device. Initial results encourage development of an inlet configuration sensitive to low flow such as collapsible inlet cannulae. Combining this with the existing baroreceptor-like response of the passive controller will render a highly stable passively controlled BiVAD configuration. The prototype controller’s passive interaction with the vasculature is a significant step towards a highly stable new generation of artificial heart.

HVAC system size – getting it right

There is evidence that many heating, ventilating & air conditioning (HVAC) systems, installed in larger buildings, have more capacity than is ever required to keep the occupants comfortable. This paper explores the reasons why this can occur, by examining a typical brief/design/documentation process. Over-sized HVAC systems cost more to install and operate and may not be able to control thermal comfort as well as a “right-sized” system. These impacts are evaluated, where data exists. Finally, some suggestions are developed to minimise both the extent of, and the negative impacts of, HVAC system over-sizing, for example: • Challenge “rules of thumb” and/or brief requirements which may be out of date. • Conduct an accurate load estimate, using AIRAH design data, specific to project location, and then resist the temptation to apply “safety factors • Use a load estimation program that accounts for thermal storage and diversification of peak loads for each zone and air handling system. • Select chiller sizes and staged or variable speed pumps and fans to ensure good part load performance. • Allow for unknown future tenancies by designing flexibility into the system, not by over-sizing. For example, generous sizing of distribution pipework and ductwork will allow available capacity to be redistributed. • Provide an auxiliary tenant condenser water loop to handle high load areas. • Consider using an Integrated Design Process, build an integrated load and energy use simulation model and test different operational scenarios • Use comprehensive Life Cycle Cost analysis for selection of the most optimal design solutions. This paper is an interim report on the findings of CRC-CI project 2002-051-B, Right-Sizing HVAC Systems, which is due for completion in January 2006.

Improvements in sustainable energy and water practice in the food processing industry : an in depth analysis of the manufacture of Ghee at the Butter Producers' Cooperative Federation Limited, Brisbane

This thesis is a documented energy audit and long term study of energy and water reduction in a ghee factory. Global production of ghee exceeds 4 million tonnes annually. The factory in this study refines dairy products by non-traditional centrifugal separation and produces 99.9% pure, canned, crystallised Anhydrous Milk Fat (Ghee). Ghee is traditionally made by batch processing methods. The traditional method is less efficient, than centrifugal separation. An in depth systematic investigation was conducted of each item of major equipment including; ammonia refrigeration, a steam boiler, canning equipment, pumps, heat exchangers and compressed air were all fine-tuned. Continuous monitoring of electrical usage showed that not every initiative worked, others had pay back periods of less than a year. In 1994-95 energy consumption was 6,582GJ and in 2003-04 it was 5,552GJ down 16% for a similar output. A significant reduction in water usage was achieved by reducing the airflow in the refrigeration evaporative condensers to match the refrigeration load. Water usage has fallen 68% from18ML in 1994-95 to 5.78ML in 2003-04. The methods reported in this thesis could be applied to other industries, which have similar equipment, and other ghee manufacturers.

Integrated Diagnosis and Prognosis Model for High Pressure LNG Pump

In condition-based maintenance (CBM), effective diagnostics and prognostics are essential tools for maintenance engineers to identify imminent fault and to predict the remaining useful life before the components finally fail. This enables remedial actions to be taken in advance and reschedules production if necessary. This paper presents a technique for accurate assessment of the remnant life of machines based on historical failure knowledge embedded in the closed loop diagnostic and prognostic system. The technique uses the Support Vector Machine (SVM) classifier for both fault diagnosis and evaluation of health stages of machine degradation. To validate the feasibility of the proposed model, the five different level data of typical four faults from High Pressure Liquefied Natural Gas (HP-LNG) pumps were used for multi-class fault diagnosis. In addition, two sets of impeller-rub data were analysed and employed to predict the remnant life of pump based on estimation of health state. The results obtained were very encouraging and showed that the proposed prognosis system has the potential to be used as an estimation tool for machine remnant life prediction in real life industrial applications.

Axial magnetic bearing development for the BiVACOR Rotary BiVAD/TAH

A suspension system for the BiVACOR biventricular assist device (BiVAD) has been developed and tested. The device features two semi-open centrifugal impellers mounted on a common rotating hub. Flow balancing is achieved through the movement of the rotor in the axial direction. The rotor is suspended in the pump casings by an active magnetic suspension system in the axial direction and a passive hydrodynamic bearing in the radial direction. This paper investigates the axial movement capacity of themagnetic bearing system and the power consumption at various operating points. The force capacity of the passive hydrodynamic bearing is investigated using a viscous glycerol solution. Axial rotor movement in the range of ±0.15 mm is confirmed and power consumption is under 15.5 W. The journal bearing is shown to stabilize the rotor in the radial direction at the required operating speed. Magnetic levitation is a viable suspension technique for the impeller of an artificial heart to improve device lifetime and reduce blood damage.

Remediation strategies of shaft and common mode voltages in adjustable speed drive systems

AC motors are largely used in a wide range of modern systems, from household appliances to automated industry applications such as: ventilations systems, fans, pumps, conveyors and machine tool drives. Inverters are widely used in industrial and commercial applications due to the growing need for speed control in ASD systems. Fast switching transients and the common mode voltage, in interaction with parasitic capacitive couplings, may cause many unwanted problems in the ASD applications. These include shaft voltage and leakage currents. One of the inherent characteristics of Pulse Width Modulation (PWM) techniques is the generation of the common mode voltage, which is defined as the voltage between the electrical neutral of the inverter output and the ground. Shaft voltage can cause bearing currents when it exceeds the amount of breakdown voltage level of the thin lubricant film between the inner and outer rings of the bearing. This phenomenon is the main reason for early bearing failures. A rapid development in power switches technology has lead to a drastic decrement of switching rise and fall times. Because there is considerable capacitance between the stator windings and the frame, there can be a significant capacitive current (ground current escaping to earth through stray capacitors inside a motor) if the common mode voltage has high frequency components. This current leads to noises and Electromagnetic Interferences (EMI) issues in motor drive systems. These problems have been dealt with using a variety of methods which have been reported in the literature. However, cost and maintenance issues have prevented these methods from being widely accepted. Extra cost or rating of the inverter switches is usually the price to pay for such approaches. Thus, the determination of cost-effective techniques for shaft and common mode voltage reduction in ASD systems, with the focus on the first step of the design process, is the targeted scope of this thesis. An introduction to this research – including a description of the research problem, the literature review and an account of the research progress linking the research papers – is presented in Chapter 1. Electrical power generation from renewable energy sources, such as wind energy systems, has become a crucial issue because of environmental problems and a predicted future shortage of traditional energy sources. Thus, Chapter 2 focuses on the shaft voltage analysis of stator-fed induction generators (IG) and Doubly Fed Induction Generators DFIGs in wind turbine applications. This shaft voltage analysis includes: topologies, high frequency modelling, calculation and mitigation techniques. A back-to-back AC-DC-AC converter is investigated in terms of shaft voltage generation in a DFIG. Different topologies of LC filter placement are analysed in an effort to eliminate the shaft voltage. Different capacitive couplings exist in the motor/generator structure and any change in design parameters affects the capacitive couplings. Thus, an appropriate design for AC motors should lead to the smallest possible shaft voltage. Calculation of the shaft voltage based on different capacitive couplings, and an investigation of the effects of different design parameters are discussed in Chapter 3. This is achieved through 2-D and 3-D finite element simulation and experimental analysis. End-winding parameters of the motor are also effective factors in the calculation of the shaft voltage and have not been taken into account in previous reported studies. Calculation of the end-winding capacitances is rather complex because of the diversity of end winding shapes and the complexity of their geometry. A comprehensive analysis of these capacitances has been carried out with 3-D finite element simulations and experimental studies to determine their effective design parameters. These are documented in Chapter 4. Results of this analysis show that, by choosing appropriate design parameters, it is possible to decrease the shaft voltage and resultant bearing current in the primary stage of generator/motor design without using any additional active and passive filter-based techniques. The common mode voltage is defined by a switching pattern and, by using the appropriate pattern; the common mode voltage level can be controlled. Therefore, any PWM pattern which eliminates or minimizes the common mode voltage will be an effective shaft voltage reduction technique. Thus, common mode voltage reduction of a three-phase AC motor supplied with a single-phase diode rectifier is the focus of Chapter 5. The proposed strategy is mainly based on proper utilization of the zero vectors. Multilevel inverters are also used in ASD systems which have more voltage levels and switching states, and can provide more possibilities to reduce common mode voltage. A description of common mode voltage of multilevel inverters is investigated in Chapter 6. Chapter 7 investigates the elimination techniques of the shaft voltage in a DFIG based on the methods presented in the literature by the use of simulation results. However, it could be shown that every solution to reduce the shaft voltage in DFIG systems has its own characteristics, and these have to be taken into account in determining the most effective strategy. Calculation of the capacitive coupling and electric fields between the outer and inner races and the balls at different motor speeds in symmetrical and asymmetrical shaft and balls positions is discussed in Chapter 8. The analysis is carried out using finite element simulations to determine the conditions which will increase the probability of high rates of bearing failure due to current discharges through the balls and races.

Engineering an Ecosystem : Taking Cues from Nature’s Paradigm to Build Tissue in the Lab and the Body

This manuscript took a 'top down' approach to understanding survival of inhabitant cells in the ecosystem bone, working from higher to lower length and time scales through the hierarchical ecosystem of bone. Our working hypothesis is that nature “engineered” the skeleton using a 'bottom up' approach,where mechanical properties of cells emerge from their adaptation to their local me-chanical milieu. Cell aggregation and formation of higher order anisotropic struc- ture results in emergent architectures through cell differentiation and extracellular matrix secretion. These emergent properties, including mechanical properties and architecture, result in mechanical adaptation at length scales and longer time scales which are most relevant for the survival of the vertebrate organism [Knothe Tate and von Recum 2009]. We are currently using insights from this approach to har-ness nature’s regeneration potential and to engineer novel mechanoactive materials [Knothe Tate et al. 2007, Knothe Tate et al. 2009]. In addition to potential applications of these exciting insights, these studies may provide important clues to evolution and development of vertebrate animals. For instance, one might ask why mesenchymal stem cells condense at all? There is a putative advantage to self-assembly and cooperation, but this advantage is somewhat outweighed by the need for infrastructural complexity (e.g., circulatory systems comprised of specific differentiated cell types which in turn form conduits and pumps to overcome limitations of mass transport via diffusion, for example; dif-fusion is untenable for multicellular organisms larger than 250 microns in diameter. A better question might be: Why do cells build skeletal tissue? Once cooperatingcells in tissues begin to deplete local sources of food in their aquatic environment, those that have evolved a means to locomote likely have an evolutionary advantage. Once the environment becomes less aquarian and more terrestrial, self-assembled organisms with the ability to move on land might have conferred evolutionary ad-vantages as well. So did the cytoskeleton evolve several length scales, enabling the emergence of skeletal architecture for vertebrate animals? Did the evolutionary advantage of motility over noncompliant terrestrial substrates (walking on land) favor adaptations including emergence of intracellular architecture (changes in the cytoskeleton and upregulation of structural protein manufacture), inter-cellular con- densation, mineralization of tissues, and emergence of higher order architectures?How far does evolutionary Darwinism extend and how can we exploit this knowl- edge to engineer smart materials and architectures on Earth and new, exploratory environments?[Knothe Tate et al. 2008]. We are limited only by our ability to imagine. Ultimately, we aim to understand nature, mimic nature, guide nature and/or exploit nature’s engineering paradigms without engineer-ing ourselves out of existence.

Development of a diagnostic tool for condition monitoring of rotating machinery

This paper presents an overview of the CRC for Infrastructure and Engineering Asset Management (CIEAM)’s rotating machine health monitoring project and the status of the research progress. The project focuses on the development of a comprehensive diagnostic tool for condition monitoring and systematic analysis of rotating machinery. Particularly attention focuses on the machine health monitoring of diesel engines, compressors and pumps by using acoustic emission and vibration-based monitoring techniques. The paper also provides a brief summary of the work done by the three main research collaborating partners in the project, namely, Queensland University of Technology (QUT), Curtin University of Technology (CUT) and the University of Western Australia (UWA). Preliminary test and analysis results from this work are also reported in the paper

Retrofitting commercial office buildings for sustainability : tenants’ expectations and experiences

Introduction Buildings, which account for approximately half of all annual energy and greenhouse gas emissions, are an important target area for any strategy addressing climate change. Whilst new commercial buildings increasingly address sustainability considerations, incorporating green technology in the refurbishment process of older buildings is technically, financially and socially challenging. This research explores the expectations and experiences of commercial office building tenants, whose building was under-going green refurbishment. Methodology Semi-structured in-depth interviews with seven residents and neighbours of a large case-study building under-going green refurbishment in Melbourne, Australia. Built in 1979, the 7,008m² ‘B’ grade building consists of 11 upper levels of office accommodation, ground floor retail, and a basement area leased as a licensed restaurant. After refurbishment, which included the installation of chilled water pumps, solar water heating, waterless urinals, insulation, disabled toilets, and automatic dimming lights, it was expected that the environmental performance of the building would move from a non-existent zero ABGR (Australian Building Greenhouse Rating) star rating to 3.5 stars, with a 40% reduction in water consumption and 20% reduction in energy consumption. Interviews were transcribed, with responses analysed using a thematic approach, identifying categories, themes and patterns. Results Commercial property tenants are on a journey to sustainability - they are interested and willing to engage in discussions about sustainability initiatives, but the process, costs and benefits need to be clear. Critically, whilst sustainability was an essential and non-negotiable criterion in building selection for government and larger corporate tenants, sustainability was not yet a core business value for smaller organisations – whilst they could see it as an emerging issue, they wanted detailed cost-benefit analyses, pay-back calculations of proposed technologies and, ideally, wished they could trial the technology first-hand in some way. Although extremely interested in learning more, most participants reported relatively minimal knowledge of specific sustainability features, designs or products. In discussions about different sustainable technologies (e.g., waterless urinals, green-rated carpets), participants frequently commented that they knew little about the technology, had not heard of it or were not sure exactly how it worked. Whilst participants viewed sustainable commercial buildings as the future, they had varied expectations about the fate of existing older buildings – most felt that they would have to be retrofitted at some point to meet market expectations and predicted the emergence of a ‘non-sustainability discount’ for residing in a building without sustainable features. Discussion This research offers a beginning point for understanding the difficulty of integrating green technology in older commercial buildings. Tenants currently have limited understandings of technology and potential building performance outcomes, which ultimately could impede the implementation of sustainable initiatives in older buildings. Whilst the commercial property market is interested in learning about sustainability in the built environment, the findings highlight the importance of developing a strong business case, communication and transition plan for implementing sustainability retrofits in existing commercial buildings.

Water lubricated bearings

The increasing ecological awareness and stringent requirements for environmental protection have led to the development of water lubricated bearings in many applications where oil was used as the lubricant. The chapter details the theoretical analysis to determine both the static and dynamic characteristics,including the stability (using both the linearised perturbation method and the nonlinear transient analysis) of multiple axial groove water lubricated bearings. Experimental measurements and computational fluid dynamics (CFD) simulations by the Tribology research group at Queensland University of Technology,Australia and Manipal Institute of Technology, India, have highlighted a significant gap in the understanding of the flow phenomena and pressure conditions within the lubricating fluid. An attempt has been made to present a CFD approach to model fluid flow in the bearing with three equi-spaced axial grooves and supplied with water from one end of the bearing. Details of the experimental method used to measure the film pressure in the bearing are outlined. The lubricant is subjected to a velocity induced flow (as the shaft rotates) and a pressure induced flow (as the water is forced from one end of the bearing to the other). Results are presented for the circumferential and axial pressure distribution in the bearing clearance for different loads, speeds and supply pressures. The axial pressure profile along the axial groove located in the loaded part of the bearing is measured. The theoretical analysis shows that smaller the groove angle better will be the load-carrying capacity and stability of these bearings. Results are compared with experimentally measured pressure distributions.