Effect of differentially heating and consequent transient behaviour for natural convection within an enclosure of sinusoidal corrugated side walls

Unsteady natural convection due to differentially heating of the sinusoidal corrugated side walls of a modified square enclosure has been numerically investigated. The fluid inside the enclosure is air, initially as quiescent. The flat top and bottom surfaces are considered as adiabatic. The numerical scheme is based on the finite element method adapted to triangular non-uniform mesh element by a non-linear parametric solution algorithm. The results are obtained for the Rayleigh number, Ra ranging from 1e+05 to 1e+08 for different corrugation amplitude and frequency with constant physical properties for the fluid medium considered. The streamlines, isotherms and average Nusselt numbers are presented to observe the effect of sudden heating and its consequent transient behavior on fluid flow and heat transfer characteristics for the range of governing parameters. The present results show that the transient phenomena are greatly influenced by the variation of the aforementioned parameters.

Rational design of serine protease inhibitors

Proteases regulate a spectrum of diverse physiological processes, and dysregulation of proteolytic activity drives a plethora of pathological conditions. Understanding protease function is essential to appreciating many aspects of normal physiology and progression of disease. Consequently, development of potent and specific inhibitors of proteolytic enzymes is vital to provide tools for the dissection of protease function in biological systems and for the treatment of diseases linked to aberrant proteolytic activity. The studies in this thesis describe the rational design of potent inhibitors of three proteases that are implicated in disease development. Additionally, key features of the interaction of proteases and their cognate inhibitors or substrates are analysed and a series of rational inhibitor design principles are expounded and tested. Rational design of protease inhibitors relies on a comprehensive understanding of protease structure and biochemistry. Analysis of known protease cleavage sites in proteins and peptides is a commonly used source of such information. However, model peptide substrate and protein sequences have widely differing levels of backbone constraint and hence can adopt highly divergent structures when binding to a protease’s active site. This may result in identical sequences in peptides and proteins having different conformations and diverse spatial distribution of amino acid functionalities. Regardless of this, protein and peptide cleavage sites are often regarded as being equivalent. One of the key findings in the following studies is a definitive demonstration of the lack of equivalence between these two classes of substrate and invalidation of the common practice of using the sequences of model peptide substrates to predict cleavage of proteins in vivo. Another important feature for protease substrate recognition is subsite cooperativity. This type of cooperativity is commonly referred to as protease or substrate binding subsite cooperativity and is distinct from allosteric cooperativity, where binding of a molecule distant from the protease active site affects the binding affinity of a substrate. Subsite cooperativity may be intramolecular where neighbouring residues in substrates are interacting, affecting the scissile bond’s susceptibility to protease cleavage. Subsite cooperativity can also be intermolecular where a particular residue’s contribution to binding affinity changes depending on the identity of neighbouring amino acids. Although numerous studies have identified subsite cooperativity effects, these findings are frequently ignored in investigations probing subsite selectivity by screening against diverse combinatorial libraries of peptides (positional scanning synthetic combinatorial library; PS-SCL). This strategy for determining cleavage specificity relies on the averaged rates of hydrolysis for an uncharacterised ensemble of peptide sequences, as opposed to the defined rate of hydrolysis of a known specific substrate. Further, since PS-SCL screens probe the preference of the various protease subsites independently, this method is inherently unable to detect subsite cooperativity. However, mean hydrolysis rates from PS-SCL screens are often interpreted as being comparable to those produced by single peptide cleavages. Before this study no large systematic evaluation had been made to determine the level of correlation between protease selectivity as predicted by screening against a library of combinatorial peptides and cleavage of individual peptides. This subject is specifically explored in the studies described here. In order to establish whether PS-SCL screens could accurately determine the substrate preferences of proteases, a systematic comparison of data from PS-SCLs with libraries containing individually synthesised peptides (sparse matrix library; SML) was carried out. These SML libraries were designed to include all possible sequence combinations of the residues that were suggested to be preferred by a protease using the PS-SCL method. SML screening against the three serine proteases kallikrein 4 (KLK4), kallikrein 14 (KLK14) and plasmin revealed highly preferred peptide substrates that could not have been deduced by PS-SCL screening alone. Comparing protease subsite preference profiles from screens of the two types of peptide libraries showed that the most preferred substrates were not detected by PS SCL screening as a consequence of intermolecular cooperativity being negated by the very nature of PS SCL screening. Sequences that are highly favoured as result of intermolecular cooperativity achieve optimal protease subsite occupancy, and thereby interact with very specific determinants of the protease. Identifying these substrate sequences is important since they may be used to produce potent and selective inhibitors of protolytic enzymes. This study found that highly favoured substrate sequences that relied on intermolecular cooperativity allowed for the production of potent inhibitors of KLK4, KLK14 and plasmin. Peptide aldehydes based on preferred plasmin sequences produced high affinity transition state analogue inhibitors for this protease. The most potent of these maintained specificity over plasma kallikrein (known to have a very similar substrate preference to plasmin). Furthermore, the efficiency of this inhibitor in blocking fibrinolysis in vitro was comparable to aprotinin, which previously saw clinical use to reduce perioperative bleeding. One substrate sequence particularly favoured by KLK4 was substituted into the 14 amino acid, circular sunflower trypsin inhibitor (SFTI). This resulted in a highly potent and selective inhibitor (SFTI-FCQR) which attenuated protease activated receptor signalling by KLK4 in vitro. Moreover, SFTI-FCQR and paclitaxel synergistically reduced growth of ovarian cancer cells in vitro, making this inhibitor a lead compound for further therapeutic development. Similar incorporation of a preferred KLK14 amino acid sequence into the SFTI scaffold produced a potent inhibitor for this protease. However, the conformationally constrained SFTI backbone enforced a different intramolecular cooperativity, which masked a KLK14 specific determinant. As a consequence, the level of selectivity achievable was lower than that found for the KLK4 inhibitor. Standard mechanism inhibitors such as SFTI rely on a stable acyl-enzyme intermediate for high affinity binding. This is achieved by a conformationally constrained canonical binding loop that allows for reformation of the scissile peptide bond after cleavage. Amino acid substitutions within the inhibitor to target a particular protease may compromise structural determinants that support the rigidity of the binding loop and thereby prevent the engineered inhibitor reaching its full potential. An in silico analysis was carried out to examine the potential for further improvements to the potency and selectivity of the SFTI-based KLK4 and KLK14 inhibitors. Molecular dynamics simulations suggested that the substitutions within SFTI required to target KLK4 and KLK14 had compromised the intramolecular hydrogen bond network of the inhibitor and caused a concomitant loss of binding loop stability. Furthermore in silico amino acid substitution revealed a consistent correlation between a higher frequency of formation and the number of internal hydrogen bonds of SFTI-variants and lower inhibition constants. These predictions allowed for the production of second generation inhibitors with enhanced binding affinity toward both targets and highlight the importance of considering intramolecular cooperativity effects when engineering proteins or circular peptides to target proteases. The findings from this study show that although PS-SCLs are a useful tool for high throughput screening of approximate protease preference, later refinement by SML screening is needed to reveal optimal subsite occupancy due to cooperativity in substrate recognition. This investigation has also demonstrated the importance of maintaining structural determinants of backbone constraint and conformation when engineering standard mechanism inhibitors for new targets. Combined these results show that backbone conformation and amino acid cooperativity have more prominent roles than previously appreciated in determining substrate/inhibitor specificity and binding affinity. The three key inhibitors designed during this investigation are now being developed as lead compounds for cancer chemotherapy, control of fibrinolysis and cosmeceutical applications. These compounds form the basis of a portfolio of intellectual property which will be further developed in the coming years.

Scaling analysis of natural convection boundary layers : Application to attic space

The natural convection thermal boundary layer adjacent to an inclined flat plate and inclined walls of an attic space subject to instantaneous and ramp heating and cooling is investigated. A scaling analysis has been performed to describe the flow behaviour and heat transfer. Major scales quantifying the flow velocity, flow development time, heat transfer and the thermal and viscous boundary layer thicknesses at different stages of the flow development are established. Scaling relations of heating-up and cooling-down times and heat transfer rates have also been reported for the case of attic space. The scaling relations have been verified by numerical simulations over a wide range of parameters. Further, a periodic temperature boundary condition is also considered to show the flow features in the attic space over diurnal cycles.

Influence of rainfall and catchment characteristics on urban stormwater quality

This thesis presents the outcomes of a comprehensive research study undertaken to investigate the influence of rainfall and catchment characteristics on urban stormwater quality. The knowledge created is expected to contribute to a greater understanding of urban stormwater quality and thereby enhance the design of stormwater quality treatment systems. The research study was undertaken based on selected urban catchments in Gold Coast, Australia. The research methodology included field investigations, laboratory testing, computer modelling and data analysis. Both univariate and multivariate data analysis techniques were used to investigate the influence of rainfall and catchment characteristics on urban stormwater quality. The rainfall characteristics investigated included average rainfall intensity and rainfall duration whilst catchment characteristics included land use, impervious area percentage, urban form and pervious area location. The catchment scale data for the analysis was obtained from four residential catchments, including rainfall-runoff records, drainage network data, stormwater quality data and land use and land cover data. Pollutants build-up samples were collected from twelve road surfaces in residential, commercial and industrial land use areas. The relationships between rainfall characteristics, catchment characteristics and urban stormwater quality were investigated based on residential catchments and then extended to other land uses. Based on the influence rainfall characteristics exert on urban stormwater quality, rainfall events can be classified into three different types, namely, high average intensity-short duration (Type 1), high average intensity-long duration (Type 2) and low average intensity-long duration (Type 3). This provides an innovative approach to conventional modelling which does not commonly relate stormwater quality to rainfall characteristics. Additionally, it was found that the threshold intensity for pollutant wash-off from urban catchments is much less than for rural catchments. High average intensity-short duration rainfall events are cumulatively responsible for the generation of a major fraction of the annual pollutants load compared to the other rainfall event types. Additionally, rainfall events less than 1 year ARI such as 6- month ARI should be considered for treatment design as they generate a significant fraction of the annual runoff volume and by implication a significant fraction of the pollutants load. This implies that stormwater treatment designs based on larger rainfall events would not be feasible in the context of cost-effectiveness, efficiency in treatment performance and possible savings in land area needed. This also suggests that the simulation of long-term continuous rainfall events for stormwater treatment design may not be needed and that event based simulations would be adequate. The investigations into the relationship between catchment characteristics and urban stormwater quality found that other than conventional catchment characteristics such as land use and impervious area percentage, other catchment characteristics such as urban form and pervious area location also play important roles in influencing urban stormwater quality. These outcomes point to the fact that the conventional modelling approach in the design of stormwater quality treatment systems which is commonly based on land use and impervious area percentage would be inadequate. It was also noted that the small uniformly urbanised areas within a larger mixed catchment produce relatively lower variations in stormwater quality and as expected lower runoff volume with the opposite being the case for large mixed use urbanised catchments. Therefore, a decentralised approach to water quality treatment would be more effective rather than an "end-of-pipe" approach. The investigation of pollutants build-up on different land uses showed that pollutant build-up characteristics vary even within the same land use. Therefore, the conventional approach in stormwater quality modelling, which is based solely on land use, may prove to be inappropriate. Industrial land use has relatively higher variability in maximum pollutant build-up, build-up rate and particle size distribution than the other two land uses. However, commercial and residential land uses had relatively higher variations of nutrients and organic carbon build-up. Additionally, it was found that particle size distribution had a relatively higher variability for all three land uses compared to the other build-up parameters. The high variability in particle size distribution for all land uses illustrate the dissimilarities associated with the fine and coarse particle size fractions even within the same land use and hence the variations in stormwater quality in relation to pollutants adsorbing to different sizes of particles.

Internet/computer addiction among juveniles in Turkey

Internet and computer addiction has been a popular research area since the 90s. Studies on Internet and computer addiction have usually been conducted in the US, and the investigation of computer and Internet addiction at different countries is an interesting area of research. This study investigates computer and Internet addiction among teenagers and Internet cafe visitors in Turkey. We applied a survey to 983 visitors in the Internet cafes. The results show that the Internet cafe visitors are usually teenagers, mostly middle and high-school students and usually are busy with computer and Internet applications like chat, e-mail, browsing and games. The teenagers come to the Internet cafe to spend time with friends and the computers. In addition, about 30% of cafe visitors admit to having an Internet addiction, and about 20% specifically mention the problems that they are having with the Internet. It is rather alarming to consider the types of activities that the teenagers are performing in an Internet cafe, their reasons for being there, the percentage of self-awareness about Internet addiction, and the lack of control of applications in the cafe.

Performance and scalability assessment for non-certificate-based public key management in VANETS

Current research in secure messaging for Vehicular Ad hoc Networks (VANETs) appears to focus on employing a digital certificate-based Public Key Cryptosystem (PKC) to support security. The security overhead of such a scheme, however, creates a transmission delay and introduces a time-consuming verification process to VANET communications. This paper proposes a non-certificate-based public key management for VANETs. A comprehensive evaluation of performance and scalability of the proposed public key management regime is presented, which is compared to a certificate-based PKC by employing a number of quantified analyses and simulations. Not only does this paper demonstrate that the proposal can maintain security, but it also asserts that it can improve overall performance and scalability at a lower cost, compared to the certificate-based PKC. It is believed that the proposed scheme will add a new dimension to the key management and verification services for VANETs.

The use of virtual prototyping for hazard identification in the early design stage

Purpose: The construction industry is well known for its high accident rate and many practitioners consider a preventative approach to be the most important means of bringing about improvements. This paper addresses previous research and the weaknesses of existing preventative approaches and a new application is described and illustrated involving the use of a multi-dimensional simulation tool - Construction Virtual Prototyping (CVP). Methodology: A literature review was conducted to investigate previous studies of hazard identification and safety management and to develop the new approach. Due to weaknesses in current practice, the research study explored the use of computer simulation techniques to create virtual environments where users can explore and identify construction hazards. Specifically, virtual prototyping technology was deployed to develop typical construction scenarios in which unsafe or hazardous incidents occur. In a case study, the users’ performance was evaluated their responses to incidents within the virtual environment and the effectiveness of the computer simulation system established though interviews with the safety project management team. Findings: The opinions and suggestions provided by the interviewees led to the initial conclusion that the simulation tool was useful in assisting the safety management team’s hazard identification process during the early design stage. Originality: The research introduces an innovative method to support the management teams’ reviews of construction site safety. The system utilises three-dimensional modelling and four-dimensional simulation of worker behaviour, a configuration that has previously not been employed in construction simulations. An illustration of the method’s use is also provided, together with a consideration of its strengths and weaknesses.

Quality metrics for assessing security-critical computer programs

Existing secure software development principles tend to focus on coding vulnerabilities, such as buffer or integer overflows, that apply to individual program statements, or issues associated with the run-time environment, such as component isolation. Here we instead consider software security from the perspective of potential information flow through a program’s object-oriented module structure. In particular, we define a set of quantifiable "security metrics" which allow programmers to quickly and easily assess the overall security of a given source code program or object-oriented design. Although measuring quality attributes of object-oriented programs for properties such as maintainability and performance has been well-covered in the literature, metrics which measure the quality of information security have received little attention. Moreover, existing securityrelevant metrics assess a system either at a very high level, i.e., the whole system, or at a fine level of granularity, i.e., with respect to individual statements. These approaches make it hard and expensive to recognise a secure system from an early stage of development. Instead, our security metrics are based on well-established compositional properties of object-oriented programs (i.e., data encapsulation, cohesion, coupling, composition, extensibility, inheritance and design size), combined with data flow analysis principles that trace potential information flow between high- and low-security system variables. We first define a set of metrics to assess the security quality of a given object-oriented system based on its design artifacts, allowing defects to be detected at an early stage of development. We then extend these metrics to produce a second set applicable to object-oriented program source code. The resulting metrics make it easy to compare the relative security of functionallyequivalent system designs or source code programs so that, for instance, the security of two different revisions of the same system can be compared directly. This capability is further used to study the impact of specific refactoring rules on system security more generally, at both the design and code levels. By measuring the relative security of various programs refactored using different rules, we thus provide guidelines for the safe application of refactoring steps to security-critical programs. Finally, to make it easy and efficient to measure a system design or program’s security, we have also developed a stand-alone software tool which automatically analyses and measures the security of UML designs and Java program code. The tool’s capabilities are demonstrated by applying it to a number of security-critical system designs and Java programs. Notably, the validity of the metrics is demonstrated empirically through measurements that confirm our expectation that program security typically improves as bugs are fixed, but worsens as new functionality is added.

Computer planning of stereotactic iodine-125 seed brachytherapy for recurrent malignant gliomas

At St Thomas' Hospital, we have developed a computer program on a Titan graphics supercomputer to plan the stereotactic implantation of iodine-125 seeds for the palliative treatment of recurrent malignant gliomas. Use of the Gill-Thomas-Cosman relocatable frame allows planning and surgery to be carried out at different hospitals on different days. Stereotactic computed tomography (CT) and positron emission tomography (PET) scans are performed and the images transferred to the planning computer. The head, tumour and frame fiducials are outlined on the relevant images, and a three-dimensional model generated. Structures which could interfere with the surgery or radiotherapy, such as major vessels, shunt tubing etc., can also be outlined and included in the display. Catheter target and entry points are set using a three-dimensional cursor controlled by a set of dials attached to the computer. The program calculates and displays the radiation dose distribution within the target volume for various catheter and seed arrangements. The CT co-ordinates of the fiducial rods are used to convert catheter co-ordinates from CT space to frame space and to calculate the catheter insertion angles and depths. The surgically implanted catheters are after-loaded the next day and the seeds left in place for between 4 and 6 days, giving a nominal dose of 50 Gy to the edge of the target volume. 25 patients have been treated so far.

Natural convection in a triangular enclosure due to non-uniform cooling on top

Natural convection in a triangular enclosure subject to non-uniformly cooling at the inclined surfaces and uniformly heating at the base is investigated numerically. The numerical simulations of the unsteady flows over a range of Rayleigh numbers and aspect ratios are carried out using Finite Volume Method. Since the upper surface is cooled and the bottom surface is heated, the air flow in the enclosure is potentially unstable to Rayleigh Benard instability. It is revealed that the transient flow development in the enclosure can be classified into three distinct stages; an early stage, a transitional stage and a steady stage. It is also found that the flow inside the enclosure strongly depends on the governing parameters; Rayleigh number and aspect ratio. The asymmetric behaviour of the flow about the geometric centre line is discussed in detailed. The heat transfer through the roof and the ceiling as a form of Nusselt number is also reported in this study.

Natural convection in the attic-shaped spaces

Heat transfer through an attic space into or out of buildings is an important issue for attic-shaped houses in both hot and cold climates. One of the important objectives for design and construction of houses is to provide thermal comfort for occupants. In the present energy-conscious society, it is also a requirement for houses to be energy efficient, i.e. the energy consumption for heating or air-conditioning houses must be minimized. Relevant to these objectives, research into heat transfer in attics has been conducted for about three decades. The transient behaviour of an attic space is directly relevant to our daily life. Certain periods of the day or night may be considered as having a constant ambient temperature (e.g. during 11am - 2pm or 11pm - 2am). However, at other times during the day or night the ambient temperature changes with time (e.g. between 5am - 9am or 5pm - 9pm). Therefore, the analysis of steady state solution is not sufficient to describe the fluid flow and heat transfer in the attic space. The discussion of the transient development of the boundary is required. A theoretical understanding of the transient behaviour of the flow in the enclosure is performed through scaling analysis for sudden and ramp heating conditions. A proper identification of the timescales, the velocity and the thickness relevant to the flow that develops inside the cavity makes it possible to predict theoretically the basic flow features that will survive once the thermal flow in the enclosure reaches a steady state. Those scaling predictions have been verified by a series of numerical simulations.

Standardisation of digital human models

Digital human models (DHM) have evolved as useful tools for ergonomic workplace design and product development, and found in various industries and education. DHM systems which dominate the market were developed for specific purposes and differ significantly, which is not only reflected in non-compatible results of DHM simulations, but also provoking misunderstanding of how DHM simulations relate to real world problems. While DHM developers are restricted by uncertainty about the user need and lack of model data related standards, users are confined to one specific product and cannot exchange results, or upgrade to another DHM system, as their previous results would be rendered worthless. Furthermore, origin and validity of anthropometric and biomechanical data is not transparent to the user. The lack of standardisation in DHM systems has become a major roadblock in further system development, affecting all stakeholders in the DHM industry. Evidently, a framework for standardising digital human models is necessary to overcome current obstructions.

Design of fixed order robust power oscillation damper for TCSC

This paper illustrates robust fixed order power oscillation damper design for mitigating power systems oscillations. From implementation and tuning point of view, such low and fixed structure is common practice for most practical applications, including power systems. However, conventional techniques of optimal and robust control theory cannot handle the constraint of fixed-order as it is, in general, impossible to ensure a target closed-loop transfer function by a controller of any given order. This paper deals with the problem of synthesizing or designing a feedback controller of dynamic order for a linear time-invariant plant for a fixed plant, as well as for an uncertain family of plants containing parameter uncertainty, so that stability, robust stability and robust performance are attained. The desired closed-loop specifications considered here are given in terms of a target performance vector representing a desired closed-loop design. The performance of the designed controller is validated through non-linear simulations for a range of contingencies.

Improving trust and securing data accessibility for e-health decision making by using data encryption techniques

In the medical and healthcare arena, patients‟ data is not just their own personal history but also a valuable large dataset for finding solutions for diseases. While electronic medical records are becoming popular and are used in healthcare work places like hospitals, as well as insurance companies, and by major stakeholders such as physicians and their patients, the accessibility of such information should be dealt with in a way that preserves privacy and security. Thus, finding the best way to keep the data secure has become an important issue in the area of database security. Sensitive medical data should be encrypted in databases. There are many encryption/ decryption techniques and algorithms with regard to preserving privacy and security. Currently their performance is an important factor while the medical data is being managed in databases. Another important factor is that the stakeholders should decide more cost-effective ways to reduce the total cost of ownership. As an alternative, DAS (Data as Service) is a popular outsourcing model to satisfy the cost-effectiveness but it takes a consideration that the encryption/ decryption modules needs to be handled by trustworthy stakeholders. This research project is focusing on the query response times in a DAS model (AES-DAS) and analyses the comparison between the outsourcing model and the in-house model which incorporates Microsoft built-in encryption scheme in a SQL Server. This research project includes building a prototype of medical database schemas. There are 2 types of simulations to carry out the project. The first stage includes 6 databases in order to carry out simulations to measure the performance between plain-text, Microsoft built-in encryption and AES-DAS (Data as Service). Particularly, the AES-DAS incorporates implementations of symmetric key encryption such as AES (Advanced Encryption Standard) and a Bucket indexing processor using Bloom filter. The results are categorised such as character type, numeric type, range queries, range queries using Bucket Index and aggregate queries. The second stage takes the scalability test from 5K to 2560K records. The main result of these simulations is that particularly as an outsourcing model, AES-DAS using the Bucket index shows around 3.32 times faster than a normal AES-DAS under the 70 partitions and 10K record-sized databases. Retrieving Numeric typed data takes shorter time than Character typed data in AES-DAS. The aggregation query response time in AES-DAS is not as consistent as that in MS built-in encryption scheme. The scalability test shows that the DBMS reaches in a certain threshold; the query response time becomes rapidly slower. However, there is more to investigate in order to bring about other outcomes and to construct a secured EMR (Electronic Medical Record) more efficiently from these simulations.

Experimental validation of an unpowered unmanned aerial system : application to forced landing scenarios

The ability to perform autonomous emergency (forced) landings is one of the key technology enablers identified for UAS. This paper presents the flight test results of forced landings involving a UAS, in a controlled environment, and which was conducted to ascertain the performances of previously developed (and published) path planning and guidance algorithms. These novel 3-D nonlinear algorithms have been designed to control the vehicle in both the lateral and longitudinal planes of motion. These algorithms have hitherto been verified in simulation. A modified Boomerang 60 RC aircraft is used as the flight test platform, with associated onboard and ground support equipment sourced Off-the-Shelf or developed in-house at the Australian Research Centre for Aerospace Automation(ARCAA). HITL simulations were conducted prior to the flight tests and displayed good landing performance, however, due to certain identified interfacing errors, the flight results differed from that obtained in simulation. This paper details the lessons learnt and presents a plausible solution for the way forward.