A computer image analysis system for microvessel density measurement in solid tumours

Microvessel density (MVD) is a widely used surrogate measure of angiogenesis in pathological specimens and tumour models. Measurement of MVD can be achieved by several methods. Automation of counting methods aims to increase the speed, reliability and reproducibility of these techniques. The image analysis system described here enables MVD measurement to be carried out with minimal expense in any reasonably equipped pathology department or laboratory. It is demonstrated that the system translates easily between tumour types which are suitably stained with minimal calibration. The aim of this paper is to offer this technique to a wider field of researchers in angiogenesis.

Analysis of linear relationships in block ciphers

This thesis is devoted to the study of linear relationships in symmetric block ciphers. A block cipher is designed so that the ciphertext is produced as a nonlinear function of the plaintext and secret master key. However, linear relationships within the cipher can still exist if the texts and components of the cipher are manipulated in a number of ways, as shown in this thesis. There are four main contributions of this thesis. The first contribution is the extension of the applicability of integral attacks from word-based to bitbased block ciphers. Integral attacks exploit the linear relationship between texts at intermediate stages of encryption. This relationship can be used to recover subkey bits in a key recovery attack. In principle, integral attacks can be applied to bit-based block ciphers. However, specific tools to define the attack on these ciphers are not available. This problem is addressed in this thesis by introducing a refined set of notations to describe the attack. The bit patternbased integral attack is successfully demonstrated on reduced-round variants of the block ciphers Noekeon, Present and Serpent. The second contribution is the discovery of a very small system of equations that describe the LEX-AES stream cipher. LEX-AES is based heavily on the 128-bit-key (16-byte) Advanced Encryption Standard (AES) block cipher. In one instance, the system contains 21 equations and 17 unknown bytes. This is very close to the upper limit for an exhaustive key search, which is 16 bytes. One only needs to acquire 36 bytes of keystream to generate the equations. Therefore, the security of this cipher depends on the difficulty of solving this small system of equations. The third contribution is the proposal of an alternative method to measure diffusion in the linear transformation of Substitution-Permutation-Network (SPN) block ciphers. Currently, the branch number is widely used for this purpose. It is useful for estimating the possible success of differential and linear attacks on a particular SPN cipher. However, the measure does not give information on the number of input bits that are left unchanged by the transformation when producing the output bits. The new measure introduced in this thesis is intended to complement the current branch number technique. The measure is based on fixed points and simple linear relationships between the input and output words of the linear transformation. The measure represents the average fraction of input words to a linear diffusion transformation that are not effectively changed by the transformation. This measure is applied to the block ciphers AES, ARIA, Serpent and Present. It is shown that except for Serpent, the linear transformations used in the block ciphers examined do not behave as expected for a random linear transformation. The fourth contribution is the identification of linear paths in the nonlinear round function of the SMS4 block cipher. The SMS4 block cipher is used as a standard in the Chinese Wireless LAN Wired Authentication and Privacy Infrastructure (WAPI) and hence, the round function should exhibit a high level of nonlinearity. However, the findings in this thesis on the existence of linear relationships show that this is not the case. It is shown that in some exceptional cases, the first four rounds of SMS4 are effectively linear. In these cases, the effective number of rounds for SMS4 is reduced by four, from 32 to 28. The findings raise questions about the security provided by SMS4, and might provide clues on the existence of a flaw in the design of the cipher.

Analysis of stream cipher based authenticated encryption schemes

Authenticated Encryption (AE) is the cryptographic process of providing simultaneous confidentiality and integrity protection to messages. This approach is more efficient than applying a two-step process of providing confidentiality for a message by encrypting the message, and in a separate pass providing integrity protection by generating a Message Authentication Code (MAC). AE using symmetric ciphers can be provided by either stream ciphers with built in authentication mechanisms or block ciphers using appropriate modes of operation. However, stream ciphers have the potential for higher performance and smaller footprint in hardware and/or software than block ciphers. This property makes stream ciphers suitable for resource constrained environments, where storage and computational power are limited. There have been several recent stream cipher proposals that claim to provide AE. These ciphers can be analysed using existing techniques that consider confidentiality or integrity separately; however currently there is no existing framework for the analysis of AE stream ciphers that analyses these two properties simultaneously. This thesis introduces a novel framework for the analysis of AE using stream cipher algorithms. This thesis analyzes the mechanisms for providing confidentiality and for providing integrity in AE algorithms using stream ciphers. There is a greater emphasis on the analysis of the integrity mechanisms, as there is little in the public literature on this, in the context of authenticated encryption. The thesis has four main contributions as follows. The first contribution is the design of a framework that can be used to classify AE stream ciphers based on three characteristics. The first classification applies Bellare and Namprempre's work on the the order in which encryption and authentication processes take place. The second classification is based on the method used for accumulating the input message (either directly or indirectly) into the into the internal states of the cipher to generate a MAC. The third classification is based on whether the sequence that is used to provide encryption and authentication is generated using a single key and initial vector, or two keys and two initial vectors. The second contribution is the application of an existing algebraic method to analyse the confidentiality algorithms of two AE stream ciphers; namely SSS and ZUC. The algebraic method is based on considering the nonlinear filter (NLF) of these ciphers as a combiner with memory. This method enables us to construct equations for the NLF that relate the (inputs, outputs and memory of the combiner) to the output keystream. We show that both of these ciphers are secure from this type of algebraic attack. We conclude that using a keydependent SBox in the NLF twice, and using two different SBoxes in the NLF of ZUC, prevents this type of algebraic attack. The third contribution is a new general matrix based model for MAC generation where the input message is injected directly into the internal state. This model describes the accumulation process when the input message is injected directly into the internal state of a nonlinear filter generator. We show that three recently proposed AE stream ciphers can be considered as instances of this model; namely SSS, NLSv2 and SOBER-128. Our model is more general than a previous investigations into direct injection. Possible forgery attacks against this model are investigated. It is shown that using a nonlinear filter in the accumulation process of the input message when either the input message or the initial states of the register is unknown prevents forgery attacks based on collisions. The last contribution is a new general matrix based model for MAC generation where the input message is injected indirectly into the internal state. This model uses the input message as a controller to accumulate a keystream sequence into an accumulation register. We show that three current AE stream ciphers can be considered as instances of this model; namely ZUC, Grain-128a and Sfinks. We establish the conditions under which the model is susceptible to forgery and side-channel attacks.

The B subunit of coagulation factor XIII is linked to renin and the Duffy blood group to α-spectrin on human chromosome 1

Family linkage studies were used to detect two linkage relationships on human chromosome 1. The B subunit of coagulation factor XIII showed significant linkage to renin with a maximum lod score of 5.071 at a distance of 10 cM. Significant linkage was also shown between the Duffy blood group and α-spectrin with linkage results giving a combined lod score of 3.194 at 5 cM.

Improving the detection of donations within the RHD negative blood donor panel which weakly express the RHD antigen

This project improved the detection and classification of very weakly expressed RhD variants in the Australian blood donor panel and contributed to the knowledge of anti-D reactivity patterns of RHD alleles that are undescribed. As such, the management of donations possessing these RHD alleles can be improved upon and the overall safety of transfusion medicine pertaining to the Rh blood group system will be increased. Future projects at ARCBS will be able to utilise the procedures developed in this project, thereby decreasing throughput time. The specificity of current testing will be improved and the need for outsourced RHD testing diminished.

Improving the railway’s understanding of accident causation through an integrated approach to human factors analysis and technical safety data recording

This paper describes a safety data recording and analysis system that has been developed to capture safety occurrences including precursors using high-definition forward-facing video from train cabs and data from other train-borne systems. The paper describes the data processing model and how events detected through data analysis are related to an underlying socio-technical model of accident causation. The integrated approach to safety data recording and analysis insures systemic factors that condition, influence or potentially contribute to an occurrence are captured both for safety occurrences and precursor events, providing a rich tapestry of antecedent causal factors that can significantly improve learning around accident causation. This can ultimately provide benefit to railways through the development of targeted and more effective countermeasures, better risk models and more effective use and prioritization of safety funds. Level crossing occurrences are a key focus in this paper with data analysis scenarios describing causal factors around near-miss occurrences. The paper concludes with a discussion on how the system can also be applied to other types of railway safety occurrences.

Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspects

Introduction: A number of genetic-association studies have identified genes contributing to ankylosing spondylitis (AS) susceptibility but such approaches provide little information as to the gene activity changes occurring during the disease process. Transcriptional profiling generates a 'snapshot' of the sampled cells' activity and thus can provide insights into the molecular processes driving the disease process. We undertook a whole-genome microarray approach to identify candidate genes associated with AS and validated these gene-expression changes in a larger sample cohort. Methods: A total of 18 active AS patients, classified according to the New York criteria, and 18 gender- and age-matched controls were profiled using Illumina HT-12 whole-genome expression BeadChips which carry cDNAs for 48,000 genes and transcripts. Class comparison analysis identified a number of differentially expressed candidate genes. These candidate genes were then validated in a larger cohort using qPCR-based TaqMan low density arrays (TLDAs). Results: A total of 239 probes corresponding to 221 genes were identified as being significantly different between patients and controls with a P-value <0.0005 (80% confidence level of false discovery rate). Forty-seven genes were then selected for validation studies, using the TLDAs. Thirteen of these genes were validated in the second patient cohort with 12 downregulated 1.3- to 2-fold and only 1 upregulated (1.6-fold). Among a number of identified genes with well-documented inflammatory roles we also validated genes that might be of great interest to the understanding of AS progression such as SPOCK2 (osteonectin) and EP300, which modulate cartilage and bone metabolism. Conclusions: We have validated a gene expression signature for AS from whole blood and identified strong candidate genes that may play roles in both the inflammatory and joint destruction aspects of the disease.

Hip power analysis in individuals with transfemoral amputation: A different strategy different from stabilisation during gait stance

Introduction and Objectives Joint moments and joint powers during gait are widely used to determine the effects of rehabilitation programs as well as prosthetic fitting. Following the definition of power (dot product of joint moment and joint angular velocity) it has been previously proposed to analyse the 3D angle between both vectors, αMw. Basically, joint power is maximised when both vectors are parallel and cancelled when both vectors are orthogonal. In other words, αMw < 60° reveals a propulsion configuration (more than 50% of the moment contribute to positive power) while αMw > 120° reveals a resistance configuration (more than 50% of the moment contribute to negative power). A stabilisation configuration (less than 50% of the moment contribute to power) corresponds to 60° < αMw < 120°. Previous studies demonstrated that hip joints of able-bodied adults (AB) are mainly in a stabilisation configuration (αMw about 90°) during the stance phase of gait. [1, 2] Individuals with transfemoral amputation (TFA) need to maximise joint power at the hip while controlling the prosthetic knee during stance. Therefore, we tested the hypothesis that TFAs should adopt a strategy that is different from a continuous stabilisation. The objective of this study was to compute joint power and αMw for TFA and to compare them with AB. Methods Three trials of walking at self-selected speed were analysed for 8 TFAs (7 males and 1 female, 46±10 years old, 1.78±0.08 m 82±13 kg) and 8 ABs (males, 25±3 years old, 1.75±0.04, m 67±6 kg). The joint moments are computed from a motion analysis system (Qualisys, Goteborg, Sweden) and a multi-axial transducer (JR3, Woodland, USA) mounted above the prosthetic knee for TFAs and from a motion analysis system (Motion Analysis, Santa Rosa, USA) and force plates (Bertec, Columbus, USA) for ABs. The TFAs were fitted with an OPRA (Integrum, AB, Gothengurg, Sweden) osseointegrated implant system and their prosthetic designs include pneumatic, hydraulic and microprocessor knees. Previous studies showed that the inverse dynamics computed from the multi-axial transducer is the proper method considering the absorption at the foot and resistance at the knee. Results The peak of positive power at loading response (H1) was earlier and lower for TFA compared to AB. Although the joint power is lower, the 3D angle between joint moment and joint angular velocity, αMw, reveals an obvious propulsion configuration (mean αMw about 20°) for TFA compared to a stabilisation configuration (mean αMw about 70°) for AB. The peaks of negative power at midstance (H2) and of positive power at preswing / initial swing (H3) occurred later, lower and longer for TFA compared to AB. Again, the joint powers are lower for TFA but, in this case, αMw is almost comparable (with a time lag), demonstrating a stabilisation (almost a resistance for TFA, mean αMw about 120°) and a propulsion configuration, respectively. The swing phase is not analysed in the present study. Conclusion The analysis of hip joint power may indicate that TFAs demonstrated less propulsion and resistance than ABs during the stance phase of gait. This is true from a quantitative point of view. On the contrary, the 3D angle between joint moment and joint angular velocity, αMw, reveals that TFAs have a remarkable propulsion strategy at loading response and almost a resistance strategy at midstance while ABs adopted a stabilisation strategy. The propulsion configuration, with αMw close to 0°, seems to aim at maximising the positive joint power. The configuration close to resistance, with αMw far from 180°, might aim at unlocking the prosthetic knee before swing while minimising the negative power. This analysis of both joint power and 3D angle between the joint moment and the joint angular velocity provides complementary insights into the gait strategies of TFA that can be used to support evidence-based rehabilitation and fitting of prosthetic components.

Investigation into submicrometer particle and gaseous emissions from airport ground running procedures

Emissions from airport operations are of significant concern because of their potential impact on local air quality and human health. The currently limited scientific knowledge of aircraft emissions is an important issue worldwide, when considering air pollution associated with airport operation, and this is especially so for ultrafine particles. This limited knowledge is due to scientific complexities associated with measuring aircraft emissions during normal operations on the ground. In particular this type of research has required the development of novel sampling techniques which must take into account aircraft plume dispersion and dilution as well as the various particle dynamics that can affect the measurements of the aircraft engine plume from an operational aircraft. In order to address this scientific problem, a novel mobile emission measurement method called the Plume Capture and Analysis System (PCAS), was developed and tested. The PCAS permits the capture and analysis of aircraft exhaust during ground level operations including landing, taxiing, takeoff and idle. The PCAS uses a sampling bag to temporarily store a sample, providing sufficient time to utilize sensitive but slow instrumental techniques to be employed to measure gas and particle emissions simultaneously and to record detailed particle size distributions. The challenges in relation to the development of the technique include complexities associated with the assessment of the various particle loss and deposition mechanisms which are active during storage in the PCAS. Laboratory based assessment of the method showed that the bag sampling technique can be used to accurately measure particle emissions (e.g. particle number, mass and size distribution) from a moving aircraft or vehicle. Further assessment of the sensitivity of PCAS results to distance from the source and plume concentration was conducted in the airfield with taxiing aircraft. The results showed that the PCAS is a robust method capable of capturing the plume in only 10 seconds. The PCAS is able to account for aircraft plume dispersion and dilution at distances of 60 to 180 meters downwind of moving a aircraft along with particle deposition loss mechanisms during the measurements. Characterization of the plume in terms of particle number, mass (PM2.5), gaseous emissions and particle size distribution takes only 5 minutes allowing large numbers of tests to be completed in a short time. The results were broadly consistent and compared well with the available data. Comprehensive measurements and analyses of the aircraft plumes during various modes of the landing and takeoff (LTO) cycle (e.g. idle, taxi, landing and takeoff) were conducted at Brisbane Airport (BNE). Gaseous (NOx, CO2) emission factors, particle number and mass (PM2.5) emission factors and size distributions were determined for a range of Boeing and Airbus aircraft, as a function of aircraft type and engine thrust level. The scientific complexities including the analysis of the often multimodal particle size distributions to describe the contributions of different particle source processes during the various stages of aircraft operation were addressed through comprehensive data analysis and interpretation. The measurement results were used to develop an inventory of aircraft emissions at BNE, including all modes of the aircraft LTO cycle and ground running procedures (GRP). Measurements of the actual duration of aircraft activity in each mode of operation (time-in-mode) and compiling a comprehensive matrix of gas and particle emission rates as a function of aircraft type and engine thrust level for real world situations was crucial for developing the inventory. The significance of the resulting matrix of emission rates in this study lies in the estimate it provides of the annual particle emissions due to aircraft operations, especially in terms of particle number. In summary, this PhD thesis presents for the first time a comprehensive study of the particle and NOx emission factors and rates along with the particle size distributions from aircraft operations and provides a basis for estimating such emissions at other airports. This is a significant addition to the scientific knowledge in terms of particle emissions from aircraft operations, since the standard particle number emissions rates are not currently available for aircraft activities.

BLAST Atlas : a function based multiple genome browser

BLAST Atlas is a visual analysis system for comparative genomics that supports genome-wide gene characterisation, functional assignment and function-based browsing of one or more chromosomes. Inspired by applications such as the WorldWide Telescope, Bing Maps 3D and Google Earth, BLAST Atlas uses novel three-dimensional gene and function views that provide a highly interactive and intuitive way for scientists to navigate, query and compare gene annotations. The system can be used for gene identification and functional assignment or as a function-based multiple genome comparison tool which complements existing position based comparison and alignment viewers.

Learning domain-specific sentiment lexicons for predicting product sales

Generic sentiment lexicons have been widely used for sentiment analysis these days. However, manually constructing sentiment lexicons is very time-consuming and it may not be feasible for certain application domains where annotation expertise is not available. One contribution of this paper is the development of a statistical learning based computational method for the automatic construction of domain-specific sentiment lexicons to enhance cross-domain sentiment analysis. Our initial experiments show that the proposed methodology can automatically generate domain-specific sentiment lexicons which contribute to improve the effectiveness of opinion retrieval at the document level. Another contribution of our work is that we show the feasibility of applying the sentiment metric derived based on the automatically constructed sentiment lexicons to predict product sales of certain product categories. Our research contributes to the development of more effective sentiment analysis system to extract business intelligence from numerous opinionated expressions posted to the Web

Effects of enhanced somatosensory information on postural stability in older people and people with Parkinson’s disease

The somatosensory system plays an important role in balance control and age-related changes to this system have been implicated in falls. Parkinson’s disease (PD) is a chronic and progressive disease of the brain, characterized by postural instability and gait disturbance. Previous research has shown that deficiencies in somatosensory feedback may contribute to the poorer postural control demonstrated by PD individuals. However, few studies have comprehensively explored differences in somatosensory function and postural control between PD participants and healthy older individuals. The soles of the feet contain many cutaneous mechanoreceptors that provide important somatosensory information sources for postural control. Different types of insole devices have been developed to enhance this somatosensory information and improve postural stability, but these devices are often too complex and expensive to integrate into daily life. Textured insoles provide a more passive intervention that may be an inexpensive and accessible means to enhance the somatosensory input from the plantar surface of the feet. However, to date, there has been little work conducted to test the efficacy of enhanced somatosensory input induced by textured insoles in both healthy and PD populations during standing and walking. Therefore, the aims of this thesis were to determine: 1) whether textured insole surfaces can improve postural stability by enhancing somatosensory information in younger and older adults, 2) the differences between healthy older participants and PD participants for measures of physiological function and postural stability during standing and walking, 3) how changes in somatosensory information affect postural stability in both groups during standing and walking; and 4), whether textured insoles can improve postural stability in both groups during standing and walking. To address these aims, Study 1 recruited seven older individuals and ten healthy young controls to investigate the effects of two textured insole surfaces on postural stability while performing standing balance tests on a force plate. Participants were tested under three insole surface conditions: 1) barefoot; 2) standing on a hard textured insole surface; and 3), standing on a soft textured insole surface. Measurements derived from the centre of pressure displacement included the range of anterior-posterior and medial-lateral displacement, path length and the 90% confidence elliptical area (C90 area). Results of study 1 revealed a significant Group*Surface*Insole interaction for the four measures. Both textured insole surfaces reduced postural sway for the older group, especially in the eyes closed condition on the foam surface. However, participants reported that the soft textured insole surface was more comfortable and, hence, the soft textured insoles were adopted for Studies 2 and 3. For Study 2, 20 healthy older adults (controls) and 20 participants with Parkinson’s disease were recruited. Participants were evaluated using a series of physiological assessments that included touch sensitivity, vibratory perception, and pain and temperature threshold detection. Furthermore, nerve function and somatosensory evoked potentials tests were utilized to provide detailed information regarding peripheral nerve function for these participants. Standing balance and walking were assessed on different surfaces using a force plate and the 3D Vicon motion analysis system, respectively. Data derived from the force plate included the range of anterior-posterior and medial-lateral sway, while measures of stride length, stride period, cadence, double support time, stance phase, velocity and stride timing variability were reported for the walking assessment. The results of this study demonstrated that the PD group had decrements in somatosensory function compared to the healthy older control group. For electrodiagnosis, PD participants had poorer nerve function than controls, as evidenced by slower nerve conduction velocities and longer latencies in sural nerve and prolonged latency in the P37 somatosensory evoked potential. Furthermore, the PD group displayed more postural sway in both the anterior-posterior and medial-lateral directions relative to controls and these differences were increased when standing on a foam surface. With respect to the gait assessment, the PD group took shorter strides and had a reduced stride period compared with the control group. Furthermore, the PD group spent more time in the stance phase and had increased cadence and stride timing variability than the controls. Compared with walking on the firm surface, the two groups demonstrated different gait adaptations while walking on the uneven surface. Controls increased their stride length and stride period and decreased their cadence, which resulted in a consistent walking velocity on both surfaces. Conversely, while the PD patients also increased their stride period and decreased their cadence and stance period on the uneven surface, they did not increase their stride length and, hence walked slower on the uneven surface. In the PD group, there was a strong positive association between decreased somatosensory function and decreased clinical balance, as assessed by the Tinetti test. Poorer somatosensory function was also strongly positively correlated with the temporospatial gait parameters, especially shorter stride length. Study 3 evaluated the effects of manipulating the somatosensory information from the plantar surface of the feet using textured insoles in the same populations assessed in Study 2. For this study, participants performed the standing and walking balance tests under three footwear conditions: 1) barefoot; 2) with smooth insoles; and 3), with textured insoles. Standing balance and walking were evaluated using a force plate and a Vicon motion analysis system and the data were analysed in the same way outlined for Study 2. The findings showed that the smooth and textured insoles caused different effects on postural control during both the standing and walking trials. Both insoles decreased medial-lateral sway to the same level on the firm surface. The greatest benefits were observed in the PD group while wearing the textured insole. When standing under a more challenging condition on the foam surface with eyes closed, only the textured insole decreased medial-lateral sway in the PD group. With respect to the gait trials, both insoles increased walking velocity, stride length and stride time and decreased cadence, but these changes were more pronounced for the textured insoles. The effects of the textured insoles were evident under challenging conditions in the PD group and increased walking velocity and stride length, while decreasing cadence. Textured insoles were also effective in reducing the time spent in the double support and stance phases of the gait cycle and did not increase stride timing variability, as was the case for the smooth insoles for the PD group. The results of this study suggest that textured insoles, such as those evaluated in this research, may provide a low-cost means of improving postural stability in high-risk groups, such as people with PD, which may act as an important intervention to prevent falls.