The expression, regulation and function of kallikrein 4 in prostate cancer

Prostate cancer is a significant health problem faced by aging men. Currently, diagnostic strategies for the detection of prostate cancer are either unreliable, yielding high numbers of false positive results, or too invasive to be used widely as screening tests. Furthermore, the current therapeutic strategies for the treatment of the disease carry considerable side effects. Although organ confined prostate cancer can be curable, most detectable clinical symptoms occur in advanced disease when primary tumour cells have metastasised to distant sites - usually lymph nodes and bone. Many growth factors and steroids assist the continued growth and maintenance of prostatic tumour cells. Of these mitogens, androgens are important in the development of the normal prostate but are also required to sustain the growth of prostate cancer cells in the early stage of the disease. Not only are androgens required in the early stage of disease, but also many other growth factors and hormones interact to cause uncontrolled proliferation of malignant cells. The early, androgen sensitive phase of disease is followed by an androgen insensitive phase, whereby androgens are no longer required to stimulate the growth of the tumour cells. Growth factors such as transforming growth factor  and  (TGF/), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), insulin-like growth factors (IGFs), Vitamin D and thyroid hormone have been suggested to be important at this stage of disease. Interestingly, some of the kallikrein family of genes, including prostate specific antigen (PSA), the current serum diagnostic marker for prostate cancer, are regulated by androgens and many of the aforementioned growth factors. The kallikrein gene family is a group of serine proteases that are involved in a diverse range of physiological processes: regulation of local blood flow, angiogenesis, tissue invasion and mitogenesis. The earliest members of the kallikrein gene family (KLK1-KLK3) have been strongly associated with general disease states, such as hypertension, inflammation, pancreatitis and renal disease, but are also linked to various cancers. Recently, this family was extended to include 15 genes (KLK1-15). Several newer members of the kallikrein family have been implicated in the carcinogenesis and tumour metastasis of hormone-dependent cancers such as prostate, breast, endometrial and ovarian cancer. The aims of this project were to investigate the expression of the newly identified kallikrein, KLK4, in benign and malignant prostate tissues, and prostate cancer cell lines. This thesis has demonstrated the elevated expression of KLK4 mRNA transcripts in malignant prostate tissue compared to benign prostates. Additionally, expression of the full length KLK4 transcript was detected in the androgen dependent prostate cancer cell line, LNCaP. Based on the above finding, the LNCaP cell line was chosen to assess the potential regulation of full length KLK4 by androgen, thyroid hormone and epidermal growth factor. KLK4 mRNA and protein was found to be up-regulated by androgen and a combination of androgen and thyroid hormone. Thyroid hormone alone produced no significant change in KLK4 mRNA or protein over the control. Epidermal growth factor treatment also resulted in elevated expression levels of KLK4 mRNA and protein. To assess the potential functional role(s) of KLK4/hK4 in processes associated with tumour progression, full length KLK4 was transfected into PC-3 cells - a prostate cancer cell line originally derived from a secondary bone lesion. The KLK4/hK4 over-expressing cells were assessed for their proliferation, migration, invasion and attachment properties. The KLK4 over-expressing clones exhibited a marked change in morphology, indicative of a more aggressive phenotype. The KLK4 clones were irregularly shaped with compromised adhesion to the growth surface. In contrast, the control cell lines (parent PC-3 and empty vector clones) retained a rounded morphology with obvious cell to cell adhesion, as well as significant adhesion to their growth surface. The KLK4 clones exhibited significantly greater attachment to Collagen I and IV than native PC-3s and empty vector controls. Over a 12 hour period, in comparison to the control cells, the KLK4 clones displayed an increase in migration towards PC-3 native conditioned media, a 3 fold increase towards conditioned media from an osteoblastic cell line (Saos-2) and no change in migration towards conditioned media from neonatal foreskin fibroblast cells or 20% foetal bovine serum. Furthermore, the increase in migration exhibited by the KLK4 clones was partially blocked by the serine protease inhibitor, aprotinin. The data presented in this thesis suggests that KLK4/hK4 is important in prostate carcinogenesis due to its over-expression in malignant prostate tissues, its regulation by hormones and growth factors associated with prostate disease and the functional consequences of over-expression of KLK4/hK4 in the PC-3 cell line. These results indicate that KLK4/hK4 may play an important role in tumour invasion and bone metastasis via increased attachment to the bone matrix protein, Collagen I, and enhanced migration due to soluble factors produced by osteoblast cells. This suggestion is further supported by the morphological changes displayed by the KLK4 over-expressing cells. Overall, this data suggests that KLK4/hK4 should be further studied to more fully investigate the potential value of KLK4/hK4 as a diagnostic/prognostic biomarker or in therapeutic applications.

An integrated approach for precise road reconstruction from aerial imagery and LiDAR data

Accurate and detailed road models play an important role in a number of geospatial applications, such as infrastructure planning, traffic monitoring, and driver assistance systems. In this thesis, an integrated approach for the automatic extraction of precise road features from high resolution aerial images and LiDAR point clouds is presented. A framework of road information modeling has been proposed, for rural and urban scenarios respectively, and an integrated system has been developed to deal with road feature extraction using image and LiDAR analysis. For road extraction in rural regions, a hierarchical image analysis is first performed to maximize the exploitation of road characteristics in different resolutions. The rough locations and directions of roads are provided by the road centerlines detected in low resolution images, both of which can be further employed to facilitate the road information generation in high resolution images. The histogram thresholding method is then chosen to classify road details in high resolution images, where color space transformation is used for data preparation. After the road surface detection, anisotropic Gaussian and Gabor filters are employed to enhance road pavement markings while constraining other ground objects, such as vegetation and houses. Afterwards, pavement markings are obtained from the filtered image using the Otsu's clustering method. The final road model is generated by superimposing the lane markings on the road surfaces, where the digital terrain model (DTM) produced by LiDAR data can also be combined to obtain the 3D road model. As the extraction of roads in urban areas is greatly affected by buildings, shadows, vehicles, and parking lots, we combine high resolution aerial images and dense LiDAR data to fully exploit the precise spectral and horizontal spatial resolution of aerial images and the accurate vertical information provided by airborne LiDAR. Objectoriented image analysis methods are employed to process the feature classiffcation and road detection in aerial images. In this process, we first utilize an adaptive mean shift (MS) segmentation algorithm to segment the original images into meaningful object-oriented clusters. Then the support vector machine (SVM) algorithm is further applied on the MS segmented image to extract road objects. Road surface detected in LiDAR intensity images is taken as a mask to remove the effects of shadows and trees. In addition, normalized DSM (nDSM) obtained from LiDAR is employed to filter out other above-ground objects, such as buildings and vehicles. The proposed road extraction approaches are tested using rural and urban datasets respectively. The rural road extraction method is performed using pan-sharpened aerial images of the Bruce Highway, Gympie, Queensland. The road extraction algorithm for urban regions is tested using the datasets of Bundaberg, which combine aerial imagery and LiDAR data. Quantitative evaluation of the extracted road information for both datasets has been carried out. The experiments and the evaluation results using Gympie datasets show that more than 96% of the road surfaces and over 90% of the lane markings are accurately reconstructed, and the false alarm rates for road surfaces and lane markings are below 3% and 2% respectively. For the urban test sites of Bundaberg, more than 93% of the road surface is correctly reconstructed, and the mis-detection rate is below 10%.

Genesis and role of standards : theoretical foundations and socio-economical model for the construction and use of standards

A key issue in the economic development and performance of organizations is the existence of standards. Their definition and control are sources of power and it is important to understand their concept, as it gives standards their direction and their legitimacy, and to explore how they are represented and applied. The difficulties posed by classical micro-economics in establishing a theory of standardization that is compatible with its fundamental axiomatic are acknowledged. We propose to reconsider the problem by taking the opposite perspective in questioning its theoretical base and by reformulating assumptions about the independent and autonomous decisions taken by actors. The Theory of Conventions will offer us a theoretical framework and tools enabling us to understand the systemic dimension and dynamic structure of standards. These will be seen as a special case of conventions. This work aims to provide a sound basis and promote a better consciousness in the development of global project management standards. It aims also to emphasize that social construction is not a matter of copyright but a matter of open minds, collective cognitive process and freedom for the common wealth.

Genesis and role of standards : theoretical foundations and socio-economical model for the construction and use of standards

A key issue for the economic development and for performance of organizations is the existence of standards. As their definitions and control are source of power, it seems to be important to understand the concept and to wonder about the representations authorized by the concept which give their direction and their legitimacy. The difficulties of classical microeconomics of establishing a theory of standardisation compatible with its fundamental axiomatic are underlined. We propose to reconsider the problem by carrying out the opposite way: to question the theoretical base, by reformulating assumptions on the autonomy of the choice of the actors. The theory of conventions will offer us both a theoretical framework and tools, enabling us to understand the systemic dimension and dynamic structure of standards seen as special case of conventions. This work aims thus to provide a sound basis and promote a better consciousness in the development of global project management standards, aiming also to underline that social construction is not a matter of copyright but a matter of open minds, collective cognitive process and freedom for the common wealth.

Windows

In this video, words emerge out of an abstract, ‘digital’, animated horizon line. The words are accompanied by a female voice-over who narrates a seductive relaxation and visualization activity. This work examines the nature of consciousness and identity in a contemporary context. It mixes the languages of meditation, new age philosophy and pop-psychology. Drawing on Zygmunt Bauman’s theoretical work on “liquid modernity”, this work questions how and where we find space for contemplation and reflection in a contemporary context increasingly defined by temporary social bonds and consumer choices.

The drift

In this video, text floats on screen amidst a field of swirling coloured orbs and a stock music soundtrack. The text is sourced from Internet dating websites and combine into a single animated portrait charting an array of likes, dislikes, influences, beliefs and hobbies. This work examines the nature of consciousness and identity in a contemporary context. It reworks the languages of Internet dating websites to question how we construct and communicate our sense of self. Drawing on Zygmunt Bauman’s theoretical work on “liquid modernity”, this work presents an exaggerated take on contemporary identity that emphasizes its construction through consumer tastes, lifestyle choices and relationships with popular culture.

Swell

In this video, an abstract kaleidoscopic pattern slowly morphs and changes colour. It is accompanied by a male voice performing a word association or stream-of-consciousness activity. This work examines the nature of consciousness and identity in a contemporary context. It mixes the languages of meditation, new age philosophy and pop-psychology. Drawing on Zygmunt Bauman’s theoretical work on “liquid modernity”, this work questions how and where we find space for contemplation in a contemporary context increasingly defined by temporary social bonds, consumer choices and private anxieties.

Geologically ancient DNA: fact or artefact?

Studies continue to report ancient DNA sequences and viable microbial cells that are many millions of years old. In this paper we evaluate some of the most extravagant claims of geologically ancient DNA. We conclude that although exciting, the reports suffer from inadequate experimental setup and insufficient authentication of results. Consequently, it remains doubtful whether amplifiable DNA sequences and viable bacteria can survive over geological timescales. To enhance the credibility of future studies and assist in discarding false-positive results, we propose a rigorous set of authentication criteria for work with geologically ancient DNA.

Sequential Fusion Using Correlated Decisions for Controlled Verification Errors

Fusion techniques have received considerable attention for achieving lower error rates with biometrics. A fused classifier architecture based on sequential integration of multi-instance and multi-sample fusion schemes allows controlled trade-off between false alarms and false rejects. Expressions for each type of error for the fused system have previously been derived for the case of statistically independent classifier decisions. It is shown in this paper that the performance of this architecture can be improved by modelling the correlation between classifier decisions. Correlation modelling also enables better tuning of fusion model parameters, ‘N’, the number of classifiers and ‘M’, the number of attempts/samples, and facilitates the determination of error bounds for false rejects and false accepts for each specific user. Error trade-off performance of the architecture is evaluated using HMM based speaker verification on utterances of individual digits. Results show that performance is improved for the case of favourable correlated decisions. The architecture investigated here is directly applicable to speaker verification from spoken digit strings such as credit card numbers in telephone or voice over internet protocol based applications. It is also applicable to other biometric modalities such as finger prints and handwriting samples.

Sequential fusion of decisions from adaptive and random samples for controlled verification of errors

Fusion techniques have received considerable attention for achieving performance improvement with biometrics. While a multi-sample fusion architecture reduces false rejects, it also increases false accepts. This impact on performance also depends on the nature of subsequent attempts, i.e., random or adaptive. Expressions for error rates are presented and experimentally evaluated in this work by considering the multi-sample fusion architecture for text-dependent speaker verification using HMM based digit dependent speaker models. Analysis incorporating correlation modeling demonstrates that the use of adaptive samples improves overall fusion performance compared to randomly repeated samples. For a text dependent speaker verification system using digit strings, sequential decision fusion of seven instances with three random samples is shown to reduce the overall error of the verification system by 26% which can be further reduced by 6% for adaptive samples. This analysis novel in its treatment of random and adaptive multiple presentations within a sequential fused decision architecture, is also applicable to other biometric modalities such as finger prints and handwriting samples.

Big-five personality factors affecting pedestrian crossing behaviours

Human personality is an important component of psychological factors affecting pedestrian crossing. This paper reports a questionnaire survey on the effects of pedestrian personalities (including neuroticism, extraversion, openness, agreeableness and conscientiousness) on pedestrian violation in China. 675 feedbacks were obtained, of which 535 samples were valid for analysis. The results of the hierarchical regression analysis showed that educational level had significant effect on violation; agreeableness had significant effect on violation, conditional compliance and unconditional compliance; consciousness had significant effect on violation and conditional compliance; extraversion had significant effect on unconditional compliance; neuroticism had significant effect on violation; educational level had significant effect on violation. The results implied that psychological measures played a very important role in pedestrian safety.

'Rebellion in the backland': discourse, truth and power

This article sets out to interpret the construction of truth discourse in the War of Canudos, through the classic 'Rebellion in the backland' by Euclides da Cunha. To enrich the research, the articles wrote by Cunha, while he was a war correspondent for the Estado de São Paulo newspaper, will be analyzed, too. Along with the text, the expression “truth-effects” designed by French philosopher Michel Foucault is being used. “Effects of truth” is an expression in reference to the idea of discourses being neither true nor false. In Os sertões, the effects of truth emerge from strategic power disputes amongst the Church, landowners, politicians and a seaside ruling elite that ignores the reality of the poor and forsaken hinterlands. Keywords: discourse, power, truth.

Experiences of a walking intervention in a University community : Qualitative perspectives

Background: This study explored the experiences of university employees that participated in a walking intervention that encouraged individuals to walk more throughout their workday. The 10-week program was comprised of 5 phases (i.e. baseline, anticipating barriers, short planned walks, longer planned walks and maintenance) and utilized a pedometer diary and an online website for logging steps. The pedometer diary included “action plans” for addressing barriers and planning walking and the online dashboard provided graphical outputs that allowed participants to visualize whether they were reaching or exceeding their step targets. Methods: A subsample of 12 academic and administrative employees from the study completed open ended questionnaires at the end of the study. The questions focused on capturing the major themes of benefits/mediators and problems/moderators of the program and were assessed using phenomenological approaches. Results: Participants found a raised consciousness of physical inactivity throughout the work day. They also found it useful to have a graphical display of physical activity patterns, but found time constraints and lack of managerial support to be the primary barriers/moderators of the program. Those most likely to withdraw from the program experienced technical difficulties with objective monitors and the online website. Conclusions: Findings highlight the value in being involved in a group forum and provide insights into the challenges of supporting such programs within the workplace.

The influence of motorcyclist behavior in crash involvement

Introduction: In Singapore, motorcycle crashes account for 50% of traffic fatalities and 53% of injuries. While extensive research efforts have been devoted to improve the motorcycle safety, the relationship between the rider behavior and the crash risk is still not well understood. The objective of this study is to evaluate how behavioral factors influence crash risk and to identify the most vulnerable group of motorcyclists. Methods: To explore the rider behavior, a 61-item questionnaire examining sensation seeking (Zuckerman et al., 1978), impulsiveness (Eysenck et al., 1985), aggressiveness (Buss & Perry, 1992), and risk-taking behavior (Weber et al., 2002) was developed. A total of 240 respondents with at least one year riding experience form the sample that relate behavior to their crash history, traffic penalty awareness, and demographic characteristics. By clustering the crash risk using the medoid portioning algorithm, the log-linear model relating the rider behavior to crash risk was developed. Results and Discussions: Crash-involved motorcyclists scored higher in impulsive sensation seeking, aggression and risk-taking behavior. Aggressive and high risk-taking motorcyclists were respectively 1.30 and 2.21 times more likely to fall under the high crash involvement group while impulsive sensation seeking was not found to be significant. Based on the scores on risk-taking and aggression, the motorcyclists were clustered into four distinct personality combinations namely, extrovert (aggressive, impulsive risk-takers), leader (cautious, aggressive risk-takers), follower (agreeable, ignorant risk-takers), and introvert (self-consciousness, fainthearted risk-takers). “Extrovert” motorcyclists were most prone to crashes, being 3.34 times more likely to involve in crash and 8.29 times more vulnerable than the “introvert”. Mediating factors like demographic characteristics, riding experience, and traffic penalty awareness were found not to be significant in reducing crash risk. Conclusion: The findings of this study will be useful for road safety campaign planners to be more focused in the target group as well as those who employ motorcyclists for their delivery business.

RCA method for fault diagnosis in digital substations of power systems

The authors present a Cause-Effect fault diagnosis model, which utilises the Root Cause Analysis approach and takes into account the technical features of a digital substation. The Dempster/Shafer evidence theory is used to integrate different types of fault information in the diagnosis model so as to implement a hierarchical, systematic and comprehensive diagnosis based on the logic relationship between the parent and child nodes such as transformer/circuit-breaker/transmission-line, and between the root and child causes. A real fault scenario is investigated in the case study to demonstrate the developed approach in diagnosing malfunction of protective relays and/or circuit breakers, miss or false alarms, and other commonly encountered faults at a modern digital substation.