A secure framework and related protocols for ubiquitous access to electronic health records using Java sim cards

Ubiquitous access to patient medical records is an important aspect of caring for patient safety. Unavailability of sufficient medical information at the point-ofcare could possibly lead to a fatality. The U.S. Institute of Medicine has reported that between 44,000 and 98,000 people die each year due to medical errors, such as incorrect medication dosages, due to poor legibility in manual records, or delays in consolidating needed information to discern the proper intervention. In this research we propose employing emergent technologies such as Java SIM Cards (JSC), Smart Phones (SP), Next Generation Networks (NGN), Near Field Communications (NFC), Public Key Infrastructure (PKI), and Biometric Identification to develop a secure framework and related protocols for ubiquitous access to Electronic Health Records (EHR). A partial EHR contained within a JSC can be used at the point-of-care in order to help quick diagnosis of a patient’s problems. The full EHR can be accessed from an Electronic Health Records Centre (EHRC) when time and network availability permit. Moreover, this framework and related protocols enable patients to give their explicit consent to a doctor to access their personal medical data, by using their Smart Phone, when the doctor needs to see or update the patient’s medical information during an examination. Also our proposed solution would give the power to patients to modify the Access Control List (ACL) related to their EHRs and view their EHRs through their Smart Phone. Currently, very limited research has been done on using JSCs and similar technologies as a portable repository of EHRs or on the specific security issues that are likely to arise when JSCs are used with ubiquitous access to EHRs. Previous research is concerned with using Medicare cards, a kind of Smart Card, as a repository of medical information at the patient point-of-care. However, this imposes some limitations on the patient’s emergency medical care, including the inability to detect the patient’s location, to call and send information to an emergency room automatically, and to interact with the patient in order to get consent. The aim of our framework and related protocols is to overcome these limitations by taking advantage of the SIM card and the technologies mentioned above. Briefly, our framework and related protocols will offer the full benefits of accessing an up-to-date, precise, and comprehensive medical history of a patient, whilst its mobility will provide ubiquitous access to medical and patient information everywhere it is needed. The objective of our framework and related protocols is to automate interactions between patients, healthcare providers and insurance organisations, increase patient safety, improve quality of care, and reduce the costs.

Creativity, knowledge, engagement : keys to finding the right governance model for a regional community precinct

This paper investigates the Cooroy Mill community precinct (Sunshine Coast, Queensland), as a case study, seeking to understand the way local dynamics interplay and work with the community strengths to build a governance model of best fit. As we move to an age of ubiquitous computing and creative economies, the definition of public place and its governance take on new dimensions, which – while often utilizing models of the past – will need to acknowledge and change to the direction of the future. This paper considers a newly developed community precinct that has been built on three key principles: to foster creative expression with new media, to establish a knowledge economy in a regional area, and to subscribe to principles of community engagement. The study involved qualitative interviews with key stakeholders and a review of common practice models of governance along a spectrum from community control to state control. The paper concludes with a call for governance structures that are locally situated and tailored, inclusive, engaging, dynamic and flexible in order to build community capacity, encourage creativity, and build knowledge economies within emerging digital media cityscapes.

Close encounter, withdrawn effects

Extending Deleuze’s later writing on the cinema and engaging both film and built work, the article explores what I call the "close-up," an immanent subjectivity of architectural encounter, whereby the architectural surface aggressively colonizes the subject at close range through a touch or by another mechanism I describe as the "withdrawn effect," the surface assimilates the subject.

Old Brisbane Botanic Gardens: Conservation Plan Review 2005, Report of Stage 1 Heritage Significance and Conservation Policies

Report for City Design, for Environment and Parks, within the Brisbane City Council. Context of this Project A Conservation Study for the Old Brisbane Botanic Gardens, formerly called the Brisbane City Botanic Gardens, was finalised in 1995 and prepared by Jeannie Sim for the Landscape Section of Brisbane City Council, the same author of the present report. This unpublished report was the first conservation plan prepared for the place and it was recommended that it be reviewed in five years time. That time has arrived finally with the preparation of the 2005 Review. The present project was commissioned by City Design on behalf of Environment and Parks Section of Brisbane City Council. The author has purposely chosen to call the study site the 'Old Brisbane Botanic Gardens' (OBBG) to differentiate it from the Brisbane Botanic Gardens, Mt. Coot-tha (BBG-MC), and to maintain the claim for this original garden to remain as a botanic garden for Brisbane. This name immediately brings to mind an association with history, as in the precedent set by the naming of the nearby 'Old Government House' at Gardens Point.

A review of simulation models for railway systems

With the advances in computer hardware and software development techniques in the past 25 years, digital computer simulation of train movement and traction systems has been widely adopted as a standard computer-aided engineering tool [1] during the design and development stages of existing and new railway systems. Simulators of different approaches and scales are used extensively to investigate various kinds of system studies. Simulation is now proven to be the cheapest means to carry out performance predication and system behaviour characterisation. When computers were first used to study railway systems, they were mainly employed to perform repetitive but time-consuming computational tasks, such as matrix manipulations for power network solution and exhaustive searches for optimal braking trajectories. With only simple high-level programming languages available at the time, full advantage of the computing hardware could not be taken. Hence, structured simulations of the whole railway system were not very common. Most applications focused on isolated parts of the railway system. It is more appropriate to regard those applications as primarily mechanised calculations rather than simulations. However, a railway system consists of a number of subsystems, such as train movement, power supply and traction drives, which inevitably contains many complexities and diversities. These subsystems interact frequently with each other while the trains are moving; and they have their special features in different railway systems. To further complicate the simulation requirements, constraints like track geometry, speed restrictions and friction have to be considered, not to mention possible non-linearities and uncertainties in the system. In order to provide a comprehensive and accurate account of system behaviour through simulation, a large amount of data has to be organised systematically to ensure easy access and efficient representation; the interactions and relationships among the subsystems should be defined explicitly. These requirements call for sophisticated and effective simulation models for each component of the system. The software development techniques available nowadays allow the evolution of such simulation models. Not only can the applicability of the simulators be largely enhanced by advanced software design, maintainability and modularity for easy understanding and further development, and portability for various hardware platforms are also encouraged. The objective of this paper is to review the development of a number of approaches to simulation models. Attention is, in particular, given to models for train movement, power supply systems and traction drives. These models have been successfully used to enable various ‘what-if’ issues to be resolved effectively in a wide range of applications, such as speed profiles, energy consumption, run times etc.

Strengthening and formally verifying privacy in identity management systems

In a digital world, users’ Personally Identifiable Information (PII) is normally managed with a system called an Identity Management System (IMS). There are many types of IMSs. There are situations when two or more IMSs need to communicate with each other (such as when a service provider needs to obtain some identity information about a user from a trusted identity provider). There could be interoperability issues when communicating parties use different types of IMS. To facilitate interoperability between different IMSs, an Identity Meta System (IMetS) is normally used. An IMetS can, at least theoretically, join various types of IMSs to make them interoperable and give users the illusion that they are interacting with just one IMS. However, due to the complexity of an IMS, attempting to join various types of IMSs is a technically challenging task, let alone assessing how well an IMetS manages to integrate these IMSs. The first contribution of this thesis is the development of a generic IMS model called the Layered Identity Infrastructure Model (LIIM). Using this model, we develop a set of properties that an ideal IMetS should provide. This idealized form is then used as a benchmark to evaluate existing IMetSs. Different types of IMS provide varying levels of privacy protection support. Unfortunately, as observed by Jøsang et al (2007), there is insufficient privacy protection in many of the existing IMSs. In this thesis, we study and extend a type of privacy enhancing technology known as an Anonymous Credential System (ACS). In particular, we extend the ACS which is built on the cryptographic primitives proposed by Camenisch, Lysyanskaya, and Shoup. We call this system the Camenisch, Lysyanskaya, Shoup - Anonymous Credential System (CLS-ACS). The goal of CLS-ACS is to let users be as anonymous as possible. Unfortunately, CLS-ACS has problems, including (1) the concentration of power to a single entity - known as the Anonymity Revocation Manager (ARM) - who, if malicious, can trivially reveal a user’s PII (resulting in an illegal revocation of the user’s anonymity), and (2) poor performance due to the resource-intensive cryptographic operations required. The second and third contributions of this thesis are the proposal of two protocols that reduce the trust dependencies on the ARM during users’ anonymity revocation. Both protocols distribute trust from the ARM to a set of n referees (n > 1), resulting in a significant reduction of the probability of an anonymity revocation being performed illegally. The first protocol, called the User Centric Anonymity Revocation Protocol (UCARP), allows a user’s anonymity to be revoked in a user-centric manner (that is, the user is aware that his/her anonymity is about to be revoked). The second protocol, called the Anonymity Revocation Protocol with Re-encryption (ARPR), allows a user’s anonymity to be revoked by a service provider in an accountable manner (that is, there is a clear mechanism to determine which entity who can eventually learn - and possibly misuse - the identity of the user). The fourth contribution of this thesis is the proposal of a protocol called the Private Information Escrow bound to Multiple Conditions Protocol (PIEMCP). This protocol is designed to address the performance issue of CLS-ACS by applying the CLS-ACS in a federated single sign-on (FSSO) environment. Our analysis shows that PIEMCP can both reduce the amount of expensive modular exponentiation operations required and lower the risk of illegal revocation of users’ anonymity. Finally, the protocols proposed in this thesis are complex and need to be formally evaluated to ensure that their required security properties are satisfied. In this thesis, we use Coloured Petri nets (CPNs) and its corresponding state space analysis techniques. All of the protocols proposed in this thesis have been formally modeled and verified using these formal techniques. Therefore, the fifth contribution of this thesis is a demonstration of the applicability of CPN and its corresponding analysis techniques in modeling and verifying privacy enhancing protocols. To our knowledge, this is the first time that CPN has been comprehensively applied to model and verify privacy enhancing protocols. From our experience, we also propose several CPN modeling approaches, including complex cryptographic primitives (such as zero-knowledge proof protocol) modeling, attack parameterization, and others. The proposed approaches can be applied to other security protocols, not just privacy enhancing protocols.

Improving the performance of model-order selection criteria by partial-model selection search

The traditional searching method for model-order selection in linear regression is a nested full-parameters-set searching procedure over the desired orders, which we call full-model order selection. On the other hand, a method for model-selection searches for the best sub-model within each order. In this paper, we propose using the model-selection searching method for model-order selection, which we call partial-model order selection. We show by simulations that the proposed searching method gives better accuracies than the traditional one, especially for low signal-to-noise ratios over a wide range of model-order selection criteria (both information theoretic based and bootstrap-based). Also, we show that for some models the performance of the bootstrap-based criterion improves significantly by using the proposed partial-model selection searching method. Index Terms— Model order estimation, model selection, information theoretic criteria, bootstrap 1. INTRODUCTION Several model-order selection criteria can be applied to find the optimal order. Some of the more commonly used information theoretic-based procedures include Akaike’s information criterion (AIC) [1], corrected Akaike (AICc) [2], minimum description length (MDL) [3], normalized maximum likelihood (NML) [4], Hannan-Quinn criterion (HQC) [5], conditional model-order estimation (CME) [6], and the efficient detection criterion (EDC) [7]. From a practical point of view, it is difficult to decide which model order selection criterion to use. Many of them perform reasonably well when the signal-to-noise ratio (SNR) is high. The discrepancies in their performance, however, become more evident when the SNR is low. In those situations, the performance of the given technique is not only determined by the model structure (say a polynomial trend versus a Fourier series) but, more importantly, by the relative values of the parameters within the model. This makes the comparison between the model-order selection algorithms difficult as within the same model with a given order one could find an example for which one of the methods performs favourably well or fails [6, 8]. Our aim is to improve the performance of the model order selection criteria in cases where the SNR is low by considering a model-selection searching procedure that takes into account not only the full-model order search but also a partial model order search within the given model order. Understandably, the improvement in the performance of the model order estimation is at the expense of additional computational complexity.

Workplace Equality in International Organizations: A Way Forward

In this contribution, I am interested in how discrimination issues are manifested in employment relations in the United Nations (UN), a public forum to all states political leaders to advance their concerns, the World Bank, a financial organization that promotes economic development, mainly in developing countries, and the Consultative Group on International Agricultural Research (CGIAR), the eldest and largest global public program of the World Bank with a strategic network of diverse stakeholders that harnesses the best in science to produce more and better food, reduce poverty and sustain environments. Considering the immunity and privileges granted to international organizations, what are the current available legal procedures, at the national or international level, for workplace equality? How accountable and transparent are they, based on the practice of these organizations? Can discrimination biases that go beyond the known individual-based discrimination claims be identified? If so, how can they be challenged and changed? Based of the special position of international civil servants in international organizations and the duty to protect their fundamental rights, I claim that the limitation of opportunity by discriminatory biases and the psychic burden on the individual staff member, on daily basis, qualify for a workplace wrong and call for independent and impartial legal procedures that would ensure due process and fair treatment.

Suzumushi : the silent swarm

This silent swarm of stylized crickets is downloading data from Internet and catalogue searches being undertaken by the public at the State Library Queensland. These searches are being displayed on the screen on their backs. Each cricket downloads the searches and communicates this information with other crickets. Commonly found searches spread like a meme through the swarm. In this work memes replace the crickets’ song, washing like a wave through the swarm and changing on the whim of Internet users. When one cricket begins calling others, the swarm may respond to produce emergent patterns of text. When traffic is slow or of now interest to the crickets, they display onomatopoeia. The work is inspired by R. Murray Schafer’s research into acoustic ecologies. In the 1960’s Schafer proposed that many species develop calls that fit niches within their acoustic environment. An increasing background of white noise dominates the acoustic environment of urban human habitats, leaving few acoustic niches for other species to communicate. The popularity of headphones and portable music may be seen as an evolution of our acoustic ecology driven by our desire to hear expressive, meaningful sound, above the din of our cities. Similarly, the crickets in this work are hypothetical creatures that have evolved to survive in a noisy human environment. This speculative species replaces auditory calls with onomatopoeia and information memes, communicating with the swarm via radio frequency chirps instead of sound. Whilst these crickets cannot make sound, each individual has been programmed respond to sound generated by the audience, by making onomatopoeia calls in text. Try talking to a cricket, blowing on its tail, or making other sounds to trigger a call.

Informational city

Many cities worldwide face the prospect of major transformation as the world moves towards a global information order. In this new era, urban economies are being radically altered by dynamic processes of economic and spatial restructuring. The result is the creation of ‘informational cities’ or its new and more popular name, ‘knowledge cities’. For the last two centuries, social production had been primarily understood and shaped by neo-classical economic thought that recognized only three factors of production: land, labor and capital. Knowledge, education, and intellectual capacity were secondary, if not incidental, factors. Human capital was assumed to be either embedded in labor or just one of numerous categories of capital. In the last decades, it has become apparent that knowledge is sufficiently important to deserve recognition as a fourth factor of production. Knowledge and information and the social and technological settings for their production and communication are now seen as keys to development and economic prosperity. The rise of knowledge-based opportunity has, in many cases, been accompanied by a concomitant decline in traditional industrial activity. The replacement of physical commodity production by more abstract forms of production (e.g. information, ideas, and knowledge) has, however paradoxically, reinforced the importance of central places and led to the formation of knowledge cities. Knowledge is produced, marketed and exchanged mainly in cities. Therefore, knowledge cities aim to assist decision-makers in making their cities compatible with the knowledge economy and thus able to compete with other cities. Knowledge cities enable their citizens to foster knowledge creation, knowledge exchange and innovation. They also encourage the continuous creation, sharing, evaluation, renewal and update of knowledge. To compete nationally and internationally, cities need knowledge infrastructures (e.g. universities, research and development institutes); a concentration of well-educated people; technological, mainly electronic, infrastructure; and connections to the global economy (e.g. international companies and finance institutions for trade and investment). Moreover, they must possess the people and things necessary for the production of knowledge and, as importantly, function as breeding grounds for talent and innovation. The economy of a knowledge city creates high value-added products using research, technology, and brainpower. Private and the public sectors value knowledge, spend money on its discovery and dissemination and, ultimately, harness it to create goods and services. Although many cities call themselves knowledge cities, currently, only a few cities around the world (e.g., Barcelona, Delft, Dublin, Montreal, Munich, and Stockholm) have earned that label. Many other cities aspire to the status of knowledge city through urban development programs that target knowledge-based urban development. Examples include Copenhagen, Dubai, Manchester, Melbourne, Monterrey, Singapore, and Shanghai. Knowledge-Based Urban Development To date, the development of most knowledge cities has proceeded organically as a dependent and derivative effect of global market forces. Urban and regional planning has responded slowly, and sometimes not at all, to the challenges and the opportunities of the knowledge city. That is changing, however. Knowledge-based urban development potentially brings both economic prosperity and a sustainable socio-spatial order. Its goal is to produce and circulate abstract work. The globalization of the world in the last decades of the twentieth century was a dialectical process. On one hand, as the tyranny of distance was eroded, economic networks of production and consumption were constituted at a global scale. At the same time, spatial proximity remained as important as ever, if not more so, for knowledge-based urban development. Mediated by information and communication technology, personal contact, and the medium of tacit knowledge, organizational and institutional interactions are still closely associated with spatial proximity. The clustering of knowledge production is essential for fostering innovation and wealth creation. The social benefits of knowledge-based urban development extend beyond aggregate economic growth. On the one hand is the possibility of a particularly resilient form of urban development secured in a network of connections anchored at local, national, and global coordinates. On the other hand, quality of place and life, defined by the level of public service (e.g. health and education) and by the conservation and development of the cultural, aesthetic and ecological values give cities their character and attract or repel the creative class of knowledge workers, is a prerequisite for successful knowledge-based urban development. The goal is a secure economy in a human setting: in short, smart growth or sustainable urban development.

The textures of globalization : biopolitics and the closure of xenotourism

In this paper, we explore the tensions around a recent controversial development in medical tourism: xenotourism in Mexico. We take this bioendeavor - now ceased - to be emblematic of the global character of contemporary biomedicine, providing insights into the production and operation of scientific knowledge. We explore this through what we call the “textures of globalization”: the anxiety regarding the extent to which Mexico was understood as an (in)appropriate venue for the generation of novel knowledge on xenotransplantation, and as a location for xenotourism. These tensions, which oscillated between calls for individual freedom (choice) and global regulation (standardization), ultimately led to the closure of xenotourism in Mexico.

Common mode voltage in a motor drive system with PFC

Common mode voltage generated by a power converter in combination with parasitic capacitive couplings is a potential source of shaft voltage in an AC motor drive system. In this paper, a three-phase motor drive system supplied with a single-phase AC-DC diode rectifier is investigated in order to reduce shaft voltage in a three-phase AC motor drive system. In this topology, the common mode voltage generated by the inverter is influenced by the AC-DC diode rectifier because the placement of the neutral point is changing in different rectifier circuit states. A pulse width modulation technique is presented by a proper placement of the zero vectors to reduce the common mode voltage level, which leads to a cost effective shaft voltage reduction technique without load current distortion, while keeping the switching frequency constant. Analysis and simulations have been presented to investigate the proposed method.

The low-affinity site of the β1-adrenoceptor and its relevance to cardiovascular pharmacology

β-Adrenoceptor blocking agents (β-blockers) that at low concentrations antagonize cardiostimulant effects of catecholamines, but at high concentrations also cause cardiostimulation, have been appearing since the late 1960s. These cardiostimulant β-blockers, coined non-conventional partial agonists, antagonize the effects of catecholamines through a high-affinity site (β1HAR), but cause cardiostimulation mainly through a low-affinity site (β1LAR) of the myocardial β1-adrenoceptor. The experimental non-conventional partial agonist (−)-CGP12177 increases cardiac L-type Ca2+ current density and Ca2+ transients, shortens action potential duration but augments action potential plateau, increases heart rate and force, as well as causes arrhythmic Ca2+ transients and arrhythmic cardiocyte contractions. Other β-blockers, which do not cause cardiostimulation, consistently have lower affinity for β1LAR than β1HAR. These sites were verified and the cardiac pharmacology of non-conventional partial agonists confirmed on recombinant β1-adrenoceptors and on β1-adrenoceptors overexpressed into the heart. A targeted mutation of Asp138 to Glu138 virtually abolished the pharmacology of β1HAR but left intact the pharmacology of β1LAR. Non-conventional partial agonists may be beneficial for the treatment of peripheral autonomic neuropathy but probably due to their arrhythmic propensities, may be harmful for the treatment of chronic heart failure.

Dimensions of coupling in middleware

It is well accepted that different types of distributed architectures require different degrees of coupling. For example, in client-server and three-tier architectures, application components are generally tightly coupled, both with one another and with the underlying middleware. Meanwhile, in off-line transaction processing, grid computing and mobile applications, the degree of coupling between application components and with the underlying middleware needs to be minimized. Terms such as ‘synchronous’, ‘asynchronous’, ‘blocking’, ‘non-blocking’, ‘directed’, and ‘non-directed’ are often used to refer to the degree of coupling required by an architecture or provided by a middleware. However, these terms are used with various connotations. Although various informal definitions have been provided, there is a lack of an overarching formal framework to unambiguously communicate architectural requirements with respect to (de-)coupling. This article addresses this gap by: (i) formally defining three dimensions of (de-)coupling; (ii) relating these dimensions to existing middleware; and (iii) proposing notational elements to represent various coupling integration patterns. This article also discusses a prototype that demonstrates the feasibility of its implementation.

In vitro and in vivo examination of the cell surface glycoprotein CDCP1

A number of reports have demonstrated the importance of the CUB domaincontaining protein 1 (CDCP1) in facilitating cancer progression in animal models and the potential of this protein as a prognostic marker in several malignancies. CDCP1 facilitates metastasis formation in animal models by negatively regulating anoikis, a type of apoptosis triggered by the loss of attachment signalling from cell-cell contacts or cell-extra cellular matrix (ECM) contacts. Due to the important role CDCP1 plays in cancer progression in model systems, it is considered a potential drug target to prevent the metastatic spread of cancers. CDCP1 is a highly glycosylated 836 amino acid cell surface protein. It has structural features potentially facilitating protein-protein interactions including 14 N-glycosylation sites, three CUB-like domains, 20 cysteine residues likely to be involved in disulfide bond formation and five intracellular tyrosine residues. CDCP1 interacts with a variety of proteins including Src family kinases (SFKs) and protein kinase C ä (PKCä). Efforts to understand the mechanisms regulating these interactions have largely focussed on three CDCP1 tyrosine residues Y734, Y743 and Y762. CDCP1-Y734 is the site where SFKs phosphorylate and bind to CDCP1 and mediate subsequent phosphorylation of CDCP1-Y743 and -Y762 which leads to binding of PKCä at CDCP1-Y762. The resulting trimeric protein complex of SFK•CDCP1•PKCä has been proposed to mediate an anti-apoptotic cell phenotype in vitro, and to promote metastasis in vivo. The effect of mutation of the three tyrosines on interactions of CDCP1 with SFKs and PKCä and the consequences on cell phenotype in vitro and in vivo have not been examined. CDCP1 has a predicted molecular weight of ~90 kDa but is usually detected as a protein which migrates at ~135 kDa by Western blot analysis due to its high degree of glycosylation. A low molecular weight form of CDCP1 (LMWCDCP1) of ~70 kDa has been found in a variety of cancer cell lines. The mechanisms leading to the generation of LMW-CDCP1 in vivo are not well understood but an involvement of proteases in this process has been proposed. Serine proteases including plasmin and trypsin are able to proteolytically process CDCP1. In addition, the recombinant protease domain of the serine protease matriptase is also able to cleave the recombinant extracellular portion of CDCP1. Whether matriptase is able to proteolytically process CDCP1 on the cell surface has not been examined. Importantly, proteolytic processing of CDCP1 by trypsin leads to phosphorylation of its cell surface-retained portion which suggests that this event leads to initiation of an intracellular signalling cascade. This project aimed to further examine the biology of CDCP1 with a main of focus on exploring the roles played by CDCP1 tyrosine residues. To achieve this HeLa cells stably expressing CDCP1 or the CDCP1 tyrosine mutants Y734F, Y743F and Y762F were generated. These cell lines were used to examine: • The roles of the tyrosine residues Y734, Y743 and Y762 in mediating interactions of CDCP1 with binding proteins and to examine the effect of the stable expression on HeLa cell morphology. • The ability of the serine protease matriptase to proteolytically process cell surface CDCP1 and to examine the consequences of this event on HeLa cell phenotype and cell signalling in vitro. • The importance of these residues in processes associated with cancer progression in vitro including adhesion, proliferation and migration. • The role of these residues on metastatic phenotype in vivo and the ability of a function-blocking anti-CDCP1 antibody to inhibit metastasis in the chicken embryo chorioallantoic membrane (CAM) assay. Interestingly, biochemical experiments carried out in this study revealed that mutation of certain CDCP1 tyrosine residues impacts on interactions of this protein with binding proteins. For example, binding of SFKs as well as PKCä to CDCP1 was markedly decreased in HeLa-CDCP1-Y734F cells, and binding of PKCä was also reduced in HeLa-CDCP1-Y762F cells. In contrast, HeLa-CDCP1-Y743F cells did not display altered interactions with CDCP1 binding proteins. Importantly, observed differences in interactions of CDCP1 with binding partners impacted on basal phosphorylation of CDCP1. It was found that HeLa-CDCP1, HeLa-CDCP1-Y743F and -Y762F displayed strong basal levels of CDCP1 phosphorylation. In contrast, HeLa-CDCP1-Y734F cells did not display CDCP1 phosphorylation but exhibited constitutive phosphorylation of focal adhesion kinase (FAK) at tyrosine 861. Significantly, subsequent investigations to examine this observation suggested that CDCP1-Y734 and FAK-Y861 are competitive substrates for SFK-mediated phosphorylation. It appeared that SFK-mediated phosphorylation of CDCP1- Y734 and FAK-Y861 is an equilibrium which shifts depending on the level of CDCP1 expression in HeLa cells. This suggests that the level of CDCP1 expression may act as a regulatory mechanism allowing cells to switch from a FAK-Y861 mediated pathway to a CDCP1-Y734 mediated pathway. This is the first time that a link between SFKs, CDCP1 and FAK has been demonstrated. One of the most interesting observations from this work was that CDCP1 altered HeLa cell morphology causing an elongated and fibroblastic-like appearance. Importantly, this morphological change depended on CDCP1- Y734. In addition, it was observed that this change in cell morphology was accompanied by increased phosphorylation of SFK-Y416. This suggests that interactions of SFKs with CDCP1-Y734 increases SFK activity since SFKY416 is critical in regulating kinase activity of these proteins. The essential role of SFKs in mediating CDCP1-induced HeLa cell morphological changes was demonstrated using the SFK-selective inhibitor SU6656. This inhibitor caused reversion of HeLa-CDCP1 cell morphology to an epithelial appearance characteristic of HeLa-vector cells. Significantly, in vitro studies revealed that certain CDCP1-mediated cell phenotypes are mediated by cellular pathways dependent on CDCP1 tyrosine residues whereas others are independent of these sites. For example, CDCP1 expression caused a marked increase in HeLa cell motility that was independent of CDCP1 tyrosine residues. In contrast, CDCP1- induced decrease in HeLa cell proliferation was most prominent in HeLa- CDCP1-Y762F cells, potentially indicating a role for this site in regulating proliferation in HeLa cells. Another cellular event which was identified to require phosphorylation of a particular CDCP1 tyrosine residue is adhesion to fibronectin. It was observed that the CDCP1-mediated strong decrease in adhesion to fibronectin is mostly restored in HeLa-CDCP1-Y743F cells. This suggests a possible role for CDCP1-Y743 in causing a CDCP1-mediated decrease in adhesion. Data from in vivo experiments indicated that HeLa-CDCP1-Y734F cells are more metastic than HeLa-CDCP1 cells in vivo. This indicates that interaction of CDCP1 with SFKs and PKCä may not be required for CDCP1-mediated metastasis formation of HeLa cells in vivo. The metastatic phenotype of these cells may be caused by signalling involving FAK since HeLa-CDCP1- Y734F cells are the only CDCP1 expressing cells displaying constitutive phosphorylation of FAK-Y861. HeLa-CDCP1-Y762F cells displayed a very low metastatic ability which suggests that this CDCP1 tyrosine residue is important in mediating a pro-metastatic phenotype in HeLa cells. More detailed exploration of cellular events occurring downstream of CDCP1-Y734 and -Y762 may provide important insights into the mechanisms altering the metastatic ability of CDCP1 expressing HeLa cells. Complementing the in vivo studies, anti-CDCP1 antibodies were employed to assess whether these antibodies are able to inhibit metastasis of CDCP1 and CDCP1 tyrosine mutants expressing HeLa cells. It was found that HeLa- CDCP1-Y734F cells were the only cell line which was markedly reduced in the ability to metastasise. In contrast, the ability of HeLa-CDCP1, HeLa- CDCP1-Y743F and -Y762F cells to metastasise in vivo was not inhibited. These data suggest a possible role of interactions of CDCP1 with SFKs, occurring at CDCP1-Y734, in preventing an anti-metastatic effect of anti- CDCP1 antibodies in vivo. The proposal that SFKs may play a role in regulating anti-metastatic effects of anti-CDCP1 antibodies was supported by another experiment where differences between HeLa-CDCP1 cells and CDCP1 expressing HeLa cells (HeLa-CDCP1-S) from collaborators at the Scripps Research Institute were examined. It was found that HeLa-CDCP1-S cells express different SFKs than CDCP1 expressing HeLa cells generated for this study. This is important since HeLa-CDCP1-S cells can be inhibited in their metastatic ability using anti-CDCP1 antibodies in vivo. Importantly, these data suggest that further examinations of the roles of SFKs in facilitating anti-metastatic effects of anti-CDCP1 antibodies may give insights into how CDCP1 can be blocked to prevent metastasis in vivo. This project also explored the ability of the serine protease matriptase to proteolytically process cell surface localised CDCP1 because it is unknown whether matriptase can cleave cell surface CDCP1 as it has been reported for other proteases such as trypsin and plasmin. Furthermore, the consequences of matriptase-mediated proteolysis on cell phenotype in vitro and cell signalling were examined since recent reports suggested that proteolysis of CDCP1 leads to its phosphorylation and may initiate cell signalling and consequently alter cell phenotype. It was found that matriptase is able to proteolytically process cell surface CDCP1 at low nanomolar concentrations which suggests that cleavage of CDCP1 by matriptase may facilitate the generation of LWM-CDCP1 in vivo. To examine whether matriptase-mediated proteolysis induced cell signalling anti-phospho Erk 1/2 Western blot analysis was performed as this pathway has previously been examined to study signalling in response to proteolytic processing of cell surface proteins. It was found that matriptase-mediated proteolysis in CDCP1 expressing HeLa cells initiated intracellular signalling via Erk 1/2. Interestingly, this increase in phosphorylation of Erk 1/2 was also observed in HeLa-vector cells. This suggested that initiation of cell signalling via Erk 1/2 phosphorylation as a result of matriptase-mediated proteolysis occurs by pathways independent of CDCP1. Subsequent investigations measuring the flux of free calcium ions and by using a protease-activated receptor 2 (PAR2) agonist peptide confirmed this hypothesis. These data suggested that matriptase-mediated proteolysis results in cell signalling via a pathway induced by the activation of PAR2 rather than by CDCP1. This indicates that induction of cell signalling in HeLa cells as a consequence of matriptase-mediated proteolysis occurs via signalling pathways which do not involve phosphorylation of Erk 1/2. Consequently, it appears that future attempts should focus on the examination of cellular pathways other than Erk 1/2 to elucidate cell signalling initiated by matriptase-mediated proteolytic processing of CDCP1. The data presented in this thesis has explored in vitro and in vivo aspects of the biology of CDCP1. The observations summarised above will permit the design of future studies to more precisely determine the role of CDCP1 and its binding partners in processes relevant to cancer progression. This may contribute to further defining CDCP1 as a target for cancer treatment.