Prostate cancer biomarkers and the emerging proteomic techniques used in biomarker research

Prostate cancer (CaP) is the second leading cause of cancer-related deaths in North American males and the most common newly diagnosed cancer in men world wide. Biomarkers are widely used for both early detection and prognostic tests for cancer. The current, commonly used biomarker for CaP is serum prostate specific antigen (PSA). However, the specificity of this biomarker is low as its serum level is not only increased in CaP but also in various other diseases, with age and even body mass index. Human body fluids provide an excellent resource for the discovery of biomarkers, with the advantage over tissue/biopsy samples of their ease of access, due to the less invasive nature of collection. However, their analysis presents challenges in terms of variability and validation. Blood and urine are two human body fluids commonly used for CaP research, but their proteomic analyses are limited both by the large dynamic range of protein abundance making detection of low abundance proteins difficult and in the case of urine, by the high salt concentration. To overcome these challenges, different techniques for removal of high abundance proteins and enrichment of low abundance proteins are used. Their applications and limitations are discussed in this review. A number of innovative proteomic techniques have improved detection of biomarkers. They include two dimensional differential gel electrophoresis (2D-DIGE), quantitative mass spectrometry (MS) and functional proteomic studies, i.e., investigating the association of post translational modifications (PTMs) such as phosphorylation, glycosylation and protein degradation. The recent development of quantitative MS techniques such as stable isotope labeling with amino acids in cell culture (SILAC), isobaric tags for relative and absolute quantitation (iTRAQ) and multiple reaction monitoring (MRM) have allowed proteomic researchers to quantitatively compare data from different samples. 2D-DIGE has greatly improved the statistical power of classical 2D gel analysis by introducing an internal control. This chapter aims to review novel CaP biomarkers as well as to discuss current trends in biomarker research from two angles: the source of biomarkers (particularly human body fluids such as blood and urine), and emerging proteomic approaches for biomarker research.

Dutch tilt, Aussie auteur : the films of Rolf de Heer. 2nd ed.

Dutch-born Australian director, Rolf de Heer, is Australia's most successful and unpredictable film-maker, with thirteen feature films of widely varying style and genre to his name. Arising from the author's 2006 - 2009 PhD research at the Queensland University of Technology (which focussed on the psychoanalytic use of sound in his films), and a fixed term Research Fellowship at the National Film and Sound Archive in Canberra, Australia, "Dutch Tilt, Aussie Auteur: The Films of Rolf de Heer" was first published in 2009 by VDM in Saarbrucken, Germany. This second edition addresses de Heer's additional film-making since 2009, and as with the first edition, is an auteur analysis of the thirteen feature films he has directed (and mostly written and produced). The book explores the theoretical instability of the concept of auteurism and concludes that there is a signature world view to be detected in his oeuvre, and that de Heer (quite possibly unconsciously) promotes unlikely protagonists who are non-hyper masculine, child-like and nurturing, as opposed to the typical Hollywood hero who is macho, exploitative and hyper masculine. Rolf de Heer was born in Heemskerk, Holland, in 1951 and migrated to Australia with his family in 1959. He spent seven years working for the ABC before gaining entry to Australia's Film, Television and Radio School, where he studied Producing and Directing. From his debut feature film after graduating, the children's story about the restoration of a Tiger Moth biplane, "Tail of a Tiger" (1984) to his breakout cult sensation "Bad Boy Bubby" (1993) which "tore Venice [Film Festival] apart" to the first Aboriginal Australian language film "Ten Canoes" (2006) which scooped the pool at the Australian Film Institute awards, de Heer has consistently proven himself unpredictable. This analysis of his widely disparate films, however, suggests that Australia's most innovative film-maker has a signature pre-occupation with giving a voice to marginalised, non-hyper masculine protagonists. Demonstrating a propensity to write and direct in a European-like style, his 'Dutch tilt' is very much not Hollywood, but is nevertheless representative of a typically Aussie world-view.

Utilising Reliability and Condition Monitoring Data for Asset Health Prognosis

The ability to forecast machinery health is vital to reducing maintenance costs, operation downtime and safety hazards. Recent advances in condition monitoring technologies have given rise to a number of prognostic models which attempt to forecast machinery health based on condition data such as vibration measurements. This paper demonstrates how the population characteristics and condition monitoring data (both complete and suspended) of historical items can be integrated for training an intelligent agent to predict asset health multiple steps ahead. The model consists of a feed-forward neural network whose training targets are asset survival probabilities estimated using a variation of the Kaplan–Meier estimator and a degradation-based failure probability density function estimator. The trained network is capable of estimating the future survival probabilities when a series of asset condition readings are inputted. The output survival probabilities collectively form an estimated survival curve. Pump data from a pulp and paper mill were used for model validation and comparison. The results indicate that the proposed model can predict more accurately as well as further ahead than similar models which neglect population characteristics and suspended data. This work presents a compelling concept for longer-range fault prognosis utilising available information more fully and accurately.

Machine prognostics based on health state estimation using SVM

The ability to accurately predict the remaining useful life of machine components is critical for machine continuous operation, and can also improve productivity and enhance system safety. In condition-based maintenance (CBM), maintenance is performed based on information collected through condition monitoring and an assessment of the machine health. Effective diagnostics and prognostics are important aspects of CBM for maintenance engineers to schedule a repair and to acquire replacement components before the components actually fail. All machine components are subjected to degradation processes in real environments and they have certain failure characteristics which can be related to the operating conditions. This paper describes a technique for accurate assessment of the remnant life of machines based on health state probability estimation and involving historical knowledge embedded in the closed loop diagnostics and prognostics systems. The technique uses a Support Vector Machine (SVM) classifier as a tool for estimating health state probability of machine degradation, which can affect the accuracy of prediction. To validate the feasibility of the proposed model, real life historical data from bearings of High Pressure Liquefied Natural Gas (HP-LNG) pumps were analysed and used to obtain the optimal prediction of remaining useful life. The results obtained were very encouraging and showed that the proposed prognostic system based on health state probability estimation has the potential to be used as an estimation tool for remnant life prediction in industrial machinery.

FOXC2 expression links epithelial-mesenchymal transition and stem cell properties in breast cancer

Resistance to chemotherapy and metastases are the major causes of breast cancer-related mortality. Moreover, cancer stem cells (CSC) play critical roles in cancer progression and treatment resistance. Previously, it was found that CSC-like cells can be generated by aberrant activation of epithelial–mesenchymal transition (EMT), thereby making anti-EMT strategies a novel therapeutic option for treatment of aggressive breast cancers. Here, we report that the transcription factor FOXC2 induced in response to multiple EMT signaling pathways as well as elevated in stem cell-enriched factions is a critical determinant of mesenchymal and stem cell properties, in cells induced to undergo EMT- and CSC-enriched breast cancer cell lines. More specifically, attenuation of FOXC2 expression using lentiviral short hairpin RNA led to inhibition of the mesenchymal phenotype and associated invasive and stem cell properties, which included reduced mammosphere-forming ability and tumor initiation. Whereas, overexpression of FOXC2 was sufficient to induce CSC properties and spontaneous metastasis in transformed human mammary epithelial cells. Furthermore, a FOXC2-induced gene expression signature was enriched in the claudin-low/basal B breast tumor subtype that contains EMT and CSC features. Having identified PDGFR-β to be regulated by FOXC2, we show that the U.S. Food and Drug Administration-approved PDGFR inhibitor, sunitinib, targets FOXC2-expressing tumor cells leading to reduced CSC and metastatic properties. Thus, FOXC2 or its associated gene expression program may provide an effective target for anti-EMT-based therapies for the treatment of claudin-low/basal B breast tumors or other EMT-/CSC-enriched tumors.

Cellular model systems to study the tumor biological role of kallikrein-related peptidases in ovarian and prostate cancer

Since the identification of the gene family of kallikrein related peptidases (KLKs), their function has been robustly studied at the biochemical level. In vitro biochemical studies have shown that KLK proteases are involved in a number of extracellular processes that initiate intracellular signaling pathways by hydrolysis, as reviewed in Chapters 8, 9, and 15, Volume 1. These events have been associated with more invasive phenotypes of ovarian, prostate, and other cancers. Concomitantly, aberrant expression of KLKs has been associated with poor prognosis of patients with ovarian and prostate cancer (Borgoño and Diamandis, 2004; Clements et al., 2004; Yousef and Diamandis, 2009), with prostate-specific antigen (PSA, KLK3) being a long standing, clinically employed biomarker for prostate cancer (Lilja et al., 2008). Data generated from patient samples in clinical studies, alongwith biochemical activity, suggests that KLKs function in the development and progression of these diseases. To bridge the gap between their function at the molecular level and the clinical need for efficacious treatment and prognostic biomarkers, functional assessment at the in vitro cellular level, using various culture models, is increasing, particularly in a three-dimensional (3D) context (Abbott, 2003; Bissell and Radisky, 2001; Pampaloni et al., 2007; Yamada and Cukierman, 2007).

Genetic polymorphisms in the human tissue kallikrein (KLK) locus and their implication in various malignant and non-malignant diseases

The Kallikrein (KLK) gene locus encodes a family of serine proteases and is the largest contiguous cluster of protease-encoding genes attributed an evolutionary age of 330 million years. The KLK locus has been implicated as a high susceptibility risk loci in numerous cancer studies through the last decade. The KLK3 gene already has established clinical relevance as a biomarker in prostate cancer prognosis through its encoded protein, prostate-specific antigen. Data mined through genome-wide association studies (GWAS) and next-generation sequencing point to many important candidate single nucleotide polymorphisms (SNPs) in KLK3 and other KLK genes. SNPs in the KLK locus have been found to be associated with several diseases including cancer, hypertension, cardiovascular disease and atopic dermatitis. Moreover, introducing a model incorporating SNPs to improve the efficiency of prostate-specific antigen in detecting malignant states of prostate cancer has been recently suggested. Establishing the functional relevance of these newly-discovered SNPs, and their interactions with each other, through in silico investigations followed by experimental validation, can accelerate the discovery of diagnostic and prognostic biomarkers. In this review, we discuss the various genetic association studies on the KLK loci identified either through candidate gene association studies or at the GWAS and post-GWAS front to aid researchers in streamlining their search for the most significant, relevant and therapeutically promising candidate KLK gene and/or SNP for future investigations.

Heritage language for young Chinese Australian adults in urban Australia : Capital and habitus in fields

Studies of Heritage Language learners‟ commitment and their ethnic identity are increasing, yet there is scant sociological research addressing topics relating to Chinese Heritage Language learners. Drawing on Bourdieu‟s signature notions of „habitus‟, „capital‟, and „field‟, this mixed methods study investigates two problems: (1) impacts of “Chineseness” and accessible resources on Chinese Heritage Language proficiency of young Chinese Australian adults in urban Australia; and (2) the meanings of Chinese Heritage Language to these young people.

Internet and e-commerce law, business and policy

Over the last two decades, the internet and e-commerce have reshaped the way we communicate, interact and transact. In the converged environment enabled by high speed broadband, web 2.0, social media, virtual worlds, user-generated content, cloud computing, VoIP, open source software and open content have rapidly become established features of our online experience. Business and government alike are increasingly using the internet as the preferred platform for delivery of their goods and services and for effective engagement with their clients. New ways of doing things online and challenges to existing business, government and social activities have tested current laws and often demand new policies and laws, adapted to the new realities. The focus of this book is the regulation of social, cultural and commercial activity on the World Wide Web. It considers developments in the law that have been, and continue to be, brought about by the emergence of the internet and e-commerce. It analyses how the law is applied to define rights and obligations in relation to online infrastructure, content and practices.

Enhancing security of linux-based android devices

Our daily lives become more and more dependent upon smartphones due to their increased capabilities. Smartphones are used in various ways from payment systems to assisting the lives of elderly or disabled people. Security threats for these devices become increasingly dangerous since there is still a lack of proper security tools for protection. Android emerges as an open smartphone platform which allows modification even on operating system level. Therefore, third-party developers have the opportunity to develop kernel-based low-level security tools which is not normal for smartphone platforms. Android quickly gained its popularity among smartphone developers and even beyond since it bases on Java on top of "open" Linux in comparison to former proprietary platforms which have very restrictive SDKs and corresponding APIs. Symbian OS for example, holding the greatest market share among all smartphone OSs, was closing critical APIs to common developers and introduced application certification. This was done since this OS was the main target for smartphone malwares in the past. In fact, more than 290 malwares designed for Symbian OS appeared from July 2004 to July 2008. Android, in turn, promises to be completely open source. Together with the Linux-based smartphone OS OpenMoko, open smartphone platforms may attract malware writers for creating malicious applications endangering the critical smartphone applications and owners� privacy. In this work, we present our current results in analyzing the security of Android smartphones with a focus on its Linux side. Our results are not limited to Android, they are also applicable to Linux-based smartphones such as OpenMoko Neo FreeRunner. Our contribution in this work is three-fold. First, we analyze android framework and the Linux-kernel to check security functionalities. We survey wellaccepted security mechanisms and tools which can increase device security. We provide descriptions on how to adopt these security tools on Android kernel, and provide their overhead analysis in terms of resource usage. As open smartphones are released and may increase their market share similar to Symbian, they may attract attention of malware writers. Therefore, our second contribution focuses on malware detection techniques at the kernel level. We test applicability of existing signature and intrusion detection methods in Android environment. We focus on monitoring events on the kernel; that is, identifying critical kernel, log file, file system and network activity events, and devising efficient mechanisms to monitor them in a resource limited environment. Our third contribution involves initial results of our malware detection mechanism basing on static function call analysis. We identified approximately 105 Executable and Linking Format (ELF) executables installed to the Linux side of Android. We perform a statistical analysis on the function calls used by these applications. The results of the analysis can be compared to newly installed applications for detecting significant differences. Additionally, certain function calls indicate malicious activity. Therefore, we present a simple decision tree for deciding the suspiciousness of the corresponding application. Our results present a first step towards detecting malicious applications on Android-based devices.

Static analysis of executables for collaborative malware detection on Android

Smartphones are getting increasingly popular and several malwares appeared targeting these devices. General countermeasures to smartphone malwares are currently limited to signature-based antivirus scanners which efficiently detect known malwares, but they have serious shortcomings with new and unknown malwares creating a window of opportunity for attackers. As smartphones become host for sensitive data and applications, extended malware detection mechanisms are necessary complying with the corresponding resource constraints. The contribution of this paper is twofold. First, we perform static analysis on the executables to extract their function calls in Android environment using the command readelf. Function call lists are compared with malware executables for classifying them with PART, Prism and Nearest Neighbor Algorithms. Second, we present a collaborative malware detection approach to extend these results. Corresponding simulation results are presented.

Framework for evaluating collaborative intrusion detection systems

Securing IT infrastructures of our modern lives is a challenging task because of their increasing complexity, scale and agile nature. Monolithic approaches such as using stand-alone firewalls and IDS devices for protecting the perimeter cannot cope with complex malwares and multistep attacks. Collaborative security emerges as a promising approach. But, research results in collaborative security are not mature, yet, and they require continuous evaluation and testing. In this work, we present CIDE, a Collaborative Intrusion Detection Extension for the network security simulation platform ( NeSSi 2 ). Built-in functionalities include dynamic group formation based on node preferences, group-internal communication, group management and an approach for handling the infection process for malware-based attacks. The CIDE simulation environment provides functionalities for easy implementation of collaborating nodes in large-scale setups. We evaluate the group communication mechanism on the one hand and provide a case study and evaluate our collaborative security evaluation platform in a signature exchange scenario on the other.

Monitoring android for collaborative anomaly detection : a first architectural draft

Our daily lives become more and more dependent upon smartphones due to their increased capabilities. Smartphones are used in various ways, e.g. for payment systems or assisting the lives of elderly or disabled people. Security threats for these devices become more and more dangerous since there is still a lack of proper security tools for protection. Android emerges as an open smartphone platform which allows modification even on operating system level and where third-party developers first time have the opportunity to develop kernel-based low-level security tools. Android quickly gained its popularity among smartphone developers and even beyond since it bases on Java on top of "open" Linux in comparison to former proprietary platforms which have very restrictive SDKs and corresponding APIs. Symbian OS, holding the greatest market share among all smartphone OSs, was even closing critical APIs to common developers and introduced application certification. This was done since this OS was the main target for smartphone malwares in the past. In fact, more than 290 malwares designed for Symbian OS appeared from July 2004 to July 2008. Android, in turn, promises to be completely open source. Together with the Linux-based smartphone OS OpenMoko, open smartphone platforms may attract malware writers for creating malicious applications endangering the critical smartphone applications and owners privacy. Since signature-based approaches mainly detect known malwares, anomaly-based approaches can be a valuable addition to these systems. They base on mathematical algorithms processing data that describe the state of a certain device. For gaining this data, a monitoring client is needed that has to extract usable information (features) from the monitored system. Our approach follows a dual system for analyzing these features. On the one hand, functionality for on-device light-weight detection is provided. But since most algorithms are resource exhaustive, remote feature analysis is provided on the other hand. Having this dual system enables event-based detection that can react to the current detection need. In our ongoing research we aim to investigates the feasibility of light-weight on-device detection for certain occasions. On other occasions, whenever significant changes are detected on the device, the system can trigger remote detection with heavy-weight algorithms for better detection results. In the absence of the server respectively as a supplementary approach, we also consider a collaborative scenario. Here, mobile devices sharing a common objective are enabled by a collaboration module to share information, such as intrusion detection data and results. This is based on an ad-hoc network mode that can be provided by a WiFi or Bluetooth adapter nearly every smartphone possesses.

Solving inherent problems of anomaly detection by cooperation

Anomaly detection compensates shortcomings of signature-based detection such as protecting against Zero-Day exploits. However, Anomaly Detection can be resource-intensive and is plagued by a high false-positive rate. In this work, we address these problems by presenting a Cooperative Intrusion Detection approach for the AIS, the Artificial Immune System, as an example for an anomaly detection approach. In particular we show, how the cooperative approach reduces the false-positive rate of the detection and how the overall detection process can be organized to account for the resource constraints of the participating devices. Evaluations are carried out with the novel network simulation environment NeSSi as well as formally with an extension to the epidemic spread model SIR

Multipurpose identity-based signcryption : a Swiss army knife for identity-based cryptography

Identity-Based (IB) cryptography is a rapidly emerging approach to public-key cryptography that does not require principals to pre-compute key pairs and obtain certificates for their public keys— instead, public keys can be arbitrary identifiers such as email addresses, while private keys are derived at any time by a trusted private key generator upon request by the designated principals. Despite the flurry of recent results on IB encryption and signature, some questions regarding the security and efficiency of practicing IB encryption (IBE) and signature (IBS) as a joint IB signature/encryption (IBSE) scheme with a common set of parameters and keys, remain unanswered. We first propose a stringent security model for IBSE schemes. We require the usual strong security properties of: (for confidentiality) indistinguishability against adaptive chosen-ciphertext attacks, and (for nonrepudiation) existential unforgeability against chosen-message insider attacks. In addition, to ensure as strong as possible ciphertext armoring, we also ask (for anonymity) that authorship not be transmitted in the clear, and (for unlinkability) that it remain unverifiable by anyone except (for authentication) by the legitimate recipient alone. We then present an efficient IBSE construction, based on bilinear pairings, that satisfies all these security requirements, and yet is as compact as pairing-based IBE and IBS in isolation. Our scheme is secure, compact, fast and practical, offers detachable signatures, and supports multirecipient encryption with signature sharing for maximum scalability.