Insulin increases De Novo Steroidogenesis in prostate cancer cells

Androgen-dependent pathways regulate maintenance and growth of normal and malignant prostate tissues. Androgen deprivation therapy (ADT) exploits this dependence and is used to treat metastatic prostate cancer; however, regression initially seen with ADT gives way to development of incurable castration-resistant prostate cancer (CRPC). Although ADT generates a therapeutic response, it is also associated with a pattern of metabolic alterations consistent with metabolic syndrome including elevated circulating insulin. Because CRPC cells are capable of synthesizing androgens de novo, we hypothesized that insulin may also influence steroidogenesis in CRPC. In this study, we examined this hypothesis by evaluating the effect of insulin on steroid synthesis in prostate cancer cell lines. Treatment with 10 nmol/L insulin increased mRNA and protein expression of steroidogenesis enzymes and upregulated the insulin receptor substrate insulin receptor substrate 2 (IRS-2). Similarly, insulin treatment upregulated intracellular testosterone levels and secreted androgens, with the concentrations of steroids observed similar to the levels reported in prostate cancer patients. With similar potency to dihydrotestosterone, insulin treatment resulted in increased mRNA expression of prostate-specific antigen. CRPC progression also correlated with increased expression of IRS-2 and insulin receptor in vivo. Taken together, our findings support the hypothesis that the elevated insulin levels associated with therapeutic castration may exacerbate progression of prostate cancer to incurable CRPC in part by enhancing steroidogenesis.

Next-generation sequencing of cervical DNA detects human papillomavirus types not detected by commercial kits

Background Human papillomavirus (HPV) is the aetiological agent for cervical cancer and genital warts. Concurrent HPV and HIV infection in the South African population is high. HIV positive (+) women are often infected with multiple, rare and undetermined HPV types. Data on HPV incidence and genotype distribution are based on commercial HPV detection kits, but these kits may not detect all HPV types in HIV + women. The objectives of this study were to (i) identify the HPV types not detected by commercial genotyping kits present in a cervical specimen from an HIV positive South African woman using next generation sequencing, and (ii) determine if these types were prevalent in a cohort of HIV-infected South African women. Methods Total DNA was isolated from 109 cervical specimens from South African HIV + women. A specimen within this cohort representing a complex multiple HPV infection, with 12 HPV genotypes detected by the Roche Linear Array HPV genotyping (LA) kit, was selected for next generation sequencing analysis. All HPV types present in this cervical specimen were identified by Illumina sequencing of the extracted DNA following rolling circle amplification. The prevalence of the HPV types identified by sequencing, but not included in the Roche LA, was then determined in the 109 HIV positive South African women by type-specific PCR. Results Illumina sequencing identified a total of 16 HPV genotypes in the selected specimen, with four genotypes (HPV-30, 74, 86 and 90) not included in the commercial kit. The prevalence's of HPV-30, 74, 86 and 90 in 109 HIV positive South African women were found to be 14.6 %, 12.8 %, 4.6 % and 8.3 % respectively. Conclusions Our results indicate that there are HPV types, with substantial prevalence, in HIV positive women not being detected in molecular epidemiology studies using commercial kits. The significance of these types in relation to cervical disease remains to be investigated.

IGF2 increases de novo steroidogenesis in prostate cancer cells

Androgen-dependent pathways regulate maintenance and growth of normal and malignant prostate tissues. Androgen deprivation therapy (ADT) exploits this dependence and is used to treat metastatic prostate cancer; however, regression initially seen with ADT gives way to development of incurable castration-resistant prostate cancer (CRPC). Although ADT generates a therapeutic response, it is also associated with a pattern of metabolic alterations consistent with metabolic syndrome including elevated circulating insulin. Because CRPC cells are capable of synthesizing androgens de novo, we hypothesized that insulin may also influence steroidogenesis in CRPC. In this study, we examined this hypothesis by evaluating the effect of insulin on steroid synthesis in prostate cancer cell lines. Treatment with 10 nmol/L insulin increased mRNA and protein expression of steroidogenesis enzymes and upregulated the insulin receptor substrate insulin receptor substrate 2 (IRS-2). Similarly, insulin treatment upregulated intracellular testosterone levels and secreted androgens, with the concentrations of steroids observed similar to the levels reported in prostate cancer patients. With similar potency to dihydrotestosterone, insulin treatment resulted in increased mRNA expression of prostate-specific antigen. CRPC progression also correlated with increased expression of IRS-2 and insulin receptor in vivo. Taken together, our findings support the hypothesis that the elevated insulin levels associated with therapeutic castration may exacerbate progression of prostate cancer to incurable CRPC in part by enhancing steroidogenesis.

Social innovation and social enterprise : evidence from Australia

‘Social innovation’ is a construct increasingly used to explain the practices, processes and actors through which sustained positive transformation occurs in the network society (Mulgan, G., Tucker, S., Ali, R., Sander, B. (2007). Social innovation: What it is, why it matters and how can it be accelerated. Oxford:Skoll Centre for Social Entrepreneurship; Phills, J. A., Deiglmeier, K., & Miller, D. T. Stanford Social Innovation Review, 6(4):34–43, 2008.). Social innovation has been defined as a “novel solution to a social problem that is more effective, efficient, sustainable, or just than existing solutions, and for which the value created accrues primarily to society as a whole rather than private individuals.” (Phills,J. A., Deiglmeier, K., & Miller, D. T. Stanford Social Innovation Review, 6 (4):34–43, 2008: 34.) Emergent ideas of social innovation challenge some traditional understandings of the nature and role of the Third Sector, as well as shining a light on those enterprises within the social economy that configure resources in novel ways. In this context, social enterprises – which provide a social or community benefit and trade to fulfil their mission – have attracted considerable policy attention as one source of social innovation within a wider field of action (see Leadbeater, C. (2007). ‘Social enterprise and social innovation: Strategies for the next 10 years’, Cabinet office,Office of the third sector http://www.charlesleadbeater.net/cms xstandard/social_enterprise_innovation.pdf. Last accessed 19/5/2011.). And yet, while social enterprise seems to have gained some symbolic traction in society, there is to date relatively limited evidence of its real world impacts.(Dart, R. Not for Profit Management and Leadership, 14(4):411–424, 2004.) In other words, we do not know much about the social innovation capabilities and effects of social enterprise. In this chapter, we consider the social innovation practices of social enterprise, drawing on Mulgan, G., Tucker, S., Ali, R., Sander, B. (2007). Social innovation: What it is, why it matters and how can it be accelerated. Oxford: Skoll Centre for Social Entrepreneurship: 5) three dimensions of social innovation: new combinations or hybrids of existing elements; cutting across organisational, sectoral and disciplinary boundaries; and leaving behind compelling new relationships. Based on a detailed survey of 365 Australian social enterprises, we examine their self-reported business and mission-related innovations, the ways in which they configure and access resources and the practices through which they diffuse innovation in support of their mission. We then consider how these findings inform our understanding of the social innovation capabilities and effects of social enterprise,and their implications for public policy development.

Polycaprolactone-based scaffold plus recombinant human bone morphogenic protein rhBMP-2) in a sheep thoracic spine fusion model

Adolescent idiopathic scoliosis is a complex three dimensional deformity affecting 2-3% of the general population. The resulting spinal deformity consists of coronal curvature, hypokyphosis of the thoracic spine and vertebral rotation in the axial plane with posterior elements turned into the curve concavity. The potential for curve progression is heightened during the adolescent growth spurt. Success of scoliosis deformity correction depends on solid bony fusion between adjacent vertebrae after the intervertebral (IV) discs have been surgically cleared and the disc spaces filled with graft material. Recently a bioactive and resorbable scaffold fabricated from medical grade polycaprolactone has been developed for bone regeneration at load bearing sites. Combined with rhBMP-2, this has been shown to be successful in acting as a bone graft substitute in a porcine lumbar interbody fusion model when compared to autologous bone graft alone. The study aimed to establish a large animal thoracic spine interbody fusion model, develop spine biodegradable scaffolds (PCL) in combination with biologics (rhBMP-2) and to establish a platform for research into spine tissue engineering constructs. Preliminary results demonstrate higher grades of radiologically evident bony fusion across all levels when comparing fusion scores between the 3 and 6 month postop groups at the PCL CaP coated scaffold level, which is observed to be a similar grade to autograft, while no fusion is seen at the scaffold only level. Results to date suggest that the combination of rhBMP-2 and scaffold engineering actively promotes bone formation, laying the basis of a viable tissue engineered constructs.

On the probability density function of the product of Rayleigh distributed random variables

In this paper we investigate the distribution of the product of Rayleigh distributed random variables. Considering the Mellin-Barnes inversion formula and using the saddle point approach we obtain an upper bound for the product distribution. The accuracy of this tail-approximation increases as the number of random variables in the product increase.

I sang Amazing Grace for about 3 hours that day : understanding Indigenous Australians’ experience of seclusion

Research shows that Indigenous Australians suspicion and fear of being ‘locked up’ may influence mental health service avoidance. Given this, the aim of this study was to explore, by qualitative analysis of in depth interviews (N = 3), how three Indigenous people experienced the controversial practice of seclusion Hans-Georg Gadamer’s phenomenology guided analysis of the material, and allowed narrated experiences to be understood within their cultural and historical context. Participants viewed seclusion negatively: police involvement in psychiatric care; perceptions of being punished and powerless; occasions of extreme use of force; and lack of care were prominent themes throughout the interviews. While power imbalances inherent in seclusion are problematic for all mental health clients, the distinguishing factor in the Indigenous clients’ experience is that seclusion is continuous with the discriminatory and degrading treatment by governments, police and health services that many Indigenous people have experienced since colonisation. The participants’ experiences echoed Goffman’s (1961) findings that institutional practices act to degrade and dehumanise clients whose resulting conformity eases the work of nursing staff. While some nurses perceive that seclusion reduces clients’ agitation (Meehan, Bergen & Fjeldsoe, 2004; Wynaden et al., 2001), one must ask at what cost to clients’ dignity, humanity and basic human rights.

Design of open source framework for traffic and travel simulation

For the evaluation, design, and planning of traffic facilities and measures, traffic simulation packages are the de facto tools for consultants, policy makers, and researchers. However, the available commercial simulation packages do not always offer the desired work flow and flexibility for academic research. In many cases, researchers resort to designing and building their own dedicated models, without an intrinsic incentive (or the practical means) to make the results available in the public domain. To make matters worse, a substantial part of these efforts pertains to rebuilding basic functionality and, in many respects, reinventing the wheel. This problem not only affects the research community but adversely affects the entire traffic simulation community and frustrates the development of traffic simulation in general. For this problem to be addressed, this paper describes an open source approach, OpenTraffic, which is being developed as a collaborative effort between the Queensland University of Technology, Australia; the National Institute of Informatics, Tokyo; and the Technical University of Delft, the Netherlands. The OpenTraffic simulation framework enables academies from geographic areas and disciplines within the traffic domain to work together and contribute to a specific topic of interest, ranging from travel choice behavior to car following, and from response to intelligent transportation systems to activity planning. The modular approach enables users of the software to focus on their area of interest, whereas other functional modules can be regarded as black boxes. Specific attention is paid to a standardization of data inputs and outputs for traffic simulations. Such standardization will allow the sharing of data with many existing commercial simulation packages.

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.

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.

Evaluation of Attacks and Countermeasures in Large Scale Networks

Computer worms represent a serious threat for modern communication infrastructures. These epidemics can cause great damage such as financial losses or interruption of critical services which support lives of citizens. These worms can spread with a speed which prevents instant human intervention. Therefore automatic detection and mitigation techniques need to be developed. However, if these techniques are not designed and intensively tested in realistic environments, they may cause even more harm as they heavily interfere with high volume communication flows. We present a simulation model which allows studies of worm spread and counter measures in large scale multi-AS topologies with millions of IP addresses.

From simulation to emulation : an integrated approach for network security evaluation

We present a virtual test bed for network security evaluation in mid-scale telecommunication networks. Migration from simulation scenarios towards the test bed is supported and enables researchers to evaluate experiments in a more realistic environment. We provide a comprehensive interface to manage, run and evaluate experiments. On basis of a concrete example we show how the proposed test bed can be utilized.

Developing and benchmarking native Linux applications on Android

Smartphones get increasingly popular where more and more smartphone platforms emerge. Special attention was gained by the open source platform Android which was presented by the Open Handset Alliance (OHA) hosting members like Google, Motorola, and HTC. Android uses a Linux kernel and a stripped-down userland with a custom Java VM set on top. The resulting system joins the advantages of both environments, while third-parties are intended to develop only Java applications at the moment. In this work, we present the benefit of using native applications in Android. Android includes a fully functional Linux, and using it for heavy computational tasks when developing applications can bring in substantional performance increase. We present how to develop native applications and software components, as well as how to let Linux applications and components communicate with Java programs. Additionally, we present performance measurements of native and Java applications executing identical tasks. The results show that native C applications can be up to 30 times as fast as an identical algorithm running in Dalvik VM. Java applications can become a speed-up of up to 10 times if utilizing JNI.

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.