Towards self-protecting ubiquitous systems : monitoring trust-based interactions

The requirement for spontaneous interaction in ubiquitous computing creates security issues over and above those present in other areas of computing, deeming traditional approaches ineffective. As a result, to support secure collaborations entities must implement self-protective measures. Trust management is a solution well suited to this task as reasoning about future interactions is based on the outcome of past ones. This requires monitoring of interactions as they take place. Such monitoring also allows us to take corrective action when interactions are proceeding unsatisfactorily. In this vein, we first present a trust-based model of interaction based on event structures. We then describe our ongoing work in the development of a monitor architecture which enables self-protective actions to be carried out at critical points during principal interaction. Finally, we discuss some potential directions for future work

The suppression of DNA repair induced by PARP-1 inhibitors rucaparib and olaparib in combination with the radiopharmaceutical 131I-MIBG in noradrenaline transporter-expressing xenograft tumors

No abstract available

A formal model of trust lifecycle management

The rapid development of collaborative environments over the internet has highlighted new concerns over security and trust in such global computing systems. The global computing infrastructure poses an issue of uncertainty about the potential collaborators. Reaching a trusting decision in such environments encompasses both risk and trust assessments. While much work has been done in terms of modelling trust, the investigation of the management of trust lifecycle issues with consideration of both trust and risk is less examined. Our previous work addressed the dynamic aspects of trust lifecycle with a consideration of trust formation, exploitation, and evolution. In this paper we provide an approach for formalizing these aspects. As part of the formalization of the trust lifecycle,we introduce a notion of attraction to model the effect of new pieces of evidence on our opinion. The formalization described in this paper constitutes the basis of ongoing work to investigate the properties of the model

Security models for trusting network appliances

A significant characteristic of pervasive computing is the need for secure interactions between highly mobile entities and the services in their environment. Moreover,these decentralised systems are also characterised by partial views over the state of the global environment, implying that we cannot guarantee verification of the properties of the mobile entity entering an unfamiliar domain. Secure in this context encompasses both the need for cryptographic security and the need for trust, on the part of both parties, that the interaction is functioning as expected. In this paper we make a broad assumption that trust and cryptographic security can be considered as orthogonal concerns (i.e. cryptographic measures do not ensure transmission of correct information). We assume the existence of reliable encryption techniques and focus on the characteristics of a model that supports the management of the trust relationships between two devices during ad-hoc interactions

Trust dynamics for collaborative global computing

Recent advances in networking technology have increased the potential for dynamic enterprise collaborations between an open set of entities on a global scale. The security of these collaborations is a major concern, and requires novel approaches suited to this new environment to be developed. Trust management appears to be a promising approach. Due to the dynamic nature of these collaborations,dynamism in the formation, evolution and exploitation of trust is essential. In this paper we explore the properties of trust dynamics in this context. Trust is formed and evolves according to personal experience and recommendations. The properties of trust dynamics are expressed through a formal model of trust. Specific examples, based on an e-purse application scenario are used to demonstrate these properties

Peri-prostatic fat volume measurement as a predictive tool for castration resistance in advanced prostate cancer

Background: Obesity and aggressive prostate cancer (PC) may be linked, but how local peri-prostatic fat relates to tumour response following androgen deprivation therapy (ADT) is unknown. Objective: To test if peri-prostatic fat volume (PPFV) predicts tumour response to ADT. Design, setting, and participants: We performed a retrospective study on consecutive patients receiving primary ADT. From staging pelvic magnetic resonance imaging scans, the PPFV was quantified with OsirixX 6.5 imaging software. Statistical (univariate and multivariate) analysis were performed using R Version 3.2.1. Results and limitations: Of 224 consecutive patients, 61 with advanced (≥T3 or N1 or M1) disease had (3-mm high resolution axial sections) pelvic magnetic resonance imaging scan before ADT. Median age = 75 yr; median PPFV = 24.8 cm3 (range, 7.4–139.4 cm3). PPFV was significantly higher in patients who developed castration resistant prostate cancer (CRPC; n = 31), with a median of 37.9 cm3 compared with 16.1 cm3 (p < 0.0001, Wilcoxon rank sum test) in patients who showed sustained response to ADT (n = 30). Multivariate analysis using Cox proportional hazards models were performed controlling for known predictors of CRPC. PPFV was shown to be independent of all included factors, and the most significant predictor of time to CRPC. Using our multivariate model consisting of all known factors prior to ADT, PPFV significantly improved the area under the curve of the multivariate models receiver operating characteristic analysis. The main study limitation is a relatively small cohort to account for multiple variables, necessitating a future large-scale prospective analysis of PPFV in advanced PC. Conclusions: PPFV quantification in patients with advanced PC predicts tumour response to ADT

Pragmatic science? Reflections on the academic - industry interactions in a European aviation research programme

In this article we explore the types of science produced and disseminated in human factors research in the cognitive domain. We reflect on the methods and techniques used in the European, Horizon 2020 Future Sky Safety Project: Human Performance Envelope (P6). This project has spanned multiple research paradigms successfully, and engaged academia and research organizations throughout. We discuss the challenges of conducting practically focused work that can also be brought to publication in peer-reviewed journals. Finally, we frame our research contributions within this project using a model of practitioner engagement

Opposing effects of TIGAR- and RAC1-derived ROS on Wnt-driven proliferation in the mouse intestine

Reactive oxygen species (ROS) participate in numerous cell responses, including proliferation, DNA damage, and cell death. Based on these disparate activities, both promotion and inhibition of ROS have been proposed for cancer therapy. However, how the ROS response is determined is not clear. We examined the activities of ROS in a model of Apc deletion, where loss of the Wnt target gene Myc both rescues APC loss and prevents ROS accumulation. Following APC loss, Myc has been shown to up-regulate RAC1 to promote proliferative ROS through NADPH oxidase (NOX). However, APC loss also increased the expression of TIGAR, which functions to limit ROS. To explore this paradox, we used three-dimensional (3D) cultures and in vivo models to show that deletion of TIGAR increased ROS damage and inhibited proliferation. These responses were suppressed by limiting damaging ROS but enhanced by lowering proproliferative NOX-derived ROS. Despite having opposing effects on ROS levels, loss of TIGAR and RAC1 cooperated to suppress intestinal proliferation following APC loss. Our results indicate that the pro- and anti-proliferative effects of ROS can be independently modulated in the same cell, with two key targets in the Wnt pathway functioning to integrate the different ROS signals for optimal cell proliferation

The RNA-binding protein hnRNPA2 regulates β-catenin protein expression and is overexpressed in prostate cancer

The RNA-binding protein hnRNPA2 (HNRNPA2B1) is upregulated in cancer, where it controls alternative pre-mRNA splicing of cancer-relevant genes. Cytoplasmic hnRNPA2 is reported in aggressive cancers, but is functionally uncharacterized. We explored the role of hnRNPA2 in prostate cancer (PCa). Methods: hnRNPA2 function/localization/expression in PCa was determined using biochemical approaches (colony forming/proliferation/luciferase reporter assays/flow cytometry/immunohistocytochemistry). Binding of hnRNPA2 within cancer-relevant 3′-UTR mRNAs was identified by bioinformatics. Results: RNAi-mediated knockdown of hnRNPA2 reduced colony forming and proliferation, while hnRNPA2 overexpression increased proliferation of PCa cells. Nuclear hnRNPA2 is overexpressed in high-grade clinical PCa, and is also observed in the cytoplasm in some cases. Ectopic expression of a predominantly cytoplasmic variant hnRNPA2-ΔRGG also increased PCa cell proliferation, suggesting that cytoplasmic hnRNPA2 may also be functionally relevant in PCa. Consistent with its known cytoplasmic roles, hnRNPA2 was associated with 3′-UTR mRNAs of several cancer-relevant mRNAs including β-catenin (CTNNB1). Both wild-type hnRNPA2 and hnRNPA2-ΔRGG act on CTNNB1 3′-UTR mRNA, increasing endogenous CTNNB1 mRNA expression and β-catenin protein expression and nuclear localization. Conclusion: Nuclear and cytoplasmic hnRNPA2 are present in PCa and appear to be functionally important. Cytoplasmic hnRNPA2 may affect the cancer cell phenotype through 3′-UTR mRNA-mediated regulation of β-catenin expression and other cancer-relevant genes

AMP-activated protein kinase (AMPK) as a potential therapeutic target independent of PI3K/Akt signaling in prostate cancer

Depletion of cellular energy activates the AMP-activated protein kinase (AMPK) to favor energy-producing catabolic processes during tumorigenesis. Using a panel of in vitro cell lines and resected tumors, we investigated the therapeutic value of manipulating AMPK in prostate cancer (PC). Phospho-AMPK expression was significantly elevated in human PC cells and clinical PC samples. In clinical PC, we observed a trend for increasing phospho-AMPK with increasing Gleason sum score; Phospho-AMPK expression was associated with phospho-ACC (p=0.0023). Using the paired PC3 and PC3M cells to model progressive androgen-independent PC, treatment with either 5-aminoimidazole-4-carboxamide riboside (AICAR) or A-769662 suppressed proliferation, migration and invasion in both cell lines, and down-regulated mTOR and P70S6Ki levels regardless of the Akt status. Involvement of AMPK was confirmed by Compound C (AMPK inhibitor) and siRNA-mediated AMPK silencing. Despite similar functional responses in PC3 and PC3M cells, AMPK activation resulted in sustained phospho-Akt activation in PC3M cells, but not in PC3 cells. This prompted the addition of the PI3K inhibitor LY-294002 to AICAR treatment of PC3M cells in a proliferation assay. Interestingly, we found no synergistic effects upon combined treatment. Collectively, these findings support AMPK as a potential therapeutic target independent of PI3K/Akt signalling