Inferring affordances using learning techniques

Interoperability among heterogeneous systems is a key challenge in today’s networked environment, which is characterised by continual change in aspects such as mobility and availability. Automated solutions appear then to be the only way to achieve interoperability with the needed level of flexibility and scalability. While necessary, the techniques used to achieve interaction, working from the highest application level to the lowest protocol level, come at a substantial computational cost, especially when checks are performed indiscriminately between systems in unrelated domains. To overcome this, we propose to use machine learning to extract the high-level functionality of a system and thus restrict the scope of detailed analysis to systems likely to be able to interoperate

Intermediate CONNECT Architecture

Interoperability remains a fundamental challenge when connecting heterogeneous systems which encounter and spontaneously communicate with one another in pervasive computing environments. This challenge is exasperated by the highly heterogeneous technologies employed by each of the interacting parties, i.e., in terms of hardware, operating system, middleware protocols, and application protocols. The key aim of the CONNECT project is to drop this heterogeneity barrier and achieve universal interoperability. Here we report on the activities of WP1 into developing the CONNECT architecture that will underpin this solution. In this respect, we present the following key contributions from the second year. Firstly, the intermediary CONNECT architecture that presents a more concrete view of the technologies and principles employed to enable interoperability between heterogeneous networked systems. Secondly, the design and implementation of the discovery enabler with emphasis on the approaches taken to match compatible networked systems. Thirdly, the realisation of CONNECTors that can be deployed in the environment; we provide domain specific language solutions to generate and translate between middleware protocols. Fourthly, we highlight the role of ontologies within CONNECT and demonstrate how ontologies crosscut all functionality within the CONNECT architecture

Experiment scenarios, prototypes and report - Iteration 2

The task of WP6 is to evaluate the CONNECT technologies under realistic situations. To achieve this goal, WP6 concentrated its 3rd year effort on the development of a main scenario in the context of GMES, which requires the connection of highly heterogeneous and independently built systems provided by the industry partners. The resulting scenario allows the consortium to assess the validity of CONNECT claims and to investigate the exploitation of CONNECT technologies in the context of the integration of real systems. Another objective of this report is to provide a first assessment of CONNECT solutions against the project's objectives stated in the DoW. The proposed assessment spans: (i) the project's overall objective of enabling on-the-fly interoperability among heterogeneous networked systems as well as (ii) the project's specific objectives related to the foundations and associated enablers to be elaborated for learning and reasoning about the interaction behaviours of networked systems and for synthesizing mediators so as to make systems interoperate

Progesterone receptor modulates ERα action in breast cancer.

Progesterone receptor (PR) expression is used as a biomarker of oestrogen receptor-α (ERα) function and breast cancer prognosis. Here we show that PR is not merely an ERα-induced gene target, but is also an ERα-associated protein that modulates its behaviour. In the presence of agonist ligands, PR associates with ERα to direct ERα chromatin binding events within breast cancer cells, resulting in a unique gene expression programme that is associated with good clinical outcome. Progesterone inhibited oestrogen-mediated growth of ERα(+) cell line xenografts and primary ERα(+) breast tumour explants, and had increased anti-proliferative effects when coupled with an ERα antagonist. Copy number loss of PGR, the gene coding for PR, is a common feature in ERα(+) breast cancers, explaining lower PR levels in a subset of cases. Our findings indicate that PR functions as a molecular rheostat to control ERα chromatin binding and transcriptional activity, which has important implications for prognosis and therapeutic interventions.We would like to acknowledge the support of the University of Cambridge, Cancer Research UK and Hutchison Whampoa Limited. Research reported in this manuscript was supported by the National Cancer Institute of the National Institutes of Health under award number 5P30CA142543 (to UT Southwestern) and Department of Defense grants W81XWH-12-1-0288-03 (GVR). W.D.T. is supported by grants from the National Health and Medical Research Council of Australia (ID 1008349; ID 1084416) and Cancer Australia (ID 627229) T.E.H held a Fellowship Award from the US Department of Defense Breast Cancer Research Program (BCRP; #W81XWH-11-1-0592) and currently is supported by a Florey Fellowship from the Royal Adelaide Hospital Research Foundation. J.S.C is supported by an ERC starting grant and an EMBO Young investigator award.This is the accepted manuscript. The final version is available at www.nature.com/nature/journal/v523/n7560/full/nature14583.htm

Experiment Scenarios

The scenarios proposed in this deliverable are intended to identify the multiple dimensions of interoperability, and also foster further discussions with other work packages (WP1 to WP5). These will be refined and extended as the project progresses. The scenarios have been grouped into three computing domains: Ubiquitous computing, Daily life support and Telco Web 2.0 & Cloud Computing. Although the scenarios are partitioned into domains, they all have common properties such as the presence of disparate devices, a large proportion of peer-to-peer traffic and disparate interaction patterns

Final CONNECT Architecture

Interoperability remains a fundamental challenge when connecting heterogeneous systems which encounter and spontaneously communicate with one another in pervasive computing environments. This challenge is exasperated by the highly heterogeneous technologies employed by each of the interacting parties, i.e., in terms of hardware, operating system, middleware protocols, and application protocols. The key aim of the CONNECT project is to drop this heterogeneity barrier and achieve universal interoperability. Here we report on the revised CONNECT architecture, highlighting the integration of the work carried out to integrate the CONNECT enablers developed by the different partners; in particular, we present the progress of this work towards a finalised concrete architecture. In the third year this architecture has been enhanced to: i) produce concrete CONNECTors, ii) match networked systems based upon their goals and intent, and iii) use learning technologies to find the affordance of a system. We also report on the application of the CONNECT approach to streaming based systems, further considering exploitation of CONNECT in the mobile environment

Deliverable D6.4: Assessment report: Experimenting with CONNECT in Systems of Systems, and Mobile Environments

The core objective of WP6 is to evaluate the CONNECT technologies under realistic situations. To achieve this goal, WP6 concentrated a significant amount of its 4th year effort on the finalization of the implementation of the GMES scenario defined during the 3rd year. The GMES scenario allows the consortium to assess the validity of CONNECT claims and to investigate the exploitation of CONNECT technologies to deal with the integration of real systems. In particular, GMES requires the connection of highly heterogeneous and independently built systems provided by the industry partners. WP6 contributed also in providing mobile collaborative applications and case studies showing the exploitation of CONNECTORs on mobile devices

Revised CONNECT Architecture

Interoperability remains a fundamental challenge when connecting heterogeneous systems which encounter and spontaneously communicate with one another in pervasive computing environments. This challenge is exasperated by the highly heterogeneous technologies employed by each of the interacting parties, i.e., in terms of hardware, operating system, middleware protocols, and application protocols. The key aim of the CONNECT project is to drop this heterogeneity barrier and achieve universal interoperability. Here we report on the revised CONNECT architecture, highlighting the integration of the work carried out to integrate the CONNECT enablers developed by the different partners; in particular, we present the progress of this work towards a finalised concrete architecture. In the third year this architecture has been enhanced to: i) produce concrete CONNECTors, ii) match networked systems based upon their goals and intent, and iii) use learning technologies to find the affordance of a system. We also report on the application of the CONNECT approach to streaming based systems, further considering exploitation of CONNECT in the mobile environment

Dietary Curcuma, a Powerful Epigenome Modulator in Breast Cancer: an In Silico Study

The inhibition of DNA methyltransferase-1 enzyme can strongly decrease the capacity of cells to enhance the tumour-genesis process. Members of the Estrogen-Related Receptors family regulate several elements of cellular metabolism. These are orphan nuclear receptors that regulate a wide range of functional gene networks involved in breast carcinogenesis and the regulation of associated methionine and folate cycles, providing a proven direct relationship to DNA methylation as a result. Moreover, dietary phytochemicals, such as Curcumin, can involve epigenetic modification, which may decrease the development of many types of cancer, especially breast cancer in women. We conducted this study to investigate the effect of Curcuma (PubChem ID: 969516) on the epigenetic modification and inhibition of the DNA methyltransferase-1 (PDB ID: 3PTA) activity and Estrogen-Related Receptors (PDB ID: 1XB7) using Molecular docking approach and computational tools that may inform whether the Curcuma could provide this protective anticancer effect or not. Interestingly, the DNA methyltrasferase1-Curcumin and Estrogen-Related Receptors-Curcumin complexes display a docking score of -6.9 and -7.1 kcal/mol, respectively. Furthermore, Curcumin displays hydrogen, Pi-Cation, Pi-Anion and Van der Waals bonds with active site residues of the targeted molecules. By targeting DNA methylation via the combined inhibition of estrogen-related receptors and DNMT1, our research opens up a new therapeutic path for breast cancer treatment.Keywords: curcumin, breast cancer, epigenetic, molecular docking, treatment

Epidemiological profile and distribution of prognostic factors in invasive breast cancer among Algerian women

Although the widespread of early screening and advanced medical therapies, the breast cancer incidence rate continues to rise among Algerian women. This retrospective study investigated mammary lesions’ epidemiological profile and histopathological characteristics and evaluated primary invasive breast cancer prognostic factors. We found that the incidence of breast cancer increases in middle- aged women between 40 and 60 years. Scarff Bloom Richardson grade II predominates in invasive breast cancer samples. In this study, molecular profiling shows that 82.1% of invasive tumours are hormone receptor-positive. A significant correlation is observed between the age of the patient and the SBR grade (p = 0.001) and with the hormone receptor expression (p = 0.001). In addition, the tumour grade is significantly correlated to oestrogen and progesterone receptor expression (p = 0.000; p = 0.000, respectively). Twenty-two per cent of cases were human epidermal growth factor receptor 2-positive. The Ki-67 proliferation index is expressed in 91% of breast cancer patients and was significantly associated with Scarff Bloom Richardson grade (p = 0.030), the progesterone receptor expression (p = 0.029) and with human epidermal growth factor receptor 2-positivity (p = 0.023). Primary breast cancer with a high grade is more frequent (31%) in young women under 40 years old, presenting 17% of our population. In summary, breast cancer patients in Algeria develop an unfavourable profile. Immunohistochemistry assay has played a pivotal role in assessing breast cancer predictive biomarkers improving the tumour behaviour and response to treatment