A trigger-based middleware cache for ORMs

ACM/IFIP/USENIX 12th International Middleware Conference, Lisbon, Portugal, December 12-16, 2011. ProceedingsCaching is an important technique in scaling storage for high-traffic web applications. Usually, building caching mechanisms involves significant effort from the application developer to maintain and invalidate data in the cache. In this work we present CacheGenie, a caching middleware which makes it easy for web application developers to use caching mechanisms in their applications. CacheGenie provides high-level caching abstractions for common query patterns in web applications based on Object-RelationalMapping (ORM) frameworks. Using these abstractions, the developer does not have to worry about managing the cache (e.g., insertion and deletion) or maintaining consistency (e.g., invalidation or updates) when writing application code. We design and implement CacheGenie in the popular Django web application framework, with PostgreSQL as the database backend and memcached as the caching layer. To automatically invalidate or update cached data, we use triggers inside the database. CacheGenie requires no modifications to PostgreSQL or memcached. To evaluate our prototype, we port several Pinax web applications to use our caching abstractions. Our results show that it takes little effort for application developers to use CacheGenie, and that CacheGenie improves throughput by 2-2.5× for read-mostly workloads in Pinax.Quanta Computer (Firm

Distributed Ledger for Provenance Tracking of Artificial Intelligence Assets

High availability of data is responsible for the current trends in Artificial Intelligence (AI) and Machine Learning (ML). However, high-grade datasets are reluctantly shared between actors because of lacking trust and fear of losing control. Provenance tracing systems are a possible measure to build trust by improving transparency. Especially the tracing of AI assets along complete AI value chains bears various challenges such as trust, privacy, confidentiality, traceability, and fair remuneration. In this paper we design a graph-based provenance model for AI assets and their relations within an AI value chain. Moreover, we propose a protocol to exchange AI assets securely to selected parties. The provenance model and exchange protocol are then combined and implemented as a smart contract on a permission-less blockchain. We show how the smart contract enables the tracing of AI assets in an existing industry use case while solving all challenges. Consequently, our smart contract helps to increase traceability and transparency, encourages trust between actors and thus fosters collaboration between them

Anticancer efficacy of the hypoxia-activated prodrug evofosfamide (TH-302) in osteolytic breast cancer murine models

Tumor hypoxia is a major cause of treatment failure for a variety of malignancies. However, hypoxia offers treatment opportunities, exemplified by the development of compounds that target hypoxic regions within tumors. Evofosfamide (TH-302) is a prodrug created by the conjugation of 2-nitroimidazole to bromo-isophosphoramide mustard (Br-IPM). When evofosfamide is delivered to hypoxic regions, the DNA cross-linking effector, Br-IPM, is released. This study assessed the cytotoxic activity of evofosfamide in vitro and its antitumor activity against osteolytic breast cancer either alone or in combination with paclitaxel in vivo. A panel of human breast cancer cell lines were treated with evofosfamide under hypoxia and assessed for cell viability. Osteolytic MDA-MB-231-TXSA cells were transplanted into the mammary fat pad, or into tibiae of mice, allowed to establish and treated with evofosfamide, paclitaxel, or both. Tumor burden was monitored using bioluminescence, and cancer-induced bone destruction was measured using micro-CT. In vitro, evofosfamide was selectively cytotoxic under hypoxic conditions. In vivo evofosfamide was tumor suppressive as a single agent and cooperated with paclitaxel to reduce mammary tumor growth. Breast cancer cells transplanted into the tibiae of mice developed osteolytic lesions. In contrast, treatment with evofosfamide or paclitaxel resulted in a significant delay in tumor growth and an overall reduction in tumor burden in bone, whereas combined treatment resulted in a significantly greater reduction in tumor burden in the tibia of mice. Evofosfamide cooperates with paclitaxel and exhibits potent tumor suppressive activity against breast cancer growth in the mammary gland and in bone.Vasilios Liapis, Irene Zinonos, Agatha Labrinidis, Shelley Hay, Vladimir Ponomarev, Vasilios Panagopoulos, Aneta Zysk, Mark DeNichilo, Wendy Ingman, Gerald J. Atkins, David M. Findlay, Andrew C. W. Zannettino, Andreas Evdokio

Bone marrow lesions detected by specific combination of MRI sequences are associated with severity of osteochondral degeneration

Background: Bone marrow lesions (BMLs) are useful diagnostic and prognostic markers in knee osteoarthritis (OA), but what they represent at the tissue level remains unclear. The aim of this study was to provide comprehensive tissue characterization of BMLs detected using two specific MRI sequences. Methods: Tibial plateaus were obtained from 60 patients (29 females, 31 males), undergoing knee arthroplasty for OA. To identify BMLs, MRI was performed ex vivo using T1 and PDFS-weighted sequences. Multi-modal tissue level analyses of the osteochondral unit (OCU) were performed, including cartilage volume measurement, OARSI grading, micro-CT analysis of bone microstructure, routine histopathological assessment and quantitation of bone turnover indices.Results: BMLs were detected in 74 % of tibial plateaus, the remainder comprising a No BML group. Of all BMLs, 59 % were designated BML 1 (detected only by PDFS) and 41 % were designated BML 2 (detected by both PDFS + T1). The presence of a BML was related to degeneration of the OCU, particularly within BML 2. When compared to No BML, BML 2 showed reduced cartilage volume (p = 0.008), higher OARSI scores (p = 0.004), thicker subchondral plate (p = 0.002), increased trabecular bone volume and plate-like structure (p = 0.0004), increased osteoid volume (p = 0.002) and thickness (p = 0.003), more bone marrow oedema (p = 0.03), fibrosis (p = 0.002), necrosis (p = 0.01) and fibrovascular cysts (p = 0.04). For most measures, BML 1 was intermediate between No BML and BML 2. Conclusions: BMLs detected by specific MRI sequences identify different degrees of degeneration in the OCU. This suggests that MRI characteristics of BMLs may enable identification of different BML phenotypes and help target novel approaches to treatment and prevention of OA.Dzenita Muratovic, Flavia Cicuttini, Anita Wluka, David Findlay, Yuanyuan Wang, Sophia Otto, David Taylor, Julia Humphries, Yearin Lee, Agatha Labrinidis, Ruth Williams and Julia Kuliwab

Progressive resistance of BTK-143 osteosarcoma cells to Apo2L/TRAIL-induced apoptosis is mediated by acquisition of DcR2/TRAIL-R4 expression: resensitisation with chemotherapy

© 2003 Cancer Research UKApo2 ligand (Apo2L, also known as TRAIL) is a member of the tumour necrosis factor (TNF) family of cytokines that selectively induces the death of cancer cells, but not of normal cells. We observed that recombinant Apo2L/TRAIL was proapoptotic in early-passage BTK-143 osteogenic sarcoma cells, inducing 80% cell death during a 24 h treatment period. Apo2L/TRAIL-induced apoptosis was blocked by caspase inhibition. With increasing passage in culture, BTK-143 cells became progressively resistant to the apoptotic effects of Apo2L/TRAIL . RNA and flow cytometric analysis demonstrated that resistance to Apo2L/TRAIL was paralleled by progressive acquisition of the decoy receptor, DcR2. Blocking of DcR2 function with a specific anti-DcR2 antibody restored sensitivity to Apo2L/TRAIL in a dose-dependent manner. Importantly, treatment of resistant cells with the chemotherapeutic agents doxorubicin, cisplatin and etoposide reversed the resistance to Apo2L/TRAIL, which was associated with drug-induced upregulation of mRNA encoding the death receptors DR4 and DR5. BTK-143 cells thus represent a useful model system to investigate both the mechanisms of acquisition of resistance of tumour cells to Apo2L/TRAIL and the use of conventional drugs and novel agents to overcome resistance to Apo2L/TRAIL.S Bouralexis, D M Findlay, G J Atkins, A Labrinidis, S Hay & A Evdokio

Big data-driven fuzzy cognitive map for prioritising IT service procurement in the public sector

YesThe prevalence of big data is starting to spread across the public and private sectors however, an impediment to its widespread adoption orientates around a lack of appropriate big data analytics (BDA) and resulting skills to exploit the full potential of big data availability. In this paper, we propose a novel BDA to contribute towards this void, using a fuzzy cognitive map (FCM) approach that will enhance decision-making thus prioritising IT service procurement in the public sector. This is achieved through the development of decision models that capture the strengths of both data analytics and the established intuitive qualitative approach. By taking advantages of both data analytics and FCM, the proposed approach captures the strength of data-driven decision-making and intuitive model-driven decision modelling. This approach is then validated through a decision-making case regarding IT service procurement in public sector, which is the fundamental step of IT infrastructure supply for publics in a regional government in the Russia federation. The analysis result for the given decision-making problem is then evaluated by decision makers and e-government expertise to confirm the applicability of the proposed BDA. In doing so, demonstrating the value of this approach in contributing towards robust public decision-making regarding IT service procurement.EU FP7 project Policy Compass (Project No. 612133

Tracking human multiple myeloma xenografts in NOD-Rag-1/IL-2 receptor gamma chain-null mice with the novel biomarker AKAP-4

<p>Abstract</p> <p>Background</p> <p>Multiple myeloma (MM) is a fatal malignancy ranking second in prevalence among hematological tumors. Continuous efforts are being made to develop innovative and more effective treatments. The preclinical evaluation of new therapies relies on the use of murine models of the disease.</p> <p>Methods</p> <p>Here we describe a new MM animal model in NOD-Rag1null IL2rgnull (NRG) mice that supports the engraftment of cell lines and primary MM cells that can be tracked with the tumor antigen, AKAP-4.</p> <p>Results</p> <p>Human MM cell lines, U266 and H929, and primary MM cells were successfully engrafted in NRG mice after intravenous administration, and were found in the bone marrow, blood and spleen of tumor-challenged animals. The AKAP-4 expression pattern was similar to that of known MM markers, such as paraproteins, CD38 and CD45.</p> <p>Conclusions</p> <p>We developed for the first time a murine model allowing for the growth of both MM cell lines and primary cells in multifocal sites, thus mimicking the disease seen in patients. Additionally, we validated the use of AKAP-4 antigen to track tumor growth <it>in vivo </it>and to specifically identify MM cells in mouse tissues. We expect that our model will significantly improve the pre-clinical evaluation of new anti-myeloma therapies.</p