On autonomic platform-as-a-service: characterisation and conceptual model

In this position paper, we envision a Platform-as-a-Service conceptual and architectural solution for large-scale and data intensive applications. Our architectural approach is based on autonomic principles, therefore, its ultimate goal is to reduce human intervention, the cost, and the perceived complexity by enabling the autonomic platform to manage such applications itself in accordance with highlevel policies. Such policies allow the platform to (i) interpret the application specifications; (ii) to map the specifications onto the target computing infrastructure, so that the applications are executed and their Quality of Service (QoS), as specified in their SLA, enforced; and, most importantly, (iii) to adapt automatically such previously established mappings when unexpected behaviours violate the expected. Such adaptations may involve modifications in the arrangement of the computational infrastructure, i.e. by re-designing a different communication network topology that dictates how computational resources interact, or even the live-migration to a different computational infrastructure. The ultimate goal of these challenges is to (de)provision computational machines, storage and networking links and their required topologies in order to supply for the application the virtualised infrastructure that better meets the SLAs. Generic architectural blueprints and principles have been provided for designing and implementing an autonomic computing system.We revisit them in order to provide a customised and specific viewfor PaaS platforms and integrate emerging paradigms such as DevOps for automate deployments, Monitoring as a Service for accurate and large-scale monitoring, or well-known formalisms such as Petri Nets for building performance models

p53 Aberrations do not predict individual response to fludarabine in patients with B-cell chronic lymphocytic leukaemia in advanced stages Rai III/IV

Abnormalities of p53 have been associated with short survival and non-response to therapy in chronic lymphocytic leukaemia (CLL). We have evaluated the rate of response to fludarabine as first-line therapy in 54 patients with advanced stage CLL, analysing the cytogenetic profile, aberrations in p53, including the methylation status of its promoter, and the immunoglobulin heavy-chain variable-region (IGVH) mutation status. According to the advanced stage of the disease in this series, 75% of patients presented genetic aberrations associated with poor prognosis: del(17p) and/or del(11q), and no-mutated IGVH genes. Ten patients (18.5%) had methylation in the promoter region of p53. Eighty-three per cent of patients treated achieved a response, with a high rate of complete remission (47.6%). Although we found a significant correlation between failures and the presence of p53 aberrations (P = 0.0065), either with methylation (P = 0.018) or deletion (P = 0.015), 64% of the patients with aberrations in this gene responded to treatment (11/17), suggesting that fludarabine induces high remission rates, even in these patients. This is the first time that the significance of p53 promoter methylation status is described in this pathology, and our data support that this epigenetic phenomenon could be involved in the pathogenesis and clinical evolution of CLL

Promoter hypermethylation of cancer-related genes: a strong independent prognostic factor in acute lymphoblastic leukemia

Promoter hypermethylation plays an important role in the inactivation of cancerrelated genes. This abnormality occurs early in leukemogenesis and seems to be associated with poor prognosis in acute lymphoblastic leukemia (ALL). To determine the extent of hypermethylation in ALL, we analyzed the methylation status of the CDH1, p73, p16, p15, p57, NES-1, DKK-3, CDH13, p14, TMS-1, APAF-1, DAPK, PARKIN, LATS-1, and PTEN genes in 251 consecutive ALL patients.Atotal of 77.3% of samples had at least 1 gene methylated, whereas 35.9% of cases had 4 or more genes methylated. Clinical features and complete remission rate did not differ among patients without methylated genes, patients with 1 to 3 methylated genes (methylated group A), or patients with more than 3 methylated genes (methylated group B). Estimated disease-free survival (DFS) and overall survival (OS) at 11 years were 75.5% and 66.1%, respectively, for the nonmethylated group; 37.2% and 45.5% for methylated group A; and 9.4% and 7.8% for methylated group B (P < .0001 and P .0004, respectively). Multivariate analysis demonstrated that the methylation profile was an independent prognostic factor in predicting DFS (P < .0001) and OS (P .003). Our results suggest that the methylation profile may be a potential new biomarker of risk prediction in AL