A multi-dimensional hierarchical model methodology for autonomic computing system

Autonomic computing system is complex and expected to be self-managing. When designing autonomic computing system, we have to consider its special characteristics. To support the system design, collaborations, and semantic information understanding, this paper proposes a multi-dimensional hierarchical model methodology based on agent-oriented software engineering, to model the system from the design, organization and semantic dimensions. Design model adopts a hierarchical development method based on the component reusability. Organization model mainly study the relation web model to support complex collaborations. And semantic model make use of hierarchical ontology to support heterogeneous resource integration and policy conflicts resolution. The model methodology is efficient and systematic for complex system development. ?2010 IEEE.EI

A Self-Adaptive Mechanism for Software Configuration Based on Case-based Reasoning and Policy

Self-adaptive software expects the system to adapt its behaviors to environment changes. One main challenge is how to improve self-adaptation efficiency. In this paper case-based reasoning method is used to support the self-configuration case reuse which results in the configuration efficiency improvement. If there is no case to reuse directly, the policy-based technique is utilized to achieve the self-configuring plan. Moreover, the new generated configuration plan will be stored to the case repository for later reuse. This self-adaptive mechanism is more flexible and efficient which also is applicable to the self-optimizing, self-healing and selfprotecting etc. It has proved to be available and very helpful in software system self-configuration. ? 2010 IEEE.EI

Significant longevity-extending effects of EGCG on Caenorhabditis elegans under stress

Epigallocatechin gallate (EGCG), a main active ingredient of green tea, is believed to be beneficial in association with anticarcinogenesis, antiobesity, and blood pressure reduction. Here we report that EGCG extended Caenorhabditis elegans longevity under stress. Under heat stress (35 degrees C), EGCG improved the meal) longevity by 13.1% at 0.1 mu g/ml, 8.0% at 1.0 mu g/ml, and 11.8% at 10.0 mu g/ml. Under oxidative stress, EGCG could improve the mean longevity of C. elegans by 172.9% at 0.1 mu g/ml, 177.7% at 1.0 mu g/ml, and 88.5% at 10.0 mu g/ml. However, EGCG could not extend the life span of C. elegans under normal culture conditions. Further studies demonstrated that the significant longevity-extending effects of EGCG on C elegans could be attributed to its in vitro and in vivo free radical-scavenging effects and its up-regulating effects on stress-resistance-related proteins, including superoxide dismutase-3 (SOD-3) and heat shock protein-16.2 (HSP-16.2), in transgenic C elegans with SOD-3: :green fluorescent protein (GFP) and HSP-16.2: :GFP expression. Quantitative real-time PCR results showed that the up-regulation of aging-associated genes such as daf-16, sod-3, and skn-1 could also contribute to the stress resistance attributed to EGCG. As the death rate of a population is closely related to the mortality caused by external stress, it could be concluded that the survival-enhancing effects of EGCG on C. elegans under stress are very important for antiaging research.Epigallocatechin gallate (EGCG), a main active ingredient of green tea, is believed to be beneficial in association with anticarcinogenesis, antiobesity, and blood pressure reduction. Here we report that EGCG extended Caenorhabditis elegans longevity under stress. Under heat stress (35 degrees C), EGCG improved the meal) longevity by 13.1% at 0.1 mu g/ml, 8.0% at 1.0 mu g/ml, and 11.8% at 10.0 mu g/ml. Under oxidative stress, EGCG could improve the mean longevity of C. elegans by 172.9% at 0.1 mu g/ml, 177.7% at 1.0 mu g/ml, and 88.5% at 10.0 mu g/ml. However, EGCG could not extend the life span of C. elegans under normal culture conditions. Further studies demonstrated that the significant longevity-extending effects of EGCG on C elegans could be attributed to its in vitro and in vivo free radical-scavenging effects and its up-regulating effects on stress-resistance-related proteins, including superoxide dismutase-3 (SOD-3) and heat shock protein-16.2 (HSP-16.2), in transgenic C elegans with SOD-3: :green fluorescent protein (GFP) and HSP-16.2: :GFP expression. Quantitative real-time PCR results showed that the up-regulation of aging-associated genes such as daf-16, sod-3, and skn-1 could also contribute to the stress resistance attributed to EGCG. As the death rate of a population is closely related to the mortality caused by external stress, it could be concluded that the survival-enhancing effects of EGCG on C. elegans under stress are very important for antiaging research. (C) 2008 Elsevier Inc. All rights reserved

Treatment-induced arteriolar revascularization and miR-126 enhancement in bone marrow niche protect leukemic stem cells in AML

BackgroundDuring acute myeloid leukemia (AML) growth, the bone marrow (BM) niche acquires significant vascular changes that can be offset by therapeutic blast cytoreduction. The molecular mechanisms of this vascular plasticity remain to be fully elucidated. Herein, we report on the changes that occur in the vascular compartment of the FLT3-ITD+ AML BM niche pre and post treatment and their impact on leukemic stem cells (LSCs).MethodsBM vasculature was evaluated in FLT3-ITD+ AML models (MllPTD/WT/Flt3ITD/ITD mouse and patient-derived xenograft) by 3D confocal imaging of long bones, calvarium vascular permeability assays, and flow cytometry analysis. Cytokine levels were measured by Luminex assay and miR-126 levels evaluated by Q-RT-PCR and miRNA staining. Wild-type (wt) and MllPTD/WT/Flt3ITD/ITD mice with endothelial cell (EC) miR-126 knockout or overexpression served as controls. The impact of treatment-induced BM vascular changes on LSC activity was evaluated by secondary transplantation of BM cells after administration of tyrosine kinase inhibitors (TKIs) to MllPTD/WT/Flt3ITD/ITD mice with/without either EC miR-126 KO or co-treatment with tumor necrosis factor alpha (TNFα) or anti-miR-126 miRisten.ResultsIn the normal BM niche, CD31+Sca-1high ECs lining arterioles have miR-126 levels higher than CD31+Sca-1low ECs lining sinusoids. We noted that during FLT3-ITD+ AML growth, the BM niche lost arterioles and gained sinusoids. These changes were mediated by TNFα, a cytokine produced by AML blasts, which induced EC miR-126 downregulation and caused depletion of CD31+Sca-1high ECs and gain in CD31+Sca-1low ECs. Loss of miR-126high ECs led to a decreased EC miR-126 supply to LSCs, which then entered the cell cycle and promoted leukemia growth. Accordingly, antileukemic treatment with TKI decreased the BM blast-produced TNFα and increased miR-126high ECs and the EC miR-126 supply to LSCs. High miR-126 levels safeguarded LSCs, as shown by more severe disease in secondary transplanted mice. Conversely, EC miR-126 deprivation via genetic or pharmacological EC miR-126 knock-down prevented treatment-induced BM miR-126high EC expansion and in turn LSC protection.ConclusionsTreatment-induced CD31+Sca-1high EC re-vascularization of the leukemic BM niche may represent a LSC extrinsic mechanism of treatment resistance that can be overcome with therapeutic EC miR-126 deprivation