60 research outputs found

    Service workload patterns for QoS-driven cloud resource management

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    Cloud service providers negotiate SLAs for customer services they offer based on the reliability of performance and availability of their lower-level platform infrastructure. While availability management is more mature, performance management is less reliable. In order to support a continuous approach that supports the initial static infrastructure configuration as well as dynamic reconfiguration and auto-scaling, an accurate and efficient solution is required. We propose a prediction technique that combines a workload pattern mining approach with a traditional collaborative filtering solution to meet the accuracy and efficiency requirements. Service workload patterns abstract common infrastructure workloads from monitoring logs and act as a part of a first-stage high-performant configuration mechanism before more complex traditional methods are considered. This enhances current reactive rule-based scalability approaches and basic prediction techniques by a hybrid prediction solution. Uncertainty and noise are additional challenges that emerge in multi-layered, often federated cloud architectures. We specifically add log smoothing combined with a fuzzy logic approach to make the prediction solution more robust in the context of these challenges

    Estrogen receptor transcription and transactivation: Estrogen receptor alpha and estrogen receptor beta - regulation by selective estrogen receptor modulators and importance in breast cancer

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    Estrogens display intriguing tissue-selective action that is of great biomedical importance in the development of optimal therapeutics for the prevention and treatment of breast cancer, for menopausal hormone replacement, and for fertility regulation. Certain compounds that act through the estrogen receptor (ER), now referred to as selective estrogen receptor modulators (SERMs), can demonstrate remarkable differences in activity in the various estrogen target tissues, functioning as agonists in some tissues but as antagonists in others. Recent advances elucidating the tripartite nature of the biochemical and molecular actions of estrogens provide a good basis for understanding these tissue-selective actions. As discussed in this thematic review, the development of optimal SERMs should now be viewed in the context of two estrogen receptor subtypes, ERα and ERβ, that have differing affinities and responsiveness to various SERMs, and differing tissue distribution and effectiveness at various gene regulatory sites. Cellular, biochemical, and structural approaches have also shown that the nature of the ligand affects the conformation assumed by the ER-ligand complex, thereby regulating its state of phosphorylation and the recruitment of different coregulator proteins. Growth factors and protein kinases that control the phosphorylation state of the complex also regulate the bioactivity of the ER. These interactions and changes determine the magnitude of the transcriptional response and the potency of different SERMs. As these critical components are becoming increasingly well defined, they provide a sound basis for the development of novel SERMs with optimal profiles of tissue selectivity as medical therapeutic agents

    Blood Glucose Levels Regulate Pancreatic β-Cell Proliferation during Experimentally-Induced and Spontaneous Autoimmune Diabetes in Mice

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    Type 1 diabetes mellitus is caused by immune-mediated destruction of pancreatic beta-cells leading to insulin deficiency, impaired intermediary metabolism, and elevated blood glucose concentrations. While at autoimmune diabetes onset a limited number of beta-cells persist, the cells' regenerative potential and its regulation have remained largely unexplored. Using two mouse autoimmune diabetes models, this study examined the proliferation of pancreatic islet ss-cells and other endocrine and non-endocrine subsets, and the factors regulating that proliferation.We adapted multi-parameter flow cytometry techniques (including DNA-content measurements and 5'-bromo-2'-deoxyuridine [BrdU] incorporation) to study pancreatic islet single cell suspensions. These studies demonstrate that beta-cell proliferation rapidly increases at diabetes onset, and that this proliferation is closely correlated with the diabetic animals' elevated blood glucose levels. For instance, we show that when normoglycemia is restored by exogenous insulin or islet transplantation, the beta-cell proliferation rate returns towards low levels found in control animals, yet surges when hyperglycemia recurs. In contrast, other-than-ss endocrine islet cells did not exhibit the same glucose-dependent proliferative responses. Rather, disease-associated alterations of BrdU-incorporation rates of delta-cells (minor decrease), and non-endocrine islet cells (slight increase) were not affected by blood glucose levels, or were inversely related to glycemia control after diabetes onset (alpha-cells).We conclude that murine beta-cells' ability to proliferate in response to metabolic need (i.e. rising blood glucose concentrations) is remarkably well preserved during severe, chronic beta-cell autoimmunity. These data suggest that timely control of the destructive immune response after disease manifestation could allow spontaneous regeneration of sufficient beta-cell mass to restore normal glucose homeostasis

    Myocyte membrane and microdomain modifications in diabetes: determinants of ischemic tolerance and cardioprotection

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    Antimalarial activity and clinical safety of traditionally used Nyctanthes arbor-tristis Linn.

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    330-334Traditional systems of medicine, such as Ayurveda and Chinese medicine in Asia have been provided novel concepts and modalities for healthcare. Critical bedside observations by astute physicians have been followed up by systematic trans-disciplinary research. Such clinical hits of novel biodynamic actions can lead to new drug candidates. In the study, this path was taken up to document antimalarial activity of Nyctanthes arbor-tristis Linn. (Parijat). Nyctanthes arbor-tristis Linn., a popular plant with fragrant flowers described in Ayurveda is being sporadically used for malaria by several Ayurvedic physicians. Patients with malaria were treated with the paste of five fresh leaves of Nyctanthes arbor-tristis Linn, Given orally three times in a day for 7-10 days. The relief of symptoms and signs of malaria and the features of Visham jwara were graded basally and daily. Of 120 patients, ninety two (76.7%) showed complete clinical and parasitic cure within 7 days. Other 20 patients, who then continued on the same treatment, were cured by 10 days. Those patients who did not respond clinically and by parasite clearance were treated with standard antimalarial therapy. Parasite clearance was gradual and showed a direct temporal relationship with the level of initial parasitemia. The paste was well tolerated and no severe side effects were reported. Nyctanthes arbor-tristis Linn, with the dose used showed significant clinical antimalarial activity and good tolerability. A standardized formulation has to be prepared for further studies with critical markers of disease severity as well as parasite clearance

    Psychopathology, trauma and delinquency: subtypes of aggression and their relevance for understanding young offenders

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    OBJECTIVE: To examine the implications of an ontology of aggressive behavior which divides aggression into reactive, affective, defensive, impulsive (RADI) or "emotionally hot"; and planned, instrumental, predatory (PIP) or "emotionally cold." Recent epidemiological, criminological, clinical and neuroscience studies converge to support a connection between emotional and trauma related psychopathology and disturbances in the emotions, self-regulation and aggressive behavior which has important implications for diagnosis and treatment, especially for delinquent populations. METHOD: Selective review of preclinical and clinical studies in normal, clinical and delinquent populations. RESULTS: In delinquent populations we observe an increase in psychopathology, and especially trauma related psychopathology which impacts emotions and self-regulation in a manner that hotly emotionally charged acts of aggression become more likely. The identification of these disturbances can be supported by findings in cognitive neuroscience. These hot aggressive acts can be delineated from planned or emotionally cold aggression. CONCLUSION: Our findings support a typology of diagnostic labels for disruptive behaviors, such as conduct disorder and oppositional defiant disorder, as it appears that these acts of hot emotional aggression are a legitimate target for psychopharmacological and other trauma specific interventions. The identification of this subtype of disruptive behavior disorders leads to more specific clinical interventions which in turn promise to improve hitherto unimpressive treatment outcomes of delinquents and patients with disruptive behavior
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