A Monitoring System for the BaBar INFN Computing Cluster

Monitoring large clusters is a challenging problem. It is necessary to observe a large quantity of devices with a reasonably short delay between consecutive observations. The set of monitored devices may include PCs, network switches, tape libraries and other equipments. The monitoring activity should not impact the performances of the system. In this paper we present PerfMC, a monitoring system for large clusters. PerfMC is driven by an XML configuration file, and uses the Simple Network Management Protocol (SNMP) for data collection. SNMP is a standard protocol implemented by many networked equipments, so the tool can be used to monitor a wide range of devices. System administrators can display informations on the status of each device by connecting to a WEB server embedded in PerfMC. The WEB server can produce graphs showing the value of different monitored quantities as a function of time; it can also produce arbitrary XML pages by applying XSL Transformations to an internal XML representation of the cluster's status. XSL Transformations may be used to produce HTML pages which can be displayed by ordinary WEB browsers. PerfMC aims at being relatively easy to configure and operate, and highly efficient. It is currently being used to monitor the Italian Reprocessing farm for the BaBar experiment, which is made of about 200 dual-CPU Linux machines.Comment: Talk from the 2003 Computing in High Energy and Nuclear Physics (CHEP03), La Jolla, Ca, USA, March 2003, 10 pages, LaTeX, 4 eps figures. PSN MOET00

MR blockade protects against diet induced obesity, adipocyte dysfunction and cardiac inflammation in mice, through browning of the adipose organ and modulation of autophagy

Obesity is a key factor in the development of insulin resistance (IR), cardiovascular disease, hypertension, type 2 diabetes etc. Given the near epidemic incidence of obesity in western society there is a clear need for effective treatment options. Mineralocorticoid receptor (MR) blockade has shown significant promise in transgenic mouse models of obesity in limiting IR and adipocyte dysfunction, a disease that is independent of classical MR actions (renal). Female 10-weekold C57bl6 mice were fed with normal chow or a high fat (HF) diet for 12 weeks. Mice fed HF diet were concomitantly treated for 12 weeks with drospirenone (DRSP, 6 mg/kg/day), a potent MR antagonist with antiadipogenic activity, or spironolactone (SPIRO, 20 mg/kg/day). Mice fed HF diet showed a significant increase in total body weight, fat mass, mean adipocyte size, expression of white adipose tissue (WAT) marker genes and showed impaired glucose tolerance after intraperitoneal plasma glucose tolerance test. DRSP and SPIRO prevented weight gain and white fat mass expansion induced by HF diet in parametrial, perivescical, and inguinal depots without affecting interscapular fat pad weight. Magnetic Resonance Imaging (MRI) confirmed that MR antagonists blocked the HF dietdriven expansion of abdomino-pelvic (parametrial and perivescical) fat volume. High levels of MR mRNA were detected in all depots of adipose tissue. HF fed mice showed no increase in heart or kidney weight and tissue fibrosis. Cardiac macrophage recruitment and osteopontin staining was increased in hearts of HF fed mice and reversed by both MR antagonists. Moreover, both DRSP and SPIRO prevented the impaired glucose tolerance in mice fed HF diet, and countered HF diet-induced up-regulation of WAT markers transcripts and adipocyte hypertrophy. Importantly, MR antagonists increased uncoupling protein 1 (UCP-1) positive brown-like adipocyte content in WAT, and improved metabolic activity of adipose tissue, as indicated by PET/CT imaging. In keeping with this, MR antagonism significantly increased expression of brown-like adipocyte marker genes such PRDM16, CIDEA, beta-3 adrenergic receptor (ADRB3) and UCP-1 in all WAT depots analysed. In exploring the mechanism, we demonstrated that MR antagonism induced brown adipose tissue (BAT) markers, and reduced the autophagic rate, a key remodelling process in adipocyte differentiation, in WAT depots in vivo as well as in primary cultured adipocytes. We conclude that adipocyte MR regulates BAT-like remodeling of WAT through modulation of autophagy. MR blockade therefore has promise as a novel therapeutic option for the prevention of metabolic dysfunctions and the cardiac consequences of obesity. doi:10.1016/j.ijcme.2015.05.012 Transcriptional control of ICAM-1 in human coronary artery endothelial cells by Mineralocorticoid Receptor (MR): Implications for the protective effects of MR antagonists in cardiovascular diseases V. Marzolla, A. Armani, A. Fabbri, I.Z. Jaffe, M. Caprio Laboratory of Cardiovascular Endocrinology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Pisana, Rome, Italy Department of Medicina dei Sistemi, Endocrinology Unit, S. Eugenio & CTO A. Alesini Hospitals, University Tor Vergata, Rome, Italy Molecular Cardiology Research Institute, Tufts Medical Center, Boston

Essential role of ICAM-1 in aldosterone-induced atherosclerosis.

OBJECTIVE: Elevated aldosterone is associated with increased risk of atherosclerosis complications, whereas treatment with mineralocorticoid receptor (MR) antagonists decreases the rate of cardiovascular events. Here we test the hypothesis that aldosterone promotes early atherosclerosis by modulating intercellular adhesion molecule-1 (ICAM-1) expression and investigate the molecular mechanisms by which aldosterone regulates ICAM-1 expression. METHODS AND RESULTS: Apolipoprotein-E (ApoE)-/- mice fed an atherogenic diet and treated with aldosterone for 4weeks showed increased vascular expression of ICAM-1, paralleled by enhanced atherosclerotic plaque size in the aortic root. Moreover, aldosterone treatment resulted in increased plaque lipid and inflammatory cell content, consistent with an unstable plaque phenotype. ApoE/ICAM-1 double knockout (ApoE-/-/ICAM-1-/-) littermates were protected from the aldosterone-induced increase in plaque size, lipid content and macrophage infiltration. Since aldosterone is known to regulate ICAM-1 transcription via MR in human endothelial cells, we explored MR regulation of the ICAM-1 promoter. Luciferase reporter assays performed in HUVECs using deletion constructs of the human ICAM-1 gene promoter showed that a region containing a predicted MR-responsive element (MRE) is required for MR-dependent transcriptional regulation of ICAM-1. CONCLUSIONS: Pro-atherogenic effects of aldosterone are mediated by increased ICAM-1 expression, through transcriptional regulation by endothelial MR. These data enhance our understanding of the molecular mechanism by which MR activation promotes atherosclerosis complications

A Novel Mix of Polyphenols and Micronutrients Reduces Adipogenesis and Promotes White Adipose Tissue Browning via UCP1 Expression and AMPK Activation

Background: Obesity is a pandemic disease characterized by excessive severe body comorbidities. Reduction in fat accumulation represents a mechanism of prevention, and the replacement of white adipose tissue (WAT) with brown adipose tissue (BAT) has been proposed as one promising strategy against obesity. In the present study, we sought to investigate the ability of a natural mixture of polyphenols and micronutrients (A5(+)) to counteract white adipogenesis by promoting WAT browning. Methods: For this study, we employed a murine 3T3-L1 fibroblast cell line treated with A5(+), or DMSO as control, during the differentiation in mature adipocytes for 10 days. Cell cycle analysis was performed using propidium iodide staining and cytofluorimetric analysis. Intracellular lipid contents were detected by Oil Red O staining. Inflammation Array, along with qRT-PCR and Western Blot analyses, served to measure the expression of the analyzed markers, such as pro-inflammatory cytokines. Results: A5(+) administration significantly reduced lipids' accumulation in adipocytes when compared to control cells (p < 0.005). Similarly, A5(+) inhibited cellular proliferation during the mitotic clonal expansion (MCE), the most relevant stage in adipocytes differentiation (p < 0.0001). We also found that A5(+) significantly reduced the release of pro-inflammatory cytokines, such as IL-6 and Leptin (p < 0.005), and promoted fat browning and fatty acid oxidation through increasing expression levels of genes related to BAT, such as UCP1 (p < 0.05). This thermogenic process is mediated via AMPK-ATGL pathway activation. Conclusion: Overall, these results demonstrated that the synergistic effect of compounds contained in A5(+) may be able to counteract adipogenesis and then obesity by inducing fat browning

Antiviral activity of the mineralocorticoid receptor NR3C2 against Herpes simplex virus Type 1 (HSV-1) infection

Abstract Analysis of a genome-scale RNA interference screen of host factors affecting herpes simplex virus type 1 (HSV-1) revealed that the mineralocorticoid receptor (MR) inhibits HSV-1 replication. As a ligand-activated transcription factor the MR regulates sodium transport and blood pressure in the kidney in response to aldosterone, but roles have recently been elucidated for the MR in other cellular processes. Here, we show that the MR and other members of the mineralocorticoid signalling pathway including HSP90 and FKBP4, possess anti-viral activity against HSV-1 independent of their effect on sodium transport, as shown by sodium channel inhibitors. Expression of the MR is upregulated upon infection in an interferon (IFN) and viral transcriptional activator VP16-dependent fashion. Furthermore, the MR and VP16, together with the cellular co-activator Oct-1, transactivate the hormone response element (HRE) present in the MR promoter and those of its transcriptional targets. As the MR induces IFN expression, our data suggests the MR is involved in a positive feedback loop that controls HSV-1 infection

The Physics of the B Factories

This work is on the Physics of the B Factories. Part A of this book contains a brief description of the SLAC and KEK B Factories as well as their detectors, BaBar and Belle, and data taking related issues. Part B discusses tools and methods used by the experiments in order to obtain results. The results themselves can be found in Part C

Cellular mechanisms of MR regulation of adipose tissue physiology and pathophysiology

In addition to the well-documented expression and activity of the mineralocorticoid receptor (MR) in the kidney, in the last decade research on MR has also revealed its important role in regulating functions of extrarenal tissues, including adipose tissue, where MR is involved in adipocyte fundamental processes such as differentiation, autophagy and adipokine secretion. MR expression is increased in adipose tissue of murine models of obesity and in obese human subjects, suggesting that over-activation of the mineralocorticoid signaling leads to dysfunctional adipocyte and associated metabolic disorders. Notably, pharmacological blockade of MR prevents metabolic dysfunctions observed in obese mice and suggests a potential therapeutic use of MR antagonists in the treatment of obesity and metabolic syndrome. However, the molecular pathways affected by MR blockade have been poorly investigated. This review summarizes the functions of MR in the adipocyte, discusses potential signaling pathways mediating MR action, and describes post-translational modifications regulating its activity

GoPrime: a fully decentralized middleware for utility-aware service assembly

Modern applications, e.g., for pervasive computing scenarios, are increasingly reliant on systems built from multiple distributed components, which must be suitably composed to meet some specified functional and non-functional requirements. A key challenge is how to efficiently and effectively manage such complex systems. The use of self-management capabilities has been suggested as a possible way to address this challenge. To cope with the scalability and robustness issues of large distributed systems, self-management should ideally be architected in a decentralized way, where the overall system behavior emerges from local decisions and interactions. Within this context, we propose GOPRIME, a fully decentralized middleware solution for the adaptive self-assembly of distributed services. The GOPRIME goal is to build and maintain an assembly of services that, besides functional requirements, fulfils also global quality-of-service and structural requirements. The key aspect of GOPRIME is the use of a gossip protocol to achieve decentralized information dissemination and decision making. To show the validity of our approach, we present results from the experimentation of a prototype implementation of GOPRIME in a mobile health application, and an extensive set of simulation experiments that assess the effectiveness of GOPRIME in terms of scalability, robustness and convergence speed