Measuring performances of linux hypervisors

Virtualization is a now proven software technology that is rapidly transforming the IT landscape and fundamentally changing the way people make computations and implement services. Recently, all major software producers (e.g., Microsoft and RedHat) developed or acquired virtualization technologies. Our institute (http://www.cnaf.infn.it) is a Tier1 for experiments carried on at the Large Hadron Collider at CERN (http://lhc.web.cern.ch/lhc/) and is experiencing several benefits from virtualization technologies, like improving fault tolerance, providing efficient hardware resource usage and increasing security. Currently, the virtualization solution we adopted is xen, which is well supported by the Scientific Linux distribution, widely used by the High-Energy Physics (HEP) community. Since Scientific Linux is based on RedHat ES, we felt the need to investigate performances and usability differences with the new kvm technology, recently acquired by RedHat. The case study of this work is the Tier2 site for the LHCb experiment hosted at our institute; all major grid elements for this Tier2 run on xen virtual machines smoothly. We will investigate the impact on performance and stability that a migration to kvm would entail on the Tier2 site, as well as the effort required by a system administrator to deploy the migration

Alcohol-abuse drug disulfiram targets pediatric glioma via MLL degradation

Pediatric gliomas comprise a broad range of brain tumors derived from glial cells. While high-grade gliomas are often resistant to therapy and associated with a poor outcome, children with low-grade gliomas face a better prognosis. However, the treatment of low-grade gliomas is often associated with severe long-term adverse effects. This shows that there is a strong need for improved treatment approaches. Here, we highlight the potential for repurposing disulfiram to treat pediatric gliomas. Disulfiram is a drug used to support the treatment of chronic alcoholism and was found to be effective against diverse cancer types in preclinical studies. Our results show that disulfiram efficiently kills pediatric glioma cell lines as well as patient-derived glioma stem cells. We propose a novel mechanism of action to explain disulfiram’s anti-oncogenic activities by providing evidence that disulfiram induces the degradation of the oncoprotein MLL. Our results further reveal that disulfiram treatment and MLL downregulation induce similar responses at the level of histone modifications and gene expression, further strengthening that MLL is a key target of the drug and explaining its anti-oncogenic properties

Field-free all-optical switching and electrical read-out of Tb/Co-based magnetic tunnel junctions

Switching of magnetic tunnel junction using femto-second laser enables a possible path for THz frequency memory operation, which means writing speeds 2 orders of magnitude faster than alternative electrical approaches based on spin transfer or spin orbit torque. In this work we demonstrate successful field-free 50fs single laser pulse driven magnetization reversal of [Tb/Co] based storage layer in a perpendicular magnetic tunnel junction. The nanofabricated magnetic tunnel junction devices have an optimized bottom reference electrode and show Tunnel Magnetoresistance Ratio values (TMR) up to 74\% after patterning down to sub-100nm lateral dimensions. Experiments on continuous films reveal peculiar reversal patterns of concentric rings with opposite magnetic directions, above certain threshold fluence. These rings have been correlated to patterned device switching probability as a function of the applied laser fluence. Moreover, the magnetization reversal is independent on the duration of the laser pulse. According to our macrospin model, the underlying magnetization reversal mechanism can be attributed to an in-plane reorientation of the magnetization due to a fast reduction of the out-of-plane uniaxial anisotropy. These aspects are of great interest both for the physical understanding of the switching phenomenon and their consequences for all-optical-switching memory devices, since they allow for a large fluence operation window with high resilience to pulse length variability

Effetto del genotipo e del trattamento antipiralide sulla contaminazione da specie afferenti al clade Gibberella fujikuroi in mais coltivato in Lombardia

Fusarium ear rot (FER) of maize is caused by Fusarium species belonging to Gibberella fujikuroi species complex (GFC) well known as fumonisin (FUM) producers. European corn borer (ECB), the most common maize pest in northern Italy, favors the infection of maize by GFC strains. Since ECB control is not completely effective in lowering fumonisin contamination, additional preventive means, such as increased maize resistance, are required in order to assure a more effective protection. Flavonoids in maize pericarp seem to be able to reduce the fumonisin accumulation. The goal of this study was to assess the effect of flavonoids associated with insecticides on ECB and FER rating under field conditions in Lombardy. Two maize hybrids were sown in 2011 and 2012, one hybrid characterized by the presence of flavonoids in pericarp and the other without pigmentation. The ECB damage incidence, frequency and severity of FER, together with the incidence of GFC strains and FUM in kernels, were assessed in each genotype. In 2012, the ECB control associated with flavonoids presence reduced all the measured parameters except FUM contamination. FUM contamination seemed to be more influenced by the local GFC population and the environment rather than pesticides and pericarp pigmentation

In plane reorientation induced single laser pulse magnetization reversal in rare-earth based multilayer

Single Pulse All Optical Helicity Independent Switching (AO-HIS) represents the ability to reverse the magnetic moment of a nanostructure using a femtosecond single laser pulse. It is an ultrafast method to manipulate magnetization without the use of any applied field. Since the first switching experiments carried on GdFeCo ferrimagnetic systems, single pulse AO-HIS has been restricted for a while to Gd-based alloys or Gd/FM bilayers where FM is a ferromagnetic layer. Only recently has AO-HIS been extended to a few other materials: MnRuGa ferrimagnetic Heusler alloys and Tb/Co multilayers with a very specific range of thickness and composition. Here, we demonstrate that single pulse AO-HIS observed in Tb/Co results from a different mechanism than the one for Gd based samples and that it can be obtained for a large range of rare earth-transition metal (RE-TM) multilayers, making this phenomenon much more general. Surprisingly, in this large family of (RE-TM) multilayer systems, the threshold fluence for switching is observed to be independent of the pulse duration, up to at least 12 ps. Moreover, at high laser intensities, concentric ring domain structures are induced, unveiling multiple fluence thresholds. These striking switching features, which are in contrast to those of AO-HIS in GdFeCo alloys, concomitant with the demonstration of an in-plane reorientation of the magnetization, point towards an intrinsic precessional reversal mechanism. Our results allow expanding the variety of materials with tunable magnetic properties that can be integrated in complex heterostructures and provide a pathway to engineer materials for future applications based on all-optical control of magnetic order

The helicase HAGE prevents interferon-a-induced PML expression in ABCB5+ malignant melanoma-initiating cells by promoting the expression of SOCS1

The tumour suppressor PML (promyelocytic leukaemia protein) regulates several cellular pathways involving cell growth, apoptosis, differentiation and senescence. PML also has an important role in the regulation of stem cell proliferation and differentiation. Here, we show the involvement of the helicase HAGE in the transcriptional repression of PML expression in ABCB5 + malignant melanoma-initiating cells (ABCB5 + MMICs), a population of cancer stem cells which are responsible for melanoma growth, progression and resistance to drug-based therapy. HAGE prevents PML gene expression by inhibiting the activation of the JAK-STAT (janus kinase-signal transducers and activators of transcription) pathway in a mechanism which implicates the suppressor of cytokine signalling 1 (SOCS1). Knockdown of HAGE led to a significant decrease in SOCS1 protein expression, activation of the JAK-STAT signalling cascade and a consequent increase of PML expression. To confirm that the reduction in SOCS1 expression was dependent on the HAGE helicase activity, we showed that SOCS1, effectively silenced by small interfering RNA, could be rescued by re-introduction of HAGE into cells lacking HAGE. Furthermore, we provide a mechanism by which HAGE promotes SOCS1 mRNA unwinding and protein expression in vitro

Calcium-dependent dephosphorylation of the histone chaperone DAXX regulates H3.3 loading and transcription upon neuronal activation.

Activity-dependent modifications of chromatin are believed to contribute to dramatic changes in neuronal circuitry. The mechanisms underlying these modifications are not fully understood. The histone variant H3.3 is incorporated in a replication-independent manner into different regions of the genome, including gene regulatory elements. It is presently unknown whether H3.3 deposition is involved in neuronal activity-dependent events. Here, we analyze the role of the histone chaperone DAXX in the regulation of H3.3 incorporation at activity-dependent gene loci. DAXX is found to be associated with regulatory regions of selected activity-regulated genes, where it promotes H3.3 loading upon membrane depolarization. DAXX loss not only affects H3.3 deposition but also impairs transcriptional induction of these genes. Calcineurin-mediated dephosphorylation of DAXX is a key molecular switch controlling its function upon neuronal activation. Overall, these findings implicate the H3.3 chaperone DAXX in the regulation of activity-dependent events, thus revealing a new mechanism underlying epigenetic modifications in neurons

Cytoplasmic PML promotes TGF-β-associated epithelial–mesenchymal transition and invasion in prostate cancer

Epithelial–mesenchymal transition (EMT) is a key event that is involved in the invasion and dissemination of cancer cells. Although typically considered as having tumour-suppressive properties, transforming growth factor (TGF)-β signalling is altered during cancer and has been associated with the invasion of cancer cells and metastasis. In this study, we report a previously unknown role for the cytoplasmic promyelocytic leukaemia (cPML) tumour suppressor in TGF-β signalling-induced regulation of prostate cancer-associated EMT and invasion. We demonstrate that cPML promotes a mesenchymal phenotype and increases the invasiveness of prostate cancer cells. This event is associated with activation of TGF-β canonical signalling pathway through the induction of Sma and Mad related family 2 and 3 (SMAD2 and SMAD3) phosphorylation. Furthermore, the cytoplasmic localization of promyelocytic leukaemia (PML) is mediated by its nuclear export in a chromosomal maintenance 1 (CRM1)-dependent manner. This was clinically tested in prostate cancer tissue and shown that cytoplasmic PML and CRM1 co-expression correlates with reduced disease-specific survival. In summary, we provide evidence of dysfunctional TGF-β signalling occurring at an early stage in prostate cancer. We show that this disease pathway is mediated by cPML and CRM1 and results in a more aggressive cancer cell phenotype. We propose that the targeting of this pathway could be therapeutically exploited for clinical benefit

Successful immunosenescence and the remodelling of immune responses with ageing.

In recent decades, major theoretical and technological advances have been achieved in the field of immunology. These have allowed the scientific community to analyse the immune system in a much more sophisticated manner than was possible even 20 years ago. Moreover, great theoretical changes have also occurred in gerontology - in particular, the hypothesis has been put forward that ageing and diseases are two different phenomena, and that successful ageing, i.e. ageing in good psychophysical conditions, is really possible for most humans and animals. Immunosenescence was then carefully investigated, either in selected healthy people of advanced age or in the oldest old people, such as healthy centenarians. The main results showed that most immune parameters are indeed well preserved even at this far advanced age. This paper deals with some of the most important theoretical problems of immunosenescence. An immunological tenet was that the most important phenomenon of immunosenescence is the involution of the thymus. In most textbooks and papers it is taken for granted that the thymus starts its involution immediately after puberty. When people aged 60-65 were considered old, it was not difficult to think that they could live for the rest of their life with a fully involuted thymus. The findings on centenarians challenge this tenet, as they have only a small reduction of T lymphocytes, and a relatively normal number of virgin and memory T cells, together with a functional T cell repertoire. Other observations reported here on centenarians, concerning the activity of B lymphocytes and the cytokine network, as well as those on the well-preserved innate immunity and the cells' capability of undergoing proliferation after appropriate stimuli, suggest that complex immune changes occur with age, but also indicate that we have to modify our attitude, to grasp the new scenario which is emerging. Immunosenescence can no longer be considered as a unidirectional deterioration, and this complex phenomenon is much better described by terms such as 'remodelling', 'reshaping' or 'retuning'