Targeted Immunotherapy with Rituximab Leads to a Transient Alteration of the IgG Autoantibody Profile in Pemphigus Vulgaris

In pemphigus vulgaris (PV), IgG autoantibodies against the ectodomain of desmoglein 3 (Dsg3) have been shown to be directly responsible for the loss of keratinocyteadhesion. The aim of the present study was to study the effect of the B cell depleting anti-CD20 monoclonal antibody, rituximab, on the profile of pathogenic IgG against distinct regions of the Dsg3 ectodomain in 22 PV patients who were followed up clinically and serologically by Dsg3 ELISA over 12-24 months. Prior to rituximab, all the 22 PV patients showed IgG against Dsg3 (Dsc3EC1-5). Specifically, 14/22 showed IgG reactivity against the Dsg3EC1 subdomain, 5/22 patients against Dsg3EC2, 7/22 against Dsg3EC3, 11/22 against Dsg3EC4, and 2/22 against Dsg3EC5. Within 6 months after rituximab, all the patients showed significant clinical improvement and reduced IgG against Dsg3 (5/22) and the various subdomains, that is, Dsg3EC1 (7/22), Dsg3EC2 (3/22), Dsg3EC3 (2/22), sg3EC4 (2/22), and Dsg3EC5 (0/22). During the entire observation period, 6/22 PV patients experienced a clinical relapse which was associated with the reappearance of IgG against previously recognized Dsg3 subdomains, particularly against the Dsg3EC1. Thus, in PV, rituximab only temporarily depletes pathogenic B cell responses against distinct subdomains of Dsg3 which reappear upon clinical relapse

New results on solar neutrino fluxes from 192 days of Borexino data

We report the direct measurement of the ^7Be solar neutrino signal rate performed with the Borexino detector at the Laboratori Nazionali del Gran Sasso. The interaction rate of the 0.862 MeV ^7Be neutrinos is 49+-3(stat)+-4(syst) counts/(day * 100ton). The hypothesis of no oscillation for ^7Be solar neutrinos is inconsistent with our measurement at the 4sigma level. Our result is the first direct measurement of the survival probability for solar nu_e in the transition region between matter-enhanced and vacuum-driven oscillations. The measurement improves the experimental determination of the flux of ^7Be, pp, and CNO solar nu_e, and the limit on the magnetic moment of neutrinos

Clinical response of severe mechanobullous epidermolysis bullosa acquisita to combined treatment with immunoadsorption and rituximab (anti-CD20 monoclonal antibodies)

Background: Epidermolysis bullosa acquisita (EBA) is an autoimmune bullous disorder with mucocutaneous involvement, skin fragility, and tendency to scarring. The mechanobullous form of EBA has a chronic relapsing course and is difficult to treat. We describe herein the therapeutic response of 2 patients with recalcitrant mechanobullous EBA to combined treatment with immunoadsorption and rituximab, an anti-CD20 monoclonal antibody that induces depletion of B cells in vivo. Observations: Two patients with mechanobullous EBA received combined treatment with immunoadsorption and rituximab, resulting in an almost complete clinical remission in one patient and stable disease in the other patient. In the patient with complete remission, prolonged B-cell depletion and clinical improvement with disappearance of mucocutaneous erosions paralleled the decline in titers of circulating anti-basement membrane zone autoantibodies. In the other patient, combined treatment with immunoadsorption and rituximab reduced the de novo appearance of blisters but did not lead to significant improvement of gingivitis, despite depleted B cells for 6 months that remained at 5% 12 months after the last administration of rituximab, as well as a reduction in autoantibody titers. Conclusion: The patients' response suggests that combined treatment with immunoadsorption and rituximab may be a valuable adjuvant treatment regimen for severe mechanobullous EBA, which is in line with recently observed beneficial effects in inflammatory EBA

DC4Cities, An environmentally Sustainable Data Centre for Smart Cities : Project Nº 609304 : D 7.1 - Description of Energy Metrics for Datacentres

The general objective of DC4Cities is to develop technologies and methodologies to increase in a significant, permanent way the share of renewable power used by DCs in their operation. In this general context, the establishment of a recognized set of metrics is an essential element, both to answer the need of tools to measure energy parameters in a datacentre and to assess the achievements of the technologies developed within the project. In WP7 we wish to go beyond current energy metrics, towards the development of new tools capable of better capturing energy utilization efficiency and workload-based energy efficiency parameters. Moreover, the project aims at establishing a method to compare the measurements processes and finally to establish a standardization process. The idea is to establish a common methodological framework which could be adopted by ICT sector and shared with the international bodies of standardisation – such as CEN-CENELEC-ETSI – in order to evaluate the feasibility of standardisation efforts. The present document, D7.1, fulfils the task that was outlined in the project for this first year of activity, which is mainly to analyse the current state of the art of the energy-related metrics scenario for DCs. In addition, the document describes the establishment of a complex network among 8 different EU projects, where the metrics scenario is discussed and developments are undertaken. Finally the document describes a few hypotheses and workplans for the development of original workload-based energy efficiency metrics. A plan for future work is outlined

DC4Cities, An environmentally Sustainable Data Centre for Smart Cities : Project Nº 609304 : D 7.1 - Description of Energy Metrics for Datacentres

The general objective of DC4Cities is to develop technologies and methodologies to increase in a significant, permanent way the share of renewable power used by DCs in their operation. In this general context, the establishment of a recognized set of metrics is an essential element, both to answer the need of tools to measure energy parameters in a datacentre and to assess the achievements of the technologies developed within the project. In WP7 we wish to go beyond current energy metrics, towards the development of new tools capable of better capturing energy utilization efficiency and workload-based energy efficiency parameters. Moreover, the project aims at establishing a method to compare the measurements processes and finally to establish a standardization process. The idea is to establish a common methodological framework which could be adopted by ICT sector and shared with the international bodies of standardisation – such as CEN-CENELEC-ETSI – in order to evaluate the feasibility of standardisation efforts. The present document, D7.1, fulfils the task that was outlined in the project for this first year of activity, which is mainly to analyse the current state of the art of the energy-related metrics scenario for DCs. In addition, the document describes the establishment of a complex network among 8 different EU projects, where the metrics scenario is discussed and developments are undertaken. Finally the document describes a few hypotheses and workplans for the development of original workload-based energy efficiency metrics. A plan for future work is outlined