The Cryogenic System for the LHC Test String 2: Design, Commissioning and Operation

A 107-m long superconducting magnet string representing a full-cell of the LHC machine was designed for assembly and commissioning at CERN in order to validate the final design choices. This new facility, thereafter called Test String 2, and its cryogenic infrastructure cons ist of feed and return boxes coupled via transfer lines to a 6 kW @ 4.5 K refrigerator and to a low pressure pumping group, a separate cryogenic distribution line, an electrical feed box with HTS current leads, 2 quadrupole and 6 dipole prototype and pre-series superconducting magnets

Miniatures from domestic contexts in Iron age Iberia

This article reviews a set of miniatures from domestic contexts in Iron Age eastern Iberia, and interprets them in terms of their role in forging social personae. After an introduction to the historical case under consideration, the miniatures are described in terms of their typology and their contexts of provenance are outlined. Though not abundant, they tend to occur in central places in the landscape; specifically, they are often found in houses of the powerful. The vast majority are miniatures of pottery and tools, though some miniature weapons are recorded. We contend that these objects were used as a means of enculturation and for the learning of values and norms. It is no coincidence that they emerge in the archaeological record of Iron Age Iberia at the same time as the rise of a social structure based on hereditary power

Notch1 signaling in NOTCH1-mutated mantle cell lymphoma depends on Delta-Like ligand 4 and is a potential target for specific antibody therapy.

Background NOTCH1 gene mutations in mantle cell lymphoma (MCL) have been described in about 5-10% of cases and are associated with significantly shorter survival rates. The present study aimed to investigate the biological impact of this mutation in MCL and its potential as a therapeutic target. Methods Activation of Notch1 signaling upon ligand-stimulation and inhibitory effects of the monoclonal anti-Notch1 antibody OMP-52M51 in NOTCH1-mutated and -unmutated MCL cells were assessed by Western Blot and gene expression profiling. Effects of OMP-52M51 treatment on tumor cell migration and tumor angiogenesis were evaluated with chemotaxis and HUVEC tube formation assays. The expression of Delta-like ligand 4 (DLL4) in MCL lymph nodes was analyzed by immunofluorescence staining and confocal microscopy. A MCL mouse model was used to assess the activity of OMP-52M51 in vivo. Results Notch1 expression can be effectively stimulated in NOTCH1-mutated Mino cells by DLL4, whereas in the NOTCH1-unmutated cell line JeKo-1, less effect was observed upon any ligand-stimulation. DLL4 was expressed by histiocytes in both, NOTCH1-mutated and -unmutated MCL lymph nodes. Treatment of NOTCH1-mutated MCL cells with the monoclonal anti-Notch1 antibody OMP-52M51 effectively prevented DLL4-dependent activation of Notch1 and suppressed the induction of numerous direct Notch target genes involved in lymphoid biology, lymphomagenesis and disease progression. Importantly, in lymph nodes from primary MCL cases with NOTCH1/2 mutations, we detected an upregulation of the same gene sets as observed in DLL4-stimulated Mino cells. Furthermore, DLL4 stimulation of NOTCH1-mutated Mino cells enhanced tumor cell migration and angiogenesis, which could be abolished by treatment with OMP-52M51. Importantly, the effects observed were specific for NOTCH1-mutated cells as they did not occur in the NOTCH1-wt cell line JeKo-1. Finally, we confirmed the potential activity of OMP-52M51 to inhibit DLL4-induced Notch1-Signaling in vivo in a xenograft mouse model of MCL. Conclusion DLL4 effectively stimulates Notch1 signaling in NOTCH1-mutated MCL and is expressed by the microenvironment in MCL lymph nodes. Our results indicate that specific inhibition of the Notch1-ligand-receptor interaction might provide a therapeutic alternative for a subset of MCL patients

The SPL (II) at CERN, a Superconducting 3.5 GeV H- Linac

A revision of the physics needs and recent progress in the technology of superconducting (SC) RF cavities have triggered major changes in the design of a SC H-linac at CERN. With up to 5MW beam power, the SPL can be the proton driver for a next generation ISOL-type radioactive beam facility (âEURISOLâ) and/or supply protons to a neutrino () facility (conventional superbeam + beta-beam or -factory). Furthermore the SPL can replace Linac2 and the PS booster (PSB), improving significantly the beam performance in terms of brightness, intensity, and reliability for the benefit of all proton users at CERN, including LHC and its luminosity upgrade. Compared with the first conceptual design, the beam energy is almost doubled (3.5GeV instead of 2.2 GeV) while the length is reduced by 40%. At a repetition rate of 50 Hz, the linac reuses decommissioned 352.2MHz RF equipment from LEP in the low-energy part. Beyond 90MeV the RF frequency is doubled, and from 180MeV onwards high-gradient SC bulkniobium cavities accelerate the beam to its final energy of 3.5GeV. This paper presents the overall design approach, together with the technical progress since the first conceptual design in 2000

Conceptual design of the SPL II: A high-power superconducting H−H^- linac at CERN

An analysis of the revised physics needs and recent progress in the technology of superconducting RF cavities have led to major changes in the speci cation and in the design for a Superconducting Proton Linac (SPL) at CERN. Compared with the rst conceptual design report (CERN 2000012) the beam energy is almost doubled (3.5 GeV instead of 2.2 GeV), while the length of the linac is reduced by 40% and the repetition rate is reduced to 50 Hz. The basic beam power is at a level of 45MW and the approach chosen offers enough margins for upgrades. With this high beam power, the SPL can be the proton driver for an ISOL-type radioactive ion beam facility of the next generation (`EURISOL'), and for a neutrino facility based on superbeam C beta-beam or on muon decay in a storage ring (`neutrino factory'). The SPL can also replace the Linac2 and PS Booster in the low-energy part of the CERN proton accelerator complex, improving signi cantly the beam performance in terms of brightness and intensity for the bene t of all users including the LHC and its luminosity upgrade. Decommissioned LEP klystrons and RF equipment are used to provide RF power at a frequency of 352.2 MHz in the lowenergy part of the accelerator. Beyond 90 MeV, the RF frequency is doubled to take advantage of more compact normal-conducting accelerating structures up to an energy of 180 MeV. From there, state-ofthe- art, high-gradient, bulk-niobium superconducting cavities accelerate the beam up to its nal energy of 3.5 GeV. The overall design approach is presented, together with the progress that has been achieved since the publication of the rst conceptual design report

Withdrawal of infliximab therapy in ankylosing spondylitis in persistent clinical remission, results from the REMINEA study

Altres ajuts: This work is conducted under the umbrella of the Rheumatology Society of Catalonia and supported by Merck Research Laboratories.Background: Recent data suggest that anti-TNF doses can be reduced in ankylosing spondylitis (AS) patients. Some authors even propose withdrawing treatment in patients in clinical remission; however, at present there is no evidence to support this. Objective: To assess how long AS patients with persistent clinical remission remained free of flares after anti-TNF withdrawal and to evaluate the effects of treatment reintroduction. We also analyze the characteristics of patients who did not present clinical relapse. Methods: Multicenter, prospective, observational study of a cohort of patients with active AS who had received infliximab as a first anti-TNF treatment and who presented persistent remission (more than 6 months). We recorded at baseline and every 6-8 weeks over the 12-month period the age, gender, disease duration, peripheral arthritis or enthesitis, HLA-B27 status, BASDAI, CRP, ESR, BASFI, and three visual analogue scales, spine global pain, spinal night time pain, and patient's global assessment. Results: Thirty-six out of 107 patients (34%) presented persistent remission and were included in our study. After treatment withdrawal, 21 of these 36 patients (58%) presented clinical relapse during follow-up. Infliximab therapy was reintroduced and only 52% achieved clinical remission, as they had before the discontinuation of infliximab; in an additional 10%, reintroduction of infliximab was ineffective, obliging us to change the anti-TNF therapy. No clinical or biological factors were associated with the occurrence of relapse during the follow-up. Conclusions: Two thirds of patients in clinical remission presented clinical relapse shortly after infliximab withdrawal. Although the reintroduction of infliximab treatment was safe, half of the patients did not present the same clinical response that they had achieved prior to treatment withdrawal