Construction and Installation of the New CERN Proton Synchrotron Internal Beam Dumps

Source at https://inspirehep.net/literature/1961952.In the framework of the CERN Large Hadron Collider Injectors Upgrade (LIU) Project, the Proton Synchrotron (PS) has been equipped with two new movable Internal Dumps (PSID), each of them capable of absorbing particle beams of an energy of up to 100 kJ. These dumps replace the old Internal Dumps, which have been operated in the accelerator complex since their installation in 1975 until their decommissioning and removal from the machine during the second LHC Long Shut down (LS2). This contribution will address the construction and testing phases of the new PSIDs, including the assembly of the dump core, its actuation system and the respective shielding, mechanical running-in tests, metrology adjustments, Ultra-High Vacuum (UHV) and impedance acceptance tests. The described installation work was completed successfully, and the new generation Dumps are currently operational in the PS machine

Histoire du monde au XVe siècle

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Neutral aldoses derived from sequential acid hydrolysis of sediments as indicators of diagenesis over 120,000 years.

International audienceNeutral aldoses of the upper 50 m (representing ca. 120 kyr) of sediments from the Cariaco Basin were studied using a new technique based on water extraction followed by sequential acid hydrolysis with 2N, 4N and 6N trifluoroacetic acid (TFA) to investigate the fate of carbohydrates during diagenesis. The distribution and abundance of neutral aldoses and their evolution with depth shed light on the origin and fate of carbohydrates upon burial. The carbohydrates originated mainly from phytoplanktonic production, in particular diatoms. The porewater carbohydrate fraction was invariant and its composition attested to considerable biodegradation of the source material. Bacteria in the sediment may have also contributed to this fraction. The carbohydrates in the 2N fraction represented a decreasing fraction of the total organic carbon (TOC) with increasing depth/age. This fraction likely derived from storage polysaccharides, which were progressively degraded in the sediment. The 4N fraction was dominated by hexoses, suggesting that it comprised sugars derived from structural polysaccharides and exopolymeric substances. It showed a slight decrease with depth, over the 120 kyr. The 6N fraction comprised a relatively constant fraction of TOC with sediment depth. The aldose distribution suggested that the 6N fraction showed the imprint of the initial biological signal preserved by a proteinaceous macromolecular structure and/or a mineral matrix, but not from condensation in the sediment of more labile polysaccharide

Aspects cliniques et évolutifs des tendinopathies aux fluoroquinolones (expérience du centre Régional de Pharmacovigilance de Saint-Etienne)

L'etude reprend une serie de 36 cas de tendinopathies sous Fluoroquinolones notifiees au Centre Regional de Pharmacovigilance de Saint-Etienne sur la periode de 1992 a 2002. Les medecins traitants des patients puis les patients eux-memes ont ete recontactes afin de connaître l'evolution a long terme de leur atteinte tendineuse. Au terme de l'etude, on constate que 20 patients (55.5%) sont guéris sans sequelle, 7 patients sont perdus de vue (19.5%) et 9 patients presentent des douleurs encore evolutives (25%) dont 7 sequelles : induration et nodule, douleur au repos, impossibilite de courir, de se mettre sur la pointe des pieds, douleur a la palpation, a la marche, boiterie, amyotrophie du mollet, Les sequelles sont liees a la gravite de l'atteinte initiale (3 cas de rupture du tendon d'Achille dont une bilaterale) mais aussi au delai d'arret de la fluoroquinolone par rapport aux premiers symptomes. La prise en charge par la mise au repos permet une guerison plus rapide. La gravite de cette pathologie et les consequences importantes en terme de morbidite doivent faire reflechir les prescripteurs sur le rapport benefice/risque de ces molecules mais aussi sur l'information a apporter aux patients afin d'arreter le plus tot possible la molecule en cas d'apparition des premiers symptomes et la necessite d'une bonne prise en charge orthopedique (mise au repos bilaterale).ST ETIENNE-BU Médecine (422182102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Antibiothérapie chez des patients bactériémiques admis aux urgences (analyse de sa pertinence)

ST ETIENNE-BU Médecine (422182102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

DAP12 and CD11b contribute to the microglial-induced death of dopaminergic neurons in vitro but not in vivo in the MPTP mouse model of Parkinson's disease.

International audienceBACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by a loss of dopaminergic neurons (DN) in the substantia nigra (SN). Several lines of evidence suggest that apoptotic cell death of DN is driven in part by non-cell autonomous mechanisms orchestrated by microglial cell-mediated inflammatory processes. Although the mechanisms and molecular network underlying this deleterious cross-talk between DN and microglial cells remain largely unknown, previous work indicates that, upon DN injury, activation of the β2 integrin subunit CD11b is required for microglia-mediated DN cell death. Interestingly, during brain development, the CD11b integrin is also involved in microglial induction of neuronal apoptosis and has been shown to act in concert with the DAP12 immunoreceptor. Whether such a developmental CD11b/DAP12 pathway could be reactivated in a pathological context such as PD and play a role in microglia-induced DN cell death is a tantalizing hypothesis that we wished to test in this study. METHODS: To test the possibility that DAP12 could be involved in microglia-associated DN injury, we used both in vitro and in vivo toxin-based experimental models of PD recapitulating microglial-mediated non-cell autonomous mechanisms of DN cell death. In vitro, enriched mesencephalic neuronal/microglial co-cultures were exposed to the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP+) whereas in vivo, mice were administrated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) according to acute or subchronic mode. Mice deficient for DAP12 or CD11b were used to determine the pathological function of the CD11b/DAP12 pathway in our disease models. RESULTS: Our results show that DAP12 and CD11b partially contribute to microglia-induced DN cell death in vitro. Yet, in vivo, mice deficient for either of these factors develop similar neuropathological alterations as their wild-type counterparts in two different MPTP mouse models of PD. CONCLUSION: Overall, our data suggest that DAP12 and CD11b contribute to microglial-induced DN cell death in vitro but not in vivo in the MPTP mouse model of PD. Therefore, the CD11b/DAP12 pathway may not be considered as a promising therapeutic target for PD

MFGE8 does not orchestrate clearance of apoptotic neurons in a mouse model of Parkinson's disease

International audienceParkinson's disease (PD) is an age-related neurodegenerative disorder characterized by a loss of dopaminergic neurons (DN) in the substantia nigra (SN). Several lines of evidence suggest that apoptotic cell death of DN is driven in part by non-cell autonomous mechanisms implicating microglial cells and inflammatory processes. Yet, how apoptotic DNs get removed by professional phagocytes and how this process modulates inflammatory processes are still unresolved issues. In this study, we investigated the role of MFGE8, a soluble factor involved in phagocytic recognition, in apoptotic DN clearance and neuroinflammation in PD. We report that glial expression of MFGE8 is enhanced in post-mortem PD brains compared to control individuals. Then, in vivo functional analysis of Mfge8 was assessed in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mouse model of PD using wild-type (WT) and Mfge8-deficient mice. Neuropathological analysis consisted in evaluating (i) the loss of nigral DN and striatal DN terminals, (ii) the extent of glial cell activation and (iii) the number of apoptotic profiles. In vivo microglial phagocytic activity was further assessed by measuring the engulfment of apoptotic DN preloaded with fluorescent latex beads. Here we show that Mfge8 deficiency neither impact the phagocytic clearance of apoptotic bodies nor change the overall neuropathological parameters (DN cell loss and glial cell activation). In summary, our data argue that MFGE8 is not likely involved in the phagocytic clearance of neuronal debris associated with nigrostriatal pathway injury

A viral peptide that targets mitochondria protects against neuronal degeneration in models of Parkinson's disease

International audienceMitochondrial dysfunction is a common feature of many neurodegenerative disorders, notably Parkinson's disease. Consequently, agents that protect mitochondria have strong therapeutic potential. Here, we sought to divert the natural strategy used by Borna disease virus (BDV) to replicate in neurons without causing cell death. We show that the BDV X protein has strong axoprotective properties, thereby protecting neurons from degeneration both in tissue culture and in an animal model of Parkinson's disease, even when expressed alone outside of the viral context. We also show that intranasal administration of a cell-permeable peptide derived from the X protein is neuroprotective. We establish that both the X protein and the X-derived peptide act by buffering mitochondrial damage and inducing enhanced mitochondrial filamentation. Our results open the way to novel therapies for neurodegenerative diseases by targeting mitochondrial dynamics and thus preventing the earliest steps of neurodegenerative processes in axons