Gaseous Helium storage and management in the cryogenic system for the LHC

The Large Hadron Collider (LHC) is presently under construction at CERN. Its main components are superconducting magnets which will operate in superfluid helium requiring cryogenics on a length of about 24 km around the machine ring with a total helium inventory of about 100 tonnes. As no permanent liquid helium storage is foreseen and for reasons of investment costs, only half of the total helium content can be stored in gaseous form in medium pressure vessels. During the LHC operation part of these vessels will be used as helium buffer in the case of multiple magnet quenches. This paper describes the storage, distribution and management of the helium, the layout and the connection to the surface and underground equipment of the cryogenic system

A High Reliability Gas-driven Helium Cryogenic Centrifugal Compressor

A helium cryogenic compressor was developed and tested in real conditions in 1996. The achieved objective was to compress 0.018 kg/s Helium at 4 K @ 1000 Pa (10 mbar) up to 3000 Pa (30 mbar). This project was an opportunity to develop and test an interesting new concept in view of future needs. The main features of this new specific technology are described. Particular attention is paid to the gas bearing supported rotor and to the pneumatic driver. Trade off between existing technologies and the present work are presented with special stress on the bearing system and the driver. The advantages are discussed, essentially focused on life time and high reliability without maintenance as well as non pollution characteristic. Practical operational modes are also described together with the experimental performances of the compressor. The article concludes with a brief outlook of future work

Helium Recovery in the LHC Cryogenic System following Magnet Resistive Transitions

A resistive transition (quench) of the Large Hadron Collider magnets provokes the expulsion of helium from the magnet cryostats to the helium recovery system. A high-volume, vacuum-insulated recovery line connected to several uninsulated medium-pressure gas storage tanks, forms the main constituents of the system. Besides a dedicated hardware configuration, helium recovery also implies specific procedures that should follow a quench, in order to conserve the discharged helium and possibly make use of its refrigeration capability. The amount of energy transferred after a quench from the magnets to the helium leaving the cold mass has been estimated on the basis of experimental data. Based on these data, the helium thermodynamic state in the recovery system is calculated using a lumped parameter approach. The LHC magnet quenches are classified ina parametric way from their cryogenic consequences and procedures that should follow the quench are proposed

A cryogenic axial-centrifugal compressor for superfluid helium refrigeration

CERN's new project, the Large Hadron Collider (LHC), will use superfluid helium as coolant for its high-field superconducting magnets and therefore require large capacity refrigeration at 1.8 K. This may only be achieved by subatmospheric compression of gaseous helium at cryogenic temperature. To stimulate development of this technology, CERN has procured from industry prototype Cold Compressor Units (CCU). This unit is based on a cryogenic axial-centrifugal compressor, running on ceramic ball bearings and driven by a variable-frequency electrical motor operating under low-pressure helium at ambient temperature. The machine has been commissioned and is now in operation. After describing basic constructional features of the compressor, we report on measured performance

Early onset of Chanarin-Dorfman syndrome with severe liver involvement in a patient with a complex rearrangement of ABHD5 promoter

BACKGROUND: \u3b1/\u3b2-hydrolase domain-containing protein 5 (ABHD5) plays an important role in the triacylglycerols (TAG) hydrolysis. Indeed, ABHD5 is the co-activator of adipose triglyceride lipase (ATGL), that catalyses the initial step of TAG hydrolysis. Mutations in ABHD5 gene are associated with the onset of Chanarin-Dorfman syndrome (CDS), a rare autosomal recessive lipid storage disorder, characterized by non-bullous congenital ichthyosiform erythroderma (NCIE), hepatomegaly and liver steatosis. CASE PRESENTATION: We describe here a 5-years-old Brazilian child who presented with NCIE at birth and diffuse micro and macro-vesicular steatosis on liver biopsy since she was 2 years old. Molecular analysis of coding sequence and putative 5' regulatory region of ABHD5 gene was performed. A homozygous novel deletion, affecting the promoter region and the exon 1, was identified, confirming the suspected diagnosis of CDS for this patient. RT-PCR analysis showed that the genomic rearrangement completely abolished the ABHD5 gene expression in the patient, while only a partial loss of expression was detected in her parents. This is the first report describing the identification of a large deletion encompassing the promoter region of ABHD5 gene. The total loss of ABHD5 expression may explain the early onset of CDS and the severe liver involvement. After molecular diagnosis, the patient started a special diet, poor in fatty acids with medium chain triglycerides (MCT), and showed hepatic and dermatologic improvement in spite of severe molecular defect. CONCLUSIONS: This case report extends the spectrum of disease-causing ABHD5 mutations in CDS providing evidence for a novel pathogenic mechanism for this rare disorder. Moreover, our preliminary data show that early diagnosis and prompt treatment of neutral lipid accumulation might be useful for CD patients

A Simplified Cryogenic Distribution Scheme for the Large Hadron Collider

The Large Hadron Collider (LHC), currently under construction at CERN, will make use of superconducting magnets operating in superfluid helium below 2 K. The reference cryogenic distribution scheme was based, in each 3.3 km sector served by a cryogenic plant, on a separate cryogenic distribution line which feeds elementary cooling loops corresponding to the length of a half-cell (53 m). In order to decrease the number of active components, cryogenic modules and jumper connections between distribution line and magnet strings a simplified cryogenic scheme is now implemented, based on cooling loops corresponding to the length of a full-cell (107 m) and compatible with the LHC requirements. Performance and redundancy limitations are discussed with respect to the previous scheme and balanced against potential cost savings

Commissioning the Cryogenic System of the First LHC Sector

The LHC machine, composed of eight sectors with superconducting magnets and accelerating cavities requires a complex cryogenic system providing high cooling capacities (18 kW equivalent at 4.5 K and 2.4  W at 1.8 K per sector produced in large cold boxes and distributed via 3.3-km cryogenic transfer lines). After individual reception tests of the cryogenic subsystems (cryogen storages, refrigerators, cryogenic transfer lines and distribution boxes) performed since 2000, the commissioning of the cryogenic system of the first LHC sector has been under way since November 2006. After a brief introduction to the LHC cryogenic system and its specificities, the commissioning is reported detailing the preparation phase (pressure and leak tests, circuit conditioning and flushing), the cool-down sequences including the handling of cryogenic fluids, the magnet powering phase and finally the warm-up. Preliminary conclusions on the commissioning of the first LHC sector will be drawn with the review of the critical points already solved or still pending. The last part of the paper reports on the first operational experience of the LHC cryogenic system in the perspective of the commissioning of the remaining LHC sectors and the beam injection test

Generation of induced Pluripotent Stem Cells as disease modelling of NLSDM

Neutral Lipid Storage Disease with Myopathy (NLSDM) is a rare defect of triacylglycerol metabolism, characterized by the abnormal storage of neutral lipid in organelles known as lipid droplets (LDs). The main clinical features are progressive myopathy and cardiomyopathy. The onset of NLSDM is caused by autosomal recessive mutations in the PNPLA2 gene, which encodes adipose triglyceride lipase (ATGL). Despite its name, this enzyme is present in a wide variety of cell types and catalyzes the first step in triacylglycerol lipolysis and the release of fatty acids. Here, we report the derivation of NLSDM-induced pluripotent stem cells (NLSDM-iPSCs) from fibroblasts of two patients carrying different PNPLA2 mutations. The first patient was homozygous for the c.541delAC, while the second was homozygous for the c.662G>C mutation in the PNPLA2 gene. We verified that the two types of NLSDM-iPSCs possessed properties of embryonic-like stem cells and could differentiate into the three germ layers in vitro. Immunofluorescence analysis revealed that iPSCs had an abnormal accumulation of triglycerides in LDs, the hallmark of NLSDM. Furthermore, NLSDM-iPSCs were deficient in long chain fatty acid lipolysis, when subjected to a pulse chase experiment with oleic acid. Collectively, these results demonstrate that NLSDM-iPSCs are a promising in vitro model to investigate disease mechanisms and screen drug compounds for NLSDM, a rare disease with few therapeutic options

A novel PNPLA2 mutation causing total loss of RNA and protein expression in two NLSDM siblings with early onset but slowly progressive severe myopathy

Neutral lipid storage disease with myopathy (NLSDM) is a rare autosomal recessive disorder, due to an enzymatic error of lipid metabolism. Patients present always with skeletal muscle myopathy and variable cardiac and hepatic involvement. NLSDM is caused by mutations in the PNPLA2 gene, which encodes the adipose triglyceride lipase (ATGL). Here we report the molecular characterization and clinical findings of two NLSDM siblings carrying the novel c.187+1G > C homozygous PNPLA2 mutation, localized in the splice site of intron 2. Molecular analyses revealed that neither aberrant PNPLA2 mRNA isoforms, nor ATGL mutated protein were detectable in patient's cells. Clinically, both patients presented early onset muscle weakness, in particular of proximal upper limb muscles. In almost 15 years, muscle damage affected also distal upper limbs. This is a NLSDM family, displaying a severe PNPLA2 mutation in two siblings with clinical presentation characterized by an early onset, but a slowly evolution of severe myopathy