Cryogenic R&D at the CERN Central Cryogenic Laboratory

The Central Cryogenic Laboratory operates since many years at CERN in the framework of cryogenic R&D for accelerators and experiments. The laboratory hosts several experimental posts for small cryogen ic tests, all implemented with pumping facility for GHe and vacuum, and is equipped with a He liquefier producing 6.105 l/year, which is distributed in dewars. Tests include thermomechanical qualifica tion of structural materials, cryogenic and vacuum qualification of prototypes, evaluation of thermal losses of components. Some of the most relevant results obtained at the laboratory in the last yea rs are outlined in this paper

Heat Flow Measurements on LHC Components

The refrigeration and liquefaction capacity necessary to operate at 1.9 K the 27 km long string of superconducting magnets of the LHC has been determined on the basis of heat load estimates, including static heat inleaks from ambient temperature, resistive heating and dynamic beam-induced heat loads. At all temperature levels, the static heat inleaks determine at least one third of the total heat loads in nominal operating conditions of the machine. Design validation of individual cryocomponents therefore requires a correct estimate of the heat inleaks they induce at all temperature levels, in order not to exceed the allocated heat budget. This paper illustrates the measurements of heat inleaks for several cold components of the future machine, including insulating supports, radiation shields, multi-layer insulation, instrumentation current leads. Distinct methods to determine the heat flow are chosen, depending on the expected heat loads, the temperature range spanned by the heat intercepts, and the working conditions of the component itself

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

Relationship between solid state structure and solution stability of copper(ii)-hydroxypyridinecarboxylate complexes

The complementary solid state/solution studies of the systematic series of bioactive ligands 3-hydroxy- 1-methyl-4-pyridinecarboxylate (L1), 3-hydroxy-1,2,6-trimethyl-4-pyridinecarboxylate (L2), 4-hydroxy-1- methyl-3-pyridinecarboxylate (L3), 4-hydroxy-1,6-dimethyl-3-pyridinecarboxylate (L4), 4-hydroxy-1-(2- hydroxyethyl)-6-methyl-3-pyridinecarboxylate (L5) and 4-hydroxy-1-(2-carboxyethyl)-6-methyl-3- pyridinecarboxylate (L6) with copper(II) have been performed in order to design efficient chelating drugs for the treatment of metal overloading conditions. Single crystals of [Cu(L1)2(H2O)]3H2O (1) (monomer) with axial water coordination, [Cu2(L2)4]6H2O (2) and [Cu2(L3)4]4H2O (3) (cyclic dimers), where pyridinolato and carboxylato oxygens, respectively, act as linkers between adjacent copper complexes, [Cu(L4)2]n3H2O (4) (1D polymer) and [Cu3(L5)6]18H2O (5) (trimer), constructed using two square-pyramidal and one elongated octahedral Cu(II) complexes have been determined by SXRD. The bidentate coordination mode of the ligands has been found preferentially with cis arrangements in 1 and 2 and trans arrangements in 3\u20135. The solution speciation and complex stability of aqueous solutions have been studied by pH-dependent electron paramagnetic resonance spectroscopy resulting in the detection of solely monomeric [CuL]+ and [CuL2] complexes. The stability order obtained for the [CuL]+ complexes could be correlated with the deprotonation constants of their hydroxyl group (log bLH) reflecting that the higher acidity increases the complex stability in the order L2 o L1 E L6 o L4 E L5 o L3. This stability order elucidates the different axial linkers in the cyclic dimers 2 and 3. DFT quantum-chemical calculations support the effect of the electron distribution on the established stability order

FSH treatment improves sperm DNA damage in men with idiopathic infertility carriers of the FSH receptor p.N680S homozygous N genotype: an interim analysis

Study question: To assess whether in men with idiopathic infertility, the sperm DNA fragmentation (sDF) improves depending on the FSH receptor (FSHR) genotype as assessed by the non-synonymous polymorphisms (SNP) rs6166 (wild type or p.N680S). Summary answer: FSH treatment improves sDF in a subgroup of idiopathic infertile men, although 40% of these men do not show any significant improve- ment. The response of sDF, a surrogate marker of sperm quality, together with the evaluation of FSHR SNP p.N680S might be useful to predict the response to FSH treatment. What is known already: FSH is fundamental for spermatogenesis and is em- pirically used to treat male idiopathic infertility. Several studies suggest that sDF could be a candidate predictor of response to FSH treatment, in terms of probability to conceive. Furthermore, it is widely accepted that the FSHR SNP p.N680S influences ovarian response in women and testicular volume in men. Study design, size, duration: Multicenter, longitudinal, prospective, open-la- bel, two-arms clinical trial. Subjects enrolled were idiopathic infertile men and received 150 IU of recombinant FSH (Gonal f®) every other day for 12 weeks and were then followed-up for further 12 weeks after FSH-withdrawal. Patients were evaluated at baseline and at the end of the two phases. Participants/materials, setting, methods: Eighty-eight men with idiopathic male infertility carrier of the homozygous FSHR p.N680S N or S genotype, FSH 15%, were enrolled. 66 patients completed the sDF analysis. sDF was centrally evaluated by TUNEL/PI assay coupled to flow cy- tometry, resolving two different sperm populations, namely: PIbrighter and PIdimmer. Main results and the role of chance: Thirty-seven men (56%) were carriers of the p.N680S homozygous-N and 29 (44%) of the homozygous-S genotype, respectively. Total sDF (PIbrighter + PIdimmer) was significantly lower at the end of the study in patients carriers of the p.N680S-N allele than patients carri- ers of p.N680S-S allele (p = 0.008). Only in patients carriers of the p.N680S-N allele, total sDF decreased significantly from baseline to the end of the study (p = 0.021) and this decrease was entirely sustained by the sperm population containing vital sperms (i.e., PIbrighter fraction) (p = 0.008). PIdimmer frac- tion, including only non-vital sperms, was significantly higher in patients car- riers of the p.N680S-S allele than in carriers of N allele (p = 0.018). Total sDF was inversely related to total sperm number (p = 0.020) and progressive sperm motility (p = 0.014). Limitations, reason for caution: The statistical power of the results obtained so far is 86.9%, with alpha-error 0.05. This is an interim-analysis. Wider implications of the findings: The study suggests that FSH treatment induces a significant improvement of total sDF in men carriers of the p.N680S homozygous N allele. This sDF decrease awaits confirmation, since the study will be completed by June 2015. Study funding/competing interest(s): Funding by commercial/corporate company(ies) – The study was supported by unrestricted grant by Merck Serono. Trial registration number: EudraCT number 2010-020240-35. Keywords: FSH treatment, male infertility, Sperm-DNA fragmentatio

Profiling Insulin Like Factor 3 (INSL3) Signaling in Human Osteoblasts

Abstract BACKGROUND: Young men with mutations in the gene for the INSL3 receptor (Relaxin family peptide 2, RXFP2) are at risk of reduced bone mass and osteoporosis. Consistent with the human phenotype, bone analyses of Rxfp2(-/-) mice showed decreased bone volume, alterations of the trabecular bone, reduced mineralizing surface, bone formation, and osteoclast surface. The aim of this study was to elucidate the INSL3/RXFP2 signaling pathways and targets in human osteoblasts. METHODOLOGY/PRINCIPAL FINDINGS: Alkaline phosphatase (ALP) production, protein phosphorylation, intracellular calcium, gene expression, and mineralization studies have been performed. INSL3 induced a significant increase in ALP production, and Western blot and ELISA analyses of multiple intracellular signaling pathway molecules and their phosphorylation status revealed that the MAPK was the major pathway influenced by INSL3, whereas it does not modify intracellular calcium concentration. Quantitative Real Time PCR and Western blotting showed that INSL3 regulates the expression of different osteoblast markers. Alizarin red-S staining confirmed that INSL3-stimulated osteoblasts are fully differentiated and able to mineralize the extracellular matrix. CONCLUSIONS/SIGNIFICANCE: Together with previous findings, this study demonstrates that the INSL3/RXFP2 system is involved in bone metabolism by acting on the MAPK cascade and stimulating transcription of important genes of osteoblast maturation/differentiation and osteoclastogenesis

Commissioning of the cryogenics of the LHC long straight sections

The LHC is made of eight circular arcs interspaced with eight Long Straight Sections (LSS). Most powering interfaces to the LHC are located in these sections where the particle beams are focused and shaped for collision, cleaning and acceleration. The LSSs are constituted of several unique cryogenic devices and systems like electrical feed-boxes, standalone superconducting magnets, superconducting links, RF cavities and final focusing superconducting magnets. This paper presents the cryogenic commissioning and the main results obtained during the first operation of the LHC Long Straight Sections.Comment: 8 pp. Cryogenic Engineering Conference and International Cryogenic Materials Conference, 28 Jun - 2 Jul 2009. Tucson, Arizon

Bone health and body composition in transgender adults before gender-affirming hormonal therapy: data from the COMET study

Purpose: Preliminary data suggested that bone mineral density (BMD) in transgender adults before initiating gender-affirming hormone therapy (GAHT) is lower when compared to cisgender controls. In this study, we analyzed bone metabolism in a sample of transgender adults before GAHT, and its possible correlation with biochemical profile, body composition and lifestyle habits (i.e., tobacco smoke and physical activity). Methods: Medical data, smoking habits, phospho-calcic and hormonal blood tests and densitometric parameters were collected in a sample of 125 transgender adults, 78 Assigned Females At Birth (AFAB) and 47 Assigned Males At Birth (AMAB) before GAHT initiation and 146 cisgender controls (57 females and 89 males) matched by sex assigned at birth and age. 55 transgender and 46 cisgender controls also underwent a complete body composition evaluation and assessment of physical activity using the International Physical Activity Questionnaire (IPAQ). Results: 14.3% of transgender and 6.2% of cisgender sample, respectively, had z-score values < -2 (p = 0.04). We observed only lower vitamin D values in transgender sample regarding biochemical/hormonal profile. AFAB transgender people had more total fat mass, while AMAB transgender individuals had reduced total lean mass as compared to cisgender people (53.94 ± 7.74 vs 58.38 ± 6.91, p < 0.05). AFAB transgender adults were more likely to be active smokers and tend to spend more time indoor. Fat Mass Index (FMI) was correlated with lumbar and femur BMD both in transgender individuals, while no correlations were found between lean mass parameters and BMD in AMAB transgender people. Conclusions: Body composition and lifestyle factors could contribute to low BMD in transgender adults before GAHT