Measurements of the LHC Corrector Magnets at Room and Cryogenic Temperatures

The superconducting twin aperture main dipole magnets of the LHC accelerator are equipped with pairs of sextupole and decapole correctors at their ends. Similarly, octupole correctors are aligned at t he end of the main quadrupole magnets. Dedicated stations have been built for tests of these correctors at room temperature as well as superfluid helium temperature. Measurements of the training behav iour and of the magnetic field quality are routinely performed. The search for the magnetic axis and the transfer of its position to fiducials are performed at room temperature. A description and the performances obtained with these two benches are also presented

Radical-free hyperpolarized MRI using endogenously-occurring pyruvate analogues and UV-induced nonpersistent radicals

It was demonstrated that nonpersistent radicals can be generated in frozen solutions of metabolites such as pyruvate by irradiation with ultraviolet (UV) light, enabling radical-free dissolution DNP. Although pyruvate is endogenous, an excess of additional pyruvate may perturb metabolic processes, making it potentially unsuitable as a polarizing agent when studying fatty acids or carbohydrate metabolism. Therefore, the aim of the study was to characterize solutions containing endogenously-occurring alternatives to pyruvate as UV-induced nonpersistent radical precursors for in vivo hyperpolarized MRI. The metabolites alpha-ketovalerate (AKV) and alpha-ketobutyrate (AKB) are analogues of pyruvate and were chosen as potential radical precursors. Sample formulations containing AKV and AKB were studied with UV-visible spectroscopy, irradiated with UV light, and their nonpersistent radical yields were quantified with ESR and compared to pyruvate. The addition of 13C labeled substrates to the sample matrix altered the radical yield of the precursors. Using AKB increased the 13C-labeled glucose liquid state polarization to 16.3 +/- 1.3% compared with 13.3 +/- 1.5% obtained with pyruvate, and 8.9 +/- 2.1% with AKV. For [1-13C]butyric acid, polarization levels of 12.1 +/- 1.1% for AKV and 12.9 +/- 1.7% for AKB were achieved. Hyperpolarized [1-13C]butyrate metabolism in the heart revealed label incorporation into [1-13C]acetylcarnitine, [1-13C]acetoacetate, [1-13C]butyrylcarnitine, [5-13C]glutamate and [5-13C]citrate. This study demonstrates the potential of AKV and AKB as endogenous polarizing agents for in vivo radical-free hyperpolarized MRI. UV-induced, nonpersistent radicals generated in endogenous metabolites enable high polarization without requiring radical filtration, thus simplifying the quality-control tests in clinical applications.Comment: 38 pages, 5 Tables, 8 Figures, Submitted to NMR in Biomedicin

Complex controls on nitrous oxide flux across a large elevation gradient in the tropical Peruvian Andes

Acknowledgements The authors would like to acknowledge the agencies that funded this research; the UK Natural Environment Research Council (NERC; joint grant references NE/H006583, NE/H007849 and NE/H006753). Patrick Meir was supported by an Australian Research Council Fellowship (FT110100457). Javie Eduardo Silva Espejo, Walter Huaraca Huasco and the ABIDA NGO provided critical fieldwork and logistical support. Angus Calder (University of St.Andrews) and Vicky Munro (University of Aberdeen) provided invaluable laboratory support. Thanks to Adrian Tejedor from the Amazon Conservation Association, who provided assistance with site access and site selection at Hacienda Villa Carmen. This publication is a contribution from the Scottish Alliance for Geoscience, Environment and Society (http://www.sages.ac.uk).Peer reviewedPublisher PD

Drivers of atmospheric methane uptake by montane forest soils in the southern Peruvian Andes

The authors would like to acknowledge the agencies that funded this research; the UK Natural Environment Research Council (NERC; joint grant references NE/G018278/1, NE/H006583, NE/H007849 and NE/H006753) and the Norwegian Agency for Development Cooperation (Norad; via a sub-contract to Yit Arn Teh managed by the Amazon Conservation Association). Patrick Meir was also supported by an Australian Research Council Fellowship (FT110100457).The soils of tropical montane forests can act as sources or sinks of atmospheric methane (CH4). Understanding this activity is important in regional atmospheric CH4 budgets, given that these ecosystems account for substantial portions of the landscape in mountainous areas like the Andes. Here we investigate the drivers of CH4 fluxes from premontane, lower and upper montane forests, experiencing a seasonal climate, in southeastern Peru. Between February 2011 and June 2013, these soils all functioned as net sinks for atmospheric CH4. Mean (standard error) net CH4 fluxes for the dry and wet season were −1.6 (0.1) and −1.1 (0.1) mg CH4 – C m−2 d−1 in the upper montane forest; −1.1 (0.1) and −1.0 (0.1) mg CH4 – C m−2 d−1 in the lower montane forest; and −0.2 (0.1) and −0.1 (0.1) mg CH4 – C m−2 d−1 in the premontane forest. Variations among forest types were best explained by available nitrate and water-filled pore space, indicating that nitrate inhibition of oxidation or diffusional constraints imposed by changes in water-filled pore space on methanotrophic communities represent important controls on soil-atmosphere CH4 exchange. Seasonality in CH4 exchange varied among forests with an increase in wet season net CH4 flux only apparent in the upper montane forest. Net CH4 flux was inversely related to elevation; a pattern that differs to that observed in Ecuador, the only other extant study site of soil-atmosphere CH4 exchange in the tropical Andes. This may result from differences in rainfall patterns between the regions, suggesting that attention should be paid to the role of rainfall and soil moisture dynamics in modulating CH4 uptake by the organic-rich soils typical of high elevation tropical forests.Publisher PDFPeer reviewe

Tropical forests post-logging are a persistent net carbon source to the atmosphere

Acknowledgments This study was part of the SAFE Project, the Global Ecosystems Monitoring network (gem.tropicalforests.ox.ac.uk) and Imperial College's Grand Challenges in Ecosystems and the Environment Initiative. We acknowledge funding from the Sime Darby Foundation, the Biodiversity And Land-use Impacts on tropical ecosystem function (BALI) Project (NE/K016377/1) within the Natural Environment Research Council Human-Modified Tropical Forests Programme, the Malaysian Palm Oil Board (MPOB), and Centre for Tropical Forest Science (CTFS) in collaboration with HSBC Climate Partnership. The 52-ha Long-Term Ecological Research Project in Lambir is a collaborative project of the Forest Department of Sarawak, Malaysia, the Center for Tropical Forest Science of the Smithsonian Tropical Research Institute, USA (NSF awards DEB- 9107247 and DEB- 9629601), and Osaka City, Ehime & Kyoto Universities, Japan (Monbusho grants 06041094, 08NP0901 and 09NP0901). M.B.M. was supported by NERC studentship awarded through the Central England NERC Training Alliance (CENTA; grant referenceNE/S007350/1) and the University of Leicester, Y.M. was supported by the Jackson Foundation and European Research Council Advanced Investigator Grant, GEM-TRAIT (321131), Y.M., RME, and T.R. by NERC grant NE/P002218/1, and R.M.E. is supported by the NOMIS Foundation. TR also acknowledges support from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 865403). Maliau Basin and Danum Valley Management Committees, Royal Society South East Asia Rainforest Research Partnership (SEARRP), Sabah Foundation, Benta Wawasan, the State Secretary, Sabah Chief Minister’s Departments, Sabah Forestry Department, Sabah Biodiversity Council, and the Economic Planning Unit are acknowledged for their support and access to the sites in Sabah. Rostin Jantan, Rohid Kailoh, Suhaini Patik, Ampat Siliwong, Yehezekiel Jahuri, Robecca Siwaring, Jeffry Amin, Sarah Watson, Ryan Gray, Johnny Larenus, Unding Jami, Toby Marthews, Alexander Karolus, the Danum 50 ha plot team, Sylvester Tan, Xyxtus Tan, Nasir Muhi and Abilano Deres helped with the data collection. We thank Susan Page, Juan Carlos Berrio, Jörg Kaduk and Katie O’Brien for their constructive comments.Peer reviewedPublisher PD

Complex controls on nitrous oxide flux across a large-elevation gradient in the tropical Peruvian Andes

Current bottom–up process models suggest that montane tropical ecosystems are weak atmospheric sources of N2O, although recent empirical studies from the southern Peruvian Andes have challenged this idea. Here we report N2O flux from combined field and laboratory experiments that investigated the process-based controls on N2O flux from montane ecosystems across a large-elevation gradient (600–3700 m a.s.l.) in the southern Peruvian Andes. Nitrous oxide flux and environmental variables were quantified in four major habitats (premontane forest, lower montane forest, upper montane forest and montane grassland) at monthly intervals over a 30-month period from January 2011 to June 2013. The role of soil moisture content in regulating N2O flux was investigated through a manipulative, laboratory-based 15N-tracer experiment. The role of substrate availability (labile organic matter, NO3−) in regulating N2O flux was examined through a field-based litter-fall manipulation experiment and a laboratory-based 15N–NO3− addition study, respectively. Ecosystems in this region were net atmospheric sources of N2O, with an unweighted mean flux of 0.27 ± 0.07 mg N–N2O m−2 d−1. Weighted extrapolations, which accounted for differences in land surface area among habitats and variations in flux between seasons, predicted a mean annual flux of 1.27 ± 0.33 kg N2O–N ha−1 yr−1. Nitrous oxide flux was greatest from premontane forest, with an unweighted mean flux of 0.75 ± 0.18 mg N–N2O m−2 d−1, translating to a weighted annual flux of 0.66 ± 0.16 kg N2O–N ha−1 yr−1. In contrast, N2O flux was significantly lower in other habitats. The unweighted mean fluxes for lower montane forest, montane grasslands, and upper montane forest were 0.46 ± 0.24 mg N–N2O m−2 d−1, 0.07 ± 0.08 mg N–N2O m−2 d−1, and 0.04 ± 0.07 mg N–N2O m−2 d−1, respectively. This corresponds to weighted annual fluxes of 0.52 ± 0.27 kg N2O–N ha−1 yr−1, 0.05 ± 0.06 kg N2O–N ha−1 yr−1, and 0.04 ± 0.07 kg N2O–N ha−1 yr−1, respectively. Nitrous oxide flux showed weak seasonal variation across the region; only lower montane forest showed significantly higher N2O flux during the dry season compared to wet season. Manipulation of soil moisture content in the laboratory indicated that N2O flux was significantly influenced by changes in water-filled pore space (WFPS). The relationship between N2O flux and WFPS was complex and non-linear, diverging from theoretical predictions of how WFPS relates to N2O flux. Nitrification made a negligible contribution to N2O flux, irrespective of soil moisture content, indicating that nitrate reduction was the dominant source of N2O. Analysis of the pooled data indicated that N2O flux was greatest at 90 and 50 % WFPS, and lowest at 70 and 30 % WFPS. This trend in N2O flux suggests a complex relationship between WFPS and nitrate-reducing processes (i.e. denitrification, dissimilatory nitrate reduction to ammonium). Changes in labile organic matter inputs, through the manipulation of leaf litter-fall, did not alter N2O flux. Comprehensive analysis of field and laboratory data demonstrated that variations in NO3− availability strongly constrained N2O flux. Habitat – a proxy for NO3− availability under field conditions – was the best predictor for N2O flux, with N-rich habitats (premontane forest, lower montane forest) showing significantly higher N2O flux than N-poor habitats (upper montane forest, montane grassland). Yet, N2O flux did not respond to short-term changes in NO3− concentration.The authors would like to acknowledge the agencies that funded this research; the UK Natural Environment Research Council (NERC; joint grant references NE/H006583, NE/H007849, and NE/H006753). Patrick Meir was supported by an Australian Research Council Fellowship (FT110100457)

Selenoprotein gene nomenclature

The human genome contains 25 genes coding for selenocysteine-containing proteins (selenoproteins). These proteins are involved in a variety of functions, most notably redox homeostasis. Selenoprotein enzymes with known functions are designated according to these functions: TXNRD1, TXNRD2, and TXNRD3 (thioredoxin reductases), GPX1, GPX2, GPX3, GPX4 and GPX6 (glutathione peroxidases), DIO1, DIO2, and DIO3 (iodothyronine deiodinases), MSRB1 (methionine-R-sulfoxide reductase 1) and SEPHS2 (selenophosphate synthetase 2). Selenoproteins without known functions have traditionally been denoted by SEL or SEP symbols. However, these symbols are sometimes ambiguous and conflict with the approved nomenclature for several other genes. Therefore, there is a need to implement a rational and coherent nomenclature system for selenoprotein-encoding genes. Our solution is to use the root symbol SELENO followed by a letter. This nomenclature applies to SELENOF (selenoprotein F, the 15 kDa selenoprotein, SEP15), SELENOH (selenoprotein H, SELH, C11orf31), SELENOI (selenoprotein I, SELI, EPT1), SELENOK (selenoprotein K, SELK), SELENOM (selenoprotein M, SELM), SELENON (selenoprotein N, SEPN1, SELN), SELENOO (selenoprotein O, SELO), SELENOP (selenoprotein P, SeP, SEPP1, SELP), SELENOS (selenoprotein S, SELS, SEPS1, VIMP), SELENOT (selenoprotein T, SELT), SELENOV (selenoprotein V, SELV) and SELENOW (selenoprotein W, SELW, SEPW1). This system, approved by the HUGO Gene Nomenclature Committee, also resolves conflicting, missing and ambiguous designations for selenoprotein genes and is applicable to selenoproteins across vertebrates

Diagnosis and treatment trends in mucopolysaccharidosis I: findings from the MPS I Registry

Our objective was to assess how the diagnosis and treatment of mucopolysaccharidosis I (MPS I) have changed over time. We used data from 891 patients in the MPS I Registry, an international observational database, to analyze ages at symptom onset, diagnosis, treatment initiation, and treatment allocation (hematopoietic stem cell transplantation, enzyme replacement therapy with laronidase, both, or neither) over time for all disease phenotypes (Hurler, Hurler–Scheie, and Scheie syndromes). The interval between diagnosis and treatment has become shorter since laronidase became available in 2003 (gap during 2006–2009: Hurler—0.2 year, Hurler–Scheie—0.5 year, Scheie—1.4 years). However, the age at diagnosis has not decreased for any MPS I phenotype over time, and the interval between symptom onset and treatment initiation remains substantial for both Hurler–Scheie and Scheie patients (gap during 2006–2009, 2.42 and 6.71 years, respectively). Among transplanted patients, an increasing proportion received hematopoietic stem cells from cord blood (34 out of 64 patients by 2009) and was also treated with laronidase (42 out of 45 patients by 2009). Conclusions: Despite the availability of laronidase since 2003, the diagnosis of MPS I is still substantially delayed for patients with Hurler–Scheie and Scheie phenotypes, which can lead to a sub-optimal treatment outcome. Increased awareness of MPS I signs and symptoms by primary care providers and pediatric subspecialists is crucial to initiate early treatment and to improve the quality of life of MPS I patients

Insight in Genome-Wide Association of Metabolite Quantitative Traits by Exome Sequence Analyses

Metabolite quantitative traits carry great promise for epidemiological studies, and their genetic background has been addressed using Genome-Wide Association Studies (GWAS). Thus far, the role of less common variants has not been exhaustively studied. Here, we set out a GWAS for metabolite quantitative traits in serum, followed by exome sequence analysis to zoom in on putative causal variants in the associated genes. 1H Nuclear Magnetic Resonance (1H-NMR) spectroscopy experiments yielded successful quantification of 42 unique metabolites in 2,482 individuals from The Erasmus Rucphen Family (ERF) study. Heritability of metabolites were estimated by SOLAR. GWAS was performed by linear mixed models, using HapMap imputations. Based on physical vicinity and pathway analyses, candidate genes were screened for coding region variation using exome sequence data. Heritability estimates for metabolites ranged between 10% and 52%. GWAS replicated three known loci in the metabolome wide significance: CPS1 with glycine (P-value  = 1.27×10−32), PRODH with proline (P-value  = 1.11×10−19), SLC16A9 with carnitine level (P-value  = 4.81×10−14) and uncovered a novel association between DMGDH and dimethyl-glycine (P-value  = 1.65×10−19) level. In addition, we found three novel, suggestively significant loci: TNP1 with pyruvate (P-value  = 1.26×10−8), KCNJ16 with 3-hydroxybutyrate (P-value  = 1.65×10−8) and 2p12 locus with valine (P-value  = 3.49×10−8). Exome sequence analysis identified potentially causal coding and regulatory variants located in the genes CPS1, KCNJ2 and PRODH, and revealed allelic heterogeneity for CPS1 and PRODH. Combined GWAS and exome analyses of metabolites detected by high-resolution 1H-NMR is a robust approach to uncover metabolite quantitative trait loci (mQTL), and the likely causative variants in these loci. It is anticipated that insight in the genetics of intermediate phenotypes will provide additional insight into the genetics of complex traits