| 1. |
- Aamodt, K., et al.
(författare)
-
The ALICE experiment at the CERN LHC
- 2008
-
Ingår i: Journal of Instrumentation. - 1748-0221. ; 3:S08002
-
Forskningsöversikt (refereegranskat)abstract
- ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries, Its overall dimensions are 16 x 16 x 26 m(3) with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008.
|
|
| 2. |
- Mikkelsen, Tarjei S, et al.
(författare)
-
Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences
- 2007
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7141, s. 167-177
-
Tidskriftsartikel (refereegranskat)abstract
- We report a high-quality draft of the genome sequence of the grey, short-tailed opossum (Monodelphis domestica). As the first metatherian ('marsupial') species to be sequenced, the opossum provides a unique perspective on the organization and evolution of mammalian genomes. Distinctive features of the opossum chromosomes provide support for recent theories about genome evolution and function, including a strong influence of biased gene conversion on nucleotide sequence composition, and a relationship between chromosomal characteristics and X chromosome inactivation. Comparison of opossum and eutherian genomes also reveals a sharp difference in evolutionary innovation between protein-coding and non-coding functional elements. True innovation in protein-coding genes seems to be relatively rare, with lineage-specific differences being largely due to diversification and rapid turnover in gene families involved in environmental interactions. In contrast, about 20% of eutherian conserved non-coding elements (CNEs) are recent inventions that postdate the divergence of Eutheria and Metatheria. A substantial proportion of these eutherian-specific CNEs arose from sequence inserted by transposable elements, pointing to transposons as a major creative force in the evolution of mammalian gene regulation.
|
|
| 3. |
- Aksentijevich, Ivona, et al.
(författare)
-
An Autoinflammatory Disease with Deficiency of the Interleukin-1-Receptor Antagonist
- 2009
-
Ingår i: New England Journal of Medicine. - 0028-4793. ; 360:23, s. 2426-2437
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Autoinflammatory diseases manifest inflammation without evidence of infection, high-titer autoantibodies, or autoreactive T cells. We report a disorder caused by mutations of IL1RN, which encodes the interleukin-1-receptor antagonist, with prominent involvement of skin and bone. METHODS We studied nine children from six families who had neonatal onset of sterile multifocal osteomyelitis, periostitis, and pustulosis. Response to empirical treatment with the recombinant interleukin-1-receptor antagonist anakinra in the first patient prompted us to test for the presence of mutations and changes in proteins and their function in interleukin-1-pathway genes including IL1RN. RESULTS We identified homozygous mutations of IL1RN in nine affected children, from one family from Newfoundland, Canada, three families from the Netherlands, and one consanguineous family from Lebanon. A nonconsanguineous patient from Puerto Rico was homozygous for a genomic deletion that includes IL1RN and five other interleukin-1-family members. At least three of the mutations are founder mutations; heterozygous carriers were asymptomatic, with no cytokine abnormalities in vitro. The IL1RN mutations resulted in a truncated protein that is not secreted, thereby rendering cells hyperresponsive to interleukin-1 beta stimulation. Patients treated with anakinra responded rapidly. CONCLUSIONS We propose the term deficiency of the interleukin-1-receptor antagonist, or DIRA, to denote this autosomal recessive autoinflammatory disease caused by mutations affecting IL1RN. The absence of interleukin-1-receptor antagonist allows unopposed action of interleukin-1, resulting in life-threatening systemic inflammation with skin and bone involvement. (ClinicalTrials.gov number, NCT00059748.)
|
|
| 4. |
- Frank, J., et al.
(författare)
-
Dietary flavonoids with a catechol structure increase alpha-tocopherol in rats and protect the vitamin from oxidation in vitro
- 2006
-
Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 47:12, s. 2718-2725
-
Tidskriftsartikel (refereegranskat)abstract
- To identify dietary phenolic compounds capable of improving vitamin E status, male Sprague-Dawleyrats were fed for 4 weeks either a basal diet ( control) with 2 g/kg cholesterol and an adequate content of vitamin E or the basal diet fortified with quercetin ( Q), (2)-epicatechin (EC), or (1)-catechin ( C) at concentrations of 2 g/kg. All three catechol derivatives substantially increased concentrations of alpha-tocopherol (alpha-T) in blood plasma and liver. To study potential mechanisms underlying the observed increase of alpha-T, the capacities of the Flavonoids to i) protect alpha-T from oxidation in LDL exposed to peroxyl radicals, ii) reduce alpha-tocopheroxyl radicals (alpha-T-.) in SDS micelles, and iii) inhibit the metabolism of tocopherols in HepG2 cells were determined. All flavonoids protected alpha-T from oxidation in human LDL ex vivo and dose-dependently reduced the concentrations of alpha-T-.. None of the test compounds affected vitamin E metabolism in the hepatocyte cultures. In conclusion, fortification of the diet of Sprague-Dawley rats with Q, EC, or C considerably improved their vitamin E status. The underlying mechanism does not appear to involve vitamin E metabolism but may involve direct quenching of free radicals or reduction of the alpha-T-. by the flavonoids.
|
|
| 5. |
- Durand, Caylib A, et al.
(författare)
-
Phosphoinositide 3-kinase p110 delta regulates natural antibody production, marginal zone and B-1 B cell function, and autoantibody responses.
- 2009
-
Ingår i: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 183:9, s. 5673-84
-
Tidskriftsartikel (refereegranskat)abstract
- B-1 and marginal zone (MZ) B cells produce natural Abs, make Ab responses to microbial pathogens, and contribute to autoimmunity. Although the delta isoform of the PI3K p110 catalytic subunit is essential for development of these innate-like B cells, its role in the localization, activation, and function of normal B-1 and MZ B cells is not known. Using IC87114, a highly selective inhibitor of p110delta enzymatic activity, we show that p110delta is important for murine B-1 and MZ B cells to respond to BCR clustering, the TLR ligands LPS and CpG DNA, and the chemoattractants CXCL13 and sphingosine 1-phosphate. In these innate-like B cells, p110delta activity mediates BCR-, TLR- and chemoattractant-induced activation of the Akt prosurvival kinase, chemoattractant-induced migration, and TLR-induced proliferation. Moreover, we found that TLR-stimulated Ab responses by B-1 and MZ B cells, as well as the localization of MZ B cells in the spleen, depend on p110delta activity. Finally, we show that the in vivo production of natural Abs requires p110delta and that p110delta inhibitors can reduce in vivo autoantibody responses. Thus, targeting p110delta may be a novel approach for regulating innate-like B cells and for treating Ab-mediated autoimmune diseases.
|
|
| 6. |
- Lindblad-Toh, Kerstin, et al.
(författare)
-
Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
-
Tidskriftsartikel (refereegranskat)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
|
|
| 7. |
- Moazzami, Ali A., et al.
(författare)
-
Dietary phytosterols inhibit the lipid modulating effects of sesamin in rats
- 2007
-
Ingår i: Current Topics in Nutraceutical Research. - 1540-7535. ; 5:2-3, s. 93-97
-
Tidskriftsartikel (refereegranskat)abstract
- The major lignan in the unsaponifiable fraction of sesame lipids, sesamin, is known to affect lipid metabolism. For example, sesamin inhibits the clearance of tocopherols, the activity of Delta 5-desaturase during fatty acid metabolism, and reduces cholesterol absorption and biosynthesis. In order to study whether dietary phytosterols, which are known to reduce the absorption of lipid soluble dietary factors, may influence the lipid-modulating effects of sesamin, rats were fed, in a 2x2 Latin-square design, diets containing two concentrations of sesamin and pbytosterols for 4 weeks. Tocopherols and cholesterol were analyzed in plasma and liver and the fatty acid profile was determined in liver lipids. Sesamin increased a-tocopherol concentrations in plasma and liver (p< 0. 001), whereas the phytosterols had no effect. However, an increase in the phytosterol content of the diet resulted in a reduction of the alpha-tocopherol-elevating effect of sesamin in plasma (p< 0. 01). Similarly, sesamin increased the percentage of dihomo-gamma-linolenic acid in liver lipids (p<0.05), which was abolished by the addition of pbytosterols. Neither sesamin nor phytosterols significantly altered cholesterol concentrations in plasma or liver. In conclusion, these results suggest that in rats, dietary phytosterols may interact with sesamin in a way reducing its biological activities.
|
|
| 8. |
- Nälsén, C, et al.
(författare)
-
Plasma antioxidant capacity among middle-aged men : the contribution of uric acid
- 2006
-
Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 66:3, s. 239-248
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. Although assays of plasma antioxidant capacity encompass interactions between various antioxidants, uric acid concentration can exert a predominant effect on results. Therefore, individual differences in uric acid concentration may explain a many of the differences in antioxidant capacity. The objective of this study was to measure the antioxidant capacity of plasma samples with and without uric acid in order to provide more information about how the concept of antioxidant capacity could be applied. Material and methods. Antioxidant capacity was measured using an enhanced chemiluminescence assay, and uric acid was removed from the samples using uricase. Results. Antioxidant capacity was positively correlated with uric acid concentration, body mass index, waist circumference, abdominal sagittal diameter and the concentrations of insulin and triglycerides. These correlations were not evident when uric acid was eliminated from the sample, but antioxidant capacity was correlated with lipid concentration; this may partly reflect tocopherols that are transported by lipid molecules. Conclusions. The significance of the contribution of uric acid to the antioxidant capacity could differ according to the type of study. Antioxidant capacity measurements in cross‐sectional studies may be presented both with and without the contribution of uric acid, because the absence of such data complicates interpretation of results when different populations are compared.
|
|
