1. |
- Aamodt, K., et al.
(författare)
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The ALICE experiment at the CERN LHC
- 2008
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 3:S08002
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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.
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2. |
- Abdesselam, A., et al.
(författare)
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Engineering for the ATLAS SemiConductor Tracker (SCT) end-cap
- 2008
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- The ATLAS SemiConductor Tracker (SCT) is a silicon-strip tracking detector which forms part of the ATLAS inner detector. The SCT is designed to track charged particles produced in proton-proton collisions at the Large Hadron Collider (LHC) at CERN at an energy of 14 TeV. The tracker is made up of a central barrel and two identical end-caps. The barrel contains 2112 silicon modules, while each end-cap contains 988 modules. The overall tracking performance depends not only on the intrinsic measurement precision of the modules but also on the characteristics of the whole assembly, in particular, the stability and the total material budget. This paper describes the engineering design and construction of the SCT end-caps, which are required to support mechanically the silicon modules, supply services to them and provide a suitable environment within the inner detector. Critical engineering choices are highlighted and innovative solutions are presented - these will be of interest to other builders of large-scale tracking detectors. The SCT end-caps will be fully connected at the start of 2008. Further commissioning will continue, to be ready for proton-proton collision data in 2008.
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3. |
- Abdesselam, A., et al.
(författare)
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The ATLAS semiconductor tracker end-cap module
- 2007
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 575:3, s. 353-389
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Tidskriftsartikel (refereegranskat)abstract
- The challenges for the tracking detector systems at the LHC are unprecedented in terms of the number of channels, the required read-out speed and the expected radiation levels. The ATLAS Semiconductor Tracker. (SCT) end-caps have a total of about 3 million electronics channels each reading out every 25 ns into its own on-chip 3.3 mu s buffer. The highest anticipated dose after 10 years operation is 1.4x10(14) cm(-2) in units of 1 MeV neutron equivalent (assuming the damage factors scale with the non-ionising energy loss). The forward tracker has 1976 double-sided modules, mostly of area similar to 70 cm(2), each having 2 x 768 strips read out by six ASICs per side. The requirement to achieve an average perpendicular radiation length of 1.5% X-0, while coping with up to 7 W dissipation per module (after irradiation), leads to stringent constraints on the thermal design. The additional requirement of 1500e(-) equivalent noise charge (ENC) rising to only 1800e(-) ENC after irradiation, provides stringent design constraints on both the high-density Cu/Polyimide flex read-out circuit and the ABCD3TA read-out ASICs. Finally, the accuracy of module assembly must not compromise the 16 mu m (r phi) resolution perpendicular to the strip directions or 580 mu m radial resolution coming from the 40 mrad front-back stereo angle. A total of 2210 modules were built to the tight tolerances and specifications required for the SCT. This was 234 more than the 1976 required and represents a yield of 93%. The component flow was at times tight, but the module production rate of 40-50 per week was maintained despite this. The distributed production was not found to be a major logistical problem and it allowed additional flexibility to take advantage of where the effort was available, including any spare capacity, for building the end-cap modules. The collaboration that produced the ATLAS SCT end-cap modules kept in close contact at all times so that the effects of shortages or stoppages at different sites could be rapidly resolved.
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4. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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5. |
- Elsik, Christine G., et al.
(författare)
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The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
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Tidskriftsartikel (refereegranskat)abstract
- To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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6. |
- Margulies, Elliott H, et al.
(författare)
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Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome
- 2007
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 17:6, s. 760-774
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Tidskriftsartikel (refereegranskat)abstract
- A key component of the ongoing ENCODE project involves rigorous comparative sequence analyses for the initially targeted 1% of the human genome. Here, we present orthologous sequence generation, alignment, and evolutionary constraint analyses of 23 mammalian species for all ENCODE targets. Alignments were generated using four different methods; comparisons of these methods reveal large-scale consistency but substantial differences in terms of small genomic rearrangements, sensitivity (sequence coverage), and specificity (alignment accuracy). We describe the quantitative and qualitative trade-offs concomitant with alignment method choice and the levels of technical error that need to be accounted for in applications that require multisequence alignments. Using the generated alignments, we identified constrained regions using three different methods. While the different constraint-detecting methods are in general agreement, there are important discrepancies relating to both the underlying alignments and the specific algorithms. However, by integrating the results across the alignments and constraint-detecting methods, we produced constraint annotations that were found to be robust based on multiple independent measures. Analyses of these annotations illustrate that most classes of experimentally annotated functional elements are enriched for constrained sequences; however, large portions of each class (with the exception of protein-coding sequences) do not overlap constrained regions. The latter elements might not be under primary sequence constraint, might not be constrained across all mammals, or might have expendable molecular functions. Conversely, 40% of the constrained sequences do not overlap any of the functional elements that have been experimentally identified. Together, these findings demonstrate and quantify how many genomic functional elements await basic molecular characterization.
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7. |
- Gross, O, et al.
(författare)
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Stem cell therapy for Alport syndrome: the hope beyond the hype
- 2009
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Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 24:3, s. 731-734
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Tidskriftsartikel (refereegranskat)
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8. |
- Lip, Gregory Y. H., et al.
(författare)
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Oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation: a randomized dose-guiding, safety, and tolerability study of four doses of AZD0837 vs. vitamin K antagonists
- 2009
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 30:23, s. 2897-2907
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Tidskriftsartikel (refereegranskat)abstract
- Aims Oral anticoagulation with vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF) is effective but has significant limitations. AZD0837, a new oral anticoagulant, is a prodrug converted to a selective and reversible direct thrombin inhibitor (AR-H067637). We report from a Phase II randomized, dose-guiding study (NCT00684307) to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of extended-release AZD0837 in patients with AF. Methods and results Atrial fibrillation patients (n = 955) with >= 1 additional risk factor for stroke were randomized to receive AZD0837 (150, 300, or 450 mg once daily or 200 mg twice daily) or VKA (international normalized ratio 2-3, target 2.5) for 3-9 months. Approximately 30% of patients were naive to VKA treatment. Total bleeding events were similar or lower in all AZD0837 groups (5.3-14.7%, mean exposure 138-145 days) vs. VKA (14.5%, mean exposure 161 days), with fewer clinically relevant bleeding events on AZD0837 150 and 300 mg once daily. Adverse events were similar between treatment groups; with AZD0837, the most common were gastrointestinal disorders (e.g. diarrhoea, flatulence, or nausea). D-Dimer, used as a biomarker of thrombogenesis, decreased in all groups in VKA-naive subjects with treatment, whereas in VKA pre-treated patients, D-dinner levels started tow and remained low in all groups. As expected, only a few strokes or systemic embolic events occurred. In the AZD0837 groups, mean S-creatinine increased by similar to 10% from baseline and returned to baseline following treatment cessation. The frequency of serum alanine aminotransferase >= 3 x upper limit of normal was similar for AZD0837 and VKA. Conclusion AZD0837 was generally well tolerated at all doses tested. AZD0837 treatment at an exposure corresponding to the 300 mg od dose in this study provides similar suppression of thrombogenesis at a potentially lower bleeding risk compared with dose-adjusted VKA.
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9. |
- Pasquini, Ricardo, et al.
(författare)
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HLA-matched sibling hematopoietic stem cell transplantation for fanconi anemia: comparison of irradiation and nonirradiation containing conditioning regimens.
- 2008
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Ingår i: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. - : Elsevier BV. - 1523-6536. ; 14:10, s. 1141-7
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Tidskriftsartikel (refereegranskat)abstract
- Related to the underlying DNA repair defect that is the hallmark of Fanconi anemia (FA), preparatory regimen-related toxicities have been obstacles to hematopoietic cell transplantation (HCT). In an attempt to decrease the risk and severity of regimen-related toxicities, nonirradiation regimens have been explored. The aim of this study is to compare outcomes after irradiation and nonirradiation regimens in 148 FA patients and identify risk factors impacting upon HCT outcomes. Hematopoietic recovery, acute and chronic graft-versus-host disease (aGVHD, GVHD), and mortality were similar after irradiation and nonirradiation regimens. In both groups of recipients aged >10 years, prior use of androgens and cytomegalovirus seropositivity in either the donor or recipient were associated with higher mortality. With median follow-ups >5 years, the 5-year probability of overall survival, adjusted for factors impacting overall mortality was 78% and 81% after irradiation and nonirradiation regimens, P = .61. In view of the high risk of cancer and other radiation-related effects on growth and development, these results support the use of nonirradiation preparatory regimens. As the peak time for developing solid tumors after HCT is 8 to 9 years, longer follow-up is required before definitive statements can be made regarding the impact of nonirradiation regimens on cancer risk.
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13. |
- Bogdanis, Gregory C., et al.
(författare)
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Influence of resistive load on power output and fatigue during intermittent sprint cycling exercise in children
- 2007
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Ingår i: European Journal of Applied Physiology. - : Springer. - 1439-6319 .- 1439-6327. ; 101:3, s. 313-320
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Tidskriftsartikel (refereegranskat)abstract
- This study examined the effects of two resistive loads on fatigue during repeated sprints in children. Twelve 11.8 (0.2) year old boys performed a force-velocity test to determine the load (Fopt) corresponding to the optimal pedal rate. On two separate occasions, ten 6-s sprints interspersed with 24-s recovery intervals were performed on a friction-loaded cycle ergometer, against a load equal to Fopt or 50%Fopt. Although mean power output (MPO) was higher in the Fopt [397 (24) and 356 (19) W, P < 0.01], the decline in MPO over the 10 sprints was similar in Fopt [8.8 (1.9) %] and 50%Fopt [9.0 (2.4) %]. In contrast, peak power (PPO) was not different in sprint 1 between the two conditions [459 (24) and 460 (28) W], but was decreased only in 50%Fopt [11.4 (3.2) %, P < 0.01], while it was maintained in the Fopt despite the higher total work during each sprint. Fatigue within each sprint (percent drop from peak to end power output) was also higher in the 50%Fopt compared with the Fopt [32 (2.5) vs. 10 (1.6) %, P < 0.01]. Peak and mean pedal rate in Fopt condition were close to the optimum (Vopt), while a large part of the sprint time in 50%Fopt was spent far from Vopt. The present study shows that sprinting against Fopt reduces fatigue within and between repeated short sprints in children. It is suggested that fatigue during repeated sprints is modified when pedal rate is not close to Vopt, according to the parabolic power versus pedal rate relationship.
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14. |
- Bromley, Elizabeth H. C., et al.
(författare)
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The Tumbleweed: towards a synthetic protein motor
- 2009
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Ingår i: HFSP Journal. - : Informa UK Limited. - 1955-2068. ; 3:3, s. 204-212
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Tidskriftsartikel (refereegranskat)abstract
- Biomolecular motors have inspired the design and construction of artificial nanoscale motors and machines based on nucleic acids, small molecules, and inorganic nanostructures. However, the high degree of sophistication and efficiency of biomolecular motors, as well as their specific biological function, derives from the complexity afforded by protein building blocks. Here, we discuss a novel bottom-up approach to understanding biological motors by considering the construction of synthetic protein motors. Specifically, we present a design for a synthetic protein motor that moves along a linear track, dubbed the "Tumbleweed." This concept uses three discrete ligand-dependent DNA-binding domains to perform cyclically ligand-gated, rectified diffusion along a synthesized DNA molecule. Here we describe how de novo peptide design and molecular biology could be used to produce the Tumbleweed, and we explore the fundamental motor operation of such a design using numerical simulations. The construction of this and more sophisticated protein motors is an exciting challenge that is likely to enhance our understanding of the structure-function relationship in biological motors. [DOI: 10.2976/1.3111282]
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15. |
- Chang-Claude, Jenny, et al.
(författare)
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Age at menarche and menopause and breast cancer risk in the International BRCA1/2 Carrier Cohort Study
- 2007
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Ingår i: Cancer Epidemiology Biomarkers and Prevention. - 1055-9965. ; 16:4, s. 740-746
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early menarche and late menopause are important risk factors for breast cancer, but their effects on breast cancer risk in BRCA1 and BRCA2 carriers are unknown. Methods: We assessed breast cancer risk in a large series of 1,187 BRCA1 and 414 BRCA2 carriers from the International BRCA1/2 Carrier Cohort Study. Rate ratios were estimated using a weighted Cox-regression approach. Results: Breast cancer risk was not significantly related to age at menopause {hazard ratio [HR] for menopause below age 35 years, 0.60 [95% confidence interval (95% CI), 0.25-1.44]; 35 to 40 years, 1.15 [0.65-2.04]; 45 to 54 years, 1.02 [0.65-1.60]; ≥55 years, 1.12 [0.12-5.02], as compared with premenopausal women}. However, there was some suggestion of a reduction in risk after menopause in BRCA2 carriers. There was some evidence of a protective effect of oophorectomy (HR, 0.56; 95% CI, 0.29-1.09) and a significant trend of decreasing risk with increasing time since oophorectomy, but no apparent effect of natural menopause. There was no association between age at menarche and breast cancer risk, nor any apparent association with the estimated total duration of breast mitotic activity. Conclusions: These results are consistent with other observations suggesting a protective effect of oophorectomy, similar in relative effect to that in the general population. The absence of an effect of age at natural menopause is, however, not consistent with findings in the general population and may reflect the different natural history of the disease in carriers.
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17. |
- Daley, Allison C., 1980-, et al.
(författare)
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The Burgess Shale Anomalocaridid Hurdia and Its Significance for Early Euarthropod Evolution
- 2009
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Ingår i: Science. - Washington, DC : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 323:5921, s. 1597-1600
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Tidskriftsartikel (refereegranskat)abstract
- As the largest predators of the Cambrian seas, the anomalocaridids had an important impact in structuring the first complex marine animal communities, but many aspects of anomalocaridid morphology, diversity, ecology, and affinity remain unclear owing to a paucity of specimens. Here we describe the anomalocaridid Hurdia, based on several hundred specimens from the Burgess Shale in Canada. Hurdia possesses a general body architecture similar to Anomalocaris and Laggania, including the presence of exceptionally well-preserved gills, but differs from those anomalocaridids by possessing a prominent anterior carapace structure. These features amplify and clarify the diversity of known anomalocaridid morphology and provide insight into the origins of important arthropod features, such as the head shield and respiratory exites.
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18. |
- Dunn, Casey W, et al.
(författare)
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Broad phylogenomic sampling improves resolution of the animal tree of life.
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 452:7188, s. 745-9
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Tidskriftsartikel (refereegranskat)abstract
- Long-held ideas regarding the evolutionary relationships among animals have recently been upended by sometimes controversial hypotheses based largely on insights from molecular data. These new hypotheses include a clade of moulting animals (Ecdysozoa) and the close relationship of the lophophorates to molluscs and annelids (Lophotrochozoa). Many relationships remain disputed, including those that are required to polarize key features of character evolution, and support for deep nodes is often low. Phylogenomic approaches, which use data from many genes, have shown promise for resolving deep animal relationships, but are hindered by a lack of data from many important groups. Here we report a total of 39.9 Mb of expressed sequence tags from 29 animals belonging to 21 phyla, including 11 phyla previously lacking genomic or expressed-sequence-tag data. Analysed in combination with existing sequences, our data reinforce several previously identified clades that split deeply in the animal tree (including Protostomia, Ecdysozoa and Lophotrochozoa), unambiguously resolve multiple long-standing issues for which there was strong conflicting support in earlier studies with less data (such as velvet worms rather than tardigrades as the sister group of arthropods), and provide molecular support for the monophyly of molluscs, a group long recognized by morphologists. In addition, we find strong support for several new hypotheses. These include a clade that unites annelids (including sipunculans and echiurans) with nemerteans, phoronids and brachiopods, molluscs as sister to that assemblage, and the placement of ctenophores as the earliest diverging extant multicellular animals. A single origin of spiral cleavage (with subsequent losses) is inferred from well-supported nodes. Many relationships between a stable subset of taxa find strong support, and a diminishing number of lineages remain recalcitrant to placement on the tree.
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19. |
- Fletcher, John, 1978, et al.
(författare)
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Uncovering new challenges in bio-analysis with ToF-SIMS
- 2008
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Ingår i: Applied Surface Science. - : Elsevier BV. - 0169-4332. ; 255:4, s. 1264-1270
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Konferensbidrag (refereegranskat)abstract
- The introduction of cluster ion beams for routine SIMS analysis has greatly improved the prospects for characterising biological samples. The ultimate quality of the secondary ion image remains limited by the efficiency of the primary beam. Without overcoming the low ionisation probabilities associated with SIMS, the highest lateral resolution available for molecular imaging becomes limited by the statistical probability of any ions being generated from the area of the pixel. C(60)(+) primary ions are currently the most efficient available for routine analysis but although commercial systems have been demonstrated to produce spot sizes under 200 nm, focusing the beam produced in such electron impact sources results in rather low ion currents. The time scale for such high lateral resolution analysis can become impractical on conventional time-of-flight instruments. Molecular depth pro. ling capability has been revealed using SF(5)(+) and C(60)(+) ion beams and recent work has advanced the technique by combining the pro. ling and imaging abilities of these high efficiency projectiles to generate 3D molecular maps of biological systems. In this paper we discuss the challenges associated with 2D and 3D bio-analysis with emphasis on how instrumental advances aid such investigations yet demonstrating the obstacles that need to be overcome using a range of model and real world biological samples. We discuss complications with the biological matrix, challenges in manipulating and visualising the data and look at how instrumental advantages might aid the routine generation of these 3D molecular maps. (C) 2008 Elsevier B. V. All rights reserved.
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22. |
- Gudbjartsson, Daniel F., et al.
(författare)
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Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:3, s. 342-347
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).
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23. |
- Houde, Magali, et al.
(författare)
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POLYBROMINATED DIPHENYL ETHERS AND THEIR HYDROXYLATED ANALOGS IN PLASMA OF BOTTLENOSE DOLPHINS (TURSIOPS TRUNCATUS) FROM THE UNITED STATES EAST COAST.
- 2009
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Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 28:10, s. 2061-2068
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Tidskriftsartikel (refereegranskat)abstract
- Polybrominated diphenyl ethers (PBDEs) and hydroxylated-PBDEs (OH-PBDE) were determined in plasma of free-ranging bottlenose dolphins (Tursiops truncatus) from Charleston (CHS), South Carolina, and the Indian River Lagoon (IRL), Florida, US. Significantly lower sum (Sigma) of PBDE concentrations (sum of 12 congeners) were found in animals from the IRL [arithmetic mean: 5.454.63 ng/g wet weight (ww)] compared to CHS (3040 ng/g ww). BDE-47 was the predominant PBDE in dolphins from the IRL (50% of the SigmaPBDEs) and CHS (58%). SigmaPBDE concentrations in plasma of dolphins were negatively correlated with age at both locations. Fifteen and sixteen individual OH-PBDE congeners could be quantified in plasma of dolphins from IRL and CHS, respectively. Similar to SigmaPBDE, mean SigmaOH-PBDE concentrations were significantly higher in plasma of dolphins at CHS (1150708 pg/g ww) compared to IRL (624393 pg/g ww). The predominant congener at both locations was 6-OH-PBDE 47 (IRL: 384319 pg/g ww; CHS: 541344 pg/g ww) representing 61.5% of total SigmaOH-PBDE at IRL and 47.0% at CHS. Concentrations of SigmaOH-PBDEs were weakly negatively correlated with age in dolphins from both locations (P<0.05; IRL, R2=0.048; CHS, R2=0.021). In addition to the OH-PBDE congeners identified with technical standards, eight and four unidentified OH-PBDEs were detected and quantified respectively in animals from CHS (sum of unidentified OH-PBDEs=1.350.90 pg/g ww) and IRL (0.730.40 pg/g ww). Our results suggest that, unlike OH-PCBs, OH-PBDEs in bottlenose dolphins are minor products in plasma relative to SigmaPBDEs and a significant proportion may be a consequence of the dietary uptake of naturally produced methoxylated- and OH-PBDEs.
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24. |
- Kabosova, Andrea, et al.
(författare)
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Compositional differences between infant and adult human corneal basement membranes
- 2007
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 48:11, s. 4989-4999
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. Adult human corneal epithelial basement membrane ( EBM) and Descemet's membrane ( DM) components exhibit heterogeneous distribution. The purpose of the study was to identify changes of these components during postnatal corneal development. METHODS. Thirty healthy adult corneas and 10 corneas from 12-day- to 3-year-old children were studied by immunofluorescence with antibodies against BM components. RESULTS. Type IV collagen composition of infant corneal central EBM over Bowman's layer changed from alpha 1-alpha 2 to alpha 3-alpha 4 chains after 3 years of life; in the adult, alpha 1-alpha 2 chains were retained only in the limbal BM. Laminin alpha 2 and beta 2 chains were present in the adult limbal BM where epithelial stem cells are located. By 3 years of age, beta 2 chain appeared in the limbal BM. In all corneas, limbal BM contained laminin gamma 3 chain. In the infant DM, type IV collagen alpha 1-alpha 6 chains, perlecan, nidogen-1, nidogen-2, and netrin-4 were found on both faces, but they remained only on the endothelial face of the adult DM. The stromal face of the infant but not the adult DM was positive for tenascin-C, fibrillin-1, SPARC, and laminin-332. Type VIII collagen shifted from the endothelial face of infant DM to its stromal face in the adult. Matrilin-4 largely disappeared after the age of 3 years. CONCLUSIONS. The distribution of laminin gamma 3 chain, nidogen-2, netrin-4, matrilin-2, and matrilin-4 is described in the cornea for the first time. The observed differences between adult and infant corneal BMs may relate to changes in their mechanical strength, corneal cell adhesion and differentiation in the process of postnatal corneal maturation.
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25. |
- Keenan, Thomas M, et al.
(författare)
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Automated identification of axonal growth cones in time-lapse image sequences.
- 2006
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Ingår i: Journal of Neuroscience Methods. - : Elsevier BV. - 0165-0270 .- 1872-678X. ; 151:2, s. 232-8
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Tidskriftsartikel (refereegranskat)abstract
- The isolation and purification of axon guidance molecules has enabled in vitro studies of the effects of axon guidance molecule gradients on numerous neuronal cell types. In a typical experiment, cultured neurons are exposed to a chemotactic gradient and their growth is recorded by manual identification of the axon tip position from two or more micrographs. Detailed and statistically valid quantification of axon growth requires evaluation of a large number of neurons at closely spaced time points (e.g. using a time-lapse microscopy setup). However, manual tracing becomes increasingly impractical for recording axon growth as the number of time points and/or neurons increases. We present a software tool that automatically identifies and records the axon tip position in each phase-contrast image of a time-lapse series with minimal user involvement. The software outputs several quantitative measures of axon growth, and allows users to develop custom measurements. For, example analysis of growth velocity for a dissociated E13 mouse cortical neuron revealed frequent extension and retraction events with an average growth velocity of 0.05 +/- 0.14 microm/min. Comparison of software-identified axon tip positions with manually identified axon tip positions shows that the software's performance is indistinguishable from that of skilled human users.
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