| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Arking, D. E., et al.
(author)
-
Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
- 2014
-
In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
-
Journal article (peer-reviewed)abstract
- The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc.
|
|
| 7. |
- Berthomier, M., et al.
(author)
-
Alfven : magnetosphere-ionosphere connection explorers
- 2012
-
In: Experimental astronomy. - Dordrecht : Springer. - 0922-6435 .- 1572-9508. ; 33:2-3, s. 445-489
-
Journal article (peer-reviewed)abstract
- The aurorae are dynamic, luminous displays that grace the night skies of Earth's high latitude regions. The solar wind emanating from the Sun is their ultimate energy source, but the chain of plasma physical processes leading to auroral displays is complex. The special conditions at the interface between the solar wind-driven magnetosphere and the ionospheric environment at the top of Earth's atmosphere play a central role. In this Auroral Acceleration Region (AAR) persistent electric fields directed along the magnetic field accelerate magnetospheric electrons to the high energies needed to excite luminosity when they hit the atmosphere. The "ideal magnetohydrodynamics" description of space plasmas which is useful in much of the magnetosphere cannot be used to understand the AAR. The AAR has been studied by a small number of single spacecraft missions which revealed an environment rich in wave-particle interactions, plasma turbulence, and nonlinear acceleration processes, acting on a variety of spatio-temporal scales. The pioneering 4-spacecraft Cluster magnetospheric research mission is now fortuitously visiting the AAR, but its particle instruments are too slow to allow resolve many of the key plasma physics phenomena. The Alfv,n concept is designed specifically to take the next step in studying the aurora, by making the crucial high-time resolution, multi-scale measurements in the AAR, needed to address the key science questions of auroral plasma physics. The new knowledge that the mission will produce will find application in studies of the Sun, the processes that accelerate the solar wind and that produce aurora on other planets.
|
|
| 8. |
- Fernandez, J. L. Abelleira, et al.
(author)
-
A Large Hadron Electron Collider at CERN
- 2012
-
In: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 39:7
-
Journal article (peer-reviewed)
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Regev, A, et al.
(author)
-
The Human Cell Atlas
- 2017
-
In: eLife. - : ELIFE SCIENCES PUBLICATIONS LTD. - 2050-084X. ; 6
-
Journal article (peer-reviewed)
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
- Zhang, W., et al.
(author)
-
EULAR evidence-based recommendations for the diagnosis of hand osteoarthritis: report of a task force of ESCISIT
- 2009
-
In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 68:1, s. 8-17
-
Research review (peer-reviewed)abstract
- Objectives: To develop evidence-based recommendations for the diagnosis of hand osteoarthritis (OA). Methods: The multidisciplinary guideline development group, representing 15 European countries, generated 10 key propositions regarding diagnosis using a Delphi consensus approach. For each recommendation, research evidence was searched for systematically. Whenever possible, the sensitivity, specificity and likelihood ratio (LR) were calculated; relative risk and odds ratios were estimated for risk factors for hand OA. Quality of evidence was categorised using the European League Against Rheumatism (EULAR) hierarchy, and strength of recommendation was assessed by the EULAR visual analogue scale. Results: Diagnostic topics included clinical manifestations, radiographic features, subgroups, differential diagnosis, laboratory tests, risk factors and comorbidities. The sensitivity, specificity and LR varied between tests depending upon the cut-off level, gold standard and controls. Overall, no single test could be used to define hand OA on its own (LR,10) but a composite of the tests greatly increased the chance of the diagnosis. The probability of a subject having hand OA was 20% when Heberden nodes alone were present, but this increased to 88% when in addition the subject was over 40 years old, had a family history of nodes and had joint space narrowing in any finger joint. Conclusion: Ten key recommendations for diagnosis of hand OA were developed using research evidence and expert consensus. Diagnosis of hand OA should be based on assessment of a composite of features.
|
|
| 17. |
- Andersen, J. R., et al.
(author)
-
Small-x phenomenology - Summary of the 3rd Lund small-x workshop in 2004
- 2006
-
In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 48:1, s. 53-105
-
Research review (peer-reviewed)abstract
- A third workshop on small-x physics, within the Small-x Collaboration, was held in Hamburg in May 2004 with the aim of overviewing recent theoretical progress in this area and summarizing the experimental status.
|
|
| 18. |
- Clark, Pip C.J., et al.
(author)
-
The passivating effect of cadmium in PbS/CdS colloidal quantum dots probed by nm-scale depth profiling
- 2017
-
In: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 9:18, s. 6056-6067
-
Journal article (peer-reviewed)abstract
- Achieving control of the surface chemistry of colloidal quantum dots (CQDs) is essential to fully exploit their properties in solar cells, but direct measurement of the chemistry and electronic structure in the outermost atomic layers is challenging. Here we probe the surface oxidation and passivation of cation-exchanged PbS/CdS core/shell CQDs with sub nm-scale precision using synchrotron-radiation-excited depth-profiling photoemission. We investigate the surface composition of the topmost 1-2.5 nm of the CQDs as a function of depth, for CQDs of varying CdS shell thickness, and examine how the surface changes after prolonged air exposure. We demonstrate that the Cd is localized at the surface of the CQDs. The surface-localized products of oxidation are identified, and the extent of oxidation quantified. We show that oxidised sulfur species are progressively eliminated as Cd replaces Pb at the surface. A sub-monolayer surface 'decoration' of Cd is found to be effective in passivating the CQDs. We show that the measured energy-level alignments at PbS/CdS colloidal quantum dot surfaces differ from those expected on the basis of bulk band offsets, and are strongly affected by the oxidation products. We develop a model for the passivating action of Cd. The optimum shell thickness (of around 0.1 nm, previously found to give maximised power conversion efficiency in PbS/CdS solar cells) is found to correspond to a trade-off between the rate of oxidation and the introduction of a surface barrier to charge transport.
|
|
| 19. |
- Forsyth, C., et al.
(author)
-
In situ spatiotemporal measurements of the detailed azimuthal substructure of the substorm current wedge
- 2014
-
In: Journal of Geophysical Research: Space Physics. - 2169-9380. ; 119:2, s. 927-946
-
Journal article (peer-reviewed)abstract
- The substorm current wedge (SCW) is a fundamental component of geomagnetic substorms. Models tend to describe the SCW as a simple line current flowing into the ionosphere toward dawn and out of the ionosphere toward dusk, linked by a westward electrojet. We use multispacecraft observations from perigee passes of the Cluster 1 and 4 spacecraft during a substorm on 15 January 2010, in conjunction with ground-based observations, to examine the spatial structuring and temporal variability of the SCW. At this time, the spacecraft traveled east-west azimuthally above the auroral region. We show that the SCW has significant azimuthal substructure on scales of 100km at altitudes of 4000-7000km. We identify 26 individual current sheets in the Cluster 4 data and 34 individual current sheets in the Cluster 1 data, with Cluster 1 passing through the SCW 120-240s after Cluster 4 at 1300-2000km higher altitude. Both spacecraft observed large-scale regions of net upward and downward field-aligned current, consistent with the large-scale characteristics of the SCW, although sheets of oppositely directed currents were observed within both regions. We show that the majority of these current sheets were closely aligned to a north-south direction, in contrast to the expected east-west orientation of the preonset aurora. Comparing our results with observations of the field-aligned current associated with bursty bulk flows (BBFs), we conclude that significant questions remain for the explanation of SCW structuring by BBF-driven wedgelets. Our results therefore represent constraints on future modeling and theoretical frameworks on the generation of the SCW.
|
|
| 20. |
- Forsyth, C., et al.
(author)
-
Temporal evolution and electric potential structure of the auroral acceleration region from multispacecraft measurements
- 2012
-
In: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 117:12, s. A12203-
-
Journal article (peer-reviewed)abstract
- Bright aurorae can be excited by the acceleration of electrons into the atmosphere in violation of ideal magnetohydrodynamics. Modeling studies predict that the accelerating electric potential consists of electric double layers at the boundaries of an acceleration region but observations suggest that particle acceleration occurs throughout this region. Using multispacecraft observations from Cluster, we have examined two upward current regions on 14 December 2009. Our observations show that the potential difference below C4 and C3 changed by up to 1.7 kV between their respective crossings, which were separated by 150 s. The field-aligned current density observed by C3 was also larger than that observed by C4. The potential drop above C3 and C4 was approximately the same in both crossings. Using a novel technique of quantitively comparing the electron spectra measured by Cluster 1 and 3, which were separated in altitude, we determine when these spacecraft made effectively magnetically conjugate observations, and we use these conjugate observations to determine the instantaneous distribution of the potential drop in the AAR. Our observations show that an average of 15% of the potential drop in the AAR was located between C1 at 6235 km and C3 at 4685 km altitude, with a maximum potential drop between the spacecraft of 500 V, and that the majority of the potential drop was below C3. Assuming a spatial invariance along the length of the upward current region, we discuss these observations in terms of temporal changes and the vertical structure of the electrostatic potential drop and in the context of existing models and previous single- and multispacecraft observations.
|
|
| 21. |
- Grose, R, et al.
(author)
-
A crucial role of beta 1 integrins for keratinocyte migration in vitro and during cutaneous wound repair
- 2002
-
In: Development: For advances in developmental biology and stem cells. - 1477-9129. ; 129:9, s. 2303-2315
-
Journal article (peer-reviewed)abstract
- Integrins are ubiquitous transmembrane receptors that play crucial roles in cell-cell and cell-matrix interactions. In this study, we have determined the effects of the loss of beta1 integrins in keratinocytes in vitro and during cutaneous wound repair. Flow cytometry of cultured beta1-deficient keratinocytes confirmed the absence of beta1 integrins and showed downregulation of alpha6beta4 but not of alphanu integrins. beta1-null keratinocytes were characterised by poor adhesion to various substrates, by a reduced proliferation rate and by a strongly impaired migratory capacity. In vivo, the loss of 01 integrins in keratinocytes caused a severe defect in wound healing. beta1-null keratinocytes showed impaired migration and were more densely packed in the hyperproliferative epithelium. Surprisingly, their proliferation rate was not reduced in early wounds and even increased in late wounds. The failure in re-epithelialisation resulted in a prolonged inflammatory response, leading to dramatic alterations in the expression of important wound-regulated genes. Ultimately, beta1-deficient epidermis did cover the wound bed, but the epithelial architecture was abnormal. These findings demonstrate a crucial role of beta1 integrins in keratinocyte migration and wound re-epithelialisation.
|
|
| 22. |
- Kettle, B., et al.
(author)
-
Single-Shot Multi-keV X-Ray Absorption Spectroscopy Using an Ultrashort Laser-Wakefield Accelerator Source
- 2019
-
In: Physical Review Letters. - 0031-9007. ; 123:25
-
Journal article (peer-reviewed)abstract
- Single-shot absorption measurements have been performed using the multi-keV x rays generated by a laser-wakefield accelerator. A 200 TW laser was used to drive a laser-wakefield accelerator in a mode which produced broadband electron beams with a maximum energy above 1 GeV and a broad divergence of ≈15 mrad FWHM. Betatron oscillations of these electrons generated 1.2±0.2×106 photons/eV in the 5 keV region, with a signal-to-noise ratio of approximately 300 1. This was sufficient to allow high-resolution x-ray absorption near-edge structure measurements at the K edge of a titanium sample in a single shot. We demonstrate that this source is capable of single-shot, simultaneous measurements of both the electron and ion distributions in matter heated to eV temperatures by comparison with density functional theory simulations. The unique combination of a high-flux, large bandwidth, few femtosecond duration x-ray pulse synchronized to a high-power laser will enable key advances in the study of ultrafast energetic processes such as electron-ion equilibration.
|
|
| 23. |
|
|
| 24. |
- Tyrrell, Jessica, et al.
(author)
-
Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) interacts with maternal self-reported smoking status during pregnancy to influence birth weight.
- 2012
-
In: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 21:24, s. 5344-5358
-
Journal article (peer-reviewed)abstract
- Maternal smoking during pregnancy is associated with low birth weight. Common variation at rs1051730 is robustly associated with smoking quantity and was recently shown to influence smoking cessation during pregnancy, but its influence on birth weight is not clear. We aimed to investigate the association between this variant and birth weight of term, singleton offspring in a well-powered meta-analysis. We stratified 26 241 European origin study participants by smoking status (women who smoked during pregnancy versus women who did not smoke during pregnancy) and, in each stratum, analysed the association between maternal rs1051730 genotype and offspring birth weight. There was evidence of interaction between genotype and smoking (P = 0.007). In women who smoked during pregnancy, each additional smoking-related T-allele was associated with a 20 g [95% confidence interval (95% CI): 4-36 g] lower birth weight (P = 0.014). However, in women who did not smoke during pregnancy, the effect size estimate was 5 g per T-allele (95% CI: -4to 14 g; P = 0.268). To conclude, smoking status during pregnancy modifies the association between maternal rs1051730 genotype and offspring birth weight. This strengthens the evidence that smoking during pregnancy is causally related to lower offspring birth weight and suggests that population interventions that effectively reduce smoking in pregnant women would result in a reduced prevalence of low birth weight.
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
- Winbanks, Catherine E., et al.
(author)
-
The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass
- 2013
-
In: Journal of Cell Biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 203:2, s. 345-357
-
Journal article (peer-reviewed)abstract
- Although the canonical transforming growth factor. signaling pathway represses skeletal muscle growth and promotes muscle wasting, a role in muscle for the parallel bone morphogenetic protein (BMP) signaling pathway has not been defined. We report, for the first time, that the BMP pathway is a positive regulator of muscle mass. Increasing the expression of BMP7 or the activity of BMP receptors in muscles induced hypertrophy that was dependent on Smad1/5-mediated activation of mTOR signaling. In agreement, we observed that BMP signaling is augmented in models of muscle growth. Importantly, stimulation of BMP signaling is essential for conservation of muscle mass after disruption of the neuromuscular junction. Inhibiting the phosphorylation of Smad1/5 exacerbated denervation-induced muscle atrophy via an HDAC4-myogenin-dependent process, whereas increased BMP-Smad1/5 activity protected muscles from denervation- induced wasting. Our studies highlight a novel role for the BMP signaling pathway in promoting muscle growth and inhibiting muscle wasting, which may have significant implications for the development of therapeutics for neuromuscular disorders.
|
|
| 28. |
- Zhang, W., et al.
(author)
-
EULAR evidence-based recommendations for the diagnosis of knee osteoarthritis
- 2010
-
In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 69:3, s. 483-489
-
Research review (peer-reviewed)abstract
- Objective To develop evidence-based recommendations for the diagnosis of knee osteoarthritis (OA). Methods The multidisciplinary guideline development group, representing 12 European countries, generated 10 key propositions regarding diagnosis using a Delphi consensus approach. For each recommendation, research evidence was searched systematically. Whenever possible, the sensitivity, specificity and likelihood ratio were calculated for individual diagnostic indicators and a diagnostic ladder was developed using Bayes' method. Secondary analyses were undertaken to test directly the recommendations using multiple predictive models in two populations from the UK and the Netherlands. Strength of recommendation was assessed by the EULAR visual analogue scale. Results Recommendations covered the definition of knee OA and its risk factors, subsets, typical symptoms and signs, the use of imaging and laboratory tests and differential diagnosis. Three symptoms (persistent knee pain, limited morning stiffness and reduced function) and three signs (crepitus, restricted movement and bony enlargement) appeared to be the most useful. Assuming a 12.5% background prevalence of knee OA in adults aged >= 45 years, the estimated probability of having radiographic knee OA increased with increasing number of positive features, to 99% when all six symptoms and signs were present. The performance of the recommendations in the study populations varied according to the definition of knee OA, background risk and number of tests applied. Conclusion 10 key recommendations for diagnosis of knee OA were developed using both research evidence and expert consensus. Although there is no agreed reference standard, thorough clinical assessment alone can provide a confident rule-in diagnosis.
|
|
