| 1. |
-
- 2019
-
Tidskriftsartikel (refereegranskat)
|
|
| 2. |
- Abelev, Betty, et al.
(författare)
-
Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
-
Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
-
Tidskriftsartikel (refereegranskat)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
|
|
| 3. |
- Abelev, Betty, et al.
(författare)
-
Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
-
Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
-
Tidskriftsartikel (refereegranskat)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
|
|
| 4. |
- Hollestelle, Antoinette, et al.
(författare)
-
No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
-
Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
|
|
| 5. |
- Abelev, Betty, et al.
(författare)
-
Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
-
Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
-
Tidskriftsartikel (refereegranskat)abstract
- We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
|
|
| 6. |
- Kehoe, Laura, et al.
(författare)
-
Make EU trade with Brazil sustainable
- 2019
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 7. |
- Agemark, Maria, et al.
(författare)
-
Reconstitution of water channel function and 2D-crystallization of human aquaporin 8.
- 2012
-
Ingår i: Biochimica et Biophysica Acta. - : Elsevier BV. - 0006-3002 .- 0005-2736. ; 1818:3, s. 839-850
-
Tidskriftsartikel (refereegranskat)abstract
- Among the thirteen human aquaporins (AQP0-12), the primary structure of AQP8 is unique. By sequence alignment it is evident that mammalian AQP8s form a separate subfamily distinct from the other mammalian aquaporins. The constriction region of the pore determining the solute specificity deviates in AQP8 making it permeable to both ammonia and H(2)O(2) in addition to water. To better understand the selectivity and gating mechanism of aquaporins, high-resolution structures are necessary. So far, the structure of one human aquaporin (HsAQP5) has been solved at atomic resolution. For mammalian aquaporins in general, high-resolution structures are only available for those belonging to the water-specific subfamily (including HsAQP5). Thus, it is of interest to solve structures of other aquaporin subfamily members with different solute specificities. To achieve this the aquaporins need to be overexpressed heterologously and purified. Here we use the methylotrophic yeast Pichia pastoris as a host for the overexpression. A wide screen of different detergents and detergent-lipid combinations resulted in the solubilization of functional human AQP8 protein and in well-ordered 2D crystals. It also became evident that removal of amino acids constituting affinity tags was crucial to achieve highly ordered 2D crystals diffracting to 3Å.
|
|
| 8. |
- Álvarez-Muñiz, Jaime, et al.
(författare)
-
The Giant Radio Array for Neutrino Detection (GRAND) : Science and design
- 2020
-
Ingår i: Science China Physics, Mechanics & Astronomy. - : Springer Science and Business Media LLC. - 1674-7348 .- 1869-1927. ; 63:1
-
Forskningsöversikt (refereegranskat)abstract
- The Giant Radio Array for Neutrino Detection (GRAND) is a planned large-scale observatory of ultra-high-energy (UHE) cosmic particles, with energies exceeding 108 GeV. Its goal is to solve the long-standing mystery of the origin of UHE cosmic rays. To do this, GRAND will detect an unprecedented number of UHE cosmic rays and search for the undiscovered UHE neutrinos and gamma rays associated to them with unmatched sensitivity. GRAND will use large arrays of antennas to detect the radio emission coming from extensive air showers initiated by UHE particles in the atmosphere. Its design is modular: 20 separate, independent sub-arrays, each of 10000 radio antennas deployed over 10000 km(2). A staged construction plan will validate key detection techniques while achieving important science goals early. Here we present the science goals, detection strategy, preliminary design, performance goals, and construction plans for GRAND.
|
|
| 9. |
- Dimov, Stefan S., et al.
(författare)
-
4M Network of Excellence : Progress Report 2004-2006
- 2007
-
Ingår i: 4M 2007. - Dunbeath : Whittles Publishing. - 9781904445531 - 9781420070040 ; , s. xvii-xxxi
-
Konferensbidrag (refereegranskat)abstract
- The 4M Network of Excellence started on 1st October 2004. It is a consortium of 30 academic and research organisations that came together to form the network under the European Commission's 6th Framework Research Programme. The Network has developed a knowledge community in Micro- and Nano- Technology (MNT) for the batch-manufacture of microcomponents and devices in a variety of materials for future microsystems products, particularly in non-silicon materials. This paper gives an overview of the structure, operation and activity of the network since its inception, illustrating the network's progress towards its goals.
|
|
| 10. |
- Dimov, Stefan S., et al.
(författare)
-
4M Network of Excellence, Progress Report 2006-2008
- 2008
-
Ingår i: 4M 2008. - Dunbeath : Whittles Publishing. - 9781904445760 ; , s. xv-xxxi
-
Konferensbidrag (refereegranskat)abstract
- This report follows on from last year's "Progress Report 2004-2006" and gives an update on the continuing activities, such as the 4M Network cross-divisional projects and annual conference, as well as a description of the new activities in its third and forth year, such as the first 4M Summer School and Book Series. Finally, as the end of the funded lifetime of the network approaches the steps being taken to set up a 4M Association, which aims to create the organizational infrastructure to support the 4M Knowledge Community established in the last five years, are described.
|
|
| 11. |
- Dimov, Stefan S., et al.
(författare)
-
4M Network of Excellence, Progress report 2009
- 2009
-
Ingår i: 4M/ICOMM 2009. ; , s. s.1-9
-
Konferensbidrag (refereegranskat)abstract
- This paper gives a brief overview of the activities of the 4M Network of Excellence during the last nine months of its funded period. The 4M Divisions summarise their activity and outline their plans to continue to working together in future. Finally a summary of achievements during the whole lifetime of the Network is given
|
|
| 12. |
|
|
| 13. |
- Engel, Andreas K., et al.
(författare)
-
Introduction Where's the Action?
- 2015
-
Ingår i: PRAGMATIC TURN. - : MIT PRESS. - 9780262034326 ; , s. 1-
-
Konferensbidrag (refereegranskat)abstract
- Cognitive science is witnessing a pragmatic turn away from the traditional representation-centered framework of cognition toward one that focuses on understanding cognition as being "enactive." The enactive view holds that cognition does not produce models of the world but rather subserves action, as it is grounded in sensorimotor skills. The conclusions of this Ernst Strungmann Forum suggest that strong conceptual advances are possible when cognition is framed by an action-oriented paradigm. Experimental evidence from cognitive science, neuroscience, psychology, robotics, and philosophy of mind supports this position. This chapter provides an overview of the discourse surrounding this collaborative effort. Core topics which guided this multidisciplinary perusal are identified and challenges that emerged are highlighted. Action-oriented views from a variety of disciplines have started to cross-fertilize, thus promoting an integration of concepts and creating fertile ground for a novel theory of cognition to emerge.
|
|
| 14. |
- Engel, Robin Y., et al.
(författare)
-
Electron population dynamics in resonant non-linear x-ray absorption in nickel at a free-electron laser
- 2023
-
Ingår i: Structural Dynamics. - : American Institute of Physics (AIP). - 2329-7778. ; 10:5
-
Tidskriftsartikel (refereegranskat)abstract
- Free-electron lasers provide bright, ultrashort, and monochromatic x-ray pulses, enabling novel spectroscopic measurements not only with femtosecond temporal resolution: The high fluence of their x-ray pulses can also easily enter the regime of the non-linear x-ray-matter interaction. Entering this regime necessitates a rigorous analysis and reliable prediction of the relevant non-linear processes for future experiment designs. Here, we show non-linear changes in the L-3-edge absorption of metallic nickel thin films, measured with fluences up to 60 J/cm(2). We present a simple but predictive rate model that quantitatively describes spectral changes based on the evolution of electronic populations within the pulse duration. Despite its simplicity, the model reaches good agreement with experimental results over more than three orders of magnitude in fluence, while providing a straightforward understanding of the interplay of physical processes driving the non-linear changes. Our findings provide important insights for the design and evaluation of future high-fluence free-electron laser experiments and contribute to the understanding of non-linear electron dynamics in x-ray absorption processes in solids at the femtosecond timescale.
|
|
| 15. |
- Engel, Stephanie, et al.
(författare)
-
FLIM-FRET and FRAP reveal association of influenza virus haemagglutinin with membrane rafts.
- 2010
-
Ingår i: Biochemical Journal. - 0264-6021 .- 1470-8728. ; 425:3, s. 567-73
-
Tidskriftsartikel (refereegranskat)abstract
- It has been supposed that the HA (haemagglutinin) of influenza virus must be recruited to membrane rafts to perform its function in membrane fusion and virus budding. In the present study, we aimed at substantiating this association in living cells by biophysical methods. To this end, we fused the cyan fluorescent protein Cer (Cerulean) to the cytoplasmic tail of HA. Upon expression in CHO (Chinese-hamster ovary) cells HA-Cer was glycosylated and transported to the plasma membrane in a similar manner to authentic HA. We measured FLIM-FRET (Förster resonance energy transfer by fluorescence lifetime imaging microscopy) and showed strong association of HA-Cer with Myr-Pal-YFP (myristoylated and palmitoylated peptide fused to yellow fluorescent protein), an established marker for rafts of the inner leaflet of the plasma membrane. Clustering was significantly reduced when rafts were disintegrated by cholesterol extraction and when the known raft-targeting signals of HA, the palmitoylation sites and amino acids in its transmembrane region, were removed. FRAP (fluorescence recovery after photobleaching) showed that removal of raft-targeting signals moderately increased the mobility of HA in the plasma membrane, indicating that the signals influence access of HA to slowly diffusing rafts. However, Myr-Pal-YFP exhibited a much faster mobility compared with HA-Cer, demonstrating that HA and the raft marker do not diffuse together in a stable raft complex for long periods of time.
|
|
| 16. |
|
|
| 17. |
- Johnsson, Filip, 1960, et al.
(författare)
-
In-furnace processes in a 235 MWe CFB boiler
- 2002
-
Ingår i: Proc. of the 7th International Conference on Circulating Fluidized Beds. - 9780920804988 ; , s. 607-614
-
Konferensbidrag (refereegranskat)abstract
- In an experimental project funded by the 5th Framework Programme of the European Community (EC), different measurement techniques are used to analyze in-furnace processes in a 235 MWe Circulating Fluidized Bed (CFB) boiler in Turow, Poland. The purpose of the project is to assess the insufficiently known features of large-scale CFB boilers. The furnace of the boiler has a cross-section of 21 x 10 meters and a height of 43 meters. The boiler is operated on a local brown coal. Steady state, as well as dynamic conditions, are studied. The project is unique in two respects: Firstly, several measurement ports are provided in the large CFB furnace for in-situ measurements in various locations on the furnace. Secondly, a number of measurement techniques are employed. These facilitate studies of hydrodynamic processes as well as local variations in gas components (such as O2, CO, THC) and solids materials. The paper describes the measurement techniques and provides examples of the first (hydrodynamic) results obtained by the in-situ measurements.
|
|
| 18. |
- Karlsson, Maria, 1985, et al.
(författare)
-
Reconstitution of water channel function of an aquaporin overexpressed and purified from Pichia pastoris.
- 2003
-
Ingår i: FEBS Letters. - 1873-3468 .- 0014-5793. ; 537:1-3, s. 68-72
-
Tidskriftsartikel (refereegranskat)abstract
- The aquaporin PM28A is one of the major integral proteins in spinach leaf plasma membranes. Phosphorylation/dephosphorylation of Ser274 at the C-terminus and of Ser115 in the first cytoplasmic loop has been shown to regulate the water channel activity of PM28A when expressed in Xenopus oocytes. To understand the mechanisms of the phosphorylation-mediated gating of the channel the structure of PM28A is required. In a first step we have used the methylotrophic yeast Pichia pastoris for expression of the pm28a gene. The expressed protein has a molecular mass of 32462 Da as determined by matrix-assisted laser desorption ionization-mass spectrometry, forms tetramers as revealed by electron microscopy and is functionally active when reconstituted in proteoliposomes. PM28A was efficiently solubilized from urea- and alkali-stripped Pichia membranes by octyl-beta-D-thioglucopyranoside resulting in a final yield of 25 mg of purified protein per liter of cell culture.
|
|
| 19. |
- Knirck, Stefan, et al.
(författare)
-
A first look on 3D effects in open axion haloscopes
- 2019
-
Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; 2019:08, s. 026-026
-
Tidskriftsartikel (refereegranskat)abstract
- We explore finite size 3D effects in open axion haloscopes such as a dish antenna, a dielectric disk and a minimal dielectric haloscope consisting of a mirror and one dielectric disk. Particularly dielectric haloscopes are a promising new method for detecting dark matter axions in the mass range above 40 mu eV. By using two specialized independent approaches - based on finite element methods and Fourier optics - we compute the electromagnetic fields in these settings expected in the presence of an axion dark matter field. This allows us to study diffraction and near field effects for realistically sized experimental setups in contrast to earlier idealized 1D studies with infinitely extended mirrors and disks. We also study axion velocity effects and disk tiling. Diffraction effects are found to become less relevant towards larger axion masses and for the larger disk radii for example aimed at in full size dielectric haloscopes such as MADMAX. The insights of our study not only provide a foundation for a realistic modelling of open axion dark matter search experiments in general, they are in particular also the first results taking into account 3D effects for dielectric haloscopes.
|
|
| 20. |
- Lojewski, Tobias, et al.
(författare)
-
The interplay of local electron correlations and ultrafast spin dynamics in fcc Ni
- 2023
-
Ingår i: Materials Research Letters. - : Taylor & Francis. - 2166-3831. ; 11:8, s. 655-661
-
Tidskriftsartikel (refereegranskat)abstract
- The complex electronic structure of metallic ferromagnets is determined by a balance between exchange interaction, electron hopping leading to band formation, and local Coulomb repulsion. By combining high energy and temporal resolution in femtosecond time-resolved X-ray absorption spectroscopy with ab initio time-dependent density functional theory we analyze the electronic structure in fcc Ni on the time scale of these interactions in a pump-probe experiment. We distinguish transient broadening and energy shifts in the absorption spectra, which we demonstrate to be captured by electron repopulation respectively correlation-induced modifications of the electronic structure, requiring to take the local Coulomb interaction into account.
|
|
| 21. |
- Lubenow, Norbert, et al.
(författare)
-
The severity of trauma determines the immune response to PF4/heparin and the frequency of heparin-induced thrombocytopenia.
- 2010
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 115:9, s. 1797-803
-
Tidskriftsartikel (refereegranskat)abstract
- Heparin can induce heparin-induced thrombocytopenia (HIT). The combined effect of type of surgery (major vs minor) and heparin on this prothrombotic immune reaction to platelet factor 4 (PF4)/heparin was analyzed. In a randomized, double-blind study, trauma patients receiving low-molecular-weight (LMWH) or unfractionated heparin (UFH) for thrombosis prophylaxis were assessed for PF4/heparin-antibody seroconversion, HIT, and thrombosis according to type of surgery. The risk for seroconversion was higher than major versus minor surgery odds ratio, 7.98 [95% confidence interval, 2.06-31.00], P = .003, controlled for potential confounders, as was the risk for HIT (2.2% [95% confidence interval, 0.3%-4.1%] vs 0.0%, P = .010). During LMWH compared with UFH thromboprophylaxis, HIT (1 of 298 vs 4 of 316; P = .370) and PF4/heparin seroconversion (1.7% vs 6.6%; P = .002) were less frequent, driven by differences in patients undergoing major surgery (incidence of HIT: LMWH 0.8% vs UFH 4.0%; P = .180; seroconversion rates: 4.0% vs 17.0%; P = .001). After minor surgery, no case of HIT occurred. The severity of trauma and the need for major surgery strongly influence the risk of an anti-PF4/heparin immune response, which is then increased by UFH. In major trauma certoparin may be safer than UFH because it induces HIT-antibody seroconversion, and the corresponding risk of HIT, less frequently.
|
|
| 22. |
- Lundbäck, Anna-Karin, et al.
(författare)
-
Assembly of Kch, a putative potassium channel from Escherichia coli
- 2009
-
Ingår i: Journal of Structural Biology. - : Elsevier BV. - 1047-8477 .- 1095-8657. ; 168:2, s. 288-293
-
Tidskriftsartikel (refereegranskat)abstract
- Attempts to explore the structure and function of Kch, a putative potassium channel of Escherichia coli have yielded varying results; potassium-associated functions have been found in vivo but not in vitro. Here the kch gene is shown to produce two proteins, full-length Kch and the large C-terminal cytosolic domain (the RCK domain). Further, these two proteins are associated at the initial stages of purification. Previous structural studies of full-length Kch claim that the isolated protein forms large aggregates that are not suitable for analysis. The results presented here show that the purified protein sample, although heterogeneous, has one major population with a mass of about 400 kDa, implying the presence of two Kch tetramers in a complex form. A three dimensional reconstruction at 25 angstrom based on electron microscopy data from negatively stained particles, revealed a 210 angstrom long and 95 angstrom wide complex in which the two tetrameric Kch units are linked by their RCK domains, giving rise to a large central ring of density. The formation of this dimer of tetramers on expression or during purification, may explain why attempts to reconstitute Kch into liposomes for activity measurements have failed.
|
|
| 23. |
- Miehlke, Stephan, et al.
(författare)
-
European guidelines on microscopic colitis : United European Gastroenterology (UEG) and European Microscopic Colitis Group (EMCG) statements and recommendations
- 2021
-
Ingår i: United European Gastroenterology journal. - : Sage Publications. - 2050-6406 .- 2050-6414. ; 9:1, s. 13-37
-
Forskningsöversikt (refereegranskat)abstract
- Introduction: Microscopic colitis is a chronic inflammatory bowel disease characterised by normal or almost normal endoscopic appearance of the colon, chronic watery, non-bloody diarrhoea and distinct histological abnormalities, which identify three histological subtypes, the collagenous colitis, the lymphocytic colitis and the incomplete microscopic colitis. With ongoing uncertainties and new developments in the clinical management of microscopic colitis, there is a need for evidence-based guidelines to improve the medical care of patients suffering from this disorder.Methods: Guidelines were developed by members from the European Microscopic Colitis Group and United European Gastroenterology in accordance with the Appraisal of Guidelines for Research and Evaluation II instrument. Following a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the certainty of the evidence. Statements and recommendations were developed by working groups consisting of gastroenterologists, pathologists and basic scientists, and voted upon using the Delphi method.Results: These guidelines provide information on epidemiology and risk factors of microscopic colitis, as well as evidence-based statements and recommendations on diagnostic criteria and treatment options, including oral budesonide, bile acid binders, immunomodulators and biologics. Recommendations on the clinical management of microscopic colitis are provided based on evidence, expert opinion and best clinical practice.Conclusion: These guidelines may support clinicians worldwide to improve the clinical management of patients with microscopic colitis.
|
|
| 24. |
- Olsen, Laerke Müller, et al.
(författare)
-
Histological disease activity in patients with microscopic colitis is not related to clinical disease activity or long-term prognosis
- 2021
-
Ingår i: Alimentary Pharmacology and Therapeutics. - Chichester, United Kingdom : Wiley-Blackwell. - 0269-2813 .- 1365-2036. ; 54:1, s. 43-52
-
Tidskriftsartikel (refereegranskat)abstract
- Background Microscopic colitis (MC) is a common cause of chronic watery diarrhea. Biopsies with characteristic histological features are crucial for establishing the diagnosis. The two main subtypes are collagenous colitis (CC) and lymphocytic colitis (LC) but incomplete forms exist. The disease course remains unpredictable varying from spontaneous remission to a relapsing course.Aim To identify possible histological predictors of course of disease.Methods Sixty patients from the European prospective MC registry (PRO-MC Collaboration) were included. Digitised histological slides stained with CD3 and Van Gieson were available for all patients. Total cell density and proportion of CD3 positive lymphocytes in lamina propria and surface epithelium were estimated by automated image analysis, and measurement of the subepithelial collagenous band was performed. Histopathological features were correlated to the number of daily stools and daily watery stools at time of endoscopy and at baseline as well as the clinical disease course (quiescent, achieved remission after treatment, relapsing or chronic active) at 1-year follow-up.Results Neither total cell density in lamina propria, proportion of CD3 positive lymphocytes in lamina propria or surface epithelium, or thickness of collagenous band showed significant correlation to the number of daily stools or daily watery stools at any point of time. None of the assessed histological parameters at initial diagnosis were able to predict clinical disease course at 1-year follow-up.Conclusions Our data indicate that the evaluated histological parameters were neither markers of disease activity at the time of diagnosis nor predictors of disease course.
|
|
| 25. |
|
|
| 26. |
- Osorio, Ana, et al.
(författare)
-
DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
- 2014
-
Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:4
-
Tidskriftsartikel (refereegranskat)abstract
- Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7×10-3) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8×10-3). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
|
|
| 27. |
|
|
| 28. |
- Scolari, Silvia, et al.
(författare)
-
Lateral distribution of the transmembrane domain of influenza virus hemagglutinin revealed by time-resolved fluorescence imaging.
- 2009
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 284:23, s. 15708-16
-
Tidskriftsartikel (refereegranskat)abstract
- Influenza virus hemagglutinin (HA) has been suggested to be enriched in liquid-ordered lipid domains named rafts, which represent an important step in virus assembly. We employed Förster resonance energy transfer (FRET) via fluorescence lifetime imaging microscopy to study the interaction of the cytoplasmic and transmembrane domain (TMD) of HA with agly co sylphos pha tidyl ino si tol (GPI)-anchored peptide, an established marker for rafts in the exoplasmic leaflet of living mammalian plasma membranes. Cyan fluorescent protein (CFP) was fused to GPI, whereas the HA sequence was tagged with yellow fluorescent protein (YFP) on its exoplasmic site (TMD-HA-YFP), avoiding any interference of fluorescent proteins with the proposed role of the cytoplasmic domain in lateral organization of HA. Constructs were expressed in Chinese hamster ovary cells (CHO-K1) for which cholesterol-sensitive lipid nanodomains and their dimension in the plasma membrane have been described (Sharma, P., Varma, R., Sarasij, R. C., Ira, Gousset, K., Krishnamoorthy, G., Rao, M., and Mayor, S. (2004) Cell 116, 577-589). Upon transfection in CHO-K1 cells, TMD-HA-YFP is partially expressed as a dimer. Only dimers are targeted to the plasma membrane. Clustering of TMD-HA-YFP with GPI-CFP was observed and shown to be reduced upon cholesterol depletion, a treatment known to disrupt rafts. No indication for association of TMD-HA-YFP with GPI-CFP was found when palmitoylation, an important determinant of raft targeting, was suppressed. Clustering of TMD-HA-YFP and GPI-CFP was also observed in purified plasma membrane suspensions by homoFRET. We concluded that the pal mit oy lated TMD-HA alone is sufficient to recruit HA to cholesterol-sensitive nanodomains. The corresponding construct of the spike protein E2 of Semliki Forest virus did not partition preferentially in such domains.
|
|
| 29. |
- Shu, Xiang, et al.
(författare)
-
Associations of obesity and circulating insulin and glucose with breast cancer risk : a Mendelian randomization analysis
- 2019
-
Ingår i: International Journal of Epidemiology. - : OXFORD UNIV PRESS. - 0300-5771 .- 1464-3685. ; 48:3, s. 795-806
-
Tidskriftsartikel (refereegranskat)abstract
- Background: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. Methods: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. Results: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p = 5.09 x 10(-4)], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p = 4.02 x 10(-4)), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p = 5.05 x 10(-19)) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p = 9.22 x 10(-6)). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. Conclusions: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer.
|
|
| 30. |
- Stevens, Kristen N, et al.
(författare)
-
19p13.1 is a triple negative-specific breast cancer susceptibility locus
- 2012
-
Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 72, s. 1795-
-
Tidskriftsartikel (refereegranskat)abstract
- The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with risk of ovarian cancer. Here we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 Odds Ratio (OR)=1.10, 95% Confidence Interval (CI) 1.05 - 1.15, p=3.49 x 10-5] and triple negative (TN) (ER, PR and HER2 negative) breast cancer [rs8170 OR=1.22, 95% CI 1.13 - 1.31, p=2.22 x 10-7]. However, rs8170 was no longer associated with ER-negative breast cancer risk when TN cases were excluded [OR=0.98, 95% CI 0.89 - 1.07, p=0.62]. In addition, a combined analysis of TN cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC) (n=3,566) identified a genome-wide significant association between rs8170 and TN breast cancer risk [OR=1.25, 95% CI 1.18 - 1.33, p=3.31 x 10-13]. Thus, 19p13.1 is the first triple negative-specific breast cancer risk locus and the first locus specific to a histological subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple negative tumors and other subtypes likely arise through distinct etiologic pathways.
|
|
| 31. |
|
|
