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| 2. |
- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 12. |
- Hayes, A., et al.
(författare)
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A European multicentre evaluation of detection and typing methods for human enteroviruses and parechoviruses using RNA transcripts
- 2020
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Ingår i: Journal of Medical Virology. - : Wiley. - 0146-6615 .- 1096-9071. ; 92:8, s. 1065-1074
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Tidskriftsartikel (refereegranskat)abstract
- Polymerase chain reaction (PCR) detection has become the gold standard for diagnosis and typing of enterovirus (EV) and human parechovirus (HPeV) infections. Its effectiveness depends critically on using the appropriate sample types and high assay sensitivity as viral loads in cerebrospinal fluid samples from meningitis and sepsis clinical presentation can be extremely low. This study evaluated the sensitivity and specificity of currently used commercial and in-house diagnostic and typing assays. Accurately quantified RNA transcript controls were distributed to 27 diagnostic and 12 reference laboratories in 17 European countries for blinded testing. Transcripts represented the four human EV species (EV-A71, echovirus 30, coxsackie A virus 21, and EV-D68), HPeV3, and specificity controls. Reported results from 48 in-house and 15 commercial assays showed 98% detection frequencies of high copy (1000 RNA copies/5 µL) transcripts. In-house assays showed significantly greater detection frequencies of the low copy (10 copies/5 µL) EV and HPeV transcripts (81% and 86%, respectively) compared with commercial assays (56%, 50%; P = 7 × 10−5). EV-specific PCRs showed low cross-reactivity with human rhinovirus C (3 of 42 tests) and infrequent positivity in the negative control (2 of 63 tests). Most or all high copy EV and HPeV controls were successfully typed (88%, 100%) by reference laboratories, but showed reduced effectiveness for low copy controls (41%, 67%). Stabilized RNA transcripts provide an effective, logistically simple and inexpensive reagent for evaluation of diagnostic assay performance. The study provides reassurance of the performance of the many in-house assay formats used across Europe. However, it identified often substantially reduced sensitivities of commercial assays often used as point-of-care tests.
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| 14. |
- Chatzikonstantinou, T, et al.
(författare)
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COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study
- 2021
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 35:12, s. 3444-3454
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Tidskriftsartikel (refereegranskat)abstract
- Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41–0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02–1.04; HR = 1.79, 95% CI:1.04–3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated.
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| 15. |
- Martin-Izquierdo, M, et al.
(författare)
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Co-occurrence of cohesin complex and Ras signaling mutations during progression from myelodysplastic syndromes to secondary acute myeloid leukemia
- 2021
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 106:8, s. 2215-2223
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Tidskriftsartikel (refereegranskat)abstract
- Myelodysplastic syndromes (MDS) are hematological disorders at high risk of progression to secondary acute myeloid leukemia (sAML). However, the mutational dynamics and clonal evolution underlying disease progression are poorly understood at present. To elucidate the mutational dynamics of pathways and genes occurring during the evolution to sAML, next generation sequencing was performed on 84 serially paired samples of MDS patients who developed sAML (discovery cohort) and 14 paired samples from MDS patients who did not progress to sAML during follow-up (control cohort). Results were validated in an independent series of 388 MDS patients (validation cohort). We used an integrative analysis to identify how mutations, alone or in combination, contribute to leukemic transformation. The study showed that MDS progression to sAML is characterized by greater genomic instability and the presence of several types of mutational dynamics, highlighting increasing (STAG2) and newly-acquired (NRAS and FLT3) mutations. Moreover, we observed cooperation between genes involved in the cohesin and Ras pathways in 15-20% of MDS patients who evolved to sAML, as well as a high proportion of newly acquired or increasing mutations in the chromatin-modifier genes in MDS patients receiving a disease-modifying therapy before their progression to sAML.
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| 16. |
- Burrell, Jamie, et al.
(författare)
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Using Curvature Power to Map the Domain of Inverse Micellar Cubic Phases : The Case of Aliphatic Aldehydes in 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine
- 2017
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 33:44, s. 12804-12813
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Tidskriftsartikel (refereegranskat)abstract
- Oxylipins, or fatty aldehydes, are a class of molecules produced from membrane lipids as a result of oxidative stress or enzyme-mediated peroxidation. Here we report the effects of two biologically important fatty aldehydes, trans,trans-2,4-decanedienal (DD) and cis-11-hexadecenal (HD), on the phase behavior of the lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) in water. We compare the phase behavior of DD/DOPE and HD/DOPE mixtures to the phase behavior of oleic acid/DOPE mixtures and show that DD, HD, and oleic acid have similar effects on the phase diagrams of DOPE. Notably, both DD and HD, like oleic acid, induce the formation of Fd3m inverse micellar cubic phases in DOPE/water mixtures. This is the first time that Fd3m phases in fatty aldehyde-containing mixtures have been reported. We assess the effects of DD, HD, and oleic acid on DOPE in terms of lipid spontaneous curvatures and propose a method to predict the formation of Fd3m phases from the curvature power of amphiphiles. This methodology predicts that Fd3m phases will become stable if the spontaneous curvature of a lipid mixture is -0.48 ± 0.05 nm-1 or less.
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| 17. |
- Dymond, Marcus K., et al.
(författare)
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Lipid Spontaneous Curvatures Estimated from Temperature-Dependent Changes in Inverse Hexagonal Phase Lattice Parameters : Effects of Metal Cations
- 2016
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 32:39, s. 10083-10092
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Tidskriftsartikel (refereegranskat)abstract
- Recently we reported a method for estimating the spontaneous curvatures of lipids from temperature-dependent changes in the lattice parameter of inverse hexagonal liquid crystal phases of binary lipid mixtures. This method makes use of 1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine (DOPE) as a host lipid, which preferentially forms an inverse hexagonal phase to which a guest lipid of unknown spontaneous curvature is added. The lattice parameters of these binary lipid mixtures are determined by small-angle X-ray diffraction at a range of temperatures and the spontaneous curvature of the guest lipid is determined from these data. Here we report the use of this method on a wide range of lipids under different ionic conditions. We demonstrate that our method provides spontaneous curvature values for DOPE, cholesterol, and monoolein that are within the range of values reported in the literature. Anionic lipids 1,2-dioleoyl-sn-glycerol-3-phosphatidic acid (DOPA) and 1,2-dioleoyl-sn-glycerol-3-phosphoserine (DOPS) were found to exhibit spontaneous curvatures that depend on the concentration of divalent cations present in the mixtures. We show that the range of curvatures estimated experimentally for DOPA and DOPS can be explained by a series of equilibria arising from lipid-cation exchange reactions. Our data indicate a universal relationship between the spontaneous curvature of a lipid and the extent to which it affects the lattice parameter of the hexagonal phase of DOPE when it is part of a binary mixture. This universal relationship affords a rapid way of estimating the spontaneous curvatures of lipids that are expensive, only available in small amounts, or are of limited chemical stability.
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| 19. |
- Porcar-Castell, A., et al.
(författare)
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EUROSPEC: at the interface between remote-sensing and ecosystem CO2 flux measurements in Europe
- 2015
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4189. ; 12:20, s. 6103-6124
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Forskningsöversikt (refereegranskat)abstract
- Resolving the spatial and temporal dynamics of gross primary productivity (GPP) of terrestrial ecosystems across different scales remains a challenge. Remote sensing is regarded as the solution to upscale point observations conducted at the ecosystem level, using the eddy covariance (EC) technique, to the landscape and global levels. In addition to traditional vegetation indices, the photochemical reflectance index (PRI) and the emission of solar-induced chlorophyll fluorescence (SIF), now measurable from space, provide a new range of opportunities to monitor the global carbon cycle using remote sensing. However, the scale mismatch between EC observations and the much coarser satellite-derived data complicates the integration of the two sources of data. The solution is to establish a network of in situ spectral measurements that can act as bridge between EC measurements and remote sensing data. In situ spectral measurements have been already conducted for many years at EC sites, but using variable instrumentation, setups, and measurement standards. In Europe in particular, in situ spectral measurements remain highly heterogeneous. The goal of EUROSPEC Cost Action ES0930 was to promote the development of common measuring protocols and new instruments towards establishing best practices and standardization of in situ spectral measurements. In this review we describe the background and main tradeoffs of in situ spectral measurements, review the main results of EUROSPEC Cost Action, and discuss the future challenges and opportunities of in situ spectral measurements for improved estimation of local and global carbon cycle.
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| 20. |
- Sans, J A, et al.
(författare)
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Thermal instability of implanted Mn ions in ZnO
- 2010
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Ingår i: JOURNAL OF APPLIED PHYSICS. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 107:2, s. 023507-
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Tidskriftsartikel (refereegranskat)abstract
- This letter reports on the site configuration of implanted Mn cations in ZnO. The samples studied were obtained by means of ion implantation in m-plane ZnO single crystals. Synchrotron radiation based fluorescence shows no contamination during the implantation process. The results of micro-x-ray absorption spectroscopy indicate that Mn ions are located in substitutional sites without detectable traces of secondary phases. The postgrowth thermal annealing in O-2 atmosphere induces a change in the coordination of a large amount of Mn cations, corresponding to alpha-Mn2O3.
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| 21. |
- Aguilera Medina, Luis, 1983, et al.
(författare)
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The effect of lithium salt doping on the nanostructure of ionic liquids
- 2015
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Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9084 .- 1463-9076. ; 17:40, s. 27082-27087
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Tidskriftsartikel (refereegranskat)abstract
- In this work we report on the evolution of the structure of two model ionic liquid families, N-alkyl-N-methylpyrrolidinium (Pyr1n-TFSI) and 1-alkyl-3-methylimidazolium (CnMIm-TFSI) (n = 3, 4, 6 and 8) both containing the bis(trifluoromethanesulfonyl)imide (TFSI) anion, upon the addition of LiTFSI using small angle X-ray scattering (SAXS). The introduction of a lithium salt (Li-salt) tunes the interactions through the substitution of the large cation in the ionic liquid with the small and charge localized lithium ion, thus increasing the coulombic contribution from ion-ion interactions. We find that the introduction of lithium ions results in a restructuring of the polar groups in the ionic liquids. These changes are manifested as an increase in the correlation lengths related to charge alternation of the ions and a more disordered structure. This restructuring is interpreted as a reconfiguration of the anions as they coordinate to the small and ionic lithium. In contrast, the length scale of the mesoscopic heterogeneities related to the clustering of alkyl chains is virtually unchanged with lithium doping. Moreover, the correlation corresponding to alkyl chain domains becomes more well defined with increasing salt concentration, suggesting that Li-salt doping, i.e. an increased columbic interaction in the system, promotes clustering of the alkyl tails.
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| 22. |
- Balmer, G., et al.
(författare)
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ISAAC : A REXUS STUDENT EXPERIMENT TO DEMONSTRATE AN EJECTION SYSTEM WITH PREDEFINED DIRECTION
- 2015
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Ingår i: EUROPEAN ROCKET AND BALLOON. - 9789292212940 ; , s. 235-242
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Konferensbidrag (refereegranskat)abstract
- ISAAC - Infrared Spectroscopy to Analyse the middle Atmosphere Composition was a student experiment launched from SSC's Esrange Space Centre, Sweden, on 29th May 2014, on board the sounding rocket REXUS 15 in the frame of the REXUS/BEXUS programme. The main focus of the experiment was to implement an ejection system for two large Free Falling Units (FFUs) (240 mm x 80 mm) to be ejected from a spinning rocket into a predefined direction. The system design relied on a spring-based ejection system. Sun and angular rate sensors were used to control and time the ejection. The flight data includes telemetry from the Rocket Mounted Unit (RMU), received and saved during flight, as well as video footage from the GoPro camera mounted inside the RMU and recovered after the flight. The FFUs' direction, speed and spin frequency as well as the rocket spin frequency were determined by analyzing the video footage. The FFU-Rocket-Sun angles were 64.3 degrees and 104.3 degrees, within the required margins of 90 degrees +/- 45 degrees. The FFU speeds were 3.98 m/s and 3.74 m/s, lower than the expected 5 +/- 1 m/s. The FFUs' spin frequencies were 1.38 Hz and 1.60 Hz, approximately half the rocket's spin frequency. The rocket spin rate slightly changed from 3.163 Hz before the ejection to 3.117 Hz after the ejection of the two FFUs. The angular rate, sun sensor data and temperature on the inside of the rocket module skin were also recorded. The experiment design and results of the data analysis are presented in this paper.
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| 24. |
- Labrador-Páez, Lucia, et al.
(författare)
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pH dependence of water anomaly temperature investigated by Eu(III) cryptate luminescence
- 2020
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 412:1, s. 73-80
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Tidskriftsartikel (refereegranskat)abstract
- Although water has been extensively studied, not all of its unique properties have been fully understood. There is still controversy about the temperature at which hydrogen bonds are broken or weakened, producing the anomalous temperature dependence of many water properties. Different temperatures between 23 and 48 °C have been reported, but no study has scrutinized the reasons for this discrepancy. We suggest the determining role of pH in the alteration of the water anomaly temperature. We employed a luminescent europium trisbipyridine cryptate, which is highly sensitive to changes in the arrangement of water molecules and whose luminescence intensity and lifetime are not significantly influenced by variations over a broad pH range. Our results revealed an increase of the crossover temperature from circa 35 °C at pH 3.5 to circa 45 °C at pH 7 to 9, which explains the discrepancies of previous studies. The pH dependence of water anomaly temperature is an important property for a better understanding of water and water-based systems and applications.
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| 25. |
- Plivelic, Tomas S., et al.
(författare)
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Concentrated protein solutions investigated using acoustic levitation and small-Angle X-ray scattering
- 2020
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Ingår i: Journal of Synchrotron Radiation. - : International Union of Crystallography. - 0909-0495 .- 1600-5775. ; 27, s. 396-404
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Tidskriftsartikel (refereegranskat)abstract
- An acoustically levitated droplet has been used to collect synchrotron SAXS data on human serum albumin protein solutions up to a protein concentration of 400mgml-1. A careful selection of experiments allows for fast data collection of a large amount of data, spanning a protein concentration/solvent concentration space with limited sample consumption (down to 3μL per experiment) and few measurements. The data analysis shows data of high quality that are reproducible and comparable with data from standard flow-Through capillary-based experiments. Furthermore, using this methodology, it is possible to achieve concentrations that would not be accessible by conventional cells. The protein concentration and ionic strength parameter space diagram may be covered easily and the amount of protein sample is significantly reduced (by a factor of 100 in this work). Used in routine measurements, the benefits in terms of protein cost and time spent are very significant.
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