| 1. |
- Johansson, Mattias, et al.
(författare)
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The influence of obesity-related factors in the etiology of renal cell carcinoma—A mendelian randomization study
- 2019
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation.Methods and findings: Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44–1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40–1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44–1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30–2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11–1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84–1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose.Conclusions: This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.
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| 2. |
- Din, Lennox, et al.
(författare)
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Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes
- 2019
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Ingår i: Genetic Epidemiology. - : WILEY. - 0741-0395 .- 1098-2272. ; 43:7, s. 844-863
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p =.0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.
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| 3. |
- Hoffmann, Jean-Marc, et al.
(författare)
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Differences in Expansion Potential of Naive Chimeric Antigen Receptor T Cells from Healthy Donors and Untreated Chronic Lymphocytic Leukemia Patients
- 2018
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Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Therapy with chimeric antigen receptor T (CART) cells for hematological malignancies has shown promising results. Effectiveness of CART cells may depend on the ratio of naive (T-N) vs. effector (T-E) T cells, TN cells being responsible for an enduring antitumor activity through maturation. Therefore, we investigated factors influencing the T-N/T-E ratio of CART cells.Materials and methods: CART cells were generated upon transduction of peripheral blood mononuclear cells with a CD19.CAR-CD28-CD137zeta third generation retroviral vector under two different stimulating culture conditions: anti-CD3/anti-CD28 antibodies adding either interleukin (IL)-7/1L-15 or IL-2. CART cells were maintained in culture for 20 days. We evaluated 24 healthy donors (HDs) and 11 patients with chronic lymphocytic leukemia (CLL) for the composition of cell subsets and produced CART cells. Phenotype and functionality were tested using flow cytometry and chromium release assays.Results: IL -7/1L-15 preferentially induced differentiation into T-N, stem cell memory (T-SCM: naive CD27+ CD95+), CD4+ and CXCR3+ CART cells, while IL-2 increased effector memory (T-EM), CD56+ and CD4+ T regulatory (T-Reg) CART cells. The net amplification of different CART subpopulations derived from HDs and untreated CLL patients was compared. Particularly the expansion of CD4+ CART(N) cells differed significantly between the two groups. For HDs, this subtype expanded >60-fold, whereas CD4+ CART(N) cells of untreated CLL patients expanded less than 10-fold. Expression of exhaustion marker programmed cell death 1 on CART(N) cells on day 10 of culture was significantly higher in patient samples compared to HD samples. As the percentage of malignant B cells was expectedly higher within patient samples, an excessive amount of B cells during culture could account for the reduced expansion potential of CART(N) cells in untreated CLL patients. Final T-N/T-E ratio stayed <0.3 despite stimulation condition for patients, whereas this ratio was >2 in samples from HDs stimulated with IL-7/1L-15, thus demonstrating efficient CART(N) expansion.Conclusion: Untreated CLL patients might constitute a challenge for long-lasting CART effects in vivo since only a low number of T-N among the CART product could be generated. Depletion of malignant B cells before starting CART production might be considered to increase the T-N/T-E ratio within the CART product.
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| 4. |
- Lai, Ian-Lin, et al.
(författare)
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Gas outflow and dust transport of comet 67P/Churyumov-Gerasimenko
- 2016
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Ingår i: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 462, s. S533-S546
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Tidskriftsartikel (refereegranskat)abstract
- Because of the diurnal thermal cycle and the irregular shape of the nucleus, gas outflow of comet 67P/Churyumov-Gerasimenko could be highly anisotropic as indicated by the colliminated dust jet structures on the sunlit side. Based on the OSIRIS imaging observations of the outgassing effect, a simple model of surface sublimation can be constructed by taking into account the dependence on the solar insolation. With preliminary information on the time variability of the global gas production rate, a sequence of gas coma models can be generated at different epochs before and after perihelion. We also investigate different patterns of dust particle dynamics under the influences of nuclear rotation and gas drag. From these considerations, a consistent picture of the spatial distribution of dusty materials across the surface of comet 67P as it moves around the perihelion can be developed. It is found that because of the redeposition of the ejected dust from the Southern hemisphere to the Northern hemisphere during the southern summer season the Hapi region could gain up to 0.4 m while the Wosret region would lose up to 1.8 m of dust mantle per orbit.
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| 5. |
- Lee, Jui-Chi, et al.
(författare)
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Geomorphological mapping of comet 67P/Churyumov-Gerasimenko's Southern hemisphere
- 2016
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 462, s. S573-S592
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Tidskriftsartikel (refereegranskat)abstract
- In 2015 May, the Southern hemisphere of comet 67P/Churyumov-Gerasimenko became visible by the OSIRIS cameras on-board the Rosetta spacecraft. The resolution was high enough to carry out a detailed analysis of the surface morphology, which is quite different from the Northern hemisphere. Previous works show that fine particle deposits are the most extensive geological unit in the Northern hemisphere. In contrast, the Southern hemisphere is dominated by outcropping consolidated terrain. In this work, we provide geomorphological maps of the Southern hemisphere with the distinction of both geological units and linear features. The geomorphological maps described in this study allow us to gain a better understanding of the processes shaping the comet nucleus and the distribution of primary structures such as fractures and strata.
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| 6. |
- Lee, Natuschka N, et al.
(författare)
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The extreme biology of meteorites : their role in understanding the origin and distribution of life on earth and in the Universe
- 2017. - 2
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Ingår i: Adaption of microbial life to environmental extremes. - Cham : Springer Publishing Company. - 9783319483252 - 9783319483276 ; , s. 283-325
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Bokkapitel (refereegranskat)abstract
- Meteorites have captured our fascination since our early history – they have evoked awe, fear, an irresistible curiosity, and numerous lively debates. Former historians have indicated that many of the ancient cultures and civilizations in Europe, Africa, Asia, the Inuit, and the native Indians in America regarded both the meteorite and the location of their fall as sacred. Thus, they used the meteorites as religious objects or for craft design like jewelry, weapons, or even practical things like tools and horse shoes. Today, meteorites continue to capture our fascination through popular cultural formats such as science fiction and also as a scientific window that reveals the secrets of the Solar System formation. Within academia, meteorites have always fomented keen scientific debate. It was not until the early nineteenth century that the cosmic origin of meteorites, i.e., being truly not tellurian, was approved by the scientific community after the late eighteenth-century work of Ernst F. Chladni (1794). This implied for the first time that there are other smaller bodies in the sky besides the Moon. After this, several other lively debates followed on controversial findings and hypotheses around the role of meteorites in the universe and for the evolutionary course of life on Earth, often in connection with the profound difficulties to approach this subject in an adequate scientific way. Principally the different types of meteorites (asteroids, meteors, etc.) can be viewed as a most extreme or exotic substrate, habitat, and transport mode of chemicals and possibly even of cell-based life forms for several reasons:(i)They have experienced a remarkable history since their origin as condensates from the Solar Nebula, more or less metamorphosed or molten fragments of asteroids, or rocks from Mars or our Moon.(ii)The meteorites have been exposed to multiple extreme conditions ranging from milliseconds to billions of years duration when traveling through the interplanetary space, until they fell down on an astronomical body like Earth.(iii)Once on Earth, the meteorites get exposed to different weathering conditions, which often makes it a challenge to retrieve their former history in an unambiguous way.
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| 7. |
- Li, Yanzeng, et al.
(författare)
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Optical dielectric function of Si(2,6-bis(benzimidazol-2 -yl)pyridine)(2) determined by spectroscopic ellipsometry
- 2019
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Ingår i: Optical Materials Express. - : OPTICAL SOC AMER. - 2159-3930 .- 2159-3930. ; 9:8, s. 3469-3475
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Tidskriftsartikel (refereegranskat)abstract
- Si(bzimpy)(2), a fluorescent organic complex, has been demonstrated as a potential electron transport and electroluminescent layer for organic electronic devices. Despite the successful synthesis and encouraging electroluminescence at 560 nm, the complex dielectric function of the water-stable complex has not been reported yet. In this letter, we report on the first spectroscopic ellipsometry data obtained from a Si(bzimpy)(2) thin film in the spectral range from 300 nm to 1900 nm (0.65 eV to 4.1 eV). A parameterized model dielectric function composed of a Tauc-Lorentz and Gaussian oscillators is employed to analyze the experimental ellipsometry data. We find a good agreement between the absorption energies observed experimentally here and density functional theory calculations reported earlier.
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| 8. |
- Machiela, Mitchell J, et al.
(författare)
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Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma.
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 72:5, s. 747-754
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings.OBJECTIVE: We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations.DESIGN, SETTING, AND PARTICIPANTS: Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis.RESULTS AND LIMITATIONS: Longer genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p<0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R2>0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, p<0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N=5573, OR=1.93, 95% CI=1.50-2.49, p<0.0001), papillary (N=573, OR=1.96, 95% CI=1.01-3.81, p=0.046), and chromophobe RCC (N=203, OR=2.37, 95% CI=0.78-7.17, p=0.13).CONCLUSIONS: Our investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk.PATIENT SUMMARY: Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma.
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| 9. |
- Pajola, Maurizio, et al.
(författare)
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The southern hemisphere of 67P/Churyumov-Gerasimenko : Analysis of the preperihelion size-frequency distribution of boulders >= 7m
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 592
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Tidskriftsartikel (refereegranskat)abstract
- Aims. We calculate the size-frequency distribution of the boulders on the southern hemisphere of comet 67P Churyumov-Gerasimenko (67P), which was in shadow before the end of April 2015. We compare the new results with those derived from the northern hemisphere and equatorial regions of 67P, highlighting the possible physical processes that lead to these boulder size distributions. Methods. We used images acquired by the OSIRIS Narrow Angle Camera (NAC) on 2 May 2015 at a distance of 125 km from the nucleus. The scale of this dataset is 2.3 m/px; the high resolution of the images, coupled with the favorable observation phase angle of 62 degrees, provided the possibility to unambiguously identify boulders >= 7 m on the surface of 67P and to manually extract them with the software ArcGIS. We derived the size-frequency distribution of the illuminated southern hemisphere. Results. We found a power-law index of -3.6 +/- 0.2 for the boulders on the southern hemisphere with a diameter range of 7-35 m. The power-law index is equal to the one previously found on northern and equatorial regions of 67P, suggesting that similar boulder formation processes occur in both hemispheres. The power-law index is related to gravitational events triggered by sublimation and/or thermal fracturing causing regressive erosion. In addition, the presence of a larger number of boulders per km(2) in the southern hemisphere, which is a factor of 3 higher with respect to the northern hemisphere, suggests that the southernmost terrains of 67P are affected by a stronger thermal fracturing and sublimating activity, hence possibly causing larger regressive erosion and gravitational events.
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| 10. |
- Park, Serang, et al.
(författare)
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Terahertz optical properties of polymethacrylates after thermal annealing
- 2019
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Ingår i: Journal of Vacuum Science and Technology B. - : A V S AMER INST PHYSICS. - 2166-2746 .- 2166-2754. ; 37:6
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Tidskriftsartikel (refereegranskat)abstract
- Polymer-based stereolithographic additive manufacturing has been established for the rapid and low-cost fabrication of terahertz (THz) optical components due to its ability to construct complex 3D geometries with high resolution. For polymer-based or integrated optics, thermal annealing processes are often used to optimize material properties. However, despite the growing interest in THz optics fabricated using stereolithography, the effects of thermal annealing on the THz dielectric properties of polymethacrylates compatible with stereolithography have not yet been studied. In this paper, the authors report on the THz ellipsometric response of thermally annealed polymethacrylates prepared using UV polymerization. The findings indicate that the investigated polymethacrylates maintain a stable optical response in the THz spectral range from 650 to 950 GHz after thermal annealing at temperatures up to 70 degrees C for several hours. Published by the AVS.
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