| 1. |
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| 2. |
- Hantke, Max F., et al.
(författare)
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A data set from flash X-ray imaging of carboxysomes
- 2016
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Ultra-intense femtosecond X-ray pulses from X-ray lasers permit structural studies on single particles and biomolecules without crystals. We present a large data set on inherently heterogeneous, polyhedral carboxysome particles. Carboxysomes are cell organelles that vary in size and facilitate up to 40% of Earth’s carbon fixation by cyanobacteria and certain proteobacteria. Variation in size hinders crystallization. Carboxysomes appear icosahedral in the electron microscope. A protein shell encapsulates a large number of Rubisco molecules in paracrystalline arrays inside the organelle. We used carboxysomes with a mean diameter of 115±26 nm from Halothiobacillus neapolitanus. A new aerosol sample-injector allowed us to record 70,000 low-noise diffraction patterns in 12 min. Every diffraction pattern is a unique structure measurement and high-throughput imaging allows sampling the space of structural variability. The different structures can be separated and phased directly from the diffraction data and open a way for accurate, high-throughput studies on structures and structural heterogeneity in biology and elsewhere.
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| 3. |
- Hantke, Max F., et al.
(författare)
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High-throughput imaging of heterogeneous cell organelles with an X-ray laser
- 2014
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Ingår i: Nature Photonics. - : Springer Science and Business Media LLC. - 1749-4885 .- 1749-4893. ; 8:12, s. 943-949
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Tidskriftsartikel (refereegranskat)abstract
- We overcome two of the most daunting challenges in single-particle diffractive imaging: collecting many high-quality diffraction patterns on a small amount of sample and separating components from mixed samples. We demonstrate this on carboxysomes, which are polyhedral cell organelles that vary in size and facilitate up to 40% of Earth's carbon fixation. A new aerosol sample-injector allowed us to record 70,000 low-noise diffraction patterns in 12 min with the Linac Coherent Light Source running at 120 Hz. We separate different structures directly from the diffraction data and show that the size distribution is preserved during sample delivery. We automate phase retrieval and avoid reconstruction artefacts caused by missing modes. We attain the highest-resolution reconstructions on the smallest single biological objects imaged with an X-ray laser to date. These advances lay the foundations for accurate, high-throughput structure determination by flash-diffractive imaging and offer a means to study structure and structural heterogeneity in biology and elsewhere.
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| 4. |
- van der Schot, Gijs, et al.
(författare)
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Imaging single cells in a beam of live cyanobacteria with an X-ray laser
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- There exists a conspicuous gap of knowledge about the organization of life at mesoscopic levels. Ultra-fast coherent diffractive imaging with X-ray free-electron lasers can probe structures at the relevant length scales and may reach sub-nanometer resolution on micron-sized living cells. Here we show that we can introduce a beam of aerosolised cyanobacteria into the focus of the Linac Coherent Light Source and record diffraction patterns from individual living cells at very low noise levels and at high hit ratios. We obtain two-dimensional projection images directly from the diffraction patterns, and present the results as synthetic X-ray Nomarski images calculated from the complex-valued reconstructions. We further demonstrate that it is possible to record diffraction data to nanometer resolution on live cells with X-ray lasers. Extension to sub-nanometer resolution is within reach, although improvements in pulse parameters and X-ray area detectors will be necessary to unlock this potential.
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| 5. |
- van der Schot, Gijs, et al.
(författare)
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Open data set of live cyanobacterial cells imaged using an X-ray laser
- 2016
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 3
-
Tidskriftsartikel (refereegranskat)abstract
- Structural studies on living cells by conventional methods are limited to low resolution because radiation damage kills cells long before the necessary dose for high resolution can be delivered. X-ray free-electron lasers circumvent this problem by outrunning key damage processes with an ultra-short and extremely bright coherent X-ray pulse. Diffraction-before-destruction experiments provide high-resolution data from cells that are alive when the femtosecond X-ray pulse traverses the sample. This paper presents two data sets from micron-sized cyanobacteria obtained at the Linac Coherent Light Source, containing a total of 199,000 diffraction patterns. Utilizing this type of diffraction data will require the development of new analysis methods and algorithms for studying structure and structural variability in large populations of cells and to create abstract models. Such studies will allow us to understand living cells and populations of cells in new ways. New X-ray lasers, like the European XFEL, will produce billions of pulses per day, and could open new areas in structural sciences.
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| 6. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 7. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 8. |
- Carlsson, Tomas, et al.
(författare)
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Scaling maximal oxygen uptake to predict performance in elite-standard men cross-country skiers
- 2013
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Ingår i: Journal of Sports Sciences. - : Routledge. - 0264-0414 .- 1466-447X. ; 31:16, s. 1753-1760
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to: 1) establish the optimal body-mass exponent for maximal oxygen uptake (O2max) to indicate performance in elite-standard men cross-country skiers; and 2) evaluate the influence of course inclination on the body-mass exponent. Twelve elite-standard men skiers completed an incremental treadmill roller-skiing test to determine O2max and performance data came from the 2008 Swedish National Championship 15-km classic-technique race. Log-transformation of power-function models was used to predict skiing speeds. The optimal models were found to be: Race speed = 7.86 · O2max · m −0.48 and Section speed = 5.96 · O2max · m −(0.38 + 0.03 · α) · e−0.003 · Δ (where m is body mass, α is the section's inclination and Δ is the altitude difference of the previous section), that explained 68% and 84% of the variance in skiing speed, respectively. A body-mass exponent of 0.48 (95% confidence interval: 0.19 to 0.77) best described O2max as an indicator of performance in elite-standard men skiers. The confidence interval did not support the use of either “1” (simple ratio-standard scaled) or “0” (absolute expression) as body-mass exponents for expressing O2max as an indicator of performance. Moreover, results suggest that course inclination increases the body-mass exponent for O2max.
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| 9. |
- Lakens, Daniel, et al.
(författare)
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Justify your alpha
- 2018
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Ingår i: Nature Human Behaviour. - : Nature Publishing Group. - 2397-3374. ; 2:3, s. 168-171
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Tidskriftsartikel (refereegranskat)abstract
- In response to recommendations to redefine statistical significance to P ≤ 0.005, we propose that researchers should transparently report and justify all choices they make when designing a study, including the alpha level.
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| 10. |
- Bielecki, Johan, 1982, et al.
(författare)
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Electrospray sample injection for single-particle imaging with x-ray lasers
- 2019
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Ingår i: Science advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 5:5
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Tidskriftsartikel (refereegranskat)abstract
- The possibility of imaging single proteins constitutes an exciting challenge for x-ray lasers. Despite encouraging results on large particles, imaging small particles has proven to be difficult for two reasons: not quite high enough pulse intensity from currently available x-ray lasers and, as we demonstrate here, contamination of the aerosolized molecules by nonvolatile contaminants in the solution. The amount of contamination on the sample depends on the initial droplet size during aerosolization. Here, we show that, with our electrospray injector, we can decrease the size of aerosol droplets and demonstrate virtually contaminant-free sample delivery of organelles, small virions, and proteins. The results presented here, together with the increased performance of next-generation x-ray lasers, constitute an important stepping stone toward the ultimate goal of protein structure determination from imaging at room temperature and high temporal resolution.
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| 11. |
- Carlsson, Magnus, et al.
(författare)
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Prediction of race performance of elite cross-country skiers by lean mass
- 2014
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Ingår i: International Journal of Sports Physiology and Performance. - : Human Kinetics. - 1555-0265 .- 1555-0273. ; 9:6, s. 1040-1045
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the relationship between race performance and lean mass (LM) variables, as well as to examine sex differences in body composition in elite-standard cross-country skiers. Methods: Thirty-four elite cross-country skiers (18 men and 16 women) underwent a dual-emission x-ray absorptiometry body composition test to determine LM, fat mass, and bone mineral content. For both sexes, performance data were collected from a sprint prologue and a distance race. Results: The absolute expression of LM variables [whole body (LMWB), upper body (LMUB), and lower body (LMLB)] was significantly correlated with finishing time in the sprint prologue independent of sex. Distance-race performance was significantly related to LMWB, LMUB, and LMLB in women; however, no correlation was found in men. Men had a significantly higher LM and lower fat mass, independent of expression (absolute or relative), for the whole body, arms, trunk, and legs, except for the absolute fat mass in the trunk. Conclusions: The absolute expressions of LMWB, LMUB, and LMLB were significant predictors of sprint-prologue performance in both sexes, as well as of distance-race performance in women only. Compared with women, male skiers have a higher LM in the body segments that are major contributors to propelling forces. These results suggest that muscle mass in the lower and upper body is equally important for race performance; thus, more focus of elite skiers’ training should be directed to increasing whole-body muscle mass to improve their competitive performance capability.
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| 12. |
- Carlsson, Magnus, et al.
(författare)
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Time trials predict the competitive performance capacity of junior cross-country skiers
- 2014
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Ingår i: International Journal of Sports Physiology and Performance. - 1555-0265 .- 1555-0273. ; 9:1, s. 12-18
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study investigated whether there is a correlation between time-trial performance and competitive performance capacity of male and female junior cross-country skiers and sought to explain sex-specific competitive performance capacity through multiple-regression modeling.Methods: The International Ski Federation's (FIS) junior ranking points for distance (FISdist) and sprint (FISsprint) competitions were used as performance parameters. A total of 38 elite junior (age 18.5 +/- 1.0 y) cross-country skiers (24 men and 14 women) completed 3 time-trial tests: a 3-km level-running time trial (TTRun), a 2-km moderate uphill (1.2 slope) roller-skiing time trial using the double-poling technique (TTDP), and a 2-km uphill (2.8 slope) roller-skiing time trial using the diagonal-stride technique (TTDiag). The correlations were investigated using Pearson correlation analysis, and regression models were created using multiple-linear-regression analysis. Results: For men, FISsprint and FISdist were correlated with the times for TTRun, TTDP, and TTDiag (all P < .001). For women, FISsprint was correlated with the times for TTRun (P < .05), TTDP (P < .01), and TTDiag (P < .01), whereas FISdist was correlated only with the times for TTDP (P < .01) and TTDiag (P < .05). The models developed for FISdist and FISsprint explained 73.9-82.3% of the variance in the performance capacity of male junior cross-country skiers. No statistically valid regression model was found for the women.Conclusions: Running and roller-skiing time trials are useful tests for accurately predicting the performance capacity of junior cross-country skiers.
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| 13. |
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| 14. |
- Carlsson, Magnus, et al.
(författare)
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Validation of physiological tests in relation to competitive performances in elite male distance cross-country skiing
- 2012
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Ingår i: Journal of Strength and Conditioning Research. - : National Strength and Conditioning Association. - 1064-8011 .- 1533-4287. ; 26:6, s. 1496-1504
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the present study was to establish which physiological test parameters reflects the distance performances in the Swedish National Championships in cross-country skiing (SNC) and the International Ski Federation's ranking points for distance performances (FISdist). The present study also aimed to create multiple regression models to describe skiing performance for the SNC distance races and International Ski Federation's (FIS) ranking. Twelve male, Swedish, national elite, cross-country skiers (maximal oxygen consumption [(V) over dotO(2)max] = 5.34 +/- 0.34 L.min(-1)) volunteered to participate in the study. Their results in the 2008 SNC (15 km race [SNC15] and 30 km race [SNC30]) and FISdist points were used as performance data. On the week preceding the Championship, subjects completed a test battery consisting of 7 physiological tests: isokinetic knee extension peak torque (PT), vertical jumps (VJ), lactate threshold (LT), (V) over dotO(2)max, and 3 double poling tests of different durations (DP20, DP60, and DP360). Correlations were established using Pearson's correlation analysis, and models to describe skiing performance were created using standard multiple linear regression analysis. Significant correlations were found between the performance parameters and test parameters derived from LT, (V) over dotO(2)max, and DP60 tests. No correlations with any performance parameter were found for PT, VJ, DP20, and DP360 tests. For FISdist and SNC15, the models explain 81% and 78% of the variance in performance, respectively. No statistically valid regression model was found for SNC30. The results of this study imply that the physiological demands in male elite distance cross-country skiing performances are different in different events. To adequately evaluate a skier's performance ability in distance cross-country skiing, it is necessary to use test parameters and regression models that reflect the specific performance.
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| 15. |
- Carlsson, Tomas, 1969-, et al.
(författare)
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Optimal Formula V̇O 2max -to-mass ratio for performance among elite male cross-country skiers
- 2015
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Ingår i: Open Access Journal of Sports Medicine. - 1179-1543. ; 6, s. 353-360
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was 1) to validate the 0.5 body-mass exponent for maximal. oxygen uptake [Formula: see text] as the optimal predictor of performance in a 15 km classical-technique skiing competition among elite male cross-country skiers and 2) to evaluate the influence of distance covered on the body-mass exponent for [Formula: see text] among elite male skiers. Twenty-four elite male skiers (age: 21.4±3.3 years [mean ± standard deviation]) completed an incremental treadmill roller-skiing test to determine their [Formula: see text]. Performance data were collected from a 15 km classical-technique cross-country skiing competition performed on a 5 km course. Power-function modeling (ie, an allometric scaling approach) was used to establish the optimal body-mass exponent for [Formula: see text] to predict the skiing performance. The optimal power-function models were found to be [Formula: see text] and [Formula: see text], which explained 69% and 81% of the variance in skiing speed, respectively. All the variables contributed to the models. Based on the validation results, it may be recommended that [Formula: see text] divided by the square root of body mass (mL · min(-1) · kg(-0.5)) should be used when elite male skiers' performance capability in 15 km classical-technique races is evaluated. Moreover, the body-mass exponent for [Formula: see text] was demonstrated to be influenced by the distance covered, indicating that heavier skiers have a more pronounced positive pacing profile (ie, race speed gradually decreasing throughout the race) compared to that of lighter skiers.
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| 16. |
- Carlsson, Tomas, et al.
(författare)
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Optimal V. O2max-to-mass ratio for predicting 15 km performance among elite male cross-country skiers
- 2015
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Ingår i: Open Access Journal of Sports Medicine. - : Dove Medical Press. - 1179-1543. ; 6, s. 353-360
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was 1) to validate the 0.5 body-mass exponent for maximal oxygen uptake (V. O2max) as the optimal predictor of performance in a 15 km classical-technique skiing competition among elite male cross-country skiers and 2) to evaluate the influence of distance covered on the body-mass exponent for V. O2max among elite male skiers. Twenty-four elite male skiers (age: 21.4±3.3 years [mean ± standard deviation]) completed an incremental treadmill roller-skiing test to determine their V. O2max. Performance data were collected from a 15 km classicaltechnique cross-country skiing competition performed on a 5 km course. Power-function modeling (ie, an allometric scaling approach) was used to establish the optimal body-mass exponent for V . O2max to predict the skiing performance. The optimal power-function models were found to be race speed = 8.83⋅(V . O2max m-0.53) 0.66 and lap speed = 5.89⋅(V . O2max m-(0.49+0.018lap)) 0.43e0.010age, which explained 69% and 81% of the variance in skiing speed, respectively. All the variables contributed to the models. Based on the validation results, it may be recommended that V. O2max divided by the square root of body mass (mL⋅min−1 ⋅kg−0.5) should be used when elite male skiers’ performance capability in 15 km classical-technique races is evaluated. Moreover, the body-mass exponent for V . O2max was demonstrated to be influenced by the distance covered, indicating that heavier skiers have a more pronounced positive pacing profile (ie, race speed gradually decreasing throughout the race) compared to that of lighter skiers.
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| 17. |
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| 18. |
- Carlsson, Tomas, et al.
(författare)
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Scaling of upper-body power output to predict time-trial roller skiing performance
- 2013
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Ingår i: Journal of Sports Sciences. - : Taylor & Francis. - 0264-0414 .- 1466-447X. ; 31:6, s. 582-588
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the present study was to establish the most appropriate allometric model to predict mean skiing speed during a double-poling roller skiing time-trial using scaling of upper-body power output. Forty-five Swedish junior cross-country skiers (27 men and 18 women) of national and international standard were examined. The skiers, who had a body mass (m) of 69.3 ± 8.0 kg (mean ± s), completed a 120-s double-poling test on a ski ergometer to determine their mean upper-body power output (W). Performance data were subsequently obtained from a 2-km time-trial, using the double-poling technique, to establish mean roller skiing speed. A proportional allometric model was used to predict skiing speed. The optimal model was found to be: Skiing speed = 1.057 · W 0.556 · m −0.315, which explained 58.8% of the variance in mean skiing speed (P < 0.001). The 95% confidence intervals for the scaling factors ranged from 0.391 to 0.721 for W and from −0.626 to −0.004 for m. The results in this study suggest that allometric scaling of upper-body power output is preferable for the prediction of performance of junior cross-country skiers rather than absolute expression or simple ratio-standard scaling of upper-body power output.
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| 19. |
- Carlsson, Tomas, et al.
(författare)
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Scaling oxygen consumption to body mass in real elite cross-country skiing performances
- 2009
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Ingår i: Book of Abstracts. - 9788250204201 ; , s. 351-352
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Konferensbidrag (refereegranskat)abstract
- Introduction: Which are the main physiological differences between a successful and less successful cross-country skier? To our knowledgeno previous studies have examined a real elite cross-country ski competition. Main purpose of this study was therefore to validatecommonly used test parameters to skiing time and to International Ski Federation (FIS) overall seasonal ranking points and to createmultiple regression models to predict skiing performances.Methods: Twelve highly motivated male Swedish national elite cross-country skiers completed a test battery consisting of: isokinetic kneeextensor peak torque tests at three different velocities; three different vertical jumps tests; two-part treadmill roller skiing test determininglactate markers, maximal oxygen consumption (VO2max) and time to exhaustion; 60 and 360 s double poling tests determining meanupper-body power (DP60Pmean) (DP360Pmean) and mean oxygen consumption (DP60VO2mean) (DP360VO2mean).Performance data were collected from the Swedish National Championship (SNC) in cross-country skiing (13-17 March 2008): 15-km withindividual start in classical technique (SNC15); 30-km double pursuit with mass-start (SNC30); sprint prolog in free-style technique(SNCsprint). In addition to ski races, overall seasonal ski ranking points were collected from FIS 3rd Cross-Country Points List 2007/2008published before SNC for distance (FISdist) and sprint (FISsprint) races.Correlations between test parameters and performance data were established using Pearson´s correlation analysis. Prediction modelswere created using standard multiple linear regression analysis.Results: Time to exhaustion during the incremental treadmill roller ski test is best correlated with both SNC15 (r = -0.86, p < 0.001) andSNC30 (r = -0.81, p < 0.01). For SNC15 significant correlations were shown with VO2max both absolute and relative to body weight, lactatemarkers, DP60Pmean and DP60VO2mean. Corresponding correlations for SNC30 were: lactate markers, DP60VO2mean and percentagedecrease in mean knee extension peak torque when comparing highest and lowest velocities. Highest correlation coefficient forSNCsprint was found for DP60Pmean (r = -0.93, p < 0.05). Significant correlations for SNCsprint was also detected for DP360Pmean aswell as DP360VO2mean and jump height in squat jump.Prediction models explain 68, 91, 68, 77 and 82% of the variance in performance for SNC15, SNC30, SNCsprint, FISdist and FISsprint,respectively.Discussion: Correlations found in this study have validated several commonly used physiological tests with real elite cross-country skiingperformances. Frequently investigated test parameters like VO2max and anaerobic thresholds are of great importance for success incross-country skiing. Many recent research studies have focused on upper-body capacity and we could confirm that high mean powerproduction in double poling is necessary to be successful as elite skier in both sprint and distance races.
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| 20. |
- Carlsson, Tomas, et al.
(författare)
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The importance of scaling VO2MAX to predict cross-country skiing performance
- 2013
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Konferensbidrag (refereegranskat)abstract
- Introduction A high maximal oxygen uptake (VO2max) is of importance for success in elite male competitive distance cross-country skiing (Carlsson et al. 2012). However, it is still debatable how VO2max should be expressed to best indicate skiing performance. Therefore, the purpose of this study was to establish the optimal body mass exponent for VO2max to indicate performance in elite-standard male cross-country skiers. Methods Twenty-four elite-standard male cross-country skiers completed an incremental treadmill roller skiing test in diagonal stride technique determining VO2max. Performance data was compiled from a 15-km classic technique race. To predict performance a log-transformation of power-function model: Race speed = β0 • VO2max^β1 • m^β2 was used, where β0 to β2 are constants, and m is body mass. Statistical analyses used R version 2.13.2 (R Development Core Team, New Zeeland) and alpha was 0.05. Results Participants’ VO2max was 5.39 ± 0.57 l/min (mean ± s) and m was 75.5 ± 6.3 kg. Mean race speed was 5.83 ± 0.41 m/s. The model that best predicted performance was: Race speed = 8.829 • VO2max^0.663 • m^-0.355 = 8.829 • (VO2max • m^–0.535 )^0.663, that explains 69.2% of the variance in race speed for the 15-km classic technique race (P < 0.001). For the VO2max-to-mass ratio within the model, the 95% confidence interval (CI) for the body-mass exponent ranged from -0.947 to -0.122. Discussion The optimal body mass exponent for VO2max to indicate performance in elite-standard male cross-country skiers was -0.535. Moreover, the CI for the body-mass exponent does not support the use of simple ratio-standard scaling and absolute expression of VO2max as indicators of 15 km classic ski racing performance in elite-standard men skiers.
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| 21. |
- Daurer, Benedikt J., et al.
(författare)
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Experimental strategies for imaging bioparticles with femtosecond hard X-ray pulses
- 2017
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Ingår i: IUCrJ. - : INT UNION CRYSTALLOGRAPHY. - 2052-2525. ; 4, s. 251-262
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Tidskriftsartikel (refereegranskat)abstract
- This study explores the capabilities of the Coherent X-ray Imaging Instrument at the Linac Coherent Light Source to image small biological samples. The weak signal from small samples puts a significant demand on the experiment. Aerosolized Omono River virus particles of similar to 40 nm in diameter were injected into the submicrometre X-ray focus at a reduced pressure. Diffraction patterns were recorded on two area detectors. The statistical nature of the measurements from many individual particles provided information about the intensity profile of the X-ray beam, phase variations in the wavefront and the size distribution of the injected particles. The results point to a wider than expected size distribution (from similar to 35 to similar to 300 nm in diameter). This is likely to be owing to nonvolatile contaminants from larger droplets during aerosolization and droplet evaporation. The results suggest that the concentration of nonvolatile contaminants and the ratio between the volumes of the initial droplet and the sample particles is critical in such studies. The maximum beam intensity in the focus was found to be 1.9 * 10(12) photons per mu m(2) per pulse. The full-width of the focus at half-maximum was estimated to be 500 nm (assuming 20% beamline transmission), and this width is larger than expected. Under these conditions, the diffraction signal from a sample-sized particle remained above the average background to a resolution of 4.25 nm. The results suggest that reducing the size of the initial droplets during aerosolization is necessary to bring small particles into the scope of detailed structural studies with X-ray lasers.
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| 22. |
- Drott, Carl Johan, 1984-, et al.
(författare)
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Irisin is present in α cells and decreases islet blood flow
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Irisin is a myokine involved in glucose homeostasis, and is primarily expressed in skeletal muscle and adipose tissue but also in multiple tissues, among them, the pancreas. We aimed to elucidate the cell-specific expression and secretion of irisin, as well as the effect of irisin, in the pancreas. Irisin was observed to be expressed predominantly in α cells, and perifusion of human islets with glucose demonstrated that irisin was secreted in a glucose-dependent manner. Intravenous infusion of irisin in Sprague-Dawley rats resulted in a nearly 50% reduction of islet blood flow compared to control. However, neither irisin nor an irisin neutralizing antibody affected insulin secretion from rat or human islets in vitro. We conclude that irisin has a novel role in pancreatic islet physiology, being secreted by α cells in response to glucose, i.e. in an inverse manner to glucagon, and exerting local vascular effects diminishing islet blood flow while not affecting insulin secretion per se.
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| 23. |
- Hägg, Daniel, 1974, et al.
(författare)
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Expression profiling of macrophages from subjects with atherosclerosis to identify novel susceptibility genes.
- 2008
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Ingår i: International journal of molecular medicine. - 1107-3756. ; 21:6, s. 697-704
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Tidskriftsartikel (refereegranskat)abstract
- Although a number of environmental risk factors for atherosclerosis have been identified, heredity seems to be a significant independent risk factor. The aim of our study was to identify novel susceptibility genes for atherosclerosis. The screening process consisted of three steps. First, expression profiles of macrophages from subjects with atherosclerosis were compared to macrophages from control subjects. Secondly, the subjects were genotyped for promoter region polymorphisms in genes with altered gene expression. Thirdly, a population of subjects with coronary heart disease and control subjects were genotyped to test for an association with identified polymorphisms that affected gene expression. Twenty-seven genes were differentially expressed in both macrophages and foam cells from subjects with atherosclerosis. Three of these genes, IRS2, CD86 and SLC11A1 were selected for further analysis. Foam cells from subjects homozygous for the C allele at the -765C-->T SNP located in the promoter region of IRS2 had increased gene expression compared to foam cells from subjects with the nonCC genotype. Also, macrophages and foam cells from subjects homozygous for allele 2 at a repeat element in the promoter region of SLC11A1 had increased gene expression compared to macrophages and foam cells from subjects with the non22 genotype. Genotyping of 512 pairs of subjects with coronary heart disease (CHD) and matched controls revealed that subjects homozygous for C of the IRS2 SNP had an increased risk for CHD; odds ratio 1.43, p=0.010. Immunohistochemical staining of human carotid plaques showed that IRS2 expression was localised to macrophages and endothelial cells in vivo. Our method provides a reliable approach for identifying susceptibility genes for atherosclerosis, and we conclude that elevated IRS2 gene expression in macrophages may be associated with an increased risk of CHD.
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| 24. |
- Hägg, Daniel, 1974, et al.
(författare)
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Oxidized LDL induces a coordinated up-regulation of the glutathione and thioredoxin systems in human macrophages.
- 2006
-
Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 185:2, s. 282-9
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Tidskriftsartikel (refereegranskat)abstract
- Using DNA microarray analysis, we found that human macrophages respond to oxidized low-density lipoprotein (oxLDL) by activating the antioxidative glutathione and thioredoxin systems. Several genes of the glutathione and thioredoxin systems were expressed at high levels in macrophages when compared to 80 other human tissues and cell types, indicating that these systems may be of particular importance in macrophages. The up-regulation of three genes in these systems, thioredoxin (P < 0.005), thioredoxin reductase 1 (P < 0.001) and glutathione reductase (P < 0.001) was verified with real-time RT-PCR, using human macrophages from 10 healthy donors. To investigate the possible role of these antioxidative systems in the development of atherosclerosis, expression levels in macrophages from 15 subjects with atherosclerosis (12 men, 3 women) and 15 matched controls (12 men, 3 women) were analyzed using DNA microarrays. Two genes in the glutathione system Mn superoxide dismutase (P < 0.05) and catalase (P < 0.05) differed in expression between the groups. We conclude that macrophage uptake of oxidized LDL induces a coordinated up-regulation of genes of the glutathione and thioredoxin systems, suggesting that these systems may participate in the cellular defense against oxidized LDL and possibly modulate the development of atherosclerosis.
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| 25. |
- Johansson, Ellen, et al.
(författare)
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Revising the embryonic origin of thyroid C cells in mice and humans
- 2015
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Ingår i: Development (Cambridge, England). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 142:20, s. 3519-3528
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Tidskriftsartikel (refereegranskat)abstract
- Current understanding infers a neural crest origin of thyroid C cells, the major source of calcitonin in mammals and ancestors to neuroendocrine thyroid tumors. The concept is primarily based on investigations in quail-chick chimeras involving fate-mapping of neural crest cells to the ultimobranchial glands that regulate Ca(2+) homeostasis in birds, reptiles, amphibians and fishes, but whether mammalian C cell development implicates a homologous ontogenetic trajectory has not been experimentally verified. With lineage tracing we now provide direct evidence that Sox17+ anterior endoderm is the only source of differentiated C cells and their progenitors in mice. In similarity with many gut endoderm derivatives embryonic C cells were found to co-express pioneer factors forkhead box (Fox) a1 and Foxa2 before neuroendocrine differentiation takes place. In the ultimobranchial body epithelium emerging from pharyngeal pouch endoderm in early organogenesis differential Foxa1/Foxa2 expression distinguished two spatially separated pools of C cell precursors with different growth properties. A similar expression pattern was recapitulated in medullary thyroid carcinoma cells in vivo consistent with a growth-promoting role of Foxa1. Contrasting embryonic precursor cells, C cell-derived tumor cells invading the stromal compartment down-regulated Foxa2 foregoing epithelial-mesenchymal transition designated by loss of E-cadherin; both Foxa2 and E-cadherin were re-expressed at metastatic sites. These findings revise mammalian C cell ontogeny, expand the neuroendocrine repertoire of endoderm, and redefine the boundaries of neural crest diversification. The data further underpin distinct functions of Foxa1 and Foxa2 in both embryonic and tumor development.
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| 26. |
- Lau, Joey, et al.
(författare)
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Implantation site-dependent dysfunction of transplanted pancreatic islets
- 2007
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 56:6, s. 1544-1550
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE—Clinical islet transplantations are performed through infusion of islets via the portal vein into the liver. This study aimed at characterizing the influence of the implantation microenvironment on islet graft metabolism and function. RESEARCH DESIGN AND METHODS—Islets were transplanted into their normal environment, i.e., the pancreas, or intraportally into the liver of mice. One month posttransplantation, the transplanted islets were retrieved and investigated for changes in function and gene expression. RESULTS—Insulin content, glucose-stimulated insulin release, (pro)insulin biosynthesis, and glucose oxidation rate were markedly decreased in islets retrieved from the liver, both when compared with islets transplanted into the pancreas and endogenous islets. Islets transplanted into the pancreas showed normal insulin content, (pro)insulin biosynthesis, and glucose oxidation rate but increased basal insulin secretion and impaired glucose stimulation index. Gene expression data for retrieved islets showed downregulation of pancreatic and duodenal homeobox gene-1, GLUT-2, glucokinase, mitochondrial glycerol-phosphate dehydrogenase, and pyruvate carboxylase, preferentially in intraportally transplanted islets. CONCLUSIONS—Islets transplanted into their normal microenvironment, i.e., the pancreas, display gene expression changes when compared with endogenous islets but only moderate changes in metabolic functions. In contrast, site-specific properties of the liver markedly impaired the metabolic functions of intraportally transplanted islets.
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| 27. |
- Lundgren, Markus, et al.
(författare)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
-
Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 28. |
- Norman, Daniel, et al.
(författare)
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Irisin-A Pancreatic Islet Hormone
- 2022
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Ingår i: Biomedicines. - : MDPI. - 2227-9059. ; 10:2
-
Tidskriftsartikel (refereegranskat)abstract
- Irisin is a myokine involved in glucose homeostasis. It is primarily expressed in skeletal muscle, but also in the pancreas. This study aimed to elucidate its presence and role in the islets of Langerhans-i.e., its effect on insulin and glucagon secretion as well as on blood flow in the pancreas. The precursor of irisin, fibronectin type III domain-containing protein 5 (FNDC5), was identified in rat and human islets by both qPCR and immunohistochemistry. Both alpha- and beta-cells stained positive for FNDC5. In human islets, we found that irisin was secreted in a glucose-dependent manner. Neither irisin nor an irisin-neutralizing antibody affected insulin or glucagon secretion from human or rat islets in vitro. The insulin and glucagon content in islets was not altered by irisin. The intravenous infusion of irisin in Sprague Dawley rats resulted in nearly 50% reduction in islet blood flow compared to the control. We conclude that irisin is an islet hormone that has a novel role in pancreatic islet physiology, exerting local vascular effects by diminishing islet blood flow without affecting insulin secretion per se.
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| 29. |
- Norman, Daniel, 1997-
(författare)
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Physiological Studies of Native and Stem Cell-Derived Islets
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In type 1 and type 2 diabetes, the β-cells of the islets of Langerhans are either destroyed by the immune system or stressed due to peripheral insulin resistance. To improve the life of patients with these diseases, new treatments are needed. This thesis examined the role of irisin and cocaine and amphetamine regulated transcript (CART) in islets of Langerhans and their potential pharmaceutical role in type 2 diabetes. Furthermore, β-cell replacement with stem cell-derived islets of Langerhans (SC-islets) for type 1 diabetes was evaluated for optimal implantation site.In paper I, the physiological role of CART in rat islets was examined. CART was shown to specifically lower islet blood flow, which could be a protective effect in type 2 diabetes. No effect from CART on glucose tolerance or insulin release was seen in rat islets, which highlights species differences.In paper II, the expression of irisin and its effect on hormone secretion and pancreatic blood flow was examined. Irisin was expressed in human islets and was secreted glucose dependently. It also lowered islet blood flow but did not affect glucose-stimulated insulin secretion in isolated human or rat islets. Thus, local secretion of irisin could serve as a protective function by lowering islet blood flow in a high glucose state.In paper III, the expression of irisin in SC-islets and its potential beneficial effects in transplantation was examined. SC-islets were found to express higher levels of irisin than human islets. Irisin treatment had no effects on viability and proliferation in SC-islets, in contrast to previous studies in other species. Thus, irisin signaling likely differs between SC-islets and murine and native human islets.In paper IV, SC-islets were transplanted to multiple sites in mice to find the optimal implantation site in terms of graft maturity, function and composition. The liver proved to be the most favorable site due to its higher expression of islet maturity genes and a higher β-cell function and fraction. This poses a dilemma, as the liver site is the most challenging to biopsy and monitor for safety.In summary, this thesis uncovered new physiological functions of irisin and CART, potentially offering insights relevant to the treatment of type 2 diabetes. Meanwhile, the role of irisin in transplantation of SC-islets seems limited.
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| 30. |
- Rath, Asawari D., et al.
(författare)
-
Explosion dynamics of sucrose nanospheres monitored by time of flight spectrometry and coherent diffractive imaging at the split-and-delay beam line of the FLASH soft X-ray laser
- 2014
-
Ingår i: Optics Express. - 1094-4087. ; 22:23, s. 28914-28925
-
Tidskriftsartikel (refereegranskat)abstract
- We use a Mach-Zehnder type autocorrelator to split and delay XUV pulses from the FLASH soft X-ray laser for triggering and subsequently probing the explosion of aerosolised sugar balls. FLASH was running at 182 eV photon energy with pulses of 70 fs duration. The delay between the pump-probe pulses was varied between zero and 5 ps, and the pulses were focused to reach peak intensities above 1016 W/cm2 with an off-axis parabola. The direct pulse triggered the explosion of single aerosolised sucrose nano-particles, while the delayed pulse probed the exploding structure. The ejected ions were measured by ion time of flight spectrometry, and the particle sizes were measured by coherent diffractive imaging. The results show that sucrose particles of 560-1000 nm diameter retain their size for about 500 fs following the first exposure. Significant sample expansion happens between 500 fs and 1 ps. We present simulations to support these observations.
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| 31. |
- Silberzahn, Raphael, et al.
(författare)
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Many analysts, one dataset : Making transparent how variations in analytical choices affect results
- 2018
-
Ingår i: Advances in Methods and Practices in Psychological Science. - : Sage Publications. - 2515-2459 .- 2515-2467. ; 1:3, s. 337-356
-
Tidskriftsartikel (refereegranskat)abstract
- Twenty-nine teams involving 61 analysts used the same dataset to address the same research question: whether soccer referees are more likely to give red cards to dark skin toned players than light skin toned players. Analytic approaches varied widely across teams, and estimated effect sizes ranged from 0.89 to 2.93 in odds ratio units, with a median of 1.31. Twenty teams (69%) found a statistically significant positive effect and nine teams (31%) observed a non-significant relationship. Overall 29 differentanalyses used 21 unique combinations of covariates. We found that neither analysts' prior beliefs about the effect, nor their level of expertise, nor peer-reviewed quality of analysis readily explained variation in analysis outcomes. This suggests that significant variation in the results of analyses of complex data may be difficult to avoid, even by experts with honest intentions. Crowdsourcing data analysis, a strategy by which numerous research teams are recruited to simultaneously investigate the same research question, makes transparent how defensible, yet subjective analytic choices influence research results.
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| 32. |
- Svensson, Per Anders, 1959, et al.
(författare)
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Identification of genes predominantly expressed in human macrophages
- 2004
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Ingår i: Atherosclerosis. - : Elsevier BV. ; 177, s. 287-290
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Tidskriftsartikel (refereegranskat)abstract
- Identification of cell and tissue specific genes may provide novel insights to signaling systems and functions. Macrophages play a key role in many diseases including atherosclerosis. Using DNA microarrays we compared the expression of approximately 10,000 genes in 56 human tissues and identified 23 genes with predominant expression in macrophages. The identified genes include both genes known to be macrophage specific and genes previously not well described in this cell type. Tissue distribution of two genes, liver X receptor (LXR) alpha and interleukin-1 receptor antagonist (IL1RN), was verified by real-time RT-PCR. We conclude that comparison of expression profiles from a large number of tissues can be used to identify genes that are predominantly expressed in certain tissues. Identification of novel macrophage specific genes may increase our understanding of the role of this cell in different diseases.
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| 33. |
- Svensson, Per-Arne, 1969, et al.
(författare)
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Regulation and splicing of scavenger receptor class B type I in human macrophages and atherosclerotic plaques
- 2005
-
Ingår i: BMC Cardiovasc Disord. - : Springer Science and Business Media LLC. - 1471-2261. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The protective role of high-density lipoprotein (HDL) in the cardiovascular system is related to its role in the reverse transport of cholesterol from the arterial wall to the liver for subsequent excretion via the bile. Scavenger receptor class B type I (SR-BI) binds HDL and mediates selective uptake of cholesterol ester and cellular efflux of cholesterol to HDL. The role of SR-BI in atherosclerosis has been well established in murine models but it remains unclear whether SR-BI plays an equally important role in atherosclerosis in humans. The aim of this study was to investigate the expression of SR-BI and its isoforms in human macrophages and atherosclerotic plaques. METHODS: The effect of hypoxia and minimally modified low-density lipoprotein (mmLDL), two proatherogenic stimuli, on SR-BI expression was studied in human monocyte-derived macrophages from healthy subjects using real-time PCR. In addition, SR-BI expression was determined in macrophages obtained from subjects with atherosclerosis (n = 15) and healthy controls (n = 15). Expression of SR-BI isoforms was characterized in human atherosclerotic plaques and macrophages using RT-PCR and DNA sequencing. RESULTS: SR-BI expression was decreased in macrophages after hypoxia (p < 0.005). In contrast, SR-BI expression was increased by exposure to mmLDL (p < 0.05). There was no difference in SR-BI expression in macrophages from patients with atherosclerosis compared to controls. In both groups, SR-BI expression was increased by exposure to mmLDL (p < 0.05). Transcripts corresponding to SR-BI and SR-BII were detected in macrophages. In addition, a third isoform, referred to as SR-BIII, was discovered. All three isoforms were also expressed in human atherosclerotic plaque. Compared to the other isoforms, the novel SR-BIII isoform was predicted to have a unique intracellular C-terminal domain containing 53 amino acids. CONCLUSION: We conclude that SR-BI is regulated by proatherogenic stimuli in humans. However, we found no differences between subjects with atherosclerosis and healthy controls. This indicates that altered SR-BI expression is not a common cause of atherosclerosis. In addition, we identified SR-BIII as a novel isoform expressed in human macrophages and in human atherosclerotic plaques.
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| 34. |
- Säll, Johanna, et al.
(författare)
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The antimicrobial peptide LL-37 alters human osteoblast Ca2+ handling and induces Ca2+-independent apoptosis
- 2013
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Ingår i: Journal of Innate Immunity. - : S. Karger. - 1662-811X .- 1662-8128. ; 3:5, s. 290-300
-
Tidskriftsartikel (refereegranskat)abstract
- The human antimicrobial peptide cathelicidin LL-37 has, besides its antimicrobial properties, also been shown to regulate apoptosis in a cell type-specific manner. Mechanisms involved in LL-37-regulated apoptotic signaling are not identified. Here, we show that LL-37 reduces the human osteoblast-like MG63 cell number and cell viability in the micromolar concentration range with an IC50 value of about 5 µM. Treatment with 4 µM LL-37 increased the number of annexin V-positive cells and stimulated activation of caspase 3 showing that LL-37 promotes apoptosis. Treatment with 4 µM LL-37 caused an acute and sustained rise in intracellular Ca(2+) concentration assessed by laser-scanning confocal microscopy of Fluo-4-AM-loaded MG63 cells. LL-37 increased Ca(2+) also in the presence of the respective L- and T-type voltage-sensitive Ca(2+) channel blockers nifedipine and NiCl2. LL-37 had no effect on Ca(2+) in cells incubated with Ca(2+)-free solution. LL-37 (4 and 8 µM) reduced the MG63 cell number both in the presence and absence of Ca(2+) in the medium. In conclusion, LL-37 reduces the osteoblast cell number by promoting apoptosis, and furthermore, LL-37 stimulates Ca(2+) inflow via a mechanism independent of voltage-sensitive Ca(2+) channels. Interestingly, LL-37-induced lowering of the cell number seems to be mediated via a mechanism independent of Ca(2+).
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| 35. |
- Aaro, Gustav, 1995-, et al.
(författare)
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Toolset for Run-time Dataset Collection of Deep-scene Information
- 2020
-
Ingår i: Symposium on Modelling, Analysis, and Simulation of Computer and Telecommunication Systems (MASCOTS). - Cham : Springer. - 9783030681098 ; , s. 224-236
-
Konferensbidrag (refereegranskat)abstract
- Virtual reality (VR) provides many exciting new application opportunities, but also present new challenges. In contrast to 360° videos that only allow a user to select its viewing direction, in fully immersive VR, users can also move around and interact with objects in the virtual world. To most effectively deliver such services it is therefore important to understand how users move around in relation to such objects. In this paper, we present a methodology and software tool for generating run-time datasets capturing a user’s interactions with such 3D environments, evaluate and compare different object identification methods that we implement within the tool, and use datasets collected with the tool to demonstrate example uses. The tool was developed in Unity, easily integrates with existing Unity applications through the use of periodic calls that extracts information about the environment using different ray-casting methods. The software tool and example datasets are made available with this paper.
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| 36. |
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| 37. |
- Agardh, Daniel, et al.
(författare)
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Prediction of silent celiac disease at diagnosis of childhood type 1 diabetes by tissue transglutaminase autoantibodies and HLA
- 2001
-
Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X. ; 2:2, s. 58-65
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The aims were to estimate the diagnostic sensitivity and specificity of autoantibodies to tissue transglutaminase (IgA- and IgG-tTG), gliadin (AGA) and endomysium (EMA) in relation to human leukocyte antigen (HLA)-DQB1 alleles to identify silent celiac disease at diagnosis of type 1 diabetes. Methods: IgA- and IgG-tTG were measured in radioligand binding assays in 165 type 1 diabetic patients. Data on HLA-DQB1 were available for 148 patients and on both AGA and EMA for 164 patients. For patients considered positive for AGA or EMA, or both, an intestinal biopsy was suggested. HLA-DQB1 typing was carried out by polymerase chain reaction and hybridization with allele specific probes. Results: Three patients, left out from further study of antibodies, but not from HLA-DQB1 analysis, had treated celiac disease at diagnosis. Out of the other 162 type 1 diabetic patients tested, nine had IgA-tTG, six IgG-tTG, eight EMA, and 11 AGA. Biopsy was suggested for nine patients, of whom six showed villous atrophy, one did not and two refused to participate. Thus, silent celiac disease was probable in 8/162 and biopsy-verified in 6/162, where five patients were AGA-positive and six either EMA-, IgA-tTG- or IgG-tTG-positive. Of the 11 patients with celiac disease (three with treated and eight with silent celiac disease), 10 were HLA-DQB1-typed, of whom 65% (13/20) had the DQB1*02 allele, compared with 36% (100/276; p = 0.011) of those without celiac disease. IgA-tTG levels were higher in patients having either *02 or *0302 (0.6; −1.3–112.4 RU) compared with those not having these alleles (0.4; −0.7–3.4 RU; p = 0.023). Conclusion: IgA-tTG are HLA-DQB1*02-associated autoantibodies with high sensitivity and specificity for silent celiac disease at diagnosis of type 1 diabetes.
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| 38. |
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| 39. |
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| 40. |
- Ahlberg, Erik, et al.
(författare)
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"Vi klimatforskare stödjer Greta och skolungdomarna"
- 2019
-
Ingår i: Dagens nyheter (DN debatt). - 1101-2447.
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 15/3. Sedan industrialiseringens början har vi använt omkring fyra femtedelar av den mängd fossilt kol som får förbrännas för att vi ska klara Parisavtalet. Vi har bara en femtedel kvar och det är bråttom att kraftigt reducera utsläppen. Det har Greta Thunberg och de strejkande ungdomarna förstått. Därför stödjer vi deras krav, skriver 270 klimatforskare.
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| 41. |
- Almroth, Melody, 1989-, et al.
(författare)
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The role of working conditions in educational differences in all-cause and ischemic heart disease mortality among Swedish men
- 2024
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Ingår i: Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 50:4, s. 300-309
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives This study aims to investigate the extent to which low job control and heavy physical workload in middle age explain educational differences in all-cause and ischemic heart disease (IHD) mortality while accounting for important confounding factors.Methods The study is based on a register-linked cohort of men who were conscripted into the Swedish military at around the age of 18 in 1969/1970 and were alive and registered in Sweden in 2005 (N=46 565). Cox proportional hazards regression models were built to estimate educational differences in all-cause and IHD mortality and the extent to which this was explained by physical workload and job control around age 55 by calculating the reduction in hazard ratio (HR) after adjustments. Indicators of health, health behavior, and other factors measured during conscription were accounted for.Results We found a clear educational gradient for all-cause and IHD mortality (HR 2.07 and 2.47, respectively, for the lowest compared to the highest education level). A substantial part was explained by the differential distribution of the confounding factors. However, work-related factors, especially high physical workload, also played important explanatory roles.Conclusion Even after accounting for earlier life factors, low job control and especially high physical workload seem to be important mechanistic factors in explaining educational inequalities in all-cause and IHD mortality. It is therefore important to find ways to reduce physical workload and increase job control in order to decrease inequalities in mortality.
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| 42. |
- Anwar, Mohiemen, et al.
(författare)
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Ixovex-1, a novel oncolytic E1B-mutated adenovirus
- 2022
-
Ingår i: Cancer Gene Therapy. - : Springer Nature. - 0929-1903 .- 1476-5500. ; 29:11, s. 1628-1635
-
Tidskriftsartikel (refereegranskat)abstract
- There is a great demand for improved oncolytic viruses that selectively replicate within cancer cells while sparing normal cells. Here, we describe a novel oncolytic adenovirus, Ixovex-1, that obtains a cancer-selective replication phenotype by modulating the level of expression of the different, alternatively spliced E1B mRNA isoforms. Ixovex-1 is a recombinant adenovirus that carries a single point mutation in the E1B-93R 3' splice acceptor site that results in overexpression of the E1B-156R splice isoform. In this paper, we studied the characteristics of this novel oncolytic adenovirus by validating its in vitro behaviour in a panel of normal cells and cancer cells. We additionally studied its anti-tumour efficacy in vivo. Ixovex-1 significantly inhibited tumour growth and prolonged survival of mice in an immune-deficient lung carcinoma tumour implantation model. In complementation experiments, overexpression of E1B-156R was shown to increase the oncolytic index of both Ad5wt and ONYX-015. In contrast to prior viruses of similar type, Ixovex-1 includes a functional E3B region for better in vivo efficacy. Throughout this study, the Ixovex-1 virus has been proven to be superior in competency compared to a virus with multiple deletions.
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| 43. |
- Asan, Noor Badariah, 1984-, et al.
(författare)
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Intra-body microwave communication through adipose tissue
- 2017
-
Ingår i: Healthcare technology letters. - : The Institution of Engineering and Technology. - 2053-3713. ; 4:4, s. 115-121
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Tidskriftsartikel (refereegranskat)abstract
- The human body can act as a medium for the transmission of electromagnetic waves in the wireless body sensor networks context. However, there are transmission losses in biological tissues due to the presence of water and salts. This Letter focuses on lateral intra-body microwave communication through different biological tissue layers and demonstrates the effect of the tissue thicknesses by comparing signal coupling in the channel. For this work, the authors utilise the R-band frequencies since it overlaps the industrial, scientific and medical radio (ISM) band. The channel model in human tissues is proposed based on electromagnetic simulations, validated using equivalent phantom and ex-vivo measurements. The phantom and ex-vivo measurements are compared with simulation modelling. The results show that electromagnetic communication is feasible in the adipose tissue layer with a low attenuation of approximate to 2 dB per 20 mm for phantom measurements and 4 dB per 20 mm for ex-vivo measurements at 2 GHz. Since the dielectric losses of human adipose tissues are almost half of ex-vivo tissue, an attenuation of around 3 dB per 20 mm is expected. The results show that human adipose tissue can be used as an intra-body communication channel.
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| 44. |
- Asgeirsson, Daniel, et al.
(författare)
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Longitudinal shortening remains the principal component of left ventricular pumping in patients with chronic myocardial infarction even when the absolute atrioventricular plane displacement is decreased
- 2017
-
Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 17:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The majority (60%) of left ventricular (LV) stroke volume (SV) is generated by longitudinal shortening causing apical atrioventricular plane displacement (AVPD) in systole. The remaining SV is caused by radial inward motion of the epicardium both in the septal and the lateral wall. We aimed to determine if these longitudinal, septal and lateral contributions to LVSV are changed in patients with chronic myocardial infarction (MI). Methods: Patients with a chronic (>3 months) ST-elevation MI in the left anterior descending (LAD, n = 20) or right coronary artery (RCA, n = 16) and healthy controls (n = 20) were examined with cardiovascular magnetic resonance (CMR). AVPD was quantified in long axis cine CMR images and LV volumes and dimensions in short axis cine images. Results: AVPD was decreased both in patients with LAD-MI (11 ± 1 mm, p < 0.001) and RCA-MI (13 ± 1 mm, p < 0.05) compared to controls (15 ± 0 mm). However, the longitudinal contribution to SV was unchanged for both LAD-MI (58 ± 3%, p = 0.08) and RCA-MI (59 ± 3%, p = 0.09) compared to controls (64 ± 2%). The preserved longitudinal contribution despite decreased absolute AVPD was a results of increased epicardial dimensions (p < 0.01 for LAD-MI and p = 0.06 for RCA-MI). In LAD-MI the septal contribution to LVSV was decreased (5 ± 1%) compared to both controls (10 ± 1%, p < 0.01) and patients with RCA-MIs (10 ± 1%, p < 0.01). The lateral contribution was increased in LAD-MI patients (44 ± 3%) compared to both RCA-MI (35 ± 2%, p < 0.05) and controls (29 ± 2%, p < 0.001). Conclusion: Longitudinal shortening remains the principal component of left ventricular pumping in patients with chronic MI even when the absolute AVPD is decreased.
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| 45. |
- Ashton, Nicholas J., et al.
(författare)
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Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology
- 2024
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Ingår i: JAMA NEUROLOGY. - 2168-6149 .- 2168-6157.
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Tidskriftsartikel (refereegranskat)abstract
- ImportancePhosphorylated tau (p-tau) is a specific blood biomarker for Alzheimer disease (AD) pathology, with p-tau217 considered to have the most utility. However, availability of p-tau217 tests for research and clinical use has been limited. Expanding access to this highly accurate AD biomarker is crucial for wider evaluation and implementation of AD blood tests. ObjectiveTo determine the utility of a novel and commercially available immunoassay for plasma p-tau217 to detect AD pathology and evaluate reference ranges for abnormal amyloid beta (A beta) and longitudinal change across 3 selected cohorts. Design, Setting, and ParticipantsThis cohort study examined data from 3 single-center observational cohorts: cross-sectional and longitudinal data from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort (visits October 2017-August 2021) and Wisconsin Registry for Alzheimer's Prevention (WRAP) cohort (visits February 2007-November 2020) and cross-sectional data from the Sant Pau Initiative on Neurodegeneration (SPIN) cohort (baseline visits March 2009-November 2021). Participants included individuals with and without cognitive impairment grouped by amyloid and tau (AT) status using PET or CSF biomarkers. Data were analyzed from February to June 2023. ExposuresMagnetic resonance imaging, A beta positron emission tomography (PET), tau PET, cerebrospinal fluid (CSF) biomarkers (A beta 42/40 and p-tau immunoassays), and plasma p-tau217 (ALZpath pTau217 assay). Main Outcomes and MeasuresAccuracy of plasma p-tau217 in detecting abnormal amyloid and tau pathology, longitudinal p-tau217 change according to baseline pathology status. ResultsThe study included 786 participants (mean [SD] age, 66.3 [9.7] years; 504 females [64.1%] and 282 males [35.9%]). High accuracy was observed in identifying elevated A beta (area under the curve [AUC], 0.92-0.96; 95% CI, 0.89-0.99) and tau pathology (AUC, 0.93-0.97; 95% CI, 0.84-0.99) across all cohorts. These accuracies were comparable with CSF biomarkers in determining abnormal PET signal. The detection of abnormal A beta pathology using a 3-range reference yielded reproducible results and reduced confirmatory testing by approximately 80%. Longitudinally, plasma p-tau217 values showed an annual increase only in A beta-positive individuals, with the highest increase observed in those with tau positivity. Conclusions and RelevanceThis study found that a commercially available plasma p-tau217 immunoassay accurately identified biological AD, comparable with results using CSF biomarkers, with reproducible cut-offs across cohorts. It detected longitudinal changes, including at the preclinical stage.
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| 46. |
- Ashton, Nicholas J., et al.
(författare)
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Diagnostic accuracy of the plasma ALZpath pTau217 immunoassay to identify Alzheimer's disease pathology.
- 2023
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Ingår i: medRxiv : the preprint server for health sciences.
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Tidskriftsartikel (refereegranskat)abstract
- Phosphorylated tau (pTau) is a specific blood biomarker for Alzheimer's disease (AD) pathology, with pTau217 considered to have the most utility. However, availability of pTau217 tests for research and clinical use has been limited. Expanding access to this highly accurate AD biomarker is crucial for wider evaluation and implementation of AD blood tests.To determine the utility of a novel and commercially available Single molecule array (Simoa) for plasma pTau217 (ALZpath) to detect AD pathology. To evaluate references ranges for abnormal Aβ across three selected cohorts.Three single-centre observational cohorts were involved in the study: Translational Biomarkers in Aging and Dementia (TRIAD), Wisconsin Registry for Alzheimer's Prevention (WRAP), and Sant Pau Initiative on Neurodegeneration (SPIN). MRI, Aβ-PET, and tau-PET data were available for TRIAD and WRAP, while CSF biomarkers were additionally measured in a subset of TRIAD and SPIN. Plasma measurements of pTau181, pTau217 (ALZpath), pTau231, Aβ42/40, GFAP, and NfL, were available for all cohorts. Longitudinal blood biomarker data spanning 3 years for TRIAD and 8 years for WRAP were included.MRI, Aβ-PET, tau-PET, CSF biomarkers (Aβ42/40 and pTau immunoassays) and plasma pTau217 (ALZpath Simoa).The accuracy of plasma pTau217 for detecting abnormal amyloid and tau pathology. Longitudinal pTau217 change according to baseline pathology status.The study included 786 participants (mean [SD] age, 66.3 [9.7] years; 504 females [64.1%]) were included in the study. High accuracy was observed in identifying elevated Aβ (AUC, 0.92-0.96; 95%CI 0.89-0.99) and tau pathology (AUC, 0.93-0.97; 95%CI 0.84-0.99) across all cohorts. These accuracies were significantly higher than other plasma biomarker combinations and comparable to CSF biomarkers. The detection of abnormal Aβ pathology using binary or three-range references yielded reproducible results. Longitudinally, plasma pTau217 showed an annual increase only in Aβ-positive individuals, with the highest increase observed in those with tau-positivity.The ALZpath plasma pTau217 Simoa assay accurately identifies biological AD, comparable to CSF biomarkers, with reproducible cut-offs across cohorts. It detects longitudinal changes, including at the preclinical stage, and is the first widely available, accessible, and scalable blood test for pTau217 detection.
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| 47. |
- Babu Moparthi, Satish, et al.
(författare)
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Transient conformational remodeling of folding proteins by GroES - Individually and in concert with GroEL
- 2014
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Ingår i: Journal of chemical biology. - : Springer Berlin/Heidelberg. - 1864-6158 .- 1864-6166. ; 7:1, s. 1-15
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Forskningsöversikt (refereegranskat)abstract
- The commonly accepted dogma of the bacterial GroE chaperonin system entails protein folding mediated by cycles of several ATP-dependent sequential steps where GroEL interacts with the folding client protein. In contrast, we herein report GroES-mediated dynamic remodeling (expansion and compression) of two different protein substrates during folding: the endogenous substrate MreB and carbonic anhydrase (HCAII), a well-characterized protein folding model. GroES was also found to influence GroEL binding induced unfolding and compression of the client protein underlining the synergistic activity of both chaperonins, even in the absence of ATP. This previously unidentified activity by GroES should have important implications for understanding the chaperonin mechanism and cellular stress response. Our findings necessitate a revision of the GroEL/ES mechanism.
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| 48. |
- Beausang, Angela, et al.
(författare)
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"Möjligheten att rädda några av dessa kvinnors liv har inte vägts in"
- 2014
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Ingår i: Dagens Medicin. - : Dagens Medicin.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Namnet på Socialstyrelsens vägledning lyder: Hur upptäcka våldsutsatthet? Ja, det kan man verkligen fråga sig efter att ha läst detta föga vägledande dokument, skriver ett stort antal kritiska debattörer.
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| 49. |
- Berg, Jonathan, et al.
(författare)
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Mild hypothermia attenuates ischemia/reperfusion injury - insights from serial non-invasive pressure-volume loops
- 2023
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Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 1755-3245 .- 0008-6363. ; 119:12, s. 2230-2243
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mild hypothermia, 32-35°C, reduces infarct size in experimental studies, potentially mediating reperfusion injuries, but human trials have been ambiguous. To elucidate the cardioprotective mechanisms of mild hypothermia, we analyzed cardiac performance in a porcine model of ischemia/reperfusion, with serial cardiovascular magnetic resonance (CMR) imaging throughout one week using non-invasive pressure-volume loops.METHODS AND RESULTS: Normothermia and Hypothermia groups sessions (n=7+7 pigs, nonrandom allocation) were imaged with CMR at baseline and subjected to 40 minutes of normothermic ischemia by catheter intervention. Thereafter, the Hypothermia group was rapidly cooled (mean 34.5°C) for 5 minutes before reperfusion. Additional CMR sessions at two hours, 24 hours, and seven days acquired ventricular volumes and ischemic injuries (unblinded analysis).Stroke volume (-24%; p=0.029; Friedmans test) and ejection fraction (-20%; p=0.068) were notably reduced at 24h in the Normothermia group compared to baseline. In contrast, the decreases were ameliorated in the Hypothermia group (stroke volume: -6%; p=0.77; ejection fraction: -6%; p=0.13). Mean arterial pressure remained stable in Normothermic animals (-3%, p=0.77) but dropped two hours post-reperfusion in hypothermic animals (-18%, p=0.007). Both groups experienced a decrease and partial recovery pattern for PV loop-derived variables over one week, but the adverse effects tended attenuated in the Hypothermia group. Infarct sizes were 10±8% in Hypothermic and 15±8% in Normothermic animals (p=0.32). Analysis of covariance at 24 hours indicated that hypothermia has cardioprotective properties incremental to reducing infarct size, such as higher external power (p=0.061) and lower arterial elastance (p=0.015).CONCLUSION: Using non-invasive pressure-volume loops by CMR, we observed that mild hypothermia at reperfusion alleviates the heart's work after ischemia/reperfusion injuries during the first week and preserves short-term cardiac performance. This hypothesis-generating study suggests hypothermia to have cardioprotective properties, incremental to reducing infarct size. The primary cardioprotective mechanism was likely an afterload reduction acutely unloading the left ventricle.
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| 50. |
- Bergman, Becky, 1970, et al.
(författare)
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Forming effective culturally diverse work teams in project courses
- 2017
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Ingår i: 13th international CDIO conference proceedings CDIO, June 18-22 2017, Calgary. - 1796-9964. - 9780889533998 ; 2017:13, s. 508-518
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Konferensbidrag (refereegranskat)abstract
- A culturally diverse student population at Master’s level is a reality at many universities today, as it is at Chalmers University of Technology in Sweden. However, a common issue is the lack of interaction between home and international students, which counteracts university goals of fostering intercultural cooperation. This paper will discuss and evaluate a pilot project in one Master’s program in production engineering, where activities around group diversity were integrated into a company-based project course. Students were assigned groups where a mixture of backgrounds and expertise were prioritised.The project used a number of group dynamics activities including a pre-survey of expectations of group work; negotiating a group contract; and continuous peer group assessment in order to develop and reflect on the skills required in a culturally diverse work team.From reflective essays that students wrote, as well as interviews carried out, the project and tasks were evaluated. The following themes were identified: attitudes to diversity; the importance of well-functioning communication; and attitudes and roles within the group.Results show that students found this a challenging but useful environment to work in and found the group dynamics activities helpful in negotiating this environment. Continuous peer group assessment, in particular, was seen as helpful in providing a forum for feedback and discussion on individual performance in the group and challenges for the group as a whole.Recommendations include constructive alignment within the program in terms of clear goals, activities and assessment, in order to build up these skills and awareness, not only in a single course but throughout the program.
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