| 51. |
- Bender, P., et al.
(författare)
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Relating Magnetic Properties and High Hyperthermia Performance of Iron Oxide Nanoflowers
- 2018
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Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 122:5, s. 3068-3077
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Tidskriftsartikel (refereegranskat)abstract
- We investigated, in depth, the interrelations among structure, magnetic properties, relaxation dynamics and magnetic hyperthermia performance of magnetic nanoflowers. The nanoflowers are about 39 nm in size, and consist of densely packed iron oxide cores. They display a remanent magnetization, which we explain by the exchange coupling between the cores, but we observe indications for internal spin disorder. By polarized small-angle neutron scattering, we unambiguously confirm that, on average, the nanoflowers are preferentially magnetized along one direction. The extracted discrete relaxation time distribution of the colloidally dispersed particles indicates the presence of three distinct relaxation contributions. We can explain the two slower processes by Brownian and classical Néel relaxation, respectively. The additionally observed very fast relaxation contributions are attributed by us to the relaxation of disordered spins within the nanoflowers. Finally, we show that the intrinsic loss power (ILP, magnetic hyperthermia performance) of the nanoflowers measured in colloidal dispersion at high frequency is comparatively large and independent of the viscosity of the surrounding medium. This concurs with our assumption that the observed relaxation in the high frequency range is primarily a result of internal spin relaxation, and possibly connected to the disordered spins within the individual nanoflowers.
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| 52. |
- 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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| 53. |
- Biemann, R., et al.
(författare)
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Serum bile acids and GLP-1 decrease following telemetric induced weight loss: results of a randomized controlled trial
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Bile acids (BAs) are increasingly recognised as metabolic regulators, potentially improving insulin sensitivity following bariatric surgery. However, physiological relevance of such observations remains unknown. Hence, we analysed serum BA composition and associated gut-derived hormone levels following lifestyle-induced weight loss in individuals with metabolic syndrome (MetS). 74 non-smoking men (45-55 yr) with MetS were randomised to a lifestyle-induced weight loss program (supervision via telemonitoring) or to a control arm. Before and after a 6 months intervention period clinical and laboratory parameters, body composition, serum BA profile, FGF-19, and GLP-1 concentrations were determined in fasting blood samples. 30 participants in the control and 33 participants in the treatment arm completed the study and were included in the data analysis. In participants of the treatment arm lifestyle-induced weight loss resulted in markedly improved insulin sensitivity. Serum levels of BA species and total GLP-1 decreased, while FGF-19 remained stable. Serum BA composition changed towards an increased 12 alpha-hydroxylated/non-12 alpha-hydroxylated ratio. None of these parameters changed in participants of the control arm. Our results demonstrate that improved metabolic control by lifestyle modifications lowers serum levels of BAs and GLP-1 and changes serum BA composition towards an increased 12 alpha/non-12 alpha ratio (ICTRP Trial Number: U1111-1158-3672).
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| 54. |
- Carlsson, Björn, 1958, et al.
(författare)
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Obese (ob) gene defects are rare in human obesity
- 1997
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Ingår i: Obesity Research. - 1071-7323 .- 1550-8528. ; 5:1, s. 30-5
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Tidskriftsartikel (refereegranskat)abstract
- Our knowledge of the role of the recently cloned ob-protein (leptin) in the regulation of body fat stores is largely derived from experiments performed in mice. Different mouse models exhibit abnormalities in ob-gene expression, with extreme overexpression in mice which lack bioactive ob-protein, have nonfunctional ob-receptors or hypothalamic lesions, and undetectable expression in mice with suggested defects in regulatory elements. The aim of this study is to examine if defects, corresponding to those in mice, exist in human obesity. Adipose tissue was obtained from 94 adult obese subjects and from six children who had developed obesity after surgery in the hypothalamic region. Total RNA was isolated and ob-gene expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blot. The coding region of the ob-gene was sequenced in both directions in the 94 obese adults. No mutations were detected in the coding region of the ob-gene and ob-gene expression was detectable in all subjects and none of the subjects had an extreme overexpression. There was no systematic increase in ob-expression in obese children with hypothalamic disease compared to their healthy brothers and sisters. These results show that severe abnormalities involving the ob-gene, analogous to those described in mouse models, are rare in human obesity. We therefore conclude that the cloning and subsequent analysis of the ob-gene has not provided information that can, by itself, explain the genetic component in the development of human obesity.
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| 55. |
- Charpentier Ljungqvist, Fredrik, et al.
(författare)
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Linking European building activity with plague history
- 2018
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Ingår i: Journal of Archaeological Science. - : Elsevier BV. - 0305-4403 .- 1095-9238. ; 98, s. 81-92
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Tidskriftsartikel (refereegranskat)abstract
- Variations in building activity reflect demographic, economic and social change during history. Tens of thousands of wooden constructions in Europe have been dendrochronologically dated in recent decades. We use the annually precise evidence from a unique dataset of 49 640 tree felling dates of historical constructions to reconstruct temporal changes in building activity between 1250 and 1699 CE across a large part of western and central Europe largely corresponding to the former Holy Roman Empire of the German Nation. Comparison with annual records of 9772 plague outbreaks shows that construction activity was significantly negatively correlated to the number of plague outbreaks, with the greatest decrease in construction following the larger outbreaks by three to four years after the start of the epidemics. Preceding the Black Death (1346-1353 CE) by five decades and the Great Famine (1315-1322 CE) by two decades, a significant decline in construction activity at c. 1300 CE is indicative of a societal crisis, associated with population stagnation or decline. Another dramatic decline in building activity coincides with the Thirty Years' War (1618-1648 CE) and confirms the devastating nature of this conflict. While construction activity was significantly lower during periods of high grain prices, no statistically robust relationship between the number of felling dates and past temperature or hydroclimate variations is found. This study demonstrates the value of dendrochronological felling dates as an indicator for times of crisis and prosperity during periods when documentary evidence is limited.
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| 56. |
- 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
-
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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| 57. |
- Ekeberg, Tomas, et al.
(författare)
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Single-shot diffraction data from the Mimivirus particle using an X-ray free-electron laser
- 2016
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 3
-
Tidskriftsartikel (refereegranskat)abstract
- Free-electron lasers (FEL) hold the potential to revolutionize structural biology by producing X-ray pules short enough to outrun radiation damage, thus allowing imaging of biological samples without the limitation from radiation damage. Thus, a major part of the scientific case for the first FELs was three-dimensional (3D) reconstruction of non-crystalline biological objects. In a recent publication we demonstrated the first 3D reconstruction of a biological object from an X-ray FEL using this technique. The sample was the giant Mimivirus, which is one of the largest known viruses with a diameter of 450 nm. Here we present the dataset used for this successful reconstruction. Data-analysis methods for single-particle imaging at FELs are undergoing heavy development but data collection relies on very limited time available through a highly competitive proposal process. This dataset provides experimental data to the entire community and could boost algorithm development and provide a benchmark dataset for new algorithms.
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| 58. |
- Hantke, Max F., et al.
(författare)
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A data set from flash X-ray imaging of carboxysomes
- 2016
-
Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 3
-
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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| 59. |
- Hantke, Max F., et al.
(författare)
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High-throughput imaging of heterogeneous cell organelles with an X-ray laser
- 2014
-
Ingår i: Nature Photonics. - : Springer Science and Business Media LLC. - 1749-4885 .- 1749-4893. ; 8:12, s. 943-949
-
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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| 60. |
- Hertel, N T, et al.
(författare)
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Growth hormone treatment in 35 prepubertal children with achondroplasia: A five-year dose-response trial
- 2005
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Ingår i: Acta Pædiatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 94:10, s. 1402-1410
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Tidskriftsartikel (refereegranskat)abstract
- Background: Achondroplasia is a skeletal dysplasia with extreme, disproportionate, short stature. Aim: In a 5-y growth hormone (GH) treatment study including 1 y without treatment, we investigated growth and body proportion response in 35 children with achondroplasia. Methods: Patients were randomized to either 0.1 IU/kg (n=18) or 0.2 IU/kg (n=17) per day. GH treatment was interrupted for 12 mo after 2 y of treatment in prepubertal patients to study catch-down growth. Mean height SDS (HSDS) at start was -5.6 and -5.2 for the low- and high-dose groups, respectively, and mean age 7.3 and 6.6 y. Results: Mean growth velocity (baseline 4.5/4.6 cm/y for the groups) increased significantly by 1.9/3.6 cm/y during the first year and by 0.5/1.5 cm/y during the second year. During the third year, a decrease of growth velocity was observed at 1.9/1.3 cm/y below baseline values. HSDS increased significantly by 0.6/0.8 during the first year of treatment and in total by 1.3/1.6 during the 5 y of study. Sitting height SDS improved significantly from -2.1/-1.7 to -0.8/0.2 during the study. Body proportion (sitting height/total height) or arm span did not show any significant change. Conclusion: GH treatment of children with achondroplasia improves height during 4 y of therapy without adverse effect on trunk-leg disproportion. The short-term effect is comparable to that reported in Turner and Noonan syndrome and in idiopathic short stature.
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