| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
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| 3. |
- Rydén, Lars, et al.
(författare)
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ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD
- 2013
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 34:39, s. 3035-3087
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Tidskriftsartikel (refereegranskat)abstract
- This is the second iteration of the European Society of Cardiology (ESC) and European Association for the Study of Diabetes (EASD) joining forces to write guidelines on the management of diabetes mellitus (DM), pre-diabetes, and cardiovascular disease (CVD), designed to assist clinicians and other healthcare workers to make evidence-based management decisions. The growing awareness of the strong biological relationship between DM and CVD rightly prompted these two large organizations to collaborate to generate guidelines relevant to their joint interests, the first of which were published in 2007. Some assert that too many guidelines are being produced but, in this burgeoning field, five years in the development of both basic and clinical science is a long time and major trials have reported in this period, making it necessary to update the previous Guidelines.
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| 4. |
- Aidas, Kestutis, et al.
(författare)
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The Dalton quantum chemistry program system
- 2014
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Ingår i: WIREs Computational Molecular Science. - : Wiley. - 1759-0876 .- 1759-0884. ; 4:3, s. 269-284
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Tidskriftsartikel (refereegranskat)abstract
- Dalton is a powerful general-purpose program system for the study of molecular electronic structure at the Hartree-Fock, Kohn-Sham, multiconfigurational self-consistent-field, MOller-Plesset, configuration-interaction, and coupled-cluster levels of theory. Apart from the total energy, a wide variety of molecular properties may be calculated using these electronic-structure models. Molecular gradients and Hessians are available for geometry optimizations, molecular dynamics, and vibrational studies, whereas magnetic resonance and optical activity can be studied in a gauge-origin-invariant manner. Frequency-dependent molecular properties can be calculated using linear, quadratic, and cubic response theory. A large number of singlet and triplet perturbation operators are available for the study of one-, two-, and three-photon processes. Environmental effects may be included using various dielectric-medium and quantum-mechanics/molecular-mechanics models. Large molecules may be studied using linear-scaling and massively parallel algorithms. Dalton is distributed at no cost from for a number of UNIX platforms.
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| 5. |
- Koettgen, Anna, et al.
(författare)
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Genome-wide association analyses identify 18 new loci associated with serum urate concentrations
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:2, s. 145-154
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Tidskriftsartikel (refereegranskat)abstract
- Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SEMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.
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| 6. |
- Koopmann, Rudolf, et al.
(författare)
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In vivo protein crystallization opens new routes in structural biology
- 2012
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Ingår i: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 9:3, s. 259-262
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Tidskriftsartikel (refereegranskat)abstract
- Protein crystallization in cells has been observed several times in nature. However, owing to their small size these crystals have not yet been used for X-ray crystallographic analysis. We prepared nano-sized in vivo–grown crystals of Trypanosoma brucei enzymes and applied the emerging method of free-electron laser-based serial femtosecond crystallography to record interpretable diffraction data. This combined approach will open new opportunities in structural systems biology.
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| 7. |
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| 8. |
- Aquila, Andrew, et al.
(författare)
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Time-resolved protein nanocrystallography using an X-ray free-electron laser
- 2012
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Ingår i: Optics Express. - 1094-4087. ; 20:3, s. 2706-2716
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate the use of an X-ray free electron laser synchronized with an optical pump laser to obtain X-ray diffraction snapshots from the photoactivated states of large membrane protein complexes in the form of nanocrystals flowing in a liquid jet. Light-induced changes of Photosystem I-Ferredoxin co-crystals were observed at time delays of 5 to 10 µs after excitation. The result correlates with the microsecond kinetics of electron transfer from Photosystem I to ferredoxin. The undocking process that follows the electron transfer leads to large rearrangements in the crystals that will terminally lead to the disintegration of the crystals. We describe the experimental setup and obtain the first time-resolved femtosecond serial X-ray crystallography results from an irreversible photo-chemical reaction at the Linac Coherent Light Source. This technique opens the door to time-resolved structural studies of reaction dynamics in biological systems.
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| 9. |
- Dawes, Melissa A., et al.
(författare)
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An alpine treeline in a carbon dioxide-rich world : synthesis of a nine-year free-air carbon dioxide enrichment study
- 2013
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Ingår i: Oecologia. - : Springer Science and Business Media LLC. - 0029-8549 .- 1432-1939. ; 171:3, s. 623-637
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the impacts of elevated CO2 in a treeline ecosystem in the Swiss Alps in a 9-year free-air CO2 enrichment (FACE) study. We present new data and synthesize plant and soil results from the entire experimental period. Light-saturated photosynthesis (A max) of ca. 35-year-old Larix decidua and Pinus uncinata was stimulated by elevated CO2 throughout the experiment. Slight down-regulation of photosynthesis in Pinus was consistent with starch accumulation in needle tissue. Above-ground growth responses differed between tree species, with a 33 % mean annual stimulation in Larix but no response in Pinus. Species-specific CO2 responses also occurred for abundant dwarf shrub species in the understorey, where Vaccinium myrtillus showed a sustained shoot growth enhancement (+11 %) that was not apparent for Vaccinium gaultherioides or Empetrum hermaphroditum. Below ground, CO2 enrichment did not stimulate fine root or mycorrhizal mycelium growth, but increased CO2 effluxes from the soil (+24 %) indicated that enhanced C assimilation was partially offset by greater respiratory losses. The dissolved organic C (DOC) concentration in soil solutions was consistently higher under elevated CO2 (+14 %), suggesting accelerated soil organic matter turnover. CO2 enrichment hardly affected the C–N balance in plants and soil, with unaltered soil total or mineral N concentrations and little impact on plant leaf N concentration or the stable N isotope ratio. Sustained differences in plant species growth responses suggest future shifts in species composition with atmospheric change. Consistently increased C fixation, soil respiration and DOC production over 9 years of CO2 enrichment provide clear evidence for accelerated C cycling with no apparent consequences on the N cycle in this treeline ecosystem.
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| 10. |
- Johansson, Linda C, 1983, et al.
(författare)
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Lipidic phase membrane protein serial femtosecond crystallography.
- 2012
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Ingår i: Nature methods. - : Springer Science and Business Media LLC. - 1548-7105 .- 1548-7091. ; 9:3, s. 263-265
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Tidskriftsartikel (refereegranskat)abstract
- X-ray free electron laser (X-FEL)-based serial femtosecond crystallography is an emerging method with potential to rapidly advance the challenging field of membrane protein structural biology. Here we recorded interpretable diffraction data from micrometer-sized lipidic sponge phase crystals of the Blastochloris viridis photosynthetic reaction center delivered into an X-FEL beam using a sponge phase micro-jet.
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| 11. |
- Kassemeyer, Stephan, et al.
(författare)
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Femtosecond free-electron laser x-ray diffraction data sets for algorithm development
- 2012
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Ingår i: Optics Express. - 1094-4087. ; 20:4, s. 4149-4158
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Tidskriftsartikel (refereegranskat)abstract
- We describe femtosecond X-ray diffraction data sets of viruses and nanoparticles collected at the Linac Coherent Light Source. The data establish the first large benchmark data sets for coherent diffraction methods freely available to the public, to bolster the development of algorithms that are essential for developing this novel approach as a useful imaging technique. Applications are 2D reconstructions, orientation classification and finally 3D imaging by assembling 2D patterns into a 3D diffraction volume.
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| 12. |
- Lauten, Alexander, et al.
(författare)
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Percutaneous Left-Ventricular Support With the Impella-2.5-Assist Device in Acute Cardiogenic Shock Results of the Impella-EUROSHOCK-Registry
- 2013
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Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 6:1, s. 23-30
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Tidskriftsartikel (refereegranskat)abstract
- Background-Acute cardiogenic shock after myocardial infarction is associated with high in-hospital mortality attributable to persisting low-cardiac output. The Impella-EUROSHOCK-registry evaluates the safety and efficacy of the Impella-2.5-percutaneous left-ventricular assist device in patients with cardiogenic shock after acute myocardial infarction. Methods and Results-This multicenter registry retrospectively included 120 patients (63.6 +/- 12.2 years; 81.7% male) with cardiogenic shock from acute myocardial infarction receiving temporary circulatory support with the Impella-2.5-percutaneous left-ventricular assist device. The primary end point evaluated mortality at 30 days. The secondary end point analyzed the change of plasma lactate after the institution of hemodynamic support, and the rate of early major adverse cardiac and cerebrovascular events as well as long-term survival. Thirty-day mortality was 64.2% in the study population. After Impella-2.5-percutaneous left-ventricular assist device implantation, lactate levels decreased from 5.8 +/- 5.0 mmol/L to 4.7 +/- 5.4 mmol/L (P=0.28) and 2.5 +/- 2.6 mmol/L (P=0.023) at 24 and 48 hours, respectively. Early major adverse cardiac and cerebrovascular events were reported in 18 (15%) patients. Major bleeding at the vascular access site, hemolysis, and pericardial tamponade occurred in 34 (28.6%), 9 (7.5%), and 2 (1.7%) patients, respectively. The parameters of age >65 and lactate level >3.8 mmol/L at admission were identified as predictors of 30-day mortality. After 317 +/- 526 days of follow-up, survival was 28.3%. Conclusions-In patients with acute cardiogenic shock from acute myocardial infarction, Impella 2.5-treatment is feasible and results in a reduction of lactate levels, suggesting improved organ perfusion. However, 30-day mortality remains high in these patients. This likely reflects the last-resort character of Impella-2.5-application in selected patients with a poor hemodynamic profile and a greater imminent risk of death. Carefully conducted randomized controlled trials are necessary to evaluate the efficacy of Impella-2.5-support in this high-risk patient group.
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| 13. |
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| 14. |
- Lomb, Lukas, et al.
(författare)
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Radiation damage in protein serial femtosecond crystallography using an x-ray free-electron laser
- 2011
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 84:21, s. 214111-1-214111-6
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Tidskriftsartikel (refereegranskat)abstract
- X-ray free-electron lasers deliver intense femtosecond pulses that promise to yield high resolution diffraction data of nanocrystals before the destruction of the sample by radiation damage. Diffraction intensities of lysozyme nanocrystals collected at the Linac Coherent Light Source using 2 keV photons were used for structure determination by molecular replacement and analyzed for radiation damage as a function of pulse length and fluence. Signatures of radiation damage are observed for pulses as short as 70 fs. Parametric scaling used in conventional crystallography does not account for the observed effects.
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| 15. |
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| 16. |
- Speliotes, Elizabeth K., et al.
(författare)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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| 17. |
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| 18. |
- With, Sebastian, et al.
(författare)
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Fast Diffusion-Limited Lyotropic Phase Transitions Studied in-situ Using Continuous Flow Microfluidics / Microfocus-SAXS
- 2014
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 30:42, s. 12494-12502
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Tidskriftsartikel (refereegranskat)abstract
- Fast concentration-induced diffusion-limited lyotropic phase transitions can be studied in situ with millisecond time resolution using continuous flow microfluidics in combination with microfocus small-angle X-ray scattering. The method was applied to follow a classical self-assembly sequence where amphiphiles assemble into micelles, which subsequently assemble into an ordered lattice via a disorder/order transition. As a model system we selected the self-assembly of an amphiphilic block copolymer induced by the addition of a nonsolvent. Using microchannel hydrodynamic flow-focusing, large concentration gradients can be generated, leading to a deep quench from the miscible to the microphase-separated state. Within milliseconds the block copolymers assembly via a spinodal microphase separation into micelles, followed by a disorder/order transition into an FCC liquid-crystalline phase with late-stage domain growth and shear-induced domain orientation into a mesocrystal. A comparison with a slow macroscopic near-equilibrium kinetic experiment shows that the fast structural transitions follow a direct pathway to the equilibrium structure without the trapping of metastable states.
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| 19. |
- Aurand, Bastian, et al.
(författare)
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Preparation and characterization of nanometer-thin freestanding polymer foils for laser-ion acceleration
- 2013
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Ingår i: Journal of Polymer Science. Part B, Polymer Physics. - : Wiley. - 0887-6266. ; 51:18, s. 1355-1360
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Tidskriftsartikel (refereegranskat)abstract
- We report on the production and characterization of polymer-based ultra-thin (sub 10 nm) foils suited for experiments on laser-ion acceleration in the regime of radiation pressure acceleration. Beside the remarkable mechanical stability compared with commonly used diamond-like-carbon foils, a very homogeneous layer thickness and a small surface roughness have been achieved. We describe the technical issues of the production process as well as detailed studies of the mechanical stability and surface roughness tests. The capability of producing uniform targets of large area is essential for advanced laser-ion acceleration projects which are dealing with high repetition rate and extended measurement series, but might also be useful for other applications which require ultra-thin and freestanding substrates of high quality. (c) 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2013, 51, 1355-1360
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| 20. |
- Barthel, Stephan, 1968-, et al.
(författare)
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Urban gardens, agriculture, and water management : Sources of resilience forlong-term food security in cities
- 2013
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Ingår i: Ecological Economics. - Amsterdam : Elsevier. - 0921-8009 .- 1873-6106. ; 86, s. 224-234
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Tidskriftsartikel (refereegranskat)abstract
- Food security has always been a key resilience facet for people living in cities. This paper discusses lessons for food security fromhistoric and prehistoric cities. The Chicago school of urban sociology established amodernist understanding of urbanism as an essentialist reality separate from its larger life-support system. However, different urban histories have given rise to a remarkable spatial diversity and temporal variation viewed at the global and long-term scales that are often overlooked in urban scholarship.Drawing on two case studies fromwidely different historical and cultural contexts – the Classic Maya civilization of the late first millennium AD and Byzantine Constantinople – this paper demonstrates urban farming as a pertinent feature of urban support systems over the long-term and global scales. We show how urban gardens, agriculture, and water management as well as the linked social–ecological memories of how to uphold such practices over time have contributed to long-term food security during eras of energy scarcity. We exemplify with the function of such local blue–green infrastructures during chocks to urban supply lines. We conclude that agricultural production is not “the antithesis of the city," but often an integrated urban activity that contribute to the resilience of cities.
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| 21. |
- Barthtel, Stephan, 1968-, et al.
(författare)
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Urban Gardens, Agricultures and Waters : Sources of Resilience for Long-Term Food Security in Cities
- 2013
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Ingår i: Ecological Economics. - : Elsevier BV. - 0921-8009 .- 1873-6106. ; 86, s. 224-234
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Tidskriftsartikel (refereegranskat)abstract
- Food security has always been a key resilience facet for people living in cities. This paper discusses lessons for food security from historic and prehistoric cities. The Chicago school of urban sociology established a modernist understanding of urbanism as an essentialist reality separate from its larger life-support system. However, different urban histories have given rise to a remarkable spatial diversity and temporal variation viewed at the global and long-term scales that are often overlooked in urban scholarship. Drawing on two case studies from widely different historical and cultural contexts - the Classic Maya civilization of the late first millennium AD and Byzantine Constantinople - this paper demonstrates urban farming as a pertinent feature of urban support systems over the long-term and global scales. We show how urban gardens, agriculture, and water management as well as the linked social-ecological memories of how to uphold such practices over time have contributed to long-term food security during eras of energy scarcity. We exemplify with the function of such local blue-green infrastructures during chocks to urban supply lines. We conclude that agricultural production is not "the antithesis of the city," but often an integrated urban activity that contribute to the resilience of cities.
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| 22. |
- Beritelli, Pietro, et al.
(författare)
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Das St.Galler modell für destinationsmanagement : geschäftsfeldinnovation in netzwerken
- 2013
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Viele touristische Leistungsträger und Organisationen orientierten sich bisher in der strategischen Planung und Produktentwicklung zu einseitig an den vorhandenen Ressourcen, Angebotspotentialen sowie groben Kundengruppen und Markdefinitionen. Daraus resultierte eine ungenügende Nachfrageorientierung. Angebote wurden an den Reisemotiven vorbei entwickelt. Letztere bestimmen jedoch die Reiseströme von Touristen im Raum und die daraus resultierenden Angebotssysteme.Aktuelle Entwicklungen des Marktumfelds (Globalisierung, Ausdifferenzierung und Veränderungen in den Kommunkations-, Marketing- und Verkaufskanälen) zeigen, dass sich Tourismusanbieter und Destinationen verstärkt an neuen marktorientierten, dynamischen Prozessen ausrichten müssen. Das vorliegende, durch das SECO (InnoTour) unterstützte Innovationsprojekt will dazu einen neuartigen Beitrag leisten. Die Resultate und praktischen Erfahrungen, die in diesem Buch präsentiert werden, rücken gemeinschaftlich und geographisch-variabel geführte Geschäftsfelder als strategische Planungseinheiten für mehr Wettbewerbsfähigkeit in den Vordergrund. Das Werk deckt durch die gemeinsame Entwicklung eines Standards für betriebsübergreifende Innovationen in Netzwerken mit sechs Pilotdestinationen ein bedeutentes Defizit auf und stellt eine praxistaugliche Lösungsmethodik auf.
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| 23. |
- Beritelli, Pietro, et al.
(författare)
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Prozessorientierung im Destinationsmanagement
- 2014
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Ingår i: Marketing Review St. Gallen. - : Springer. - 1865-6544 .- 1865-7516. ; 31:6, s. 34-47
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Tidskriftsartikel (refereegranskat)abstract
- Der Beitrag führt in ein neues Verständnis der Destination und den darauf basierenden Ansatz des St. Galler Modells für Destinationsmanagement ein und zeigt die weitreichenden Konsequenzen für das Entscheidungsverhalten sowie die Handlungen der Akteure auf.
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| 24. |
- Boeger, Carsten A., et al.
(författare)
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CUBN Is a Gene Locus for Albuminuria
- 2011
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 22:3, s. 555-570
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Tidskriftsartikel (refereegranskat)abstract
- Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria. We identified an association between a missense variant (I2984V) in the CUBN gene, which encodes cubilin, and both UACR (P = 1.1 x 10(-11)) and microalbuminuria (P = 0.001). We observed similar associations among 6981 African Americans in the CARe Consortium. The associations between this variant and both UACR and microalbuminuria were significant in individuals of European ancestry regardless of diabetes status. Finally, this variant associated with a 41% increased risk for the development of persistent microalbuminuria during 20 years of follow-up among 1304 participants with type 1 diabetes in the prospective DCCT/EDIC Study. In summary, we identified a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes.
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| 25. |
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| 26. |
- Chapman, Henry N, et al.
(författare)
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Femtosecond X-ray protein nanocrystallography.
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 470:7332, s. 73-7
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Tidskriftsartikel (refereegranskat)abstract
- X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded. It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction 'snapshots' are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source. We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes. More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals (∼200nm to 2μm in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes. This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage.
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| 27. |
- Flachskampf, Frank, 1957-, et al.
(författare)
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Cardiac imaging after myocardial infarction
- 2011
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 32:3, s. 272-283
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Tidskriftsartikel (refereegranskat)abstract
- After myocardial infarction, optimal clinical management depends critically on cardiac imaging. Remodelling and heart failure, presence of inducible ischaemia, presence of dysfunctional viable myocardium, future risk of adverse events including risk of ventricular arrhythmias, need for anticoagulation, and other questions should be addressed by cardiac imaging. Strengths and weaknesses, recent developments, choice, and timing of the different non-invasive techniques are reviewed for this frequent clinical scenario.
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| 28. |
- Häkkinen, Jari, et al.
(författare)
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Laboratory data and sample management for proteomics.
- 2011
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Ingår i: Data Mining in Proteomics : From Standards to Applications. - Totowa, NJ : Humana Press. - 1940-6029. - 9781607619864 ; 696, s. 79-92
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Bokkapitel (refereegranskat)abstract
- Proteomic experiments can be difficult to handle because of the large amount of data in different formats that is generated. Samples need to be managed and generated, data needs to be integrated with samples and annotation information. A laboratory information management system (LIMS) can be used to overcome some of the data handling problems. In this chapter, we discuss the role of a LIMS in the proteomics laboratory, and show two step-by-step examples of usage of the Proteios Software Environment (ProSE) to handle two different proteomics workflows.
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| 29. |
- Kacerovsky-Bielesz, Gertrud, et al.
(författare)
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A Single Nucleotide Polymorphism Associates With the Response of Muscle ATP Synthesis to Long-Term Exercise Training in Relatives of Type 2 Diabetic Humans
- 2012
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 35:2, s. 350-357
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-Myocellular ATP synthesis (fATP) associates with insulin sensitivity in first-degree relatives of subjects with type 2 diabetes. Short-term endurance training can modify their fATP and insulin sensitivity. This study examines the effects of moderate long-term exercise using endurance or resistance training in this cohort. RESEARCH DESIGN AND METHODS-A randomized, parallel-group trial tested 16 glucose-tolerant nonobese relatives (8 subjects in the endurance training group and 8 subjects in the resistance training group) before and after 26 weeks of endurance or resistance training. Exercise performance was assessed from power output and oxygen uptake (VO2) during incremental tests and from maximal torque of knee flexors (MaxT(flex)) and extensors (MaxT(ext)) using isokinetic dynamometry. fATP and ectopic lipids were measured with H-1/P-31 magnetic resonance spectroscopy. RESULTS Endurance training increased power output and VO2 by 44 and 30%, respectively (both P < 0.001), whereas resistance training increased MaxT(ext) and MaxT(flex) by 23 and 40%, respectively (both P < 0.001). Across all groups, insulin sensitivity (382 +/- 90 vs. 389 +/- 40 mL.min.m(-2)) and ectopic lipid contents were comparable after exercise training. However, 8 of 16 relatives had 26% greater fATP, increasing from 9.5 +/- 2.3 to 11.9 +/- 2.4 mu mol.mL(-1).m(-1) (P < 0.05). Six of eight responders were carriers of the G/G single nucleotide polymorphism rs540467 of the NDUFB6 gene (P = 0.019), which encodes a subunit of mitochondrial complex I. CONCLUSIONS-Moderate exercise training for 6 months does not necessarily improve insulin sensitivity but may increase ATP synthase flux. Genetic predisposition can modify the individual response of the ATP synthase flux independently of insulin sensitivity.
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| 30. |
- Kuepper, Jochen, et al.
(författare)
-
X-Ray Diffraction from Isolated and Strongly Aligned Gas-Phase Molecules with a Free-Electron Laser
- 2014
-
Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 112:8, s. 083002-
-
Tidskriftsartikel (refereegranskat)abstract
- We report experimental results on x-ray diffraction of quantum-state-selected and strongly aligned ensembles of the prototypical asymmetric rotor molecule 2,5-diiodobenzonitrile using the Linac Coherent Light Source. The experiments demonstrate first steps toward a new approach to diffractive imaging of distinct structures of individual, isolated gas-phase molecules. We confirm several key ingredients of single molecule diffraction experiments: the abilities to detect and count individual scattered x-ray photons in single shot diffraction data, to deliver state-selected, e.g., structural-isomer-selected, ensembles of molecules to the x-ray interaction volume, and to strongly align the scattering molecules. Our approach, using ultrashort x-ray pulses, is suitable to study ultrafast dynamics of isolated molecules.
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| 31. |
- Kulyk, Oksana, et al.
(författare)
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Electronic Voting with Fully Distributed Trust and Maximized Flexibility Regarding Ballot Design
- 2014
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Ingår i: 2014 6TH INTERNATIONAL CONFERENCE ON ELECTRONIC VOTING. - : IEEE. - 9783200036970
-
Konferensbidrag (refereegranskat)abstract
- One common way to ensure the security in voting schemes is to distribute critical tasks between different entities so called trustees. While in most election settings election authorities perform the task of trustees, elections in small groups such as board elections can be implemented in a way that all voters are also trustees. This is actually the ideal case for an election as trust is maximally distributed. A number of voting schemes have been proposed for facilitating such elections. Our focus is on a mix net based approach to maximize flexibility regarding ballot design. We proposed and implemented a corresponding voting scheme as an Android smartphone application. We believe smartphones are most likely to be used in the election settings that we consider in the paper. Our implementation also enables voters to remotely participate in the voting process. The implementation enables us to measure timings for the tallying phase for different settings in order to analyze whether the chosen mix net based scheme is suitable for the considered election settings.
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| 32. |
- Laesser, Christian, et al.
(författare)
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Der Wert der Wohnstandort-Erschliessung mit Öffentlichem Verkehr
- 2010
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Standortentscheide privater Haushalte werden auf Basis unterschiedlicher Attribute gefällt. Hierzu gehört u.a. auch die Erschliessung mit Verkehr und damit die Erreichbar-keit. Die Preisbildung auf dem Markt für Wohnliegenschaften bildet sodann die Präferenz-hierarchie der Wirtschaftssubjekte ab. Verschiedene internationale Studien zeigen, dass Standorte, welche gut mit Verkehrsinfrastruktur und -dienstleistungen erschlossen sind, vergleichsweise höher bepreist werden. Allerdings ist die Bestimmungskraft des Attributs Erreichbarkeit für die Zahlungsbereitschaft für Wohnraum deutlich kleiner als die vieler wohnungsbezogener Attribute. Die Resultate der vorliegenden Untersuchung für die Schweiz stützen bestehende Forschungsresultate. Allerdings - und dies ist neu - wird gezeigt, dass insbesondere Langstrecken-Pendler für gut erreichbare Wohnstandorte eine Zahlungsbereitschaft aufweisen, die weit über den Marktpreis einer Wohnung hinausgeht
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| 33. |
- Laesser, Christian, et al.
(författare)
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Finanzierung des OeV in der Schweiz : Was zahlt der Nutzer, was die Allgemeinheit?
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Immer mehr Menschen in der Schweiz fahren Bahn, Bus oder Tram. Der Ausbau des Verkehrsnetzes treibt die Kosten in die Höhe. Wer soll diese künftigen Mehrkosten über-nehmen: Bahnfahrer oder Staat? Dieser Frage ging das SBB Lab am Institut für Systemi-sches Management und Public Governance (IMP-HSG) nach. Eine breit angelegte repräsen-tative Befragung der Schweizer Wohnbevölkerung (zwischen 24. Juni und 05. Juli mit 2‘000 Probanden) zeigt, dass der gewünschte staatliche Subventionsbeitrag bei rund 50 Prozent, und damit nahe am heutigen Kostenteiler liegt. Knapp mehr als die Hälfte der Befragten wäre bereit, Zusatzkosten für einen weiter ausgebauten öffentlichen Verkehr zu tragen.Diese Einschätzung ist von mehreren Faktoren abhängig. Personen ohne Abonnement ziehen eher eine Finanzierung durch die Nutzer vor. Personen mit Abonnement sprechen sich eher für eine Finanzierung durch die Allgemeinheit aus. Dies gilt unabhängig davon, wer dieses Abo bezahlt (selbst oder beispielweise Arbeitgeber). Unterschiede zeigen sich auch in Sachen Beruf: Personen in Ausbildung und Personen ohne Arbeitseinkommen, beispielswei-se Pensionierte, neigen zu einer Finanzierung durch die Allgemeinheit. Selbständig Erwer-bende oder auch Personen des mittleren und oberen Managements bevorzugen eine Finanzierung durch die Nutzer. Alleinige Nutzerfinanzierung oder alleinige Finanzierung durch die Allgemeinheit sind unpopuläre Positionen. Die Mehrheit der Befragten will einen adäquaten Beitrag zum öffentlichen Verkehr beisteuern.Konsens über gerechte Verteilung der Mehrkosten. Steuererhöhungen zur Finanzierung von Mehrkosten durch die Allgemeinheit sind wenig populär. Vielmehr würde eine grosse Mehrheit der Befragten hierzu lieber in anderen Bereichen sparen: Bei Landesverteidigung, Beziehungen zum Ausland und - unter Einschränkungen - bei der sozialen Wohlfahrt; nicht aber beispielweise bei der Bildung. Bestünde keine Alternative zu Steuererhöhungen, sprächen sich mehr Befragte dafür aus, die Nutzer bezahlen zu lassen. Die unmittelbare Spürbarkeit der steuerlichen Mehrkosten lässt die Finanzierung durch die Allgemeinheit offensichtlich weniger attraktiv erscheinen. Dennoch sind auch in diesem Fall Extrempositio-nen sehr selten. Es besteht Konsens, dass auch unter solchen eher härteren Annahmen steuerlicher Mehrbelastung beide Seiten zur Deckung der Kosten beitragen müssen, wenn auch etwas mehr zu Lasten der Nutzer.Zukünftige Fahrtkosten weniger gut kalkulier- und planbar als Steuern. Man würde nun erwarten, dass Personen mit hohen Einkommen eher für eine Finanzierung durch die Nutzer plädieren, da sie aufgrund der Progression höhere Steuern bezahlen und von einer Finanzie-rung durch die Allgemeinheit eher betroffen wären. Dies trifft nur eingeschränkt zu bzw. der Zusammenhang ist nur schwach ausgeprägt. Der Grund liegt darin, dass viele dieser Personen auch im Besitz eines Abonnements sind und damit von einer Finanzierung durch die Allgemeinheit unmittelbar profitieren. So lässt sich denn auch bei vielen Befragten feststellen, dass die Summe ihrer derzeitigen Mobilitätskosten und zukünftigen Steuern über dem persönlich möglichen Minimum liegt: In der Festlegung des Mixes zwischen Nutzer- und öffentlicher Finanzierung wählen sie lieber - auch für sich selbst - höhere Steuern als unbedingt notwendig, um den finanziellen Spielraum für potentielle zukünftige Mehrfahrten für Freizeit oder Arbeitsplatzwechsel zu haben. Die Höhe der Steuern ist sicher. Mehrkosten durch zukünftige Mehrfahrten dagegen nicht.
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| 34. |
- Laesser, Christian, et al.
(författare)
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Multiple rationalitäten in Tourismus und Verkehr
- 2011
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Ingår i: IMPacts. - St. Gallen : IMP-HSG. ; :01, s. 19-21
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Tourismus gibt es, weil Leute reisen wollen, Verkehr dagegen weil Leute mobil sein wollen. Tourismus und Verkehr muss man sich deshalb als Phänomene vorstellen, welche als Resultat bzw. 'Outcome' individueller Bedürfnisbefriedigungen entstehen. Beide Phänomene finden im öffentlichen Raum statt und erzeugen unterschiedliche positive und negative (externe) Effekte. Anders als in vielen Wirtschaftsbereichen üblich, sind deshalb weder Tourismus noch Verkehr allein wirtschaftlich orientierte Erwerbsveranstaltungen. Vielmehr sind, aufgrund ihrer Raumbezogenheit sowie ihrer Effekte, nicht nur Nachfrager (Kunden) und Anbieter (Unternehmen) aktive Marktteilnehmer, sondern auch eine Vielzahl anderer Stakeholder.
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| 35. |
- Leidlmair, Christian, et al.
(författare)
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Structures, Energetics, and Dynamics of Helium Adsorbed on Isolated Fullerene Ions
- 2012
-
Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 108:7
-
Tidskriftsartikel (refereegranskat)abstract
- Helium adsorbed on C60+ and C70+ exhibits phenomena akin to helium on graphite. Mass spectra suggest that commensurate layers form when all carbon hexagons and pentagons are occupied by one He each, but that the solvation shell does not close until 60 He atoms are adsorbed on C60+, or 62 on C70+. Molecular dynamics simulations of C60Hen+ at 4 K show that the commensurate phase is solid. Helium added to C60He32+ will displace some atoms from pentagonal sites, leading to coexistence of a registered layer of immobile atoms interlaced with a nonregistered layer of mobile atoms.
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| 36. |
- Liu, Jimmy Z, et al.
(författare)
-
Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis.
- 2013
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:6, s. 670-5
-
Tidskriftsartikel (refereegranskat)abstract
- Primary sclerosing cholangitis (PSC) is a severe liver disease of unknown etiology leading to fibrotic destruction of the bile ducts and ultimately to the need for liver transplantation. We compared 3,789 PSC cases of European ancestry to 25,079 population controls across 130,422 SNPs genotyped using the Immunochip. We identified 12 genome-wide significant associations outside the human leukocyte antigen (HLA) complex, 9 of which were new, increasing the number of known PSC risk loci to 16. Despite comorbidity with inflammatory bowel disease (IBD) in 72% of the cases, 6 of the 12 loci showed significantly stronger association with PSC than with IBD, suggesting overlapping yet distinct genetic architectures for these two diseases. We incorporated association statistics from 7 diseases clinically occurring with PSC in the analysis and found suggestive evidence for 33 additional pleiotropic PSC risk loci. Together with network analyses, these findings add to the genetic risk map of PSC and expand on the relationship between PSC and other immune-mediated diseases.
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| 37. |
- Loh, N. Duane, et al.
(författare)
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Sensing the wavefront of x-ray free-electron lasers using aerosol spheres
- 2013
-
Ingår i: Optics Express. - 1094-4087. ; 21:10, s. 12385-12394
-
Tidskriftsartikel (refereegranskat)abstract
- Characterizing intense, focused x-ray free electron laser (FEL) pulses is crucial for their use in diffractive imaging. We describe how the distribution of average phase tilts and intensities on hard x-ray pulses with peak intensities of 1021 W/m(2) can be retrieved from an ensemble of diffraction patterns produced by 70 nm-radius polystyrene spheres, in a manner that mimics wavefront sensors. Besides showing that an adaptive geometric correction may be necessary for diffraction data from randomly injected sample sources, our paper demonstrates the possibility of collecting statistics on structured pulses using only the diffraction patterns they generate and highlights the imperative to study its impact on single-particle diffractive imaging.
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| 38. |
- Marz, Manja, et al.
(författare)
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Animal snoRNAs and scaRNAs with exceptional structures
- 2011
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Ingår i: RNA Biology. - : Informa UK Limited. - 1547-6286 .- 1555-8584. ; 8:6, s. 938-946
-
Tidskriftsartikel (refereegranskat)abstract
- The overwhelming majority of small nucleolar RNAs (snoRNAs) fall into two clearly defined classes characterized by distinctive secondary structures and sequence motifs. A small group of diverse ncRNAs, however, shares the hallmarks of one or both classes of snoRNAs but differs substantially from the norm in some respects. Here, we compile the available information on these exceptional cases, conduct a thorough homology search throughout the available metazoan genomes, provide improved and expanded alignments, and investigate the evolutionary histories of these ncRNA families as well as their mutual relationships.
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| 39. |
- Mattsson, Niklas, 1979, et al.
(författare)
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The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers.
- 2011
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 7:4
-
Tidskriftsartikel (refereegranskat)abstract
- The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program.
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| 40. |
- Mayer, Gerhard, et al.
(författare)
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The HUPO proteomics standards initiative-mass spectrometry controlled vocabulary
- 2013
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Ingår i: Database: the journal of biological databases and curation. - : Oxford University Press (OUP). - 1758-0463. ; , s. 009-009
-
Tidskriftsartikel (refereegranskat)abstract
- Controlled vocabularies (CVs), i.e. a collection of predefined terms describing a modeling domain, used for the semantic annotation of data, and ontologies are used in structured data formats and databases to avoid inconsistencies in annotation, to have a unique (and preferably short) accession number and to give researchers and computer algorithms the possibility for more expressive semantic annotation of data. The Human Proteome Organization (HUPO)-Proteomics Standards Initiative (PSI) makes extensive use of ontologies/CVs in their data formats. The PSI-Mass Spectrometry (MS) CV contains all the terms used in the PSI MS-related data standards. The CV contains a logical hierarchical structure to ensure ease of maintenance and the development of software that makes use of complex semantics. The CV contains terms required for a complete description of an MS analysis pipeline used in proteomics, including sample labeling, digestion enzymes, instrumentation parts and parameters, software used for identification and quantification of peptides/proteins and the parameters and scores used to determine their significance. Owing to the range of topics covered by the CV, collaborative development across several PSI working groups, including proteomics research groups, instrument manufacturers and software vendors, was necessary. In this article, we describe the overall structure of the CV, the process by which it has been developed and is maintained and the dependencies on other ontologies.
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| 41. |
- Nilsson, Johanna, et al.
(författare)
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Polyglucosan body myopathy caused by defective ubiquitin ligase RBCK1.
- 2013
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Ingår i: Annals of neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 74:6, s. 914-919
-
Tidskriftsartikel (refereegranskat)abstract
- Glycogen storage diseases are important causes of myopathy and cardiomyopathy. We describe ten patients from eight families with childhood or juvenile onset of myopathy, eight of whom also had rapidly progressive cardiomyopathy requiring heart transplant in four. The patients were homozygous or compound heterozygous for missense or truncating mutations in the ubiquitin ligase RBCK1 and had extensive polyglucosan accumulation in skeletal muscle and in the heart in cases of cardiomyopathy. We conclude that RBCK1 deficiency is a frequent cause of polyglucosan storage myopathy associated with progressive muscle weakness and cardiomyopathy. ANN NEUROL 2013. © 2013 American Neurological Association.
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| 42. |
- Noc, Marko, et al.
(författare)
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Invasive coronary treatment strategies for out-of-hospital cardiac arrest: a consensus statement from the European Association for Percutaneous Cardiovascular Interventions (EAPCI/Stent for Life (SFL) groups
- 2014
-
Ingår i: EuroIntervention. - 1969-6213. ; 10:1, s. 31-37
-
Tidskriftsartikel (refereegranskat)abstract
- Due to significant improvement in the pre-hospital treatment of patients with out-of-hospital cardiac arrest (OHCA), an increasing number of initially resuscitated patients are being admitted to hospitals. Because of the limited data available and lack of clear guideline recommendations, experts from the EAPCI and "Stent for Life" (SFL) groups reviewed existing literature and provided practical guidelines on selection of patients for immediate coronary angiography (CAG), PCI strategy, concomitant antiplatelet/anticoagulation treatment, haemodynamic support and use of therapeutic hypothermia. Conscious survivors of OHCA with suspected acute coronary syndrome (ACS) should be treated according to recommendations for ST-segment elevation myocardial infarction (STEMI) and high-risk non-ST-segment elevation -ACS (NSTE-ACS) without OHCA and should undergo immediate (if STEMI) or rapid (less than two hours if NSTE-ACS) coronary invasive strategy. Comatose survivors of OHCA with ECG criteria for STEMI on the post-resuscitation ECG should be admitted directly to the catheterisation laboratory. For patients without STEMI ECG criteria, a short "emergency department or intensive care unit stop" is advised to exclude non-coronary causes. In the absence of an obvious non-coronary cause, CAG should be performed as soon as possible (less than two hours), in particular in haemodynamically unstable patients. Immediate PCI should be mainly directed towards the culprit lesion if identified. Interventional cardiologists should become an essential part of the "survival chain" for patients with OHCA. There is a need to centralise the care of patients with OHCA to experienced centres.
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| 43. |
- Pagels, Martin, et al.
(författare)
-
Redox sensing by a Rex-family repressor is involved in the regulation of anaerobic gene expression in Staphylococcus aureus
- 2010
-
Ingår i: Molecular Microbiology. - : Wiley. - 1365-2958 .- 0950-382X. ; 76:5, s. 1142-1161
-
Tidskriftsartikel (refereegranskat)abstract
- P>An alignment of upstream regions of anaerobically induced genes in Staphylococcus aureus revealed the presence of an inverted repeat, corresponding to Rex binding sites in Streptomyces coelicolor. Gel shift experiments of selected upstream regions demonstrated that the redox-sensing regulator Rex of S. aureus binds to this inverted repeat. The binding sequence - TTGTGAAW(4)TTCACAA - is highly conserved in S. aureus. Rex binding to this sequence leads to the repression of genes located downstream. The binding activity of Rex is enhanced by NAD+ while NADH, which competes with NAD+ for Rex binding, decreases the activity of Rex. The impact of Rex on global protein synthesis and on the activity of fermentation pathways under aerobic and anaerobic conditions was analysed by using a rex-deficient strain. A direct regulatory effect of Rex on the expression of pathways that lead to anaerobic NAD+ regeneration, such as lactate, formate and ethanol formation, nitrate respiration, and ATP synthesis, is verified. Rex can be considered a central regulator of anaerobic metabolism in S. aureus. Since the activity of lactate dehydrogenase enables S. aureus to resist NO stress and thus the innate immune response, our data suggest that deactivation of Rex is a prerequisite for this phenomenon.
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| 44. |
- Park, Hyung Joo, et al.
(författare)
-
Toward unsupervised single-shot diffractive imaging of heterogeneous particles using X-ray free-electron lasers
- 2013
-
Ingår i: Optics Express. - 1094-4087. ; 21:23, s. 28729-28742
-
Tidskriftsartikel (refereegranskat)abstract
- Single shot diffraction imaging experiments via X-ray free-electron lasers can generate as many as hundreds of thousands of diffraction patterns of scattering objects. Recovering the real space contrast of a scattering object from these patterns currently requires a reconstruction process with user guidance in a number of steps, introducing severe bottlenecks in data processing. We present a series of measures that replace user guidance with algorithms that reconstruct contrasts in an unsupervised fashion. We demonstrate the feasibility of automating the reconstruction process by generating hundreds of contrasts obtained from soot particle diffraction experiments.
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| 45. |
- Redecke, Lars, et al.
(författare)
-
Natively inhibited Trypanosoma brucei cathepsin B structure determined by using an X-ray laser.
- 2013
-
Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 339:6116, s. 227-30
-
Tidskriftsartikel (refereegranskat)abstract
- The Trypanosoma brucei cysteine protease cathepsin B (TbCatB), which is involved in host protein degradation, is a promising target to develop new treatments against sleeping sickness, a fatal disease caused by this protozoan parasite. The structure of the mature, active form of TbCatB has so far not provided sufficient information for the design of a safe and specific drug against T. brucei. By combining two recent innovations, in vivo crystallization and serial femtosecond crystallography, we obtained the room-temperature 2.1 angstrom resolution structure of the fully glycosylated precursor complex of TbCatB. The structure reveals the mechanism of native TbCatB inhibition and demonstrates that new biomolecular information can be obtained by the "diffraction-before-destruction" approach of x-ray free-electron lasers from hundreds of thousands of individual microcrystals.
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| 46. |
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| 47. |
- Reinhold, Michael, et al.
(författare)
-
Exhibitor satisfaction in business-to-business trade shows : Understanding performance patterns from Vavra’s Importance Grid perspective
- 2010
-
Konferensbidrag (refereegranskat)abstract
- Tradeshows are an essential instrument in the marketing of goods and services. Thus, the fair and tradeshow business has become a multi-billion dollar industry, in which trade fair organizers earn the biggest share of sales with exhibitors, paying fees for exhibition services. In order to increase service quality on trade shows, trade fair organizers strive for achieving a high level of exhibitor satisfaction. Despite its major importance for the fair and tradeshow industry, instruments to poll exhibitors satisfaction remain very basic. This research focuses on exhibitor satisfaction in a business-to-business context. The paper contributes to the field of trade show research by (1) exploring relevant issues of exhibitor satisfaction, (2) developing a measurement approach, (3) collecting data from a number of 362 exhibitors in business-to-business trade shows and 404 exhibitors in business-to-consumer fairs, and finally (4) omparing results upon the Vavra's importance grid.
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| 48. |
- Rossbauer, Stephan, et al.
(författare)
-
Comparative Study of the N-Type Doping Efficiency in Solution-processed Fullerenes and Fullerene Derivatives
- 2014
-
Ingår i: Advanced Functional Materials. - : Wiley. - 1616-3028 .- 1616-301X. ; 24:45, s. 7116-7124
-
Tidskriftsartikel (refereegranskat)abstract
- Molecular doping of organic semiconductors and devices represents an enabling technology for a range of emerging optoelectronic applications. Although p-type doping has been demonstrated in a number of organic semiconductors, efficient n-type doping has proven to be particularly challenging. Here, n-type doping of solution-processed C60, C70, [60]PCBM, [70]PCBM and indene-C60 bis-adduct by 1H-benzimidazole (N-DMBI) is reported. The doping efficiency for each system is assessed using field-effect measurements performed under inert atmosphere at room temperature in combination with optical absorption spectroscopy and atomic force microscopy. The highest doping efficiency is observed for C60 and C70 and electron mobilities up to ≈2 cm2/Vs are obtained. Unlike in substituted fullerenes-based transistors where the electron mobility is found to be inversely proportional to N-DMBI concentration, C60 and C70 devices exhibit a characteristic mobility increase by approximately an order of magnitude with increasing dopant concentration up to 1 mol%. Doping also appears to significantly affect the bias stability of the transistors. The work contributes towards understanding of the molecular doping mechanism in fullerene-based semiconductors and outlines a simple and highly efficient approach that enables significant improvement in device performance through facile chemical doping.
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| 49. |
- Rutemark, Christian, et al.
(författare)
-
Requirement for complement in antibody responses is not explained by the classic pathway activator IgM
- 2011
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 108:43, s. 17589-17590
-
Tidskriftsartikel (refereegranskat)abstract
- Animals lacking complement factors C1q, C2, C3, or C4 have severely impaired Ab responses, suggesting a major role for the classic pathway. The classic pathway is primarily initiated by antigen-Ab complexes. Therefore, its role for primary Ab responses seems paradoxical because only low amounts of specific Abs are present in naive animals. A possible explanation could be that the classic pathway is initiated by IgM from naive mice, binding with sufficient avidity to the antigen. To test this hypothesis, a knock-in mouse strain, Cμ13, with a point mutation in the gene encoding the third constant domain of the μ-heavy chain was constructed. These mice produce IgM in which proline in position 436 is substituted with serine, a mutation previously shown to abrogate the ability of mouse IgM to activate complement. Unexpectedly, the Ab response to sheep erythrocytes and keyhole limpet hemocyanin in Cμ13 mice was similar to that in WT mice. Thus, although secreted IgM and the classic pathway activation are both required for the normal primary Ab response, this does not require that IgM activate C. This led us to test Ab responses in animals lacking one of three other endogenous activators of the classic pathway: specific intracellular adhesion molecule-grabbing nonintegrin R1, serum amyloid P component, and C-reactive protein. Ab responses were also normal in these animals.
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| 50. |
- Schmitt, Jochen, et al.
(författare)
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Towards global consensus on outcome measures for atopic eczema research: results of the HOME II meeting
- 2012
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 67:9, s. 1111-1117
-
Tidskriftsartikel (refereegranskat)abstract
- The use of nonstandardized and inadequately validated outcome measures in atopic eczema trials is a major obstacle to practising evidence-based dermatology. The Harmonising Outcome Measures for Eczema (HOME) initiative is an international multiprofessional group dedicated to atopic eczema outcomes research. In June 2011, the HOME initiative conducted a consensus study involving 43 individuals from 10 countries, representing different stakeholders (patients, clinicians, methodologists, pharmaceutical industry) to determine core outcome domains for atopic eczema trials, to define quality criteria for atopic eczema outcome measures and to prioritize topics for atopic eczema outcomes research. Delegates were given evidence-based information, followed by structured group discussion and anonymous consensus voting. Consensus was achieved to include clinical signs, symptoms, long-term control of flares and quality of life into the core set of outcome domains for atopic eczema trials. The HOME initiative strongly recommends including and reporting these core outcome domains as primary or secondary endpoints in all future atopic eczema trials. Measures of these core outcome domains need to be valid, sensitive to change and feasible. Prioritized topics of the HOME initiative are the identification/development of the most appropriate instruments for the four core outcome domains. HOME is open to anyone with an interest in atopic eczema outcomes research.
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