| 1. |
- Walsh, Roddy, et al.
(författare)
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Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls
- 2021
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Ingår i: Genetics in Medicine. - : Nature Publishing Group. - 1098-3600 .- 1530-0366. ; 23:1, s. 47-58
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate.Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants.Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 x 10(-18)) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 x 10(-13)). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency.Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.
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| 2. |
- Gericke, Sabrina Maria, et al.
(författare)
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In Situ H2 Reduction of Al2O3-Supported Ni- and Mo-Based Catalysts
- 2022
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Ingår i: Catalysts. - : MDPI. - 2073-4344. ; 12:7
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Tidskriftsartikel (refereegranskat)abstract
- Nickel (Ni)-promoted Molybdenum (Mo)-based catalysts are used for hydrotreatment processes in the chemical industry where the catalysts are exposed to high-pressure H2 at elevated temperature. In this environment, the catalyst transforms into the active phase, which involves the reduction of the oxide. Here, we report on the first in situ study on the reduction of alumina supported Ni- and Mo-based catalysts in 1 mbar H2 using ambient-pressure X-ray photoelectron spectroscopy (APXPS). The study confirms that mixing Ni and Mo lowers the reduction temperature of both Ni- and Mo-oxide as compared to the monometallic catalysts and shows that the MoO3 reduction starts at a lower temperature than the reduction of NiO in NiMo/Al2O3 catalysts. Additionally, the reduction of Ni and Mo foil was directly compared to the reduction of the Al2O3-supported catalysts and it was observed that the reduction of the supported catalysts is more gradual than the reduction of the foils, indicating a strong interaction between the Ni/Mo and the alumina support. © 2022 by the authors.
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| 3. |
- Fornell, Anna, et al.
(författare)
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A microfluidic platform for SAXS measurements of liquid samples
- 2022
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Konferensbidrag (refereegranskat)abstract
- Small-angle X-ray scattering (SAXS) is a technique that can measure the size and shape of small particles such as proteins and nanoparticles using X-rays. At MAX IV, we are developing a microfluidic sample delivery platform to measure liquid samples containing proteins under flow using SAXS. One of the main advantages of using microfluidics is that the sample is continuously flowing, thus minimizing the risk of radiation damage as the sample is continuously refreshed. Other advantages include low sample volume and the possibility to study dynamic processes, e.g. mixing. To obtain good SAXS signals, the X-ray properties of the chip material are essential. The microfluidic chip must have low attenuation of X-rays, low background scattering, and high resistance to X-ray-induced damage, and preferably be low cost and easy to fabricate. In this work, we have evaluated the performance of two different polymer microfluidic chips for SAXS measurements.
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| 4. |
- Fornell, Anna, et al.
(författare)
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A Microfluidic Platform for Synchrotron X-ray Studies of Proteins
- 2021
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Konferensbidrag (refereegranskat)abstract
- New tools are needed to allow for complex protein dynamics studies, especially to study proteins in their native states. In the AdaptoCell project a microfluidic platform for academic and industrial users at MAX IV Laboratory is being developed. MAX IV is a Swedish national laboratory providing brilliant synchrotron X-rays for research. Due to the high photon flux, sensitive samples such as proteins are prone to rapid radiation damage; thus, it is advantageous to have the liquid sample underflow to refresh the sample continuously. This, in combination with small volumes, makes microfluidics a highly suitable sample environment for protein studies at MAX IV. The AdaptoCell platform is being integrated at three beamlines:Balder (X-ray absorption/emission spectroscopy), CoSAXS (small angle x-ray scattering) and Micromax (serial synchrotron crystallography). Currently, the platform is fully available atBalder, under commissioning at CoSAXS and being developed for MicroMAX.
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| 5. |
- Fornell, Anna, et al.
(författare)
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AdaptoCell : Microfluidics at MAX IV Laboratory
- 2022
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Ingår i: 25th Swedish Conference on Macromolecular Structure and Function.
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Konferensbidrag (refereegranskat)abstract
- The AdaptoCell project at MAX IV has developed a microfluidic sample delivery platform for academic and industrial users to enable studies of protein samples in solution and in microcrystals underflow. The platform is compatible with various X-ray techniques and has so far been integrated onto two beamlines at MAX IV: the CoSAXS beamline for small angle X-ray scattering studies and the Balder beamline for X-ray absorption spectroscopy studies. Initial implementation of the platform for serial crystallography sample delivery is ongoing and will be integrated onto the BioMAX and MicroMAX beamlines once commissioned. With this platform, we aim to meet the demand from our user community for studying proteins at physiologically relevant temperatures and give the ability to follow dynamical processes in situ as well as decreasing sample volumes and radiation damage.To determine the optimized flow rates and components for mixing etc. using different microfluidic chips, a dedicated off(beam)line test station with a microscope has been established at the Biolab. The Biolab also provides a number of characterization techniques, such as Dynamic Light Scattering, UV-Vis spectrophotometry, for quality control of the samples; as well as an anaerobic chamber for preparation and characterization of metalloproteins. The microfluidic flows are controlled via syringe pumps or a pressure-driven system. Channel design varies, depending on the needs of the experiment, from straight channel, cross-junction to herringbone micromixers etc. On-chip mixing of buffers with different viscosity, pH, ion strength and protein concentrations has been demonstrated successful and will be presented.
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| 6. |
- Fornell, Anna, et al.
(författare)
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AdaptoCell – Microfluidic Platforms at MAX IV Laboratory
- 2021
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Konferensbidrag (refereegranskat)abstract
- In the AdaptoCell project, we are developing microfluidic platforms for X-ray studies of liquid samples. Microfluidics is a suitable technology for samples that are prone to radiation damage, such as proteins. By having the sample underflow, the sample is continuously refreshed, and the risk of radiation damage is reduced. The technology is also suitable for investigating dynamic events such as in situ mixing. The microfluidic platforms are being integrated at three beamlines at MAX IV Laboratory: Balder (X-ray absorption/emission spectroscopy), CoSAXS (small angle x-ray scattering) and MicroMAX (serial synchrotron crystallography). Currently, the platforms are available for users at Balder and CoSAXS, which is under development at MicroMAX. In addition, we also provide a microfluidic offline test station where users can test their samples and optimise their devices before the beam time. The main components of the microfluidic setup are the pressure-driven flow controller and the microfluidic chip. We mainly use commercially available polymer microfluidic chips made of COC (cyclic olefin copolymer). COC is used as a chip material as it has high X-ray transmission and high resistance to radiation damage. There are several different chip designs available such as straight channel chips, droplet generator chips and mixing chips. We believe the AdaptoCell platforms will be useful and versatile sample environments for academic and industrial users at MAX IV Laboratory who want to perform experiments with liquid samples under flow.
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| 7. |
- Leinonen, Päivi H., et al.
(författare)
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Local adaptation in European populations of Arabidopsis lyrata (Brassicaceae)
- 2009
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Ingår i: American Journal of Botany. - : Wiley. - 0002-9122 .- 1537-2197. ; 96:6, s. 1129-1137
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Tidskriftsartikel (refereegranskat)abstract
- We studied local adaptation to contrasting environments usingan organism that is emerging as a model for evolutionary plantbiology—the outcrossing, perennial herb Arabidopsis lyratasubsp. petraea (Brassicaceae). With reciprocal transplant experiments,we found variation in cumulative fitness, indicating adaptivedifferentiation among populations. Nonlocal populations didnot have significantly higher fitness than the local population.Experimental sites were located in Norway (alpine), Sweden (coastal),and Germany (continental). At all sites after one year, thelocal population had higher cumulative fitness, as quantifiedby survival combined with rosette area, than at least one ofthe nonlocal populations. At the Norwegian site, measurementswere done for two additional years, and fitness differencespersisted. The fitness components that contributed most to differencesin cumulative fitness varied among sites. Relatively small rosettearea combined with a large number of inflorescences producedby German plants may reflect differentiation in life history.The results of the current study demonstrate adaptive populationdifferentiation in A. lyrata along a climatic gradient in Europe.The studied populations harbor considerable variation in severalcharacters contributing to adaptive population differentiation.The wealth of genetic information available makes A. lyrataa highly attractive system also for examining the functionaland genetic basis of local adaptation in plants.
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| 8. |
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| 9. |
- Micheal Raj, Pushparani, et al.
(författare)
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Fabrication and characterisation of a silicon-borosilicate glass microfluidic device for synchrotron-based hard X-ray spectroscopy studies
- 2021
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Ingår i: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 11:47, s. 29859-29869
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Tidskriftsartikel (refereegranskat)abstract
- Some of the most fundamental chemical building blocks of life on Earth are the metal elements. X-ray absorption spectroscopy (XAS) is an element-specific technique that can analyse the local atomic and electronic structure of, for example, the active sites in catalysts and energy materials and allow the metal sites in biological samples to be identified and understood. A microfluidic device capable of withstanding the intense hard X-ray beams of a 4th generation synchrotron and harsh chemical sample conditions is presented in this work. The device is evaluated at the K-edges of iron and bromine and the L-3-edge of lead, in both transmission and fluorescence mode detection and in a wide range of sample concentrations, as low as 0.001 M. The device is fabricated in silicon and glass with plasma etched microchannels defined in the silicon wafer before anodic bonding of the glass wafer into a complete device. The device is supported with a well-designed printed chip holder that made the microfluidic device portable and easy to handle. The chip holder plays a pivotal role in mounting the delicate microfluidic device on the beamline stage. Testing validated that the device was sufficiently robust to contain and flow through harsh acids and toxic samples. There was also no significant radiation damage to the device observed, despite focusing with intense X-ray beams for multiple hours. The quality of X-ray spectra collected is comparable to that from standard methods; hence we present a robust microfluidic device to analyse liquid samples using synchrotron XAS.
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| 10. |
- Raj, Pushparani, et al.
(författare)
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Fabrication and characterisation of a silicon-borosilicate glass microfluidic device for synchrotron-based hard X-ray spectroscopy studies
- 2021
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Ingår i: RSC Advances. - Cambridge : RSC Publishing. - 2046-2069. ; 11:47, s. 29859-29869
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Tidskriftsartikel (refereegranskat)abstract
- Some of the most fundamental chemical building blocks of life on Earth are the metal elements. X-ray absorption spectroscopy (XAS) is an element-specific technique that can analyse the local atomic and electronic structure of, for example, the active sites in catalysts and energy materials and allow the metal sites in biological samples to be identified and understood. A microfluidic device capable of withstanding the intense hard X-ray beams of a 4th generation synchrotron and harsh chemical sample conditions is presented in this work. The device is evaluated at the K-edges of iron and bromine and the L3-edge of lead, in both transmission and fluorescence mode detection and in a wide range of sample concentrations, as low as 0.001 M. The device is fabricated in silicon and glass with plasma etched microchannels defined in the silicon wafer before anodic bonding of the glass wafer into a complete device. The device is supported with a well-designed printed chip holder that made the microfluidic device portable and easy to handle. The chip holder plays a pivotal role in mounting the delicate microfluidic device on the beamline stage. Testing validated that the device was sufficiently robust to contain and flow through harsh acids and toxic samples. There was also no significant radiation damage to the device observed, despite focusing with intense X-ray beams for multiple hours. The quality of X-ray spectra collected is comparable to that from standard methods; hence we present a robust microfluidic device to analyse liquid samples using synchrotron XAS.
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