| 1. |
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| 2. |
- Judd, N., et al.
(författare)
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Cognitive and brain development is independently influenced by socioeconomic status and polygenic scores for educational attainment
- 2020
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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. ; 117:22, s. 12411-12418
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Tidskriftsartikel (refereegranskat)abstract
- Genetic factors and socioeconomic status (SES) inequalities play a large role in educational attainment, and both have been associated with variations in brain structure and cognition. However, genetics and SES are correlated, and no prior study has assessed their neural associations independently. Here we used a polygenic score for educational attainment (EduYears-PGS), as well as SES, in a longitudinal study of 551 adolescents to tease apart genetic and environmental associations with brain development and cognition. Subjects received a structural MRI scan at ages 14 and 19. At both time points, they performed three working memory (WM) tasks. SES and EduYears-PGS were correlated (r = 0.27) and had both common and independent associations with brain structure and cognition. Specifically, lower SES was related to less total cortical surface area and lower WM. EduYears-PGS was also related to total cortical surface area, but in addition had a regional association with surface area in the right parietal lobe, a region related to nonverbal cognitive functions, including mathematics, spatial cognition, and WM. SES, but not EduYears-PGS, was related to a change in total cortical surface area from age 14 to 19. This study demonstrates a regional association of EduYears-PGS and the independent prediction of SES with cognitive function and brain development. It suggests that the SES inequalities, in particular parental education, are related to global aspects of cortical development, and exert a persistent influence on brain development during adolescence.
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| 3. |
- Noort, S., et al.
(författare)
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Analysis of rare driving events in pediatric acute myeloid leukemia
- 2023
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 108:1, s. 48-60
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Tidskriftsartikel (refereegranskat)abstract
- Elucidating genetic aberrations in pediatric acute myeloid leukemia (AML) provides insight in biology and may impact on risk-group stratification and clinical outcome. This study aimed to detect such aberrations in a selected series of samples without known (cyto)genetic aberration using molecular profiling. A cohort of 161 patients was selected from various study groups: DCOG, BFM, SJCRH, NOPHO and AEIOP. Samples were analyzed using RNA sequencing (n=152), whole exome (n=135) and/or whole genome sequencing (n=100). In 70 of 156 patients (45%), of whom RNA sequencing or whole genome sequencing was available, rearrangements were detected, 22 of which were novel; five involving ERG rearrangements and four NPM1 rearrangements. ERG rearrangements showed self-renewal capacity in vitro, and a distinct gene expression pattern. Gene set enrichment analysis of this cluster showed upregulation of gene sets derived from Ewing sarcoma, which was confirmed comparing gene expression profiles of AML and Ewing sarcoma. Furthermore, NPM1-rearranged cases showed cytoplasmic NPM1 localization and revealed HOXA/B gene overexpression, as described for NPM1 mutated cases. Single-gene mutations as identified in adult AML were rare. Patients had a median of 24 coding mutations (range, 7-159). Novel recurrent mutations were detected in UBTF (n=10), a regulator of RNA transcription. In 75% of patients an aberration with a prognostic impact could be detected. Therefore, we suggest these techniques need to become standard of care in diagnostics.
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| 4. |
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| 5. |
- Lensink, Marc F., et al.
(författare)
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Impact of AlphaFold on structure prediction of protein complexes: The CASP15-CAPRI experiment
- 2023
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Ingår i: Proteins. - : WILEY. - 0887-3585 .- 1097-0134.
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Tidskriftsartikel (refereegranskat)abstract
- We present the results for CAPRI Round 54, the 5th joint CASP-CAPRI protein assembly prediction challenge. The Round offered 37 targets, including 14 homodimers, 3 homo-trimers, 13 heterodimers including 3 antibody-antigen complexes, and 7 large assemblies. On average similar to 70 CASP and CAPRI predictor groups, including more than 20 automatics servers, submitted models for each target. A total of 21 941 models submitted by these groups and by 15 CAPRI scorer groups were evaluated using the CAPRI model quality measures and the DockQ score consolidating these measures. The prediction performance was quantified by a weighted score based on the number of models of acceptable quality or higher submitted by each group among their five best models. Results show substantial progress achieved across a significant fraction of the 60+ participating groups. High-quality models were produced for about 40% of the targets compared to 8% two years earlier. This remarkable improvement is due to the wide use of the AlphaFold2 and AlphaFold2-Multimer software and the confidence metrics they provide. Notably, expanded sampling of candidate solutions by manipulating these deep learning inference engines, enriching multiple sequence alignments, or integration of advanced modeling tools, enabled top performing groups to exceed the performance of a standard AlphaFold2-Multimer version used as a yard stick. This notwithstanding, performance remained poor for complexes with antibodies and nanobodies, where evolutionary relationships between the binding partners are lacking, and for complexes featuring conformational flexibility, clearly indicating that the prediction of protein complexes remains a challenging problem.
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| 7. |
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| 8. |
- Bühler, David, et al.
(författare)
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A comparison between solar plage and network properties
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 630
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Tidskriftsartikel (refereegranskat)abstract
- Aims. We compare the properties of kG magnetic structures in the solar network and in active region plage at high spatial resolution.Methods. Our analysis used six SP scans of the solar disc centre aboard Hinode SOT and inverted the obtained spectra of the photospheric 6302 angstrom line pair using the 2D SPINOR code.Results. Photospheric magnetic field concentrations in network and plage areas are on average 1.5 kG strong with inclinations of 10 degrees-20 degrees, and have <400 m s(-1) internal and 2-3 km s(-1) external downflows. At the disc centre, the continuum intensity of magnetic field concentrations in the network are on average 10% brighter than the mean quiet Sun, whilst their plage counterparts are 3% darker. A more detailed analysis revealed that all sizes of individual kG patches in the network have 150 G higher field strengths on average, 5% higher continuum contrasts, and 800 m s(-1) faster surrounding downflows than similarly sized patches in the plage. The speed of the surrounding downflows also correlates with the patch area, and patches containing pores can produce supersonic flows exceeding 11 km s(-1) in individual pixels. Furthermore, the magnetic canopies of kG patches are on average 9 degrees more horizontal in the plage compared to the network.Conclusions. Most of the differences between the network and plage are due to their different patch size distributions, but the intrinsic differences between similarly sized patches likely results from the modification of the convection photospheric convection with increasing amounts of magnetic flux.
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| 9. |
- Kim, Taehoon H., et al.
(författare)
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Solenoid Driven Pressure Valve System: Toward Versatile Fluidic Control in Paper Microfluidics
- 2018
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Ingår i: Analytical Chemistry. - : AMER CHEMICAL SOC. - 0003-2700 .- 1520-6882. ; 90:4, s. 2534-2541
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Tidskriftsartikel (refereegranskat)abstract
- As paper-based diagnostics has become predominantly driven by more advanced microfluidic technology, many of the research efforts are still focused on developing reliable and versatile fluidic control devices, apart from improving sensitivity and reproducibility. In this work, we introduce a novel and robust paper fluidic control system enabling versatile fluidic control. The system comprises a linear push-pull solenoid and an Arduino Uno micro controller. The precisely controlled pressure exerted on the paper stops the flow. We first determined the stroke distance of the solenoid to obtain a constant pressure while examining the fluidic time delay as a function of the pressure. Results showed that strips of grade 1 chromatography paper had superior reproducibility in fluid transport. Next, we characterized the reproducibility of the fluidic velocity which depends on the type and grade of paper used. As such, we were able to control the flow velocity on the paper and also achieve a complete stop of flow with a pressure over 2.0 MPa. Notably, after the actuation of the pressure driven valve (PDV), the previously pressed area regained its original flow properties. This means that, even on a previously pressed area, multiple valve operations can be successfully conducted. To the best of our knowledge, this is the first demonstration of an active and repetitive valve operation in paper microfluidics. As a proof of concept, we have chosen to perform a multistep detection system in the form of an enzyme-linked immunosorbent assay with mouse IgG as the target analyte.
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| 10. |
- Lee, Seung Joon, et al.
(författare)
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Microslit on a chip: A simplified filter to capture circulating tumor cells enlarged with microbeads
- 2019
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 14:10
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Tidskriftsartikel (refereegranskat)abstract
- Microchips are widely used to separate circulating tumor cells (CTCs) from whole blood by virtues of sophisticated manipulation for microparticles. Here, we present a chip with an 8 µm high and 27.9 mm wide slit to capture cancer cells bound to 3 µm beads. Apart from a higher purity and recovery rate, the slit design allows for simplified fabrication, easy cell imaging, less clogging, lower chamber pressure and, therefore, higher throughput. The beads were conjugated with anti-epithelial cell adhesion molecules (anti-EpCAM) to selectively bind to breast cancer cells (MCF-7) used to spike the whole blood. The diameter of the cell-bead construct was in average 23.1 µm, making them separable from other cells in the blood. As a result, the cancer cells were separated from 5 mL of whole blood with a purity of 52.0% and a recovery rate of 91.1%, and also we confirmed that the device can be applicable to clinical samples of human breast cancer patients. The simple design with microslit, by eliminating any high-aspect ratio features, is expected to reduce possible defects on the chip and, therefore, more suitable for mass production without false separation outputs.
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| 11. |
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| 12. |
- Shin, Hyun Young, et al.
(författare)
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Cell Seeding Technology for Microarray-Based Quantitative Human Primary Skeletal Muscle Cell Analysis
- 2019
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Ingår i: Analytical Chemistry. - : AMER CHEMICAL SOC. - 0003-2700 .- 1520-6882. ; 91:22, s. 14214-14219
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Tidskriftsartikel (refereegranskat)abstract
- Pipetting techniques play a crucial role in obtaining reproducible and reliable results, especially when seeding cells on small target areas, such as on microarrays, biochips or microfabricated cell culture systems. For very rare cells, such as human primary skeletal muscle cells (skMCs), manual (freehand) cell seeding techniques invariably result in nonuniform cell spreading and heterogeneous cell densities, giving rise to undesirable variations in myogenesis and differentiation. To prevent such technique-dependent variation, we have designed and fabricated a simple, low-cost pipet guidance device (PGD), and holder that works with hand-held pipettes. This work validates the accuracy and reproducibility of the PGD platform and compares its effectiveness with manual and robotic seeding techniques. The PGD system ensures reproducibility of cell seeding, comparable to that of more expensive robotic dispensing systems, resulting in a high degree of cell uniformity and homogeneous cell densities, while also enabling cell community studies. As compared to freehand pipetting, PGD-assisted seeding of C2C12 mouse myoblasts showed 5.3 times more myotube formation and likewise myotubes derived from PGD-seeded human primary skMCs were 3.6 times thicker and 2.2 times longer. These results show that this novel, yet simple PGD-assisted pipetting technique provides precise cell seeding on small targets, ensuring reproducible and reliable high-throughput cell assays.
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| 13. |
- van Noort, M., et al.
(författare)
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A prototype of a microlensed hyperspectral imager for solar observations
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 668
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Tidskriftsartikel (refereegranskat)abstract
- Context. When spectropolarimetric data are recorded at high spatial, spectral, and temporal resolution, the quality of the data is generally limited by the signal-to-noise ratio.Aims. We present a prototype of an integral field spectrograph for solar observations. This prototype overcomes the limitations of traditional solar instrumentation and captures the spectral information for all points in a given field of view without scanning, in order to optimize the efficiency and to minimize spectral and spatial crosstalk.Methods. The prototype was executed as a plug-in for the TRIPPEL spectrograph at the Swedish 1-meter Solar Telescope (SST) and uses an array of microlenses to shrink each image element, so that dark space is created in between. The light is then dispersed in this space, allowing for the independent detection of each spatio-spectral image element on a 2D detector.Results. The prototype was built and installed at the SST, yielding several good-quality data sets. These data sets were used to determine the imaging performance and efficiency of the prototype.Conclusions. Although the instrument required high-accuracy optics, the transparency of the prototype was found to be about 25%, and the straylight properties were found to be typical for spectrographic instruments.
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| 14. |
- van Noort, Suus A M, et al.
(författare)
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Early onset ataxia with comorbid myoclonus and epilepsy : A disease spectrum with shared molecular pathways and cortico-thalamo-cerebellar network involvement
- 2023
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Ingår i: European Journal of Paediatric Neurology. - 1090-3798. ; 45, s. 47-54
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Early onset ataxia (EOA) concerns a heterogeneous disease group, often presenting with other comorbid phenotypes such as myoclonus and epilepsy. Due to genetic and phenotypic heterogeneity, it can be difficult to identify the underlying gene defect from the clinical symptoms. The pathological mechanisms underlying comorbid EOA phenotypes remain largely unknown. The aim of this study is to investigate the key pathological mechanisms in EOA with myoclonus and/or epilepsy.METHODS: For 154 EOA-genes we investigated (1) the associated phenotype (2) reported anatomical neuroimaging abnormalities, and (3) functionally enriched biological pathways through in silico analysis. We assessed the validity of our in silico results by outcome comparison to a clinical EOA-cohort (80 patients, 31 genes).RESULTS: EOA associated gene mutations cause a spectrum of disorders, including myoclonic and epileptic phenotypes. Cerebellar imaging abnormalities were observed in 73-86% (cohort and in silico respectively) of EOA-genes independently of phenotypic comorbidity. EOA phenotypes with comorbid myoclonus and myoclonus/epilepsy were specifically associated with abnormalities in the cerebello-thalamo-cortical network. EOA, myoclonus and epilepsy genes shared enriched pathways involved in neurotransmission and neurodevelopment both in the in silico and clinical genes. EOA gene subgroups with myoclonus and epilepsy showed specific enrichment for lysosomal and lipid processes.CONCLUSIONS: The investigated EOA phenotypes revealed predominantly cerebellar abnormalities, with thalamo-cortical abnormalities in the mixed phenotypes, suggesting anatomical network involvement in EOA pathogenesis. The studied phenotypes exhibit a shared biomolecular pathogenesis, with some specific phenotype-dependent pathways. Mutations in EOA, epilepsy and myoclonus associated genes can all cause heterogeneous ataxia phenotypes, which supports exome sequencing with a movement disorder panel over conventional single gene panel testing in the clinical setting.
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| 15. |
- Vargas Domínguez, S, et al.
(författare)
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Moat Flow in the Vicinity of Sunspots for Various Penumbral Configurations
- 2008
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Ingår i: The Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 679:1, s. 900-909
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Tidskriftsartikel (refereegranskat)abstract
- High-resolution time series of sunspots have been obtained with the Swedish 1 m Solar Telescope between 2003 and 2006 at different locations on the solar disk. Proper motions in seven different active regions have been studied. The analysis was performed by applying local correlation tracking to every series of sunspots, each of them more than 40 minutes long. The sunspots' shapes include a different variety of penumbral configurations. We report on the systematic behavior of the large-scale outflows surrounding the sunspots, commonly known as moat flows, that are essentially present only when preceded by a penumbra not tangential but perpendicular to the sunspot border. We present one case for which this rule appears not to be confirmed. We speculate that the magnetic neutral line, which is located in the vicinity of the anomalous region, might be responsible for blocking the outflow. These new results confirm the systematic and strong relation between the moat flows and the existence of penumbrae. A comparative statistical study between moats and standard granulation is also performed.
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| 16. |
- Yelles Chaouche, L., et al.
(författare)
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Spectropolarimetric Diagnostics at the Solar Photosphere near the Limb
- 2009
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Ingår i: <em>Solar Polarization 5</em>. - : Astronomical Society of the Pacific. ; , s. 189-
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Konferensbidrag (refereegranskat)abstract
- In the present work, we investigate the formation of Stokes profiles and spectro-polarimetric diagnostics in an active region plage near the limb. We use 3-D radiation-MHD simulations with unipolar fields of an average strength of 400 G, which is largely concentrated in flux tubes in which the field reaches typical kilo-Gauss values. We generate synthetic Stokes spectra by radiative transfer calculations, then we degrade the simulated Stokes signal to account for observational conditions. The synthetic data treated in this manner are compared with and found to roughly reproduce spectro-polarimetric high-resolution observations at μ=0.39 obtained by the SOUP instrument with the Swedish 1-m Solar Telescope at the beginning of 2006.
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