| 1. |
- Kim, Joon Tae, et al.
(författare)
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Dual antiplatelet Use for extended period taRgeted to AcuTe ischemic stroke with presumed atherosclerotic OrigiN (DURATION) trial : Rationale and design
- 2023
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Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4930 .- 1747-4949. ; 18:8, s. 1015-1020
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: The optimal duration of dual antiplatelet therapy (DAPT) with clopidogrel-aspirin for the large artery atherosclerotic (LAA) stroke subtype has been debated. Aims: To determine whether the 1-year risk of recurrent vascular events could be reduced by a longer duration of DAPT in patients with the LAA stroke subtype. Methods and study design: A total of 4806 participants will be recruited to detect a statistically significant relative risk reduction of 22% with 80% power and a two-sided alpha error of 0.05, including a 10% loss to follow-up. This is a registry-based, multicenter, prospective, randomized, open-label, blinded end point study designed to evaluate the efficacy and safety of a 12-month duration of DAPT compared with a 3-month duration of DAPT in the LAA stroke subtype. Patients will be randomized (1:1) to either DAPT for 12 months or DAPT for 3 months, followed by monotherapy (either aspirin or clopidogrel) for the remaining 9 months. Study outcomes: The primary efficacy outcome of the study is a composite of stroke (ischemic or hemorrhagic), myocardial infarction, and all-cause mortality for 1 year after the index stroke. The secondary efficacy outcomes are (1) stroke, (2) ischemic stroke or transient ischemic attack, (3) hemorrhagic stroke, and (4) all-cause mortality. The primary safety outcome is major bleeding. Discussion: This study will help stroke physicians determine the appropriate duration of dual therapy with clopidogrel-aspirin for patients with the LAA stroke subtype. Trial registration: URL: https://cris.nih.go.kr/cris. CRIS Registration Number: KCT0004407.
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| 2. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- An, Junghwa, et al.
(författare)
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Permanent Genetic Resources added to Molecular Ecology Resources Database 1 October 2009-30 November 2009
- 2010
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:2, s. 404-408
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Tidskriftsartikel (refereegranskat)abstract
- This article documents the addition of 411 microsatellite marker loci and 15 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Acanthopagrus schlegeli, Anopheles lesteri, Aspergillus clavatus, Aspergillus flavus, Aspergillus fumigatus, Aspergillus oryzae, Aspergillus terreus, Branchiostoma japonicum, Branchiostoma belcheri, Colias behrii, Coryphopterus personatus, Cynogolssus semilaevis, Cynoglossus semilaevis, Dendrobium officinale, Dendrobium officinale, Dysoxylum malabaricum, Metrioptera roeselii, Myrmeciza exsul, Ochotona thibetana, Neosartorya fischeri, Nothofagus pumilio, Onychodactylus fischeri, Phoenicopterus roseus, Salvia officinalis L., Scylla paramamosain, Silene latifo, Sula sula, and Vulpes vulpes. These loci were cross-tested on the following species: Aspergillus giganteus, Colias pelidne, Colias interior, Colias meadii, Colias eurytheme, Coryphopterus lipernes, Coryphopterus glaucofrenum, Coryphopterus eidolon, Gnatholepis thompsoni, Elacatinus evelynae, Dendrobium loddigesii Dendrobium devonianum, Dysoxylum binectariferum, Nothofagus antarctica, Nothofagus dombeyii, Nothofagus nervosa, Nothofagus obliqua, Sula nebouxii, and Sula variegata. This article also documents the addition of 39 sequencing primer pairs and 15 allele specific primers or probes for Paralithodes camtschaticus.
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| 4. |
- Lee, Ja Kyung, et al.
(författare)
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Strain-induced indium clustering in non-polar a-plane InGaN quantum wells
- 2018
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Ingår i: Acta Materialia. - : PERGAMON-ELSEVIER SCIENCE LTD. - 1359-6454 .- 1873-2453. ; 145, s. 109-122
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Tidskriftsartikel (refereegranskat)abstract
- In conventional light-emitting diodes the epitaxial strain and related piezoelectric polarization arising along the polar [0001] growth direction of the InGaN/GaN quantum wells (QWs) induce internal fields which adversely affect the radiative recombination of electron-hole pairs therein. Growing the quantum wells along a nonpolar orientation can, in principle, avoid this problem but seems to face with another problem associated with indium clustering. In this study, we present experimental evidence that supports the inhomogeneous distribution of indium in non-polar a-plane InGaN QWs by using dark-field inline electron holography as well as atom probe tomography measurements and discuss the possible origin by density functional theory calculation. A model non-polar a-plane QW structure with 10 nm-thick In0.1Ga0.9N double QWs was investigated and compared with the polar c-plane QWs with the same QW structure. Unlike the random distribution in the polar QWs, the indium atoms in the non-polar QW exhibit inhomogeneous distribution and show a tendency of periodic, clustering. We suggest the dipole interaction energy and the strain energy associated with indium substitution could have a substantial influence on the local composition of strained InGaN QWs and, particularly, triggers In clustering in the non-polar a-plane QW structure. Accompanying phase field modeling rationalizes that In clustering can also modify the in-plane polarization through piezoelectric effects, preventing the electrostatic potential from diverging along the in-plane polar direction.
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| 5. |
- Choi, Nuri, et al.
(författare)
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Influence of Manufacturing Conditions on Inclusion Characteristics and Mechanical Properties of FeCrNiMnCo Alloy
- 2020
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Ingår i: Metals. - : MDPI. - 2075-4701. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- Three CoCrFeMnNi high-entropy alloys (HEAs) were produced by vacuum induction melting, induction melting under inert gas atmosphere, and melting under inert gas atmosphere followed by air exposure, respectively. The different manufacturing conditions for the three investigated alloys resulted in different levels and types of inclusions. The alloys melted under vacuum or inert gas contained Al2O3 inclusions formed by impurity Al, due to its high oxidation tendency. The molten alloy exposed in air showed an excessive oxidation. During oxidation of the molten alloy in air, impurity Al was initially oxidized, and fine MnCr2O4 inclusions were formed rather than pure Al2O3 inclusions. This difference was analyzed based on thermodynamic calculations. Specifically, the influence of impurity content on the inclusion characteristics was investigated for the three HEAs. Moreover, the inclusion characteristics were found to have an influence on mechanical properties of the alloys also. In air-exposed HEA, smaller inclusions were formed, resulting in a higher dislocation density at the matrix/inclusion interface and thus strengthening of the HEA. Thus, it is proposed that atmospheric conditions could be an important factor to control the inclusion characteristics and to form fine inclusion particles, which could improve the mechanical properties of HEAs.
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| 6. |
- Flannick, Jason, et al.
(författare)
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Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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| 7. |
- Fuchsberger, Christian, et al.
(författare)
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The genetic architecture of type 2 diabetes
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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| 8. |
- He, Hans, 1989, et al.
(författare)
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Uniform doping of graphene close to the Dirac point by polymer-assisted assembly of molecular dopants
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Tuning the charge carrier density of two-dimensional (2D) materials by incorporating dopants into the crystal lattice is a challenging task. An attractive alternative is the surface transfer doping by adsorption of molecules on 2D crystals, which can lead to ordered molecular arrays. However, such systems, demonstrated in ultra-high vacuum conditions (UHV), are often unstable in ambient conditions. Here we show that air-stable doping of epitaxial graphene on SiC—achieved by spin-coating deposition of 2,3,5,6-tetrafluoro-tetracyano-quino-dimethane (F4TCNQ) incorporated in poly(methyl-methacrylate)—proceeds via the spontaneous accumulation of dopants at the graphene-polymer interface and by the formation of a charge-transfer complex that yields low-disorder, charge-neutral, large-area graphene with carrier mobilities ~70 000 cm2V−1s−1at cryogenic temperatures. The assembly of dopants on 2D materials assisted by a polymer matrix, demonstrated by spin-coating wafer-scale substrates in ambient conditions, opens up a scalable technological route toward expanding the functionality of 2D materials.
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| 9. |
- Ho, Joshua W. K., et al.
(författare)
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Comparative analysis of metazoan chromatin organization
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 512:7515, s. 449-U507
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Tidskriftsartikel (refereegranskat)abstract
- Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms(1-3). Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths(4,5). To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.
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| 10. |
- Hong, S. J., et al.
(författare)
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Verification of electron doping in single-layer graphene due to H-2 exposure with thermoelectric power
- 2015
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 106:14
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Tidskriftsartikel (refereegranskat)abstract
- We report the electron doping of single-layer graphene (SLG) grown by chemical vapor deposition (CVD) by means of dissociative hydrogen adsorption. The transfer characteristic showed n-type doping behavior similar to that of mechanically exfoliated graphene. Furthermore, we studied the thermoelectric power (TEP) of CVD-grown SLG before and after exposure to high-pressure H-2 molecules. From the TEP results, which indicate the intrinsic electrical properties, we observed that the CVD-grown SLG is n-type doped without degradation of the quality after hydrogen adsorption. Finally, the electron doping was also verified by Raman spectroscopy.
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| 11. |
- Jeon, Iksoo, et al.
(författare)
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Neuronal Properties, In Vivo Effects, and Pathology of a Huntington's Disease Patient-Derived Induced Pluripotent Stem Cells
- 2012
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Ingår i: Stem Cells. - : Oxford University Press (OUP). - 1549-4918 .- 1066-5099. ; 30:9, s. 2054-2062
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Tidskriftsartikel (refereegranskat)abstract
- Induced pluripotent stem cells (iPSCs) generated from somatic cells of patients can be used to model different human diseases. They may also serve as sources of transplantable cells that can be used in novel cell therapies. Here, we analyzed neuronal properties of an iPSC line derived from a patient with a juvenile form of Huntington's disease (HD) carrying 72 CAG repeats (HD-iPSC). Although its initial neural inducing activity was lower than that of human embryonic stem cells, we found that HD-iPSC can give rise to GABAergic striatal neurons, the neuronal cell type that is most susceptible to degeneration in HD. We then transplanted HD-iPSC-derived neural precursors into a rat model of HD with a unilateral excitotoxic striatal lesion and observed a significant behavioral recovery in the grafted rats. Interestingly, during our in vitro culture and when the grafts were examined at 12 weeks after transplantation, no aggregate formation was detected. However, when the culture was treated with a proteasome inhibitor (MG132) or when the cells engrafted into neonatal brains were analyzed at 33 weeks, there were clear signs of HD pathology. Taken together, these results indicate that, although HD-iPSC carrying 72 CAG repeats can form GABAergic neurons and give rise to functional effects in vivo, without showing an overt HD phenotype, it is highly susceptible to proteasome inhibition and develops HD pathology at later stages of transplantation. These unique features of HD-iPSC will serve as useful tools to study HD pathology and develop novel therapeutics. Stem Cells 2012; 30: 20542062
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| 12. |
- Kim, Ji-Hoon, et al.
(författare)
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Assessing the impact of freshwater discharge on the fluid chemistry in the Svalbard fjords
- 2022
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 835
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Tidskriftsartikel (refereegranskat)abstract
- Changes in the cryosphere extent (e.g., glacier, ice sheet, permafrost, and snow) have been speculated to impact (bio)geochemical interactions and element budgets of seawater and pore fluids in Arctic regions. However, this process has rarely been documented in Arctic fjords, which leads to a poor systematic understanding of land-ocean interactions in such a warming-susceptible region. Here, we present the chemical and isotopic (δ18O, δD, δ11B, and 87Sr/86Sr) compositions of seawater and pore fluids from five fjords in the Svalbard archipelago. Compared to bottom seawater, the low Cl− concentrations and depleted water isotopic signatures (δ18O and δD) of surface seawater and pore fluids delineate freshwater discharge originating from precipitation and/or meltwater of the cryosphere (i.e., glacier, snow, and permafrost). In contrast, the high Cl− concentrations with light water isotopic values in pore fluids from Dicksonfjorden indicate a brine probably resulted from submarine permafrost formation during the late Holocene, a timing supported by the numerical simulation of dissolved Cl− concentration.The freshwater is influenced by the local diagenetic processes such as ion exchanges indicated by δ11B signatures as well as interactions with bedrock during fluid migration inferred from pore fluid 87Sr/86Sr ratios. The interactions with bedrock significantly alter the hydrogeochemical properties of pore fluids in each fjord, yielding spatiotemporal variations. Consequently, land-ocean interactions in combination with the hydrosphere-cryosphere-lithosphere are critical factors for understanding and predicting the hydrology and elemental cycling during global climate change periods in the past, present, and future of the Svalbard archipelago.
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| 13. |
- Kim, Kyung Ho, 1984, et al.
(författare)
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Apparent Power Law Scaling of Variable Range Hopping Conduction in Carbonized Polymer Nanofibers
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- We induce dramatic changes in the structure of conducting polymer nanofibers by carbonization at 800 degrees C and compare charge transport properties between carbonized and pristine nanofibers. Despite the profound structural differences, both types of systems display power law dependence of current with voltage and temperature, and all measurements can be scaled into a single universal curve. We analyze our experimental data in the framework of variable range hopping and argue that this mechanism can explain transport properties of pristine polymer nanofibers as well.
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| 14. |
- Kim, Kyung Ho, 1984, et al.
(författare)
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Probing variable range hopping lengths by magneto conductance in carbonized polymer nanofibers
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Using magneto transport, we probe hopping length scales in the variable range hopping conduction of carbonized polyacetylene and polyaniline nanofibers. In contrast to pristine polyacetylene nanofibers that show vanishing magneto conductance at large electric fields, carbonized polymer nanofibers display a negative magneto conductance that decreases in magnitude but remains finite with respect to the electric field. We show that this behavior of magneto conductance is an indicator of the electric field and temperature dependence of hopping length in the gradual transition from the thermally activated to the activation-less electric field driven variable range hopping transport. This reveals magneto transport as a useful tool to probe hopping lengths in the non-linear hopping regime.
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| 15. |
- Kim, Kyung Ho, 1984, et al.
(författare)
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Thermal stability of epitaxial graphene electrodes for conductive polymer nanofiber devices
- 2017
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Ingår i: Crystals. - : MDPI AG. - 2073-4352. ; 7:12
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Tidskriftsartikel (refereegranskat)abstract
- We used large area, monolayer graphene epitaxially grown on SiC (0001) as contact electrodes for polymer nanofiber devices. Our fabrication process, which avoids polymer resist residues on the graphene surface, results in graphene-polyaniline nanofiber devices with Ohmic contacts and electrical conductivity comparable to that of Au-nanofiber devices. We further checked the thermal stability of the graphene contacts to polyaniline devices by annealing up to T = 800 °C, the temperature at which polyaniline nanofibers are carbonized but the graphene electrode remains intact. The thermal stability and Ohmic contact of polymer nanofibers are demonstrated here, which together with the chemical stability and atomic flatness of graphene, make epitaxial graphene on SiC an attractive contact material for future all-carbon electronic devices.
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| 16. |
- Lee, San, et al.
(författare)
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Impact of data extraction errors in meta-analyses on the association between depression and peripheral inflammatory biomarkers : an umbrella review
- 2023
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Ingår i: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 53:5, s. 2017-2030
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Accumulating evidence suggests that alterations in inflammatory biomarkers are important in depression. However, previous meta-analyses disagree on these associations, and errors in data extraction may account for these discrepancies.METHODS: PubMed/MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched from database inception to 14 January 2020. Meta-analyses of observational studies examining the association between depression and levels of tumor necrosis factor-α (TNF-α), interleukin 1-β (IL-1β), interleukin-6 (IL-6), and C-reactive protein (CRP) were eligible. Errors were classified as follows: incorrect sample sizes, incorrectly used standard deviation, incorrect participant inclusion, calculation error, or analysis with insufficient data. We determined their impact on the results after correction thereof.RESULTS: Errors were noted in 14 of the 15 meta-analyses included. Across 521 primary studies, 118 (22.6%) showed the following errors: incorrect sample sizes (20 studies, 16.9%), incorrect use of standard deviation (35 studies, 29.7%), incorrect participant inclusion (7 studies, 5.9%), calculation errors (33 studies, 28.0%), and analysis with insufficient data (23 studies, 19.5%). After correcting these errors, 11 (29.7%) out of 37 pooled effect sizes changed by a magnitude of more than 0.1, ranging from 0.11 to 1.15. The updated meta-analyses showed that elevated levels of TNF- α, IL-6, CRP, but not IL-1β, are associated with depression.CONCLUSIONS: These findings show that data extraction errors in meta-analyses can impact findings. Efforts to reduce such errors are important in studies of the association between depression and peripheral inflammatory biomarkers, for which high heterogeneity and conflicting results have been continuously reported.
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| 17. |
- 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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| 18. |
- Park, Ju Ho, et al.
(författare)
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Anti-Inflammatory Effect of Titrated Extract of Centella asiatica in Phthalic Anhydride-Induced Allergic Dermatitis Animal Model.
- 2017
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 18:4
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Tidskriftsartikel (refereegranskat)abstract
- Centella asiatica has potent antioxidant and anti-inflammatory properties. However, its anti-dermatitic effect has not yet been reported. In this study, we investigated the anti-dermatitic effects of titrated extract of Centella asiatica (TECA) in a phthalic anhydride (PA)-induced atopic dermatitis (AD) animal model as well as in vitro model. An AD-like lesion was induced by the topical application of five percent PA to the dorsal skin or ear of Hos:HR-1 mouse. After AD induction, 100 μL of 0.2% and 0.4% of TECA (40 μg or 80 μg/cm²) was spread on the dorsum of the ear or back skin three times a week for four weeks. We evaluated dermatitis severity, histopathological changes and changes in protein expression by Western blotting for inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and NF-κB activity, which were determined by electromobility shift assay (EMSA). We also measured TNF-α, IL-1β, IL-6, and IgE concentration in the blood of AD mice by enzyme-linked immunosorbent assay (ELISA). TECA treatment attenuated the development of PA-induced atopic dermatitis. Histological analysis showed that TECA inhibited hyperkeratosis, mast cells and infiltration of inflammatory cells. TECA treatment inhibited expression of iNOS and COX-2, and NF-κB activity as well as the release of TNF-α, IL-1β, IL-6, and IgE. In addition, TECA (1, 2, 5 μg/mL) potently inhibited Lipopolysaccharide (LPS) (1 μg/mL)-induced NO production, expression of iNOS and COX-2, and NF-κB DNA binding activities in RAW264.7 macrophage cells. Our data demonstrated that TECA could be a promising agent for AD by inhibition of NF-κB signaling.
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| 19. |
- Park, Ji-Won, et al.
(författare)
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Beetle Immunity
- 2010
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Ingår i: Advances in Experimental Medicine and Biology. - Boston, MA : Springer US. - 0065-2598 .- 2214-8019. ; 708, s. 163-180
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Tidskriftsartikel (refereegranskat)abstract
- Genetic studies have elegantly characterized the innate immune response in Drosophila melanogaster. However, these studies have a limited ability to reveal the biochemical mechanisms underlying the innate immune response. To investigate the biochemical basis of how insects recognize invading microbes and how these recognition signals activate the innate immune response, it is necessary to use insects, from which larger amounts of hemolymph can be extracted. Using the larvae from two species of beetle, Tenebrio molitor and Holotrichia diomphalia, we elucidated the mechanisms underlying pathogenic microbe recognition. In addition, we studied the mechanism of host defense molecule amplification. In particular, we identified several pattern recognition proteins, serine proteases, serpins and antimicrobial peptides and examined how these molecules affect innate immunity.
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| 20. |
- Park, M., et al.
(författare)
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Electrical and thermoelectric transport by variable range hopping in reduced graphene oxide
- 2017
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 111:17
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated the transport properties of single-layer reduced graphene oxides (rGOs). The rGOs were prepared by the bubble deposition method followed by thermal reduction. The crossover of the transport mechanism from Efros-Shklovskii (ES) variable range hopping (VRH) between the localized states to Mott-VRH was observed near 70K using the temperature-dependent conductance. The ES-VRH conduction below 70K is apparent in the electric field dependence of the field-driven hopping transport in the high-electric field regime. We also figure out that the thermoelectric power is consistent with the 2D Mott VRH above 70K. We argue that the VRH conduction results from the topological disorders of rGO as confirmed by Raman spectroscopy. This infers that the average distance between defects is approximately 2.0 nm.
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| 21. |
- Shim, Kyu Hwan, et al.
(författare)
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Subsequent correlated changes in complement component 3 and amyloid beta oligomers in the blood of patients with Alzheimer's disease
- 2024
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Ingår i: ALZHEIMERS & DEMENTIA. - 1552-5260 .- 1552-5279.
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTIONAlzheimer's disease (AD) involves the complement cascade, with complement component 3 (C3) playing a key role. However, the relationship between C3 and amyloid beta (A beta) in blood is limited.METHODSPlasma C3 and A beta oligomerization tendency (A beta Ot) were measured in 35 AD patients and 62 healthy controls. Correlations with cerebrospinal fluid (CSF) biomarkers, cognitive impairment, and amyloid positron emission tomography (PET) were analyzed. Differences between biomarkers were compared in groups classified by concordances of biomarkers.RESULTSPlasma C3 and A beta Ot were elevated in AD patients and in CSF or amyloid PET-positive groups. Weak positive correlation was found between C3 and A beta Ot, while both had strong negative correlations with CSF A beta 42 and cognitive performance. Abnormalities were observed for A beta Ot and CSF A beta 42 followed by C3 changes.DISCUSSIONIncreased plasma C3 in AD are associated with amyloid pathology, possibly reflecting a defense response for A beta clearance. Further studies on A beta-binding proteins will enhance understanding of A beta mechanisms in blood.
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| 22. |
- Son, Ora, et al.
(författare)
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ATHB12, an ABA-Inducible Homeodomain-Leucine Zipper (HD-Zip) Protein of Arabidopsis, Negatively Regulates the Growth of the Inflorescence Stem by Decreasing the Expression of a Gibberellin 20-Oxidase Gene
- 2010
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Ingår i: Plant and Cell Physiology. - : Oxford University Press (OUP). - 0032-0781 .- 1471-9053. ; 51:9, s. 1537-1547
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Tidskriftsartikel (refereegranskat)abstract
- Arabidopsis thaliana homeobox 12 (ATHB12) is rapidly induced by ABA and water stress. A T-DNA insertion mutant of ATHB12 with a reduced level of ATHB12 expression in stems had longer inflorescence stems and reduced sensitivity to ABA during germination. A high level of transcripts of gibberellin 20-oxidase 1 (GA20ox1), a key enzyme in the synthesis of gibberellins, was detected in athb12 stems, while transgenic lines overexpressing ATHB12 (A12OX) had a reduced level of GA20ox1 in stems. Consistent with these data, ABA treatment of wild-type plants resulted in decreased GA20ox1 expression whereas ABA treatment of the athb12 mutant gave rise to slightly decreased GA20ox1 expression. Retarded stem growth in 3-week-old A12OX plants was rescued by exogenous GA(9), but not by GA(12), and less GA(9) was detected in A12OX stems than in wild-type stems. These data imply that ATHB12 decreases GA20ox1 expression in stems. On the other hand, the stems of A12OX plants grew rapidly after the first 3 weeks, so that they were almost as high as wild-type plants at about 5 weeks after germination. We also found changes in the stems of transgenic plants overexpressing ATHB12, such as alterations of expression GA20ox and GA3ox genes, and of GA(4) levels, which appear to result from feedback regulation. Repression of GA20ox1 by ATHB12 was confirmed by transfection of leaf protoplasts. ABA-treated protoplasts also showed increased ATHB12 expression and reduced GA20ox1 expression. These findings all suggest that ATHB12 negatively regulates the expression of a GA 20-oxidase gene in inflorescence stems.
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| 23. |
- Srinivas, Vivek, et al.
(författare)
-
High-Resolution XFEL Structure of the Soluble Methane Monooxygenase Hydroxylase Complex with its Regulatory Component at Ambient Temperature in Two Oxidation States
- 2020
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 142:33, s. 14249-14266
-
Tidskriftsartikel (refereegranskat)abstract
- Soluble methane monooxygenase (sMMO)is a multicomponent metalloenzyme that catalyzes the conversion of methane to methanol at ambient temperature using a nonheme, oxygen-bridged dinuclear iron cluster in the active site. Structural changes in the hydroxylase component (sMMOH) containing the diiron cluster caused by complex formation with a regulatory component (MMOB) and by iron reduction are important for the regulation of O-2 activation and substrate hydroxylation. Structural studies of metalloenzymes using traditional synchrotron-based X-ray crystallography are often complicated by partial X-ray-induced photoreduction of the metal center, thereby obviating determination of the structure of the enzyme in pure oxidation states. Here, microcrystals of the sMMOH:MMOB complex from Methylosinus trichosporium OB3b were serially exposed to X-ray free electron laser (XFEL) pulses, where the <= 35 fs duration of exposure of an individual crystal yields diffraction data before photoreduction-induced structural changes can manifest. Merging diffraction patterns obtained from thousands of crystals generates radiation damage-free, 1.95 angstrom resolution crystal structures for the fully oxidized and fully reduced states of the sMMOH:MMOB complex for the first time. The results provide new insight into the manner by which the diiron cluster and the active site environment are reorganized by the regulatory protein component in order to enhance the steps of oxygen activation and methane oxidation. This study also emphasizes the value of XFEL and serial femtosecond crystallography (SFX) methods for investigating the structures of metalloenzymes with radiation sensitive metal active sites.
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| 24. |
- Yager, Thomas, 1987, et al.
(författare)
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Low contact resistance in epitaxial graphene devices for quantum metrology
- 2015
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Ingår i: AIP Advances. - : AIP Publishing. - 2158-3226 .- 2158-3226. ; 5:8, s. 087134-
-
Tidskriftsartikel (refereegranskat)abstract
- We investigate Ti/Au contacts to monolayer epitaxial graphene on SiC (0001) for applications in quantum resistance metrology. Using three-terminal measurements in the quantum Hall regime we observed variations in contact resistances ranging from a minimal value of 0.6 Ω up to 11 kΩ. We identify a major source of high-resistance contacts to be due bilayer graphene interruptions to the quantum Hall current, whilst discarding the effects of interface cleanliness and contact geometry for our fabricated devices. Moreover, we experimentally demonstrate methods to improve the reproducibility of low resistance contacts (
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| 25. |
- Ahmadi, Fereshteh, 1958-, et al.
(författare)
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Exploring Existential Coping Resources : The Perspective of Koreans with Cancer
- 2016
-
Ingår i: Journal of religion and health. - New York : Springer-Verlag New York. - 0022-4197 .- 1573-6571. ; 55:6, s. 2053-2068
-
Tidskriftsartikel (refereegranskat)abstract
- The present study aimed to explore the use of meaning-making coping (existential, spiritual, and religious coping) among cancer patients in Korea and to investigate the impact of culture on their choice of coping methods. Thirty-three participants with various kinds of cancer were interviewed. Four different kinds of coping resources emerged from analyses of the interview transcripts: (1) belief in the healing power of nature; (2) mind–body connection; (3) relying on transcendent power; and (4) finding oneself in relationships with others. The findings of this study suggest the importance of investigating cultural context when exploring the use of the meaning-making coping strategies in different countries.
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| 26. |
- Ahmadi, Fereshteh, 1958-, et al.
(författare)
-
Meaning-making coping among cancer patients in Sweden and South Korea : a comparative perspective
- 2017
-
Ingår i: Journal of religion and health. - : Springer Science and Business Media LLC. - 0022-4197 .- 1573-6571. ; 56:5, s. 1794-1811
-
Tidskriftsartikel (refereegranskat)abstract
- The present study compared meaning-making coping among cancer patients in Sweden and South Korea, with a focus on the sociocultural context. Semi-structured interviews were conducted with 51 Swedes and 33 Koreans. The results showed significant differences between the two countries as well as similarities in existential, spiritual, and religious coping. For example, Swedes primarily used meaning-making coping as a means of meditation or relaxation, whereas Koreans relied on coping with prayer and using healthy foods as a means to survive. The present study confirms the significance of investigating cultural context when we explore the use of meaning-making coping among people who have experienced cancer.
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| 27. |
- Ahn, Chi Woo, et al.
(författare)
-
Direct Observation of a Transiently Formed Isomer During lodoform Photolysis in Solution by Time-Resolved X-ray Liquidography
- 2018
-
Ingår i: The Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 9:3, s. 647-653
-
Tidskriftsartikel (refereegranskat)abstract
- Photolysis of iodoform (CHI3) in solution has been extensively studied, but its reaction mechanism remains elusive. In particular, iso-iodoform (iso-CHI2-I) is formed as a product of the photolysis reaction, but its detailed structure is not known, and whether it is a major intermediate species has been controversial. Here, by using time-resolved X-ray liquidography, we determined the reaction mechanism of CHI3 photodissociation in cyclohexane as well as the structure of iso-CHI2-I. Both iso-CHI2-I and CHI2 radical were found to be formed within 100 ps with a branching ratio of 40:60. Iodine radicals (I), formed during the course of CHI3 photolysis, recombine nongeminately with either CHI2 or I. Based on our structural analysis, the I-I distance and the C-I-I angle of iso-CHI2-I were determined to be 2.922 +/- 0.004 angstrom and 133.9 +/- 0.8 degrees, respectively.
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| 28. |
- Amann-Winkel, Katrin, et al.
(författare)
-
Liquid-liquid phase separation in supercooled water from ultrafast heating of low-density amorphous ice
- 2023
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Recent experiments continue to find evidence for a liquid-liquid phase transition (LLPT) in supercooled water, which would unify our understanding of the anomalous properties of liquid water and amorphous ice. These experiments are challenging because the proposed LLPT occurs under extreme metastable conditions where the liquid freezes to a crystal on a very short time scale. Here, we analyze models for the LLPT to show that coexistence of distinct high-density and low-density liquid phases may be observed by subjecting low-density amorphous (LDA) ice to ultrafast heating. We then describe experiments in which we heat LDA ice to near the predicted critical point of the LLPT by an ultrafast infrared laser pulse, following which we measure the structure factor using femtosecond x-ray laser pulses. Consistent with our predictions, we observe a LLPT occurring on a time scale < 100 ns and widely separated from ice formation, which begins at times >1 mu s. Obtaining experimental evidence of a liquid-liquid phase transition in supercooled water is challenging due to the rapid crystallization. Here the authors drive low-density amorphous ice to the conditions of liquid-liquid coexistence using ultrafast laser heating and observe the liquid-liquid phase transition with femtosecond x-ray laser pulses.
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| 29. |
- Ammenwerth, Elske, et al.
(författare)
-
International Comparison of Six Basic eHealth Indicators Across 14 Countries: An eHealth Benchmarking Study
- 2020
-
Ingår i: Methods of Information in Medicine. - : Georg Thieme Verlag KG. - 0026-1270 .- 2511-705X. ; 59:S2, s. e46-e63
-
Tidskriftsartikel (refereegranskat)abstract
- Background Many countries adopt eHealth applications to support patient-centered care. Through information exchange, these eHealth applications may overcome institutional data silos and support holistic and ubiquitous (regional or national) information logistics. Available eHealth indicators mostly describe usage and acceptance of eHealth in a country. The eHealth indicators focusing on the cross-institutional availability of patient-related information for health care professionals, patients, and care givers are rare. Objectives This study aims to present eHealth indicators on cross-institutional availability of relevant patient data for health care professionals, as well as for patients and their caregivers across 14 countries (Argentina, Australia, Austria, Finland, Germany, Hong Kong as a special administrative region of China, Israel, Japan, Jordan, Kenya, South Korea, Sweden, Turkey, and the United States) to compare our indicators and the resulting data for the examined countries with other eHealth benchmarks and to extend and explore changes to a comparable survey in 2017. We defined "availability of patient data" as the ability to access data in and to add data to the patient record in the respective country. Methods The invited experts from each of the 14 countries provided the indicator data for their country to reflect the situation on August 1, 2019, as date of reference. Overall, 60 items were aggregated to six eHealth indicators. Results Availability of patient-related information varies strongly by country. Health care professionals can access patients most relevant cross-institutional health record data fully in only four countries. Patients and their caregivers can access their health record data fully in only two countries. Patients are able to fully add relevant data only in one country. Finland showed the best outcome of all eHealth indicators, followed by South Korea, Japan, and Sweden. Conclusion Advancement in eHealth depends on contextual factors such as health care organization, national health politics, privacy laws, and health care financing. Improvements in eHealth indicators are thus often slow. However, our survey shows that some countries were able to improve on at least some indicators between 2017 and 2019. We anticipate further improvements in the future.
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| 30. |
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| 31. |
- Blattner, Mirjam, et al.
(författare)
-
SPOP Mutations in Prostate Cancer across Demographically Diverse Patient Cohorts
- 2014
-
Ingår i: Neoplasia. - New York : Elsevier. - 1522-8002 .- 1476-5586. ; 16:1, s. 14-U34
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recurrent mutations in the Speckle-Type POZ Protein (SPOP) gene occur in up to 15% of prostate cancers. However, the frequency and features of cancers with these mutations across different populations is unknown.OBJECTIVE: To investigate SPOP mutations across diverse cohorts and validate a series of assays employing high-resolution melting (HRM) analysis and Sanger sequencing for mutational analysis of formalin-fixed paraffin-embedded material.DESIGN, SETTING, AND PARTICIPANTS: 720 prostate cancer samples from six international cohorts spanning Caucasian, African American, and Asian patients, including both prostate-specific antigen-screened and unscreened populations, were screened for their SPOP mutation status. Status of SPOP was correlated to molecular features (ERG rearrangement, PTEN deletion, and CHD1 deletion) as well as clinical and pathologic features.RESULTS AND LIMITATIONS: Overall frequency of SPOP mutations was 8.1% (4.6% to 14.4%), SPOP mutation was inversely associated with ERG rearrangement (P < .01), and SPOP mutant (SPOPmut) cancers had higher rates of CHD1 deletions (P < .01). There were no significant differences in biochemical recurrence in SPOPmut cancers. Limitations of this study include missing mutational data due to sample quality and lack of power to identify a difference in clinical outcomes.CONCLUSION: SPOP is mutated in 4.6% to 14.4% of patients with prostate cancer across different ethnic and demographic backgrounds. There was no significant association between SPOP mutations with ethnicity, clinical, or pathologic parameters. Mutual exclusivity of SPOP mutation with ERG rearrangement as well as a high association with CHD1 deletion reinforces SPOP mutation as defining a distinct molecular subclass of prostate cancer.
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| 32. |
- Cho, Nam-Hyuk, et al.
(författare)
-
The Orientia tsutsugamushi genome reveals massive proliferation of conjugative type IV secretion system and host–cell interaction genes
- 2007
-
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. ; 104:19, s. 7981-7986
-
Tidskriftsartikel (refereegranskat)abstract
- Scrub typhus is caused by the obligate intracellular rickettsia Orientia tsutsugamushi (previously called Rickettsia tsutsugamushi). The bacterium is maternally inherited in trombicuid mites and transmitted to humans by feeding larvae. We report here the 2,127,051-bp genome of the Boryong strain, which represents the most highly repeated bacterial genome sequenced to date. The repeat density of the scrub typhus pathogen is 200-fold higher than that of its close relative Rickettsia prowazekii, the agent of epidemic typhus. A total of 359 tra genes for components of conjugative type IV secretion systems were identified at 79 sites in the genome. Associated with these are >200 genes for signaling and host–cell interaction proteins, such as histidine kinases, ankyrin-repeat proteins, and tetratrico peptide-repeat proteins. Additionally, the O. tsutsugamushi genome contains >400 transposases, 60 phage integrases, and 70 reverse transcriptases. Deletions and rearrangements have yielded unique gene combinations as well as frequent pseudogenization in the tra clusters. A comparative analysis of the tra clusters within the genome and across strains indicates sequence homogenization by gene conversion, whereas complexity, diversity, and pseudogenization are acquired by duplications, deletions, and transposon integrations into the amplified segments. The results suggest intragenomic duplications or multiple integrations of a massively proliferating conjugative transfer system. Diversifying selection on host–cell interaction genes along with repeated population bottlenecks may drive rare genome variants to fixation, thereby short-circuiting selection for low complexity in bacterial genomes.
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| 33. |
- Choi, Sungchul, et al.
(författare)
-
Global burden of primary liver cancer and its asso- ciation with underlying aetiologies, sociodemo- graphic status, and sex differences from 1990-2019: A DALY-based analysis of the Global Burden of Disease 2019 study
- 2023
-
Ingår i: Clinical and Molecular Hepatology. - : KOREAN ASSOC STUDY LIVER. - 2287-2728 .- 2287-285X. ; 29:2, s. 433-452
-
Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Global distribution of dominant liver cancer aetiologies has significantly changed over the past decades. This study analyzed the updated temporal trends of liver cancer aetiologies and sociodemographic status in 204 countries and territories from 1990 to 2019.Methods: The Global Burden of Disease 2019 report was used for statistical analysis. In addition, we performed stratification analysis to five quintiles using sociodemographic index and 21 geographic regions.Results: The crude numbers of liver cancer disease-adjusted life years (DALYs) and deaths significantly increased during the study period (DALYs; 11,278,630 in 1990 and 12,528,422 in 2019, deaths; 365,215 in 1990 and 484,577 in 2019). However, the Age-standardized DALY and mortality rates decreased. Hepatitis B virus (HBV) remains the leading cause of liver cancer DALYs and mortality, followed by hepatitis C virus (HCV), alcohol consumption, and non-alcoholic steatohepatitis/non-alcoholic fatty liver disease (NASH/NAFLD). Although Age-standardized DALY and mortality rates of liver cancer due to HBV and HCV have decreased, the rates due to alcohol consumption and NASH/NAFLD have increased. In 2019, the population of the East Asia region had the highest Age-standardized DALY and mortality rates, followed by high-income Asia-Pacific and Central Asia populations. Although East Asia and high-income Asia-Pacific regions showed a decrease during the study period, Age-standardized DALY rates increased in Central Asia. High-income North American and Australasian populations also showed a significant increase in Age-standardized DALY.Conclusions: Liver cancer remains an ongoing global threat. The burden of liver cancer associated with alcohol consumption and NASH/NAFLD is markedly increasing and projected to continuously increase. (Clin Mol Hepatol 2023;29:433-452)
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| 34. |
- Ha, Hojin, et al.
(författare)
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In-vitro and In-Vivo Assessment of 4D Flow MRI Reynolds Stress Mapping for Pulsatile Blood Flow
- 2021
-
Ingår i: Frontiers in Bioengineering and Biotechnology. - : Frontiers Media S.A.. - 2296-4185. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Imaging hemodynamics play an important role in the diagnosis of abnormal blood flow due to vascular and valvular diseases as well as in monitoring the recovery of normal blood flow after surgical or interventional treatment. Recently, characterization of turbulent blood flow using 4D flow magnetic resonance imaging (MRI) has been demonstrated by utilizing the changes in signal magnitude depending on intravoxel spin distribution. The imaging sequence was extended with a six-directional icosahedral (ICOSA6) flow-encoding to characterize all elements of the Reynolds stress tensor (RST) in turbulent blood flow. In the present study, we aimed to demonstrate the feasibility of full RST analysis using ICOSA6 4D flow MRI under physiological conditions. First, the turbulence analysis was performed through in vitro experiments with a physiological pulsatile flow condition. Second, a total of 12 normal subjects and one patient with severe aortic stenosis were analyzed using the same sequence. The in-vitro study showed that total turbulent kinetic energy (TKE) was less affected by the signal-to-noise ratio (SNR), however, maximum principal turbulence shear stress (MPTSS) and total turbulence production (TP) had a noise-induced bias. Smaller degree of the bias was observed for TP compared to MPTSS. In-vivo study showed that the subject-variability on turbulence quantification was relatively low for the consistent scan protocol. The in vivo demonstration of the stenosis patient showed that the turbulence analysis could clearly distinguish the difference in all turbulence parameters as they were at least an order of magnitude larger than those from the normal subjects.
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| 35. |
- Ha, Hojin, et al.
(författare)
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In vitro experiments on ICOSA6 4D flow MRI measurement for the quantification of velocity and turbulence parameters
- 2020
-
Ingår i: Magnetic Resonance Imaging. - : ELSEVIER SCIENCE INC. - 0730-725X .- 1873-5894. ; 72, s. 49-60
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To perform comprehensive in vitro experiments using six-directional icosahedral flow encoding (ICOSA6) 4D flow magnetic resonance imaging (MRI) under various scan conditions to analyze the robustness of velocity and turbulence quantification. Materials and methods: In vitro flow phantoms with steady flow rates of 10 and 20 L/min were scanned using both conventional 4D flow MRI and ICOSA6. Experiments focused on comparisons between ICOSA6 and conventional four point (4P) methods, and the effects of contrast agents, velocity encoding range (Venc), and scan direction on velocity and turbulence quantification. Results: The results demonstrated that 1) ICOSA6 improves the velocity-to-noise ratio (VNR) of velocity estimation by 33% (on average) and results in similar turbulent kinetic energy (TKE) estimation as the 4P method. 2) Measurements with a contrast agent resulted in more than a 2.5 fold increase in average VNR. However, the improvement of total TKE quantification was not obvious. 3) TKE estimation was less affected by Venc and the scan direction, whereas turbulence production (TP) estimation was largely affected by these measurement conditions. The effects of Venc and scan direction accounted for less than 11.63% of TKE estimation, but up to 33.89% of TP estimation. Conclusion: The ICOSA6 scheme is compatible with conventional 4D flow MRI for velocity and TKE measurement. Contrast agents are effective at increasing VNR, but not signal-to-noise ratio for TKE quantification. The effects of Venc and scan direction influence total TP more than total TKE.
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| 36. |
- Hamdi, Yosr, et al.
(författare)
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Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : identification of a modifier of breast cancer risk at locus 11q22.3
- 2017
-
Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 161:1, s. 117-134
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Methods: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. Results: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10−6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. Conclusion: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.
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| 37. |
- He, Hans, et al.
(författare)
-
Polymer-encapsulated molecular doped epigraphene for quantum resistance metrology
- 2019
-
Ingår i: Metrologia. - : Institute of Physics Publishing. - 0026-1394 .- 1681-7575. ; 56:4
-
Tidskriftsartikel (refereegranskat)abstract
- One of the aspirations of quantum metrology is to deliver primary standards directly to end-users thereby significantly shortening the traceability chains and enabling more accurate products. Epitaxial graphene grown on silicon carbide (epigraphene) is known to be a viable candidate for a primary realisation of a quantum Hall resistance standard, surpassing conventional semiconductor two-dimensional electron gases, such as those based on GaAs, in terms of performance at higher temperatures and lower magnetic fields. The bottleneck in the realisation of a turn-key quantum resistance standard requiring minimum user intervention has so far been the need to fine-tune the carrier density in this material to fit the constraints imposed by a simple cryo-magnetic system. Previously demonstrated methods, such as via photo-chemistry or corona discharge, require application prior to every cool-down as well as specialist knowledge and equipment. To this end we perform metrological evaluation of epigraphene with carrier density tuned by a recently reported permanent molecular doping technique. Measurements at two National Metrology Institutes confirm accurate resistance quantisation below 5n-1. Furthermore, samples show no significant drift in carrier concentration and performance on multiple thermal cycles over three years. This development paves the way for dissemination of primary resistance standards based on epigraphene
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| 38. |
- He, Hans, et al.
(författare)
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Stable and Tunable Charge Carrier Control of Graphene for Quantum Resistance Metrology
- 2018
-
Ingår i: 2018 Conference on Precision Electromagnetic Measurements (CPEM 2018). - : IEEE. - 9781538609736 - 9781538609743
-
Konferensbidrag (refereegranskat)abstract
- Here we demonstrate a stable and tunable method to alter the carrier concentration of epitaxial graphene grown on silicon carbide. This technique relies on chemical doping by an acceptor molecule. Through careful tuning one can produce chemically doped graphene quantum resistance devices which show long-term stability in ambient conditions and have performance comparable to that of GaAs quantum resistance standards. This development paves the way for controlled device fabrication of graphene quantum hall resistance standards, which can be reliably tailored to operate below 5 T and above 4 K out-of-the-box, without further adjustments from the end-user.
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| 39. |
- Jang, Kyung-Jin, et al.
(författare)
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Reproducing human and cross-species drug toxicities using a Liver-Chip
- 2019
-
Ingår i: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 11:517
-
Tidskriftsartikel (refereegranskat)abstract
- Nonclinical rodent and nonrodent toxicity models used to support clinical trials of candidate drugs may produce discordant results or fail to predict complications in humans, contributing to drug failures in the clinic. Here, we applied microengineered Organs-on-Chips technology to design a rat, dog, and human Liver-Chip containing species-specific primary hepatocytes interfaced with liver sinusoidal endothelial cells, with or without Kupffer cells and hepatic stellate cells, cultured under physiological fluid flow. The Liver-Chip detected diverse phenotypes of liver toxicity, including hepatocellular injury, steatosis, cholestasis, and fibrosis, and species-specific toxicities when treated with tool compounds. A multispecies Liver-Chip may provide a useful platform for prediction of liver toxicity and inform human relevance of liver toxicities detected in animal studies to better determine safety and human risk.
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| 40. |
- Kim, Chan-Hee, et al.
(författare)
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A three-step proteolytic cascade mediates the activation of the peptidoglycan-induced toll pathway in an insect
- 2008
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 283:12, s. 7599-7607
-
Tidskriftsartikel (refereegranskat)abstract
- The recognition of lysine-type peptidoglycans (PG) by the PG recognition complex has been suggested to cause activation of the serine protease cascade leading to the processing of Spätzle and subsequent activation of the Toll signaling pathway. So far, two serine proteases involved in the lysine-type PG Toll signaling pathway have been identified. One is a modular serine protease functioning as an initial enzyme to be recruited into the lysine-type PG recognition complex. The other is the Drosophila Spätzle processing enzyme (SPE), a terminal enzyme that converts Spätzle pro-protein to its processed form capable of binding to the Toll receptor. However, it remains unclear how the initial PG recognition signal is transferred to Spätzle resulting in Toll pathway activation. Also, the biochemical characteristics and mechanism of action of a serine protease linking the modular serine protease and SPE have not been investigated. Here, we purified and cloned a novel upstream serine protease of SPE that we named SAE, SPE-activating enzyme, from the hemolymph of a large beetle, Tenebrio molitor larvae. This enzyme was activated by Tenebrio modular serine protease and in turn activated the Tenebrio SPE. The biochemical ordered functions of these three serine proteases were determined in vitro, suggesting that the activation of a three-step proteolytic cascade is necessary and sufficient for lysine-type PG recognition signaling. The processed Spätzle by this cascade induced antibacterial activity in vivo. These results demonstrate that the three-step proteolytic cascade linking the PG recognition complex and Spätzle processing is essential for the PG-dependent Toll signaling pathway.
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| 41. |
- Kim, Dohwan, et al.
(författare)
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Sampling Rate Optimization for IEEE 802.11 Wireless Control Systems
- 2019
-
Ingår i: ICCPS '19. - New York, NY, USA : ASSOC COMPUTING MACHINERY. - 9781450362856 ; , s. 87-96
-
Konferensbidrag (refereegranskat)abstract
- Design of wireless control systems has been extensively studied, which is one of the fundamental issues in cyber-physical systems. In this paper, we empirically investigate heterogeneous sampling rate assignment with a testbed when multiple physical systems are controlled through an IEEE 802.11 network. Among the critical design variables in wireless control systems, we focus on the sampling rates because they are always key control knobs regardless of network protocols. There has been little experimental research on heterogeneous sampling rate optimization for IEEE 802.11 wireless control systems, where the sampling rates of each control loop may have different values. We first formulate the co-design problem in an optimization framework with respect to the heterogeneous sampling rates by explicitly taking into account the relations of the sampling rates with the control cost, network energy consumption, and network delay. We further relax the problem as convex optimization, which is provably solved in polynomial time. Our empirical study ensures that the approximate solution is tightly close to the original optimum. To validate the proposed optimization framework, we build a disk-levitation tube testbed, which wirelessly controls the height of 20 disks at the same time. Our empirical study confirms that our optimization formulation is highly effective in practice.
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| 42. |
- Kim, Kyung Ho, 1984, et al.
(författare)
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Ambipolar charge transport in quasi-free-standing monolayer graphene on SiC obtained by gold intercalation
- 2020
-
Ingår i: Physical Review B. - : American Physical Society. - 2469-9950 .- 2469-9969. ; 102:16
-
Tidskriftsartikel (refereegranskat)abstract
- We present a study of quasi-free-standing monolayer graphene obtained by intercalation of Au atoms at the interface between the carbon buffer layer (Bu-L) and the silicon-terminated face (0001) of 4H-silicon carbide. Au intercalation is achieved by deposition of an atomically thin Au layer on the Bu-L followed by annealing at 850 °C in an argon atmosphere. We explore the intercalation of Au and decoupling of the Bu-L into quasi-free-standing monolayer graphene by surface science characterization and electron transport in top-gated electronic devices. By gate-dependent magnetotransport we find that the Au-intercalated buffer layer displays all properties of monolayer graphene, namely gate-tunable ambipolar transport across the Dirac point, but we find no observable enhancement of spin-orbit effects in the graphene layer, despite its proximity to the intercalated Au layer.
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| 43. |
- Kim, Kyung Hwan, et al.
(författare)
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Experimental observation of the liquid-liquid transition in bulk supercooled water under pressure
- 2020
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 370:6519, s. 978-982
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Tidskriftsartikel (refereegranskat)abstract
- We prepared bulk samples of supercooled liquid water under pressure by isochoric heating of high-density amorphous ice to temperatures of 205 ± 10 kelvin, using an infrared femtosecond laser. Because the sample density is preserved during the ultrafast heating, we could estimate an initial internal pressure of 2.5 to 3.5 kilobar in the high-density liquid phase. After heating, the sample expanded rapidly, and we captured the resulting decompression process with femtosecond x-ray laser pulses at different pump-probe delay times. A discontinuous structural change occurred in which low-density liquid domains appeared and grew on time scales between 20 nanoseconds to 3 microseconds, whereas crystallization occurs on time scales of 3 to 50 microseconds. The dynamics of the two processes being separated by more than one order of magnitude provides support for a liquid-liquid transition in bulk supercooled water.
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| 44. |
- Kim, Kyung Hwan, et al.
(författare)
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Maxima in the thermodynamic response and correlation functions of deeply supercooled water
- 2017
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 358:6370, s. 1589-1593
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Tidskriftsartikel (refereegranskat)abstract
- Femtosecond x-ray laser pulses were used to probe micrometer-sized water droplets that were cooled down to 227 kelvin in vacuum. Isothermal compressibility and correlation length were extracted from x-ray scattering at the low-momentum transfer region. The temperature dependence of these thermodynamic response and correlation functions shows maxima at 229 kelvin for water and 233 kelvin for heavy water. In addition, we observed that the liquids undergo the fastest growth of tetrahedral structures at similar temperatures. These observations point to the existence of a Widom line, defined as the locus of maximum correlation length emanating from a critical point at positive pressures in the deeply supercooled regime. The difference in the maximum value of the isothermal compressibility between the two isotopes shows the importance of nuclear quantum effects.
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| 45. |
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| 46. |
- Kim, Se-Hoon, et al.
(författare)
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Nanophase oxalate precursors of thermoelectric CoSb3 by controlled coprecipitation predicted by thermodynamic modeling
- 2016
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Ingår i: Advanced Powder Technology. - : Elsevier. - 0921-8831 .- 1568-5527. ; 27:2, s. 773-778
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Tidskriftsartikel (refereegranskat)abstract
- The precursors for the formation of thermoelectric skutterudite CoSb3 nanoparticles are predicted by thermodynamic modeling of the complex chemical species. Based on the results, equimolar mixture of CoC2O4 center dot 2H(2)O and Sb(C2O4) OH are successively co-precipitated under controlled conditions of pH = 2.7 and concentration of reactants. The as synthesized powder was decomposed at 350 degrees C to remove the organic molecules and further reduced to CoSb3 phase by heating at 530 degrees C under hydrogen flow. The obtained powder was consolidated by spark plasma sintering (SPS). CoSb3 prepared by controlled chemical co-precipitation has p-type behavior with a positive sign of the Seebeck coefficient. TE transport properties were measured, which revealed that the Seebeck coefficient increased 2.5 times with increasing the temperature and it is lower than the ball milled CoSb3. Thermal conductivity of sintered CoSb3 at 773 K starts from 0.06 W/cm K at room temperature and decreases to 0.04 W/cm K at 700 K, which is lower than the bulk counterpart. The ZT of coprecipitated CoSb3 and SPS consolidated at 773 K shows 2 times higher than the ball milled one. (C) 2016 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.
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| 47. |
- Kim, Seok Jun, et al.
(författare)
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Crosstalk between WNT and STAT3 is mediated by galectin-3 in tumor progression
- 2021
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Ingår i: Gastric Cancer. - : Springer Science and Business Media LLC. - 1436-3291 .- 1436-3305. ; 24:5, s. 1050-1062
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Tidskriftsartikel (refereegranskat)abstract
- Background: Aberrant activation of the WNT/β-catenin and STAT3 signaling pathways plays a critical role in cancer progression. However, direct targeting of these pathways as an anti-cancer therapeutic approach needs to be reconsidered due to its serious side effects. Here, we demonstrate that overexpression of WNT induces STAT3 activation in a galectin-3-dependent manner. Methods: We investigated how galectin-3 mediates the crosstalk between WNT/β-catenin and STAT3 signaling and whether inhibition of galectin-3 can reduce gastric cancer. The molecular mechanisms were analyzed by biochemical assays using cultured gastric cancer cells, patient tissues, and genetically engineered mice. Moreover, we confirm of therapeutic effects of GB1107, a cell-penetrating galectin-3 specific inhibitor, using orthotopic gastric cancer-bearing mice Results: Increased levels of galectin-3 and STAT3 phosphorylation were detected in the stomach tissues of WNT1-overexpressing mouse models. Also, high expression levels and co-localization of β-catenin, pSTAT3, and galectin-3 in patients with advanced gastric cancer were correlated with a poorer prognosis. Galectin-3 depletion significantly decreased STAT3 Tyr705 phosphorylation, which regulates its nuclear localization and transcriptional activation. A peptide of galectin-3 (Y45-Q48) directly bound to the STAT3 SH2 domain and enhanced its phosphorylation. GB1107, a specific membrane-penetrating inhibitor of galectin-3, significantly reduced the activation of both STAT3 and β-catenin and inhibited tumor growth in orthotopic gastric cancer-bearing mice. Conclusions: We propose that galectin-3 mediates the crosstalk between the WNT and STAT3 signaling pathways. Therefore GB1107, a galectin-3-specific inhibitor, maybe a potent agent with anti-gastric cancer activity. Further studies are needed for its clinical application in gastric cancer therapy.
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| 48. |
- Ladd-Parada, Marjorie, et al.
(författare)
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Following the Crystallization of Amorphous Ice after Ultrafast Laser Heating
- 2022
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 126:11, s. 2299-2307
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Tidskriftsartikel (refereegranskat)abstract
- Using time-resolved wide-angle X-ray scattering, we investigated the early stages (10 μs–1 ms) of crystallization of supercooled water, obtained by the ultrafast heating of high- and low-density amorphous ice (HDA and LDA) up to a temperature T = 205 K ± 10 K. We have determined that the crystallizing phase is stacking disordered ice (Isd), with a maximum cubicity of χ = 0.6, in agreement with predictions from molecular dynamics simulations at similar temperatures. However, we note that a growing small portion of hexagonal ice (Ih) was also observed, suggesting that within our timeframe, Isd starts annealing into Ih. The onset of crystallization, in both amorphous ice, occurs at a similar temperature, but the observed final crystalline fraction in the LDA sample is considerably lower than that in the HDA sample. We attribute this discrepancy to the thickness difference between the two samples.
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| 49. |
- Ladd-Parada, Marjorie, 1985-, et al.
(författare)
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Following the Crystallization of Amorphous Ice after Ultrafast Laser Heating
- 2022
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 126:11, s. 2299-2307
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Tidskriftsartikel (refereegranskat)abstract
- Using time-resolved wide-angle X-ray scattering, we investigated the early stages (10 μs–1 ms) of crystallization of supercooled water, obtained by the ultrafast heating of high- and low-density amorphous ice (HDA and LDA) up to a temperature T = 205 K ± 10 K. We have determined that the crystallizing phase is stacking disordered ice (Isd), with a maximum cubicity of χ = 0.6, in agreement with predictions from molecular dynamics simulations at similar temperatures. However, we note that a growing small portion of hexagonal ice (Ih) was also observed, suggesting that within our timeframe, Isd starts annealing into Ih. The onset of crystallization, in both amorphous ice, occurs at a similar temperature, but the observed final crystalline fraction in the LDA sample is considerably lower than that in the HDA sample. We attribute this discrepancy to the thickness difference between the two samples.
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| 50. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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