| 1. |
- Mattis, Katia K, et al.
(författare)
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Loss of RREB1 in pancreatic beta cells reduces cellular insulin content and affects endocrine cell gene expression
- 2023
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Ingår i: Diabetologia. - : Springer Nature. - 0012-186X .- 1432-0428. ; 66:4, s. 674-694
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Genome-wide studies have uncovered multiple independent signals at the RREB1 locus associated with altered type 2 diabetes risk and related glycaemic traits. However, little is known about the function of the zinc finger transcription factor Ras-responsive element binding protein 1 (RREB1) in glucose homeostasis or how changes in its expression and/or function influence diabetes risk.METHODS: A zebrafish model lacking rreb1a and rreb1b was used to study the effect of RREB1 loss in vivo. Using transcriptomic and cellular phenotyping of a human beta cell model (EndoC-βH1) and human induced pluripotent stem cell (hiPSC)-derived beta-like cells, we investigated how loss of RREB1 expression and activity affects pancreatic endocrine cell development and function. Ex vivo measurements of human islet function were performed in donor islets from carriers of RREB1 type 2 diabetes risk alleles.RESULTS: CRISPR/Cas9-mediated loss of rreb1a and rreb1b function in zebrafish supports an in vivo role for the transcription factor in beta cell mass, beta cell insulin expression and glucose levels. Loss of RREB1 also reduced insulin gene expression and cellular insulin content in EndoC-βH1 cells and impaired insulin secretion under prolonged stimulation. Transcriptomic analysis of RREB1 knockdown and knockout EndoC-βH1 cells supports RREB1 as a novel regulator of genes involved in insulin secretion. In vitro differentiation of RREB1KO/KO hiPSCs revealed dysregulation of pro-endocrine cell genes, including RFX family members, suggesting that RREB1 also regulates genes involved in endocrine cell development. Human donor islets from carriers of type 2 diabetes risk alleles in RREB1 have altered glucose-stimulated insulin secretion ex vivo, consistent with a role for RREB1 in regulating islet cell function.CONCLUSIONS/INTERPRETATION: Together, our results indicate that RREB1 regulates beta cell function by transcriptionally regulating the expression of genes involved in beta cell development and function.
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| 2. |
- Wang, YL, et al.
(författare)
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Biomedical research publication system
- 2004
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 303:5666, s. 1974-1976
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Bestas, Burcu, et al.
(författare)
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A Type II-B Cas9 nuclease with minimized off-targets and reduced chromosomal translocations in vivo
- 2023
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Ingår i: NATURE COMMUNICATIONS. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes Cas9 (SpCas9) and derived enzymes are widely used as genome editors, but their promiscuous nuclease activity often induces undesired mutations and chromosomal rearrangements. Several strategies for mapping off-target effects have emerged, but they suffer from limited sensitivity. To increase the detection sensitivity, we develop an off-target assessment workflow that uses Duplex Sequencing. The strategy increases sensitivity by one order of magnitude, identifying previously unknown SpCas9's off-target mutations in the humanized PCSK9 mouse model. To reduce off-target risks, we perform a bioinformatic search and identify a high-fidelity Cas9 variant of the II-B subfamily from Parasutterella secunda (PsCas9). PsCas9 shows improved specificity as compared to SpCas9 across multiple tested sites, both in vitro and in vivo, including the PCSK9 site. In the future, while PsCas9 will offer an alternative to SpCas9 for research and clinical use, the Duplex Sequencing workflow will enable a more sensitive assessment of Cas9 editing outcomes. SpCas9 unintended editing is a major concern. Here the authors report an off-target method using Duplex Sequencing with increased sensitivity for Cas9 mutation detection; they also identify a Cas9 variant of the II-B subfamily with intrinsic high fidelity (PsCas9) and see improved specificity.
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| 4. |
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| 5. |
- Dahlquist, Fanny, et al.
(författare)
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Junction barrier Schottky diodes in 4H-SiC and 6H-SiC
- 1998
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Ingår i: Materials Science Forum. - : Trans Tech Publications Inc.. - 0255-5476 .- 1662-9752. ; 264-268:PART 2, s. 1061-1064
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Tidskriftsartikel (refereegranskat)abstract
- The Junction Barrier Schottky (JBS) diode in silicon carbide is a promising candidate for a low-leakage power rectifier for high switching frequencies and elevated temperature operation. It has the advantage of a low forward voltage drop while keeping a low leakage current at high blocking voltage. JBS devices have been fabricated in 4H SiC and 6H SiC and then electrically characterised in comparison with pn and Schottky diodes on the same wafer. The JBS devices reached blocking voltages up to 1.0 kV at a leakage current density of 13 ÎŒA/cm2 and the forward conduction was limited by an on-resistance close to the theoretical value.
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| 6. |
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| 7. |
- Nordell, Nils, et al.
(författare)
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Boron implantation and epitaxial regrowth studies of 6H SiC
- 1998
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Ingår i: Journal of Electronic Materials. - : Springer Science and Business Media LLC. - 0361-5235 .- 1543-186X. ; 27:7, s. 833-837
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Tidskriftsartikel (refereegranskat)abstract
- Implantation of B has been performed into an epitaxially grown layer of 6H SiC, at two different B concentrations, 2 x 10(16) cm(-3) and 2 x 10(18) cm(-3). Subsequently, an epitaxial layer was regrown on the B implanted layer. The samples were investigated by transmission electron microscopy (TEM) and secondary ion mass spectrometry (SIMS). In the highly B-doped layers plate-like defects were found, associated with large strain fields, and an increased B concentration. These defects were stable at the originally implanted region during regrowth and at anneal temperatures up to 1700 degrees C. In the samples implanted with the lower B concentration, no crystal defects could be detected by TEM. No threading dislocations or other defects were observed in the regrown epitaxial layer, which shows the possibility to grow a layer with high crystalline quality on B implanted 6H SiC. By SIMS, it was found that B piles up at the interface to the regrown layer, which could be explained by enhanced diffusion from an increased concentration of point defects created by implantation damage in the region. B is also spread out into the original crystal and in the regrown layer at a concentration of below 2 x 10(16) cm(-3), with a diffusion constant estimated to 1.3 x 10(-12) cm(2)s(-1). This diffusion is most probably not driven by implantation damage, but by intrinsic defects in the grown crystal. Our investigation shows that the combination of implantation and subsequent regrowth techniques could be used in SiC for building advanced device structures, with the crystal quality in the regrown layer not being deteriorated by crystal defects in the implanted region. A device process using B implantation and subsequent regrowth could on the other hand be limited by the diffusion of B.
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| 8. |
- Persson, P. O. Å, et al.
(författare)
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Transmission electron microscopy investigation of defects in B-implanted 6H-SiC
- 1998
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Ingår i: Silicon carbide, III-nitrides and related materials : ICSCIII-N'97. - : Trans Tech Publications Inc.. - 0878497900 ; , s. 413-416
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Konferensbidrag (refereegranskat)abstract
- Silicon carbide is due to its wide bandgap, high saturated electron drift velocity, high electric breakdown field and high thermal conductivity a suitable material for electron devices operating at high temperatures, high powers and high frequencies.[1,2] In order for SIC to reach its full potential in device technology, doping is essential. Usually ion implantation is used for doping since diffusion is difficult in SiC. Boron is a useful material for implantation because of its low atomic weight and greater penetration depth than other accepters, yet very few studies have been conducted on B-implanted 6H-SiC. [3,4] In this investigation we have used transmission electron microscopy (TEM) to study structural defects that are found in B-implanted 6H-SiC layers.
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| 9. |
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| 10. |
- Schoner, A., et al.
(författare)
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Dependence of the aluminium ionization energy on doping concentration and compensation in 6H-SiC
- 1996
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Ingår i: Silicon Carbide and Related Materials1995. - : Institute of Physics Publishing (IOPP). - 0750303352 ; , s. 493-496
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Konferensbidrag (refereegranskat)abstract
- Hall-effect measurements on aluminium (Al)-doped p-type 6H-SiC were made and the dependence of the Al ionization energy on doping concentration and compensation was investigated. It is shown that the Al ionization energy is almost constant for a degree of compensation K much less than 0.01 up to an Al concentration of 5 . 10(20)cm(-3). An average value for the Al ionization energy is found to be 241.6 +/- 5.2 meV. Additionally, we find that the Al ionization energy for a degree of compensation in a range of 0.01 to 0.5 varies with doping concentration and compensation. An impurity band model describing this dependence is discussed.
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| 11. |
- Schoner, A, et al.
(författare)
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Hydrogen incorporation in epitaxial layers of 4H- and 6H-silicon carbide grown by vapor-phase epitaxy
- 1997
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Ingår i: Diamond and related materials. - 0925-9635 .- 1879-0062. ; 6, s. 1293-1296
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Tidskriftsartikel (refereegranskat)abstract
- The incorporation of hydrogen during vapor phase epitaxy was investigated using secondary ion mass spectroscopy, low temperature photoluminescence, and capacitance-voltage measurements. It was found that hydrogen incorporation is strongly dependent on the concentration of the acceptor dopants aluminum and boron, regardless of changes in the doping concentration caused by varying the concentration ratio between carbon and silicon or the dopant precursor flow. An electrical passivation of the acceptor dopants was found and could be reduced by annealing at temperatures above 1000 degrees C. At the same anneal temperature hydrogen-related photoluminescence was considerably reduced and the diffusion of hydrogen was detected. (C) 1997 Elsevier Science S.A.
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| 12. |
- Tobias, Peter, et al.
(författare)
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Studies of the ambient dependent inversion capacitance of catalytic metal oxide silicon carbide devices based on 6H- and 4H-SiC material
- 1998
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Ingår i: Silicon Carbide, III-Nitrides and Related Materials, Part 1-2. - : Trans Tech Publications. - 0878497900 ; , s. 1089-1092
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Konferensbidrag (refereegranskat)abstract
- Platinum-oxide-silicon carbide structures change their capacitance upon gas exposure and are used as gas sensors. The decrease of the inversion capacitance within 750 to 900 degrees C due to hydrogen exposure is studied for 4H- and 6H-SiC,:both n- and p-type. A mechanism for the capacitance decrease is suggested which explains also the large change in the conductance of the structures.
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| 13. |
- Zetterling, Carl-Mikael, et al.
(författare)
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Junction barrier Schottky diodes in 6H SiC
- 1998
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Ingår i: Solid-State Electronics. - 0038-1101 .- 1879-2405. ; 42:9, s. 1757-1759
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Tidskriftsartikel (refereegranskat)abstract
- Junction barrier Schottky (JBS) diodes in 6H SiC have been fabricated and characterised electrically. This device, demonstrated in silicon technology, has the advantage of a low forward voltage drop comparable to that of Schottky diodes, as well as a high blocking voltage and low reverse leakage current of a pn junction. This is especially attractive for wide bandgap materials such as SiC in which pn junctions have a large forward voltage drop. The devices were capable of blocking up to 1100 V with a leakage current density of 0.15 A cm-2, limited by the leakage when the drift region was fully depleted, or breakdown of the SiC material itself. The forward conduction was limited by an on-resistance of 20 mΩ cm2, resulting in forward voltage drops of 2.6 V at 100 A cm-2. © 1998 Published by Elsevier Science Ltd. All rights reserved.
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