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Autophagy is a major regulator of beta cell insulin homeostasis
Riahi, Yael,Wikstrom, Jakob D.,Bachar-Wikstrom, Etty,Polin, Nava,Zucker, Hava,Lee, Myung-Shik,Quan, Wenying,Haataja, Leena,Liu, Ming,Arvan, Peter,Cerasi, Erol,Leibowitz, Gil Springer-Verlag 2016 Diabetologia Vol.59 No.7
<P>Aims/hypothesis We studied the role of protein degradation pathways in the regulation of insulin production and secretion and hypothesised that autophagy regulates proinsulin degradation, thereby modulating beta cell function. Methods Proinsulin localisation in autophagosomes was demonstrated by confocal and electron microscopy. Autophagy was inhibited by knockdown of autophagy-related (ATG) proteins and using the H+-ATPase inhibitor bafilomycin-A1. Proinsulin and insulin content and secretion were assessed in static incubations by ELISA and RIA. Results Confocal and electron microscopy showed proinsulin localised in autophagosomes and lysosomes. Beta-Atg7(-/-) mice had proinsulin-containing sequestosome 1 (p62 [also known as SQSTM1])(+) aggregates in beta cells, indicating proinsulin is regulated by autophagy in vivo. Short-term bafilomycin-A1 treatment and ATG5/7 knockdown increased steady-state proinsulin and hormone precursor chromogranin A content. ATG5/7 knockdown also increased glucose- and non-fuel-stimulated insulin secretion. Finally, mutated forms of proinsulin that are irreparably misfolded and trapped in the endoplasmic reticulum are more resistant to degradation by autophagy. Conclusions/interpretation In the beta cell, transport-competent secretory peptide precursors, including proinsulin, are regulated by autophagy, whereas efficient clearance of transport-incompetent mutated forms of proinsulin by alternative degradative pathways may be necessary to avoid beta cell proteotoxicity. Reduction of autophagic degradation of proinsulin increases its residency in the secretory pathway, followed by enhanced secretion in response to stimuli.</P>
An RC-IGCT for application at up to 5.3kV
Umamaheswara Reddy Vemulapati,Tobias Wikstrom,Matthias Luscher 전력전자학회 2019 ICPE(ISPE)논문집 Vol.2019 No.5
A 94mm, Reverse Conducting-Integrated Gate Commutated Thyristor (RC-IGCT) for application at high DC voltage, up to 5.3kV has been manufactured and characterized. The design challenges for this type of device operating at such high voltage are to balance the losses to the ability to cool the device while keeping the snappiness of the diode part and the cosmic-ray failure rate to acceptable levels. The snappiness of the diode part has been overcome by implementing a new diode design in this high voltage (10kV) RC-IGCT, without influencing the technology curve under nominal operating conditions for the same silicon thickness. Furthermore, the experimental results show that the technology curve can be improved significantly with the new diode design by thinning the silicon while maintaining the soft reverse recovery behavior of the diode. The newly developed 94mm, 10kV RC-IGCT could be a device of choice for the low switching frequency high voltage power electronics applications, where one device could replace complicated series connection of two 4.5kV or 5.5kV devices per switch position.
High-Voltage (8.5 kV) Asymmetric IGCT for MVD and HVDC Applications
U. Vemulapati,D. Johannesson,T. Wikstrom,T. Stiasny,C. Corvace,C. Winter 전력전자학회 2023 ICPE(ISPE)논문집 Vol.2023 No.-
This paper, presents the design and experimental electrical performance of the newly developed high-voltage (8.5 kV) Asymmetric Integrated Gate- Commutated Thyristor (A-IGCT) together with the 8.5 kV Fast Recovery Diode (FRD). The devices are optimized to be used in low switching frequency (e.g., <150 Hz) applications for dc-link voltages of up to 5.3 kV. Also, it presents system level simulations using Modular Multi-level Converter (MMC) topology for High-Voltage Direct Current (HVDC) systems demonstrating the benefits of high-voltage devices and their ability to conduct high currents in such applications. Furthermore, it presents the system level simulations using 3-Level Neutral Point Clamp (3L-NPC) topology with high-voltage devices for Medium Voltage Drive (MVD) applications demanding higher power with output voltages in the range of 6.0-6.9 kV<SUB>rms</SUB>.