Simulation based on learning methods

The use of simulation technology as a tool for planning and control is of increasing significance in most fields of production. The main part of the expenditure concerning simulation analyses is the modelling of the considered production. Despite the use of modern building-block-oriented modelling technology, this modelling can often not be done by the user, but only by external experts. Against this backdrop, an adaptive simulation system is being developed by the Institute for Industrial Manufacturing and Management (IFF) at the University of Stuttgart. It independently adapts to real production processes, i.e. it learns about the interdependencies of production processes, and, in this way, supports the user in constructing and maintaining the model. In terms of information technology, the research in the field of artificial intelligence, especially in the subdomain of machine learning, is the basis for the realization of such adaptive systems.     

Mol 7C experiments on local fault propagation in irradiated LMFBR fuel subassemblies

The consequences of local cooling disturbances in irradiated fuel pin bundles of Liquid Metal Fast Breeder Reactors (LMFBRs) were investigated in two in-pile experiments in the BR2 reactor at Mol/Belgium. A porous local blockage was used to initiate the fault. This caused severe local fuel pin damage, but there was no fault propagation to major parts of the bundles during four hours of full power operation. If such events occurred in a LMFBR, the delayed neutron detection (DND) signals generated by the fault would be sufficient to initiate reliable automatic shutdown of the reactor.     

Advanced Code-Division Multiplexers for Superconducting Detector Arrays

Multiplexers based on the modulation of superconducting quantum interference devices are now regularly used in multi-kilopixel arrays of superconducting detectors for astrophysics, cosmology, and materials analysis. Over the next decade, much larger arrays will be needed. These larger arrays require new modulation techniques and compact multiplexer elements that fit within each pixel. We present a new in-focal-plane code-division multiplexer that provides multiplexing elements with the required scalability. This code-division multiplexer uses compact lithographic modulation elements that simultaneously multiplex both signal outputs and superconducting transition-edge sensor (TES) detector bias voltages. It eliminates the shunt resistor used to voltage bias TES detectors, greatly reduces power dissipation, allows different dc bias voltages for each TES, and makes all elements sufficiently compact to fit inside the detector pixel area. These in-focal plane code-division multiplexers can be combined with multi-GHz readout based on superconducting microresonators to scale to even larger arrays.     

Schrifttumsberichte

Ohne Zusammenfassung     

Bundesanstalt für Forst-und Holzwirtschaft,Reinbek

Ohne Zusammenfassung     

Mitochondrial Dysfunction in Spinocerebellar Ataxia Type 3 Is Linked to VDAC1 Deubiquitination

Dysfunctional mitochondria are linked to several neurodegenerative diseases. Metabolic defects, a symptom which can result from dysfunctional mitochondria, are also present in spinocerebellar ataxia type 3 (SCA3), also known as Machado–Joseph disease, the most frequent, dominantly inherited neurodegenerative ataxia worldwide. Mitochondrial dysfunction has been reported for several neurodegenerative disorders and ataxin-3 is known to deubiquitinylate parkin, a key protein required for canonical mitophagy. In this study, we analyzed mitochondrial function and mitophagy in a patient-derived SCA3 cell model. Human fibroblast lines isolated from SCA3 patients were immortalized and characterized. SCA3 patient fibroblasts revealed circular, ring-shaped mitochondria and featured reduced OXPHOS complexes, ATP production and cell viability. We show that wildtype ataxin-3 deubiquitinates VDAC1 (voltage-dependent anion channel 1), a member of the mitochondrial permeability transition pore and a parkin substrate. In SCA3 patients, VDAC1 deubiquitination and parkin recruitment to the depolarized mitochondria is inhibited. Increased p62-linked mitophagy, autophagosome formation and autophagy is observed under disease conditions, which is in line with mitochondrial fission. SCA3 fibroblast lines demonstrated a mitochondrial phenotype and dysregulation of parkin-VDAC1-mediated mitophagy, thereby promoting mitochondrial quality control via alternative pathways.     

The RAGE/DIAPH1 Signaling Axis & Implications for the Pathogenesis of Diabetic Complications

Increasing evidence links the RAGE (receptor for advanced glycation end products)/DIAPH1 (Diaphanous 1) signaling axis to the pathogenesis of diabetic complications. RAGE is a multi-ligand receptor and through these ligand–receptor interactions, extensive maladaptive effects are exerted on cell types and tissues targeted for dysfunction in hyperglycemia observed in both type 1 and type 2 diabetes. Recent evidence indicates that RAGE ligands, acting as damage-associated molecular patterns molecules, or DAMPs, through RAGE may impact interferon signaling pathways, specifically through upregulation of IRF7 (interferon regulatory factor 7), thereby heralding and evoking pro-inflammatory effects on vulnerable tissues. Although successful targeting of RAGE in the clinical milieu has, to date, not been met with success, recent approaches to target RAGE intracellular signaling may hold promise to fill this critical gap. This review focuses on recent examples of highlights and updates to the pathobiology of RAGE and DIAPH1 in diabetic complications.