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Amyloid-β-induced disruption of axon-initial-segment mitochondria localization:consequences for TAU missorting in Alzheimer's disease pathology

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Neural Regeneration Research 2025年第5期20卷 1407-1408页

作者： Daniel Adam Felix Langerscheidt hans Zempel Institute of Human Genetics University Hospital CologneCologneGermany Center for Molecular Medicine Cologne(CMMC) University of CologneCologneGermany

TAU is a neuronal microtubule-associated protein preferentially located in *** a battery of neurodegenerative diseases termed"tauopathies,"including Alzheimer's disease (AD),TAU is missorted and abnormally phosphorylated,leading to filamentous accumulations of hyperphosphorylated TAU,a pathological hallmark and potential disease driver of AD and related tauopathies (Zempel,2024).

关键词： Alzheimer tau diseases

Effects of P301L-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice

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Neural Regeneration Research 2025年第8期20卷 2348-2360页

作者： Mohamed Aghyad Al Kabbani Christoph Köhler hans Zempel Institute of Human Genetics Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Center for Molecular Medicine Cologne(CMMC) University of CologneCologneGermany Center Anatomy Department ⅡMedical FacultyUniversity of CologneCologneGermany

TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the *** is missorted and aggregated in an array of diseases known as *** are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing *** impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule *** therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to *** investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic *** sum,P301L-TAU results in changes in micr

关键词： human induced pluripotent stem cell microtubules P301L pR5 mice TAU tauopathy tubulin code

From Single Droplet to Column Design

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Tsinghua Science and Technology 2006年第2期11卷 212-216页

作者： hans-jrg Bart Institute of Thermal Process Engineering TU Kaiserslautern D-67653 Kaiserslautern Germany

The technique state to design counter-current extraction columns is based on the performance of pilot plant experiments. The modelling is then either with the equilibrium or dispersion model, whereas in the latter the dispersion coefficient accounts for all hydrodynamic non-idealities. A new approach uses single droplet experiments to obtain the basic laws and functions governing droplet breakage, coalescence, relative velocity, and axial dispersion when using droplet populance balance models （DPBM）. The hydrodynamics simulation results show that the mean Sauter diameter, hold-up, and concentration profiles could be well predicted, which promotes the use of DPBM models for further applications in industrial scale.

关键词： single droplet column design countercurrent extraction droplet populance balance model

STABILIZED FEM FOR CONVECTION-DIFFUSION PROBLEMS ON LAYER-ADAPTED MESHES

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journal of Computational Mathematics 2009年第2期27卷 266-279页

作者： hans-Grg Roos TU Dresden Germany

The application of a standard Galerkin finite element method for convection-diffusion problems leads to oscillations in the discrete solution, therefore stabilization seems to be necessary. We discuss several recent stabilization methods, especially its combination with a Galerkin method on layer-adapted meshes. Supercloseness results obtained allow an improvement of the discrete solution using recovery techniques.

关键词： Singular perturbations Convection-diffusion Finite element method Stabi-lization Layer-adapted mesh Superconvergenee Recovery

Numerical Analysis of a System of Singularly Perturbed Convection-Diffusion Equations Related to Optimal Control

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Numerical Mathematics(Theory,Methods and Applications) 2011年第4期4卷 562-575页

作者： hans-Görg Roos Christian Reibiger Technische Universität Dresden Institut für Numerische Mathematik01062 DresdenGermany

We consider an optimal control problem with an 1D singularly perturbed differential state *** solving such problems one uses the enhanced system of the state equation and its adjoint ***,we obtain a system of two convectiondiffusion *** linear finite elements on adapted grids we treat the effects of two layers arising at different boundaries of the *** proof uniform error estimates for this method on meshes of Shishkin *** present numerical results supporting our analysis.

关键词： Convection-diffusion linear finite elements a priori analysis layer-adapted meshes singular perturbed optimal control

Dynamics and functions of E‑cadherin complexes in epithelial cell and tissue morphogenesis

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Marine Life Science & Technology 2023年第4期5卷 585-601页

作者： Na Zhang Matthias Häring Fred Wolf jörg Großhans Deqing Kong Department of Biology Philipps University35043 MarburgGermany Göttingen Campus Institute for Dynamics of Biological Networks(CIDBN) Georg August University Göttingen37073 GöttingenGermany

Cell–cell adhesion is at the center of structure and dynamics of epithelial tissue.E-cadherin–catenin complexes mediate Ca^(2+)-dependent trans-homodimerization and constitute the kernel of adherens *** the basic function of cell–cell adhesion,recent progress sheds light the dynamics and interwind interactions of individual E-cadherin–catenin complex with E-cadherin superclusters,contractile actomyosin and mechanics of the cortex and *** nanoscale architecture of E-cadherin complexes together with cis-interactions and interactions with cortical actomyosin adjust to junctional tension and mechano-transduction by reinforcement or weakening of specific features of the *** post-translational modifications such as phosphorylation and glycosylation have been implicated,their role for specific aspects of in E-cadherin function has remained ***,we provide an overview of the E-cadherin complex in epithelial cell and tissue morphogenesis focusing on nanoscale architectures by super-resolution approaches and post-translational modifications from recent,in particular in vivo,***,we review the computational modelling in E-cadherin complexes and highlight how computational modelling has contributed to a deeper understanding of the E-cadherin complexes.

关键词： Nanoscale architectures Phosphorylation Glycosylation Computational modelling

Conditional Generative Adversarial Networks for modelling fuel sprays

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Energy and AI 2023年第2期12卷 62-75页

作者： Cihan Ates Farhad Karwan Max Okraschevski Rainer Koch hans-jörg Bauer Karlsruhe Institute of Technology(KIT) Institute of Thermal TurbomachineryGermany Karlsruhe Institute of Technology(KIT) Machine Intelligence in Energy SystemsGermany

In this study, the probabilistic, data driven nature of the generative adversarial neural networks (GANs)was utilized to conduct virtual spray simulations for conditions relevant to aero engine combustors. Themodel consists of two sub-modules: (i) an autoencoder converting the variable length droplet trajectories intofixed length, lower dimensional representations and (ii) a Wasserstein GAN that learns to mimic the latentrepresentations of the evaporating droplets along their lifetime. The GAN module was also conditioned withthe injection location and the diameters of the droplets to increase the generalizability of the whole *** training data was provided from highly resolved 3D, transient Eulerian–Lagrangian, large eddy simulationsconducted with OpenFOAM. Neural network models were created and trained within the open source machinelearning framework of PyTorch. Predictive capabilities of the proposed method was discussed with respect tospray statistics and evaporation dynamics. Results show that conditioned GAN models offer a great potentialas low order model approximations with high computational efficiency. Nonetheless, the capabilities of theautoencoder module to preserve local dependencies should be improved to realize this potential. For the currentcase study, the custom model architecture was capable of conducting the simulation in the order of secondsafter a day of training, which had taken one week on HPC with the conventional CFD approach for the samenumber of droplets (200,000 trajectories).

关键词： Generative Adversarial Networks Generative learning Fuel injection Aero engines Multivariate time series

Decoding the genetic program of micronucleus formation: linking chromosomal instability to human disease

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2840-2842页

作者： jörg Fahrer Division of Food Chemistry and Toxicology Department of ChemistryRPTU Kaiserslautern-Landau67663 KaiserslauternGermany

A recent study by Adams and colleagues published in Nature unveiled more than one hundred genes that are involved in micronucleus formation,1 which is a biomarker for genomic instability and associated with aging,cancer,and other disorders.2 As an outstanding achievement,the authors identified DSCC1(DNA Replication And Sister Chromatid Cohesion 1)as a critical gene protecting against early developmental defects,genomic instability,reduced proliferative capacity,cohesinopathy-related phenotypes,and tumor development in vivo.

关键词： chromosomal linking Replication

Apples to oranges:environmentally derived,dynamic regulation of serotonin neuron subpopulations in adulthood?

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Neural Regeneration Research 2025年第9期20卷 2596-2597页

作者： Christopher j.O’Connell Matthew j.Robson Department of Genetics College of MedicineHarvard UniversityBostonMAUSA james L.Winkle College of Pharmacy Division of Pharmaceutical SciencesUniversity of CincinnatiCincinnatiOHUSA Neuroscience Graduate Program College of MedicineUniversity of CincinnatiCincinnatiOHUSA

Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).

关键词： sustained orange dynamic