Modeling APOE ε4 familial Alzheimer’s disease in directly converted 3D brain organoids

Brain organoids have become a valuable tool for studying human brain development, disease modeling, and drug testing. However, generating brain organoids with mature neurons is time-intensive and often incomplete, limiting their utility in studying age-related neurodegenerative diseases such as Alzheimer’s disease (AD). Here, we report the generation of 3D brain organoids from human fibroblasts through direct reprogramming, with simplicity, efficiency, and reduced variability. We also demonstrate that induced brain organoids from APOE ε4 AD patient fibroblasts capture some disease-specific features and pathologies associated with APOE ε4 AD. Moreover, APOE ε4-induced brain organoids with mutant APP overexpression faithfully recapitulate the acceleration of AD-related pathologies, providing a more physiologically relevant and patient-specific model of familial AD. Importantly, transcriptome analysis reveals that gene sets specific to APOE ε4 patient-induced brain organoids are highly similar to those of APOE ε4 post-mortem AD brains. Overall, induced brain organoids from direct reprogramming offer a promising approach for more efficient and controlled studies of neurodegenerative disease modeling

Thin films of electron donor–acceptor complexes: characterisation of mixed-crystalline phases and implications for electrical doping

International audienceElectron donor-acceptor (EDA) complexes are of interest as low-band gap molecular semiconductors and as dopants for molecular semiconducting matrices. This contribution establishes a link between optical, structural and vibrational properties of EDA complexes as well as the electrical doping by them. We comprehensively characterise co-deposited films of the donors dibenzotetrathiafulvalene and diindenoperylene and the acceptors tetracyanonaphthoquinodimethane and its hexa-fluorinated derivative. All co-deposited donor:acceptor systems form mixed crystalline structures and the EDA complex is characterised by the complex-related absorption and X-ray scattering features. The absorption energies of the analysed EDA complexes cross the neutral-to-ionic boundary. The degree of charge transfer is determined by vibrational spectroscopy. Here, strong spatial anisotropy is found for the diindenoperylene containing complexes. The electrical transport measurements reveal an exponential relation between electrical conductivity and activation energy of transport for all complex-doped systems. We show with this result that doping via complexes has the same dominant activation process as doping via integer charge transfer, which is the separation of Coulombically bound charges. Our results are put in a broader context and we provide an outlook on future possibilities and research on EDA complexes

LOS Stabilization Controller Design of EOTS and Performance Prediction Using Disturbance Model

The EOTS(Electro Optical Tracking System) must have stabilization performance to provide high-quality images under disturbance environment. In this paper, we present a controller that can minimize the LOS error and has a simple structure. Hence, to evaluate the performance of this controller, analysis in the frequency domain and LOS error measurement are performed. In order to measure the LOS error without a ‘rate table’ that requires a lot of facility investment, we propose a design method for disturbance model that considers the operating environment of the EOTS. Finally, the performance of the stabilization algorithm is evaluated by the proposed disturbance model.</jats:p