Unraveling the mechanisms of NK cell dysfunction in aging and Alzheimer’s disease: insights from GWAS and single-cell transcriptomics

BackgroundAging is an important factor in the development of Alzheimer’s disease (AD). The senescent cells can be recognized and removed by NK cells. However, NK cell function is gradually inactivated with age. Therefore, this study used senescence as an entry point to investigate how NK cells affect AD.MethodsThe study validated the correlation between cognition and aging through a prospective cohort of the National Health and Nutrition Examination Survey database. A cellular trajectory analysis of the aging population was performed using single-cell nuclear transcriptome sequencing data from patients with AD and different ages. The genome-wide association study (GWAS) cohort of AD patients was used as the outcome event, and the expression quantitative trait locus was used as an instrumental variable. Causal associations between genes and AD were analyzed by bidirectional Mendelian randomization (MR) and co-localization. Finally, clinical cohorts were constructed to validate the expression of key genes.ResultsA correlation between cognition and aging was demonstrated using 2,171 older adults over 60 years of age. Gene regulation analysis revealed that most of the highly active transcription factors were concentrated in the NK cell subpopulation of AD. NK cell trajectories were constructed for different age populations. MR and co-localization analyses revealed that CHD6 may be one of the factors influencing AD.ConclusionWe explored different levels of AD and aging from population cohorts, single-cell data, and GWAS cohorts and found that there may be some correlations of NK cells between aging and AD. It also provides some basis for potential causation

Open knowledge disclosure and firm value:a signalling theory perspective

A growing number of firms are openly disclosing knowledge through academic journals and conferences; however, the impact of this practice on their market value needs further research. From a signalling theory perspective, we investigate the relationship between open knowledge disclosure and firm value and identify potential contingency factors. We propose that open knowledge disclosure conveys a firm’s technical capability and commitment to open science, consequently contributing to its market value. Drawing upon data from listed companies within China’s information and communication technology sector, we confirm that open knowledge disclosure enhances firm value. Furthermore, this enhancement is more pronounced for small firms, young firms, private firms, firms with few patents, firms drafting few technical standards, or firms operating in an immature technology market. Our findings suggest that firms, especially those facing high information asymmetry or lacking alternative signals, can increase their market value by sending positive signals through open knowledge disclosure.</p

Open knowledge disclosure and firm value:a signalling theory perspective

A growing number of firms are openly disclosing knowledge through academic journals and conferences; however, the impact of this practice on their market value needs further research. From a signalling theory perspective, we investigate the relationship between open knowledge disclosure and firm value and identify potential contingency factors. We propose that open knowledge disclosure conveys a firm’s technical capability and commitment to open science, consequently contributing to its market value. Drawing upon data from listed companies within China’s information and communication technology sector, we confirm that open knowledge disclosure enhances firm value. Furthermore, this enhancement is more pronounced for small firms, young firms, private firms, firms with few patents, firms drafting few technical standards, or firms operating in an immature technology market. Our findings suggest that firms, especially those facing high information asymmetry or lacking alternative signals, can increase their market value by sending positive signals through open knowledge disclosure.</p

Stochastic Channel Allocation for Nonlinear Systems with Markovian Packet Dropout

This paper addresses a channel scheduling problem for group of dynamically decoupled nonlinear subsystems with actuators connected through digital communication channels and controlled by a centralized controller. Due to the limited communication capacity, only one channel can be activated and hence there is only one pair of sensor and actuator can communicate with the controller at each time instant. In addition, the communication channels are not reliable so Markovian packed dropout is introduced. A predictive control framework is adopted for controller/scheduler co-design to alleviate the performance loss caused by the limited communication capacity. Instead of sending a single control value, the controller sends a sequence of predicted control values to a selected actuator so that there are control input candidates which can be fed to the subsystem when the actuator does not communicate with the controller. A stochastic algorithm is proposed to schedule the usage of the communication medium and sufficient conditions on stochastic stability are given under some mild assumptions.NRF (Natl Research Foundation, S’pore)Published versio