Molecular and functional characterisation of Müller glia derived from retinal organoids formed by human pluripotent stem cells (hPSCs)

Previous studies have shown that transplantation of human Müller glia into animal models of retinal degeneration improves visual functions, possibly due to their neuroprotective ability. Since sourcing Müller glia from adult donor retinae is not acceptable for therapeutic use, differentiating Müller glia from human pluripotent stem cells (hPSCs) constitutes an attractive approach for developing cell-based therapies to treat retinal degenerative diseases. However, it is important to examine the molecular and functional characteristics of Müller glia derived from retinal organoids and compare these with cells isolated from adult retina before they can be considered for development of cell therapies. The transcriptomic profile of Müller glia isolated from retinal organoids formed by hPSCs was also examined and compared to that of the well-characterised adult Müller cell line MIO-M1. In addition, the effect of cytokines on the neuroprotective response of these cells, as well as the neuroprotective functionality of culture supernatants on rat retinal ganglion cells (RGCs) were assessed. RNA-sequencing revealed that hPSC-derived cells exhibited Müller glia-like transcriptomic profiles as compared to MIO-M1 and expressed a broad spectrum of genes known to confer neuroprotection. Short-term culture with TNF-α elicited a pleiotropic transcriptomic response in MIO-M1, with significant downregulation of gliotic genes and upregulation of antioxidant enzymes and immune mediators. Similarly, TNF-α significantly increased expression and release of several antioxidant enzymes in hPSC-derived Müller glia-like cells. Treatment of both, hPSC-derived or MIO-M1 cells with TGF-β1 did not change the expression of antioxidative enzymes in these cells in vitro. Culture supernatants of hPSC-derived cells induced neuroprotection of rat RGCs subjected to glutamate excitotoxicity, as shown by their better survival and structural integrity when compared to controls cultured without neurotrophic factors. Improved RGC survival was supported by the presence of various neuroprotective factors in the culture supernatants. In conclusion, the present study demonstrates that hPSC-derived cells displayed Müller glia-like characteristics and neuroprotective potential, which has laid a solid foundation to accelerate the clinical translation of Müller glia cell therapies

Towards a minimal order distributed observer for linear systems

In this paper we consider the distributed estimation problem for continuous-time linear time-invariant (LTI) systems. A single linear plant is observed by a network of local observers. Each local observer in the network has access to only part of the output of the observed system, but can also receive information on the state estimates of its neigbours. Each local observer should in this way generate an estimate of the plant state. In this paper we study the problem of existence of a reduced order distributed observer. We show that if the observed system is observable and the network graph is a strongly connected directed graph, then a distributed observer exists with state space dimension equal to $Nn - \sum_{i =1}^N p_i$, where $N$ is the number of network nodes, $n$ is the state space dimension of the observed plant, and $p_i$ is the rank of the output matrix of the observed output received by the $i$th local observer. In the case of a single observer, this result specializes to the well-known minimal order observer in classical observer design.Comment: 12 pages, 1 figur

Impact of Online Jewelry Consumer’s Decision-making Style on Attitudes of Product Quality and Price

Based on CSI (Consumer style inventory) theory, this article develops online jewelry consumer’s decision-making style scale to investigate 378 samples, through exploratory and confirmatory factor analysis, proposes six decision-making styles, including fashion and perfection consciousness, self-recreation consciousness, personal style consciousness, price and quality consciousness, confused by overchoice and network media consciousness. And this article analyses influence of online jewelry consumer’s decision-making style on attitudes of product quality and price toward marketing practice. The results indicate that self-recreation conscious, personal style conscious and network media conscious consumers have significant positive effect on attitude of product quality, while consumer confused by overchoice has significant negative effect on attitude of product quality; self-recreation conscious, personal style conscious and price quality conscious consumers have significant positive effect on attitude of price. These findings have an import implication for jewelry network marketing which enterprises can use differentiation marketing strategy based on consumer’s decision making style

Priming effects on labile and stable soil organic carbon decomposition: Pulse dynamics over two years.

Soil organic carbon (SOC) is a major component in the global carbon cycle. Yet how input of plant litter may influence the loss of SOC through a phenomenon called priming effect remains highly uncertain. Most published results about the priming effect came from short-term investigations for a few weeks or at the most for a few months in duration. The priming effect has not been studied at the annual time scale. In this study for 815 days, we investigated the priming effect of added maize leaves on SOC decomposition of two soil types and two treatments (bare fallow for 23 years, and adjacent old-field, represent stable and relatively labile SOC, respectively) of SOC stabilities within each soil type, using a natural 13C-isotope method. Results showed that the variation of the priming effect through time had three distinctive phases for all soils: (1) a strong negative priming phase during the first period (≈0-90 days); (2) a pulse of positive priming phase in the middle (≈70-160 and 140-350 days for soils from Hailun and Shenyang stations, respectively); and (3) a relatively stabilized phase of priming during the last stage of the incubation (>160 days and >350 days for soils from Hailun and Shenyang stations, respectively). Because of major differences in soil properties, the two soil types produced different cumulative priming effects at the end of the experiment, a positive priming effect of 3-7% for the Mollisol and a negative priming effect of 4-8% for the Alfisol. Although soil types and measurement times modulated most of the variability of the priming effect, relative SOC stabilities also influenced the priming effect for a particular soil type and at a particular dynamic phase. The stable SOC from the bare fallow treatment tended to produce a narrower variability during the first phase of negative priming and also during the second phase of positive priming. Averaged over the entire experiment, the stable SOC (i.e., the bare fallow) was at least as responsive to priming as the relatively labile SOC (i.e., the old-field) if not more responsive. The annual time scale of our experiment allowed us to demonstrate the three distinctive phases of the priming effect. Our results highlight the importance of studying the priming effect by investigating the temporal dynamics over longer time scales

A Unified Scheme of ResNet and Softmax

Large language models (LLMs) have brought significant changes to human society. Softmax regression and residual neural networks (ResNet) are two important techniques in deep learning: they not only serve as significant theoretical components supporting the functionality of LLMs but also are related to many other machine learning and theoretical computer science fields, including but not limited to image classification, object detection, semantic segmentation, and tensors. Previous research works studied these two concepts separately. In this paper, we provide a theoretical analysis of the regression problem: $\| \langle \exp(Ax) + A x , {\bf 1}_n \rangle^{-1} ( \exp(Ax) + Ax ) - b \|_2^2$, where $A$ is a matrix in $\mathbb{R}^{n \times d}$, $b$ is a vector in $\mathbb{R}^n$, and ${\bf 1}_n$ is the $n$-dimensional vector whose entries are all $1$. This regression problem is a unified scheme that combines softmax regression and ResNet, which has never been done before. We derive the gradient, Hessian, and Lipschitz properties of the loss function. The Hessian is shown to be positive semidefinite, and its structure is characterized as the sum of a low-rank matrix and a diagonal matrix. This enables an efficient approximate Newton method. As a result, this unified scheme helps to connect two previously thought unrelated fields and provides novel insight into loss landscape and optimization for emerging over-parameterized neural networks, which is meaningful for future research in deep learning models