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    Stem cells can precisely and robustly undergo cellular differentiation and lineage commitment, referred to as stemness. However, how the gene network underlying stemness regulation reliably specifies cell fates is not well understood. To address this question, we applied a recently developed computational method, ra ndom ci rcuit pe rturbation (RACIPE), to a nine-component gene regulatory network (GRN) governing stemness, from which we identified robust gene states. Among them, four out of the five most probable gene states exhibit gene expression patterns observed in single mouse embryonic cells at 32-cell and 64-cell stages. These gene states can be robustly predicted by the stemness GRN but not by randomized versions of the stemness GRN. Strikingly, we found a hierarchical structure of the GRN with the Oct4/Cdx2 motif functioning as the first decision-making module followed by Gata6/Nanog. We propose that stem cell populations, instead of being viewed as all having a specific cellular state, can be regarded as a heterogeneous mixture including cells in various states. Upon perturbations by external signals, stem cells lose the capacity to access certain cellular states, thereby becoming differentiated. The new gene states and key parameters regulating transitions among gene states proposed by RACIPE can be used to guide experimental strategies to better understand differentiation and design reprogramming. The findings demonstrate that the functions of the stemness GRN is mainly determined by its well-evolved network topology rather than by detailed kinetic parameters. 
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  4. Abstract

    Juvenile idiopathic arthritis (JIA) is a chronic disease. During its “high disease activity (HDA)” stage, JIA can cause severe pain, and thus could seriously affect patients' physical and psychological health. Early detection of the HDA stage of JIA can reduce the damage of the disease by treating it at an early stage and alleviating the painful experience of the patients. So far, no effective cure of JIA has been found, and one major goal of disease management is to improve patients' quality of life. To this end, patients' health‐related quality of life (HRQOL) scores are routinely collected over time from JIA patients. In this paper, we demonstrate that a new statistical methodology called dynamic screening system (DySS) is effective for early detection of the HDA stage of JIA. By this approach, a patient's HRQOL scores are monitored sequentially, and a signal is given by DySS once the longitudinal pattern of the scores is found to be significantly different from the pattern of patients with low disease activity. Dimension reduction of the observed HRQOL scores and the corresponding impact on the performance of DySS are also discussed.

     
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  5. A one‐step synthesis of Li‐rich layered materials with layered/spinel heterostructure has been systematically investigated. The composites are synthesized by a polyol method followed with an annealing process at 500–900 °C for 12 h. A spinel to layer phase transition is considered to take place during the heat treatment, and the samples obtained at different temperatures show diverse phase compositions. An “Li‐rich spinel phase decomposition” phase transition mechanism is proposed to explain the formation of such a heterostructure. The electrochemical properties of the heterostructure are found to be associated with the ratio of spinel to layer phases, the leach out of rock salt phase, and the change of crystallinity and particle size. Product with improved cyclic and rate performance is achieved by annealing at 700 °C for 12 h, with a discharge capacity of 214 mA h g−1remaining at 0.2 C after 60 cycles and discharge capacity of about 200 mA h g−1at 1 C.

     
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