Human high-order thalamic nuclei activity is known to closely correlate with conscious states. However, it is not clear how those thalamic nuclei and thalamocortical interactions directly contribute to the transient process of human conscious perception. We simultaneously recorded stereoelectroencephalography data from the thalamic nuclei and prefrontal cortex (PFC), while patients with implanted electrodes performed a visual consciousness task. Compared with the ventral nuclei and PFC, the intralaminar and medial nuclei presented earlier and stronger consciousness-related activity. Transient thalamofrontal neural synchrony and cross-frequency coupling were both driven by the θ phase of the intralaminar and medial nuclei during conscious perception. The intralaminar and medial thalamic nuclei thus play a gate role to drive the activity of the PFC during the emergence of conscious perception.

Background: Drug combination therapy is commonly used in clinical practice. Many methods including Bliss independence method have been proposed for drug combination design based on simulations models or experiments. Although Bliss independence method can help to solve the drug combination design problem when there are only a small number of combinations, as the number of combinations increases, it may not be scalable. Exploration of system structure becomes important to reduce the complexity of the design problem.Results: In this paper, we deduced a mathematical model which can simplify the serial structure and parallel structure of biological pathway for synergy evaluation of drug combinations. We demonstrated in steady state the sign of the synergism assessment factor derivative of the original system can be predicted by the sign of its simplified system. In addition, we analyzed the influence of feedback structure on survival ratio of the serial structure. We provided a sufficient condition under which the combination effect could be maintained. Furthermore, we applied our method to find three synergistic drug combinations on tumor necrosis factor α-induced NFκB pathway and subsequently verified by the cell experiment.Conclusions: We identified several structural properties underlying the Bliss independence criterion, and developed a systematic simplification framework for drug combiation desgin by combining simulation and system reaction network topology analysis. We hope that this work can provide insights to tackle the challenging problem of assessment of combinational drug therapy effect in a large scale signaling pathway. And hopefully in the future our method could be expanded to more general criteria.

In recent years, hydrogen-based multi-energy systems (HMESs) have received wide attention. However, existing works on the optimal operation of HMESs neglect building thermal dynamics, which means that the flexibility of thermal loads can not be utilized for reducing system operation cost. In this paper, we investigate an optimal operation problem of an HMES with the consideration of building thermal dynamics. Specifically, we first formulate an expected operational cost minimization problem related to an HMES. Due to the existence of uncertain parameters, inexplicit building thermal dynamics models, spatially and temporally coupled operational constraints, and nonlinear constraints, it is challenging to solve the formulated problem. Then, we propose an algorithm to solve the problem based on model-based optimization and data-driven based learning. The key idea of the proposed algorithm is summarized as follows: (1) transforming the long-term cost minimization problem into several single-slot subproblems using Lyapunov optimization techniques; (2) dividing each single-slot subproblem into two parts according to the availability of model information; (3) solving one part based on convex optimization and solving another part using multi-agent attention-based deep deterministic policy gradient. Simulation results based on real-world traces show the effectiveness of the proposed algorithm.