Evaluating the mitigation strategies of COVID-19 by the application of the CO2 emission data through high-resolution agent-based computational experiments.

The negative consequences, such as healthy and environmental issues, brought by rapid urbanization and interactive human activities result in increasing social uncertainties, unreliable predictions, and poor management decisions. For instance, the Coronavirus Disease (COVID-19) occurred in 2019 has been plaguing many countries. Aiming at controlling the spread of COVID-19, countries around the world have adopted various mitigation and suppression strategies. However, how to comprehensively eva luate different mitigation strategies remains unexplored. To this end, based on the Artificial societies, Computational experiments, Parallel execution (ACP) approach, we proposed a system model, which clarifies the process to collect the necessary data and conduct large-scale computational experiments to evaluate the effectiveness of different mitigation strategies. Specifically, we established an artificial society of Wuhan city through geo-environment modeling, population modeling, contact behavior modeling, disease spread modeling and mitigation strategy modeling. Moreover, we established an evaluation model in terms of the control effects and economic costs of the mitigation strategy. With respect to the control effects, it is directly reflected by indicators such as the cumulative number of diseases and deaths, while the relationship between mitigation strategies and economic costs is built based on the CO2 emission. Finally, large-scale simulation experiments are conducted to evaluate the mitigation strategies of six countries. The results reveal that the more strict mitigation strategies achieve better control effects and less economic costs.

Evolution Model of Spatial Interaction Network in Online Social Networking Services.

The development of online social networking services provides a rich source of data of social networks including geospatial information. More and more research has shown that geographical space is an important factor in the interactions of users in social networks. In this paper, we construct the spatial interaction network from the city level, which is called the city interaction network, and study the evolution mechanism of the city interaction network formed in the process of information dissemination in social networks. A network evolution model for interactions among cities is established. The evolution model consists of two core processes: the edge arrival and the preferential attachment of the edge. The edge arrival model arranges the arrival time of each edge; the model of preferential attachment of the edge determines the source node and the target node of each arriving edge. Six preferential attachment models (Random-Random, Random-Degree, Degree-Random, Geographical distance, Degree-Degree, Degree-Degree-Geographical distance) are built, and the maximum likelihood approach is used to do the comparison. We find that the degree of the node and the geographic distance of the edge are the key factors affecting the evolution of the city interaction network. Finally, the evolution experiments using the optimal model DDG are conducted, and the experiment results are compared with the real city interaction network extracted from the information dissemination data of the WeChat web page. The results indicate that the model can not only capture the attributes of the real city interaction network, but also reflect the actual characteristics of the interactions among cities.

Differential Releases of Dopamine and Neuropeptide Y from Histamine-Stimulated PC12 Cells Detected by an Aptamer-Modified Nanowire Transistor.

Silicon nanowire field-effect transistors modified with specific aptamers can directly detect the minute dopamine and neuropeptide Y released from cells. The binding of these molecules to the aptamers results in a conductance change of the transistor biosensor and illustrates the differential releasing mechanisms of these molecules stored in various vesicle pools.

Toward parallel intelligence: An interdisciplinary solution for complex systems.

The growing complexity of real-world systems necessitates interdisciplinary solutions to confront myriad challenges in modeling, analysis, management, and control. To meet these demands, the parallel systems method rooted in the artificial systems, computational experiments, and parallel execution (ACP) approach has been developed. The method cultivates a cycle termed parallel intelligence, which iteratively creates data, acquires knowledge, and refines the actual system. Over the past two decades, the parallel systems method has continuously woven advanced knowledge and technologies from various disciplines, offering versatile interdisciplinary solutions for complex systems across diverse fields. This review explores the origins and fundamental concepts of the parallel systems method, showcasing its accomplishments as a diverse array of parallel technologies and applications while also prognosticating potential challenges. We posit that this method will considerably augment sustainable development while enhancing interdisciplinary communication and cooperation.

Strategy evaluation and optimization with an artificial society toward a Pareto optimum.

Strategy evaluation and optimization in response to troubling urban issues has become a challenging issue due to increasing social uncertainty, unreliable predictions, and poor decision-making. To address this problem, we propose a universal computational experiment framework with a fine-grained artificial society that is integrated with data-based models. The purpose of the framework is to evaluate the consequences of various combinations of strategies geared towards reaching a Pareto optimum with regards to efficacy versus costs. As an example, by modeling coronavirus 2019 mitigation, we show that Pareto frontier nations could achieve better economic growth and more effective epidemic control through the analysis of real-world data. Our work suggests that a nation's intervention strategy could be optimized based on the measures adopted by Pareto frontier nations through large-scale computational experiments. Our solution has been validated for epidemic control, and it can be generalized to other urban issues as well.

Dynasore inhibits rapid endocytosis in bovine chromaffin cells.

Vesicle recycling is vital for maintaining membrane homeostasis and neurotransmitter release. Multiple pathways for retrieving vesicles fused to the plasma membrane have been reported in neuroendocrine cells. Dynasore, a dynamin GTPase inhibitor, has been shown to specifically inhibit endocytosis and vesicle recycling in nerve terminals. To characterize its effects in modulating vesicle recycling and repetitive exocytosis, changes in the whole cell membrane capacitance of bovine chromaffin cells were recorded in the perforated-patch configuration. Constitutive endocytosis was blocked by dynasore treatment, as shown by an increase in membrane capacitance. The membrane capacitance was increased during strong depolarizations and declined within 30 s to a value lower than the prestimulus level. The amplitude, but not the time constant, of the rapid exponential decay was significantly decreased by dynasore treatment. Although the maximal increase in capacitance induced by stimulation was significantly increased by dynasore treatment, the intercepts at time 0 of the curve fitted to the decay phase were all approximately 110% of the membrane capacitance before stimulation, regardless of the dynasore concentration used. Membrane depolarization caused clathrin aggregation and F-actin continuity disruption at the cell boundary, whereas dynasore treatment induced clathrin aggregation without affecting F-actin continuity. The number of invagination pits on the surface of the plasma membrane determined using atomic force microscopy was increased and the pore was wider in dynasore-treated cells. Our data indicate that dynamin-mediated endocytosis is the main pathway responsible for rapid compensatory endocytosis.

Targeted and efficient activation of channelrhodopsins expressed in living cells via specifically-bound upconversion nanoparticles.

Optogenetics is an innovative technology now widely adopted by researchers in different fields of biological sciences. However, most light-sensitive proteins adopted in optogenetics are excited by ultraviolet or visible light which has a weak tissue penetration capability. Upconversion nanoparticles (UCNPs), which absorb near-infrared (NIR) light to emit shorter wavelength light, can help address this issue. In this report, we demonstrated the target selectivity by specifically conjugating the UCNPs with channelrhodopsin-2 (ChR2). We tagged the V5 epitope to the extracellular N-terminal of ChR2 (V5-ChR2m) and functionalized the surface of UCNPs with NeutrAvidin (NAv-UCNPs). After the binding of the biotinylated antibody against V5 onto the V5-ChR2m expressed in the plasma membrane of live HEK293T cells, our results showed that the NAv-UCNPs were specifically bound to the membrane of cells expressing V5-ChR2m. Without the V5 epitope or NAv modification, no binding of UCNPs onto the cell membrane was observed. For the cells expressing V5-ChR2m and bound with NAv-UCNPs, both 488 nm illumination and the upconverted blue emission from UCNPs by 980 nm excitation induced an inward current and elevated the intracellular Ca2+ concentration. Our design reduces the distance between UCNPs and light-sensitive proteins to the molecular level, which not only minimizes the NIR energy required but also provides a way to guide the specific binding for optogenetics applications.

Detection of K+ Efflux from Stimulated Cortical Neurons by an Aptamer-Modified Silicon Nanowire Field-Effect Transistor.

The concentration gradient of K+ across the cell membrane of a neuron determines its resting potential and cell excitability. During neurotransmission, the efflux of K+ from the cell via various channels will not only decrease the intracellular K+ content but also elevate the extracellular K+ concentration. However, it is not clear to what extent this change could be. In this study, we developed a multiple-parallel-connected silicon nanowire field-effect transistor (SiNW-FET) modified with K+-specific DNA-aptamers (aptamer/SiNW-FET) for the real-time detection of the K+ efflux from cultured cortical neurons. The aptamer/SiNW-FET showed an association constant of (2.18 ± 0.44) × 106 M-1 against K+ and an either less or negligible response to other alkali metal ions. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) stimulation induced an outward current and hyperpolarized the membrane potential in a whole-cell patched neuron under a Na+/K+-free buffer. When neurons were placed atop the aptamer/SiNW-FET in a Na+/K+-free buffer, AMPA (13 µM) stimulation elevated the extracellular K+ concentration to ∼800 nM, which is greatly reduced by 6,7-dinitroquinoxaline-2,3-dione, an AMPA receptor antagonist. The EC50 of AMPA in elevating the extracellular K+ concentration was 10.3 µM. By stimulating the neurons with AMPA under a normal physiological buffer, the K+ concentration in the isolated cytosolic fraction was decreased by 75%. These experiments demonstrate that the aptamer/SiNW-FET is sensitive for detecting cations and the K+ concentrations inside and outside the neurons could be greatly changed to modulate the neuron excitability.

Calmodulin Interacts with the Sodium/Calcium Exchanger NCX1 to Regulate Activity.

Changes in intracellular Ca2+ concentrations ([Ca2+]i) are an important signal for various physiological activities. The Na+/Ca2+ exchangers (NCX) at the plasma membrane transport Ca2+ into or out of the cell according to the electrochemical gradients of Na+ and Ca2+ to modulate [Ca2+]i homeostasis. Calmodulin (CaM) senses [Ca2+]i changes and relays Ca2+ signals by binding to target proteins such as channels and transporters. However, it is not clear how calmodulin modulates NCX activity. Using CaM as a bait, we pulled down the intracellular loops subcloned from the NCX1 splice variants NCX1.1 and NCX1.3. This interaction requires both Ca2+ and a putative CaM-binding segment (CaMS). To determine whether CaM modulates NCX activity, we co-expressed NCX1 splice variants with CaM or CaM1234 (a Ca2+-binding deficient mutant) in HEK293T cells and measured the increase in [Ca2+]i contributed by the influx of Ca2+ through NCX. Deleting the CaMS from NCX1.1 and NCX1.3 attenuated exchange activity and decreased membrane localization. Without the mutually exclusive exon, the exchange activity was decreased and could be partially rescued by CaM1234. Point-mutations at any of the 4 conserved a.a. residues in the CaMS had differential effects in NCX1.1 and NCX1.3. Mutating the first two conserved a.a. in NCX1.1 decreased exchange activity; mutating the 3rd or 4th conserved a.a. residues did not alter exchange activity, but CaM co-expression suppressed activity. Mutating the 2nd and 3rd conserved a.a. residues in NCX1.3 decreased exchange activity. Taken together, our results demonstrate that CaM senses changes in [Ca2+]i and binds to the cytoplasmic loop of NCX1 to regulate exchange activity.

Monitoring extracellular K+ flux with a valinomycin-coated silicon nanowire field-effect transistor.

A silicon nanowire field-effect transistor (SiNW-FET) coated with a polyvinyl chloride (PVC) membrane containing valinomycin (VAL) was employed as a biosensor (referred to as VAL-PVC/SiNW-FET) to detect the K(+)-efflux from live chromaffin cells. The detection sensitivity of K(+) with the VAL-PVC/SiNW-FET covers a broad range of concentrations from 10(-6) to 10(-2) M. The apparent association constants between VAL and Li(+), Na(+), K(+), and Cs(+) in Tris buffer solution were determined to be 67±42, 120±23, 5974±115, and 4121±140 M(-1), respectively. By culturing chromaffin cells on the VAL-PVC/SiNW-FET, the conductance was significantly increased by nicotine stimulation in a bath buffer without Na(+). The K(+) concentration at the cell surface was determined to be ~20 µM under the stimulation of 5 mM nicotine. These results demonstrate that the VAL-PVC/SiNW-FET is sensitive and selective to detect the released K(+) from cells and is suitable for applications in cellular recording investigations.