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Human outgrowth endothelial progenitor cells (BOECs), derived from peripheral blood mononuclear express endothelial protein profiles (i.e. CD31, 144, and vWF). Endothelial nitric oxide ...synthase (eNOS) is an important regulator of vascular tone and loss of eNOS activity is a hallmark of endothelial dysfunction. In this study, we examine the expression and activity of eNOS and elucidate the cause of differential regulation of eNOS in BOECs compared to mature endothelial cells. We found that BOECs express markedly lower eNOS protein (0.34 ± 0.13), mRNA (0.29 ± 0.17) as well as activity levels (0.49 ± 0.18) when compared to HUVECs or Human Aortic Endothelial Cells. When grown on fibronectin (FN), type I collagen (Col. I), and type IV collagen (Col. IV) we found significantly decreased eNOS protein, mRNA and mRNA stability in HUVECs compared to cells on polystyrene. The matrix mediated downregulation was blocked by β1 integrin siRNA and focal adhesion kinase siRNA transfection. In addition, rho‐associated protein kinase inhibitors including fasudil and Y27632 blocked the effect of ECM on eNOS downregulation in HUVECs. In contrast, in BOECs, eNOS protein expression was unchanged by cell‐ECM interactions. Interestingly, BOECs can highly deposit ECM molecules (Col. I, FN and Laminin) that assemble to an organized mesh‐like structure whereas HUVECs only express few ECM proteins which cannot form organized structures. Blocking Col. I synthesis with siRNA significantly enhanced eNOS expression in BOECs (1.77 ± 0.41 fold increase). Taken together, our results confirm a strong matrix mediated regulation of eNOS in endothelial cells and suggest that limited eNOS expression in BOECs results from higher ECM production.
Theophylline is a potent bronchodilator for the treatment of asthma, bronchitis, and emphysema. Its narrow therapeutic window (20–100 μM) demands that the blood concentration of theophylline be ...monitored carefully, which can be achieved by aptamer capture. Thus, an understanding of what occurs when aptamers bind to theophylline is critical for identifying a high-affinity and high-specificity aptamer, which improve the sensitivity and selectivity of theophylline detection. Consequently, there is an urgent need to develop a simple, convenient, and nondestructive method to monitor conformational changes during the binding process. Here, we report the determination of the affinity of a selected aptamer and theophylline via biolayer interferometry (BLI) experiments. Additionally, using surface-enhanced Raman spectroscopy (SERS), the conformational changes on theophylline–aptamer binding were identified from differences in the SER spectra. Finally, molecular dynamics (MD) simulations were used to identify the specific conformational changes of the aptamer during the binding process. Such a combined BLI-SERS-MD method provides an in-depth understanding of the theophylline–aptamer binding processes and a comprehensive explanation for conformational changes, which helps to select, design, and modify an aptamer with high affinity and specificity. It can also be used as a scheme for the study of other aptamer–ligand interactions, which can be applied to the detection, sensing, clinical diagnosis, and treatment of diseases.
We established a method that synthesizes BLI experiments, SERS experiments, and MD simulations to analyze the conformational changes of aptamers in the process of binding to theophylline. This provides an in-depth understanding of theophylline–aptamer binding processes and a comprehensive explanation for conformational changes. Display omitted
•Method integrates BLI, SERS, and MD simulations to study the aptamer’s conformational changes.•Method acquires a comprehensive description of the conformational changes during binding process.•Method provides strong support to increase the affinity and stability of other ligand–aptamer.
Giving full play to the flexibility of hydropower and integrating more variable renewable energy (VRE) is of great significance for accelerating the transformation of China's power energy system. For ...middle- to large-sized hydropower units, its irregular vibration zone (VZ) is a major factor affecting its flexibility, because VZs limits the power output and adjustment range. In the existing studies on hydropower unit commitment and flexibility scheduling, VZs only limits the output of hydropower units, while the impact on the flexibility adjustment ability of units is ignored. The hydropower flexibility in day-ahead scheme is overestimated, which increases the risk of system flexibility shortage causing power curtailment and load loss. In this study, a novel day-ahead scheduling model considering the flexibility limited by the VZs and the probability of flexibility shortage is constructed for the day-ahead generation scheme of hydropower-VRE hybrid generation system (HVHGS) to optimize the target load, VRE output and hydropower unit commitments. The impaction of the VZs on hydropower flexibility is firstly modeled by chance constraints and stochastic programming method. Moreover, a data-driven model based on machine learning and an efficient solving approach based on successive linear programming is carry out to describe the uncertainty of VRE output more realistically and ensure the timeliness of optimization scheme, respectively. The proposed model is applied to a real hydropower station in the Hongshui River Basin in China. In 16 representative scenarios, the proposed model can complete the optimization in an acceptable time, with a maximum of 444.57 s. Compared with the traditional interval optimization model, the proposed model effectively improves the flexibility supply capacity of hydropower in the day-ahead scheme. The maximum reduction value of flexibility shortage probability and expectation reach 98.77% and 442.66 MW, respectively. In particular, the flexibility of the model is most obvious under heavy load demand in flood season, and it is almost not at the cost of daily target load adjustment, which provides practical reference for decision makers.
•The limitation of vibration zones on flexibility supply of hydropower.•Chance constrains on flexibility shortage probability considering vibration zones.•Machine learning model to describe the uncertainty of variable renewable energy.•Mitigate the risk of insufficient flexibility of day-ahead scheme.
Human cortical organoids (hCOs), derived from human embryonic stem cells (hESCs), provide a platform to study human brain development and diseases in complex three-dimensional tissue. However, ...current hCOs lack microvasculature, resulting in limited oxygen and nutrient delivery to the inner-most parts of hCOs. We engineered hESCs to ectopically express human ETS variant 2 (ETV2). ETV2-expressing cells in hCOs contributed to forming a complex vascular-like network in hCOs. Importantly, the presence of vasculature-like structures resulted in enhanced functional maturation of organoids. We found that vascularized hCOs (vhCOs) acquired several blood-brain barrier characteristics, including an increase in the expression of tight junctions, nutrient transporters and trans-endothelial electrical resistance. Finally, ETV2-induced endothelium supported the formation of perfused blood vessels in vivo. These vhCOs form vasculature-like structures that resemble the vasculature in early prenatal brain, and they present a robust model to study brain disease in vitro.
Growth of organic thin films using physical vapor deposition typically follows a three-dimensional mode, resulting in a rough surface, which undermines their application potential. To address this ...issue, we have studied the effect of electric field and temperature on the growth dynamics, especially the heterogeneous nucleation process, of croconic acid (CA) films, taking advantage of the large dipole moment of the molecules and the ferroelectric polarization of the molecular crystals. We found that the nucleation rate reaches the maximum at intermediate temperature, and the electric field shifts the maximum nucleation rate towards lower temperature. An analysis using the classical nucleation theory suggests that the electric field decreases the sublimation temperature, increases the wetting angle, and decreases the surface diffusion barrier. These results provide important insight into the growth of molecular crystal films under electric fields and pave the way to fabricating films with better surface characteristics for molecular ferroelectric films.
An external electric field can affect the growth dynamics of croconic acid (CA) films, especially the heterogeneous nucleation process, as evidenced by the shift of temperature dependence of the nucleation rate in the electric field.
Reinforcement learning (RL) has attracted much attention recently, as new and emerging AI-based applications are demanding the capabilities to intelligently react to environment changes. Unlike ...distributed deep neural network (DNN) training, the distributed RL training has its unique workload characteristics - it generates orders of magnitude more iterations with much smaller sized but more frequent gradient aggregations. More specifically, our study with typical RL algorithms shows that their distributed training is latency critical and that the network communication for gradient aggregation occupies up to 83.2% of the execution time of each training iteration.
In this paper, we present iSwitch, an in-switch acceleration solution that moves the gradient aggregation from server nodes into the network switches, thus we can reduce the number of network hops for gradient aggregation. This not only reduces the end-to-end network latency for synchronous training, but also improves the convergence with faster weight updates for asynchronous training. Upon the in-switch accelerator, we further reduce the synchronization overhead by conducting on-the-fly gradient aggregation at the granularity of network packets rather than gradient vectors. Moreover, we rethink the distributed RL training algorithms and also propose a hierarchical aggregation mechanism to further increase the parallelism and scalability of the distributed RL training at rack scale.
We implement iSwitch using a real-world programmable switch NetFPGA board. We extend the control and data plane of the programmable switch to support iSwitch without affecting its regular network functions. Compared with state-of-the-art distributed training approaches, iSwitch offers a system-level speedup of up to 3.66× for synchronous distributed training and 3.71× for asynchronous distributed training, while achieving better scalability.
Phase change materials (PCMs) have attracted numerous attention owing to their high energy storage density, cost-effective and operationally simple, however, the “solid-liquid” leakage and limited ...solar absorbance seriously hinder their widespread applications. Herein, an innovative chitosan/cellulose nanocrystal/CMK-3 (CS/CNC/CMK-3) aerogel based shape-stable PCM (SSPCM) was successfully synthesized, in which chemically cross-linked CS and CNC acted as three-dimensional supporting skeleton, CMK-3 endowed solar-to-thermal energy conversion ability and the impregnating polyethylene glycol (PEG) acted as the latent heat storage unit. The as-synthesized CS/CNC/CMK-3 aerogel/PEG (CCCA/PEG) showed ultrahigh melting/crystallization enthalpy of 178.5/171.1 J g−1 and excellent shape stability. The PEG was effectively embedded into the hierarchical porous architecture and the composite PCM could preserve its original shape without any leakage even compressed above the melting point of PEG. Meanwhile, the CCCA/PEG exhibited robust thermal reliability with an ultralow enthalpy fading rate of 0.030 ± 0.012 % per cycle over 100 thermal cycles. Intriguingly, the introduction of CMK-3 also significantly improved the solar-to-thermal energy conversion performance of CCCA/PEG, and a high solar-to-thermal conversion efficiency of 93.1 % could be realized. This work provided a potential strategy to design and synthesize high-performance sustainable SSPCM, which showed tremendous potential in the practical solar energy harvesting, conversion and storage applications.
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•Chemically crosslinked CS/CNC/CMK-3 aerogel-based SSPCM was successfully synthesized.•CCCA/PEG possessed high melting/crystallization enthalpy of 178.5/171.1 J g−1.•CCCA/PEG showed excellent thermal reliability with low enthalpy fading rate of 0.030 ± 0.012 %.•CCCA/PEG showed great potential for practical solar-energy utilization and storage.
Flexible solid-state zinc-air batteries as a wearable energy storage device with great potential, and their separators, which control ion permeability, inhibit zinc dendrite generation, and regulate ...catalytic active sites, have been developed as gel electrolyte separators with high retention of electrolyte uptake. However, the gel electrolyte separator still has problems such as poor affinity with the electrolyte and poor ionic conductivity, which limits its further application. In order to further improve the electrolyte absorption, ionic conductivity and mechanical strength of cellulose acetate(CA)/polyvinyl alcohol (PVA) nanofibers, TiO
was added to CA/PVA to increase the porosity, and glutaraldehyde (GA) was used to modify the CA/PVA/TiO
separator by acetal reaction with CA and PVA to make the molecules closely linked. The results shows that the optimal mass fractions of TiO
and GA were 2% and 5%, respectively. At this time, the porosity and absorption rate of the separator increased from 48% to 68.2% and 142.4% to 285.3%, respectively. The discharge capacity reached 179 mA cm
, and the cycle stability rate was 89% after 7 stable constant current charge/discharge cycles.
Device applications often require thin film growth with quasi-two-dimensional morphology and crystallization, which are not always compatible. In this work, we exploit the method of low-temperature ...deposition followed by restrained crystallization (LDRC) in the growth of crystalline organic molecular thin films, which tend to grow three-dimensionally with random orientations. We demonstrate that for 2-methylbenzimidazole, a molecular ferroelectric that tends to crystallize in spherulites, the quasi-two-dimensional films can be grown using LDRC with highly oriented polar axes and single-crystal-level ferroelectric properties. The crystallization process was shown to occur during the post-deposition annealing process using the in situ electrical measurements. The limited diffusion, low nucleation density, and low activation energy were found to be critical for the formation of the plate-shaped quasi-two-dimensional films. These results mark an important step in elucidating the LDRC as an effective and general approach for fabricating films with balanced crystallinity and morphology which are critical for applications.
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