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Tonic signaling of chimeric antigen receptor (CAR), i.e., the spontaneous CAR activation in the absence of tumor antigen stimulation, is considered to be a pivotal event controlling CAR-T efficacy. However, the molecular mechanism underlying the spontaneous CAR signals remains elusive. Here, we unveil that positively charged patches (PCPs) on the surface of the CAR antigen-binding domain mediate CAR clustering and result in CAR tonic signaling. For CARs with high tonic signaling (e.g., GD2.CAR and CSPG4.CAR), reducing PCPs on CARs or boosting ionic strength in the culture medium during ex vivo CAR-T cell expansion minimizes spontaneous CAR activation and alleviates CAR-T cell exhaustion. In contrast, introducing PCPs into the CAR with weak tonic signaling, such as CD19.CAR, results in improved in vivo persistence and superior antitumor function. These results demonstrate that CAR tonic signaling is induced and maintained by PCP-mediated CAR clustering. Notably, the mutations we generated to alter the PCPs maintain the antigen-binding affinity and specificity of the CAR. Therefore, our findings suggest that the rational tuning of PCPs to optimize tonic signaling and in vivo fitness of CAR-T cells is a promising design strategy for the next-generation CAR.

With rapid development in technology, asteroid mining may become a reality in the near future. This paper focuses on the possible impacts of asteroid mining on global equity. In order to evaluate the global equity situation, we developed a global equity assessment model with 5 superior indicators and 18 inferior indicators, in which analytic hierarchy process (AHP) and entropy weight method (EWM) are used to obtain the combined weight, and TOPSIS was used to calculate the National Strength Index (NSI). Then Global Equity Index (GEI) is obtained by measuring the dispersion degree of NSI. Hierarchical grouping. Finally, hierarchical cluster analysis is used to determine which countries are capable of asteroids mining, and the changes of NSI and then GEI are obtained through the mutual iteration of the value obtained from minerals and NSI. Our analysis of data from 30 European countries from 1995 to 2020 shows that unregulated asteroid mining increases global inequity, depending on factors such as the total value of minerals and the difficulty of mining. Our study provides theoretical support and policy recommendations for reducing potential inequities caused by asteroid mining.

With growing data volumes and the scaling of data center clusters, communication resources often become a bottleneck in service provisioning for many MapReduce applications (e.g., training machine learning models). Therefore, data placements that bring data blocks closer to data consumers (e.g., MapReduce applications) are seen as a promising solution. In this article, we propose an efficient data-placement technique that considers network traffic reduction as well as QoS guarantees for the data blocks to optimize the communication resources. We first formulate the joint optimization of the data-placement problem, propose a generic model for minimizing communication costs, and show that the joint data-placement problem is NP-hard. To solve this problem, we propose a heuristic algorithm considering traffic flows in the network topology of data centers by first seeking optimal QoS-aware data placement based on golden division on a Zipflike replica distribution, then transforming the joint data-placement problem into a block-dependence tree (BDT) construction problem, and finally reducing the BDT construction to a graph-partitioning problem. The experimental results demonstrate that our data-placement approach could effectively improve the performance of MapReduce jobs with lower communication costs and less job execution time for big-data processing.

Unmanned Aerial Vehicle (UAV) swarms are widely applied for service provisioning in many domains such as topographic mapping and traffic monitoring. These UAV applications are complicated as they demand not only huge computational resources but also strict latency requirements. However, due to the limited onboard resources of UAVs as well as various dynamics of applications and environments, it's challenging to obtain a feasible computation offloading policy in online environments. To cope with these problems, we propose an online algorithm for UAV swarms to jointly optimize the computation offloading and multi-hop routing scheduling in the Edge-Cloud environment. First, we propose a UAV-Edge-Cloud computing model to meet the requirements of latency and computing capability. We then formulate a joint optimization of workflow assignment and multi-hop routing scheduling in order to minimize the computation cost and latency. To tackle this NP-hard problem, an algorithm based on the Markov approximation technique is designed to obtain near-optimal solutions. Furthermore, to achieve high long-term performance in online environments, we exploit Lyapunov optimization to control the migration cost caused by the dynamics of application and environment. Finally, extensive simulation results demonstrate that our approach achieves a long-term high-efficiency and stable performance in an online environment for UAV swarms with respect to computation offloading and traffic routing.

To improve power and cycling performance of lithium-ion batteries, dual-layer or porosity-gradient electrodes have been proposed. By engineering a higher porosity close to the separator, the intention is to improve ion transport where it is most impactful. In this research, MacMullin numbers of two dual-layer anode samples are tested using an impedance measurement technique developed previously. To characterize the microstructure of each layer independently, we developed an improved transmission-line model that accounts for each layer’s properties.Virtual experiments using COMSOL Multiphysics to simulate impedance measurements are used to examine and improve the accuracy of the numerical inversion procedure. The results for the two dual-layer anodes studied show that MacMullin numbers follow expected trends, though the anodes are quite different from each other.

The microstructure determines transport properties in lithium-ion battery electrodes. There is generally a tradeoff between electronic and ionic transport when adjusting the microstructure. One way of adjusting the microstructure is through calendering, where the electrode is compressed following drying. Understanding how calendering affects not only the average but also the local electronic and ionic transport provides additional insight when developing battery electrodes and engineering better batteries. If a correlation exists between the two properties, an optimal porosity that maximizes both ionic and electronic transport could be determined. In order to better understand the influence of microstructure on these transport properties, we tested a series of commercial-grade electrodes including NMC cathodes, graphite anodes, and a graphite-silicon anode. The local electronic conductivity of the electrodes was found using a micro-flexible-surface probe previously developed by our research group [1]. Likewise, the local ionic conductivity was found using an aperture probe previously developed by our research group [2]. All electrodes were obtained from Argonne National Laboratory in calendered and un-calendered states. Through testing various electrodes before and after calendering, we found that not every electrode experienced an increase in electronic conductivity after calendering, and that in general heterogeneity of the electronic conductivity decreased after calendering. The local ionic resistance, as indicated by MacMullin number, was found to increase after calendering, as expected. Figure 1 illustrates the local ionic and electronic transport results for one cathode. Ionic transport was found to be almost solely influenced by porosity. However, electronic transport was found to be influenced by a variety of factors including the nature, distribution, and connectivity of conductive materials. [1] Vogel et al., J. Electrochem. Soc. 168, 100504 (2021). [2] Liu et al., ECS Meeting Abstracts 2021, 444. Figure 1

In this article, we propose a hybrid computing model, UAV-Edge-Cloud, bringing edge/cloud computing and UAV swarm together to achieve high quality of service (QoS) guarantees. First, we design this novel hybrid computing framework to provide powerful resources to support resource-intensive applications and real-time tasks at edge networks. Next, we discuss some potential applications for smart cities and raise open research issues of the proposed hybrid framework. We then study a joint task placement and routing problem for latency-critical applications as a case study. Finally, the simulation results show that our approach can improve the QoS of UAV swarms effectively.

In the credit business, business default often occurs. This paper maps the relationship between customer default rate and scorecard, and uses the fusion of logistic regression and lightgbm to establish the scorecard model to complete the construction of the scorecard. Firstly, the data set is loaded and analyzed. Finally, KS value and AUC value are used to evaluate the discrimination and stability of the model. Experiments show that the score card model based on the fusion model has good differentiation and stability.

Self-attention mechanism is primarily designed to capture the correlation (interaction) between any two objects in a sequence. Inspired by self-attention's success in many NLP tasks, some researchers have employed self-attention in sequential recommendation to refine user representations by capturing the correlations between the historical interacted items of a user. However, the user representations in previous self-attention based models are not flexible enough since the self-attention is only applied on user side, restricting performance improvement. In this paper, we propose a deep recommendation model with feature-level self-attention, namely SAFrec, which exhibits enhanced recommendation performance mainly due to its two advantages. The first one is that SAFrec employs self-attention mechanism on user side and item side simultaneously, to co-refine user representations and item representations. The second one is that, SAFrec leverages item features distilled from open knowledge graphs or websites, to represent users and items on fine-grained level (feature-level). Thus the correlations between users and items are discovered sufficiently. The extensive experiments conducted over two real datasets (NetEase music and Book-Crossing) not only demonstrate SAFrec's superiority on top-n recommendation over the state-of-the-art deep recommendation models, but also validate the significance of incorporating self-attention mechanism and feature-level representations.

In this paper, radio wave coverage properties inside a train located in confined space are studied by using Time-Domain Finite Difference method (FDTD). The works in this paper are mainly focused on the effect of materials of train and windows on the radio wave coverage. Calculation results show that metallic train body will cause a loss about 10 dB. When using Fiber Reinforced Plastic (FRP) as train body, the loss reduces significantly. In addition, for windows, using heat-absorbing glazing leads to an extra loss about 1 dB compared to that of dielectric glass. It is concluded that train material and windows have certain impacts on the radio wave coverage inside the train and need to be further studied.

Heterogeneity of MacMullin number within battery electrodes is a key metric affecting cell performance. To characterize this heterogeneity, an aperture probe was developed. This probe, coupled with a newly developed transmission-line model, allows for measurements of tortuosity, represented by the MacMullin number, on millimeter length scales. Local MacMullin number values of seven electrodes were measured, and the ionic resistance profiles of these electrodes are given through contour maps of the MacMullin number. The method is validated by comparing the average MacMullin number to the value obtained through other measurement methods. The results show significant local MacMullin number variation in such electrodes on a millimeter length scale. This method will allow battery manufacturers and researchers to better quantify sources of heterogeneity and improve electrode quality.

Intelligent mobile objects (mobile robots) are gradually integrated into People’s Daily life, and path planning is the core of this kind of robots. In this article, ant colony algorithm is adopted to plan a global path through all points in the global space based on pheromone changes, so as to solve the practical problem that a robot needs to walk n points at a time and cannot repeat, and its distance is the shortest. Finally, the shortest path is solved based on MATLAB simulation platform.

Lacustrine organic-rich shale with extremely heterogeneous pore structure is widespread in the second member of the Permian Lucaogou Formation (P2l2) of the Santanghu Basin. However, information on the pore structure, fluid mobility, and oiliness characteristics is still lacking, as well as the interaction between them in the organic-rich shales remains controversial. To address these problems, this study analyzed the influencing factors of pore structure, oiliness, and fluid mobility of the P2l2 shale and constrained the lower limit of movable fluid pore throat radius based on thin sections, routine core analysis, whole rock X-ray diffraction (XRD), scanning electron microscopy (SEM), high-pressure mercury injection (HPMI), nuclear magnetic resonance (NMR), constant-rate mercury injection (CMI), and nano-CT scanning data. The P2l2 shale was characterized by fine-grained minerals of felsic (tuffaceous material) and carbonate (dolomite), with poor reservoir physical properties and strong oil-bearing heterogeneity. Micro- and nano-scale pores are the main type of storage space. Among them, most of the microfractures emit green to yellow hydrocarbon fluorescence regardless of whether they are filled or not, as do the edges of dolomite grains. While the edges of the felsic minerals are characterized by stronger orange yellow fluorescence of organic matter. According to the morphology and parameters of HPMI and NMR curves, the pore structure can be divided into four types. From type 1 to type 4 pore structure, the maximum mercury saturation decreases from 95 to 47 % (avg. 70 %), indicating poor pore connectivity, and the pore throat radius that mainly contributes to permeability is > 0.04 μm. Meantime, the NMR T2 spectrum gradually transitions from right unimodal to left unimodal behavior, with a gradual decrease in the saturation of movable fluid and a transition of the mineral type from carbonate to felsic. Fluid mobility is not only influenced by macropores, but also related to the content of small pores (T2

Faced with massive amounts of data, people may not be able to choose the items they like. The recommendation system came into being, and it has achieved a breakthrough for a long time. Using deep learning can mine the hidden attributes of users' items and integrate them well, bringing new changes to the recommendation system. This article describes the deep learning-based recommendation system and the traditional recommendation system, and analyzes their advantages and disadvantages.

The porosity system of shale reservoir contains organic pore and inorganic pore, of which the gas adsorption characteristics and wettability properties differ dramatically. In order to conduct estimation of organic pore and inorganic pore in shale reservoir, six marine shale samples were selected to quantify the proportion (vol%) of different pores by using the new method, in which the NMR T2 spectra of samples saturated with deionized water and kerosene were respectively acquired, representing pore size distribution of hydrophilic pore and lipophilic pore correspondingly. The NMR T2 signals of different saturating fluids were introduced to calculate the proportion (vol%) of organic pore and inorganic pore. Further, the observation of argon milled image of shale samples which can give statistical analysis is also conducted accordingly. The results from the two methods are almost in agreement, indicating feasibility of the new method. By using the method in shales with varying maturities, the proportions of organic and inorganic pores of shales in different evolution stages were figured out. Generally, the TOC is positively correlated with organic porosity that almost an organic porosity of 1.51–1.76% (vol.) is provided for per unit TOC (1.0%, wt.) in low-mature shale. And the porosity increase caused by per unit TOC (1.0%, wt.) during organic matter maturation is 2.53–3.41%, while the proportion of inorganic porosity continuously decreases with thermal maturity. From the study, it is significant that the organic porosity and inorganic porosity of shale with given TOC and thermal maturity can be roughly estimated.

The porosity system in shale, which is a combination of organic-hosted pore and inorganic pore, plays a pivotal role in adsorbing methane for gas shale reservoir. In order to identify the porosity system with different properties and to give a quantitative characterization of pore structure for each individual porosity system, the dual liquid NMR method was conducted on six shale samples from the Lower Silurian Longmaxi Formation in the Southern Sichuan Basin. In shale reservoir, hydrophilic pore and oleophilic pore are respectively related to hydrophilic minerals and oleophilic organic matter. The NMR method detected the signal of water penetrating the water-wetting porosity system when saturated with water, which can reflect the pore size distribution (PSD) of hydrophilic porosity. The PSD of oleophilic pore can also be reflected when saturated with kerosene, vice versa. Generally, the NMR T2 spectra of sample saturated with DI water and kerosene, T2_water and T2_kerosene exhibit bimodal pattern, a dominant peak with a relaxation time range of 0.1-10 ms and a minor peak with a relaxation time ranging 10-100 ms. Generally, higher TOC content corresponds to large amounts of cumulative organic nanoscale pore. The organic-rich shale shows high content of organic-hosted pores and large amounts of inorganic pores which are validated by plane porosity statistics from the observation of SEM photographs. By correlating the two pore structure characterizing methods, the relaxivity of shale can be calculated to be 0.055-0.092 μm/ms when saturated with water. The quantitative estimation of organic-hosted porosity system and inorganic porosity system in the shale will provide a pivotal basis for elucidating gas occurrence states in shale.

Computation offloading is significant to the UAV swarms by migrating computational tasks from the UAV swarms to the edge or cloud computing infrastructure. However, when studying the computation offloading problem, existing approaches do not fully consider the characteristics of UAV swarms and do not differentiate the characteristics of cloud computing and edge computing well. In this paper, we study a joint computation offloading and routing optimization problem for UAV swarms under an UAV-Edge-Cloud computing architecture. Our contributions can be summarized as the following three aspects. First, to fully optimize the characteristics of UAV swarms, we jointly consider the computation offloading and routing for UAV swarms. Then, to highlight the characteristics of cloud computing and edge computing, we propose a novel three-layer computing model joint computation offloading and routing problem. Finally, we design a polynomial near-optimal approximation algorithm to solve the joint optimization problem using the Markov approximation technique. Finally, our simulation results demonstrate the high efficiency of our proposed algorithm.

Lithium-ion battery electrodes are known to have irregularities in their microstructure. When electrodes are not uniform in terms of conductivity, such inhomogeneities can lead to localized variability in current flow, potential, and species concentrations, which are associated with cell degradation [1]. Understanding and quantifying heterogeneity of battery electrodes is therefore an important step in engineering better batteries. Our research group has previously succeeded in quantifying the variation of electronic conductivity of electrodes using a four-line microprobe [2]. Methods have also previously been developed for measuring the average ionic conductivity of battery electrodes [3], but there was no method for measuring localized ionic conductivity. Our research group recently developed a way to do such a measurement, allowing us to investigate the heterogeneity of effective ionic conductivity across an electrode. We report the results of local MacMullin Number measurements (proportional to tortuosity or the inverse of conductivity) for various electrodes. We show the heterogeneity of both conventional Li-ion anodes and cathodes and the effect of cycling. In the future, we hope that this technology can be used as a diagnostic tool for improving design and manufacture of electrodes. Fig. 1. Map of MacMullin Number for a Li-ion cathode References: [1] Vogel et al., Electrochimica Acta 297, 820 (2019). [2] Lanterman et al., Journal of the Electrochemical Society 162, A2145 (2015). [3] Pouraghajan et al., Journal of the Electrochemical Society 165, A2644 (2018). Figure 1

Due to the nature of how porous battery electrodes are fabricated, their microstructure is not uniform. For instance, there are variations in composition, effective electronic transport, and effective ionic transport. Such heterogeneity has been associated with several battery application issues. For example, variability in transport of ions can lead to a tendency for localized plating of lithium on anodes during fast charging [1-2]. Studying the heterogeneity of electrodes is a growing research topic. Our research group has previously developed a micro-four-line probe that successfully measured the variation of electronic conductivity of electrodes [3]. Another method to study the microstructure of electrodes is by means of SEM and X-ray tomography, and the variation of tortuosity (effective ionic resistance) in electrodes was computed by analyzing the tomographic data of microstructure [4]. We report here on a new technique to measure the local ionic resistance on a sub-mm length scale. A probe was made to detect the local transport of ions through a small aperture. The probe is scanned across the surface of a porous thin-film electrode in order to create maps of tortuosity or MacMullin number. The measurement was performed using electrochemical impedance spectroscopy, and an associated model is needed to invert the experimental results. [1] Harris et al., The Journal of Physical Chemistry C 117, 6481 (2013). [2] Vogel et al., Electrochimica Acta 297, 820 (2019). [3] Lanterman et al., Journal of the Electrochemical Society 162, A2145 (2015). [4] Kehrwald et al. Journal of The Electrochemical Society 158, A1393 (2011). Figure 1

Oral chemotherapy is quickly emerging as an appealing option for cancer patients. It is less stressful because the patient has fewer hospital visits and can still maintain a close relationship with health care professionals. Three kinds of nanoparticles made from commercial poly(e-caprolactone) (PCL) and self-synthesized d-α-tocopheryl poly(ethylene glycol) 1000 succinate -b-poly(e-caprolactone-ran-glycolide) [TPGS-b-(PCL-ran-PGA)] diblock copolymer were prepared in this study for the oral delivery of antitumor agents, including chitosan-modified PCL nanoparticles, nonmodified TPGS-b-(PCL-ran-PGA) nanoparticles, and chitosan-modified TPGS-b-(PCL-ran-PGA) nanoparticles. First, the TPGS-b-(PCL-ran-PGA) diblock copolymer was synthesized and structurally characterized. Chitosan was adopted to extend the retention time at the cell surface and thus increase the chance of nanoparticle uptake by the gastrointestinal mucosa and improve the absorption of drugs after oral administration. The resulting TPGS-b-(PCL-ran-PGA) nanoparticles were found to be of spherical shape and around 200 nm in diameter with a narrow size distribution. The surface charge of the TPGS-b-(PCL-ran-PGA) nanoparticles could be reversed from anionic to cationic after surface modification. The chitosan-modified TPGS-b-(PCL-ran-PGA) nanoparticles displayed a significantly higher level of cellular uptake compared with the chitosan-modified PCL nanoparticles and nonmodified TPGS-b-(PCL-ran-PGA) nanoparticles. In vitro cell viability studies showed the advantages of the chitosan-modified TPGS-b-(PCL-ran-PGA) nanoparticles over Taxol in terms of their cytotoxicity against human RT112 cells. In summary, the oral delivery of antitumor agents by chitosan-modified TPGS-b-(PCL-ran-PGA) nanoparticles produced results that were promising for the treatment of patients with bladder cancer. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 2118–2126, 2013

To describe a novel transurethral front-firing Greenlight bladder autoaugmentation for the treatment of bladder contracture and report initial clinical outcomes. Between April 2014 and August 2015, five patients diagnosed with contracted bladder were all refractory to conservative treatment and received novel transurethral autoaugmentation. CT scan and urodynamics examination were conducted before operation for disease assessment. Mucosal and muscular layers of bladder wall in fundus were incised vertically and horizontally with front-firing Greenlight laser to enlarge bladder capacity in the operation. Imaging examination and periodical urodynamics study were performed to evaluate the clinical outcomes of the procedure in postoperative follow-up. Transurethral front-firing Greenlight bladder autoaugmentation was performed successfully on all the patients. The mean operative time was 59 min (range 52–65 min) with no significant blood loss. Urodynamic parameters of these patients after operation improved significantly compared with those before operation. Average maximum cystometric capacity (V max) increased from 91.2 to 333 ml (p

Adipose-derived stem cell (ADSC) transplantation has emerged as a potential tool for the treatment of cardiovascular disease. However, with a limited renewal capacity and the need for mass cells during the engraftment, strategies are needed to enhance ADSC proliferative capacity. In this study, we explored the effects of exendin-4 (Ex-4), a glucagon-like peptide-1 analog, on the growth of ADSCs, focusing in particular on c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) signaling pathways. Firstly, ADSCs were isolated and cultured in vitro. Then, flow cytometry demonstrated that ADSCs were positive for CD90 and CD29 but negative for CD31, CD34, and CD45. Ex-4 (0-50 nM) treatment increased ADSC proliferation in a dose-dependent manner but had no effects on stem cell markers of ADSCs. Moreover, we found that Ex-4 treatment elevated the phosphorylation levels of the JNK and ERK signaling pathways. Furthermore, utilization of Ex-4 also promoted cyclin D1 and cyclin E protein expression, which was accompanied by more Edu(+) cells and a higher percentage of cells in the S-phase of the cell cycle after Ex-4 treatment. In parallel, the application of inhibitors SP600125 and PD98059, inhibitors of the JNK and ERK signaling pathways, respectively, not only reversed such effects of Ex-4 on JNK and ERK but also resulted in lower percentages of S-phase cells and fewer numbers of Edu(+) cells. In summary, Ex-4 has no effects on stem cell markers in ADSCs but promotes ADSC growth via JNK and ERK signaling pathways.

Objective: To investigate the expression and clinical significance of TRAP1 (tumor necrosis factor receptor-associated protein 1) in kidney cancer. Methods: TRAP1 expression was detected in kidney cancer and normal kidney tissues by qRT-PCR and immunohistochemistry (IHC), respectively. Then, the correlation of TRAP1 expression with clinicopathological characters and patients’ prognosis was evaluated in kidney cancer. Results: IHC results revealed that the high-expression rates of TRAP1 in kidney cancer tissues and normal kidney tissues were 51.3% (41/80), 23.3% (7/30), and the difference was statistically significant (P=0.01). Also, TRAP1 mRNA level in kidney cancer was found to be significantly greater compared with those in normal kidney by qRT-PCR. In addition, TRAP1 expression in kidney cancer significantly correlated with lymph node metastasis and clinical stage (P

The linear trajectory is one of major performance for industrial robot. A vision-based robots' linear trajectory measure system is introduced in this paper using a structure light and a special measure track. The three inflexions of the optical strip imaging at the V shape track are used to compute the pose between the sensor frame and the track frame, then the linear trajectory of robot can be computed. The emphasis of this paper is the image processing. At this paper, the process of the image processing method for this system will be described at first, then the key methods include image segmentation and line fitting will be discussed, at last the experiment results will be given.