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Abstract This letter addresses the output consensus problem for a class of two‐dimensional (2D) multi agent systems (MASs) described by Fornasini–Marchesini model. By transforming the 2D agent into a compact form, an adaptive variable, which adjusted by the tracking errors of itself and the neighbour agents, is designed to approximate the unknown varying coefficient. Then, based on the approximated coefficient and the iteration‐varying reference surfaces, the distributed adaptive iterative learning control strategy is obtained. The output consensus of the 2D multi agent is proved. Simulations are included to verify the effectiveness of the investigated distributed adaptive ILC for 2D MASs with random variations on initial condition and reference surface.

ObjectiveRheumatoid arthritis (RA) is a systemic disease that attacks the joints and causes a heavy economic burden on humans worldwide. T cells regulate RA progression and are considered crucial targets for therapy. Therefore, we aimed to integrate multiple datasets to explore the mechanisms of RA. Moreover, we established a T cell-related diagnostic model to provide a new method for RA immunotherapy.MethodsscRNA-seq and bulk-seq datasets for RA were obtained from the Gene Expression Omnibus (GEO) database. Various methods were used to analyze and characterize the T cell heterogeneity of RA. Using Mendelian randomization (MR) and expression quantitative trait loci (eQTL), we screened for potential pathogenic T cell marker genes in RA. Subsequently, we selected an optimal machine learning approach by comparing the nine types of machine learning in predicting RA to identify T cell-related diagnostic features to construct a nomogram model. Patients with RA were divided into different T cell-related clusters using the consensus clustering method. Finally, we performed immune cell infiltration and clinical correlation analyses of T cell-related diagnostic features.ResultsBy analyzing the scRNA-seq dataset, we obtained 10,211 cells that were annotated into 7 different subtypes based on specific marker genes. By integrating the eQTL from blood and RA GWAS, combined with XGB machine learning, we identified a total of 8 T cell-related diagnostic features (MIER1, PPP1CB, ICOS, GADD45A, CD3D, SLFN5, PIP4K2A, and IL6ST). Consensus clustering analysis showed that RA could be classified into two different T-cell patterns (Cluster 1 and Cluster 2), with Cluster 2 having a higher T-cell score than Cluster 1. The two clusters involved different pathways and had different immune cell infiltration states. There was no difference in age or sex between the two different T cell patterns. In addition, ICOS and IL6ST were negatively correlated with age in RA patients.ConclusionOur findings elucidate the heterogeneity of T cells in RA and the communication role of these cells in an RA immune microenvironment. The construction of T cell-related diagnostic models provides a resource for guiding RA immunotherapeutic strategies.

ABSTRACT Smallpox is a highly contagious human disease caused by the variola virus. Although the disease was eliminated in 1979 due to its highly contagious nature and historical pathogenicity, with a mortality rate of up to 30%, this virus is an important candidate for biological weapons. Currently, vaccines are the critical measures to prevent this virus infection and spread. In this study, we designed a peptide vaccine using immunoinformatics tools, which have the potential to activate human immunity against variola virus infection efficiently. The design of peptides derives from vaccine-candidate proteins showing protective potential in vaccinia WR strains. Potential non-toxic and nonallergenic T-cell and B-cell binding and cytokine-inducing epitopes were then screened through a priority prediction using special linkers to connect B-cell epitopes and T-cell epitopes, and an appropriate adjuvant was added to the vaccine construction to enhance the immunogenicity of the peptide vaccine. The 3D structure display, docking, and free energy calculation analysis indicate that the binding affinity between the vaccine peptide and Toll-like receptor 3 is high, and the vaccine receptor complex is highly stable. Notably, the vaccine we designed is obtained from the protective protein of the vaccinia and combined with preventive measures to avoid side effects. This vaccine is highly likely to produce an effective and safe immune response against the variola virus infection in the body.IMPORTANCEIn this work, we designed a vaccine with a cluster of multiple T-cell/B-cell epitopes, which should be effective in inducing systematic immune responses against variola virus infection. Besides, this work also provides a reference in vaccine design for preventing monkeypox virus infection, which is currently prevalent.

Abstract Background Postoperative lung cancer patients belong to the high-risk group for venous thromboembolism (VTE). The standardized preventive measures for perioperative VTE in lung cancer are not perfect, especially for the prevention and treatment of catheter-related thrombosis (CRT) caused by carried central venous catheters (CVCs) in lung cancer surgery. Patients and methods This study included 460 patients with lung cancer undergoing video-assisted thoracic surgery (VATS) in our center from July 2020 to June 2021. Patients were randomized into two groups, and intraoperatively-placed CVCs would be carried to discharge. During hospitalization, the control group was treated with low-molecular-weight heparin (LMWH), and the experimental group with LMWH + intermittent pneumatic compression (IPC). Vascular ultrasound was performed at three time points which included before surgery, before discharge, and one month after discharge. The incidence of VTE between the two groups was studied by the Log-binomial regression model. Results CRT occurred in 71.7% of the experimental group and 79.7% of the control group. The multivariate regression showed that the risk of developing CRT in the experimental group was lower than in the control group (Adjusted RR = 0.889 [95%CI0.799–0.989], p = 0.031), with no heterogeneity in subgroups (P for Interaction > 0.05). Moreover, the fibrinogen of patients in the experimental group was lower than control group at follow-up (P = 0.019). Conclusion IPC reduced the incidence of CRT during hospitalization in lung cancer patients after surgery. Trial registration No. ChiCTR2000034511.

Abstract Temperature is an important load for ballastless track. However, there is little research on the system dynamic responses when a train travels on a ballastless track under the temperature gradient of ballastless track. Considering the moving train, temperature gradient of slab track, gravity of slab track, and the contact nonlinearity between interfaces of slab track, a dynamic model for a high-speed train runs along the CRTS III slab track on subgrade is developed by a nonlinear coupled way in ANSYS. The system dynamic responses under the temperature gradient of slab track with different amplitudes are theoretically investigated with the model. The results show that: (1) The proportions of the initial force and stress caused by the temperature gradient of slab track are different for different calculation items. The initial fastener tension force and positive slab bending stress have large proportions exceeding 50%. (2) The maximum dynamic responses for slab track are not uniform along the track. The maximum slab bending stress, slab acceleration, concrete base acceleration appear in the slab middle, at the slab end, and at the concrete base end, respectively. (3) The maximum accelerations of track components appear when the fifth or sixth wheel passes the measuring point, and at least two cars should be used. (4) The temperature gradient of slab track has a small influence on the car body acceleration. However, the influences on the slab acceleration, concrete base acceleration, fastener tension force are large, and the influence on the slab bending stress is huge.

BackgroundImmunotherapy has become increasingly important in the perioperative period of non-small-cell lung cancer (NSCLC). In this study, we intended to develop a mutation-based model to predict the therapeutic effificacy of immune checkpoint inhibitors (ICIs) in patients with NSCLC.MethodsRandom Forest (RF) classifiers were generated to identify tumor gene mutated features associated with immunotherapy outcomes. Then the best classifier with the highest accuracy served for the development of the predictive model. The correlations of some reported biomarkers with the model were analyzed, such as TMB, PD-(L)1, KEAP1-driven co-mutations, and immune subtypes. The training cohort and validation cohorts performed survival analyses to estimate the predictive efficiency independently.ResultsAn 18-gene set was selected using random forest (RF) classififiers. A predictive model was developed based on the number of mutant genes among the candidate genes, and patients were divided into the MT group (mutant gene ≥ 2) and WT group (mutant gene < 2). The MT group (N = 54) had better overall survival (OS) compared to the WT group (N = 290); the median OS was not reached vs. nine months (P < 0.0001, AUC = 0.73). The robust predictive performance was confifirmed in three validation cohorts, with an AUC of 0.70, 0.57, and 0.64 (P < 0.05). The MT group was characterized by high tumor neoantigen burden (TNB), increased immune infifiltration cells such as CD8 T and macrophage cells, and upregulated immune checkpoint molecules, suggesting potential biological advantages in ICIs therapy.ConclusionsThe predictive model could precisely predict the immunotherapeutic efficacy in NSCLC based on the mutant genes within the model. Furthermore, some immune-related features and cell expression could support robust efficiency.

The Journal of Business Economics and Management (JBEM) has been very active in the field of economics and management science and brought many influential outputs in the last decades. This paper investigated the current status of publications and citations from JBEM and explored the hot topics and new trends represented by most used keywords extracted from the published articles from 2007 to 2019. The data were analyzed and mapped with respect to the most cited literature, most prolific authors, and publication records categorized by authors, institutions and countries. The analysis revealed that papers published each year by the JBEM is relatively stable and published papers has an expected citation number 7.68 times. The difference in frequency of keywords in different stages give us informative clue for future studies. The emerging topics include “SMEs” “Information” “framework” “perspective”, hence the likely focus of JBEM to consider submission of papers centered on these topics, the comparison of keywords between JBEM and Hot Papers & Highly Cited Papers was made as well. Some new trends, for example, information science combining with management science are new hot topics.

Abstract Background Bluetongue virus (BTV), an emerging insect vector mediated pathogen affecting both wild ruminants and livestock, has a genome consisting of 10 linear double-stranded RNA genome segments. BTV has a severe economic impact on agriculture in many parts of the world. Current reverse genetics (RG) strategy to rescue BTV mainly rely on in vitro synthesis of RNA transcripts from cloned complimentary DNA (cDNA) corresponding to viral genome segments with the aid of helper plasmids. RNA synthesis is a laborious job which is further complicated with a need for expensive reagents and a meticulous operational procedure. Additionally, the target genes must be cloned into a specific vector to prepare templates for RNA transcription. Result In this study, we have developed a PCR based BTV RG system with easy two-step transfection. Viable viruses were recovered following a first transfection with the seven helper plasmids and a second transfection with the 10 PCR products on the BSR cells. Further, recovered viruses were characterized with indirect immunofluorescence assays (IFA) and gene sequencing. And the proliferation properties of these viruses were also compared with wild type BTV. Interestingly, we have identified that viruses containing the segment 2 of the genome from reassortant BTV, grew slightly slower than the others. Conclusion In this study, a convenient PCR based RG platform for BTV is established, and this strategy could be an effective alternative to the original available BTV rescue methods. Furthermore, this RG strategy is likely applicable for other Orbiviruses.

In order to explore the damage and mechanical properties of ballastless track after a fire, the uniaxial compressive strength, shear strength, peak strain, and elastic modulus changes due to temperature were obtained through uniaxial compressive and shear tests of concrete after exposure to high temperatures. The test results showed that with increases in temperature, the uniaxial compressive strength, shear strength, and elastic modulus of concrete all presented a decreasing trend, while the peak strain had an increasing trend. Then, based on the classical damage theory model and the strength probability distribution function of concrete micro-units, the high-temperature damage constitutive equation for concrete was established, and the compressive stress–strain curve of concrete after exposure to high temperature was reproduced. Finally, using the CFD numerical simulation software, the temperature field of a ballastless track structure in a tunnel during a fire was obtained, and the temperatures at different positions of ballastless track bed were acquired. Combined with the high-temperature damage constitutive equation for concrete deduced from tests and theoretical analysis, the strength and damage values of the ballastless track bed at different positions after a tunnel fire were obtained.

In this paper, a high-speed train–CRTS III slab track–subgrade coupled dynamic model is established. With the model, the influence of vehicle number on the dynamic characteristics of a train–CRTS III slab track–subgrade coupled system with smooth and random track irregularity conditions for conventional and vibration-reduction CRTS III slab tracks are theoretically studied and analyzed. Some conclusions are drawn from the results: (1) the largest dynamic responses of the coupled system for all items and cases are no longer changed when the vehicle number exceeds three, and three vehicles are adequate to guarantee the simulation precision to investigate the dynamic responses of the coupled system. (2) The acceleration of the car body has almost no relation with the vehicle number, and only one vehicle is needed to study the vehicle dynamics using the train–CRTS III slab track–subgrade coupled dynamic model. (3) For the conventional CRTS III slab track on a subgrade, the vehicle number has a negligible influence on the accelerations of the rail, slab, and concrete base, the positive and negative bending moments of the rail, the compressive force of the fastener, and the positive bending stress of slab, but it has a large influence on the tension force of the fastener, and the negative bending stresses of the slab and concrete base. Only one vehicle is needed to study track dynamics without considering the tension force of the fastener, the negative bending stresses of the slab and concrete base, otherwise, two or more vehicles are required. (4) For vibration reduction of the CRTS III slab track on a subgrade, the number of vehicles has some influence on the dynamic responses of all track components, and at least two vehicles are required to investigate the track dynamics.

The dynamic model for the vehicle-CRTS III slab track system is established subjected to uniform seismic excitation, and the calculation program with MATLAB is compiled and verified. The influences of track parameters, seismic intensity, and running speed of the vehicle on the dynamic responses of the system and the vehicle running safety are analyzed. The results show that (1) the track parameters have certain influence on the dynamic responses of the system, and the seismic intensity and the running speed of the vehicle have important influence on the vehicle running safety; (2) the derailment coefficient is highly sensitive to seismic intensity, and the wheel load reduction rate is also highly sensitive to the running speed of the vehicle.

In order to study the axial compression performance of the T-shaped multi-cavity concrete-filled steel tube shear wall, first, three specimens were designed to perform the axial compression test. Then three-dimensional finite element analysis by the ABAQUS software was used to obtain the axial bearing capacity of the shear wall with different parameters. According to the results of the finite element model, the computational diagram in the limit state was obtained. The diagram was simplified into the core concrete in the non-enhanced area that was not constrained by the steel tube and the core concrete in the enhanced area that was uniformly constrained by the steel tube. Finally, a new practical equation for calculating the axial bearing capacity of a multi-cavity concrete-filled steel tubular shear wall was deduced and proposed based on the theory of ultimate equilibrium. The calculation results of the proposed equation were in good agreement with the finite element results, and the proposed equation can be used in practical engineering design.

Bluetongue virus (BTV) is an important pathogen of wild and domestic ruminants. Despite extensive study in recent decades, the interplay between BTV and host cells is not clearly understood. Autophagy as a cellular adaptive response plays a part in many viral infections. In our study, we found that BTV1 infection triggers the complete autophagic process in host cells, as demonstrated by the appearance of obvious double-membrane autophagosome-like vesicles, GFP-LC3 dots accumulation, the conversion of LC3-I to LC3-II and increased levels of autophagic flux in BSR cells (baby hamster kidney cell clones) and primary lamb lingual epithelial cells upon BTV1 infection. Moreover, the results of a UV-inactivated BTV1 infection assay suggested that the induction of autophagy was dependent on BTV1 replication. Therefore, we investigated the role of autophagy in BTV1 replication. The inhibition of autophagy by pharmacological inhibitors (3-MA, CQ) and RNA interference (siBeclin1) significantly decreased viral protein synthesis and virus yields. In contrast, treating BSR cells with rapamycin, an inducer of autophagy, promoted viral protein expression and the production of infectious BTV1. These findings lead us to conclude that autophagy is activated by BTV1 and contributes to its replication, and provide novel insights into BTV-host interactions.

Eastern equine encephalitis virus (EEEV) is a mosquito-borne virus that can cause both human and equine encephalitis with high case fatality rates. EEEV can also be widespread among birds, including pheasants, ostriches, emu, turkeys, whooping cranes and chickens. The E2 protein of EEEV and other Alphaviruses is an important immunogenic protein that elicits antibodies of diagnostic value. While many therapeutic and diagnostic applications of E2 protein-specific antibodies have been reported, the specific epitopes on E2 protein recognized by the antibody responses of different susceptible hosts, including avian species, remain poorly defined. In the present study, the avian E2-reactive polyclonal antibody (PAb) response was mapped to linear peptide epitopes using PAbs elicited in chickens and ducks following immunization with recombinant EEEV E2 protein and a series of 42 partially overlapping peptides covering the entire EEEV E2 protein. We identified 12 and 13 peptides recognized by the chicken and duck PAb response, respectively. Six of these linear peptides were commonly recognized by PAbs elicited in both avian species. Among them five epitopes recognized by both avian, the epitopes located at amino acids 211-226 and 331-352 were conserved among the EEEV antigenic complex, but not other associated alphaviruses, whereas the epitopes at amino acids 11-26, 30-45 and 151-166 were specific to EEEV subtype I. The five common peptide epitopes were not recognized by avian PAbs against Avian Influenza Virus (AIV) and Duck Plague Virus (DPV). The identification and characterization of EEEV E2 antibody epitopes may be aid the development of diagnostic tools and facilitate the design of epitope-based vaccines for EEEV. These results also offer information with which to study the structure of EEEV E2 protein.

West Nile virus (WNV) is a mosquito-borne flavivirus that primarily infects birds but occasionally infects humans and horses. Certain species of birds, including crows, house sparrows, geese, blue jays and ravens, are considered highly susceptible hosts to WNV. The nonstructural protein 1 (NS1) of WNV can elicit protective immune responses, including NS1-reactive antibodies, during infection of animals. The antigenicity of NS1 suggests that NS1-reactive antibodies could provide a basis for serological diagnostic reagents. To further define serological reagents for diagnostic use, the antigenic sites in NS1 that are targeted by host immune responses need to be identified and the potential diagnostic value of individual antigenic sites also needs to be defined. The present study describes comprehensive mapping of common immunodominant linear B-cell epitopes in the WNV NS1 using avian WNV NS1 antisera. We screened antisera from chickens, ducks and geese immunized with purified NS1 for reactivity against 35 partially overlapping peptides covering the entire WNV NS1. This study identified twelve, nine and six peptide epitopes recognized by chicken, duck and goose antibody responses, respectively. Three epitopes (NS1-3, 14 and 24) were recognized by antibodies elicited by immunization in all three avian species tested. We also found that NS1-3 and 24 were WNV-specific epitopes, whereas the NS1-14 epitope was conserved among the Japanese encephalitis virus (JEV) serocomplex viruses based on the reactivity of avian WNV NS1 antisera against polypeptides derived from the NS1 sequences of viruses of the JEV serocomplex. Further analysis showed that the three common polypeptide epitopes were not recognized by antibodies in Avian Influenza Virus (AIV), Newcastle Disease Virus (NDV), Duck Plague Virus (DPV) and Goose Parvovirus (GPV) antisera. The knowledge and reagents generated in this study have potential applications in differential diagnostic approaches and subunit vaccines development for WNV and other viruses of the JEV serocomplex.