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Colorectal cancer (CRC) is known to be resistant to immunotherapy. In our phase-I clinical trial, one patient achieved a 313-day prolonged response during the combined treatment of oncolytic virotherapy and immunotherapy. To gain a deeper understanding of the potential molecular mechanisms, we performed a comprehensive multi-omics analysis on this patient and three non-responders. Our investigation unveiled that, initially, the tumor microenvironment (TME) of this responder presented minimal infiltration of T cells and natural killer cells, along with a relatively higher presence of macrophages compared to non-responders. Remarkably, during treatment, there was a progressive increase in CD4+T cells, CD8+T cells, and B cells in the responder’s tumor tissue. This was accompanied by a significant upregulation of transcription factors associated with T-cell activation and cytotoxicity, including GATA3, EOMES, and RUNX3. Furthermore, dynamic monitoring of peripheral blood samples from the responder revealed a rapid decrease in circulating tumor DNA (ctDNA), suggesting its potential as an early blood biomarker of treatment efficacy. Collectively, our findings demonstrate the effectiveness of combined oncolytic virotherapy and immunotherapy in certain CRC patients and provide molecular evidence that virotherapy can potentially transform a “cold” TME into a “hot” one, thereby improving sensitivity to immunotherapy.

Purpose: The existing medical imaging tools have a detection accuracy of 97% for peritoneal metastasis(PM) bigger than 0.5 cm, but only 29% for that smaller than 0.5 cm, the early detection of PM is still a difficult problem. This study is aiming at constructing a deep convolution neural network classifier based on meta-learning to predict PM. Method: Peritoneal metastases are delineated on enhanced CT. The model is trained based on meta-learning, and features are extracted using multi-modal deep Convolutional Neural Network(CNN) with enhanced CT to classify PM. Besides, we evaluate the performance on the test dataset, and compare it with other PM prediction algorithm. Results: The training datasets are consisted of 9574 images from 43 patients with PM and 67 patients without PM. The testing datasets are consisted of 1834 images from 21 testing patients. To increase the accuracy of the prediction, we combine the multi-modal inputs of plain scan phase, portal venous phase and arterial phase to build a meta-learning-based multi-modal PM predictor. The classifier shows an accuracy of 87.5% with Area Under Curve(AUC) of 0.877, sensitivity of 73.4%, specificity of 95.2% on the testing datasets. The performance is superior to routine PM classify based on logistic regression (AUC: 0.795), a deep learning method named ResNet3D (AUC: 0.827), and a domain generalization (DG) method named MADDG (AUC: 0.834). Conclusions: we proposed a novel training strategy based on meta-learning to improve the model’s robustness to “unseen” samples. The experiments shows that our meta-learning-based multi-modal PM predicting classifier obtain more competitive results in synchronous PM prediction compared to existing algorithms and the model’s improvements of generalization ability even with limited data.

The synthesis of isomerically pure olefins containing all-carbon quaternary centers is a challenging issue. Herein, we developed an efficient protocol for the synthesis of (Z)-olefins (27 examples, yield up to 97%, Z/Eup to 99/1) and (E)-olefins (16 examples, yield up to 94%, E/Zup to 99/1) containing all-carbon quaternary centers. This protocol is adopted for the copper-catalyzed regioselective C–H alkenylation of the tertiary C(sp3)–H bond of 3-aryl benzofuran-2(3H)-ones with alkyne and alkenes. A diverse range of functional groups in the substrates is well-tolerated, such as F, Cl, Br, Me, OMe, ester, CF3, etc. A gram scale experiment was performed in good yield, and the radical mechanisms are also proposed based on the control experiments.

The convergence of information, communication, and data technologies (ICDT) has been identified as one of the developing trends of the sixth generation(6G) network. Service-based architecture (SBA) as one of the promising information technology, has been preliminarily introduced into the fifth generation (5G) core network (CN) and successfully commercialized, which verifies its feasibility and effectiveness. However, SBA mainly focuses on the control plane of CN at present and the SBA-CN user plane is being studied by the industry. In addition to further evolving the SBA-CN, SBA radio access network (RAN) should also be considered to enable an end-to-end SBA, so as to meet more comprehensive and extreme requirements of future applications, as well as support fast rollout requirements of RAN devices.

Coxsackievirus A10 (CV-A10) infection, a prominent cause of childhood hand-foot-and-mouth disease (HFMD), frequently manifests with the intriguing phenomenon of onychomadesis, characterized by nail shedding. However, the underlying mechanism is elusive. Here, we found that CV-A10 infection in mice could suppress Wnt/β-catenin signaling by restraining LDL receptor–related protein 6 (LRP6) phosphorylation and β-catenin accumulation and lead to onychomadesis. Mechanistically, CV-A10 mimics Dickkopf-related protein 1 (DKK1) to interact with Kringle-containing transmembrane protein 1 (KRM1), the CV-A10 cellular receptor. We further found that Wnt agonist (GSK3β inhibitor) CHIR99021 can restore nail stem cell differentiation and protect against nail shedding. These findings provide novel insights into the pathogenesis of CV-A10 and related viruses in onychomadesis and guide prognosis assessment and clinical treatment of the disease.

The game between therapeutic monoclonal antibodies (mAbs) and continuously emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has favored the virus, as most therapeutic mAbs have been evaded. Addressing this challenge, we systematically explored a reproducible bispecific antibody (bsAb)-dependent synergistic effect in this study. It could effectively restore the neutralizing activity of the bsAb when any of its single mAbs is escaped by variants. This synergy is primarily attributed to the binding angle of receptor-binding domain (RBD)-5, facilitating inter-spike cross-linking and promoting cryptic epitope exposure that classical antibody cocktails cannot achieve. Furthermore, RBD-5 with RBD-2, RBD-6, and RBD-7, alongside RBD-8, also exhibit significantly enhanced effects. This study not only shifts the paradigm in understanding antibody interactions but paves the way for developing more effective therapeutic antibodies against rapidly mutating SARS-CoV-2, with Dia-19 already showing promise against emerging variants like BA.2.86, EG.5.1, and JN.1.

An outbreak of coronavirus disease 2019 (COVID-19)1–3, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)4, has spread globally. Countermeasures are needed to treat and prevent further dissemination of the virus. Here we report the isolation of two specific human monoclonal antibodies (termed CA1 and CB6) from a patient convalescing from COVID-19. CA1 and CB6 demonstrated potent SARS-CoV-2-specific neutralization activity in vitro. In addition, CB6 inhibited infection with SARS-CoV-2 in rhesus monkeys in both prophylactic and treatment settings. We also performed structural studies, which revealed that CB6 recognizes an epitope that overlaps with angiotensin-converting enzyme 2 (ACE2)-binding sites in the SARS-CoV-2 receptor-binding domain, and thereby interferes with virus–receptor interactions by both steric hindrance and direct competition for interface residues. Our results suggest that CB6 deserves further study as a candidate for translation to the clinic.

We have developed a protocol to facilitate the nickel-catalyzed decarbonyloxidation of 3-aryl benzofuran-2(3H)-ones to 2-hydroxybenzophenones under mild conditions, which is an efficient approach for the decarbonyloxidation of lactones in organic synthesis. A diverse range of substrates can undergo C(O)–O/C(O)–C bond cleavage to generate the target products in good yields. These 2-hydroxybenzophenones can be converted into a variety of compounds via reactions such as esterification, cyclization, and reduction.

Rice is an important food crop, with a long history of cultivation in China, and is one of the important staple foods for Chinese today. However, the occurrence of rice diseases has had a substantial impact on its yield. At present, chemical control is the main means of prevention and control of rice diseases. As a high-efficacy and broad-spectrum fungicide, prothioconazole shows an ideal effect on the prevention and control of common rice diseases, but the residuals that remain after its use may have an impact on human health. In this paper, ultrahigh-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) was used to develop a residue analysis method and explore the dissipation of prothioconazole and its metabolite prothioconazole-desthio in rice grain, rice husk, and rice plants, and the risks of chronic and acute dietary intake of prothioconazole in different Chinese populations were evaluated. The results showed that at a concentration range of 0.005–5.0 μg/mL, prothioconazole and its metabolites showed good linear correlations, and the correlation coefficients were all above 0.9992. The average recoveries of prothioconazole in three matrixes ranged from 80.0% to 99.7%, the RSD was between 1.54% and 11.0%, and the limit of quantitation was less than 0.01 μg/g. The sensitivity, accuracy, and precision of the established method all met the measurement requirements. The dissipation experimental results showed that the parent compound prothioconazole was rapidly metabolized to prothioconazole-desthio in the rice field environment, and the dissipation half-life in rice plants after application was 2.5–10.1 d. According to the results of dietary risk assessment, under the standardized residue test conditions, the residual level of rice at the sampling interval of 7 days was within the acceptable range for the chronic and acute dietary risks of different populations in China. Our research is important for directing the scientific application of pesticides in China.

A Cu-catalyzed protocol for cross-dehydrogenative coupling of benzofuranones with quinolines, indoles, carbazoles, and thiophene, which furnishes highly functionalized 3,3-diaryl benzofuranones bearing a three aryl quaternary carbon center at the C3 position in good yields, has been developed. A radical mechanism is proposed.

Epidermal growth factor receptor (EGFR) blockade resistance is common in the treatment of RAS wide type colorectal cancer (CRC). During the treatment of cetuximab, acquired resistant genomic alterations always occurs earlier than disease progression observed by medical images. Identification of genomic alterations dynamically might have certain clinical significance. Because of the limitation of repeated tissue biopsy, liquid biopsy is increasingly recognized. Droplet digital polymerase chain reaction (ddPCR) is the main detection methods for circulating tumor DNA (ctDNA), however, the application of next-generation sequencing (NGS) for ctDNA detection becomes more and more popular. Here we develop a NGS-based ctDNA assay and evaluated its sensitivity and specificity while using ddPCR as control. These two technologies were both used for genomic alteration detection for the peripheral blood samples from cetuximab-treated colorectal cancer patients dynamically. Fifteen patients were enrolled in this study, including eight males and seven females. The sensitivity and specificity of our NGS assay were 87.5% and 100% respectively, and liner regression analysis comparing variant allele frequency (VAF) revealed high concordance between NGS and ddPCR (R2 = 0.98). NGS actually found more mutation information than ddPCR such as the additional dynamic changes of TP53 which were observed in the disease progression patients. Moreover, the variant allele fraction of TP53 was also found by NGS to be changed along with the clinical efficacy evaluation dynamically during the whole treatment process. In conclusion, our newly developed NGS-based ctDNA assay shows similar performance with ddPCR but have more advantages of its high throughput of multigenetic detection for the dynamic monitoring during the treatment of cetuximab in metastasis CRC patients.

The occurrence of maize ear rot caused by Fusarium verticillioides(F. verticillioides) poses a threat to the yield and quality of maize. Mefentrifluconazole enantiomers appear to have strong stereoselective activity against F. verticillioidesand cause differences in fumonisin production. We evaluated the stereoselective activity of mefentrifluconazole enantiomers by determining inhibition of the strain, hyphae, and conidia. Strain inhibition by R-(−)-mefentrifluconazole was 241 times higher than S-(+)-mefentrifluconazole and 376 times higher in conidia inhibition. For the mechanism of the enantioselective bioactivity, R-mefentrifluconazole had stronger binding to proteins than S-(+)-mefentrifluconazole. Under several concentration conditions, the fumonisin concentration was 1.3–24.9-fold higher in the R-(−)-mefentrifluconazole treatment than in the S-(+)-mefentrifluconazole treatment. The R-enantiomer stimulated fumonisin despite a higher bioactivity. As the incubation time increased, the stimulation of the enantiomers on fumonisin production decreased. R-(−)-Mefentrifluconazole stimulated higher fumonisin production in F. verticillioidesat 25 °C compared to 30 °C. This study established a foundation for the development of high-efficiency and low-risk pesticides.

Nanozymes are nanomaterials exhibiting intrinsic enzyme-like characteristics that have increasingly attracted attention, owing to their high catalytic activity, low cost and high stability. This combination of properties has enabled a broad spectrum of applications, ranging from biological detection assays to disease diagnosis and biomedicine development. Since the intrinsic peroxidase activity of Fe3O4nanoparticles (NPs) was first reported in 2007, >40 types of nanozymes have been reported that possess peroxidase-, oxidase-, haloperoxidase- or superoxide dismutase–like catalytic activities. Given the complex interdependence of the physicochemical properties and catalytic characteristics of nanozymes, it is important to establish a standard by which the catalytic activities and kinetics of various nanozymes can be quantitatively compared and that will benefit the development of nanozyme-based detection and diagnostic technologies. Here, we first present a protocol for measuring and defining the catalytic activity units and kinetics for peroxidase nanozymes, the most widely used type of nanozyme. In addition, we describe the detailed experimental procedures for a typical nanozyme strip–based biological detection test and demonstrate that nanozyme-based detection is repeatable and reliable when guided by the presented nanozyme catalytic standard. The catalytic activity and kinetics assays for a nanozyme can be performed within 4 h. Nanozymes are nanomaterials that possess intrinsic enzyme-like properties and are increasingly used in various biological applications. This protocol describes standardized assays of the catalytic activity and kinetics of peroxidase-like nanozymes.

Immunometabolism in the tumor microenvironment (TME) and its influence on the immunotherapy response remain uncertain in colorectal cancer (CRC). We perform immunometabolism subtyping (IMS) on CRC patients in the training and validation cohorts. Three IMS subtypes of CRC, namely, C1, C2, and C3, are identified with distinct immune phenotypes and metabolic properties. The C3 subtype exhibits the poorest prognosis in both the training cohort and the in-house validation cohort. The single-cell transcriptome reveals that a S100A9+macrophage population contributes to the immunosuppressive TME in C3. The dysfunctional immunotherapy response in the C3 subtype can be reversed by combination treatment with PD-1 blockade and an S100A9inhibitor tasquinimod. Taken together, we develop an IMS system and identify an immune tolerant C3 subtype that exhibits the poorest prognosis. A multiomics-guided combination strategy by PD-1 blockade and tasquinimod improves responses to immunotherapy by depleting S100A9+macrophages in vivo.

Spontaneous imbibition is the main mechanism responsible for the retention of large amounts of fracturing fluid during the flowback period in shale gas development. Studying the mechanism of imbibition will help optimize flowback design and improve the accuracy of production prediction. Previous experiments have mainly focused on studying the relationship between the amount of liquid imbibed into shale samples and the time. However, these experiments could not describe visually the liquid saturation distribution along rock samples. In this paper, a chemical potential-dominated flow mechanism model is presented, and nuclear magnetic resonance is adopted to obtain the water saturation distribution curve in the shale rock sample during spontaneous imbibition. The tight sandstone sample is also investigated for comparison. The effects of clay mineral content, fluid salt concentration, and surfactant solution on the water saturation distribution curve are systematically investigated. Results show that the advancing distance of the water saturation front in shale rock is shorter than that in tight sandstone at the same time. Furthermore, the slope of the curve in shale rock is higher. A positive correlation also exists between the front forward distance and clay content. Front forward distance is longer in sample with high clay content. Given the existence of osmotic pressure, the shale rock sample imbibed with water has longer front forward distance than the one imbibed with 10 wt % KCL solution. The shale rock samples imbibed with surfactant solution have a shorter water saturation front advancing distance because of lower capillary pressure. This study aims to provide a new method for the analysis of spontaneous imbibition in shale rock. The water saturation distribution curves can be used as target-match data to get fitted capillary pressure curves in a numerical simulation model of shale gas and obtain an accurate production prediction.

Fluindapyr is a novel chiral succinate dehydrogenase inhibitor used to control fungal diseases. The enantioselective effects of fluindapyr in paddy ecosystems are unknown. We developed a new chiral determination method of fluindapyr using ultrahigh performance liquid chromatography tandem mass spectrometry. The absolute configuration of the fluindapyr enantiomers was identified by an electron circular dichroism model. A new husk-based biochar material was used to optimize and establish a QuEchERs method for paddy soil determination. Under anaerobic conditions, the half-lives of R-fluindapyr and S-fluindapyr in paddy soil were 69.6 and 101.8 days, respectively. R-fluindapyr degraded more rapidly than S-fluindapyr. S-fluindapyr was 87.8 times more active against Rhizoctonia solanithan R-fluindapyr. The enantioselective bioactivity mechanism was illustrated by molecular docking between the fluindapyr enantiomers and SDH of R. solani. The binding powers of R-fluindapyr and S-fluindapyr to proteins were −32.12 and – 42.91 kcal/mol, respectively. This study reports the stereoselectivity of fluindapyr about determination, degradation, bioactivity, and its mechanism. It provides a foundation for an in-depth study of fluindapyr at the enantiomer level.

To evaluate the subjective and objective image quality of solid liver tumors as well as the radiation dose using organ effective modulation (OEM) technology for abdominopelvic computed tomography (CT).

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The yellow fever virus (YFV) is a life-threatening human pathogen. Owing to the lack of available therapeutics, non-vaccinated individuals are at risk. Here, we isolated eight human monoclonal antibodies that neutralize YFV infection. Five recognized overlapping epitopes and exhibited potent neutralizing activity. Two (YD6 and YD73) were ultra-potent and conferred complete protection against the lethal challenge of YFV as both prophylactics and therapeutics in a mouse model. Crystal structures revealed that YD6 engaged the YFV envelope protein in both pre- and post-fusion states, suggesting viral inhibition by a “double-lock” mechanism. The recognition determinants for YD6 and YD73 are clustered at the premembrane (prM)-binding site. Notably, antibodies targeting this site were present in minute traces in YFV-infected individuals but contributed significantly to neutralization, suggesting a vulnerable supersite of YFV. We provide two promising candidates for immunotherapy against YFV, and the supersite represents an ideal target for epitope-based vaccine design.

Graphical Abstract:

In this paper, we study long-range dependence of hydrological records with high frequent and massive data set. For detecting breakpoints, we apply the Evolutionary Wavelet Spectrum (EWS) to provide a segmentation of the original time series. And rescaled range analysis (R/S) for estimating the Hurst exponent that describe the long-range dependence phenomenon are used. The results affirm that the hydrological records have long-range dependent (LRD) behaviors.

detailed analysis of mathematical model, expounded maximum power point tracking (MPPT) control principle, then a improved constant voltage tracking of maximum power point tracking control based on GRNN neural network is proposed, this control strategy uses predicted voltage of GRNN neural network to instead of constant voltage, has be simulated in Matlab /Simulink, and result is this MPPT method can be more accurate compared to traditional control strategy.

AbstractThis study investigated interdecadal variability of June–October (JJASO) the large and small warm pools in western Pacific and their association with rainfall anomalies using station and reanalysis data from 1958 to 2008. The results indicated that the large and small warm pools in western Pacific showed an interdecadal shift around 1986. The large warm pool years over western Pacific were found after 1986, whereas the small warm pool years were often seen throughout the periods before 1986. The analysis results also showed that there were obvious interdecadal variability in JJASO rainfall in Southeast China and warm pool in western Pacific. During 1958–1985 (small warm pool years), the decrease in rainfall was associated with tropospheric moisture divergence and sinking motion over Southeast China and warm pool in western Pacific. However, during 1986–2008 (large warm pool years), the increase in rainfall was associated with tropospheric moisture convergence and ascending motion. Further analysis showed that large warm pool contributed to the increase in surface latent heat fluxes over warm pool in the western Pacific. Thus, there was an increase in the amount of water vapor over Southeast China and warm pool in western Pacific, which contributed to increased rainfall in these regions.

In recent years, as the traffic congestion has been increasing serious in Beijing, many advanced transportation science and technologies have been proposed to solve the traffic problems. Intelligent control of intersection has been one of the major elements globally in the research on road traffic congestion. Based on the experience of engineering practice, this paper does research of intersection fuzzy control modeling and the fuzzy control optimization modeling based on neural network. Then, it puts forward the method of intersection fuzzy control design based on state automaton technology. Based on Matlab/VAP, it presents the method of intersection fuzzy control simulation modeling. Finally, making an actual intersection for an example, it compares the effect of timing control, induction control, fuzzy control, and neural network fuzzy control.

For enhancing low voltage ride though (LVRT) capability, this paper proposes a new protection scheme of series dynamic breaking resistor (SDBR) connected to the grid-side inverter (GSI) of directly driven permanent magnet synchronous generator (D-PMSG) wind power system, which has a lot of advantages such as possessing low cost, simple structure and high reliability. The structure, switching control strategy and matched resistance of SDBR are researched. The proposed scheme was then applied to uplift GSI voltage during a fault, maintain active power delivered to grid, inhibit DC-link overvoltage and GSI overcurrent. The simulation analysis shows that the SDBR can substantially improve the LVRT capacity of D-PMSG wind power system in PSCAD/EMTDC.

Carboxy methyl cellulose (CMC) wastewater contains high salinity (>10%) and chemical oxygen demand (COD) which results from organic by-products during production. It is usually necessary that the wastewater is pretreated before biochemical methods are employed. In this paper, distillation method was used to pretreat CMC wastewater and a kind of organic acid (Ethoxyacetic acid) was extracted. Effect of solution pH on the purity of ethoxyacetic acid was studied.

An investigation on the effects of humic acid (representing NOM) on TCE (a typical organic contaminant) removal by Fe0 in batch settings was carried out. Inhibitory effects of humic acid on Fe0 towards TCE removal were observed. At early stage of the experiments, humic acid might partition with TCE, and the adsorption or deposition of humic acid onto Fe0 surface would further facilitated TCE immobilization. Once the reduction reactive sites on Fe0 surfaces were covered by accumulated humic acid and the partition of TCE to humic acid became saturated, TCE removal in Fe0 was observed retarded.

New impulse detection and filtering algorithm is proposed in color images. Based on fast peer group filter, the proposed filtering algorithm uses different iteration times to complete filter according to different impulse noise density. The extensive experimental results show that the proposed scheme provides better performance than many of the existing vector filters. Meanwhile, the proposed approach is simple and practical for real-time application.

The goal of this paper is to look for relatively stable area in the Vehicular Ad hoc Network (VANET), thereby helping for developing more stable routing protocols. We built a theoretical model to analysis the stability of the VANET topology, and provided the simulation experiment to verify the correctness of the theoretical analysis. Results show that the vehicle traveling in the same direction is easier to maintain the stability of the topology of a VANET, and the valid time of the path will decrease with the increase of the intersection angle in the direction of the vehicle movement, the vehicle movement velocity and the time. In addition, the simulation results also show that the bigger the initial distance among the vehicles is, the less stable the network topology is. The discovery of this phenomenon is important to develop zoned routing protocols.

Abstract: Estradiol, or 17-β-estradiol (E2), the most potent naturally occurring estrogen, is involved in the hormone-immune system interaction in both mammals and fish. However, in vivo studies are largely limited, and little is known about whether E2 exerts similar effects on both female and male zebrafish (Danio rerio). Here, we show exposure of both sexes of D. rerio to 20 nmol/L E2 resulted in a significant increase in Vg1 expression, but caused little damage to the hepatocytes, suggesting that this is the optimum E2 concentration. Also, exposure to 20 nmol/L E2 for 20 days caused a marked increase in plasma IgM levels, but had little influence on the peripheral leukocyte density, providing the first evidence of a hormone-immune system interaction in this species.

This technical note deals with robust state estimation when parametric uncertainties nonlinearly affect a plant state-space model, based on a simultaneous minimization of nominal estimation errors and their sensitivities. An analytic solution is derived for the optimal estimator which can be recursively realized. This estimator has a form similar to the robust estimator of [6], and its computational complexity is comparable to the Kalman filter. Under certain conditions, this robust estimator is proved to converge to a stable system, its estimation errors have a bounded covariance matrix, and the estimate is asymptotically unbiased. Numerical simulations show that the obtained estimator has nice estimation performances. [ABSTRACT FROM AUTHOR]

Convergence and stability of the robust state estimator obtained in [6] is reinvestigated in this technical note. Some new relations have been established for matrix updates in the recursive state estimation. It is proved that under certain stabilizability and detectability conditions, this robust estimator converges to a stable time invariant system, provided that plant nominal parameters are time invariant and the filter design parameter is fixed. These results are consistent with existent ones, but different from them at the point that there are no orthogonality constraints on uncertainty related system matrices, and therefore widen theoretical guarantees for the effectiveness of the estimation procedure. [ABSTRACT FROM AUTHOR]

In the above paper, a Kalman-type robust filter is derived for descriptor systems on the basis of the framework suggested in [3]. The performance of the resulting descriptor filter in [2], however, is generally not very good, as structured perturbations in the corresponding regularized least-squares problem are directly replaced by unstructured ones. In this comment, we show that through off-line convex optimization, the filter's performance can be improved without sacrificing its recursiveness. The idea is to use the ellipsoid with the smallest volume to replace the intersection of several ellipsoids that are determined by the actual plant states and structured model uncertainties, and to re-scale the inputs and outputs of a model uncertainty block with the semi-axes of the optimal ellipsoid. Using the same numerical example and design parameter, the variance of the estimation error can be reduced by approximately 10%. Moreover, it has been shown by simulations that when a standard state-space model is adopted and model uncertainties do not include zero, the method of [2] does not always outperform that of [3]. [ABSTRACT FROM AUTHOR]

In this note, a sufficient condition is derived for the stability of a spatially invariant distributed dynamical system, based on the geometrical structure of the null space of a matrix polynomial. This condition is less conservative than the available computationally feasible criteria. More- over, using the idea of parameter dependent linear matrix inequalities, a necessary and sufficient condition is obtained. Both of these two conditions are expressed by LMIs. While the necessity of the latter is lost if the degree of the related matrix polynomials is small, its conservativeness can be sequentially reduced. [ABSTRACT FROM AUTHOR]

This note deals with generating a series of random matrices uniformly and independently from contractive lower triangular block Toeplitz (LTBT) matrices. All the contractive LTBT matrices are parameterized nonlinearly but recursively in a closed-form by a sequence of contractive unstructured matrices. Moreover, the conditional probability density function (PDF) is obtained in a closed-form for all the matrix parameters, as well as the squares of their singular values. It has been made clear that the conditional PDFs of the matrix parameters are unitarily invariant. A procedure is developed to accurately produce the required random matrix samples. [ABSTRACT FROM AUTHOR]

Frequency response estimation from closed-loop time-domain experimental data is investigated in this paper for normalized coprime factors (NCF) of a multiple-input-multiple-output (MIMO) plant. Based on a linear fractional transformation (LFT) representation for all the NCFs of plants internally stabilizable by a known controller, this estimation problem is converted into the open-loop nonparametric estimation of an inner transfer function matrix (TFM). An estimate is derived through constrained data-matching. It is proved that when the probing signals are periodic and the NCFs of the auxiliary plant are appropriately selected, the estimate is asymptotically unbiased and with a normal/complex normal distribution. It has been made clear that the estimation bias and the estimation variance are always finite. Computationally tractable procedures are suggested for choosing the desirable auxiliary TFMs. [ABSTRACT FROM AUTHOR]

Focuses on the derivation of a linear fractional transformation (LFT) perturbed model set consistent with frequency domain plant input-output data. Consistency between LFT described model set and frequency domain data; Concentration on discrete-time models and unstructured modeling errors; Effects of the consistency condition on the computation cost.

Evaluates the quality of a coprime factor perturbed model set based on the frequency-domain data. Normalization of the coprime factor perturbations; Statistical properties of the sample unfalsified probability (SUP); Impact of SUP on the quality evaluation of the model set.

Venous thromboembolism (VTE) is a major global health problem with high incidence and mortality. Vein endothelial cell (VEC) dysfunction is the primary cause of VTE. MicroRNAs (miRNAs) assist in the regulation of VEC functional pathways. Our objective was to identify potential miRNA target genes associated with VTE.

The effect of acupuncture points stimulation on the induction of plaque-forming cells (PFC) in spleen cells of BALB/c mice was investigated in vivo and in vitro tests. In in vivo experiment, mice were immunized with 2 × 10s sheep red blood cells (SRBC) and the PFC was markedly increased by daily (once a day for 4 days) acupuncture stimulation. The enhancement of PFC by acupuncture was completely blocked by preadministration of procain, hexamethonium, naloxone, propranolol, but not by phentolamine. The enhancement of PFC by acupuncture was also observed in spleen cells of non-immunoized mice when spleen cells of the acupunctured mice were cultured with SRB in vitro. The enhancement of PFC in spleen was observed after stimulation with acupuncture, and a similar effect was also found in bone marrow cells of normal mice, but not in thymic cells. The spleen cells of mice given acupuncture showed no enhancement of PFC after treatment with anti-Thy 1.2 antibody and complement. Fürthermore, these helper T cells were found to be not restricted by the H-2 gene complex.These data demonstrate that the helper T cells induced by acupuncture lack the H-2 restriction, and thus suggest that they may be drived from the bone marrow, but not from the thymus. It is therefore concluded that the helper T cells derived from the bone marrow were activated via the sympathetic nervous system stimulated by acupuncture.

The resilience of the communication constellation is an important measure of the communication mission assurance capability of the communication constellation. In order to effectively measure the strength and weakness of the communication constellation, the research on the elastic evaluation method of communication constellation is carried out. First, according to the definition of the space system elasticity of the US Air Force Space Command, the definition of the communication constellation elasticity is given. Subsequently, the covering ability and reconstruction energy index are proposed as the objective function of the restored constellation performance recovery, and the damaged constellation performance recovery model based on NSGA-II algorithm is constructed. Finally, a resilience evaluation method for communication constellation with a single communication constellation as the evaluation target is established, and the simulation calculation is carried out by taking the MUOS constellation as an example. It is concluded that the constellation is poor in terms of robustness, and because of the lack of satellite performance, the task guarantee capability is limited.

The long-range early warning radar is the key equipment in the early defense process of ballistic missile. For the problem of low working efficiency of long-range early warning radar without guidance information, this paper studies the working process of long-range early warning radar with space-based guidance information, and proposed a new long-range warning radar working mode. Firstly, the coordinate system transformation and guidance information extraction of space-based guidance information are given. Then the concept of coherent accumulation of radar signals is introduced and a new radar operation mode is proposed. Finally, the radar signal coherent accumulation process is established. A mathematical model of radar search distance and intercept probability. The typical scene is built and simulated. The results show that the proposed radar working mode will effectively reduce the search airspace of the long-range early warning radar and improve the radar detection range.

Monoclonal antibodies (mAbs) targeting the co-stimulatory molecule 4-1BB are of interest for tumor immunotherapy. We determined the complex structures of human 4-1BB with 4-1BB ligand (4-1BBL) or utomilumab to elucidate the structural basis of 4-1BB activation. The 4-1BB/4-1BBL complex displays a typical TNF/TNFR family binding mode. The structure of utomilumab/4-1BB complex shows that utomilumab binds to dimeric 4-1BB with a distinct but partially overlapping binding area with 4-1BBL. Competitive binding analysis demonstrates that utomilumab blocks the 4-1BB/4-1BBL interaction, indicating the interruption of ligand-mediated signaling. The binding profiles of 4-1BBL and utomilumab to monomeric or dimeric 4-1BB indicate limited cross-linking of 4-1BB molecules. These findings provide mechanistic insight into the binding of 4-1BB with its ligand and its agonist mAb, which may facilitate the future development of anti-4-1BB biologics for tumor immunotherapy.

The article highlights the procedure for the creation of the Will County Master Address Point Sytem in Illinois. It outlines the phases of project preparation, pilot program and formal development that the GIS department went through in developing the Will County master Address Point System. The system delivered several advantages for Will County such as improved accuracy and reduced staff time needed to answer calls regarding addressing errors and effective delivery of public services.

Zika virus–specific antibodies isolated from a single infected patient show postexposure protection in mice and reveal targets for therapy.

Abstract: A hybrid modeling method based on neural network (NN) is developed and used to model the hysteretic restoring force of a wire cable vibration isolation system for electronic equipment. Firstly, a knowledge-based model for the nonlinear hysteretic restoring force is identified using the measured data obtained from period loading tests. Secondly, the remaining characteristic of hysteretic restoring force, which cannot be modeled in an easy way, is identified using the NN method through network training. By building up a parallel hybrid NN model for the nonlinear hysteretic restoring force, the dynamic responses of the vibration isolation system under harmonic and broad band random excitations are predicted. The predicted results are compared with the measured ones to validate the effectiveness and prediction accuracy of the model. The comparative studies show the developed hybrid NN model possesses good prediction accuracy and generalization capability in contrast with the pure black box NN model. [Copyright &y& Elsevier]