Search

Background: A strategy to broaden the applicability of checkpoint inhibitors is the combined use with antibodies targeting the immune stimulatory receptors CD40 and 41BB. However, the use of anti-CD40 and anti-41BB antibodies as agonists is problematic in two ways. First, anti-CD40 and anti-41BB antibodies need plasma membrane-associated presentation by FcγR binding to exert robust agonism but this obviously limits their immune stimulatory efficacy by triggering ADCC, CDC or anti-inflammatory FcγRIIb activities. Second, off tumor activation of CD40 and 41BB may cause dose limiting systemic inflammation. Methods: To overcome the FcγR-dependency of anti-41BB and anti-CD40 antibodies, we genetically fused such antibodies with a PDL1-specific blocking scFv as anchoring domain to enable FcγR-independent plasma membrane-associated presentation of anti-CD40- and anti-41BB antibodies. By help of GpL-tagged variants of the resulting bispecific antibodies, binding to their molecular targets was evaluated by help of cellular binding studies. Membrane PDL1-restricted engagement of CD40 and 41BB but also inhibition of PDL1-induced PD1 activation were evaluated in coculture assays with PDL1-expressing tumor cell lines and 41BB, CD40 and PD1 responsible cell lines or T-cells. Results: The binding properties of the bispecific antibody fusion proteins remained largely unchanged compared to their parental molecules. Upon anchoring to membrane PDL1, the bispecific antibody fusion proteins activated CD40/41BB signaling as efficient as the parental anti-CD40/anti-41BB antibodies when bound to FcγRs or cells expressing membrane-bound CD40L/41BBL. PD1 inhibition remained intact and the anti-41BB fusion protein thus showed PDL1-restricted costimulation of T-cells activated in vitro with anti-CD3 or a BiTe. Conclusions: Targeting of anti-CD40 and anti-41BB fusion proteins to membrane PDL1 with a blocking PDL1 scFv links PD1-PDL1 checkpoint blockade intrinsically with engagement of CD40 or 41BB.

Understanding the characteristics of functional brain activity is important for motor rehabilitation of children with cerebral palsy (CP). Using the functional near-infrared spectroscopy (fNIRS) technology, the cortical response and networks of prefrontal (PFC) and motor cortices (MC) were analyzed for children with CP and typical development (CTD). Compared with CTD, the resting cortical response of dominant MC in children with CP increased, and the functional connectivity between cerebral areas decreased. In the motor state of children with CP, the coupling strength started from dominant MC increased compared with resting state, and the hemispherical autonomy index (HAI) of the dominant MC was higher than that in the CTD, which reflected the leading role of dominant MC in brain regulation during motor. The functional connectivity between bilateral MC was positively correlated with motor performance. This study provided effective indices for evaluating the motor function and real-time impact of motor on brain networks. This article is protected by copyright. All rights reserved.

The generation frequency of grid-connected units determines the power supply reliability of the grid and primary frequency regulation, as the first guarantee to stabilize the grid frequency is affected by the category of generating units and operation mode and lacks systematic real-time optimization and monitoring means. This paper takes a 300MW sub-critical heating unit as the research object, and researches, and analyzes three aspects of signal homologation, multi-dimensional optimization, and intelligent decision-making to establish the evaluation model of the primary frequency regulation capability of the unit. The evaluation accuracy of the assessment model reaches 83%, develops the control platform based on autonomous controllable PLC, realizes intelligent dynamic control and the replacement of traditional optimization technology means, also improves the qualification rate of primary frequency regulation by about 23.2%.

China Robot Competition, which integrates the theory and practice of multi-disciplinary intelligent robot system, is one of the most influential robot competitions in China. In this paper, we apply RRT * and APF to the Middle Size Simulation League of soccer on ROS and propose an attack strategy based on extremum. Our experiments showed that the implementation of RRT* and APF optimizes the multiple iterations existing in original obstacle avoidance algorithm and greatly improves the performance of robots when there are fewer obstacles and the maximum speed of obstacle avoidance is limited. Besides, our attack strategy has proved effective on boosting the chances of goal and helped the Central South University to win the championship of China Robot Competition Middle Size Simulation League in 2021.

The lower limb exoskeleton provides assistance by following the lower limb joints’ desired motion trajectory. However, angle control is not enough to meet the requirements in some special circumstances such as encountering obstacles. In the swing phase of the attached leg with the exoskeleton, there is a different contact force between the sole and the road surface in different road conditions. Therefore, it is particularly important to control the joint angle and contact force simultaneously, that is, it is not only necessary to follow the desired angle but also to minimize the influence of external contact force. In this article, a novel scheme is proposed to adjust the trajectory dynamically in the swing phase. First of all, the physical model is streamlined and the Lagrangian principle is carried out to dynamic analysis and established a model of lower limb exoskeleton in the swing phase. Furthermore, the angle dynamics equation is transformed into a Cartesian coordinate system to calculate the end contact force for the impedance model. Finally, the impedance control strategy together with a disturbance observer is designed which is suitable for nonlinear and strong coupling characteristics. The simulation result shows that the control system can follow the angle accurately in the condition of minimizing external constraints. Hardware experiment shows that lower extremity exoskeleton can adjust motion trajectory actively when encountering obstacles and complete the movement trajectory tracking at the same time.

Prosthetic alignment directly affects the biomechanical loading in individuals with lower-limb amputation, and improper alignment may be contribute to the high incidence of hip and knee osteoarthritis (OA). The biomechanical changes caused by different alignments should be considered in prosthetic fitting. However, the quantitative effect of alignment on the kinetic features of individuals with transfemoral amputation remains unclear.As important kinetics indexes, how are the hip and knee joint moments affected by prosthetic alignment in individuals with transfemoral amputation?Gait tests of ten individuals with transfemoral amputation and fifteen individuals without amputation (control group) were performed. Several prosthetic alignment conditions were used, including the so-called "initial" alignment and eight malalignments. The hip and knee joint moments of the individuals with amputation under various alignments were analysed and compared with those of the control group. Statistical analyses were performed by one-way ANOVA, repeated measure multivariate ANOVA, and paired t tests.The peaks and impulses of the hip abductor and external rotator moments on the residual side were significantly smaller than those of the control group (P 0.0056). The peaks of the hip extensor, adductor and external rotator moments on the intact side were significantly larger than those on the residual side (P 0.05). Alignment significantly affected the intact hip and knee joint moments for each individual with amputation (P 0.00625), but there was no consistent effect among individuals.The significantly larger hip joint moment on the intact side of individuals with transfemoral amputation may be associated with the higher incidence of hip OA on the intact side. Alignment significantly affects the hip and knee joint moments of each individual with transfemoral amputation, but the individual responses to alignment changes are different. This situation may imply that the method for optimizing alignment should be personalized.

Inappropriate biomechanical loading usually leads to a high incidence of hip and knee osteoarthritis (OA) in individuals with lower-limb amputation, and prosthetic alignment may be an important influencing factor. The effect of alignment on the lower limb loading remains quantitatively unclear, and the relationship between malalignment and joint diseases is undefined.How does alignment affect spatiotemporal gait parameters and ground reaction force (GRF) in individuals with transfemoral amputation?Gait tests of 10 individuals with transfemoral amputation were performed with recommended alignment and eight malalignments, including 10 mm socket translation (anterior, posterior, medial, and lateral) and 6° socket angular changes (flexion, extension, abduction, and adduction). Fifteen individuals without amputation were recruited as a control group. The differences in spatiotemporal and GRF parameters under different alignments were analyzed and compared with those of the control group. Statistical analyses were performed by one-way ANOVA, repeated measure multivariate ANOVA, and paired t tests.The medial GRF peaks and impulse on both sides and load rate on the intact side are significantly higher than those of the control group (P 0.0056). The propulsive and braking peaks, vertical impulse, and medial and vertical load rates of GRF on the intact side are higher than those on the residual side (P 0.05). The alignment of socket adduction significantly increases medial GRF peak and impulse on both sides (P 0.0056).Alignments exert remarkable and complicated effects on the biomechanical performance. The considerably higher GRF on the intact side of the individuals with transfemoral amputation may lead to internal stress changes of the intact joint, which may be an inducement for high incidence of joint diseases. Probably due to the increased lateral deviation of the center of gravity, the socket adduction alignment significantly increases medial GRF, which may lead to an increased risk of knee OA.

Rationale Gas Chromatography Mass Spectrometry (GC-MS) with electron ionization (EI)is the most widely used analysis technique of gaseous samples, but it may be time-consuming for on-line monitoring of mixtures whose concentrations relatively change rapidly. On the other hand, current ionization methods, such as chemical ionization (CI) and proton transfer reaction (PTR), also have some disadvantages such as selectivity. Appropriate soft ionization sources therefore are searched for rapid on-line detection. Methods Hollow Electrode Capillary Plasma Ionization (HECPI) is based on single electrode plasma. A hollow capillary was placed as both the electrode and the inlet of the gaseous samples. The ionization source is coupled with a mass spectrometer for performance evaluation. Results Several typical compounds have been tested with HECPI-mass spectrometer. In this process, the dominant ion peaks of all compounds can be indexed as molecular ion peaks, and the product ions of HECPI are less than that of dielectric barrier discharge ionization (DBDI). Three gaseous samples (linalool, triethylamine and styrene) with various concentrations have been employed to further confirm the performance of this source, and the detection limit of linalool is as low as 10 ppb. Conclusions HECPI is simple in structure and shows good performance. The results also show that HECPI has the potential to be an effective tool for detecting on-line gaseous samples rapidly.

Robots often collide in the process of simulation soccer match. The collision will block the robot’s own motion trajectory, which is not conducive to the robot’s ball grasping and defense. Considering that the obstacles have the characteristics of dynamics, antagonism and uncertainty, the robot’s motion trajectory, path selection and obstacle avoidance are very important. Taking ROS as the research platform, the study focuses on the path planning of simulated soccer robot. Meanwhile, we have applied some obstacle avoidance algorithms to the Middle Size Simulation League of soccer.

Fanqi Meng,1 Le Zou,2 Tengyu Zhang,3 Lei Jiang,1 Yao Ding,4 Peng Yu,1 Jie Peng5 1Department of Drug Analysis, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, Hunan Province, China; 2Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China; 3Department of Pharmacy, University of Copenhagen, København Ø, Denmark; 4Department of Analyses and Testing, Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha 410013, Hunan Province, China; 5Department of Pharmacy, Jiangxi Provincial People’s Hospital, Nanchang 330006, Jiangxi Province, China Purpose: The overexpression of ATP-binding cassette transporters (ABC transporters), mainly including permeability glycoproteins (P-gp), multidrug resistance (MDR)-related protein 1 (MRP1), and breast cancer resistance proteins (BCRP), is one of the main reasons for the development of MDR which directly leads to chemotherapy failure. However, most of the currently used detection methods in MDR-related studies are qualitative or semiquantitative, but not quantitative. As a result, the measurement criteria of different experiments are not unified. Moreover, there are many contradictory results of the studies of the induction effect of drugs on ABC transporters. So, it is necessary to establish a quantitative assay for the quantification of P-gp, MRP1, and BCRP to study the mechanism of drug resistance.Methods: In this paper, a novel and advanced liquid chromatography/mass spectrometry (MS)/MS-based targeted proteomics method for the quantification of P-gp, MRP1, and BCRP was developed and validated. Then, the cell lines MCF-7, HepG-2, andSMMC-7721 were, respectively, induced bydifferent concentrations of doxorubicin (adriamycin [ADM]), mitoxantrone (MX),and methotrexate (MTX), toestablish resistance cell lines. The method established was used to quantify the expression of P-gp, MRP1, and BCRP.Results: The result showed that the induction effects of drugs on protein were relatively stable and selective. ADM, MX, and MTX could induce overexpression of P-gp, MRP1, and BCRP. And, the induction effect of different drugs on proteins was selective. The pattern of overexpression of ABC transporters in the three types of resistance cell lines was different.Conclusion: During the development of drug resistance, the cell type and patch, but not drug type, were the most important determinant factors of the overexpression level of ABC transporters in resistance cell lines. This studyprovides a good foundation for understanding the development of drug resistance in cell lines and can be used to explain the contradictory results in other published studies as described above. Keywords: P-gp, MRP1, BCRP, multidrug resistance, quantification

A food waste treating system was proposed in this study by combining biochar-assisted high-solid anaerobic digestion and subsequent steam gasification of the digestate. The effect of solid level, biochar dosage in anaerobic digestion on the properties of biogas, syngas, and final biochar products were investigated. Results showed that at a high total solid level and biochar dosage of 25 g/L and 50 g/L, the accumulative methane yield reached 110.3 mL CH4/g VS and 126.7 mL CH4/g VS, respectively. From steam gasification of different digestates under 850 °C for 15 min, a maximum of 34.92 mmol/g for the hydrogen yield and 11.44 MJ/m3 for the higher heating value could be obtained for the syngas. Furthermore, the by-product produced from steam gasification was a nutrient-enriched porous biochar, which was suitable to be used as compost. This study demonstrated a pathway for food waste treating to produce methane-enriched biogas, hydrogen-enriched syngas, and nutrient-enriched biochar.

This work evaluates the performance of different biochar-amended anaerobic digestion systems. The Fourier Transform Infrared analysis showed that more ordered aromatic groups formed and the aromatization degree increased with the rise of gasification temperature. The biochar produced at 900 °C still showed an excellent ability to maintain the stability of anaerobic digestion performance, where the specific methane yield content steadily reached 742 mL CH4/g ethanol. Besides, the enzymatic activity test indicated an improved performance with the addition of biochar obtained at gasification temperature. The relationship between the microbial community and metabolism pathways result are signified due to the direct interspecies electron transfer among Pseudomonas or Candidatus cloacimonas and Methanosaeta via biochar. These links have promoted the methane metabolism pathway of acetate decarboxylation. Therefore, the current study helps better understand the influence of surface functional groups of biochar at different temperatures on anaerobic digestion performance.

The transformation behavior of free-volume defect in (80GeS2-20Ga2S3)100-x (CsI)x (x = 0, 5, 10, 15 mol%) chalcogenide glasses was studied by employing positron annihilation spectroscopic technique, which could reveal valuable information for in-depth understanding of nano-structural defects in glassy matrix. The results indicate that the structural changes caused by CsI additives can be adequately described by positron trapping modes determined with two-state model. The initial addition of CsI (x = 5 mol%) led to a void contraction, whereas, the void agglomeration occurred with the increase of CsI and the free-volume defects of the glasses were obviously reduced. The atomic density ρ is inversely proportional to the number of these defects. Meanwhile, the UV cut-off edge shifts toward short-wavelength with increasing of CsI. This study provides the valuable information of defects evolution in GeS2-Ga2S3-CsI glasses.