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Accurate and efficient COVID-19 diagnosis is crucial in clinical settings. However, the limited availability of labeled data poses a challenge for traditional machine learning algorithms. To address this issue, we propose Turning Point (TP), a few-shot learning (FSL) approach that leverages high-level turning point mappings to build sophisticated representations across previously labeled data. Unlike existing FSL models, TP learns using quasi-configured topological spaces and efficiently combines the outputs of diverse TP learners. We evaluated TPFSL using three COVID-19 datasets and compared it with seven different benchmarks. Results show that TPFSL outperformed the top-performing benchmark models in both one-shot and five-shot tasks, with an average improvement of 4.50% and 4.43%, respectively. Additionally, TPFSL significantly outperformed the ProtoNet benchmark by 12.966% and 11.033% in one-shot and five-shot classification problems across all datasets. Ablation experiments were also conducted to analyze the impact of variables such as TP density, network topology, distance measure, and TP placement. Overall, TPFSL has the potential to improve the accuracy and speed of diagnoses for COVID-19 in clinical settings and can be a valuable tool for medical professionals.

Efferocytosis of apoptotic cancer cells by tumor-associated macrophages or other phagocytes is reported to promote tumor immunosuppression by preventing them from secondary necrosis, which would lead to the release of intracellular components and thus enhanced immunogenicity. Therefore, current apoptosis-inducing cancer treatments (e.g., chemotherapy and radiotherapy) are less satisfactory in eliciting antitumor immunity. Herein, a nanoparticulate inhibitor of efferocytosis is prepared by encapsulating BMS777607, a hydrophobic inhibitor of receptors in macrophages responsible for phosphatidylserine-dependent efferocytosis, with biocompatible poly(lactic-co-glycolic acid) and its amphiphilic derivatives. The yielded nano-BMS can inhibit the efferocytosis of apoptotic cancer cells, thus redirecting them to immunogenic secondary necrosis. As a result, intratumorally injected nano-BMS is capable of activating both innate and adaptive antitumor immunity to achieve greatly improved therapeutic responses, when synergized with nonimmunogenic chemotherapy by cisplatin, immunogenic chemotherapy by oxaliplatin, or radiotherapy by external beams. Moreover, we further demonstrate that the inhalation of nano-BMS could significantly promote the efficacy of cisplatin chemotherapy to suppress tumor lung metastases. Therefore, this study highlights a general strategy to potentiate the immunogenicity of different cancer treatments by suppressing efferocytosis-propelled tumor immunosuppression, showing tremendous clinical potential in rescuing existing cancer therapies for more effective treatment.

Magnetic positioning technology based on magnetic dipoles limited in narrow spaces. The positioning accuracy is affected by the interference of ferromagnetic substances in the surrounding environment, and the positioning accuracy is mainly affected by the number and position of sensors. According to the position and attitude information requirements of the capsule robot, the relevant formulas of the basic principle of magnetic positioning were derived using the magnetic dipole model, and the formulas were optimized to reduce the number of unknown variables, optimize the calculation process, and improve the accuracy of magnetic positioning. At the same time, compensation is added to solve the magnetic coupling problem between the three-axis Hermann von Helmholtz coil driven by the external magnetic field and the capsule robot. Finally, the optimal sensor position, quantity, and positioning accuracy for the magnetic positioning of capsule robots were verified through experiments.

Autologous cancer vaccines constructed by nonproliferative whole tumor cells or tumor lysates together with appropriate adjuvants represent a promising strategy to suppress postsurgical tumor recurrence. Inspired by the potency of cytosolic double-stranded DNA (dsDNA) in initiating anticancer immunity by activating the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, we herein report the concise synthesis of a cGAS-STING agonist through dsDNA-templated biomineralization growth of calcium carbonate (CaCO3) microparticles. The yielded DNA@CaCO3can activate the intracellular cGAS-STING pathway of dendritic cells (DCs) by promoting endosomal escape of dsDNA, triggering their maturation and activation as a potent immune stimulator. Upon intratumoral injection, DNA@CaCO3can reverse the immunosuppressive tumor microenvironment by simultaneously provoking innate and adaptive antitumor immunity, thereby effectively suppressing the growth of murine CT26 and B16–F10 tumors in mice. Furthermore, via CaCO3-based biomineralization of complete tumor lysates, we constructed a personalized autologous cancer vaccine with intrinsic cGAS-STING activation capacity that could provoke tumor-specific immune responses to not only delay the growth of challenged tumors but also synergize with anti-PD-1 immunotherapy to suppress postsurgical tumor recurrence. This study highlights a CaCO3-based biomineralization method to prepare autologous cancer vaccines in a concise manner, which is promising for personalized immunotherapy and clinical translation.

Safe soft landing of the lander is vital to the Mars surface exploration mission. Analysis and verification of the landing stability under uncertain terrain play an important role in lander design. However, the effect of uncertain terrain is ignored in most existing studies, making the analysis incomprehensive and increasing the risk of landing failure in practice. In this paper, a Mars lander with 10 attitude control thrusters is introduced and its dynamics model is then established considering plastic deformation parts and nonlinear contact forces. The effectiveness and accuracy of the dynamics modeling method are verified by experiments with an average relative error of 10%. In order to carry out the dynamics simulation with high-fidelity terrain, a terrain generation method based on statistical data is proposed. Through Monte Carlo simulation under a 50 m × 50 m randomly generated landing terrain, the stability of the lander and the effects of attitude control thrusters are analyzed. The results show that the failure rate is 5.5%, in which the primary failure forms are overturning and abnormal attitude. When the landing simulations are repeated without thrusters, the stable ratio decreases from 94.5% to 90.7%, suggesting the positive effects of attitude control thrusters in improving landing stability under rough terrain.

Utilizing sulphidic copper tailings (SCT) with rich sulfur content in cementitious materials presents a challenge due to its incompatibility with cement. For the bulk use of SCT, this paper demonstrated that alkali-activated slag (AAS) can be a good binder for SCT, and the effects of SCT addition on the setting time, hydration products, microstructure, compressive strength, pore structure, and autogenous shrinkage of AAS were investigated. Results showed that introducing SCT into AAS facilitated the generation of sulfate-containing products during GGBS hydration, e.g., gypsum and ettringite, since the pyrite in SCT is prone to oxidation, leading to the formation of sulfates. SCT can work as an auxiliary activator for GGBS along with NaOH to accelerate the hydration of ground granulated blast furnace slag (GGBS). Consequently, the gel pores of AAS mortar increased, the microstructure of AAS mortars was densified and the compressive strength was improved by 5.5–19.8 % at 28d. In addition, the addition of SCT delayed the setting of the AAS paste, and the autogenous shrinkage of the mortars was mitigated by 27.2–35.8 %.

Tumor hypoxia and acidity are well-known features in solid tumors that cause immunosuppression and therapeutic resistance. Herein, we rationally synthesized a multifunctional fluorinated calcium carbonate (fCaCO3) nanoregulator by coating CaCO3nanoparticles with dopamine-grafted perfluorosebacic acid (DA2-PFSEA) and ferric ions by utilizing their coordination interaction. After PEGylation, the obtained fCaCO3-PEG showed high loading efficacy to perfluoro-15-crown-5-ether (PFCE), a type of perfluorocarbon with high oxygen solubility, thereby working as both oxygen nanoshuttles and proton sponges to reverse tumor hypoxia and acidity-induced resistance to radiotherapy. The as-prepared PFCE@fCaCO3-PEG could not only function as long-circulating oxygen nanoshuttles to attenuate tumor hypoxia but also neutralize the acidic tumor microenvironment by restricting the production of lactic acid and reacting with extracellular protons. As a result, treatment with PFCE@fCaCO3-PEG could improve the therapeutic outcome of radiotherapy toward two murine tumors with distinct immunogenicity. The PFCE@fCaCO3-PEG-assisted radiotherapy could also collectively inhibit the growth of unirradiated tumors and reject rechallenged tumors by synergistically eliciting protective antitumor immunity. Therefore, our work presents the preparation of fluorinated CaCO3nanoregulators to reverse tumor immunosuppression and potentiate radiotherapy through chemically modulating tumor hypoxic and acidic microenvironments tightly associated with tumor glucose metabolism.

A fast error modeling method is proposed to analyze the pose deviation of 3-RPR planar parallel mechanisms with multiple revolute joint clearances. The pose error arisen from clearances and limb deformation is modeled from the point of inverse kinematics and estimated numerically. Manipulator poses are represented by elements of the Lie group SE(2) and the discontinuous deformation of limbs due to clearances are modeled by the Heaviside function, which is then approximated with the hyperbolic tangent function. After establishing the error model, an efficient error compensation method is introduced. The proposed error modeling and accuracy analysis method are validated by case study of a 3-RPR mechanism. The results show that the hyperbolic tangent function runs faster than the step function and it provides better convergence. Finally, the singularity of the 3-RPR mechanism with load is analyzed and the results reveal the effects of loads and clearances on mechanism singularities.

An extendible support structure (ESS) used for unfolding and supporting the antenna array of the Synthetic Aperture Radar (SAR) satellite is reviewed and modeled in this paper. The structure is parameterized by calibrating 12 independent parameters, and following which, angular accuracy of the ESS with joint clearances is modeled. The maximum angular error is obtained by the particle swarm optimization (PSO) and validated by the Monte Carlo simulation. A novel error reduction method is then proposed to improve the accuracy of the structure. In the proposed method, the uncertainty of the joint clearance is eliminated using force constraints by adding small torsional springs. Various joint clearance models with force constraints are proposed to obtain the optimal spring allocation, and based on which, the angular error is further reduced by optimizing the structure of the ESS. The Quasi-Monte-Carlo-based Sobol method for global sensitivity analysis is used to select the design parameters for optimization. Finally, the angular error is greatly reduced.

Lipiodol chemotherapeutic emulsions remain one of the main choices for the treatment of unresectable hepatocellular carcinoma (HCC) via transarterial chemoembolization (TACE). However, the limited stability of Lipiodol chemotherapeutic emulsions would lead to rapid drug diffusion, which would reduce the therapeutic benefit and cause systemic toxicity of administrated chemotherapeutics. Therefore, the development of enhanced Lipiodol-based formulations is of great significance to enable effective and safe TACE treatment. Herein, a stable water-in-oil Lipiodol Pickering emulsion (LPE) stabilized by pH-dissociable calcium carbonate nanoparticles and hemin is prepared and utilized for efficient encapsulation of lipoxygenase (LOX). The obtained LOX-loaded CaCO3&hemin-stabilized LPE (LHCa-LPE) showing greatly improved emulsion stability could work as a pH-responsive and self-fueling microreactor to convert polyunsaturated fatty acids (PUFAs), a main component of Lipiodol, to cytotoxic lipid radicals through the cascading catalytic reaction driven by LOX and hemin, thus inducing ferroptosis of cancer cells. As a result, such LHCa-LPE upon transcatheter embolization can effectively suppress the progression of orthotopic N1S1 HCC in rats. This study highlights a concise strategy to prepare pH-responsive and stable LPE-based self-fueling microreactors, which could serve as bifunctional embolic and ferroptosis-inducing agents to enable proof-of-concept transarterial ferro-embolization therapy of HCC.A stable self-fueling ferroptosis-inducing microreactor constructed by LOX-loaded CaCO3&hemin co-stabilized Lipiodol pickering emulsion was rationally developed to suppress the growth of orthotopic N1S1 HCC in rats via transarterial ferro-embolization therapy.

Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder composed of Langerhans cells admixed with reactive mononuclear and granulocytic cells, associated with prominent eosinophils. LCH is considered a neoplasm, driven in most cases by oncogenic RAS/RAF/MEK/ERKpathway mutations. The disease predominantly affects children. Urinary system involvement has rarely been reported in a multisystem disease setting. We describe 7 patients who presented with LCH occurring within (6 cases) or after (1 case) a resected clear cell (n=6) or clear cell papillary (n=1) renal cell carcinoma (RCC), identified prospectively in our routine and consultation files (2012 to 2019). The patients included 5 women and 2 men, with a median age of 54 years (range, 39 to 73 y), none with a history of LCH or LCH manifestations before the time of RCC diagnosis. The median size of the RCC was 3.5 cm (range, 1.8 to 8.3 cm). Treatment included partial (5 cases), or radical (2 cases) nephrectomy. All RCCs on gross examination showed at least focal cystic changes and were low grade (World Health Organization [WHO]/International Society of Urologic Pathologists [ISUP] grade 1 to 2). The LCH foci were detected as incidental histological finding within the resected RCC in all six cases and they were limited to few high-power fields (<2 mm2) in 5 of 6 cases, but in the sixth case, they occupied almost the entire clear cell papillary RCC (2 cm nodule). No LCH manifestations were detected in the normal kidney or in perinephric fat. The seventh patient developed LCH within inguinal deep soft tissue followed by systemic manifestations 6 years after clear cell RCC. Langerhans cell immunophenotype was supported by the reactivity for S-100, CD1a, and langerin and by the negative pankeratin. Successful pyrosequencing of microdissected LCH DNA revealed the V600E BRAFmutation in all 6 cases of LCH within RCC. To our knowledge, only 3 similar cases were published since 1980; the only case tested for BRAFmutation showed wild-type BRAF. This is the first study analyzing the morphologic and genetic features of a cohort of LCH associated with RCC. In our experience, these cases may be underrecognized in practice, or may erroneously be diagnosed as RCC dedifferentiation or high-grade sarcomatoid transformation. Finally, the detection of BRAFmutation further confirms that LCH in this setting is indeed a neoplasm, rather than a reactive lesion.

A parameterized dynamics analysis model of legged lander with adaptive landing gear was established. Based on the analysis model, the landing performances under various landing conditions were analyzed by the optimized Latin hypercube experimental design method. In order to improve the landing performances, a hierarchical optimization method was proposed considering the uncertainty of landing conditions. The optimization problem was divided into a higher level (hereafter the “leader”) and several lower levels (hereafter the “follower”). The followers took conditioning factors as design variables to find out the worst landing conditions, while the leader took buffer parameters as design variables to better the landing performance under worst conditions. First of all, sensitivity analysis of landing conditioning factors was carried out according to the results of experimental design. After the sensitive factors were screened out, the response surface models were established to reflect the complicated relationships between sensitive conditioning factors, buffer parameters and landing performance indexes. Finally, the response surface model was used for hierarchical optimization iteration to improve the computational efficiency. After selecting the optimum buffer parameters from the solution set, the dynamic model with the optimum parameters was simulated again under the same landing conditions as the simulation before. After optimization, nozzle performance against damage is improved by 5.24%, the acceleration overload is reduced by 5.74%, and the primary strut improves its performance by 21.10%.

In this paper, we analysis the mechanism of corner light leakage, and in order to improve the corner light leakage, we study the influence of LC pattern design, the vas condition and oven condition on corner light leakage.

Antenna panels of a satellite are usually deployed and supported by a deployable mechanism. The accuracy of the deployable mechanism is important because it directly affects the performance of the satellite. This article focuses on the accuracy analysis of a deployable antenna considering the coupled effects of joint clearances and link tolerances, and based on which, two accuracy synthesis methods are further discussed. A novel geometric error modeling method is proposed to estimate the error space of the outer panel of the antenna. The advantages of the proposed method are that it can handle the overconstrained constraints efficiently and decouple the positioning error and orientation error. Moreover, the error space is visualized using a sampling method. Based on the proposed error modeling method, the maximum orientation and positioning errors are computed, and following which, sensitives of the antenna accuracy to tolerances considering various sizes of clearances are analyzed. Finally, two optimization methods for accuracy synthesis are discussed, and instructive conclusions are drawn.

Radiotherapy (RT), as one of the main methods in the clinical treatment of various malignant tumors, would induce systemic immunotherapeutic effects by triggering immunogenic cell death (ICD) of cancer cells. However, the antitumor immune responses produced by RT-induced ICD alone usually are not robust enough to eliminate distant tumors and thus ineffective against cancer metastases. Herein, a biomimetic mineralization method for facile synthesis of MnO2nanoparticles with high anti-programmed death ligand 1 (αPDL1) encapsulation efficiency (αPDL1@MnO2) is proposed to reinforce RT-induced systemic antitumor immune responses. This therapeutic nanoplatforms-mediated RT can significantly improve the killing of tumor cells and effectively evoke ICD by overcoming hypoxia-induced radio-resistance and reprogramming the immunosuppressive tumor microenvironment (TME). Furthermore, the released Mn2+ions from αPDL1@MnO2under acidic tumor pH can activate the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway and facilitate the dendritic cells (DCs) maturation. Meanwhile, αPDL1 released from αPDL1@MnO2nanoparticles would further promote the intratumoral infiltration of cytotoxic T lymphocytes (CTLs) and trigger systemic antitumor responses, resulting in a strong abscopal effect to effectively inhibit tumor metastases. Overall, the biomineralized MnO2-based nanoplatforms offer a simple strategy for TME modulation and immune activation, which are promising for enhanced RT immunotherapy.

This paper presents a multi-objective optimization model for the motion synthesis of four-bar mechanisms considering the effects of revolute joint clearances. A geometric method is proposed to compute the maximum clearances-induced positioning and orientation errors. The proposed error modeling method is validated using a simple example, and the results reveal its advantages of high accuracy and fast computation compared with the widely used existing methods. A multi-objective optimization model is developed to design the four-bar mechanism with the best accuracy. The positioning and orientation errors are modeled separately and equally. Moreover, three constraints are included in the optimization to ensure that the synthesized mechanism is a compact crank-rocker or double-crank mechanism free from branch and order defects. A study case of synthesizing a four-bar mechanism passing through 6 motion points is investigated to illustrate the proposed method. Finally, conclusions and a brief discussion are given.

Pericytes and vascular smooth muscle cells (VSMCs), which are recruited to developing blood vessels by platelet-derived growth factor BB, support endothelial cell survival and vascular stability. Here, we report that imatinib, a tyrosine kinase inhibitor of platelet-derived growth factor receptor β (PDGFRβ), impaired growth of lymphoma in both human xenograft and murine allograft models. Lymphoma cells themselves neither expressed PDGFRβ nor were growth inhibited by imatinib. Tumor growth inhibition was associated with decreased microvascular density and increased vascular leakage. In vivo, imatinib induced apoptosis of tumor-associated PDGFRβ+pericytes and loss of perivascular integrity. In vitro, imatinib inhibited PDGFRβ+VSMC proliferation and PDGF-BB signaling, whereas small interfering RNA knockdown of PDGFRβ in pericytes protected them against imatinib-mediated growth inhibition. Fluorescence-activated cell sorter analysis of tumor tissue revealed depletion of pericytes, endothelial cells, and their progenitors following imatinib treatment. Compared with imatinib, treatment with an anti-PDGFRβ monoclonal antibody partially inhibited lymphoma growth. Last, microarray analysis (Gene Expression Omnibus database accession number GSE30752) of PDGFRβ+VSMCs following imatinib treatment showed down-regulation of genes implicated in vascular cell proliferation, survival, and assembly, including those representing multiple pathways downstream of PDGFRβ. Taken together, these data indicate that PDGFRβ+pericytes may represent a novel, nonendothelial, antiangiogenic target for lymphoma therapy.

Pericytes and vascular smooth muscle cells (VSMCs), which are recruited to developing blood vessels by platelet-derived growth factor BB, support endothelial cell survival and vascular stability. Here, we report that imatinib, a tyrosine kinase inhibitor of platelet-derived growth factor receptor β (PDGFRβ), impaired growth of lymphoma in both human xenograft and murine allograft models. Lymphoma cells themselves neither expressed PDGFRβ nor were growth inhibited by imatinib. Tumor growth inhibition was associated with decreased microvascular density and increased vascular leakage. In vivo, imatinib induced apoptosis of tumor-associated PDGFRβ+ pericytes and loss of perivascular integrity. In vitro, imatinib inhibited PDGFRβ+ VSMC proliferation and PDGF-BB signaling, whereas small interfering RNA knockdown of PDGFRβ in pericytes protected them against imatinib-mediated growth inhibition. Fluorescence-activated cell sorter analysis of tumor tissue revealed depletion of pericytes, endothelial cells, and their progenitors following imatinib treatment. Compared with imatinib, treatment with an anti-PDGFRβ monoclonal antibody partially inhibited lymphoma growth. Last, microarray analysis (Gene Expression Omnibus database accession number GSE30752) of PDGFRβ+ VSMCs following imatinib treatment showed down-regulation of genes implicated in vascular cell proliferation, survival, and assembly, including those representing multiple pathways downstream of PDGFRβ. Taken together, these data indicate that PDGFRβ+ pericytes may represent a novel, nonendothelial, antiangiogenic target for lymphoma therapy.

Noncircular bevel gear can achieve variable transmission between intersecting axes. This article proposes the design method of high-order noncircular bevel gear with concave pitch curve. The parametric equations for driving and driven gear, addendum and dedendum surface under given transmission ratio and axis angle are established in a spherical polar coordinate system. The tooth profile equation of noncircular bevel gear is derived according to the generation method by using bevel gear cutter. The three-dimensional model for noncircular bevel gear is developed to verify the correctness of the design method.

AbstractLet p∈ (0,1)and Mpbe a space associated with the Qpspace. In this paper we show that when a| ≤ 3(p+6)/p2+14p+60, z2+a≺ z(1+a¯z2)in Mp.

Lymphocyte-specific protein 1, recently renamed leukocyte-specific protein 1 (LSP1), is an F-actin binding protein expressed in lymphocytes, macrophages, and neutrophils in mice and humans. This study examines LSP1-deficient (Lsp1-/-) mice for the development of myeloid and lymphocytic cell populations and their response to the development of peritonitis induced by thioglycollate (TG) and to a T-dependent antigen.Lsp1-/- mice exhibit significantly higher levels of resident macrophages in the peritoneum compared to wild-type (wt) mice, whereas the development of myeloid cells is normal. This increase, which is specific for conventional CD5-macrophages appears to be tissue specific and does not result from differences in adhesion to the peritoneal mesothelium. The level of peritoneal lymphocytes is decreased inLsp1-/- mice without affecting a particular lymphocytic subset. The proportions of precursor and mature lymphocytes in the central and peripheral tissues of Lsp1-/-mice are similar to those of wt mice andLsp1-/-mice mount a normal response to the T-dependent antigen, ovalbumin (OVA). On injection of TG, theLsp1-/-mice exhibit an accelerated kinetics of changes in peritoneal macrophage and neutrophil numbers as compared to wt including increased influx of these cells. LSP1- neutrophils demonstrate an enhanced chemotactic response in vitro to N-formyl methionyl-leucyl-phenylalanine (FMLP) and to the C-X-C chemokine, KC, indicating that their enhanced influx into the peritoneum may be a result of increased motility. Our data demonstrate that LSP1 is a negative regulator of neutrophil chemotaxis.

Lymphocyte-specific protein 1, recently renamed leukocyte-specific protein 1 (LSP1), is an F-actin binding protein expressed in lymphocytes, macrophages, and neutrophils in mice and humans. This study examines LSP1-deficient (Lsp1−/−) mice for the development of myeloid and lymphocytic cell populations and their response to the development of peritonitis induced by thioglycollate (TG) and to a T-dependent antigen.Lsp1−/−mice exhibit significantly higher levels of resident macrophages in the peritoneum compared to wild-type (wt) mice, whereas the development of myeloid cells is normal. This increase, which is specific for conventional CD5−macrophages appears to be tissue specific and does not result from differences in adhesion to the peritoneal mesothelium. The level of peritoneal lymphocytes is decreased inLsp1−/−mice without affecting a particular lymphocytic subset. The proportions of precursor and mature lymphocytes in the central and peripheral tissues of Lsp1−/−mice are similar to those of wt mice andLsp1−/−mice mount a normal response to the T-dependent antigen, ovalbumin (OVA). On injection of TG, theLsp1−/−mice exhibit an accelerated kinetics of changes in peritoneal macrophage and neutrophil numbers as compared to wt including increased influx of these cells. LSP1−neutrophils demonstrate an enhanced chemotactic response in vitro to N-formyl methionyl-leucyl-phenylalanine (FMLP) and to the C-X-C chemokine, KC, indicating that their enhanced influx into the peritoneum may be a result of increased motility. Our data demonstrate that LSP1 is a negative regulator of neutrophil chemotaxis.

By inducing tumor-specific immune responses, tumor vaccines have recently aroused great research interest. Herein, we design a targeted nanovaccine by equipping cell membrane vesicles (CMVs) harvested from tumor cells with functional DNA including CpG oligonucleotide, an agonist for toll-like receptor 9, as well as an aptamer targeting the dendritic cell (DC)-specific intercellular adhesion molecule (ICAM)-3 grabbing nonintegrin (DC-SIGN) receptor overexpressed on DCs. Such DNA-modified CMVs could target DCs and further stimulate their maturation. Notably, our nanovaccines could trigger robust antitumor immune responses to effective delay the tumor growth. Moreover, the combination of CMV-based nanovaccines with an immune checkpoint blockade could result in improved therapeutic responses by eliminating the majority of the tumors as well as long-term immune memory to prevent tumor recurrence. Therefore, by simply assembling functional DNA on CMVs harvested from tumor cells, we propose a general platform of DC-targeted personalized cancer vaccines for effective and specific cancer immunotherapy.

Background: Patients with post-acute anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis are often left with permanent memory impairments. Given that NMDA receptors are essential to memory encoding, and encoding processes have been suggested to contribute to the success of memory retrieval, we investigate whether post-acute anti-NMDA receptor encephalitis leads to abnormal brain activation during verbal memory encoding and its potential effects on subsequent memory retrieval performance. Methods: To address this issue, this study recruited twenty-one adult patients with anti-NMDA receptor encephalitis past the acute stage and twenty-two healthy controls (HCs). Functional magnetic resonance imaging (fMRI) data were collected when they completed an episodic memory task. Results: At the neural level, the patients showed higher brain activation than the HCs in the bilateral hippocampus/parahippocampus (HG/PHG), right superior temporal gyrus (STG) and right thalamus during memory encoding. At the behavioural level, the patients showed worse memory retrieval performance than the HCs. Importantly, greater brain activation in the left HG/PHG during memory encoding was significantly associated with worse memory retrieval performance among the patients. Conclusion: Our findings indicate that post-acute anti-NMDA receptor encephalitis is likely related to altered brain activation during memory encoding. Particularly, less memory retrieval performance often observed in patients with post-acute anti-NMDA receptor encephalitis may result from abnormal activation in hippocampus during encoding. These observations may enhance our understanding of NMDA receptor dysfunction in the human brain.

Harmonic drive transmissions are widely used in robotics, space manipulation systems because of their excellent mechanical properties including low backlash, high speed reduction ratio and compact size. Analytical investigation and modeling of backlash and hysteresis for harmonic drive are reported, but no thorough understanding of backlash as well as its attributes is available in literature. In this research, the experimental and analytical studies of backlash are conducted. First, the definition of backlash according to China National Standard (CNS) is given, which also matches the requirements in application. A dedicated apparatus was designed to measure the backlash. The results of this paper offer an insight into backlash of harmonic drive and the results are valuable in the mechanical design of harmonic drive gears as well as the dynamic modeling and precision control of harmonic drive systems.

This paper develops a geometric method to estimate the error space of 3-DOF planar mechanisms with the Minimum Volume Ellipsoid Enclosing (MVEE) approach. Both the joint clearances and actuator errors are considered in this method. Three typical planar parallel mechanisms are used to demonstrate. Error spaces of their serial limbs are analyzed. Thereafter, limb-error-space-constrained mobility of the manipulator, namely, the manipulator error space is analyzed. The MVEE method has been applied to simplify the constraint modeling. A closed-form expression for the manipulator error space is derived. The volume of the manipulator error space is numerically estimated. The approach in this paper is to develop a geometric error analysis method of parallel mechanisms with clear algebraic expressions. Moreover, no forward kinematics computations have been performed in the proposed method, in contrast to the widely used interval analysis method. Although the estimated error space is larger than the actual one, because the enclosing ellipses enlarge the regions of limb error space, the method has an attractive advantage of high computational efficiency.

A general accuracy analysis method of redundantly actuated and overconstrained parallel mechanisms is proposed. Coupled effects of actuation errors and internal elastic forces arose from the elastic deformation are both considered. The accuracy analysis approach is based on the Lie-group theory and screw theory, and it includes three steps. First, stiffness matrices of serial legs are obtained. Second, the movement of each leg is modeled based on group theory and the elastic forces arose from the deformation are represented using the stiffness matrices, following which the multiclosed-loop structure constraint and self-balanced force constraint are modeled. Finally, the error pose is estimated. The proposed method is illustrated by the accuracy study of a redundantly actuated and overconstrained Stewart platform. The error modeling is easy as the use of stiffness matrix can model the passive joint motions and deformation together. Moreover, the proposed method is computationally cheap as all computations are linear.

In the overall design and performance prediction of spacecrafts intended to accomplish soft landing on the moon, touchdown dynamics analysis during the landing phase is one of the most important tasks. Due to uncertainties of the landing site and flight states of the vehicle at touchdown, the landing stability is systematically studied in this article by employing the techniques of computer experiments. Firstly, the landing dynamics simulation model of a lunar lander is established and verified by physical tests. Then, design of experiments and response surface methodology have been utilized to analyze the landing stability. Consequently, main effects of initial landing conditions (inputs) on landing dynamics responses (outputs) have been investigated. Response surface models for approximating relationships between inputs and outputs are also acquired. The worst sets of landing conditions and boundaries of initial velocities for stable landings are finally determined with the help of response surface models. The approach for landing stability analysis proposed in this article has been proven effective and efficient and provides valuable guidance for the lander design and analysis.

In this article, the design on the shock absorber of the lunar probe soft landing can be considered as a single- or multi-objective optimization problem. Here, the optimized objective parameters include the maximum toppling stability, defined as Dmin, and the minimum stroke of primary strut energy absorption, SPmax. However, the two optimized variables are conflict objectives. In order to give an overall consideration about the multi-performances of landing, the multi-objective optimization strategy is proposed and nondominated sorting genetic algorithm II is employed to find the best decision parameters of the shock absorber design. To conduct the optimizations, firstly, the worst landing cases and safety boundaries for both toppling and primary strut energy absorptions are obtained by the computer simulation experiments. Both single- and multi-objective optimizations are then implemented aiming to expand the stability boundary. The results show that the landing stability is effectively improved after optimizations, and also demonstrate that the multi-objective optimization strategy is superior to that of the single-objective optimization.