87 research outputs found

    Docking system design and self-assembly control of distributed swarm flying robots

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    This paper presents a novel docking system design and the distributed self-assembly control strategy for a Distributed Swarm Flying Robot (DSFR). The DSFR is a swarm robot comprising many identical robot modules that are able to move on the ground, dock with each other and fly coordinately once self-assembled into a robotic structure. A generalized adjacency matrix method is proposed to describe the configurations of robotic structures. Based on the docking system and the adjacency matrix, experiments are performed to demonstrate and verify the self-assembly control strategy

    The E3 Ubiquitin Ligase AMFR and INSIG1 Bridge the Activation of TBK1 Kinase by Modifying the Adaptor STING

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    SummaryStimulator of interferon genes (STING, also known as MITA, ERIS, or MPYS) is essential for host immune responses triggered by microbial DNAs. However, the regulatory mechanisms underlying STING-mediated signaling are not fully understood. We report here that, upon cytoplasmic DNA stimulation, the endoplasmic reticulum (ER) protein AMFR was recruited to and interacted with STING in an insulin-induced gene 1 (INSIG1)-dependent manner. AMFR and INSIG1, an E3 ubiquitin ligase complex, then catalyzed the K27-linked polyubiquitination of STING. This modification served as an anchoring platform for recruiting TANK-binding kinase 1 (TBK1) and facilitating its translocation to the perinuclear microsomes. Depletion of AMFR or INSIG1 impaired STING-mediated antiviral gene induction. Consistently, myeloid-cell-specific Insig1−/− mice were more susceptible to herpes simplex virus 1 (HSV-1) infection than wild-type mice. This study uncovers an essential role of the ER proteins AMFR and INSIG1 in innate immunity, revealing an important missing link in the STING signaling pathway

    Unbalanced Oxidant-Antioxidant Status: A Potential Therapeutic Target for Coronary Chronic Total Occlusion in Very Old Patients

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    Unbalanced oxidant and antioxidant status played an important role in myocardial infarction. The present study was a clinical trial combined preclinically with targeted agent against cardiovascular injuries and ischemia in vivo model. We tried to confirm the association of unbalanced oxidant and antioxidant status with coronary chronic total occlusion (CTO) in 399 very old patients (80~89 years) and investigated the potential therapeutic value of purified polysaccharide from endothelium corneum gigeriae galli (PECGGp). We analyzed levels of circulating superoxide dismutase 3 (SOD3), nitric oxide (NO), endothelial nitric oxide synthase (eNOS), and malondialdehyde (MDA) in very old patients with coronary CTO. Levels of SOD3, NO, eNOS, and MDA in the cardiac tissue were measured in myocardial infarction rats. Levels of SOD3, eNOS, and NO were lowered (p<0.001) and levels of MDA were increased (p<0.001). PECGGp treatment increased levels of SOD3, eNOS, and NO (p<0.01) in cardiac tissue, while decreasing levels of MDA (p<0.01). PECGGp may suppress unbalanced oxidant and antioxidant status in infarcted myocardium by inhibiting levels of MDA and elevating NO, eNOS, and SOD3 levels. PECGGp could be considered as a potential therapeutic agent for coronary CTO in very old patients

    Comparative Analysis of the Glycosylation Profiles of Membrane-Anchored HIV-1 Envelope Glycoprotein Trimers and Soluble gp140

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    The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. Extensive Env glycosylation provides HIV-1 with protection from the immune system, yet the glycans are also essential components of binding epitopes for numerous broadly neutralizing antibodies. Recent studies have shown that when Env is isolated from virions, its glycosylation profile differs significantly from that of soluble forms of Env (gp120 or gp140) predominantly used in vaccine discovery research. Here we show that exogenous membrane-anchored Envs, which can be produced in large quantities in mammalian cells, also display a virion-like glycan profile, where the glycoprotein is extensively decorated with high-mannose glycans. Additionally, because we characterized the glycosylation with a high-fidelity profiling method, glycopeptide analysis, an unprecedented level of molecular detail regarding membrane Env glycosylation and its heterogeneity is presented. Each glycosylation site was characterized individually, with about 500 glycoforms characterized per Env protein. While many of the sites contain exclusively high-mannose glycans, others retain complex glycans, resulting in a glycan profile that cannot currently be mimicked on soluble gp120 or gp140 preparations. These site-level studies are important for understanding antibody-glycan interactions on native Env trimers. Additionally, we report a newly observed O-linked glycosylation site, T606, and we show that the full O-linked glycosylation profile of membrane-associated Env is similar to that of soluble gp140. These findings provide new insight into Env glycosylation and clarify key molecular-level differences between membrane-anchored Env and soluble gp140

    FANCI serve as a prognostic biomarker correlated with immune infiltrates in skin cutaneous melanoma

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    BackgroundAs a member of tumor, Skin cutaneous melanoma (SKCM) poses a serious threat to people’s health because of its strong malignancy. Unfortunately, effective treatment methods for SKCM remain lacking. FANCI plays a vital role in the occurrence and metastasis of various tumor types. However, its regulatory role in SKCM is unclear. The purpose of this study was to explore the association of FANCI with SKCM.MethodsThis study investigated the expression of FANCI in GSE46517, GSE15605, and GSE114445 from the Gene Expression Omnibus database and The Cancer Genome Atlas (TCGA)-SKCM datasets using the package “limma” or “DESeq2” in R environment and also investigated the prognostic significance of FANCI by utilizing the GEPIA database. Additionally, our research made use of real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical (IHC) staining to verify FANCI expression between SKCM and normal tissues and developed the knockdown of FANCI in A375 and A875 cells to further analyze the function of FANCI. Finally, this study analyzed the correlation of FANCI and tumor-infiltrating immune cells by CIBERSORT, ESTIMATE, and ssGSEA algorithms.ResultsThe FANCI level was increasing in SKCM tissues from GSE46517, GSE15605, GSE114445, and TCGA-SKCM. However, high FANCI expression correlated with poor overall survival. The RT-qPCR and IHC confirmed the accuracy of bioinformatics. Knocking down FANCI suppresses A375 and A875 cell proliferation, migration, and invasion. FANCI could be involved in the immunological milieu of SKCM by regulating immune responses and infiltrating numerous immune cells, particularly neutrophils, CD8+ T cells, and B cells. Furthermore, patients with SKCM who have a high FANCI expression level are reported to exhibit immunosuppression, whereas those with a low FANCI expression level are more likely to experience positive outcomes from immunotherapy.ConclusionsThe increased FANCI expression in SKCM can be a prognostic biomarker. Knockdown FANCI can reduce the occurrence and progression of SKCM. The FANCI expression provides a foundation for predicting the immune status and treatment of SKCM

    Alternating-electric-field-enhanced reversible switching of DNA nanocontainers with pH

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    Macroscopically realizable applications of DNA-based molecular devices require individual molecules to cooperate with each other. However, molecular crowding usually introduces disorder to the system, thus jeopardizing the molecular cooperation and slowing down their functional performance dramatically. A challenge remaining in this field is to obtain both smarter response and better cooperation simultaneously. Here, we report a swift-switching DNA nanodevice that is enhanced by an alternating electric field. The device, self-assembled from folded four-stranded DNA motifs, can robustly switch between closed and open states in smart response to pH stimulus, of which the closed state forms a nanometer-height container that is impermeable to small molecules. This character was used to directly and non-specifically catch and release small molecules emulating mechanical hand in a controllable way. The alternating electric field was used to accelerate molecular cooperative motion during the device switching, which in turn shortened the closing time remarkably to thirty seconds

    Molecular basis of caspase-1 polymerization and its inhibition by a new capping mechanism

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    Inflammasomes are cytosolic caspase-1-activation complexes that sense intrinsic and extrinsic danger signals, and trigger inflammatory responses and pyroptotic cell death. Homotypic interactions among Pyrin domains and caspase recruitment domains (CARDs) in inflammasome-complex components mediate oligomerization into filamentous assemblies. Several cytosolic proteins consisting of only interaction domains exert inhibitory effects on inflammasome assembly. In this study, we determined the structure of the human caspase-1 CARD domain (caspase-1[superscript CARD]) filament by cryo-electron microscopy and investigated the biophysical properties of two caspase-1-like CARD-only proteins: human inhibitor of CARD (INCA or CARD17) and ICEBERG (CARD18). Our results reveal that INCA caps caspase-1 filaments, thereby exerting potent inhibition with low-nanomolar K[subscript i] on caspase-1[superscript CARD] polymerization in vitro and inflammasome activation in cells. Whereas caspase-1[superscript CARD] uses six complementary surfaces of three types for filament assembly, INCA is defective in two of the six interfaces and thus terminates the caspase-1 filament

    Predictable Trajectory Planning of Industrial Robots with Constraints

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    Trajectory prediction is currently attracting considerable attention. This paper proposes geodesic trajectory planning with end-effector and joint constraints to predict the trajectory properties of the end-effector, such as velocities, accelerations, and smoothness. The prediction of the trajectory properties is independent of the joint trajectories. The prediction makes it possible to adjust the trajectory properties in line with a light computational burden. To demonstrate the effectiveness of the proposed method, experiments were conducted using the Efort robot. The experiments show that the proposed method can predict the properties of the trajectory and modify the trajectory to meet the constraints

    Radius and Orientation Measurement for Cylindrical Objects by a Light Section Sensor

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    In this paper, an efficient method based on a light section sensor is presented for measuring cylindrical objects’ radii and orientations in a robotic application. By this method, the cylindrical objects can be measured under some special conditions, such as when the cylindrical objects are welded with others, or in the presence of interferences. Firstly, the measurement data are roughly identified and accurately screened to effectively recognize ellipses. Secondly, the data are smoothed and homogenized to eliminate the effect of laser line loss or jump and reduce the influence of the inhomogeneity of measurement data on the ellipse fitting to a minimum. Finally, the ellipse fitting is carried out to obtain the radii and orientations of the cylindrical objects. Measuring experiments and results demonstrate the effective of the proposed radius and orientation measurement method for cylindrical object
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