Distinct Pharmacological Properties of Gaseous CO and CO-Releasing Molecule in Human Platelets

Carbon monoxide (CO)—gaseous or released by CO-RMs—both possess antiplatelet properties; however, it remains uncertain whether the mechanisms involved are the same. Here, we characterise the involvement of soluble guanylate cyclase (sGC) in the effects of CO—delivered by gaseous CO–saturated buffer (CO_G) and generated by CORM-A1—on platelet aggregation and energy metabolism, as well as on vasodilatation in aorta, using light transmission aggregometry, Seahorse XFe technique, and wire myography, respectively. ODQ completely prevented the inhibitory effect of CO_G on platelet aggregation, but did not modify antiplatelet effect of CORM-A1. In turn, CO_G did not affect, whereas CORM-A1 substantially inhibited energy metabolism in platelets. Even though activation of sGC by BAY 41-2272 or BAY 58-2667 inhibited significantly platelet aggregation, their effects on energy metabolism in platelets were absent or weak and could not contribute to antiplatelet effects of sGC activation. In contrast, vasodilatation of murine aortic rings, induced either by CO_G or CORM-A1, was dependent on sGC. We conclude that the source (CO_G vs. CORM-A1) and kinetics (rapid vs. slow) of CO delivery represent key determinants of the mechanism of antiplatelet action of CO, involving either impairment of energy metabolism or activation of sGG.     

Topology optimization of flexure hinges with a prescribed compliance matrix based on the adaptive spring model and stress constraint

This paper focuses on the configuration design of flexure hinges with a prescribed compliance matrix and preset rotational center position. A new method for the topology optimization of flexure hinges is proposed based on the adaptive spring model and stress constraint. The hinge optimization model is formulated by maximizing the bending displacement with a spring while optimizing the compliance matrix to a prescribed value. To avoid numerical instability, an artificial spring is used as an auxiliary calculation, and a new strategy is developed for adaptively adjusting the spring stiffness according to the prescribed compliance matrix. The maximum stress of flexure hinge is limited by using a normalized P-norm of the effective von Mises stress, and a position constraint of rotational center is proposed to predetermine the position of the rotational center. In addition, to reduce the error of the stress measurement, a simple but effective filtering method is presented to obtain a complete black-and-white design. Numerical examples are used to verify the proposed method. Topology results show that the obtained flexure hinges have the prescribed compliance matrix and preset rotational center position while also meeting the stress requirements.     

AQP3 Increases Intercellular Cohesion in NSCLC A549 Cell Spheroids through Exploratory Cell Protrusions

Tumor cell aggregation is critical for cell survival following the loss of extracellular matrix attachment and dissemination. However, the underlying mechanotransduction of clustering solitary tumor cells is poorly understood, especially in non-small cell lung cancers (NSCLC). Here, we examined whether cell surface protrusions played an important role in facilitating the physical contact between floating cells detached from a substrate. We employed poly-2-hydroxyethyl methacrylate-based 3D culture methods to mimic in vivo tumor cell cluster formation. The suprastructural analysis of human NSCLC A549 cell spheroids showed that finger-like protrusions clung together via the actin cytoskeleton. Time-lapse holotomography demonstrated that the finger-like protrusions of free-floating cells in 3D culture displayed exploratory coalescence. Global gene expression analysis demonstrated that the genes in the organic hydroxyl transport were particularly enriched in the A549 cell spheroids. Particularly, the knockdown of the water channel aquaporin 3 gene (AQP3) impaired multicellular aggregate formation in 3D culture through the rearrangement of the actomyosin cytoskeleton. Moreover, the cells with reduced levels of AQP3 decreased their transmigration. Overall, these data indicate that cell detachment-upregulated AQP3 contributes to cell surface protrusions through actomyosin cytoskeleton remodeling, causing the aggressive aggregation of free-floating cells dependent on the property of the substratum and collective metastasis.     

Reference guided image super-resolution via efficient dense warping and adaptive fusion

Due to the limited improvement of single-image based super-resolution (SR) methods in recent years, the reference based image SR (RefSR) methods, which super-resolve the low-resolution (LR) input with the guidance of similar high-resolution (HR) reference images are emerging. There are two main challenges in RefSR, i.e. reference image warping and exploring the guidance information from the warped references. For reference warping, we propose an efficient dense warping method to deal with large displacements, which is much faster than traditional patch (or texture) matching strategy. For the SR process, since different reference images complement each other, and have different similarities with the LR image, we further propose a similarity based feature fusion strategy to take advantage of the most similar reference regions. The SR process is realized by an encoder–decoder network and trained with pixel-level reconstruction loss, degradation loss and feature-level perceptual loss. Extensive experiments on three benchmark datasets demonstrate that the proposed method outperforms state-of-the-art SR methods in both subjective and objective measurements.     

Diphenyl-Methane Based Thyromimetic Inhibitors for Transthyretin Amyloidosis

Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simulation, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thyromimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases.     

A survey on tracking control of unmanned underwater vehicles: Experiments-based approach

This paper aims to provide a review of the conceptual design and theoretical framework of the main control schemes proposed in the literature for unmanned underwater vehicles (UUVs). Additionally, the objective of the paper is not only to present an overview of the recent control architectures validated on UUVs but also to give detailed experimental-based comparative studies of the proposed control schemes. To this end, the main control schemes, including proportional–integral–derivative (PID) based, sliding mode control (SMC) based, adaptive based, observation-based, model predictive control (MPC) based, combined control techniques, are revisited in order to consolidate the principal efforts made in the last two decades by the automatic control community in the field. Besides implementing some key tracking control schemes from the classification mentioned above on Leonard UUV, several real-time experimental scenarios are tested, under different operating conditions, to evaluate and compare the efficiency of the selected tracking control schemes. Furthermore, we point out potential investigation gaps and future research trends at the end of this survey.     

A Lane-Level Road Marking Map Using a Monocular Camera

The essential requirement for precise localization of a self-driving car is a lane-level map which includes road markings (RMs). Obviously, we can build the lane-level map by running a mobile mapping system (MMS) which is equipped with a high-end 3D LiDAR and a number of high-cost sensors. This approach, however, is highly expensive and ineffective since a single high-end MMS must visit every place for mapping. In this paper, a lane-level RM mapping system using a monocular camera is developed. The developed system can be considered as an alternative to expensive high-end MMS. The developed RM map includes the information of road lanes (RLs) and symbolic road markings (SRMs). First, to build a lane-level RM map, the RMs are segmented at pixel level through the deep learning network. The network is named RMNet. The segmented RMs are then gathered to build a lane-level RM map. Second, the lane-level map is improved through loop-closure detection and graph optimization. To train the RMNet and build a lane-level RM map, a new dataset named SeRM set is developed. The set is a large dataset for lane-level RM mapping and it includes a total of 25157 pixel-wise annotated images and 21000 position labeled images. Finally, the proposed lane-level map building method is applied to SeRM set and its validity is demonstrated through experimentation.      

An adaptive sliding mode observer based near-optimal OER tracking control approach for PEMFC under dynamic operation condition

Tracking control of oxygen excess ratio (OER) is crucial for dynamic performance and operating efficiency of the proton exchange membrane fuel cell (PEMFC). OER tracking errors and overshoots under dynamic load limit the PEMFC output power performance, and also could lead oxygen starvation which seriously affect the life of PEMFC. To solve this problem, an adaptive sliding mode observer based near-optimal OER tracking control approach is proposed in this paper. According to real time load demand, a dynamic OER optimization strategy is designed to obtain an optimal OER. A nonlinear system model based near-optimal controller is designed to minimize the OER tracking error under variable operation condition of PEMFC. An adaptive sliding mode observer is utilized to estimate the uncertain parameters of the PEMFC air supply system and update parameters in near-optimal controller. The proposed control approach is implemented in OER tracking experiments based on air supply system of a 5 kW PEMFC test platform. The experiment results are analyzed and demonstrate the efficacy of the proposed control approach under load changes, external disturbances and parameter uncertainties of PEFMC system.     

YOLSO: You Only Look Small Object

Small object detection is challenging and far from satisfactory. Most general object detectors suffer from two critical issues with small objects: (1) Feature extractor based on classification network cannot express the characteristics of small objects reasonably due to insufficient appearance information of targets and a large amount of background interference around them. (2) The detector requires a much higher location accuracy for small objects than for general objects. This paper proposes an effective and efficient small object detector YOLSO to address the above problems. For feature representation, we analyze the drawbacks in previous backbones and present a Half-Space Shortcut(HSSC) module to build a background-aware backbone. Furthermore, a coarse-to-fine Feature Pyramid Enhancement(FPE) module is introduced for layer-wise aggregation at a granular level to enhance the semantic discriminability. For loss function, we propose an exponential L1 loss to promote the convergence of regression, and a focal IOU loss to focus on prime samples with high classification confidence and high IOU. Both of them significantly improves the location accuracy of small objects. The proposed YOLSO sets state-of-the-art results on two typical small object datasets, MOCOD and VeDAI, at a speed of over 200 FPS. In the meantime, it also outperforms the baseline YOLOv3 by a wide margin on the common COCO dataset.     

A comparative study between PVO-based framework and multi-predictor mechanism in reversible data hiding

Sorting-based reversible data hiding (RDH) methods like pixel-value-ordering (PVO) can predict pixel values accurately and achieve an extremely low distortion on the embedded image. However, the excellent performance of these methods was not well explained in previous works, and there are unexploited common points among them. In this paper, we propose a general multi-predictor (GMP) framework to summarize PVO-based RDH methods and explain their high prediction accuracy. Moreover, by utilizing the proposed GMP framework, a more efficient sorting-based RDH method is given as an example to show the generality and applicability of our framework. Comparing with other PVO-based methods, the proposed example method can achieve significant improvement in embedding performance. It is hopeful that more efficient sorting-based RDH algorithms can be designed according to our proposed framework by designing better predictors and their combination methods.