Autonomous robots that operate in the field can enhance their security and efficiency by accurate terrain classification, which can be realized by means of robot-terrain interaction-generated ...vibration signals. In this paper, we explore the vibration-based terrain classification (VTC), in particular for a wheeled robot with shock absorbers. Because the vibration sensors are usually mounted on the main body of the robot, the vibration signals are dampened significantly, which results in the vibration signals collected on different terrains being more difficult to discriminate. Hence, the existing VTC methods applied to a robot with shock absorbers may degrade. The contributions are two-fold: (1) Several experiments are conducted to exhibit the performance of the existing feature-engineering and feature-learning classification methods; and (2) According to the long short-term memory (LSTM) network, we propose a one-dimensional convolutional LSTM (1DCL)-based VTC method to learn both spatial and temporal characteristics of the dampened vibration signals. The experiment results demonstrate that: (1) The feature-engineering methods, which are efficient in VTC of the robot without shock absorbers, are not so accurate in our project; meanwhile, the feature-learning methods are better choices; and (2) The 1DCL-based VTC method outperforms the conventional methods with an accuracy of 80.18%, which exceeds the second method (LSTM) by 8.23%.
Natural products generally fall into the biologically relevant chemical space and always possess novel biological activities, thus making them a rich source of lead compounds for new drug discovery. ...With the recent technological advances, natural product-based drug discovery is now reaching a new era. Natural products have also shown promise in epigenetic drug discovery, some of them have advanced into clinical trials or are presently being used in clinic. The histone lysine specific demethylase 1 (LSD1), an important class of histone demethylases, has fundamental roles in the development of various pathological conditions. Targeting LSD1 has been recognized as a promising therapeutic option for cancer treatment. Notably, some natural products with different chemotypes including protoberberine alkaloids, flavones, polyphenols, and cyclic peptides have shown effectiveness against LSD1. These natural products provide novel scaffolds for developing new LSD1 inhibitors. In this review, we mainly discuss the identification of natural LSD1 inhibitors, analysis of the co-crystal structures of LSD1/natural product complex, antitumor activity and their modes of action. We also briefly discuss the challenges faced in this field. We believe this review will provide a landscape of natural LSD1 inhibitors.
In this review, the identification of natural LSD1 inhibitors, analysis of the co-crystal structures of LSD1/natural product complex, antitumor activity, their modes of action, and the challenges faced in this field were mainly discussed. This review will provide a landscape of natural LSD1 inhibitors. Display omitted
The structural mechanics of tropomyosin are essential determinants of its affinity and positioning on F-actin. Thus, tissue-specific differences among tropomyosin isoforms may influence both access ...of actin-binding proteins along the actin filaments and the cooperativity of actin-myosin interactions. Here, 40 nm long smooth and striated muscle tropomyosin molecules were rotary-shadowed and compared by means of electron microscopy. Electron microscopy shows that striated muscle tropomyosin primarily consists of single molecules or paired molecules linked end-to-end. In contrast, smooth muscle tropomyosin is more a mixture of varying-length chains of end-to-end polymers. Both isoforms are characterized by gradually bending molecular contours that lack obvious signs of kinking. The flexural stiffness of the tropomyosins was quantified and evaluated. The persistence lengths along the shaft of rotary-shadowed smooth and striated muscle tropomyosin molecules are equivalent to each other (∼100 nm) and to values obtained from molecular-dynamics simulations of the tropomyosins; however, the persistence length surrounding the end-to-end linkage is almost twofold higher for smooth compared to cardiac muscle tropomyosin. The tendency of smooth muscle tropomyosin to form semi-rigid polymers with continuous and undampened rigidity may compensate for the lack of troponin-based structural support in smooth muscles and ensure positional fidelity on smooth muscle thin filaments.
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•Molecular Dynamics simulations describe tropomyosin binding on actin.•During MD, tropomyosin largely matches a canonical coiled-coil model conformation.•Tropomyosin’s ends twist and ...bend during MD, thus deviating from the canonical model.•C- and N-terminal torsional freedom allows tropomyosin head–tail nexus formation.
Coiled-coil tropomyosin, localized on actin filaments in virtually all eukaryotic cells, serves as a gatekeeper regulating access of the motor protein myosin and other actin-binding proteins onto the thin filament surface. Tropomyosin’s modular pseudo-repeating pattern of approximately 39 amino acid residues is designed to allow binding of the coiled-coil to successive actin subunits along thin filaments. Even though different tropomyosin isoforms contain varying numbers of repeat modules, the pseudo-repeat length, in all cases, matches that of a single actin subunit. Thus, the seven pseudo-repeats of 42nm long muscle tropomyosin bind to seven successive actin subunits along thin filaments, while simultaneously bending into a super-helical conformation that is preshaped to the actin filament helix. In order to form a continuous cable on thin filaments that is free of gaps, adjacent tropomyosin molecules polymerize head-to-tail by means of a short (∼9 residue) overlap. Several laboratories have engineered peptides to mimic the N- and C-terminal tropomyosin association and to characterize the overlap structure. All overlapping domains examined show a compact N-terminal coiled-coil inserting into a partially opened C-terminal partner, where the opposing coiled-coils at the overlap junction face each other at up to ∼90° twist angles. Here, Molecular Dynamics (MD) simulations were carried out to determine constraints on the formation of the tropomyosin overlap complex and to assess the amount of twisting exhibited by full-length tropomyosin when bound to actin. With the exception of the last 20–40 C- and N-terminal residues, we find that the average tropomyosin structure closely resembles a “canonical” model proposed in the classic work of McLachlan and Stewart, displaying perfectly symmetrical supercoil geometry matching the F-actin helix with an integral number of coiled-coil turns, a coiled-coil helical pitch of 137Å, a superhelical pitch of 770Å, and no localized pseudo-rotation. Over the middle 70% of tropomyosin, the average twisting of the coiled-coil deviates only by 10° from the canonical model and the torsional freedom is very small (std. dev. of 7°). This small degree of twisting cannot yield the orthogonal N- and C-termini configuration observed experimentally. In marked contrast, considerable coiled-coil unfolding, splaying and twisting at N- and C-terminal ends is observed, providing the conformational plasticity needed for head-to-tail nexus formation.
Ammonia decomposition has attracted significant attention in recent years due to its ability to produce hydrogen without emitting carbon dioxide and the ease of ammonia storage. This paper reviews ...the recent developments in ammonia decomposition technologies for hydrogen production, focusing on the latest advances in catalytic materials and catalyst design, as well as the research progress in the catalytic reaction mechanism. Additionally, the paper discusses the advantages and disadvantages of each method and the importance of finding non-precious metals to reduce costs and improve efficiency. Overall, this paper provides a valuable reference for further research on ammonia decomposition for hydrogen production.
A series of brightly luminescent fluorine–boron cored complexes were synthesized from readily available precursors in high yield and were structurally characterized. The molecular structures were ...based on the benzothiazole and benzoxazole frameworks. The emission maxima of these fluorine–boron cored complexes spanned 70 nm in the visible spectrum from 450 nm (blue) to 520 nm (green). The photoluminescence quantum yields ranged from 0.16 to 0.8 in dichloromethane at room temperature. Altering the chelating position on the naphthalene ring provides a means to tailor the optical properties of the complexes.
A series of brightly luminescent, fluorine–boron cored complexes were synthesized from readily available precursors and the mission maxima of these fluorine–boron complexes spanned 70 nm in the visible spectrum from 450 nm (blue) to 520 nm (green). Display omitted
•A series of brightly luminescent, BF-cored complexes were synthesized from readily available precursors in high yield.•The molecule structures were based on the benzothiazole and benzoxazole backbones.•The emission maxima of these BF-cored complexes spanned 70 nm in the visible spectrum from 450 nm (blue) to 520 nm (green).•The photoluminescence quantum yields ranged from 0.16 to 0.8 in dichloromethane.•Chelating position shifting on the naphthalene ring result in large different optical properties.
Components of rotating machines, such as shafts, bearings and gears are subject to performance degradation, which if left unattended could lead to failure or breakdown of the entire system. Analyzing ...condition monitoring data, implementing diagnostic techniques and using machinery prognostic algorithms will bring about accurate estimation of the remaining life and possible failures that may occur. This paper proposes a combination of two supervised machine learning techniques; namely, the regression model and multilayer artificial neural network model, to predict the remaining useful life of rolling element bearings. Root mean square and Kurtosis were analyzed to define the bearing failure stages. The proposed methodology was validated through two case studies involving vibration measurements of an operational wind turbine gearbox and a split cylindrical roller bearing in a test rig.
Peroxisome proliferator-activated receptor γ (PPARγ), the molecular target for antidiabetic thiazolidinediones (TZDs), is a master regulator of preadipocyte differentiation and lipid metabolism. The ...adverse side effects of TZDs, arising from their potent agonistic activity, can be minimized by PPARγ partial agonists or PPARγ non-agonists without loss of insulin sensitization. In this study, we reported that WSF-7, a synthetic chemical derived from natural monoterpene α-pinene, is a partial PPARγ agonist. We found that WSF-7 binds directly to PPARγ. Activation of PPARγ by WSF-7 promotes adipogenesis, adiponectin oligomerization and insulin-induced glucose uptake. WSF-7 also inhibits obesity-mediated PPARγ phosphorylation at serine (Ser)273 and improves insulin sensitivity of 3T3-L1 adipocytes. Our study suggested that WSF-7 activates PPARγ transcription by a mechanism different from that of rosiglitazone or luteolin. Therefore, WSF-7 might be a potential therapeutic drug to treat type 2 diabetes.
► Well-known tropomyosin mutants, D175N and E180G are linked to cardiomyopathies. ► The structural mechanics of D175N and E180G tropomyosins have been investigated. ► D175N and E180G mutations ...increase both local and global tropomyosin flexibility. ► In muscle, this increased flexibility will enhance myosin interactions on actin. ► Extra myosin interaction can alter cardiac Ca2+-switching, leading to dysfunction.
Point mutations targeting muscle thin filament proteins are the cause of a number of cardiomyopathies. In many cases, biological effects of the mutations are well-documented, whereas their structural and mechanical impact on filament assembly and regulatory function is lacking. In order to elucidate molecular defects leading to cardiac dysfunction, we have examined the structural mechanics of two tropomyosin mutants, E180G and D175N, which are associated with hypertrophic cardiomyopathy (HCM). Tropomyosin is an α-helical coiled-coil dimer which polymerizes end-to-end to create an elongated superhelix that wraps around F-actin filaments of muscle and non-muscle cells, thus modulating the binding of other actin-binding proteins. Here, we study how flexibility changes in the E180G and D175N mutants might affect tropomyosin binding and regulatory motion on F-actin. Electron microscopy and Molecular Dynamics simulations show that E180G and D175N mutations cause an increase in bending flexibility of tropomyosin both locally and globally. This excess flexibility is likely to increase accessibility of the myosin-binding sites on F-actin, thus destabilizing the low-Ca2+ relaxed-state of cardiac muscle. The resulting imbalance in the on–off switching mechanism of the mutants will shift the regulatory equilibrium towards Ca2+-activation of cardiac muscle, as is observed in affected muscle, accompanied by enhanced systolic activity, diastolic dysfunction, and cardiac compensations associated with HCM and heart failure.
In order to study the flow and erosion behavior of gas-solid exhaust in the polysilicon reduction furnace, the flow characteristics of exhaust gas and silicon particles were analyzed. The flow model ...and erosion model of exhaust gas and silicon particles were established based on the gas-solid flow theory and the erosion theory. The erosion and wear behavior of the gas-solid mixture in the flow passage pipeline were studied by numerical simulation. The results show that the wear and erosion from Nos. 1 to 8 regions at the bottom of the ring were caused by silicon particles colliding with high angle. The wear and erosion of 2 regions from Nos. 9 to 10 at the outside of the up azimuth on both sides of loop pipe outlets, 4 regions from Nos. 11 to 14 on the upper and lower wall of single furnace main channel were severely affected wear regions, which is caused by silicon particles with low angle and high velocity. Through comparative analysis, the erosion of upper wall of single furnace main channel is most serious. Increased gas velocity, particle concentration and particle size will exacerbate the erosion and wear rate of the pipeline in polysilicon reduction furnace, but the distribution and development of severe wear zone would not be affected significantly.
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