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High-voltage-activated R-type CaV2.3 channel plays pivotal roles in many physiological activities and is implicated in epilepsy, convulsions, and other neurodevelopmental impairments. Here, we determine the high-resolution cryo-electron microscopy (cryo-EM) structure of human CaV2.3 in complex with the α2δ1 and β1 subunits. The VSDIIis stabilized in the resting state. Electrophysiological experiments elucidate that the conformational change of VSDIIin response to variation in membrane potential is not required for channel activation, whereas the other VSDs are essential for channel opening. The intracellular gate is blocked by the W-helix. A pre-W-helix adjacent to the W-helix can significantly regulate closed-state inactivation (CSI) by modulating the association and dissociation of the W-helix with the gate. Electrostatic interactions formed between the negatively charged domain on S6II, which is exclusively conserved in the CaV2 family, and nearby regions at the alpha-interacting domain (AID) and S4-S5IIhelix are identified. Further functional analyses indicate that these interactions are critical for the open-state inactivation (OSI) of CaV2 channels.

Jiusha Bridge in Hangzhou city, China, is an asymmetric spatial butterfly-shaped steel arch bridge. The bridge deck and steel arch rib form a half-through structure at one end and a through structure at the other. The bridge sits on a soft soil foundation with poor thrust resistance; therefore, different force transmission structures adopted at the asymmetric ends to balance the large arch thrust during internal force transmission of the structure were researched. The mechanical behaviour of the asymmetric steel arch bridge under dead load and live load was compared with that of a symmetric half-through and through steel arch bridge. Subsequently, a full-bridge finite-element (FE) model was established in order to adjust the stiffness contribution of the middle arch and side arches to the bridge, optimise the hanger forces in the finished bridge state and analyse the bridge's stress, stiffness, stability and dynamic characteristics. The stresses in some key members and joints were calculated by means of a refined FE model consisting of beam elements, truss elements and plate elements. Some of the special construction technologies used on Jiusha Bridge are also briefly discussed.

Voltage-gated sodium (Na

Face image-sketch synthesis is widely applied in law enforcement and digital entertainment fields. Despite the extensive progression in face image-sketch synthesis, there are few methods focusing on generating a color face image from a sketch. The existing methods pay less attention to learning the illumination or highlight distribution on the face region. However, the illumination is the key factor that makes the generated color face image looks vivid and realistic. Moreover, existing methods tend to employ some image preprocessing technologies and facial region patching approaches to generate high-quality face images, which results in the high complexity and memory consumption in practice. In this paper, we propose a novel end-to-end generative adversarial fusion model, called GAF, which fuses two U-Net generators and a discriminator by jointly learning the content and adversarial loss functions. In particular, we propose a parametric tanh activation function to learn and control illumination highlight distribution over faces, which is integrated between the two U-Net generators by an illumination distribution layer. Additionally, we fuse the attention mechanism into the second U-Net generator of GAF to keep the identity consistency and refine the generated facial details. The qualitative and quantitative experiments on the public benchmark datasets show that the proposed GAF has better performance than existing image-sketch synthesis methods in synthesized face image quality (FSIM) and face recognition accuracy (NLDA). Meanwhile, the good generalization ability of GAF has also been verified. To further demonstrate the reliability and authenticity of face images generated using GAF, we use the generated face image to attack the well-known face recognition system. The result shows that the face images generated by GAF can maintain identity consistency and well maintain everyone's unique facial characteristics, which can be further used in the benchmark of facial spoofing. Moreover, the experiments are implemented to verify the effectiveness and rationality of the proposed parametric tanh activation function and attention mechanism in GAF.

In the present research, we developed a novel non-enzymatic fructose sensor by platinum decorated graphene oxide nanocomposite based cyclic voltammetry. This sensor can detect fructose in alkalized medium which converts fructose into oxidizable glucose. The dynamic range of trace detection is within 0.05–0.50 mM and the detection limit was achieved around 10 μM even in the presence of HPO42− and Cl− as interferent ions. The electrochemical signal from the fructose can be significantly discriminated from that of lactose and sucrose, leaving glucose to be further distinguished in neutral medium. This non-enzymatic fructose sensing approach potentially provides a novel strategy to measure the concentration of fructose in biological fluids with potential application for clinical diagnostics and quality control in food industry.

The hydration heat of pumped concrete in large diameter concrete-filled steel tube (CFST) arches results in considerable temperature changes, which significantly affect the development of the mechanical properties of concrete during its hardening process, making it hard to determine the loading age. Based on the heat conduction theory and finite element method, the hydration heat temperature field of large diameter CFST arches during the period of construction was analyzed. Subsequently, the effects of hydration heat on the developments of compressive strength ( f cu ) and elastic modulus of concrete ( E c ) were analyzed by using the equivalent age method. The results reveal that, because of the influence of the hydration heat, the developments of f cu and E c are uneven along the radial direction of the arch cross section in the early stage, i.e. faster at the concrete center, and slower at the concrete edge. On the 5th day, the average values of f cu and E c reach 81.6% and 90.3% of their characteristic values, respectively; the difference of f cu and E c between the concrete center and concrete edge are 13% and 7.3%, respectively; and f cu , E c of the concrete cross section tend to be uniform. Hence, in order to ensure structural safety, the loading age for large diameter CFST arches after concrete casting should not be less than 5 days at low ambient temperature.

CaMKII has long been known to be a key effector for synaptic plasticity. Recent studies have shown that a variety of modulators interact with the subunits of CaMKII to regulate the long-term potentiation (LTP) of hippocampal neurons. However, whether long non-coding RNAs modulate the activity of CaMKII and affect synaptic plasticity is still elusive. Here, we identify a previously uncharacterized long non-coding RNA Carip that functions as a scaffold, specifically interacts with CaMKIIβ, and regulates the phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptor subunits in the hippocampus. The absence of Carip causes dysfunction of synaptic transmission and attenuates LTP in hippocampal CA3-CA1 synapses, which further leads to impairment of spatial learning and memory. In summary, our findings demonstrate that Carip modulates long-term synaptic plasticity by changing AMPA receptor and NMDA receptor activities, thereby affecting spatial learning and memory in mice.

Synaptic transmission at mammalian central synapses has ongoing background activity at physiological temperature. The recycling vesicle pool, with proper kinetics, ensures sustained synaptic transmission. However, the kinetic structure of recycling vesicle pool has never been quantitatively analyzed before, and most studies were performed at room temperature and under resting conditions. With the combination of presynaptic capacitance measurement and postsynaptic EPSC recording on calyx of Held synapses at physiological temperature, we studied vesicle recycling under sustained presynaptic stimulation. The kinetics of vesicle reuse was revealed by impeding transmitter refilling with folimycin. We kinetically dissected the recycling vesicle pool as sequentially connected sub-pools and depicted the complete kinetic structure. The sizes and transition rates among these sub-pools were dynamically regulated by neuronal activity, in order to ensure efficient synaptic transmission. Our work highlights the impact of the vesicle recycling machinery on stable and reliable synaptic transmission under variable levels of neuronal activity.Impact statementThe recycling pool of vesicles are kinetically dissected as four populated pools ensuring stable and reliable synaptic transmission

Electronic waste is the fastest growing waste stream and one of the most significant constituents is electronic plastics. In this study, the combustion kinetic of typical electronic plastic waste-television set (TV) plastic shell-was investigated using two basic kinetic methods. The reaction mechanism and kinetic compensation effect were probed as well. The thermogravimetric analysis (TGA) revealed that its degradation process can be divided into four stages, namely, reaction initiation stage (20-300 °C), major reaction stage (300-450 °C), minor reaction stage (450-600 °C), and reaction cessation stage (600-1,000 °C). The activation energy (

Summary The intestinal microbiota closely interacts with the neuroendocrine system and exerts profound effects on host physiology. Here, we report that nucleotide-binding oligomerization domain 1 (Nod1) ligand derived from intestinal bacteria modulates catecholamine storage and secretion in mouse adrenal chromaffin cells. The cytosolic peptidoglycan receptor Nod1 is involved in chromogranin A (Chga) retention in dense core granules (DCGs) in chromaffin cells. Mechanistically, upon recognizing its ligand, Nod1 localizes to DCGs, and recruits Rab2a, which is critical for Chga and epinephrine retention in DCGs. Depletion of Nod1 ligand or deficiency of Nod1 leads to a profound defect in epinephrine storage in chromaffin cells and subsequently less secretion upon stimulation. The intestine-adrenal medulla cross talk bridged by Nod1 ligand modulates adrenal medullary responses during the immobilization-induced stress response in mice. Thus, our study uncovers a mechanism by which intestinal microbes modulate epinephrine secretion in response to stress, which may provide further understanding of the gut-brain axis., Graphical abstract, Highlights • Nod1 expressed in adrenal chromaffin cells senses intestinal bacteria • Bacterial Nod1 ligand promotes catecholamine storage and secretion • The microbiota-intestine- adrenal medulla axis modulates fight and flight response, Molecular biology; Neuroscience; Microbiome

Presynaptic Ca(v)2 channels are essential for Ca2+-triggered exocytosis. In addition, there are two competing models for their roles in synapse structure. First, Ca2+ channels or Ca2+ entry may control synapse assembly. Second, active zone proteins may scaffold Ca(v)2s to presynaptic release sites, and synapse structure is Ca(v)2 independent. Here, we ablated all three Ca(v)2s using conditional knockout in cultured hippocampal neurons or at the calyx of Held, which abolished evoked exocytosis. Compellingly, synapse and active zone structure, vesicle docking, and transsynaptic nano-organization were unimpaired. Similarly, long-term blockade of action potentials and Ca2+ entry did not disrupt active zone assembly. Although Ca(v)2 knockout impaired the localization of beta subunits, alpha 2 delta-1 localized normally. Rescue with Ca(v)2 restored exocytosis, and Ca(v)2 active zone targeting depended on the intracellular C-terminus. We conclude that synapse assembly is independent of Ca(v)2s or Ca2+ entry through them. Instead, active zone proteins recruit and anchor Ca(v)2s via Ca(v)2 C-termini.

Steel and concrete composite structures can give full play to mechanical advantages of the two materials, so it is widely used all over the world. As the key components to ensure the compatibility deformation of two materials, the importance of shear studs to the security of structures is self-evident. However, fatigue research on shear studs is still lagging behind, and there is a potential safety hazard. Thus, based on crack box technique, the M integral and the maximum tangential stress criterion, this paper presents a simulation method for fatigue crack propagation of studs in three-dimensional mixed fracture mode. The crack propagation of Type A fracture in studs is simulated under fatigue load of constant slip between steel and concrete. Results show that the crack deflection angle of stud increases with slip effect. In crack propagation process, the stress intensity factor KI is the highest and KIII is the smallest, whose effect on the deflection angle during crack propagation can be reasonably ignored. The crack surface inclines slightly to the bottom of welding collar while the crack expands in the stud.

The tire defect detection method can help the rehabilitation robot to achieve autonomous positioning function and improve the accuracy of the robot system behavior. Defects such as foreign matter sidewall, foreign matter tread, and sidewall bubbles will appear in the process of tire production, which will directly or indirectly affect the service life of the tire. Therefore, a novel and efficient tire defect detection method was proposed based on Faster R-CNN. At preprocessing stage, the Laplace operator and the homomorphic filter were used to sharpen and enhance the data set, the gray values of the image target and the background were significantly different, which improved the detection accuracy. Moreover, data expansion was used to increase the number of images and improve the robustness of the algorithm. To promote the accuracy of the position detection and identification, the proposed method combined the convolution features of the third layer and the convolution features of the fifth layer in the ZF network (a kind of convolution neural network). Then, the improved ZF network was used to extract deep characteristics as inputs for Faster R-CNN. From the experiment, the proposed faster R-CNN defect detection method can accurately classify and locate the tire X-ray image defects, and the average test recognition rate is up to 95.4%. Moreover, if there are additional types of defects that need to be detected, then a new detection model can be obtained by fine-tuning the network.

In recent decades, concrete-filled steel tube (CFST) arch bridges have been widely constructed in China. With the increasing span and arch rib diameter of CFST arch bridges, the hydration heat of pumped mass concrete in the CFST arch causes greater temperature changes during the period of construction, leading to potential thermal stress-induced cracking of mass concrete enclosed in the steel tube. In this paper, a finite element model was established to simulate the hydration heat transfer process of large-meter CFST arch which was compared with the measured data from the literature. Subsequently, the variation of thermal stress during hardening process was revealed combining with numerical implementation and analytical study, and there is a reasonable agreement between the analytical solutions and those obtained by numerical implementation. In addition, the effect of concrete creep on the thermal stresses due to hydration heat was taking into account in the calculation based on the relaxation coefficient method. The results show that the nonlinear temperature field generated from the hydration heat determines the nonlinear variation of the thermal stress of CFST structure during hardening process. The thermal stress increases rapidly at the beginning of the concrete hydration, and there is a large stress gradient along the radial direction of the arch cross section; the stress slowly decreases after peak, and there is residual thermal tensile stress in the concrete after the heat release. Concrete creep significantly reduces the thermal stress of the concrete in the early age, but the effect on the thermal stress of the steel tube is negligible.

Presynaptic Ca

A soluble 4H-cyclopenta[2,1-b;3,4-b′]dithiophene-4-one (CPDTO)-based polymer (C6-PCPDTO) has been synthesized from two monomers derived from nonalkylated CPDTO and didodecyl CPDTO (C12-CPDTO). Proton NMR, thermal analysis, UV–vis absorption, cyclic voltammetry, and XRD are used to characterize the polymer in solution and film. The new polymer has an optical bandgap of 1.28 eV in film, and has strong interchain interaction in chloroform solutions. The polymer contains a significant amount of homocoupled segments. The regular segments and homocoupled CPDTO segments render the polymer highly aggregating in solution. The non-planar homocoupled C12-CPDTO segments prevent the polymer from forming regular π-stacks, resulting in a low SCLC hole mobility (3.88 × 10−7 cm2V−1s−1). CV experiments show that C6-PCPDTO is stable in its oxidized and reduced states. Solar cell devices were fabricated from C6-PCPDTO2:PC60BM blends of different weight ratios. High PC60BM loading (80% or greater) was required for the devices to show measurable efficiency, indicating that the limited π-stacking of the polymer is not sufficient to cause effective phase separation. Further development of synthetic method is still needed to eliminate structural defects so that long-range ordered pi-stacking can be realized in the polymer for these applications. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017