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In the treatment of chronic hepatitis B (CHB) infection, stimulation of innate immunity may lead to hepatitis B virus (HBV) cure. Alpha-kinase 1 (ALPK1) is a pattern recognition receptor (PRR) that activates the NF-κB pathway and stimulates innate immunity. Here we characterized the preclinical anti-HBV efficacy of DF-006, an orally active agonist of ALPK1 currently in clinical development for CHB.In adeno-associated virus (AAV)-HBV mouse models and primary human hepatocytes (PHHs) infected with HBV, we evaluated the antiviral efficacy of DF-006. In the mouse models, DF-006 rapidly reduced serum HBV DNA, hepatitis B surface antigen, and hepatitis B e antigen levels using doses as low as 0.08 μg/kg, 1 μg/kg, and 5 μg/kg, respectively. DF-006 in combination with the HBV nucleoside reverse transcriptase inhibitor, entecavir, further reduced HBV DNA. Antiviral efficacy in mice was associated with an increase in immune cell infiltration and decrease of hepatitis B core antigen, encapsidated pregenomic RNA, and covalently closed circular DNA in liver. At subnanomolar concentrations, DF-006 also showed anti-HBV efficacy in PHH with significant reductions of HBV DNA. Following dosing with DF-006, there was upregulation of NF-κB-targeted genes that are involved in innate immunity.DF-006 was efficacious in mouse and PHH models of HBV without any indications of overt toxicity. In mice, DF-006 localized primarily to the liver where it potently activated innate immunity. The transcriptional response in mouse liver provides insights into mechanisms that mediate anti-HBV efficacy by DF-006.

In geostationary orbits and other quasi-vacuum environments, relativistic electron beams are affected by the initial emittance and space charge effects during the propagation process, resulting in beam quality degradation. Furthermore, axial energy distribution change in the beam and the axial transient electromagnetic effect caused by current changes in the head and tail regions of the beam also cause the beam to expand and affect its quality. In this study, the particle-in-cell method was used to construct a long-range propagation model of a relativistic electron beam in a vacuum environment. By calculating and simulating the axial energy distribution of the beam and the changes in the transient electromagnetic field, the axial effect during the propagation process was analyzed, and the parameter change law of the effective propagation of the beam was explored. This provided a theoretical reference for a more accurate assessment of the beam quality during propagation.

Angiogenesis and vascular remodeling are essential for the establishment of vascular networks during organogenesis. Here we show that the Hippo signaling pathway effectors YAP and TAZ are required, in a gene dosage-dependent manner, for the proliferation and migration of vascular endothelial cells (ECs) during retinal angiogenesis. Intriguingly, nuclear translocation of YAP and TAZ induced by Lats1/2-deletion blocked endothelial migration and phenocopied Yap/Taz-deficient mutants. Furthermore, overexpression of a cytoplasmic form of YAP (YAPS127D) partially rescued the migration defects caused by loss of YAP and TAZ function. Finally, we found that cytoplasmic YAP positively regulated the activity of the small GTPase CDC42, deletion of which caused severe defects in endothelial migration. These findings uncover a previously unrecognized role of cytoplasmic YAP/TAZ in promoting cell migration by activating CDC42 and provide insight into how Hippo signaling in ECs regulates angiogenesis.

An efficient analytical model has been developed for predicting the load response of a lossless transmission line (TL) in a rectangular double-enclosure with multiple apertures covered by conductive sheets, excited by an external plane wave of oblique incidence. First, the electromagnetic field in the enclosure is calculated using the enclosure dyadic Green’s function and the transfer impedance of the sheets against the plane wave. Then, the electric current induced at the termination loads of the TL is computed in combination of the equivalent lumped-pi circuit model of the line and the Agrawal’s model. The analytical model has been successfully verified by the full-wave software CST (Computer Simulation Technology) over a wide frequency band, and it is employed to analyze the effect of various parameters on the induced current, including the sheet conductivity, the load impedance, and the position of the line. This model consumes less time compared with numerical methods, and it can also deal wi...

The critical frequency foF2 of the ionosphere F2 layer is one of the most important parameters of the ionosphere. Based on the Elman neural network (ENN), this paper constructs a single station forecasting model to predict foF2 one hour ahead. In order to avoid the network falling into local minimum, the model is optimized by the improved particle swarm optimization (IPSO). The input parameters used in the model include local time, seasonal information, solar cycle information and magnetic activity information. Data of the Wuhan Station from 2008 to 2016 were used to train and test the model. The prediction results of foF2 show that the root mean square error (RMSE) of the Elman neural network model is 4.30% lower than that of the back-propagation neural network (BPNN) model. The RMSE is further reduced by 8.92% after using the IPSO to optimize the model. This indicates that the Elman neural network model optimized by the improved particle swarm optimization is superior to the BP neural network and Elman neural network in the forecast of foF2 one hour ahead at Wuhan station.

Based on the analysis of random error sources in the design margin evaluation of electromagnetic protection for complex electronic, it is researched on a method of evaluating electromagnetic pulse protection capability, the total error standard deviation evaluation theory is analysed. A new method for evaluating the electromagnetic pulse protection capability of complex electronic systems based on the lower limit estimation of design margin and corresponding reliability and confidence is proposed. So taking the evaluation of electromagnetic protection design interval of a certain type of electronic information system as an example, the application and the qualification conditions of the algorithm are illustrated.

An analytical formulation has been developed to evaluate the shielding effectiveness (SE) of two coplanar rectangular metallic enclosures with a circular aperture excited by an internal electric dipole source. The formulation consists of three parts: First, the near-field electromagnetic interference (EMI) of the electromagnetic leakage from the aperture is represented by the electric dipole in one enclosure. Then, the aperture equivalent magnetic and electric dipole moments are calculated according to the Bethe's small aperture coupling theory. Finally, the electric field of the other enclosure is derived by using the equivalent magnetic dipole field, equivalent electric dipole field and the corresponding enclosure's Green's functions in the two fields. In this formulation, the electric field of the enclosure can be expressed as a function of the observation point, the aperture's center point, source point, shape of the aperture and enclosure's conductivity. The formulation then is employed to analyze the effect of the above factors on the SE. The analytical results have been successfully compared with the full-wave simulation software Computer Simulation Technology (CST) from 0.3 ∼ 2. 4G Hz.

Angiogenesis defines the process in which new vessels grow from existing vessels. Using the mouse retina as a model system, we show that cysteine-rich motor neuron 1 (Crim1), a type I transmembrane protein, is highly expressed in angiogenic endothelial cells. Conditional deletion of the Crim1 gene in vascular endothelial cells (VECs) causes delayed vessel expansion and reduced vessel density. Based on known Vegfa binding by Crim1 and Crim1 expression in retinal vasculature, where angiogenesis is known to be Vegfa dependent, we tested the hypothesis that Crim1 is involved in the regulation of Vegfa signaling. Consistent with this hypothesis, we showed that VEC-specific conditional compound heterozygotes for Crim1 and Vegfa exhibit a phenotype that is more severe than each single heterozygote and indistinguishable from that of the conditional homozygotes. We further showed that human CRIM1 knockdown in cultured VECs results in diminished phosphorylation of VEGFR2, but only when VECs are required to rely on an autocrine source of VEGFA. The effect of CRIM1 knockdown on reducing VEGFR2 phosphorylation was enhanced when VEGFA was also knocked down. Finally, an anti-VEGFA antibody did not enhance the effect of CRIM1 knockdown in reducing VEGFR2 phosphorylation caused by autocrine signaling, but VEGFR2 phosphorylation was completely suppressed by SU5416, a small-molecule VEGFR2 kinase inhibitor. These data are consistent with a model in which Crim1 enhances the autocrine signaling activity of Vegfa in VECs at least in part via Vegfr2.

A large-diameter aluminum-alloy finned-tube absorbent bed collector was designed and optimized by enhancing the heat and mass transfer in the collector. The collection efficiency of the adsorbent bed collector was between 31.64% and 42.7%, and the temperature distribution in the absorbent bed was relatively uniform, beneficial to adsorption/desorption of the adsorbate in the absorbent bed. A solar-powered solid adsorption refrigeration system with the finned-tube absorbent bed collector was built. Some experiments corresponding to the adsorption/desorption process with and without a valve control were conducted in four typical weather conditions: sunny with clear sky, sunny with partly cloudy sky, cloudy sky and overcast sky. Activated carbon–methanol was utilized as the working pair for adsorption refrigeration in the experiments. The experiments achieved the maximum COP of 0.122 and the maximum daily ice-making of 6.5 kg. Under the weather conditions of sunny with clear sky, sunny with partly cloudy sky, and cloudy sky, ice-making phenomenon were observed. Even in the overcast-sky weather condition, the cooling efficiency of the system still reached 0.039 when the total solar radiation was 11.51 MJ. The cooling efficiency of the solar-powered adsorption refrigeration system with a valve control in the adsorption/desorption process was significantly higher than that without a valve control.

Endothelial cells respond to molecular and physical forces in development and vascular homeostasis. Deregulation of endothelial responses to flow-induced shear is believed to contribute to many aspects of cardiovascular diseases including atherosclerosis. However, how molecular signals and shear-mediated physical forces integrate to regulate vascular patterning is poorly understood. Here we show that endothelial non-canonical Wnt signalling regulates endothelial sensitivity to shear forces. Loss of Wnt5a/Wnt11 renders endothelial cells more sensitive to shear, resulting in axial polarization and migration against flow at lower shear levels. Integration of flow modelling and polarity analysis in entire vascular networks demonstrates that polarization against flow is achieved differentially in artery, vein, capillaries and the primitive sprouting front. Collectively our data suggest that non-canonical Wnt signalling stabilizes forming vascular networks by reducing endothelial shear sensitivity, thus keeping vessels open under low flow conditions that prevail in the primitive plexus. DOI: http://dx.doi.org/10.7554/eLife.07727.001, eLife digest Blood vessels play an essential role in growth and development as they transport many important molecules that help cells to survive. Throughout life, the forces that act on the blood vessels help to remodel the vessel network to ensure that blood gets to the parts of the body that need it. For example, the movement of blood across the surface of the endothelial cells that line the inside of the blood vessels applies a force called “shear stress” to the cells. The endothelial cells respond and adapt to the stress by altering their shape, patterns of gene activity and internal organization (known as their polarity). It was not fully understood exactly how the forces acting on endothelial cells help to remodel the blood vessel network. Franco et al. have now investigated how a signalling pathway known as non-canonical Wnt signalling affects the remodelling of blood vessels in mice, and found that this pathway stabilizes existing connections between vessels. Disrupting non-canonical Wnt signalling, by genetically engineering mice to lack proteins called Wnt5a and Wnt11, increased the sensitivity of endothelial cells to shear stress. Franco et al. then built a computer model that simulates blood flow and endothelial cell polarity in a network of blood vessels; this enabled them to measure the endothelial cells’ response to blood flow in complex vascular networks. The model was then used to show that endothelial cells lacking non-canonical Wnt signalling are able to reorient and become polarized against the direction of blood flow at lower levels of shear stress. Thus, non-canonical Wnt signalling helps to raise the threshold of shear stress above which endothelial cells change their properties. Further work is now needed to identify how non-canonical Wnt signalling interferes with the ability of the endothelial cells to sense shear stress levels. DOI: http://dx.doi.org/10.7554/eLife.07727.002

The developing lens is a powerful system for investigating the molecular basis of inductive tissue interactions and for studying cataract, the leading cause of blindness. The formation of tightly controlled cell-cell adhesions and cell-matrix junctions between lens epithelial (LE) cells, between lens fiber (LF) cells, and between these two cell populations enables the vertebrate lens to adopt a highly ordered structure and acquire optical transparency. Adhesion molecules are thought to maintain this ordered structure, but little is known about their identity or interactions. Cysteine-rich motor neuron 1 (Crim1), a type I transmembrane protein, is strongly expressed in the developing lens and its mutation causes ocular disease in both mice and humans. How Crim1 regulates lens morphogenesis is not understood. We identified a novel ENU-induced hypomorphic allele of Crim1, Crim1glcr11, which in the homozygous state causes cataract and microphthalmia. Using this and two other mutant alleles, Crim1null and Crim1cko, we show that the lens defects in Crim1 mouse mutants originate from defective LE cell polarity, proliferation and cell adhesion. Crim1 adhesive function is likely to be required for interactions both between LE cells and between LE and LF cells. We show that Crim1 acts in LE cells, where it colocalizes with and regulates the levels of active β1 integrin and of phosphorylated FAK and ERK. The RGD and transmembrane motifs of Crim1 are required for regulating FAK phosphorylation. These results identify an important function for Crim1 in the regulation of integrin- and FAK-mediated LE cell adhesion during lens development., Summary: Crim1, a type I transmembrane protein, acts in lens epithelial cells where it colocalizes with and regulates the levels of active β1 integrin to control cell adhesion during mouse lens morphogenesis.

Colobomatous macrophthalmia with microcornea syndrome (MACOM, Online Mendelian Inheritance in Man (OMIM) 602499) is an autosomal dominantly inherited malformation of the eye, which is characterized by microcornea with increased axial length, coloboma of the iris and of the optic disc, and severe myopia. We performed whole-exome sequencing (WES) in two affected individuals from the 2p23-p16-linked MACOM family, which includes 13 affected individuals in 3 generations. As no shared novel variation was found on the linked haplotype, we performed copy number variation (CNV) analysis by comparing the coverage of all exons in the WES data sets of the 2 patients with the coverage of 26 control exomes. We identified a heterozygous deletion predicted to span 22 kb including exons 14-17 of CRIM1 (cysteine-rich transmembrane bone morphogenetic protein (BMP) regulator 1). Quantitative PCR (qPCR) analysis confirmed the deletion, which was present in 11 affected individuals. Split-read analysis of WES data followed by breakpoint PCR and Sanger sequencing determined both breakpoints flanked by a 4-bp microhomology (CTTG). In the mouse, Crim1 is a growth-factor-binding protein with pleiotropic roles in the development of multiple organs, including the eye. To investigate the role of Crim1 during eye development in mice, we crossed a Crim1(flox) mouse line with the Ap2 alpha-cre mouse line, which expresses Cre in the head surface ectoderm. Strikingly, we observed alterations of eye development in homozygous mice leading to severe anatomical and morphological changes overlapping with the anomalies observed in MACOM patients. Taken together, these findings identify CRIM1 as the causative gene for MACOM syndrome and emphasize the importance of CRIM1 in eye development.

During retinal vascular development there is simultaneous regression of the hyaloid vasculature and formation of the retinal vasculature; here it is demonstrated that regression of developing vasculature is light dependent and acts via the photoreceptor melanopsin. In the developing eye, as the retinal vasculature forms the blood vessels supplying the transparent hyaloid membrane surrounding the vitreous body regress. This process is clinically important as excessive vascular growth is a major cause of blindness in premature infants. Surprisingly, this study reports that light is involved in this major change in tissue architecture. Richard Lang and colleagues find that light stimulates regression of developing hyaloid vasculature in mice, acting through the photoreceptor melanopsin. In the absence of either light or melanopsin, vascular endothelial growth factor A is upregulated and abnormal retinal angiogenesis results. Whether the same processes are involved in human eye development remains to be determined. Vascular patterning is critical for organ function. In the eye, there is simultaneous regression of embryonic hyaloid vasculature1 (important to clear the optical path) and formation of the retinal vasculature2 (important for the high metabolic demands of retinal neurons). These events occur postnatally in the mouse. Here we have identified a light-response pathway that regulates both processes. We show that when mice are mutated in the gene (Opn4) for the atypical opsin melanopsin3,4,5, or are dark-reared from late gestation, the hyaloid vessels are persistent at 8 days post-partum and the retinal vasculature overgrows. We provide evidence that these vascular anomalies are explained by a light-response pathway that suppresses retinal neuron number, limits hypoxia and, as a consequence, holds local expression of vascular endothelial growth factor (VEGFA) in check. We also show that the light response for this pathway occurs in late gestation at about embryonic day 16 and requires the photopigment in the fetus and not the mother. Measurements show that visceral cavity photon flux is probably sufficient to activate melanopsin-expressing retinal ganglion cells in the mouse fetus. These data thus show that light—the stimulus for function of the mature eye—is also critical in preparing the eye for vision by regulating retinal neuron number and initiating a series of events that ultimately pattern the ocular blood vessels.

The developing lens is a powerful system for investigating the molecular basis of inductive tissue interactions and for studying cataract, the leading cause of blindness. The formation of tightly controlled cell-cell adhesions and cell-matrix junctions between lens epithelial (LE) cells, between lens fiber (LF) cells, and between these two cell populations enables the vertebrate lens to adopt a highly ordered structure and acquire optical transparency. Adhesion molecules are thought to maintain this ordered structure, but little is known about their identity or interactions. Cysteine-rich motor neuron 1 (Crim1), a type I transmembrane protein, is strongly expressed in the developing lens and its mutation causes ocular disease in both mice and humans. How Crim1 regulates lens morphogenesis is not understood. We identified a novel ENU-induced hypomorphic allele of Crim1, Crim1(glcr11), which in the homozygous state causes cataract and microphthalmia. Using this and two other mutant alleles, Crim1(null) and Crim1(cko), we show that the lens defects in Crim1 mouse mutants originate from defective LE cell polarity, proliferation and cell adhesion. Crim1 adhesive function is likely to be required for interactions both between LE cells and between LE and LF cells. We show that Crim1 acts in LE cells, where it colocalizes with and regulates the levels of active β1 integrin and of phosphorylated FAK and ERK. The RGD and transmembrane motifs of Crim1 are required for regulating FAK phosphorylation. These results identify an important function for Crim1 in the regulation of integrin- and FAK-mediated LE cell adhesion during lens development.

With the complexity of power network, the weak link between connected systems becomes more and more fragile. As an important part of wide area protection system (WAPS), wide area backup protection system's (WABPS's) delay characteristics have raised more and more attention. To solve this problem, this paper has a research on the State Power Data Network (SPDnet) and discusses the application of phasor measurement unit (PMU) devices based on global position system (GPS) in WABPS. Through the analysis of the mesh topology, the progress of applying this structure in the network to realize data transmission between adjacent sub-station is discussed. Finally, we verify the feasibility of the network structure by OPNET.

A strong power dispatching communication network with high speed becomes the premise of the establishment of a reliable Wide Area Monitoring System (WAMS). Signal transmission of Phasor Measurement Unit (PMU) is taken into account in different collective layers in this paper. The time delay modes based on Multi-Protocol Label Switching-Virtual Private Network (MPLS VPN) and point-to-point 2M link illustrate that the time delay of the former is better than the latter. Building the VPN network under MPLS can provide quality of service and ensure the stable transmission of real-time signal through traffic engineering, differentiated services and the protection function in MPLS layer with virtual route. The time delay character of “1+1” protection on the MPLS layer is also analyzed in this paper.

Processes of digital image processing and image recognition of transformer fan state recognition are expounded in this paper. According to the features of transformer fans, analysis and studies on image processing algorithms such as annulus extraction, image segment and corrosion are given. To solve problem that the identification accuracy is directly affected by image preprocessing effects in the method of whole annulus criterion, a sub-annulus criterion method is proposed to implement fan state recognition in this paper. This method makes full use of the distribution feature of annulus pixels, divides the annulus into equal two parts at pixel number forming sub-annuluses and selects the proportions of fan blade pixels in sub-annuluses as the binary state feature quantities to realize state classification. Experimental results prove that this method can effectively reduce the high demand of recognition accuracy to image processing effects and it has advantages in many other aspects, such as simple computations, strong applicability and perfect recognition performance.

There are lots of electric equipments in the substation, whether they work properly or not is always related to the working security and stability of substation. Therefore, applying video image recognition technology in substation equipments monitoring is a method which can protect and maintain the equipments effectively. This paper introduces the application of video image recognition technology briefly in current situation and proposes different schemes of image preprocessing and image recognition based on different situations, which can solve the problems of meter display information recognition, switch position recognition and working states recognition of Transformer-fan-set of substation. The results show that video image recognition applied in substation equipments monitoring has broad prospects.

It is very useful and necessary to apply monitoring technology in electrical power system especially the transmission lines. The monitoring method of transmission line based on video technique, which is introduced in this paper, can calculate the thickness of the ice covering on the transmission line, recognize the galloping line, and give an alarm if necessary. The method principle and the technical features are described, and the calculation of ice and recognition progress of galloping line are introduced in detail. The result shows well.

Myeloid cells are a feature of most tissues. Here we show that during development, retinal myeloid cells (RMCs) produce Wnt ligands to regulate blood vessel branching. In the mouse retina, where angiogenesis occurs postnatally1, somatic deletion in RMCs of the Wnt ligand transporter Wntless2,3 results in increased angiogenesis in the deeper layers. We also show that mutation of Wnt5a and Wnt11 results in increased angiogenesis and that these ligands elicit RMC responses via a non-canonical Wnt pathway. Using cultured myeloid-like cells and RMC somatic deletion of Flt1, we show that an effector of Wnt-dependent suppression of angiogenesis by RMCs is Flt1, a naturally occurring inhibitor of vascular endothelial growth factor (VEGF)4-6. These findings indicate that resident myeloid cells can use a non-canonical, Wnt-Flt1 pathway to suppress angiogenic branching.

A two-dimension OTSU based on Simulated Annealing and Particle Swarm Optimization Algorithm is proposed for image segment and a novel contrast enhancement algorithm is presented based on it, and total variation denoising model is applied to transmission lines image denoising, aiming to the problems that the transmission lines image obtained in bad weather conditions by video monitoring system are low-contrast and often have noise. Experimental results show that the proposed preprocessing methods can solve these problems well, and the Simulated annealing particle swarm Optimization Algorithm has a better convergence and computing speed in the search of global solution. After preprocessing, image quality and segmentation effect are greatly improved, which can better meet the requirements of monitoring system for the identification of the image.