The reduction of power grid losses is of great significance to the economic operation of the power system. This paper proposes a series of limit line loss analysis indicators. The contents include limit line loss, section limit line loss rate and section limit loss reduction rate, reactive power compensation limit line loss rate and reactive power compensation limit loss reduction rate, optimized transformer limit line loss rate and optimized transformer limit loss reduction rate, three-phase Balance limit line loss rate and three-phase balance limit loss reduction rate, optimized operation limit line loss rate and optimized operation limit loss reduction rate, and comprehensive limit line loss rate and comprehensive limit loss reduction rate indicators. It is found that the decision-making method proposed in this paper can optimize each planning scheme, and has good operability and economy.
Graphene nanoribbon heterostructures and heterojunctions have attracted interest as next-generation molecular diodes with atomic precision. Their mass production via solution methods and prototypical device integration remains to be explored. Here, the bottom-up solution synthesis and characterization of liquid-phase-processable graphene nanoribbon heterostructures (GNRHs) are demonstrated. Joint photoresponsivity measurements and simulations provide evidence of the structurally defined heterostructure motif acting as a type-I heterojunction. Real-time, time-dependent density functional tight-binding simulations further reveal that the photocurrent polarity can be tuned at different excitation wavelengths. Our results introduce liquid-phase-processable, self-assembled heterojunctions for the development of nanoscale diode circuitry and adaptive hardware.
Coxsackievirus A16 (CVA16) is one of the major pathogens responsible for hand, foot and mouth disease, which affects more than two million children in the Asian-Pacific region annually. Previous studies have shown that scavenger receptor B2 is a functional receptor for CVA16 that facilitates the uncoating process. However, it remains unclear whether other receptors are required for efficient CVA16 infection. In this study, by using a variety of assays we demonstrated that CVA16 utilizes surface heparan sulfate glycosaminoglycans as its attachment receptor. We further showed that five surface-exposed positively charged residues located in a cluster at the five-fold vertex of the virion are critical to heparan sulfate binding and cellular attachment of CVA16. Among the five residues, the arginine at position 166 (R166) of VP1 capsid protein appeared to be the most important for the interaction between CVA16 and heparan sulfate. Alanine substitution at this site (R166A) almost completely abolished heparan sulfate binding and cellular attachment of the virus. Our work achieves insight into the early events of CVA16 infection, thereby providing information that may facilitate the rational design of antiviral drugs and vaccines against CVA16 infection.
Abstract Coxsackievirus A16 (CVA16) causes hand, foot and mouth disease in infants and young children. However, no vaccine or anti-viral agent is currently available for CVA16. Here, the functions and working mechanisms of two CVA16-specific neutralizing monoclonal antibodies (MAbs), 9B5 and 8C4, are comprehensively investigated. Both 9B5 and 8C4 display potent neutralization in vitro and prophylactic and therapeutic efficacy in a mouse model of CVA16 infection. Mechanistically, 9B5 exerts neutralization primarily through inhibiting CVA16 attachment to cell surface via blockade of CVA16 binding to its attachment receptor, heparan sulfate, whereas 8C4 functions mainly at the post-attachment stage of CVA16 entry by interfering with the interaction between CVA16 and its uncoating receptor SCARB2. Cryo-EM studies show that 9B5 and 8C4 target distinct epitopes located at the 5-fold and 3-fold protrusions of CVA16 capsids, respectively, and exhibit differential binding preference to three forms of naturally occurring CVA16 particles. Moreover, 9B5 and 8C4 are compatible in formulating an antibody cocktail which displays the ability to prevent virus escape seen with individual MAbs. Together, our work elucidates the functional and structural basis of CVA16 antibody-mediated neutralization and protection, providing important information for design and development of effective CVA16 vaccines and antibody therapies.
To develop an effective vaccine against multiple genotypes of enterovirus 71 (EV71), we generated chimeric virus-like particles (VLPs) repetitively displaying the common neutralizing epitopes of EV71 and evaluated their immunogenicities in mice.The two conserved epitopes, encompassing amino acids 163-177 and 208-222 of VP1 of EV71, were fused to hepatitis B core antigen (HBcAg) and expressed in E.coli.The resulting fusion proteins were found to assemble into chimeric VLPs.Both unmodified HBcAg and chimeric VLPs induced HBcAg-specific antibody responses in mice, however, only chimeric VLP-immunized sera possessed EV71 epitope-specific IgG antibodies and efficiently neutralized different EV71 strains.Collectively, our results indicate that the chimeric VLP is capable of eliciting broadly neutralizing antibody responses and is therefore a promising EV71 vaccine candidate.
Organic solar cells (OSCs) have become one of substitutes to inorganic solar cells, especially to silicon-based solar cells. Bulk-heterojunction (BHJ) OSCs, most representative OSC, which normally consist of a blend film that comprises a polymer donor well-matched with non-fullerene acceptor. Through structure design, optimal combination, relatively high power conversion efficiencies (PCEs) surpass 10% were successfully implemented. Here we showed the current breakthroughs in OSCs, together with comparison between inorganic and organic materials. Then several representative small molecule acceptors based on non-fullerene material, perylene diimide (PDI), together with their current advanced application in non-fullerene OSCs are discussed. In addition to novel non-fullerene acceptors, we provided research on ratio optimization of donors and acceptors, which is beneficial for achieving high-performance BHJ OSCs. It is crucial and considerable to fabricate highly efficient OSCs under the condition of suitable donors and acceptors which may qualify for competitive photovoltaic properties, such as charge-carrier mobility and complementary absorption spectrum. Therefore, it can pave the way for realizing superior OSCs.
ABSTRACT Antibodies play a critical role in immunity against enterovirus 71 (EV71). However, how EV71-specific antibodies neutralize infections remains poorly understood. Here we report the working mechanism for a group of three monoclonal antibodies (MAbs) that potently neutralize EV71. We found that these three MAbs (termed D5, H7, and C4, respectively) recognize the same conserved neutralizing epitope within the VP1 GH loop of EV71. Single MAbs in this group, exemplified by D5, could inhibit EV71 infection in cell cultures at both the pre- and postattachment stages in a cell type-independent manner. Specifically, MAb treatment resulted in the blockade of multiple steps of EV71 entry, including virus attachment, internalization, and subsequent uncoating and RNA release. Furthermore, we show that the D5 and C4 antibodies can interfere with EV71 binding to its key receptors, including heparan sulfate, SCARB2, and PSGL-1, thus providing a possible explanation for the observed multi-inhibitory function of the MAbs. Collectively, our study unravels the mechanism of neutralization by a unique group of anti-EV71 MAbs targeting the conserved VP1 GH loop. The findings should enhance our understanding of MAb-mediated immunity against enterovirus infections and accelerate the development of MAb-based anti-EV71 therapeutic drugs. IMPORTANCE Enterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease (HFMD), which has caused significant morbidities and mortalities in young children. Neither a vaccine nor an antiviral drug is available. Neutralizing antibodies are major protective components in EV71 immunity. Here, we unraveled an unusual mechanism of EV71 neutralization by a group of three neutralizing monoclonal antibodies (MAbs). All of these MAbs bound the same conserved epitope located at the VP1 GH loop of EV71. Interestingly, mechanistic studies showed that single antibodies in this MAb group could block EV71 attachment and internalization during the viral entry process and interfere with EV71 binding to heparan sulfate, SCARB2, and PSGL-1 molecules, which are key receptors involved in different steps of EV71 entry. Our findings greatly enhance the understanding of the interplays among EV71, neutralizing antibodies, and host receptors, which in turn should facilitate the development of an MAb-based anti-EV71 therapy.
The external severe and complex economic situation has a great impact on the efficiency of the company’s investment implementation. The in-depth implementation of the lean investment management concept also puts forward new requirements for improving the extensive distribution network investment management mode. In addition, in recent years, the proportion of investment in distribution network projects of 10kV and below has increased, and its management mode is difficult to keep up with the new investment management requirements. Therefore, this project takes the infrastructure projects of 10kV and below as the research object, constructs the investment plan curve by studying the business rules of construction, accounting and materials, and deepens its application in the early warning of investment plan implementation based on the investment plan line, and provides an effective support tool for the investment lean management and control of distribution network.
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