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Adeno-associated virus (AAV) receptor (AAVR) is an essential receptor for the entry of multiple AAV serotypes with divergent rules; however, the mechanism remains unclear. Here, we determine the structures of the AAV1-AAVR and AAV5-AAVR complexes, revealing the molecular details by which PKD1 recognizes AAV5 and PKD2 is solely engaged with AAV1. PKD2 lies on the plateau region of the AAV1 capsid. However, the AAV5-AAVR interface is strikingly different, in which PKD1 is bound at the opposite side of the spike of the AAV5 capsid than the PKD2-interacting region of AAV1. Residues in strands F/G and the CD loop of PKD1 interact directly with AAV5, whereas residues in strands B/C/E and the BC loop of PKD2 make contact with AAV1. These findings further the understanding of the distinct mechanisms by which AAVR recognizes various AAV serotypes and provide an example of a single receptor engaging multiple viral serotypes with divergent rules., Multiple adeno-associated viruses (AAV) use the same receptor (AAVR), but the binding mode is not clear. Here, the authors determine the structures of the AAV1-AAVR and AAV5-AAVR complexes, identify residues necessary for virus entry and compare the receptor interfaces of different AAV capsids.

This paper presents the detail analysis of the radial force and bending moment responsible for vibration in the stator permanent magnet synchronous motors (SPMSM). Firstly, the air gap flux density distribution and radial force density distribution are derived in detail. In addition, the relationships between these two vibrations and pole width, pole number and slot number are analyzed. The multi-probe mode-included test method of vibration acceleration is proposed and the experimental results on a6-pole/36-slot SPMSM match well with the simulation results. 0 Introduction With the advancement of the electrical vehicles such as hybrid-electric and electric vehicles, improving the noise and vibration characteristics of rotating electric machines is becoming important consideration issues for the development of vehicles[1–4]. Electrical vehicles make use of permanent magnet synchronous traction motors for their high torque density and efficiency compared with other types of motors[5–9]. The stator permanent magnet synchronous motors (SPMSM) have good advantages and are widely applied in the industry. Few papers reported to focus on the vibration characteristics of this type of motor[10ߝ12]. So, this paper investigates the vibration mode and frequencies in the stator permanent magnet synchronous motor, which is shown in Fig.1. 1The magnetic field and exciting force 1.1 analysis of Magnetic field When ignoring magnetic saturation, the flux density distribution in the air gap under no load can be expressed as$\mathrm{b}(\theta, \mathrm{t}) = \pm ({B_{\delta}} {\Lambda _{0}}+ \sum {B_{\delta}} {\Lambda _{k}} {\mathrm {coskZ}} (\theta- {\omega _{{\mathrm {r}}}}\mathrm{t})) \theta \epsilon \left[- \alpha \pi /(2\mathrm{p}) + \mathrm{j}2 \pi /(2\mathrm{p})\alpha \pi /(2\mathrm{p}) + \mathrm{j}2 \pi /(2\mathrm{p}) \right]$(1) Where Z is the number of rotor slots, ${\Lambda_{0}}$ and ${\Lambda_{k}}$ are the amplitude of average and k-th harmonic magnetic permeability. $\alpha$ is the pole arc coefficient. When $\mathrm{j=2}\mathrm{m}$,$\mathrm{m=0}$,1,2,3…, the sign in the equation takes a positive value; When $\mathrm{j=2} \mathrm{m+1}$, the sign is negative. 1.2 Force analysis The force on ferromagnetic substance in the electromagnetic field can be described by Maxwell stress tensor method. Radial force wave generated by magnetic field is${\mathrm{p}_{n}}=1 / (2 {\mu _{0}}) \left\{ {(B_{\delta}} {\Lambda_{0}})^{2}+ \sum \left[{B_{\delta}} {\Lambda _{k}} {\mathrm {coskZ}} (\theta- {\omega _{r}}\mathrm{t})\right] ^{2}+ 2 {B_{\delta}} ^{2} {\Lambda_{0}}{\Lambda _{k}} {\mathrm {coskZ}} (\theta- {\omega _{r}}\mathrm{t})\right\}$(2) The third term indicates radial force which changes with time generated by interaction of the not time-varying magnetic field and the periodic magnetic field, which causes a considerable vibration. The vibration frequencies are the integral multiples of the product of the slot number and the rotation frequency. 2 Two vibration sources In the motor, the radial force ${P_{n}}$ on one pole can be equivalent to one equivalent pulsating force ${P_{np}}$ varied with time on the center line of the pole and equivalent bending moment ${m_{np}}$ varied with time on the pole. The general expression of pulsating force is ${P_{np}}({\mathrm{t}}) =2 {\mathrm{l}_{p}} {\mathrm{RB}_{\delta}} ^{2}{\Lambda_{0}}{\Lambda _{1}} \sin ({\alpha_{1}}\pi /(2\mathrm{p}))\cos$(jZ $2 \pi /(2\mathrm{p})- \mathrm{Z}{\omega _{r}}\mathrm{t})/ (\mathrm{Z}{\mu _{0}})(3)$ Where $R$ is the radius of the inner surface of the pole, ${\alpha_{1}}$ is pole arc width expressed by rotor number. Because the uneven distribution of the force density, the corresponding bending moment is ${m_{np}}(\mathrm{t}) = {\mathrm{l}_{p}} {{\mathrm{R}^{2B}}_{\delta} ^{2}}{\Lambda_{0}}{\Lambda_{1}} \cos ({\alpha_{1}}\pi) \sin (\alpha \pi /(2\mathrm{p}))\sin$(jZ $2 \pi /(2\mathrm{p})- \mathrm{Z}{\omega _{r}}\mathrm{t})/ (\mathrm{Z}{\mu _{0}})(4)$ From the equation(3) and (4), we can know that: If $2 \pi \mathrm{Z} /(2\mathrm{p}) =2 \mathrm{n}\pi$, n is integral, the radial forces and the bending moment on the two adjacent poles are in the same phase. When ${\alpha_{1}}$ is $n$, radial force reaches minimum, bending moment reaches maximum, and the mode number equal to the pole number. When ${\alpha_{1}}$ is $n+1 /2$, radial force reaches maximum, bending moment reaches minimum, and the vibration mode equal to 0. If $2 \pi \mathrm{Z} /(2\mathrm{p}) =(2 \mathrm{n+1}) \pi$, the phases of the forces on the two adjacent poles are opposite, and so do the bending moment. When ${\alpha_{1}}$ is $n$, radial force reaches minimum, bending moment reaches maximum, and the mode number equal to the pole pairs. When ${\alpha_{1}}$ is $n+1 /2$, radial force reaches maximum, bending moment reaches minimum. The vibration mode equal to pole pairs. 3 simulation analysis In the simulation, a harmonic response analysis has been performed by using the mode-superposition method. the motor is constrained by elastic support through the end face. A damping ratios of 4.4% extracted from the modal test is used. The harmonic forces are projected on the structure mesh of the stator in order to calculate the deformation, and the vibration mode. 4 Experiment test In order to verify the validity of analytical model studied in this paper, the Operational Deflection Shapes experiment is performed. The designed motor with 6-pole, 36-slot, ${\alpha_{1}} -5$ is hanged on the bracket by elastic rope, and seven accelerometer sensors are evenly attached on the stator in the circumferential direction. The motor run at 1500rpm. Fig.2(a) compares the measured acceleration with those FEM at five frequencies associated with slot frequency. It clearly reveals that the acceleration components at the harmonic frequencies of 36fr, 72fr, 108fr, 144fr, etc.. Vibration shape at slot frequency is measured seen in Fig.2(b). It can be seen clearly that the vibration mode at slot frequency is six order, consistent with the analytical results. 5 Conclusions In this paper, a detailed analysis of vibration in stator permanent magnet synchronous motor (SPMSM) is presented. Some conclusions can be summarized from the paper: The frequencies of the exciting radial force and vibration of the SPMSMs mainly are integral multiples of the product of the slot number and the rotation frequency, which is different from the frequencies related about the pole number in the rotor permanent magnet motors. The vibration mode is decided by the radial force, which causes the pulsating mode, and the bending moment, which causes the bending mode.

AlGaN/GaN high electron mobility transistor (HEMT) devices were irradiated with swift heavy ions at different fluences. From structural and electrical studies, it was found that SHI irradiation leads to a significant deterioration of structural and electrical properties of the devices. Positive threshold voltage Vth was found to increase by about 85% as a result of irradiation with 1540-MeV 209Bi ions at fluence of 1.7 × 1011 ions/cm2, while this threshold voltage value was increased by 55% after irradiation with 2300-MeV 129Xe at a fluence of 4 × 1011 ions/cm2. The maximum saturation drain current Ids was decreased by about two orders of magnitude in the device after irradiation with 209Bi ions. Quasi-continuous tracks were observed visually in the devices after irradiation with 209Bi ions. The observed defects and disorders induced in the devices by SHI irradiation were found responsible for the decrease in carrier mobility and sheet carrier density, and finally, these defects resulted in the degradation of electrical characteristics of HEMTs.

Imaging live virus to monitor the viral entry process is essential to understand virus-host interactions during pathogen infection. However, methods for efficient labeling of live viruses, in particular labeling non-enveloped viruses and tracing virus entry processes, remain limited. Recently, labeling by using organometallic palladium reagents has provided a highly efficient and selective way to bioconjugate cysteines of virus proteins. Here, site-specific bioorthogonal labeling mediated by an organometallic palladium reagent on the surface of live enterovirus-71 (EV71) was used to visualize its entry into live cells. In contrast to currently used immunofluorescence and membrane-anchored dyes, this site-specific and quantitative labeling of live EV71 allows temporal imaging of its entry into host cell membranes on the timescale of seconds with little negative impact on its virulence. This method revealed details of EV71 virus entry and has broad applicability for monitoring virus entry that is difficult to assess by using conventional protein-labeling approaches.

The single event upset (SEU) response of 65 nm commercial double data rate static random access memory (SRAM) and quad data rate SRAM was investigated by using proton beams with energies in the range of 0.15 MeV to 8.0 MeV. Experimental results show that a significant number of SEU occurrences can be triggered when the energy of incident proton is below 1 MeV. For the low energy protons, the SEU cross section measured in these SRAMs was found to increase with increasing proton energy, attaining a peak value, and then decreases as the proton energy was further increased. While in case of quad data rate SRAMs, it seems that they are more sensitive to SEU occurrences as compared with double data rate SRAMs. The bias voltage and data pattern dependence on SEU cross section induced by the low energy protons were also investigated in this work. In addition, the over-layer thickness of the SRAMs and the impact of degrader use in proton induced SEU test were also analyzed in detail. Monte Carlo simulations results indicate that the use of degrader in case of low energy proton induced SEU test results in a significant reduction of the SEU cross section.

Enterovirus 71 (EV71) is one of the major etiological agents of human hand-foot-and-mouth disease (HFMD) worldwide. EV71 infection in young children and people with immunodeficiency causes severe symptoms with a high fatality rates. However, there is still no approved drugs to treat such infections. Based on our previous report of a peptide-aldehyde anti-EV71 protease, we present here a highly specific α-hydroxy-nitrile derivative NK-1.9k, which inhibited the proliferation of multiple EV71 strains and coxsackievirus A16 (CVA16) in various cells with EC50 of 37.0 nM with low cytotoxicity (CC50 > 200 μM). The hydroxy-nitrile covalent warhead conferred NK-1.9k high potency and selectivity to interact with the cysteine residue of the active site of the viral protease. We also documented the resistance to NK-1.9k with a N69S mutation in EV71 3Cpro. The combination of NK-1.9k and EV71 polymerase or entry inhibitors produced strong synergistic antiviral effects. Collectively, our findings suggest our compounds can potentially be developed as drugs for the treatment of HFMD.

We report a 3.5-angstrom-resolution cryo–electron microscopy structure of a respiratory supercomplex isolated from Mycobacterium smegmatis. It comprises a complex III dimer flanked on either side by individual complex IV subunits. Complex III and IV associate so that electrons can be transferred from quinol in complex III to the oxygen reduction center in complex IV by way of a bridging cytochrome subunit. We observed a superoxide dismutase-like subunit at the periplasmic face, which may be responsible for detoxification of superoxide formed by complex III. The structure reveals features of an established drug target and provides a foundation for the development of treatments for human tuberculosis.

Seneca Valley virus (SVV) is an oncolytic picornavirus with selective tropism for neuroendocrine cancers. SVV mediates cell entry by attachment to the receptor anthrax toxin receptor 1 (ANTXR1). Here we determine atomic structures of mature SVV particles alone and in complex with ANTXR1 in both neutral and acidic conditions, as well as empty “spent” particles in complex with ANTXR1 in acidic conditions by cryoelectron microscopy. SVV engages ANTXR1 mainly by the VP2 DF and VP1 CD loops, leading to structural changes in the VP1 GH loop and VP3 GH loop, which attenuate interprotomer interactions and destabilize the capsid assembly. Despite lying on the edge of the attachment site, VP2 D146 interacts with the metal ion in ANTXR1 and is required for cell entry. Though the individual substitution of most interacting residues abolishes receptor binding and virus propagation, a serine-to-alanine mutation at VP2 S177 significantly increases SVV proliferation. Acidification of the SVV–ANTXR1 complex results in a major reconfiguration of the pentameric capsid assemblies, which rotate ∼20° around the icosahedral fivefold axes to form a previously uncharacterized spent particle resembling a potential uncoating intermediate with remarkable perforations at both two- and threefold axes. These structures provide high-resolution snapshots of SVV entry, highlighting opportunities for anticancer therapeutic optimization.

Adeno-associated virus (AAV) is a leading vector for virus-based gene therapy. The receptor for AAV (AAVR; also named KIAA0319L) was recently identified, and the precise characterization of AAV-AAVR recognition is in immediate demand. Taking advantage of a particle-filtering algorithm, we report here the cryo-electron microscopy structure of the AAV2-AAVR complex at 2.8 Å resolution. This structure reveals that of the five Ig-like polycystic kidney disease (PKD) domains in AAVR, PKD2 binds directly to the spike region of the AAV2 capsid adjacent to the icosahedral three-fold axis. Residues in strands B and E, and the BC loop of AAVR PKD2 interact directly with the AAV2 capsid. The interacting residues in the AAV2 capsid are mainly in AAV-featured variable regions. Mutagenesis of the amino acids at the AAV2-AAVR interface reduces binding activity and viral infectivity. Our findings provide insights into the biology of AAV entry with high-resolution details, providing opportunities for the development of new AAV vectors for gene therapy.

Classical hormone receptors reversibly and non-covalently bind active hormone molecules, which are generated by biosynthetic enzymes, to trigger signal transduction. The α/β hydrolase DWARF14 (D14), which hydrolyses the plant branching hormone strigolactone and interacts with the F-box protein D3/MAX2, is probably involved in strigolactone detection. However, the active form of strigolactone has yet to be identified and it is unclear which protein directly binds the active form of strigolactone, and in which manner, to act as the genuine strigolactone receptor. Here we report the crystal structure of the strigolactone-induced AtD14-D3-ASK1 complex, reveal that Arabidopsis thaliana (At)D14 undergoes an open-to-closed state transition to trigger strigolactone signalling, and demonstrate that strigolactone is hydrolysed into a covalently linked intermediate molecule (CLIM) to initiate a conformational change of AtD14 to facilitate interaction with D3. Notably, analyses of a highly branched Arabidopsis mutant d14-5 show that the AtD14(G158E) mutant maintains enzyme activity to hydrolyse strigolactone, but fails to efficiently interact with D3/MAX2 and loses the ability to act as a receptor that triggers strigolactone signalling in planta. These findings uncover a mechanism underlying the allosteric activation of AtD14 by strigolactone hydrolysis into CLIM, and define AtD14 as a non-canonical hormone receptor with dual functions to generate and sense the active form of strigolactone.

Hepatitis disease caused by hepatitis C virus (HCV) is a severe threat to global public health, affecting approximately 3% of the world's population. Sofosbuvir (PSI-7977), a uridine nucleotide analog inhibitor targeting the HCV NS5B polymerase, was approved by FDA at the end of 2013 and represents a key step towards a new era in the management of HCV infection. Previous study identified NITD008, an adenosine nucleoside analog, as the specific inhibitor against dengue virus and showed good antiviral effect on other flaviviruses or enteroviruses. In this report, we systematically analyzed the anti-HCV profile of NITD008, which was discovered to effectively suppress the replication of different strains of HCV in human hepatoma cells with a low nanomolar activity. On genotype 2a virus, or 2a, 1a, and 1b replicon cells, EC50 values were 8.7 nM, 93.3 nM, 60.0 nM and 67.2 nM, and selective index values were >2298.9, >214.4, >333.3, >298.5 respectively. We demonstrated that resistance to NITD008 was conferred by mutation in NS5B (S282T) in the HCV infectious virus genotype 2a (JFH-1). Then, we compared the resistant profiles of NITD008 and PSI-7977, and found that the folds change of EC50 of NITD008 to full replicon cells containing mutation S282T was much bigger than PSI-7977(folds 76.50 vs. 4.52). Analysis of NITD008 cross-resistance against previously reported NS5B drug-selected mutations showed that the resistance pattern of NITD008 was not completely similar to PSI-7977, and meanwhile, S282T resistant mutation to NITD008 emerge more easily in cell culture than PSI-7977. Interestingly, NITD008 displayed significant synergistic effects with the NS5B polymerase inhibitor PSI-7977, however, only additive effects with alpha interferon (IFNα-2b), ribavirin, and an NS3 protease inhibitor. These results verify that NITD008 is an effective analog inhibitor against hepatitis C virus and a good research tool as a supplement to other types of nucleoside analogs.

Hantaviruses, which belong to the genus Hantavirus in the family Bunyaviridae , infect mammals, including humans, causing either hemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome (HCPS) in humans with high mortality. Hantavirus encodes a nucleocapsid protein (NP) to encapsidate the genome and form a ribonucleoprotein complex (RNP) together with viral polymerase. Here, we report the crystal structure of the core domains of NP (NP core ) encoded by Sin Nombre virus (SNV) and Andes virus (ANDV), which are two representative members that cause HCPS in the New World. The constructs of SNV and ANDV NP core exclude the N- and C-terminal portions of full polypeptide to obtain stable proteins for crystallographic study. The structure features an N lobe and a C lobe to clamp RNA-binding crevice and exhibits two protruding extensions in both lobes. The positively charged residues located in the RNA-binding crevice play a key role in RNA binding and virus replication. We further demonstrated that the C-terminal helix and the linker region connecting the N-terminal coiled-coil domain and NP core are essential for hantavirus NP oligomerization through contacts made with two adjacent protomers. Moreover, electron microscopy (EM) visualization of native RNPs extracted from the virions revealed that a monomer-sized NP-RNA complex is the building block of viral RNP. This work provides insight into the formation of hantavirus RNP and provides an understanding of the evolutionary connections that exist among bunyaviruses. IMPORTANCE Hantaviruses are distributed across a wide and increasing range of host reservoirs throughout the world. In particular, hantaviruses can be transmitted via aerosols of rodent excreta to humans or from human to human and cause HFRS and HCPS, with mortalities of 15% and 50%, respectively. Hantavirus is therefore listed as a category C pathogen. Hantavirus encodes an NP that plays essential roles both in RNP formation and in multiple biological functions. NP is also the exclusive target for the serological diagnoses. This work reveals the structure of hantavirus NP, furthering the knowledge of hantavirus RNP formation, revealing the relationship between hantavirus NP and serological specificity and raising the potential for the development of new diagnosis and therapeutics targeting hantavirus infection.

Cyanohydrin derivatives as enterovirus 71 (EV71) 3C protease (3C(pro)) inhibitors have been synthesized and assayed for their biochemical and antiviral activities. Compared with the reported inhibitors, cyanohydrins (1S,2S,2'S,5S)-16 and (1R,2S,2'S,5S)-16 exhibited significantly improved activity and attractive selectivity profiles against other proteases, which were a result of the specific interactions between the cyanohydrin moiety and the catalytic site of 3C(pro). Cyanohydrin as an anchoring group with high selectivity and excellent inhibitory activity represents a useful choice for cysteine protease inhibitors.

A mathematical model is proposed to analysis low-velocity gas–powder flow in a packed bed. The model, as an extension of the two-fluid model, consider the interactions between gas, powder and packed particles, as well as the static and dynamic holdups of powder. What's more, the sticking rate and departing rate of powder, which are derived from the filtration mechanisms, are also included in the powder phase's continuity equation. The validation of the present model is performed by comparing the simulated results with the previous experimental. On this basis, the flow characteristics of low-velocity gas–powder flow in a packed bed with lateral inlet are analysed, and the effect of gas velocity and powder mass flux on static holdup of powder have also been investigated.

An infiltration crystallisation concentrating agent was prepared using recycled concrete micropowder from construction waste as main material with instant sodium silicate, aluminium stearate and other active ingredients. The optimum mixture ratio and self-healing effect of the concentrating agent were studied. Compression experiments conducted in the laboratory were terminated when penetrating cracks appeared on the specimen. The specimen was then subjected to standard curing for 28 days after which, second pressure of the specimen was tested. Pore structures of the specimen pre-and post-curing were also tested. The self-healing property of the concentrating agent was characterised using the above comparative analysis. The results indicated that the concentrating agent possessed good self-healing capabilities. The optimum mixture ratio of the self-regenerating infiltration crystallisation concentrating agent is cement, 55%; quartz sand, 25%; instant 5% sodium silicate, 5%; aluminium stearate, 1%; ...

The function of abscisic acid (ABA) is mediated by its receptors termed RCARs/PYR1/PYLs. Modulation of ABA signaling is vital for plant growth and development. The RCAR-PP2C-SnRK2 regulatory modules have been defined as the core components in ABA signaling. However, it is still not clear whether and how the ABA receptors could be modified at the initial post-translational stage to fine-tune ABA transduction pathway. Here we identify and characterize the putative receptor-like cytoplasmic kinase (RLCK) in Arabidopsis named CARK1, which interacts with RCAR3 (PYL8) and RCAR11 (PYR1) in the manner of phosphorylation. Structural studies of CARK1 revealed the critical active site, N204, which accounts for the kinase activity and the direct interaction with RCAR3/RCAR11. CARK1 phosphorylates RCAR3/RCAR11 at one conserved threonine site, T77/T78. Our genetic analyses further demonstrated that CARK1 positively regulates ABA-mediated physiological responses and overexpression of CARK1 in Arabidopsis distinctly promotes the drought resistance. Moreover, the phosphor-mimic form of RCAR11 in the cark1 mutant is able to functionally complement the ABA sensitivity. CARK1 positively regulates ABA-responsive gene expression and enhances RCAR3/RCAR11’s inhibition to Clade A PP2C. Taken together, our studies strongly support the functional significance of CARK1 in positively regulating ABA signaling via phosphorylation on RCAR3/RCAR11 in Arabidopsis.

Genetics experiments have identified six mutations located in the subdomain IA (A17V, R23H, G32D, G32S, R34K, V372I) of Ssa1 that influence propagation of the yeast [PSI+] prion. However, the underlining molecular mechanisms of these mutations are still unclear. The six mutation sites are present in the IA subdomain of the nucleotide-binding domain (NBD). The ATPase subdomain IA is a critical mediator of inter-domain allostery in Hsp70 molecular chaperones, so the mutation and changes in this subdomain may influence the function of the substrate-binding domain. In addition, ADP release is a rate-limiting step of the ATPase cycle and dysregulation of the ATPase cycle influences the propagation of the yeast [PSI+] prion. In this work, steered molecular dynamics (SMD) simulations were performed to explore the interaction between ADP and NBD. Results suggest that during the SMD simulations, hydrophobic interactions are predominant and variations in the binding state of ADP within the mutants is a potential reason for in vivo effects on yeast [PSI+] prion propagation. Additionally, we identify the primary residues in the ATPase domain that directly constitute the main hydrophobic interaction network and directly influence the ADP interaction state with the NBD of Ssa1. Furthermore, this in silico analysis reaffirms the importance of previously experimentally-determined residues in the Hsp70 ATPase domain involved in ADP binding and also identifies new residues potentially involved in this process.

The Tomato spotted wilt virus (TSWV) belongs to the Tospovirus genus of the Bunyaviridae family and represents the sole plant-infecting group within bunyavirus. TSWV encodes a nucleocapsid protein (N) which encapsidates the RNA genome to form a ribonucleoprotein complex (RNP). In addition, the N has multiple roles during the infection of plant cells. Here, we report the crystal structure of the full-length TSWV N. The N features a body domain consisting of an N-lobe and a C-lobe. These lobes clamp a positively charged groove which may constitute the RNA binding site. Furthermore, the body domains are flanked by N- and C-terminal arms which mediate homotypic interactions to the neighboring subunits, resulting in a ring-shaped N trimer. Interestingly, the C terminus of one protomer forms an additional interaction with the protomer of an adjacent trimer in the crystal, which may constitute a higher-order oligomerization contact. In this way, this study provides insights into the structure and trimeric assembly of TSWV N, which help to explain previous functional findings, but also suggests distinct N interactions within a higher-order RNP. IMPORTANCE TSWV is one of the most devastating plant pathogens that cause severe diseases in numerous agronomic and ornamental crops worldwide. TSWV is also the prototypic member of the Tospovirus genus, which is the sole group of plant-infecting viruses in the bunyavirus family. This study determined the structure of full-length TSWV N in an oligomeric state. The structural observations explain previously identified biological properties of TSWV N. Most importantly, the additional homotypic interaction between the C terminus of one protomer with another protomer indicates that there is a distinct mechanism of RNP formation in the bunyavirus family, thereby enhancing the current knowledge of negative-sense single-stranded RNA virus-encoded N. TSWV N is the last remaining representative N with an unknown structure in the bunyavirus family. Combined with previous studies, the structure of TSWV N helps to build a complete picture of the bunyavirus-encoded N family and reveals a close evolutionary relationship between orthobunyavirus, phlebovirus, hantavirus, and tospovirus.

The Hsp70 and Hsp40 chaperone machine plays critical roles in protein folding, membrane translocation, and protein degradation by binding and releasing protein substrates in a process that utilizes ATP. The activities of the Hsp70 family of chaperones are recruited and stimulated by the J domains of Hsp40 chaperones. However, structural information on the Hsp40-Hsp70 complex is lacking, and the molecular details of this interaction are yet to be elucidated. Here we used steered molecular dynamics (SMD) simulations to investigate the molecular interactions that occur during the dissociation of the auxilin J domain from the Hsc70 nucleotide-binding domain (NBD). The changes in energy observed during the SMD simulation suggest that electrostatic interactions are the dominant type of interaction. Additionally, we found that Hsp70 mainly interacts with auxilin through the surface residues Tyr866, Arg867, and Lys868 of helix II, His874, Asp876, Lys877, Thr879, and Gln881 of the HPD loop, and Phe891, Asn895, Asp896, and Asn903 of helix III. The conservative residues Tyr866, Arg867, Lys868, His874, Asp876, Lys877, and Phe891 were also found in a previous study to be indispensable to the catalytic activity of the DnaJ J domain and the binding of it with the NBD of DnaK. The in silico identification of the importance of auxilin residues Asn895, Asp896, and Asn903 agrees with previous mutagenesis and NMR data suggesting that helix III of the J domain of the T antigen interacts with Hsp70. Furthermore, our data indicate that Thr879 and Gln881 from the HPD loop are also important as they mediate the interaction between the bovine auxilin J domain and Hsc70.

Nonstructural protein 14 (nsp14) of coronaviruses (CoV) is important for viral replication and transcription. The N-terminal exoribonuclease (ExoN) domain plays a proofreading role for prevention of lethal mutagenesis, and the C-terminal domain functions as a (guanine-N7) methyl transferase (N7-MTase) for mRNA capping. The molecular basis of both these functions is unknown. Here, we describe crystal structures of severe acute respiratory syndrome (SARS)-CoV nsp14 in complex with its activator nonstructural protein10 (nsp10) and functional ligands. One molecule of nsp10 interacts with ExoN of nsp14 to stabilize it and stimulate its activity. Although the catalytic core of nsp14 ExoN is reminiscent of proofreading exonucleases, the presence of two zinc fingers sets it apart from homologs. Mutagenesis studies indicate that both these zinc fingers are essential for the function of nsp14. We show that a DEEDh (the five catalytic amino acids) motif drives nucleotide excision. The N7-MTase domain exhibits a noncanonical MTase fold with a rare β-sheet insertion and a peripheral zinc finger. The cap-precursor guanosine-P3-adenosine-5',5'-triphosphate and S-adenosyl methionine bind in proximity in a highly constricted pocket between two β-sheets to accomplish methyl transfer. Our studies provide the first glimpses, to our knowledge, into the architecture of the nsp14-nsp10 complex involved in RNA viral proofreading.

Dehydration is one of the key steps in the biosynthesis of mycolic acids and is vital to the growth of Mycobacterium tuberculosis (Mtb). Consequently, stalling dehydration cures tuberculosis (TB). Clinically used anti-TB drugs like thiacetazone (TAC) and isoxyl (ISO) as well as flavonoids inhibit the enzyme activity of the β-hydroxyacyl-ACP dehydratase HadAB complex. How this inhibition is exerted, has remained an enigma for years. Here, we describe the first crystal structures of the MtbHadAB complex bound with flavonoid inhibitor butein, 2’,4,4’-trihydroxychalcone or fisetin. Despite sharing no sequence identity from Blast, HadA and HadB adopt a very similar hotdog fold. HadA forms a tight dimer with HadB in which the proteins are sitting side-by-side, but are oriented anti-parallel. While HadB contributes the catalytically critical His-Asp dyad, HadA binds the fatty acid substrate in a long channel. The atypical double hotdog fold with a single active site formed by MtbHadAB gives rise to a long, narrow cavity that vertically traverses the fatty acid binding channel. At the base of this cavity lies Cys61, which upon mutation to Ser confers drug-resistance in TB patients. We show that inhibitors bind in this cavity and protrude into the substrate binding channel. Thus, inhibitors of MtbHadAB exert their effect by occluding substrate from the active site. The unveiling of this mechanism of inhibition paves the way for accelerating development of next generation of anti-TB drugs. Electronic supplementary material The online version of this article (doi:10.1007/s13238-015-0181-1) contains supplementary material, which is available to authorized users.

Enterovirus (EV) is one of the major causative agents of hand, foot, and mouth disease in the Pacific-Asia region. In particular, EV71 causes severe central nervous system infections, and the fatality rates from EV71 infection are high. Moreover, an outbreak of respiratory illnesses caused by an emerging EV, EV68, recently occurred among over 1,000 young children in the United States and was also associated with neurological infections. Although enterovirus has emerged as a considerable global public health threat, no antiviral drug for clinical use is available. In the present work, we screened our compound library for agents targeting viral protease and identified a peptidyl aldehyde, NK-1.8k, that inhibits the proliferation of different EV71 strains and one EV68 strain and that had a 50% effective concentration of 90 nM. Low cytotoxicity (50% cytotoxic concentration, >200 μM) indicated a high selective index of over 2,000. We further characterized a single amino acid substitution inside protease 3C (3C pro ), N69S, which conferred EV71 resistance to NK-1.8k, possibly by increasing the flexibility of the substrate binding pocket of 3C pro . The combination of NK-1.8k and an EV71 RNA-dependent RNA polymerase inhibitor or entry inhibitor exhibited a strong synergistic anti-EV71 effect. Our findings suggest that NK-1.8k could potentially be developed for anti-EV therapy.

Ferroelectric lead-zirconate-titanate [Pb(Zr0·53Ti0·47)O3] thin films with remnant polarisation and large dielectric constant have been employed in non-volatile field-effect transistor memories as gate dielectrics. Oxide semiconductor-zinc oxide (ZnO) is introduced as the channel layer because of its low crystallization temperature, good integration with different materials and low costs. In this paper, field-effect transistors using ZnO as the channel and lead-zirconate-titanate as the gate dielectric have been fabricated and characterised. Lead-zirconate-titanate and ZnO films were deposited by Sol-Gel and radio frequency (RF)-sputtering methods, respectively. Typical n-channel properties with clear current saturation in drain current v. drain voltage (Ids-Vds) characteristics have been obtained. The transfer characteristics (source-drain current v. gate voltage, Ids-Vgs) exhibited a significantly hysteresis behaviour because of the ferroelectric polarisation properties of the lead-zirconate-tit...

Human epidermal growth factor receptors (HERs or ErbBs) play crucial roles in numerous cellular processes. ErbB2 is a key member of ErbB family, and its overexpression is recognized as a frequent molecular abnormality. In cancer, this overexpression correlates with aggressive disease and poor patient outcomes. Dimer-dependent phosphorylation is a key event for the signal transduction of ErbBs. However, the molecular mechanism of the dimerization of ErbB2 remains elusive. In the present work, we report the homodimer architecture of the ErbB2 extracellular domain (ECD) which is unique compared with other dimer-models of ErbBs. The structure of the ErbB2 ECD homodimer represents a "back to head" interaction, in which a protruding β-hairpin arm in domain II of one ErbB2 protomer is inserted into a C-shaped pocket created by domains I-III of the adjacent ErbB2 protomer. This dimerized architecture and its impact on the phosphorylation of ErbB2 intracellular domain were further verified by a mutagenesis study. We also elucidated the different impacts of two clinically administered therapeutic antibodies, trastuzumab and pertuzumab, on ErbB2 dimerization. This information not only provides an understanding of the molecular mechanism of ErbBs dimerization but also elucidates ErbB2-targeted therapy at the molecular level.

Enterovirus 71 (EV71), one of the major causative agents of Hand-Foot-Mouth Disease (HFMD), causes severe pandemics and hundreds of deaths in the Asia-Pacific region annually and is an enormous public health threat. However, effective therapeutic antiviral drugs against EV71 are rare. Nucleoside analogues have been successfully used in the clinic for the treatment of various viral infections. We evaluated a total of 27 nucleoside analogues and discovered that an adenosine nucleoside analogue NITD008, which has been reported to be an antiviral reagent that specifically inhibits flaviviruses, effectively suppressed the propagation of different strains of EV71 in RD, 293T and Vero cells with a relatively high selectivity index. Triphosphorylated NITD008 (ppp-NITD008) functions as a chain terminator to directly inhibit the RNA-dependent RNA polymerase activity of EV71, and it does not affect the EV71 VPg uridylylation process. A significant synergistic anti-EV71 effect of NITD008 with rupintrivir (AG7088) (a protease inhibitor) was documented, supporting the potential combination therapy of NITD008 with other inhibitors for the treatment of EV71 infections.

Crystal structure of the novel di-nucleotide cyclase from Vibrio cholerae (DncV) responsible for synthesizing a hybrid cyclic GMP-AMP

Genetic screens using Saccharomyces cerevisiae have identified an array of Hsp40 (Ydj1p) J-domain mutants that are impaired in the ability to cure the yeast [URE3] prion through disrupting functional interactions with Hsp70. However, biochemical analysis of some of these Hsp40 J-domain mutants has so far failed to provide major insight into the specific functional changes in Hsp40-Hsp70 interactions. To explore the detailed structural and dynamic properties of the Hsp40 J-domain, 20 ns molecular dynamic simulations of 4 mutants (D9A, D36A, A30T, and F45S) and wild-type J-domain were performed, followed by Hsp70 docking simulations. Results demonstrated that although the Hsp70 interaction mechanism of the mutants may vary, the major structural change was targeted to the critical HPD motif of the J-domain. Our computational analysis fits well with previous yeast genetics studies regarding highlighting the importance of J-domain function in prion propagation. During the molecular dynamics simulations several important residues were identified and predicted to play an essential role in J-domain structure. Among these residues, Y26 and F45 were confirmed, using both in silico and in vivo methods, as being critical for Ydj1p function.

To evaluate the safety of cardiac catheterization intervention therapy and transthoracic small incision surgery in the occlusion bydomestic occluder under echocardiography guiding in patients with atrial septal defect (ASD). Methods: A total of 1 080 patients with ASD in the occlusion by domestic occluder were analyzed retrospectively, and the interventional treatment were performed in 734 cases through cardiac catheterization intervention therapy and 346 cases through transthoracic small incision surgery. The patients undergone cardiac catheterization intervention therapy were guided under the digital substraction angiography (DSA) and were monitored by transthoracic echocardiography (TTE) in the whole interventional process, and the efficacy was evaluated with TTE. The occlusion of transthoracic small incision surgery was guided under the transesophageal echocardiography (TEE), which was used to monitor the position of occluder and evaluate the efficacy immediately. Results: Two kinds of intervention in the occlusion by domestic occluder had achieved satisfactory results in patients with ASD. There was no statistically difference in the longest size of ASD between the 2 intervention methods, while there were statistically differences in the ratio between ASD longest diameter and atrial septal length, and the size of the occlusion, and the disparity between the size of the occluder and ASD longest diameter (D value), respectively (all P0.05). When the size of arithmetic mean of the ASD was30 mm, the success rate of the 2 methods was both 100%. When the size of arithmetic mean of the ASD was ≥30 mm, the success rate was 100% in the transthoracic small incision surgery and 50% in the cardiac catheterization intervention therapy. Conclusion: Domestic occluder is safe. Compared with the imported one, its cost is lower. When the size of the defects is same, the occlusion is smaller in the transthoracic small incision surgery compared with that in the cardiac catheterization intervention therapy. When the size of arithmetic mean of the ASD is ≥30 mm, the success rate of the transthoracic small incision surgery is higher compared with the cardiac catheterization intervention therapy. When the cardiac catheterization intervention therapy fails, the transthoracic small incision surgery may be a better choice.目的：评价超声心动图引导下采用国产器材在封堵房间隔缺损(atrial septal defect，ASD)时心导管法及经胸小切口法两种介入术式的安全性。方法：回顾性分析成功采用国产器材封堵ASD共1 080例，其中心导管法734例，经胸小切口法346例。心导管法术中是在导管室用大型数字减影血管造影机引导下，并结合经胸超声心动图(transthoracic echocardiography，TTE)监测整个封堵过程，以TTE评价疗效。经胸小切口法在手术室完全使用经食管超声心动图(transesophageal echocardiography，TEE)引导整个封堵过程，指导放置封堵器，并即刻评价疗效。结果：两种介入术式中用国产器材封堵ASD均能取得满意疗效，两种介入术式比较，缺损最长径大小差异无统计学意义(P0.05)，ASD/房间隔长度、封堵器大小、封堵器大小与ASD最长径的差值差异均有统计学意义(均P0.05)。当ASD算术平均数30 mm时，两种介入术式封堵成功率均为100%；当ASD算术平均数≥30 mm时，经胸小切口法封堵成功率为100%，心导管法封堵成功率为50%。结论：国产器材封堵安全，成本低。对于同样大小的缺损，经胸小切口法选择的封堵器较小，更合适。当ASD算术平均数≥30 mm时，经胸小切口法成功率比心导管法大，心导管法失败者可转为经胸小切口法。.

Hand-foot-and-mouth disease (HFMD), caused by enterovirus, is a threat to public health worldwide. To date, enterovirus 71 (EV71) has been one of the major causative agents of HFMD in the Pacific-Asia region, and outbreaks with EV71 cause millions of infections. However, no drug is currently available for clinical therapeutics. In our previous works, we developed a set of protease inhibitors (PIs) targeting the EV71 3C protease (3C pro ). Among these are NK-1.8k and NK-1.9k, which have various active groups and high potencies and selectivities. In the study described here, we determined the structures of the PI NK-1.8k in complex with wild-type (WT) and drug-resistant EV71 3C pro . Comparison of these structures with the structure of unliganded EV71 3C pro and its complex with AG7088 indicated that the mutation of N69 to a serine residue destabilized the S2 pocket. Thus, the mutation influenced the cleavage activity of EV71 3C pro and the inhibitory activity of NK-1.8k in an in vitro protease assay and highlighted that site 69 is an additional key site for PI design. More information for the optimization of the P1′ to P4 groups of PIs was also obtained from these structures. Together with the results of our previous works, these in-depth results elucidate the inhibitory mechanism of PIs and shed light to develop PIs for the clinical treatment of infections caused by EV71 and other enteroviruses.

Unlike the well-established picture for the entry of enveloped viruses, the mechanism of cellular entry of non-enveloped eukaryotic viruses remains largely mysterious. Picornaviruses are representative models for such viruses, and initiate this entry process by their functional receptors. Here we present the structural and functional studies of SCARB2, a functional receptor of the important human enterovirus 71 (EV71). SCARB2 is responsible for attachment as well as uncoating of EV71. Differences in the structures of SCARB2 under neutral and acidic conditions reveal that SCARB2 undergoes a pivotal pH-dependent conformational change which opens a lipid-transfer tunnel to mediate the expulsion of a hydrophobic pocket factor from the virion, a pre-requisite for uncoating. We have also identified the key residues essential for attachment to SCARB2, identifying the canyon region of EV71 as mediating the receptor interaction. Together these results provide a clear understanding of cellular attachment and initiation of uncoating for enteroviruses. Electronic supplementary material The online version of this article (doi:10.1007/s13238-014-0087-3) contains supplementary material, which is available to authorized users.

Nickel based single crystal superalloy DD5 was brazed with the AWS classification filler metal BNi-2 at brazing temperature of 1323–1423 K for holding 10–240 min. The effect of the brazing temperature and brazing time on the microstructure of the brazed joint was investigated by scanning electron microscope (SEM) and electron probe microanalyser (EPMA). The result indicates that the joints exhibit sound bonding without any defect and crack. Three distinct regions can be identified in the joint: a diffusion affect zone composed of γ-γ′ phase and fine M3B2 precipitates, an interfacial bonding zone solidified isothermally at the brazing temperature, and braze alloy zone formed by the solidification of surplus molten filler alloy during cooling. The braze alloy zone consists of γ+γ′ eutectic phase, chromium boride, and ternary eutectic phase of γ-nickel, nickel boride and nickel silicide. With extending brazing time, the thickness of interfacial bonding zone and diffusion affect zone increased while b...

Ni nanotubes, with an inner diameter of about 100 nm and different wall thicknesses (approximately 20, 50, 80 and 110 nm), were successfully fabricated in porous polycarbonate (PC) ion-track templates by a novel method including two-step ion-track etching, two-step electrochemical deposition and one-step electrolysis. In our experiment, wall thickness of Ni nanotubes can be effectively controlled through the etching time of templates. The morphologies and crystal structures of the nanotubes were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD). The magnetic hysteresis loops measured via vibrating sample magnetometry (VSM) indicate that Ni nanotubes with thinner wall thickness possess larger squareness and coercivity value when magnetic field applied parallel to the nanotube׳s axis, which can be attributed to the shape anisotropy and the formation of multi-domain structure.

Enterovirus-71 (EV71) is one of the major causative reagents for hand-foot-and-mouth disease. In particular, EV71 causes severe central nervous system infections and leads to numerous dead cases. Although several inactivated whole-virus vaccines have entered in clinical trials, no antiviral agent has been provided for clinical therapy. In the present work, we screened our compound library and identified that suramin, which has been clinically used to treat variable diseases, could inhibit EV71 proliferation with an IC50 value of 40 μM. We further revealed that suramin could block the attachment of EV71 to host cells to regulate the early stage of EV71 infection, as well as affected other steps of EV71 life cycle. Our results are helpful to understand the mechanism for EV71 life cycle and provide a potential for the usage of an approved drug, suramin, as the antiviral against EV71 infection.

Highlights • Antiviral agents function as either viral targets or host factors. • Virus-targeting antivirals (VTAs) function through a direct (DVTAs) or an indirect (InDVTAs) method in the viral life cycle. • Host-targeting antivirals (HTAs) include reagents that target the host proteins that are involved in the viral life cycle., The prevalence of chronic viral infectious diseases, such as human immunodeficiency virus (HIV), hepatitis C virus (HCV), and influenza virus; the emergence and re-emergence of new viral infections, such as picornaviruses and coronaviruses; and, particularly, resistance to currently used antiviral drugs have led to increased demand for new antiviral strategies and reagents. Increased understanding of the molecular mechanisms of viral infection has provided great potential for the discovery of new antiviral agents that target viral proteins or host factors. Virus-targeting antivirals can function directly or indirectly to inhibit the biological functions of viral proteins, mostly enzymatic activities, or to block viral replication machinery. Host-targeting antivirals target the host proteins that are involved in the viral life cycle, regulating the function of the immune system or other cellular processes in host cells. Here we review key targets and considerations for the development of both antiviral strategies.

β-Sialon(Si4Al2O2N6)/ZrN/ZrO2 ceramic powder was synthesised by an in situ carbothermal reduction–nitridation (CRN) process using fly ash, zircon and active carbon as raw materials. The effects of processing parameters on the phase composition and microstructure of the products were investigated by X-ray diffraction and scanning electronic microscope. The formation process of β-Sialon/ZrN/ZrO2 ceramic powder was also discussed. Increasing carbon content in a sample, reaction temperature and soaking time all could promote the CRN reaction and benefit the formation of β-Sialon and ZrN. The β-Sialon/ZrN/ZrO2 ceramic powder could be fabricated successfully at 1450°C for 2 h, then continually at 1550°C for 4 h while heating the sample with the zircon/fly ash/active carbon mass ratio of 49∶100∶100. The as received β-Sialon particles existed as flaky and their average grain sizes were about 2–3 μm, and the average grain size of ZrN and ZrO2 reached 1–2 μm. The formation process of β-Sialon/ZrN/ZrO2 ceram...

Staphylococcal enterotoxin (SE) B is among the potent toxins produced by Staphylococcus aureus that cause toxic shock syndrome (TSS), which can result in multi-organ failure and death. Currently, neutralizing antibodies have been shown to be effective immunotherapeutic agents against this toxin, but the structural basis of the neutralizing mechanism is still unknown. In this study, we generated a neutralizing monoclonal antibody, 3E2, against SEB, and analyzed the crystal structure of the SEB-3E2 Fab complex. Crystallographic analysis suggested that the neutralizing epitope overlapped with the MHC II molecule binding site on SEB, and thus 3E2 could inhibit SEB function by preventing interaction with the MHC II molecule. Mutagenesis studies were done on SEB, as well as the related Staphylococcus aureus toxins SEA and SEC. These studies revealed that tyrosine (Y)46 and lysine (K)71 residues of SEB are essential to specific antibody–antigen recognition and neutralization. Substitution of Y at SEA glutamine (Q)49, which corresponds to SEB Y46, increased both 3E2’s binding to SEA in vitro and the neutralization of SEA in vivo. These results suggested that SEB Y46 is responsible for distinguishing SEB from SEA. These findings may be helpful for the development of antibody-based therapy for SEB-induced TSS.

Severe fever with thrombocytopenia syndrome virus (SFTSV), a member of the Phlebovirus genus from the Bunyaviridae family endemic to China, is the causative agent of life-threatening severe fever with thrombocytopenia syndrome (SFTS), which features high fever and hemorrhage. Similar to other negative-sense RNA viruses, SFTSV encodes a nucleocapsid protein (NP) that is essential for viral replication. NP facilitates viral RNA encapsidation and is responsible for the formation of ribonucleoprotein complex. However, recent studies have indicated that NP from Phlebovirus members behaves in inhomogeneous oligomerization states. In the present study, we report the crystal structure of SFTSV NP at 2.8 Å resolution and demonstrate the mechanism by which it processes a ringshaped hexameric form to accomplish RNA encapsidation. Key residues essential for oligomerization are identified through mutational analysis and identified to have a significant impact on RNA binding, which suggests that correct formation of highly ordered oligomers is a critical step in RNA encapsidation. The findings of this work provide new insights into the discovery of new antiviral reagents for Phlebovirus infection.

Numerous synthetic RNA-based controls for integrating sensing switches with function devices have been demonstrated in a variety of organisms for gene regulation. Although potential advantages of RNA-based genetic control strategies have been shown in clinical applications, successfully extending these engineered systems into medical applications has seldom been reported. Here, a synthetic RNA-based ribozyme system and its application in advancing rationally designed cellular therapy were described. The theophylline-responsive, ribozyme-based device provided a powerful platform for suicide gene expression regulation in tumor cells. Moreover, we demonstrate the ability of our synthetic controller to modulate effectively the viability of the cells in response to drug input. Our RNA-based regulatory system could dose-dependently fine-tune transgene expression in mammalian cells and address urgent limitations in existing genetic control strategies for gene- and cell-based therapies in the future.

Negative-sense single-strand RNA (-ssRNA) viruses comprise a large family of pathogens that cause severe human infectious diseases. All -ssRNA viruses encode a nucleocapsid protein (NP) to encapsidate the viral genome, which, together with polymerase, forms a ribonucleoprotein complex (RNP) that is packaged into virions and acts as the template for viral replication and transcription. In our previous work, we solved the monomeric structure of NP encoded by Crimean-Congo hemorrhagic fever virus (CCHFV), which belongs to the Nairovirus genus within the Bunyaviridae family, and revealed its unusual endonuclease activity. However, the mechanism of CCHFV RNP formation remains unclear, due to the difficulty in reconstructing the oligomeric CCHFV NP-RNA complex. Here, we identified and isolated the oligomeric CCHFV NP-RNA complex that formed in expression cells. Sequencing of RNA extracted from the complex revealed sequence specificity and suggested a potential encapsidation signal facilitating the association between NP and viral genome. A cryo-EM reconstruction revealed the ring-shaped architecture of the CCHFV NP-RNA oligomer, thus defining the interaction between the head and stalk domains that results in NP multimerization. This structure also suggested a modified gating mechanism for viral genome encapsidation, in which both the head and stalk domains participate in RNA binding. This work provides insight into the distinct mechanism underlying CCHFV RNP formation compared to other -ssRNA viruses.

Scientometric analysis and text-mining have been applied to scientific and technological trend-tracking and related scientific performance evaluations for several years in China. Since 2012, NSL-CAS provides CTI (competitive technical intelligence) services based on metrics for supporting R&D decision-making. NSL helps technology-based firms improve their innovation capabilities via CTI, for technology novelty review, selection of innovation paths, product development evaluation, competitor monitoring, identification of potential R&D partners, and support for industrial technology and development strategizing. Scientometric methods have established many indicators for technology analysis that can be applied individually or in combinations. Composite indexes are another useful option. For CTI services, we choose or customize layer or level indexes schemas for different purposes. For supporting industrial technological strategy decision-making and innovation path identification, scientometric indicators can be used for R&D trend analysis. Specifically, in meso-technology analysis, bibliometrics and patent analysis indicators can be combined in accord with different subjects or stages of an emerging technology, whose characteristics can then be reflected by these mixed indicators. Scientometric indicators can profile the framework for research subjects, and patent metrics can describe the technology development trends. In micro-technology analysis, technology trends analysis is used for new technological product development in planning strategy for technology-based firms, and bibliometric indicators can identify directions of related scientific subjects and research directions. In fact, when a client expresses a CTI need, they request the meso- and micro-, and even macro-technology analysis. So when we execute a CTI service, we run an iteration and loop analysis through bibliometric and patent metrics. We focus theme tracing or subject analysis by tech-mining and co-wording. For macro analysis, such as competition from institutions or countries and regions, we pay close attention to the combination of scientometric and patent indicators and appropriate schemas for CTI services.

Damage buildup in 80 keV Be-implanted InAs0.93Sb0.07 epitaxial layer grown by liquid epitaxy growth (LPE) with the implantation fluences ranging from 1 × 1013 to 4 × 1015 cm−2 have been detailedly investigated by high resolution X-ray diffraction (HRXRD) and transmission electron microscopy (TEM). The implantation-induced nonlinear maximum perpendicular strain em as a function of the Be fluence was deduced. Microstructural variation created by damage buildup was analyzed. The characteristics of annealing on the lattice damage were also studied. The created damages can be recovered by rapid thermal annealing at 500 °C for samples with the fluence below 1.0 × 1015 cm−2, but nano-sized residual damages still existed when the fluence reaches 4.0 × 1015 cm−2 due to the poor recrystallization of the small disorder region.

Structural basis for the impact of phosphorylation on the activation of plant receptor-like kinase BAK1

Crimean–Congo hemorrhagic fever virus (CCHFV), a virus with high mortality in humans, is a member of the genus Nairovirus in the family Bunyaviridae , and is a causative agent of severe hemorrhagic fever (HF). It is classified as a biosafety level 4 pathogen and a potential bioterrorism agent due to its aerosol infectivity and its ability to cause HF outbreaks with high case fatality (∼30%). However, little is known about the structural features and function of nucleoproteins (NPs) in the Bunyaviridae , especially in CCHFV. Here we report a 2.3-Å resolution crystal structure of the CCHFV nucleoprotein. The protein has a racket-shaped overall structure with distinct “head” and “stalk” domains and differs significantly with NPs reported so far from other negative-sense single-stranded RNA viruses. Furthermore, CCHFV NP shows a distinct metal-dependent DNA-specific endonuclease activity. Single residue mutations in the predicted active site resulted in a significant reduction in the observed endonuclease activity. Our results present a new folding mechanism and function for a negative-strand RNA virus nucleoprotein, extend our structural insight into bunyavirus NPs, and provide a potential target for antiviral drug development to treat CCHFV infection.

Plant-specific dynamin-related proteins play crucial roles in cell-plate formation, endocytosis or exocytosis, protein sorting to the vacuole and plasma membrane and the division of mitochondria and chloroplasts. In order to determine the crystal structure and thus to obtain a better understanding of the biological functions and mechanisms of dynamin-related proteins in plant cells, the GTPase domain of Arabidopsis thaliana dynamin-related protein 1A (AtDRP1A) fused to its GTPase effector domain (GED) was crystallized in a nucleotide-associated form using polyethylene glycol 3350 as precipitant. The hexagonal crystals (space group P6(1)) had unit-cell parameters a = b = 146.2, c = 204.3 Å, and diffraction data were collected to 3.6 Å resolution using synchrotron radiation. Four molecules, comprising two functional dimers, are assumed per asymmetric unit, corresponding to a Matthews coefficient of 3.9 Å(3) Da(-1) according to the molecular weight of 39 kDa.

Photoluminescence (PL) spectrum, in conjunction with X-ray photoelectron spectroscopy (XPS) is used to evaluate the surface damage of GaN layer by highly-charged Xe(q+) (18