Knowledge of the in-situ stress field in the rock mass at depth is important to provide stress boundary conditions for underground excavation design, stability evaluation, and the optimization of ...ground support systems. In the present study, in-situ stress measurement using hydraulic fracturing method is conducted in the Beishan area in Gansu Province, China, a preferred candidate site for China's high-level radioactive waste repository. Information on the stress magnitudes and orientations in three sub-areas is obtained from 136 measurement points in nine sub-vertical boreholes at depths ranging from 30 to 700m, and the distribution characteristics of the in-situ stress field is analyzed. The pressure–time records obtained from the test intervals with pre-existing fractures are discussed according to the acoustic borehole televiewer (BHTV) images. The measurement results indicate that the regional stress field is dominated by horizontal stress within most of the measurement depth ranges. A piecewise distribution of the principal stresses reveals approximately three stress domains with increasing depth. At shallow and medium depths, the stress fields are characterized by σH>σh>σv and σH>σv>σh, respectively, where σH, σh, and σv are maximum horizontal, minimum horizontal, and vertical stresses, respectively. With further increase of depth, the maximum principal stress changes from horizontal to vertical (i.e. σv>σH>σh). Fracture impression results reveal that the maximum horizontal stress is dominantly oriented in the NNE–NEE direction, which is in agreement with the orientation of regional tectonic stress field generated from movement of the Earth's tectonic plates. In addition, it is found that the orientations of σH are affected by the geological structures significantly.
•Geological features of the Beishan area are described.•The results of the hydro-fracturing in-situ stress measurements are presented.•The distribution characteristics of the in-situ stress filed are analyzed.•The regional stress field associated with the geological evolution is discussed.
Ab initio molecular dynamics (AIMD) calculations were performed on the atomic configuration of Zr41.2Ti13.8Cu12.5Ni10Be22.5 bulk metallic glass. The local structures were characterized in terms of ...structure factors (SF), pair correlation functions (PCF), coordinate numbers, bond pairs and Voronoi polyhedra. The glass transition temperature, generalized PCF and SF predicated by AIMD are in good agreement with the experimental data. Icosahedral short-range orders (ISRO) are found to be the most dominant, in view of the presence of the majority of bond pairs with 1551, 1541 and 1431, and Voronoi polyhedra with < 0,3,6,1 > , < 0,2,8,1 > , < 0,0,12,0 > and < 0,2,8,4 > . Icosahedral medium range orders (IMROs) are formed from icosahedra via the linkage of vertex-, edge-, face- and intercross-shared atoms. The glass structure on the nanometer scale is accumulated by polyhedra through an efficient packing mode. It is suggested that the extraordinary glass-forming ability of this alloy is essentially attributable to the formation of ISRO and IMRO, and the dense packing of atoms.
CD63 is a member of the four-transmembrane-domain protein superfamily and is the first characterized tetraspanin protein. In the present study, we cloned the common carp (Cyprinus Carpio) CD63 ...(ccCD63) sequence and found that the ccCD63 ORF contained 711 bp and encoded a protein of 236 amino acids. Homology analysis revealed that the complete ccCD63 sequence had 84.08% amino acid similarity to CD63 of Sinocyclocheilus anshuiensis. Subcellular localization analysis revealed that ccCD63 was localized in the cytoplasm. Quantitative real-time PCR (qRT-PCR) analysis indicated that ccCD63 was expressed in the gill, intestine, liver, spleen, brain and kidney, with higher expression in spleen and brain tissues than in the other examined tissues. After koi herpesvirus (KHV) infection, these tissues exhibited various expression levels of ccCD63. The expression level was the lowest in the liver and highest in the brain; the expression level in the brain was 8.7-fold higher than that in the liver. Furthermore, knockdown of ccCD63 promoted KHV infection. Moreover, ccCD63 was correlated with the regulation of RIG-I/MAVS/TRAF3/TBK1/IRF3 and may be involved in the antiviral response through the RIG-I viral recognition signalling pathway in a TRAF3/TBK1-dependent manner. Taken together, our results suggested that ccCD63 upregulated the interaction of KHV with the host immune system and suppressed the dissemination of KHV.
•We cloned the common carp CD63 sequence (ccCD63), and the ORF has a length of 711 bp and encodes 236 amino acids. Subcellular localization analysis revealed that ccCD63 is localized in the cytoplasm.•CcCD63 plays a crucial role in innate immune responses and can specifically stimulate the RIG-1 signaling pathway to regulate IFN production and suppress the early stage of KHV replication.•Knockdown of ccCD63 could increase ORF136 levels and promote KHV infection.•CcCD63 was correlated with the regulation of RIG-I/MAVS/TRAF3/TBK1/IRF3 and may be involved in the antiviral response through the RIG-I viral recognition signaling pathway in a TRAF3/TBK1-dependent manner.•We speculate that ccCD63 has a dual function in virus infection and host immune interactions.
The purpose of this investigation was to assess the effectiveness of an intervention program on mother-to-child transmission (MTCT) of syphilis and investigate determinants of congenital syphilis ...(CS) and adverse pregnancy outcomes (APOs). The Shenzhen local government initiated an intervention program of MTCT of syphilis in 2001. Based on this program, maternal and paternal factors associated with CS and APOs among syphilitic women were investigated from 2007 to 2012 by a prospective cohort study. From 2002 to 2012, 2,441,237 pregnant women were screened and screening coverage reached 97.2 % in 2012. In the background of continuing growth of CS in China, CS in Shenzhen significantly decreased from 109.3 cases in 2002 to 9.9 cases in 2012 per 100,000 live births. Maternal education (adjusted odds ratio aOR
CS
= 0.65; aOR
APOs
= 0.79) and history of syphilis (aOR
CS
= 0.28; aOR
APOs
= 0.61), as well as paternal age (aOR
CS
= 0.62; aOR
APOs
= 0.86) and education (aOR
CS
= 0.66; aOR
APOs
= 0.86) were negatively associated with CS and APOs, but maternal unmarried status (aOR
CS
= 1.95; aOR
APOs
= 2.61), inadequate antenatal care (ANC) (aOR
CS
= 3.61; aOR
APOs
= 1.79), more sexual partners (aOR
CS
= 1.51; aOR
APOs
= 1.39), every week of delay in treatment (aOR
CS
= 2.82; aOR
APOs
= 1.27), higher baseline titers of nontreponemal antibodies (aOR
CS
= 5.65; aOR
APOs
= 1.47), early syphilis (aOR
CS
= 23.24; aOR
APOs
= 26.95), and non-penicillin treatment (aOR
CS
= 3.00; aOR
APOs
= 2.16), as well as paternal history of cocaine use (aOR
CS
= 2.70; aOR
APOs
= 2.44) and positive (aOR
CS
= 4.14; aOR
APOs
= 1.50) or unknown (aOR
CS
= 2.37; aOR
APOs
= 2.06) status of syphilis increased the risk of CS and APOs. Condom use (aOR = 0.70) decreased MTCT of syphilis. A ten-year program consisting of screening and treatment, early ANC, health education, partners tracking, detection, and treatment, follow-up visits, and information management is an effective means to block MTCT of syphilis. Maternal and paternal factors constituted two separate profiles associated with MTCT of syphilis.
Laser-powder-bed-fusion (L-PBF) is a subset of additive manufacturing (AM) that has been increasingly used to manufacture titanium components for aerospace applications. However, titanium components ...fabricated by L-PBF exhibit high mechanical strength and poor ductility because of refined αʹ martensite. Postheating is frequently used to transform the martensitic microstructure into equilibrium α phase for achieving the desired mechanical properties. In this study, superior strength and ductility were achieved by applying low-to high-temperature (LHT) multistep heating to Ti-6Al-2Zr-1Mo-1V (TA15) samples that were as-fabricated (AF) through L-PBF. For comparison, TA15 samples were subjected to one-step annealing and hot isostatic pressing (HIP). The L-PBF AF microstructure mainly comprised acicular αʹ martensite and exhibited high strength (1383 ± 9 MPa) and low ductility (6.3 ± 0.2%). Conventional one-step annealing formed lamellar α+β microstructures that exhibited decreased strength (896–1182 MPa) and improved ductility (12.0–14.3%) compared to AF. Hot isostatic pressing (HIP) treatment formed a lamellar α+β microstructure that exhibited a strength of 1015 ± 30 MPa and ductility of 15.9 ± 0.8%. LHT formed a trimodal microstructure comprising lamellar, equiaxed, and short-rod α and provided well-balanced strength (1033 ± 4 MPa) and ductility (16.6 ± 0.5%), which are superior than those of the samples prepared by using one-step annealing or HIP. Therefore, LHT is a suitable replacement for HIP to prepare L-PBF TA15 exhibiting superior mechanical properties for aerospace applications.
Abstract The present study sought to investigate if p53 mediates autophagy activation and mitochondria dysfunction in primary striatal neurons in kainic acid (KA)-induced excitotoxicity. The ...excitotoxic model of primary striatal neurons was established with KA. The levels of p53, microtubule-associated protein 1 light chain 3 (LC3), Beclin1, and p62 were examined by Western blot and immunostaining. Autophagy activation was also determined with electron microscope. To evaluate the contribution of p53 to autophagy activation and mitochondria dysfunction in KA-induced excitotoxicity, the protein levels of LC3, Beclin1, and p62, the mitochondrial transmembrane potential and the mitochondrial Reactive oxygen species (ROS) after pretreatment with the p53 inhibitor pifithrin-alpha (PFT-α) and the autophagy inhibitor 3-methyladenine (3-MA) were analyzed. Excitotoxic neuronal injury was induced after KA treatment as demonstrated by increases in lactate dehydrogenase (LDH) leakage and was significantly inhibited by PFT-α. Western blot and immunostaining showed that the induction of p53 protein occurred in the cytosol and the nucleus. Increases in autophagic proteins LC3 and Beclin1 were observed, whereas the protein levels of p62 decreased after KA treatment. Electron microscope analysis showed increased autophagosomes in the cytoplasm. The changes in LC3, Beclin1, and p62 levels were blocked by PFT-α, PFT-μ, 3-MA, and E64d but not Z-DEVD-FMK. JC-1 staining showed the depolarization of mitochondrial membrane potential after excitotoxic insult. Mito-tracker and RedoxSensor Red CC-1 staining showed an increased production of mitochondrial ROS after excitotoxic insult. These effects were significantly suppressed after pretreatment with PFT-α and 3-MA. This study suggests that p53 mediates KA-induced autophagy activation and mitochondrial dysfunction in striatal neurons.
Dielectric loaded graphene plasmon waveguide (DLGPW) is proposed and investigated. An analytical model based on effective-index method is presented and verified by the finite element method ...simulations. The mode effective index, propagation loss, cutoff wavelength of higher order modes and single-mode operation region were derived at mid-infrared spectral region. By changing Fermi energy level, the propagation properties of fundamental mode could be tuned flexibly. The structure of the DLGPW is simple and easy for fabrication. It provided a new freedom to manipulate the graphene surface plasmons, which may led to new applications in actively tunable integrated optical devices.
End-point free-energy methods as an indispensable component in virtual screening are commonly recognized as a tool with a certain level of screening power in pharmaceutical research. While a huge ...number of records could be found for end-point applications in protein–ligand, protein–protein, and protein–DNA complexes from academic and industrial reports, up to now, there is no large-scale benchmark in host–guest complexes supporting the screening power of end-point free-energy techniques. A good benchmark requires a data set of sufficient coverage of pharmaceutically relevant chemical space, a long-time sampling length supporting the trajectory approximation of the ensemble average, and a sufficient sample size of receptor–acceptor pairs to stabilize the performance statistics. In this work, selecting a popular family of macrocyclic hosts named cucurbiturils, we construct a large data set containing 154 host–guest pairs, perform extensive end-point sampling of several hundred nanosecond lengths for each system, and extract the free-energy estimates with a variety of end-point free-energy techniques, including the advanced three-trajectory dielectric-constant-variable regime proposed in our recent work. The best-performing end-point protocol employs GAFF2 for solute descriptions, the three-trajectory end-point sampling regime, and the MM/GBSA Hamiltonian in free-energy extraction, achieving a high ranking metrics of Kendall τ > 0.6, a Pearlman predictive index of ∼0.8, and a high scoring power of Pearson r > 0.8. The current project as the first large-scale systematic benchmark of end-point methods in host–guest complexes in academic publications provides solid evidence of the applicability of end-point techniques and direct guidance of computational setups in practical host–guest systems.
Despite the massive application of end-point free energy methods in protein–ligand and protein–protein interactions, computational understandings about their performance in relatively simple and ...prototypical host–guest systems are limited. In this work, we present a comprehensive benchmark calculation with standard end-point free energy techniques in a recent host–guest dataset containing 13 host–guest pairs involving the carboxylated-pillar6arene host. We first assess the charge schemes for solutes by comparing the charge-produced electrostatics with many ab initio references, in order to obtain a preliminary albeit detailed view of the charge quality. Then, we focus on four modelling details of end-point free energy calculations, including the docking procedure for the generation of initial condition, the charge scheme for host and guest molecules, the water model used in explicit-solvent sampling, and the end-point methods for free energy estimation. The binding thermodynamics obtained with different modelling schemes are compared with experimental references, and some practical guidelines on maximizing the performance of end-point methods in practical host–guest systems are summarized. Further, we compare our simulation outcome with predictions in the grand challenge and discuss further developments to improve the prediction quality of end-point free energy methods. Overall, unlike the widely acknowledged applicability in protein–ligand binding, the standard end-point calculations cannot produce useful outcomes in host–guest binding and thus are not recommended unless alterations are performed.
Spin-based electronic devices such as magnetic memory and spin logic rely on spin information transport. Conduction electrons, due to their intrinsic spin angular momentum, become an obvious choice ...for spin information carriers. Here, we experimentally demonstrate that magnons, quasiparticles representing low-energy excitations of ferromagnetic materials, can serve as effective spin information carriers as well. Specifically, we consider two nonmagnetic heavy metals (HMs) that are separated by an electric leak-free ferrimagnetic insulator. When an electric current is applied in one of the HM layers, magnons in the ferrimagnetic insulator are excited and become an effective medium to couple the spin currents in two HMs. As a result, the charge/spin current in one HM layer can drag a charge/spin current in the other HM layer. This work provides a route for spin-based electronic devices where the spin transport is carried by quasiparticles other than electrons.
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