Mutation analyses of integrated HBV genome in hepatitis B patients

Little has been learnt in the last 30 years about detection of HBV genome as well as its mutation analysis between hepatitis B fathers （HBF） and their children. In this study, we used nest polymerase chain reaction （PCR）, fluorescence in situ hybridization （FISH）, and DNA sequencing analysis, to examine the integrated HBV genome in paraffin-embedded testis tissues, which were taken as samples from HBE and in peripheral blood mononuclear cells （PBMC） from 74 cases of HBFs and their children who were born after their fathers＇ HBV infection （caHBF）. We found that HBV DNA existed in testis tissues, mainly in the basilar parts of the seminiferous tubules, and also in PBMC of HBE It was also documented that there were point mutations of poly-loci, insertions and deletions of nucleotides in integrated HBV genomes, and the types of gene mutations in the HBFs were similar to those in caHBE This study addresses the major types of gene mutations in integrated HBV genome in human patients and also presents reliable evidence of possible genetic transmission of hepatitis B.

Regulating electrolytic Fe_(0.5)CoNiCuZn_(x) high entropy alloy electrodes for oxygen evolution reactions in alkaline solution

The properties of high entropy alloys(HEAs)depend on their phase structures and compositions.However,it is difficult to control the composition of the HEAs that contain highly volatile metals by the conventional arc melting method.In this paper,homogeneous powdery face centered cubic(FCC)phase Fe_(0.5)CoNiCuZn_(x) HEAs were prepared by the electrolysis of metal oxides in molten Na_(2)CO_(3)-K_(2)CO_(3) using a stable Ni11Fe10Cu inert oxygen-evolution anode.The use of oxide precursors and relatively low synthetic temperature are beneficial to efficiently preparing HEAs that contain highly volatile elements such as Zn.Moreover,the microstructures and compositions of the electrolytic HEAs can be easily tailored by adjusting the components of oxide precursors,then further regulating its properties.Thus,the electrocatalytic activity of Fe_(0.5)Co NiCuZn_(x) HEAs towards oxygen evolution reactions(OER)was investigated in 1 M KOH.The results show that Zn promotes the OER activity of Fe_(0.5)CoNiCuZn_(x) HEAs,i.e.,the HEA(Zn_(0.8))shows the best OER activity exhibiting a low overpotential of 340 m V at 10 m A/cm^(2) and excellent stability of 24 h.Hence,molten salt electrolysis not only provides a green approach to prepare Fe_(0.5)CoNiCuZn_(x) HEAs but also offers an effective way to regulate the structure of the alloys and thereby optimizes the electrocatalytic activities for water electrolysis.

Structure-activity relationship optimization for lassa virus fusion inhibitors targeting the transmembrane domain of GP2

Dear Editor,Lassa virus(LASV)belongs to the Mammarenavirus genus,Arenaviridae family.Arenaviruses are classified into two main groups-Old World(OW)and New World(NW)-based on virus genetics,serology,antigenic properties and geographical relationships.The OW LASV and Lujo virus(LUJV),as well as NW Jurn'n virus(JUNV),Machupo virus(MACV),Guanarito virus(GTOV),Sabia virus(SABV)and Chapare virus(CHAPV),are known to cause severe hemorrhagic fever and are listed as biosafety level 4(BSL-4)agents.The arenavirus glycoprotein complex(GPC)contains three subunits-the retained stable-signal peptide(SSP),the receptor-binding subunit GP1,and the membrane fusion subunit GP2(Lenz et al.,2001).Notably,the proximate external membrane region and TM of GP2,together with the ectodomain loop and TMs of SSP,form an SSP-GP2 interface,playing essential roles in regulating membrane fusion,and providing targets for distinct fusion inhibitors(Larson et al.,2008;Lee et al.,2008;York et al.,2008;York and Nunberg,2009;Thomas et al.,2011;Burgeson et al.,2013a;Shankar et al.,2016;Wang et al.,2016;Wang et al.,2018).Among these inhibitors,ST-161 is LASV specific(Burgeson et al.,2013a).In this study,we conducted structure-activity relationship(SAR)optimization of ST-161.As a result,21 derivatives with IC50 values<1 pmol/L are presented in Table S1.Hit compounds 21,29 and 57 exhibiting robust inhibition of the LASV pseudotype virus(LASVpv,VSV backbone enveloped by LASV GPC with single cycle infection)entry with IC50 values lower than 0.2 nmol/L(Figs.1A and S1),as well as hit compound 72 with an ester bond instead of acylhydrazone,were further investigated.To test whether the four hit compounds inhibit LASV entry by blocking the GPC-mediated membrane fusion,the inhibition effects of these compounds against LASV GPC mediated fusion were quantitatively determined by dual-luciferase assay(Thomas et al.,2011;Wang et al.,2018).

Design of readout electronics based on peak-holding circuit and multiplexer for a fast neutron spectrometer

Background Fast neutron detection is meaningful in many research fields such as space environment monitoring.A scintillating fiber array model for fast neutron detection was proposed and developed in 1980s.Aerospace applications of the model require electronics in small size.Purpose To design a dedicated electronic system to readout and process the 384-channel signals from scintillating fiber array,and to use the designed system to fabricate a neutron detector for aerospace applications.Methods With the method of nuclear recoil,fast neutron is detected by tracking recoil proton of n–p scatter in scintillating plastic fibers.Using the peak-holding circuits and multiplexers,the system size and power consumption were reduced.Results The detector fabricated with the designed system,had 34 cm×34 cm×27 cm mechanical size,20.4 kg weight,and 30.05W power consumption.Comparing to traditional waveform sampling electronics,the designed electronics was highly integrated and had a small size.The readout electronics also gave a better energy resolution of 39%in neutron detection,while the energy resolution was 43%in previous version.Conclusion In this study,a highly integrated readout electronic system was designed and verified.The detector using the system gave good performance.The designed electronics had potential development in fast neutron detection and other high energy physics detection system.

Enhancing oxide scale growth and adhesion via electrochemically regulating ion diffusion

Pre-oxidation is a common surface treatment approach to enhance the corrosion resistance of met-als,which suffers from slow ion diffusion kinetics,bad oxide scale adhesion,and weak compactness.Herein,we propose an electrochemical oxidation approach in molten carbonate to improve the oxide scale growth and adhesion via electrochemically regulating ion diffusion in the formed oxide scale.An anodic polarization applied at the metal substrate enlarges the chemical potential gradient of oxygen and offers a favorable electric field across the metal/oxide interface to the oxide scale/molten salt interface,thereby speeding up the oxide scale growth rate in terms of increasing the diffusion rate of metal cations and oxygen ions through the oxide scale.At the same time,the oxide scale adhesion is remarkedly im-proved because the metal vacancies at the oxide/alloy interface are filled by the newly formed oxide.After being treated by electrochemical oxidation,the corrosion rate of the Ni-16Fe-4Mo alloys in molten Li_(2) CO_(3)-Na_(2) CO_(3)-K_(2) CO_(3) decreased ten-fold.Overall,electrochemical oxidation enables the rapid formation of an adherent and corrosion-resistant oxide scale on the metal substrate,offering a general and effective way to fabricate corrosion-resistant films to survive in various aggressively corrosive media.

Eliminating carbon contamination with improved one-step electrochemical preparation of refractory high-entropy alloy TiZrHfNbTa

Creating refractory high-entropy alloys(RHEAs)effectively without impurities is a momentous challenge.Conventional methods for the preparation of RHEAs have exacting requirements for raw material purity and energy consumption.Molten salt electrolytic oxides are applied to the preparation of HEAs by virtue of their low cost and high efficiency.However,the use of graphite anodes in electrolysis will result in the carbon contamination of the products due to the deposition of CO_(3)^(2−)at the cathode.Increasing the reaction temperature accelerates the deoxidation of the oxide,thus reducing the amount of carbide but not eliminating it.Switching HfH_(2)instead of HfO_(2)and using Nb_(2)O_(5)to shield the precursor can effectively remove carbon contamination.However,this leads to a complicated preparation process and energy waste.Herein,we use the solid oxygen ion-conducting membrane(SOM)containing graphite and Sn(named as SOM@C/Sn)anode to separate the carbon from the molten salt and prevent the circulation of CO_(3)^(2−).The pure single-phase TiZrHfNbTa RHEA can be produced in only one-step with the SOM@C/Sn anode,which completely solves the problem of carbon contamination in the molten salt electrolysis preparation of HEAs.This work provides a feasible solution for the preparation of novel complex alloys such as carbon-free RHEAs in a low-cost short process.

Design of a high-sampling-rate electronic module for array-detector positron annihilation lifetime measurements

Introduction In this study,a high-time-resolution electronic module with a high channel density and low power consumption was designed for the measurement of the multi-detector array positron annihilation lifetimes.This electronic module consisted of 32 input channels,and each channel provided a high sampling rate up to 5.12 GSPS based on a Domino Ring Sampler 4(DRS4)chip.Compared to the high-speed flash analog-digital converter(FADC),DRS4 chip has a higher channel density with an affordable lower price and power consumption.Methods The developed electronic module was also capable of real-time data analysis for directly extracting the time information of input signals at the data acquisition site,thereby significantly decreasing the data rate.The digital constant fraction discriminator(DCFD)algorithm was implemented in the field programmable gate array(FPGA)for performing the time pick-up.Results The coincidence time resolution of the electronic module was measured,and the test results revealed a value of 26 ps.A prototypical 16-pixel detector module of the multi-detector system was evaluated using this electronic module,and the coincidence time resolution of the prototypical module was 411.84 ps.Conclusions The electronic module was confirmed to satisfy the severe requirements of the multi-array-detector positron annihilation lifetime measurement system.It was also suitable for other high-time-resolution,high-channel-density,costeffective,and low-power-consumption applications.