Background:Tandem gene repeats naturally occur as important genomic features and determine many traits in living organisms,like human diseases and microbial productivities of target bioproducts.Methods:Here,we develop...Background:Tandem gene repeats naturally occur as important genomic features and determine many traits in living organisms,like human diseases and microbial productivities of target bioproducts.Methods:Here,we developed a bacterial type-II toxin-antitoxin-mediated method to manipulate genomic integration of tandem gene repeats in Saccharomyces cerevisiae and further visualised the evolutionary trajectories of gene repeats.We designed a tri-vector system to introduce toxin-antitoxin-driven gene amplification modules.Results:This system delivered multi-copy gene integration in the form of tandem gene repeats spontaneously and independently from toxin-antitoxin-mediated selection.Inducing the toxin(RelE)expressing via a copper(II)-inducible CUP1 promoter successfully drove the in-situ gene amplification of the antitoxin(RelB)module,resulting in~40 copies of a green fluorescence reporter gene per copy of genome.Copy-number changes,copy-number increase and copy-number decrease,and stable maintenance were visualised using the green fluorescence protein and blue chromoprotein AeBlue as reporters.Copy-number increases happened spontaneously and independent on a selection pressure.Increased copy number was quickly enriched through toxin-antitoxin-mediated selection.Conclusion:In summary,the bacterial toxin-antitoxin systems provide a flexible mechanism to manipulate gene copy number in eukaryotic cells and can be exploited for synthetic biology and metabolic engineering applications.展开更多
DNA repair enzymes are important in the repair of DNA lesions for maintaining the genome stability,and their abnormal expression induced various human cancers.Simultaneous detection of these DNA enzymes could provide ...DNA repair enzymes are important in the repair of DNA lesions for maintaining the genome stability,and their abnormal expression induced various human cancers.Simultaneous detection of these DNA enzymes could provide convincing evidence based on the comparison of the activity of multiple enzymes than on that of single enzyme.Although fluorescence approach has been applied for the simultaneous detection both of DNA repair enzymes,the spectral overlap and multiwavelength excitation severely restrict the number of available fluorophores.Thus,it is difficult to simultaneously detect three enzymes in a single analysis by fluorescence detection.Herein,we developed a method for the simultaneous determination of three DNA repair enzymes including human flap DNA endonuclease 1(FEN1),human alkyladenine DNA glycosylase(hAAG)and uracil DNA glycosylase(UDG)based on the combination of template-free amplification system with capillary electrophoresis-laser induced fluorescence(CE-LIF)detection.The amplification system was adopted to transfer and amplify the enzymatic products into different length DNA fragments which could be separated effectively by CE-LIF without the complicated modification of the capillary inner wall or labeling different tails on signal probes for separation.The method demonstrated a detection limit of 0.07 U/mL(0.08-160 U/mL)for FEN1,2.40 U/mL(2.5-250U/mL)for hAAG and 2.1×10^(-4)U/mL(0.0004-2.5 U/mL)for UDG,the relative standard deviations(RSDs)of peak time and peak area for different analytes were as follows:2.50%-4,37%and 3.24%-7.18%(inter-day);1.37%-2.71%and 1.43%-3.02%(intra-day),4.28%-6.08%and 4.16%-7.57%(column to column),respectively.And it can identify the inhibitor-like drugs,evaluate enzymatic kinetics and achieve the detection of three enzymes in cell extracts,providing a simple and powerful platform for simultaneous detection of more DNA repair enzymes.展开更多
This paper applies the minimum variance V1 criterion to monitor the evolution of signal and idler modes of a composite non-degenerate optical parametric amplification （NOPA） system. The analytics and numerical calcu...This paper applies the minimum variance V1 criterion to monitor the evolution of signal and idler modes of a composite non-degenerate optical parametric amplification （NOPA） system. The analytics and numerical calculation show the influence of the transition time, the vacuum fluctuations, and the thermal noise level on the EPR entanglement of the composite NOPA system. It finds that the entanglement and the squeezing degrade as the minimum variance V1 increases.展开更多
It is well-known that the responses of a structure are different when subjected to a static load or a sudden step load.The dynamic amplification factor(DAF),which is defined as the ratio of the amplitude of the vibrat...It is well-known that the responses of a structure are different when subjected to a static load or a sudden step load.The dynamic amplification factor(DAF),which is defined as the ratio of the amplitude of the vibratory response to the static response,is normally used to depict the dynamic effect.For a single-degree-of-freedom system(SDOF)subjected to a sudden dynamic load,the maximum value of DAF is 2.Many design guidelines therefore use 2 as an upper bound to consider the dynamic effect.For a civil engineering structure,which is normally a multiple-degrees-of-freedom(MDOF)system,the DAF may exceed 2 in certain circumstances.The adoption of 2 as the upper bond as suggested by the design guidelines therefore may lead to unsafe structural design.Very limited studies systematically investigate the DAF of a MDOF sysCorrespondence to:Bi Kaiming,Centre for Infrastructure Monitoring and Protection,School of Civil and Mechanical Engineering,Curtin University,Kent Street,Bentley WA 6102,Australia Tel:(+61)892665139 E-mail:kaiming.bi@curtin.edu.autem.This study theoretically investigates the DAF of a MDOF system when it is subjected to a step load based on the fundamental theory of structural dynamics.The condition on which the DAF may exceed 2 is defined.Two numerical examples and one experimental study of a cable-stayed bridge subjected to sudden cable loss are presented to illustrate the problem.展开更多
We report on a vortex laser chirped-pulse amplification(CPA)system that delivers pulses with a peak power of 45 TW.A focused intensity exceeding 1019 W/cm2 has been demonstrated for the first time by the vortex amplif...We report on a vortex laser chirped-pulse amplification(CPA)system that delivers pulses with a peak power of 45 TW.A focused intensity exceeding 1019 W/cm2 has been demonstrated for the first time by the vortex amplification scheme.Compared with other schemes of strong-field vortex generation with high energy flux but narrowband vortex-converting elements at the end of the laser,an important advantage of our scheme is that we can use a broadband but size-limited q-plate to realize broadband mode-converting in the front end of the CPA system,and achieve high-power amplification with a series of amplifiers.This method is low cost and can be easily implemented in an existing laser system.The results have verified the feasibility to obtain terawatt and even petawatt vortex laser amplification by a CPA system,which has important potential applications in strong-field laser physics,for example,generation of vortex particle beams with orbital angular momentum,fast ignition for inertial confinement fusion and simulation of the extreme astrophysical environment.展开更多
Optical parametric chirped-pulse amplification implemented using multikilojoule Nd:glass pump lasers is a promising approach for producing ultra-intense pulses(>10^(23)W/cm^(2)).We report on the MTW-OPAL Laser Syst...Optical parametric chirped-pulse amplification implemented using multikilojoule Nd:glass pump lasers is a promising approach for producing ultra-intense pulses(>10^(23)W/cm^(2)).We report on the MTW-OPAL Laser System,an optical parametric amplifier line(OPAL)pumped by the Nd:doped portion of the multi-terawatt(MTW)laser.This midscale prototype was designed to produce 0.5-PW pulses with technologies scalable to tens of petawatts.Technology choices made for MTW-OPAL were guided by the longer-term goal of two full-scale OPALs pumped by the OMEGA EP to produce 2×25-PW beams that would be co-located with kilojoule-nanosecond ultraviolet beams.Several MTWOPAL campaigns that have been completed since“first light”in March 2020 show that the laser design is fundamentally sound,and optimization continues as we prepare for“first-focus”campaigns later this year.展开更多
The efficient generation of a 1.17-mJ laser pulse with 360 ps duration using an ytterbium （Yb）-doped fiber amplifier chain seeded by a homemade mode-locked fiber laser is demonstrated experimentally. A specially des...The efficient generation of a 1.17-mJ laser pulse with 360 ps duration using an ytterbium （Yb）-doped fiber amplifier chain seeded by a homemade mode-locked fiber laser is demonstrated experimentally. A specially designed figure-of-eight fiber laser acts as the seed source of a chirped-pulse amplification （CPA） system and generates mode-locked pulses with hundreds of picosecond widths. Two kinds of large-mode-area （LMA） double-clad Yb-doped fibers are employed to construct the pre-amplifier and main amplifier. All of the adopted instruments help avoid severe nonlinearity in fibers to raise sub-nanosecond pulse energy with acceptable signal-to-noise ratio （SNR）. The output spectrum of this fiber-based CPA system shows that amplified spontaneous emission （ASE） is suppressed to better than 30 dB, and the onset of stimulated Raman scattering is excluded.展开更多
The effects of gain narrowing and high order dispersions on the pulse duration in our kilohertz chirpedpulse amplification system have been compensated experimentally. Using an acousto-optic programmable dispersive fi...The effects of gain narrowing and high order dispersions on the pulse duration in our kilohertz chirpedpulse amplification system have been compensated experimentally. Using an acousto-optic programmable dispersive filter （AOPDF）, the spectral full-width at half-maximum （FWHM） is expanded from 30 to 50 nm. Stable laser pulses with the duration of 30 fs （FWHM）, which is 1.07 times Fourier-transformlimitation, have been acquired by pre-compensating the high order phase distortions using the phase measured by spectral phase interferometry for direct electric-field reconstruction （SPIDER）.展开更多
We present a theoretical analysis of a novel multi-channel light amplification photonic system on chip,where the nonlinear Raman amplification phenomenon in the silicon(Si)wire waveguide is considered.Particularly,a c...We present a theoretical analysis of a novel multi-channel light amplification photonic system on chip,where the nonlinear Raman amplification phenomenon in the silicon(Si)wire waveguide is considered.Particularly,a compact and temperature insensitive Mach–Zehnder interferometer filter working as demultiplexer is also exploited,allowing for the whole Si photonic system to be free from thermal interference.The propagation of the multi-channel pump and Stokes lights is described by a rigorous theoretical model that incorporates all relevant linear and nonlinear optical effects,including the intrinsic waveguide optical losses,first-and second-order frequency dispersion,self-phase and cross-phase modulation,phase shift and two-photon absorption,free-carriers dynamics,as well as the inter-pulse Raman interaction.Notably,to prevent excessive drift of the transmission window of the demultiplexer caused by ambient temperature variations and high thermo-optical coefficient of Si,an asymmetric waveguide width is adopted in the upper and lower arms of each Mach–Zehnder interferometer lattice cell.A Chebyshev half-band filter is utilized to achieve a flat pass-band transmission,achieving a temperature sensitivity of<1.4 pm=K and over 100 K temperature span.This all-Si amplifier shows a thermally robust behavior,which is desired by future Si-on-insulator(SOI)applications.展开更多
This paper theoretically studies the effects of the vacuum-induced coherence on one- and two-photon absorption in a four-level atomic medium. It finds that the one- and two-photon absorption and amplification properti...This paper theoretically studies the effects of the vacuum-induced coherence on one- and two-photon absorption in a four-level atomic medium. It finds that the one- and two-photon absorption and amplification properties are quite sensitive to the vacuum-induced coherence. It is also shown that the one- and two-photon absorption spectra can be dramatically affected by modulating the relative phase of the applied fields, With the proper choice of the relative phase, the amplification without inversion for the probe field can be realized.展开更多
With the approval of more and more genetically modified(GM)crops in our country,GM safety management has become more important.Transgenic detection is a major approach for transgenic safety management.Nevertheless,a c...With the approval of more and more genetically modified(GM)crops in our country,GM safety management has become more important.Transgenic detection is a major approach for transgenic safety management.Nevertheless,a convenient and visual technique with low equipment requirements and high sensitivity for the field detection of GM plants is still lacking.On the basis of the existing recombinase polymerase amplification(RPA)technique,we developed a multiplex RPA(multi-RPA)method that can simultaneously detect three transgenic elements,including the cauliflower mosaic virus 35S gene(CaMV35S)promoter,neomycin phosphotransferaseⅡgene(NptⅡ)and hygromycin B phosphotransferase gene(Hyg),thus improving the detection rate.Moreover,we coupled this multi-RPA technique with the CRISPR/Cas12a reporter system,which enabled the detection results to be clearly observed by naked eyes under ultraviolet(UV)light(254 nm;which could be achieved by a portable UV flashlight),therefore establishing a multi-RPA visual detection technique.Compared with the traditional test strip detection method,this multi-RPA-CRISPR/Cas12a technique has the higher specificity,higher sensitivity,wider application range and lower cost.Compared with other polymerase chain reaction(PCR)techniques,it also has the advantages of low equipment requirements and visualization,making it a potentially feasible method for the field detection of GM plants.展开更多
This article describes a newly devised autosomal short tandem repeat(STR)multiplex polymer-ase chain reaction(PCR)system for 19 autosomal loci(D12S391,D13S317,D16S539,D18S51,D19S433,D2S1338,D21S11,D3S1358,D5S818,D6S10...This article describes a newly devised autosomal short tandem repeat(STR)multiplex polymer-ase chain reaction(PCR)system for 19 autosomal loci(D12S391,D13S317,D16S539,D18S51,D19S433,D2S1338,D21S11,D3S1358,D5S818,D6S1043,D7S820,D8S1179,CSF1PO,FGA,TH01,TPOX,vWA,Penta D and Penta E),27 Y-chromosome STR loci(DYS19,DYS385,DYS3891,DYS38911,DYS390,DYS391,DYS392,DYS393,DYS437,DYS438,DYS439,DYS448,DYS449,DYS456,DYS458,DYS460,DYS481,DYS518,DYS533,DYS570,DYS576,DYS635,DYS627,YGATAH4 and DYF387S1)and amelogenin with six-colour fluorescent labelling.Various parameters were evaluated,such as its accuracy,sensitivity,specificity,stability,ability to ana-lysis of mixtures and effects of changes in the PCR-based procedures.All of the 47 selected STR loci were accurately and robustly amplified from 282 bloodstain samples.The species-spe-cificity was high and some ability to inhibit Hematin was identified.The lowest detectable DNA amount was ≥0.125 ng.All of the male loci of the secondary component were revealed precisely when the control DNA was mixed at male/female and male/male ratios of 1:4 or more.We conclude that the present 19-plex autosomal STR and 27 Y-STR assay is both accur-ate and sensitive.It constitutes an additional powerful tool for forensic applications.展开更多
With the increasing requirements of precision mechanical systems in electronic packaging,ultra-precision machining,biomedicine and other high-tech fields,it is necessary to study a precision two-stage amplification mi...With the increasing requirements of precision mechanical systems in electronic packaging,ultra-precision machining,biomedicine and other high-tech fields,it is necessary to study a precision two-stage amplification micro-drive system that can safely provide high precision and a large amplification ratio.In view of the disadvantages of the current two-stage amplification and micro-drive system,such as poor security,low motion accuracy and limited amplification ratio,an optimization design of a precise symmetrical two-stage amplification micro-drive system was completed in this study,and its related performance was studied.Based on the guiding principle of the flexure hinge,a two-stage amplification micro-drive mechanism with no parasitic motion or non-motion direction force was designed.In addition,the structure optimization design of the mechanism was completed using the particle swarm optimization algorithm,which increased the amplification ratio of the mechanism from 5 to 18 times.A precise symmetrical two-stage amplification system was designed using a piezoelectric ceramic actuator and two-stage amplification micro-drive mechanism as the micro-driver and actuator,respectively.The driving,strength,and motion performances of the system were subsequently studied.The results showed that the driving linearity of the system was high,the strength satisfied the design requirements,the motion amplification ratio was high and the motion accuracy was high(relative error was 5.31%).The research in this study can promote the optimization of micro-drive systems.展开更多
To improve the performance of real-time recombinase polymerase amplification(RPA),a microfluidic system with active mixing is developed to optimize the reaction dynamics.Instead of adopting a single typical reaction c...To improve the performance of real-time recombinase polymerase amplification(RPA),a microfluidic system with active mixing is developed to optimize the reaction dynamics.Instead of adopting a single typical reaction chamber,a specific reactor including a relatively large chamber in center with two adjacent zig-zag channels at two sides is integrated into the microfluidic chip.Active mixing is achieved by driving the viscous reagent between the chamber and the channel back and forth periodically with an outside compact peristaltic pump.To avoid reagent evapora-tion,one end of the reactor is sealed with paraffin oil.A hand-held companion device is developed to facilitate real-time RPA amplification within 20 min.The whole area of the reactor is heated with a resistance heater to provide uniform reaction temperature.To achieve real-time monitoring,a compact fluorescence detection module is integrated into the hand-held device.A smartphone with custom application software is adopted to control the hand-held device and display the real-time fluorescence curves.The performances of two cases with and without active on-chip mixing are compared between each other by detecting African swine fever viruses.It has been demonstrated that,with active on-chip mixing,the amplification efficiency and detection sensitivity can be signifi-cantly improved.展开更多
It has been found that a triple-node feed-forward motif has a function of signal amplification, where two input nodes receive the external weak signal and jointly modulate the response of the third output node [Liang ...It has been found that a triple-node feed-forward motif has a function of signal amplification, where two input nodes receive the external weak signal and jointly modulate the response of the third output node [Liang et al.,Phys. Rev. E 88（2013） 012910]. We here show that the signal amplification can be further enhanced by adding a link between the two input nodes in the feed-forward motif. We further reveal that the coupling strength of the link regulates the enhancement of signal amplification in the modified feed-forward motif. We finally analyze the mechanism of signal amplification of such simple structure.展开更多
In this paper, a new amplification scheme for adaptive MIMO systems is proposed and tested. In this ‘hybrid amplification’ configuration, different amplifiers with different peak powers are used. In this way, each t...In this paper, a new amplification scheme for adaptive MIMO systems is proposed and tested. In this ‘hybrid amplification’ configuration, different amplifiers with different peak powers are used. In this way, each transmitter RF chain has a different DC-power consumption behavior. The adaptation algorithm, which chooses power and rate for each transmitter, uses these different amplifier behaviors to minimize the overall consumed energy. Several MIMO configurations designed for constant capacity applications have been simulated with different amplification schemes. Realistic amplifier models based on measured data are used. The difference between the amplifiers’ RF powers is set in order to keep optimal system performances. Then, it is shown that energy savings higher than 10% can be obtained with the hybrid amplification. The different tests are done for MQAM constellations in uncorrelated Rayleigh fading channels detected with a VBLAST ZF-SIC algorithm but can easily be extended to other correlated channels, detection algorithms or constellations.展开更多
Amplification-free,highly sensitive,and specific nucleic acid detection is crucial for health monitoring and diagnosis.The type III CRISPR-Cas10 system,which provides viral immunity through CRISPRassociated protein ef...Amplification-free,highly sensitive,and specific nucleic acid detection is crucial for health monitoring and diagnosis.The type III CRISPR-Cas10 system,which provides viral immunity through CRISPRassociated protein effectors,enables a new amplification-free nucleic acid diagnostic tool.In this study,we develop a CRISPR-graphene field-effect transistors(GFETs)biosensor by combining the type III CRISPR-Cas10 system with GFETs for direct nucleic acid detection.This biosensor exploits the target RNA-activated continuous ss DNA cleavage activity of the d Csm3 CRISPR-Cas10 effector and the high charge density of a hairpin DNA reporter on the GFET channel to achieve label-free,amplification-free,highly sensitive,and specific RNA detection.The CRISPR-GFET biosensor exhibits excellent performance in detecting medium-length RNAs and miRNAs,with detection limits at the aM level and a broad linear range of 10^(-15)to 10^(-11)M for RNAs and 10^(-15)to 10^(-9)M for miRNAs.It shows high sensitivity in throat swabs and serum samples,distinguishing between healthy individuals(N=5)and breast cancer patients(N=6)without the need for extraction,purification,or amplification.This platform mitigates risks associated with nucleic acid amplification and cross-contamination,making it a versatile and scalable diagnostic tool for molecular diagnostics in human health.展开更多
Glial fibrillary acidic protein(GFAP)is one of the discriminative biomarkers for diagnosing traumatic brain injury(TBI),and accurate determination of GFAP is clinically significant.In this study,a novel fluorescence i...Glial fibrillary acidic protein(GFAP)is one of the discriminative biomarkers for diagnosing traumatic brain injury(TBI),and accurate determination of GFAP is clinically significant.In this study,a novel fluorescence immunoassay system was designed.We encapsulated carbon dots with a high fluorescence quantum yield(QY=92.5%)inside silicon nanocapsules to serve as fluorescent markers.These markers were then integrated with the streptavidin(SA)-biotin biomagnification system and immunomagnetic separation technology for the sensitive detection of GFAP.Based on the signal cascade amplification effect of the silicon nanocapsules and SA-biotin,the fluorescence signal of the SA-biotin-modified immunofluorescence nanocapsules increased 3.6-fold compared to the carbon dot-based immunoprobe.The fluorescence immunoassay system was constructed for GFAP using SA-biotin-modified immunocapsules as the sensing probe and immunomagnetic nanoparticles as the immunorecognition probe.The fluorescence immunoassay system can specifically and ultra-sensitively quantify GFAP in blood samples,with a detection range of 10 pg/mL–10 ng/mL and detection limits of 3.2 pg/mL(serum)and 3.6 pg/mL(plasma).Moreover,the fluorescence immunoassay system exhibited prominent recoveries of 99.4%–100.4%(phosphate buffered saline),96%–102.6%(serum),and 93.2%–110.2%(plasma),with favorable specificity and excellent stabilization.The novel fluorescence immunoassay system provides a new approach to the clinical analysis of GFAP and may serve as a potential tool for screening and diagnosing TBI.展开更多
Lateral flow immunoassay(LFIA),a rapid detection technique noted for simplicity and economy,has showcased indispensable applicability in diverse domains such as disease screening,food safety,and environmental monitori...Lateral flow immunoassay(LFIA),a rapid detection technique noted for simplicity and economy,has showcased indispensable applicability in diverse domains such as disease screening,food safety,and environmental monitoring.Nevertheless,challenges still exist in detecting ultra-low concentration analytes due to the inherent sensitivity limitations of LFIA.Recently,significant advances have been achieved by integrating enzyme activity probes and transforming LFIA into a highly sensitive tool for rapidly detecting trace analyte concentrations.Specifically,modifying natural enzymes or engineered nanozymes allows them to function as immune probes,directly catalyzing the production of signal molecules or indirectly initiating enzyme activity.Therefore,the signal intensity and detection sensitivity of LFIA are markedly elevated.The present review undertakes a comprehensive examination of pertinent research literature,offering a systematic analysis of recently proposed enzyme-based signal amplification strategies.By way of comparative assessment,the merits and demerits of current approaches are delineated,along with the identification of research avenues that still need to be explored.It is anticipated that this critical overview will garner considerable attention within the biomedical and materials science communities,providing valuable direction and insight toward the advancement of high-performance LFIA technologies.展开更多
Strand displacement-based DNA circuits have emerged as highly effective tools for molecular computation,serving purposes of amplification or decision-making.They are favored for their inherent occurrence and sensitivi...Strand displacement-based DNA circuits have emerged as highly effective tools for molecular computation,serving purposes of amplification or decision-making.They are favored for their inherent occurrence and sensitivity to external conditions.However,achieving enhanced amplification or decision-making necessitates the incorporation of multiple strands,thereby increasing the risk of contamination.Recent advancements have led to the development of CRISPR-Cas-based DNA circuits.These systems aim to simplify the complexity associated with conventional circuits,mitigate contamination risks,and enable more substantial amplification or decision-making capabilities.Here,the review article centers on current strategies of CRISPR-Cas(Cas9,Cas12a,Cas13a)system-assisted circuits in amplification and decisionmaking,and assesses their tendencies and limitations in amplification circuits and decision-making circuits.Furthermore,we discuss the challenges of CRISPR-Cas in circuits and propose prospects that will contribute to constructing more efficient and diverse CRISPR-Cas-based DNA functional circuits.展开更多
基金supported partially by the Australian Government through the Australian Research Council Centres of Excellence funding scheme(project CE200100029)。
文摘Background:Tandem gene repeats naturally occur as important genomic features and determine many traits in living organisms,like human diseases and microbial productivities of target bioproducts.Methods:Here,we developed a bacterial type-II toxin-antitoxin-mediated method to manipulate genomic integration of tandem gene repeats in Saccharomyces cerevisiae and further visualised the evolutionary trajectories of gene repeats.We designed a tri-vector system to introduce toxin-antitoxin-driven gene amplification modules.Results:This system delivered multi-copy gene integration in the form of tandem gene repeats spontaneously and independently from toxin-antitoxin-mediated selection.Inducing the toxin(RelE)expressing via a copper(II)-inducible CUP1 promoter successfully drove the in-situ gene amplification of the antitoxin(RelB)module,resulting in~40 copies of a green fluorescence reporter gene per copy of genome.Copy-number changes,copy-number increase and copy-number decrease,and stable maintenance were visualised using the green fluorescence protein and blue chromoprotein AeBlue as reporters.Copy-number increases happened spontaneously and independent on a selection pressure.Increased copy number was quickly enriched through toxin-antitoxin-mediated selection.Conclusion:In summary,the bacterial toxin-antitoxin systems provide a flexible mechanism to manipulate gene copy number in eukaryotic cells and can be exploited for synthetic biology and metabolic engineering applications.
基金supported by the National Natural Science Foundation of China(Nos.21874060 and 22174058,U21A20282)the Science and Technology program of Gansu Province(No.22JR5RA476)。
文摘DNA repair enzymes are important in the repair of DNA lesions for maintaining the genome stability,and their abnormal expression induced various human cancers.Simultaneous detection of these DNA enzymes could provide convincing evidence based on the comparison of the activity of multiple enzymes than on that of single enzyme.Although fluorescence approach has been applied for the simultaneous detection both of DNA repair enzymes,the spectral overlap and multiwavelength excitation severely restrict the number of available fluorophores.Thus,it is difficult to simultaneously detect three enzymes in a single analysis by fluorescence detection.Herein,we developed a method for the simultaneous determination of three DNA repair enzymes including human flap DNA endonuclease 1(FEN1),human alkyladenine DNA glycosylase(hAAG)and uracil DNA glycosylase(UDG)based on the combination of template-free amplification system with capillary electrophoresis-laser induced fluorescence(CE-LIF)detection.The amplification system was adopted to transfer and amplify the enzymatic products into different length DNA fragments which could be separated effectively by CE-LIF without the complicated modification of the capillary inner wall or labeling different tails on signal probes for separation.The method demonstrated a detection limit of 0.07 U/mL(0.08-160 U/mL)for FEN1,2.40 U/mL(2.5-250U/mL)for hAAG and 2.1×10^(-4)U/mL(0.0004-2.5 U/mL)for UDG,the relative standard deviations(RSDs)of peak time and peak area for different analytes were as follows:2.50%-4,37%and 3.24%-7.18%(inter-day);1.37%-2.71%and 1.43%-3.02%(intra-day),4.28%-6.08%and 4.16%-7.57%(column to column),respectively.And it can identify the inhibitor-like drugs,evaluate enzymatic kinetics and achieve the detection of three enzymes in cell extracts,providing a simple and powerful platform for simultaneous detection of more DNA repair enzymes.
基金Project supported by the Natural Science Foundation of Shanxi Province,China (Grant No. 2006011003)
文摘This paper applies the minimum variance V1 criterion to monitor the evolution of signal and idler modes of a composite non-degenerate optical parametric amplification （NOPA） system. The analytics and numerical calculation show the influence of the transition time, the vacuum fluctuations, and the thermal noise level on the EPR entanglement of the composite NOPA system. It finds that the entanglement and the squeezing degrade as the minimum variance V1 increases.
基金National Science Foundation of China(NSFC)under Grant No.51508102,China Postdoctoral Science Foundation under Grant No.2018M631292the Beijing Postdoctoral Science Foundation under Grant No.2018-ZZ-032Financial support was also provided by the China Scholarship Council(CSC)under Grant No.201406655012。
文摘It is well-known that the responses of a structure are different when subjected to a static load or a sudden step load.The dynamic amplification factor(DAF),which is defined as the ratio of the amplitude of the vibratory response to the static response,is normally used to depict the dynamic effect.For a single-degree-of-freedom system(SDOF)subjected to a sudden dynamic load,the maximum value of DAF is 2.Many design guidelines therefore use 2 as an upper bound to consider the dynamic effect.For a civil engineering structure,which is normally a multiple-degrees-of-freedom(MDOF)system,the DAF may exceed 2 in certain circumstances.The adoption of 2 as the upper bond as suggested by the design guidelines therefore may lead to unsafe structural design.Very limited studies systematically investigate the DAF of a MDOF sysCorrespondence to:Bi Kaiming,Centre for Infrastructure Monitoring and Protection,School of Civil and Mechanical Engineering,Curtin University,Kent Street,Bentley WA 6102,Australia Tel:(+61)892665139 E-mail:kaiming.bi@curtin.edu.autem.This study theoretically investigates the DAF of a MDOF system when it is subjected to a step load based on the fundamental theory of structural dynamics.The condition on which the DAF may exceed 2 is defined.Two numerical examples and one experimental study of a cable-stayed bridge subjected to sudden cable loss are presented to illustrate the problem.
基金supported by the National Natural Science Foundation of China(Nos.92050203,61925507,12174264,12004261,62075138,and 61827815)the Natural Science Foundation of Guangdong Province(Nos.2021A1515011909 and 2022A1515011457)the Shenzhen Fundamental Research Projects(Nos.JCYJ20200109105606426,JCYJ20190808164007485,JCYJ20190808121817100,JCYJ20190808143419622,and JCYJ20190808115601653).
文摘We report on a vortex laser chirped-pulse amplification(CPA)system that delivers pulses with a peak power of 45 TW.A focused intensity exceeding 1019 W/cm2 has been demonstrated for the first time by the vortex amplification scheme.Compared with other schemes of strong-field vortex generation with high energy flux but narrowband vortex-converting elements at the end of the laser,an important advantage of our scheme is that we can use a broadband but size-limited q-plate to realize broadband mode-converting in the front end of the CPA system,and achieve high-power amplification with a series of amplifiers.This method is low cost and can be easily implemented in an existing laser system.The results have verified the feasibility to obtain terawatt and even petawatt vortex laser amplification by a CPA system,which has important potential applications in strong-field laser physics,for example,generation of vortex particle beams with orbital angular momentum,fast ignition for inertial confinement fusion and simulation of the extreme astrophysical environment.
基金supported by the Department of Energy National Nuclear Security Administration under Award Number DE-NA0003856the University of Rochesterthe New York State Energy Research and Development Authority。
文摘Optical parametric chirped-pulse amplification implemented using multikilojoule Nd:glass pump lasers is a promising approach for producing ultra-intense pulses(>10^(23)W/cm^(2)).We report on the MTW-OPAL Laser System,an optical parametric amplifier line(OPAL)pumped by the Nd:doped portion of the multi-terawatt(MTW)laser.This midscale prototype was designed to produce 0.5-PW pulses with technologies scalable to tens of petawatts.Technology choices made for MTW-OPAL were guided by the longer-term goal of two full-scale OPALs pumped by the OMEGA EP to produce 2×25-PW beams that would be co-located with kilojoule-nanosecond ultraviolet beams.Several MTWOPAL campaigns that have been completed since“first light”in March 2020 show that the laser design is fundamentally sound,and optimization continues as we prepare for“first-focus”campaigns later this year.
基金supported by the National Key Natural Science Foundation of China under Grant No. 60537060
文摘The efficient generation of a 1.17-mJ laser pulse with 360 ps duration using an ytterbium （Yb）-doped fiber amplifier chain seeded by a homemade mode-locked fiber laser is demonstrated experimentally. A specially designed figure-of-eight fiber laser acts as the seed source of a chirped-pulse amplification （CPA） system and generates mode-locked pulses with hundreds of picosecond widths. Two kinds of large-mode-area （LMA） double-clad Yb-doped fibers are employed to construct the pre-amplifier and main amplifier. All of the adopted instruments help avoid severe nonlinearity in fibers to raise sub-nanosecond pulse energy with acceptable signal-to-noise ratio （SNR）. The output spectrum of this fiber-based CPA system shows that amplified spontaneous emission （ASE） is suppressed to better than 30 dB, and the onset of stimulated Raman scattering is excluded.
基金This work was supported by the National Key Basic Research Special Foundation of China under Grant No. G1999075201.
文摘The effects of gain narrowing and high order dispersions on the pulse duration in our kilohertz chirpedpulse amplification system have been compensated experimentally. Using an acousto-optic programmable dispersive filter （AOPDF）, the spectral full-width at half-maximum （FWHM） is expanded from 30 to 50 nm. Stable laser pulses with the duration of 30 fs （FWHM）, which is 1.07 times Fourier-transformlimitation, have been acquired by pre-compensating the high order phase distortions using the phase measured by spectral phase interferometry for direct electric-field reconstruction （SPIDER）.
基金This work was supported by the National Natural Science Foundation of China(No.11902358)the Scientific Researches Foundation of National University of Defense Technology(Nos.ZK18-03-36 and ZK18-01-03).
文摘We present a theoretical analysis of a novel multi-channel light amplification photonic system on chip,where the nonlinear Raman amplification phenomenon in the silicon(Si)wire waveguide is considered.Particularly,a compact and temperature insensitive Mach–Zehnder interferometer filter working as demultiplexer is also exploited,allowing for the whole Si photonic system to be free from thermal interference.The propagation of the multi-channel pump and Stokes lights is described by a rigorous theoretical model that incorporates all relevant linear and nonlinear optical effects,including the intrinsic waveguide optical losses,first-and second-order frequency dispersion,self-phase and cross-phase modulation,phase shift and two-photon absorption,free-carriers dynamics,as well as the inter-pulse Raman interaction.Notably,to prevent excessive drift of the transmission window of the demultiplexer caused by ambient temperature variations and high thermo-optical coefficient of Si,an asymmetric waveguide width is adopted in the upper and lower arms of each Mach–Zehnder interferometer lattice cell.A Chebyshev half-band filter is utilized to achieve a flat pass-band transmission,achieving a temperature sensitivity of<1.4 pm=K and over 100 K temperature span.This all-Si amplifier shows a thermally robust behavior,which is desired by future Si-on-insulator(SOI)applications.
基金Project supported by the National Natural Science Foundation of China （Grant Nos 10575040 and 90503010）.Acknowledgments The authors would like to thank Dr Wu Ying for helpful discussions.
文摘This paper theoretically studies the effects of the vacuum-induced coherence on one- and two-photon absorption in a four-level atomic medium. It finds that the one- and two-photon absorption and amplification properties are quite sensitive to the vacuum-induced coherence. It is also shown that the one- and two-photon absorption spectra can be dramatically affected by modulating the relative phase of the applied fields, With the proper choice of the relative phase, the amplification without inversion for the probe field can be realized.
基金the Experimental Technology Research Project of Zhejiang University(SYB202138)National Natural Science Foundation of China(32000195)。
文摘With the approval of more and more genetically modified(GM)crops in our country,GM safety management has become more important.Transgenic detection is a major approach for transgenic safety management.Nevertheless,a convenient and visual technique with low equipment requirements and high sensitivity for the field detection of GM plants is still lacking.On the basis of the existing recombinase polymerase amplification(RPA)technique,we developed a multiplex RPA(multi-RPA)method that can simultaneously detect three transgenic elements,including the cauliflower mosaic virus 35S gene(CaMV35S)promoter,neomycin phosphotransferaseⅡgene(NptⅡ)and hygromycin B phosphotransferase gene(Hyg),thus improving the detection rate.Moreover,we coupled this multi-RPA technique with the CRISPR/Cas12a reporter system,which enabled the detection results to be clearly observed by naked eyes under ultraviolet(UV)light(254 nm;which could be achieved by a portable UV flashlight),therefore establishing a multi-RPA visual detection technique.Compared with the traditional test strip detection method,this multi-RPA-CRISPR/Cas12a technique has the higher specificity,higher sensitivity,wider application range and lower cost.Compared with other polymerase chain reaction(PCR)techniques,it also has the advantages of low equipment requirements and visualization,making it a potentially feasible method for the field detection of GM plants.
文摘This article describes a newly devised autosomal short tandem repeat(STR)multiplex polymer-ase chain reaction(PCR)system for 19 autosomal loci(D12S391,D13S317,D16S539,D18S51,D19S433,D2S1338,D21S11,D3S1358,D5S818,D6S1043,D7S820,D8S1179,CSF1PO,FGA,TH01,TPOX,vWA,Penta D and Penta E),27 Y-chromosome STR loci(DYS19,DYS385,DYS3891,DYS38911,DYS390,DYS391,DYS392,DYS393,DYS437,DYS438,DYS439,DYS448,DYS449,DYS456,DYS458,DYS460,DYS481,DYS518,DYS533,DYS570,DYS576,DYS635,DYS627,YGATAH4 and DYF387S1)and amelogenin with six-colour fluorescent labelling.Various parameters were evaluated,such as its accuracy,sensitivity,specificity,stability,ability to ana-lysis of mixtures and effects of changes in the PCR-based procedures.All of the 47 selected STR loci were accurately and robustly amplified from 282 bloodstain samples.The species-spe-cificity was high and some ability to inhibit Hematin was identified.The lowest detectable DNA amount was ≥0.125 ng.All of the male loci of the secondary component were revealed precisely when the control DNA was mixed at male/female and male/male ratios of 1:4 or more.We conclude that the present 19-plex autosomal STR and 27 Y-STR assay is both accur-ate and sensitive.It constitutes an additional powerful tool for forensic applications.
基金The research was funded by the National Natural Science Foundation of China,No.51805428Innovation Capability Support Plan of Shaanxi Province,No.2021 TD-27.
文摘With the increasing requirements of precision mechanical systems in electronic packaging,ultra-precision machining,biomedicine and other high-tech fields,it is necessary to study a precision two-stage amplification micro-drive system that can safely provide high precision and a large amplification ratio.In view of the disadvantages of the current two-stage amplification and micro-drive system,such as poor security,low motion accuracy and limited amplification ratio,an optimization design of a precise symmetrical two-stage amplification micro-drive system was completed in this study,and its related performance was studied.Based on the guiding principle of the flexure hinge,a two-stage amplification micro-drive mechanism with no parasitic motion or non-motion direction force was designed.In addition,the structure optimization design of the mechanism was completed using the particle swarm optimization algorithm,which increased the amplification ratio of the mechanism from 5 to 18 times.A precise symmetrical two-stage amplification system was designed using a piezoelectric ceramic actuator and two-stage amplification micro-drive mechanism as the micro-driver and actuator,respectively.The driving,strength,and motion performances of the system were subsequently studied.The results showed that the driving linearity of the system was high,the strength satisfied the design requirements,the motion amplification ratio was high and the motion accuracy was high(relative error was 5.31%).The research in this study can promote the optimization of micro-drive systems.
基金supported by the National Natural Science Foundation of China(Nos.81871505,61971026)the Fundamental Research Fund for the Central Universities(No.XK1802-4)+1 种基金the National Science and Technology Major Project(No.2018ZX10732101-001-009)the Research Fund to the Top Scientific and Technological Innovation Team from Beijing University of Chemical Technology(No.buctylkjcx06).
文摘To improve the performance of real-time recombinase polymerase amplification(RPA),a microfluidic system with active mixing is developed to optimize the reaction dynamics.Instead of adopting a single typical reaction chamber,a specific reactor including a relatively large chamber in center with two adjacent zig-zag channels at two sides is integrated into the microfluidic chip.Active mixing is achieved by driving the viscous reagent between the chamber and the channel back and forth periodically with an outside compact peristaltic pump.To avoid reagent evapora-tion,one end of the reactor is sealed with paraffin oil.A hand-held companion device is developed to facilitate real-time RPA amplification within 20 min.The whole area of the reactor is heated with a resistance heater to provide uniform reaction temperature.To achieve real-time monitoring,a compact fluorescence detection module is integrated into the hand-held device.A smartphone with custom application software is adopted to control the hand-held device and display the real-time fluorescence curves.The performances of two cases with and without active on-chip mixing are compared between each other by detecting African swine fever viruses.It has been demonstrated that,with active on-chip mixing,the amplification efficiency and detection sensitivity can be signifi-cantly improved.
基金Supported by the Program for Professor of Special Appointment（Eastern Scholar） at Shanghai Institutions of Higher Learning under Grant No.QD2015016 the National Natural Science Foundation of China under Grant Nos.11505114 and 11305078
文摘It has been found that a triple-node feed-forward motif has a function of signal amplification, where two input nodes receive the external weak signal and jointly modulate the response of the third output node [Liang et al.,Phys. Rev. E 88（2013） 012910]. We here show that the signal amplification can be further enhanced by adding a link between the two input nodes in the feed-forward motif. We further reveal that the coupling strength of the link regulates the enhancement of signal amplification in the modified feed-forward motif. We finally analyze the mechanism of signal amplification of such simple structure.
文摘In this paper, a new amplification scheme for adaptive MIMO systems is proposed and tested. In this ‘hybrid amplification’ configuration, different amplifiers with different peak powers are used. In this way, each transmitter RF chain has a different DC-power consumption behavior. The adaptation algorithm, which chooses power and rate for each transmitter, uses these different amplifier behaviors to minimize the overall consumed energy. Several MIMO configurations designed for constant capacity applications have been simulated with different amplification schemes. Realistic amplifier models based on measured data are used. The difference between the amplifiers’ RF powers is set in order to keep optimal system performances. Then, it is shown that energy savings higher than 10% can be obtained with the hybrid amplification. The different tests are done for MQAM constellations in uncorrelated Rayleigh fading channels detected with a VBLAST ZF-SIC algorithm but can easily be extended to other correlated channels, detection algorithms or constellations.
基金financially supported by the National Science and Technology Innovation 2030 Grants(2021ZD0201600)the National Key R&D Program of China(2021YFA0717000)+2 种基金the Intramural Joint Program Fund of State Key Laboratory of Microbial Technology(Project No.SKLMTIJP-2024-05)the Natural Science Foundation of Qingdao-Original exploration project(Project No.24-4-4-zrjj-139-jch)the National Natural Science Foundation of China(31771380)。
文摘Amplification-free,highly sensitive,and specific nucleic acid detection is crucial for health monitoring and diagnosis.The type III CRISPR-Cas10 system,which provides viral immunity through CRISPRassociated protein effectors,enables a new amplification-free nucleic acid diagnostic tool.In this study,we develop a CRISPR-graphene field-effect transistors(GFETs)biosensor by combining the type III CRISPR-Cas10 system with GFETs for direct nucleic acid detection.This biosensor exploits the target RNA-activated continuous ss DNA cleavage activity of the d Csm3 CRISPR-Cas10 effector and the high charge density of a hairpin DNA reporter on the GFET channel to achieve label-free,amplification-free,highly sensitive,and specific RNA detection.The CRISPR-GFET biosensor exhibits excellent performance in detecting medium-length RNAs and miRNAs,with detection limits at the aM level and a broad linear range of 10^(-15)to 10^(-11)M for RNAs and 10^(-15)to 10^(-9)M for miRNAs.It shows high sensitivity in throat swabs and serum samples,distinguishing between healthy individuals(N=5)and breast cancer patients(N=6)without the need for extraction,purification,or amplification.This platform mitigates risks associated with nucleic acid amplification and cross-contamination,making it a versatile and scalable diagnostic tool for molecular diagnostics in human health.
基金supported by the AMS Funding Project(No.ZZB2023C7010).
文摘Glial fibrillary acidic protein(GFAP)is one of the discriminative biomarkers for diagnosing traumatic brain injury(TBI),and accurate determination of GFAP is clinically significant.In this study,a novel fluorescence immunoassay system was designed.We encapsulated carbon dots with a high fluorescence quantum yield(QY=92.5%)inside silicon nanocapsules to serve as fluorescent markers.These markers were then integrated with the streptavidin(SA)-biotin biomagnification system and immunomagnetic separation technology for the sensitive detection of GFAP.Based on the signal cascade amplification effect of the silicon nanocapsules and SA-biotin,the fluorescence signal of the SA-biotin-modified immunofluorescence nanocapsules increased 3.6-fold compared to the carbon dot-based immunoprobe.The fluorescence immunoassay system was constructed for GFAP using SA-biotin-modified immunocapsules as the sensing probe and immunomagnetic nanoparticles as the immunorecognition probe.The fluorescence immunoassay system can specifically and ultra-sensitively quantify GFAP in blood samples,with a detection range of 10 pg/mL–10 ng/mL and detection limits of 3.2 pg/mL(serum)and 3.6 pg/mL(plasma).Moreover,the fluorescence immunoassay system exhibited prominent recoveries of 99.4%–100.4%(phosphate buffered saline),96%–102.6%(serum),and 93.2%–110.2%(plasma),with favorable specificity and excellent stabilization.The novel fluorescence immunoassay system provides a new approach to the clinical analysis of GFAP and may serve as a potential tool for screening and diagnosing TBI.
基金Financial supports from the National Natural Science Foundation of China(NSFC,Nos.52272144 and 22205048)Heilongjiang Provincial Natural Science Foundation of China(No.JQ2022E001)+3 种基金China Postdoctoral Science Foundation(Nos.2022M710931 and 2023T160154)Heilongjiang Postdoctoral Science Foundation(No.LBH-Z22010)Natural Science Foundation of Shandong Province(No.ZR2020ZD42)the Fundamental Research funds for the Central Universities are greatly acknowledged.
文摘Lateral flow immunoassay(LFIA),a rapid detection technique noted for simplicity and economy,has showcased indispensable applicability in diverse domains such as disease screening,food safety,and environmental monitoring.Nevertheless,challenges still exist in detecting ultra-low concentration analytes due to the inherent sensitivity limitations of LFIA.Recently,significant advances have been achieved by integrating enzyme activity probes and transforming LFIA into a highly sensitive tool for rapidly detecting trace analyte concentrations.Specifically,modifying natural enzymes or engineered nanozymes allows them to function as immune probes,directly catalyzing the production of signal molecules or indirectly initiating enzyme activity.Therefore,the signal intensity and detection sensitivity of LFIA are markedly elevated.The present review undertakes a comprehensive examination of pertinent research literature,offering a systematic analysis of recently proposed enzyme-based signal amplification strategies.By way of comparative assessment,the merits and demerits of current approaches are delineated,along with the identification of research avenues that still need to be explored.It is anticipated that this critical overview will garner considerable attention within the biomedical and materials science communities,providing valuable direction and insight toward the advancement of high-performance LFIA technologies.
基金financially supported by the National Natural Science Foundation of China (Nos. 82172372 and 82260290)the Opening Research Fund of State Key Laboratory of Digital Medical Engineering (No. 2023-M04)
文摘Strand displacement-based DNA circuits have emerged as highly effective tools for molecular computation,serving purposes of amplification or decision-making.They are favored for their inherent occurrence and sensitivity to external conditions.However,achieving enhanced amplification or decision-making necessitates the incorporation of multiple strands,thereby increasing the risk of contamination.Recent advancements have led to the development of CRISPR-Cas-based DNA circuits.These systems aim to simplify the complexity associated with conventional circuits,mitigate contamination risks,and enable more substantial amplification or decision-making capabilities.Here,the review article centers on current strategies of CRISPR-Cas(Cas9,Cas12a,Cas13a)system-assisted circuits in amplification and decisionmaking,and assesses their tendencies and limitations in amplification circuits and decision-making circuits.Furthermore,we discuss the challenges of CRISPR-Cas in circuits and propose prospects that will contribute to constructing more efficient and diverse CRISPR-Cas-based DNA functional circuits.
