Metal 3D printing holds great promise for future digitalized manufacturing.However,the intricate interplay between laser and metal powders poses a significant challenge for conventional trial-and-error optimization.Me...Metal 3D printing holds great promise for future digitalized manufacturing.However,the intricate interplay between laser and metal powders poses a significant challenge for conventional trial-and-error optimization.Meanwhile,the“optimized”yet fixed parameters largely limit possible extensions to new designs and materials.Herein,we report a high throughput design coupled with machine learning(ML)guidance to eliminate the notorious cracks and porosities in metal 3D printing for improved corrosion resistance and overall performance.The high throughput methodologies are mostly on obtaining the printed samples and their structural and physical properties,while ML is used for data analysis by model building for prediction(optimization),and understanding.For 316L stainless steel,we concurrently printed 54 samples with different parameters and subjected them to parallel tests to generate an extensive dataset for ML analysis.An ensemble learning model outperformed the other five single learners while Bayesian active learning recommended optimal parameters that could reduce porosity from 0.57%to below 0.1%.Accordingly,the ML-recommended samples showed higher tensile strength(609.28 MPa)and elongation(50.67%),superior anti-corrosion(I_(corr)=4.17×10^(-8) A·cm^(-2)),and stable alkaline oxygen evolution for>100 hours(at 500 mA·cm^(-2)).Remarkably,through the correlation analysis of printing parameters and targeted properties,we find that the influence of hardness on corrosion resistance is second only to porosity.We then expedited optimization in AlSi7Mg using the learned knowledge and feed hardness and relative density,thus demonstrating the method’s general extensibility and efficiency.Our strategy can significantly accelerate the optimization of metal 3D printing and facilitate adaptable design to accommodate diverse materials and requirements.展开更多
The experiments of high throughput drilling of Ti-6Al-4V at 183 m/min cutting speed and 156 mm^3/s material removal rate using a 4 mm diameter WC-Co spiral point drill are conducted. At this material removal rate, it ...The experiments of high throughput drilling of Ti-6Al-4V at 183 m/min cutting speed and 156 mm^3/s material removal rate using a 4 mm diameter WC-Co spiral point drill are conducted. At this material removal rate, it took only 0.57 s to drill a hole in a 6.35 mm thick Ti plate. Supplying the cutting fluid via through-the-drill holes and the balance of cutting speed and feed have proven to be critical for drill life. An inverse heat transfer model is developed to predict the heat flux and the drill temperature distribution in drilling. A three-dimensional finite element modeling of drilling is con-ducted to predict the thrust force and torque. Experimental result demonstrates that, using proper machining process parameters, tool geometry, and fine-grained WC-Co tool material, the high throughput machining of Ti alloy is technically feasible.展开更多
Our aim is to study the roles of a new emerging group of non-coding RNAs, circRNAs, in tomato(Solanum lycopersicum L.) plants grown at the combination of drought and heat, two of the most usual stress conditions known...Our aim is to study the roles of a new emerging group of non-coding RNAs, circRNAs, in tomato(Solanum lycopersicum L.) plants grown at the combination of drought and heat, two of the most usual stress conditions known to frequently happen in field. Tomato seedlings from cultivar‘Jinling Meiyu’ were treated without stresses(control), at water shortage, high temperature and subjected the multiple stresses. In total, 467 circRNAs were identified with 87.82% from exon using high throughput sequencing technology. Among the circRNAs, 70 were from chr1 with the range from 23 to 49 from the other chromosomes. In detail, 156 circRNAs were shared in the four libraries, while 21, 17 and 36 circRNAs were only shown in drought, heat and multiple stresses libraries, respectively. Through a differential expression analysis, four, seven and nine circRNAs were differentially regulated in tomato at drought, heat and multiple stresses as compared with control. These circRNAs played roles on photosynthesis, starch and sucrose metabolism, RNA transport, RNA degradation, spliceosome, ribosome, etc. Our study underlined the potential role of circRNAs involved in the abiotic stress response in tomato, which might pave the way for studying biological roles of circRNAs responding to multiple stresses in plants.展开更多
Background:In-feed antibiotics are being phased out in livestock production worldwide.Alternatives to antibiotics are urgently needed to maintain animal health and production performance.Host defense peptides(HDPs)are...Background:In-feed antibiotics are being phased out in livestock production worldwide.Alternatives to antibiotics are urgently needed to maintain animal health and production performance.Host defense peptides(HDPs)are known for their broad-spectrum antimicrobial and immunomodulatory capabilities.Enhancing the synthesis of endogenous HDPs represents a promising antibiotic alternative strategy to disease control and prevention.Methods:To identify natural products with an ability to stimulate the synthesis of endogenous HDPs,we performed a high-throughput screening of 1261 natural products using a newly-established stable luciferase reporter cell line known as IPEC-J2/pBD3-luc.The ability of the hit compounds to induce HDP genes in porcine IPEC-J2 intestinal epithelial cells,3D4/31 macrophages,and jejunal explants were verified using RT-qPCR.Augmentation of the antibacterial activity of porcine 3D4/31 macrophages against a Gram-negative bacterium(enterotoxigenic E.coli)and a Gram-positive bacterium(Staphylococcus aureus)were further confirmed with four selected HDP-inducing compounds.Results:A total of 48 natural products with a minimum Z-score of 2.0 were identified after high-throughput screening,with 21 compounds giving at least 2-fold increase in luciferase activity in a follow-up dose-response experiment.Xanthohumol and deoxyshikonin were further found to be the most potent in inducing pBD3 mRNA expression,showing a minimum 10-fold increase in IPEC-J2,3D4/31 cells,and jejunal explants.Other compounds such as isorhapontigenin and calycosin also enhanced pBD3 mRNA expression by at least 10-fold in both IPEC-J2 cells and jejunal explants,but not 3D4/31 cells.In addition to pBD3,other porcine HDP genes such as pBD2,PG1-5,and pEP2C were induced to different magnitudes by xanthohumol,deoxyshikonin,isorhapontigenin,and calycosin,although clear gene-and cell type-specific patterns of regulation were observed.Desirably,these four compounds had a minimum effect on the expression of several representative inflammatory cytokine genes.Furthermore,when used at HDP-inducing concentrations,these compounds showed no obvious direct antibacterial activity,but significantly augmented the antibacterial activity of 3D4/31 macrophages(P<0.05)against both Gram-negative and Gram-positive bacteria.Conclusions:Our results indicate that these newly-identified natural HDP-inducing compounds have the potential to be developed as novel alternatives to antibiotics for prophylactic and therapeutic treatment of infectious diseases in livestock production.展开更多
A stably transfected CHO cell line coexpressing G551D-CFTR and iodide-sensitive yellow fluorescent protein mutant EYFP-H148Q-I152L was successfully established and used as assay model to identify small-molecule activa...A stably transfected CHO cell line coexpressing G551D-CFTR and iodide-sensitive yellow fluorescent protein mutant EYFP-H148Q-I152L was successfully established and used as assay model to identify small-molecule activators of G551D-CFTR chloride channel from 100000 diverse combinatorial compounds by high throughput screening on a customized Beckman robotic system. A bicyclooctane compound was identified to activate G551D-CFTR chloride channel with high-affinity(K d=1.8 μmol/L). The activity of the bicyclooctane compound is G551D-CFTR-specific, reversible and non-toxic. The G551D-CFTR activator may be useful as a tool to study the mutant G551D-CFTR chloride channel structure and transport properties and as a candidate drug to cure cystic fibrosis caused by G551D-CFTR mutation.展开更多
Single atomic catalysts(SACs),especially metal-nitrogen doped carbon(M-NC)catalysts,have been extensively explored for the electrochemical oxygen reduction reaction(ORR),owing to their high activity and atomic utiliza...Single atomic catalysts(SACs),especially metal-nitrogen doped carbon(M-NC)catalysts,have been extensively explored for the electrochemical oxygen reduction reaction(ORR),owing to their high activity and atomic utilization efficiency.However,there is still a lack of systematic screening and optimization of local structures surrounding active centers of SACs for ORR as the local coordination has an essential impact on their electronic structures and catalytic performance.Herein,we systematic study the ORR catalytic performance of M-NC SACs with different central metals and environmental atoms in the first and second coordination sphere by using density functional theory(DFT)calculation and machine learning(ML).The geometric and electronic informed overpotential model(GEIOM)based on random forest algorithm showed the highest accuracy,and its R^(2) and root mean square errors(RMSE)were 0.96 and 0.21,respectively.30 potential high-performance catalysts were screened out by GEIOM,and the RMSE of the predicted result was only 0.12 V.This work not only helps us fast screen high-performance catalysts,but also provides a low-cost way to improve the accuracy of ML models.展开更多
High throughput experimentation is employed to establish a ternary system with the compositional range of 30.8 mol.%-75.7 mol.%SiO_(2),16.6 mol.%-61.7 mol.%Yb_(2)O_(3),and 6.3 mol.%-4.1 moll.%Ho_(2)O_(3) through co-sp...High throughput experimentation is employed to establish a ternary system with the compositional range of 30.8 mol.%-75.7 mol.%SiO_(2),16.6 mol.%-61.7 mol.%Yb_(2)O_(3),and 6.3 mol.%-4.1 moll.%Ho_(2)O_(3) through co-sputtering deposition on one combinatorial material chip.Considering their application in advanced SiC_(f)/SiC CMC,the phase composition and mechanical properties of samples with various RE/Si ratios and Yb/Ho ratios are comprehensively investigated.Chemical stability and thermal expansion compatibility between SiC and RE silicates with different compositions are also validated.Optimized materials for the application of environmental barrier coating and interphase for SiC_(f)/SiC CMC are screened respectively according to the above trends and data.This work is a case study to establish a composition-property library for RE_(2)O_(3)-SiO_(2) compounds.It is inspired more complicated multicomponent RE silicates could be prepared and characterized by high throughput experimentation,accelerating the design and screening of promising optimal candidates.展开更多
A novel solid phase organic synthesis resin was synthesized for combinatorial high-throughput screening,which based on FTIR spectra self-encoding functional resin technology. A new deconvolution strategy termed positi...A novel solid phase organic synthesis resin was synthesized for combinatorial high-throughput screening,which based on FTIR spectra self-encoding functional resin technology. A new deconvolution strategy termed position encoding deconvolution had illustrated and was compared with some popular combinatorial deconvolution strategies in efficiency and information content. The mimic high throughput screening of hexapeptide library successfully proved the applying of the self-encoding functional resin technology and the position encoding deconvolution strategy.展开更多
The glycine-to-aspartic acid missense mutation at the codon 551(G551D) of the cystic fibrosis transmembrane conductance regulator(CFTR) is one of the five most frequent cystic fibrosis(CF) mutations associated with a ...The glycine-to-aspartic acid missense mutation at the codon 551(G551D) of the cystic fibrosis transmembrane conductance regulator(CFTR) is one of the five most frequent cystic fibrosis(CF) mutations associated with a severe CF phenotype. To explore the feasibility of pharmacological correction of disrupted activation of CFTR chloride channel caused by G551D mutation, we developed a halide-sensitive fluorescence miniassay for G551D-CFTR in Fisher rat thyroid(FRT) epithelial cells for the discovery of novel activators of G551D-CFTR. A class of bicyclooctane small molecule compounds that efficiently stimulate G551D-CFTR chloride channel activity was identified by high throughput screening via the FRT cell-based assay. This class of compounds selectively activates G551D-CFTR with a high affinity, whereas little effect of the compounds on wildtype CFTR can be seen. The discovery of a class of bicyclooctane G551D-CFTR activators will permit the analysis of structure-activity relationship of the compounds to identify ideal leads for in vivo therapeutic studies.展开更多
Alphaviruses,which contain a variety of mosquito-borne pathogens,are important pathogens of emerging/reemerging infectious diseases and potential biological weapons.Currently,no specific antiviral drugs are available ...Alphaviruses,which contain a variety of mosquito-borne pathogens,are important pathogens of emerging/reemerging infectious diseases and potential biological weapons.Currently,no specific antiviral drugs are available for the treatment of alphaviruses infection.For most highly pathogenic alphaviruses are classified as risk group-3 agents,the requirement of biosafety level 3(BSL-3)facilities limits the live virus-based antiviral study.To facilitate the antiviral development of alphaviruses,we developed a high throughput screening(HTS)platform based on a recombinant Semliki Forest virus(SFV)which can be manipulated in BSL-2 laboratory.Using the reverse genetics approach,the recombinant SFV and SFV reporter virus expressing eGFP(SFV-eGFP)were successfully rescued.The SFV-eGFP reporter virus exhibited robust eGFP expression and remained relatively stable after four passages in BHK-21 cells.Using a broad-spectrum alphavirus inhibitor ribavirin,we demonstrated that the SFV-eGFP can be used as an effective tool for antiviral study.The SFV-eGFP reporter virus-based HTS assay in a 96-well format was then established and optimized with a robust Z0 score.A section of reference compounds that inhibit highly pathogenic alphaviruses were used to validate that the SFV-eGFP reporter virus-based HTS assay enables rapid screening of potent broad-spectrum inhibitors of alphaviruses.This assay provides a safe and convenient platform for antiviral study of alphaviruses.展开更多
Two-dimensional(2D)semiconducting tin disulfide(SnS_(2))has been widely used for optoelectronic applications.To functionalize SnS_(2) for extending its application,we investigate the stability,electronic and magnetic ...Two-dimensional(2D)semiconducting tin disulfide(SnS_(2))has been widely used for optoelectronic applications.To functionalize SnS_(2) for extending its application,we investigate the stability,electronic and magnetic properties of substitutional doping by high throughput first-principles calculations.There are a lot of elements that can be doped in monolayer SnS_(2).Nonmetal in group A can introduce p-type and n-type carriers,while most metals in group A can only lead to p-type doping.Not only 3d,but also 4d and 5d transition metals in groups VB to VⅢB9 can introduce magnetism in SnS_(2),which is potentially applicable for spintronics.This study provides a comprehensive view of functionalization of SnS_(2) by substitutional doping,which will guide further experimental realization.展开更多
In this article, we introduce the system of high throughput screening (HTS). Its role in new drug study and current development is described. The relationship between research achievements of genome study and new type...In this article, we introduce the system of high throughput screening (HTS). Its role in new drug study and current development is described. The relationship between research achievements of genome study and new type screening model of new drugs is emphasized. The personal opinions of current problems about HTS study in China are raised.展开更多
This paper proposes a raptor-like low-density parity-check(RL-LDPC)code design together with the corresponding decoder hardware architecture aiming at next-generation mobile communication.A new kind of protograph diff...This paper proposes a raptor-like low-density parity-check(RL-LDPC)code design together with the corresponding decoder hardware architecture aiming at next-generation mobile communication.A new kind of protograph different from the 5G new radio(NR)LDPC basic matrix is presented,and a code construction algorithm is proposed to improve the error-correcting performance.A multi-core layered decoder architecture that supports up to 100 Gbit/s throughput is designed based on the special protograph structure.展开更多
RNA sequencing is the use of hight hroughput next generation sequencing technology to survey, characterize, and quantify the transcriptome of a genome. RNA sequencing has been used to analyze the pathogenesis of sever...RNA sequencing is the use of hight hroughput next generation sequencing technology to survey, characterize, and quantify the transcriptome of a genome. RNA sequencing has been used to analyze the pathogenesis of several malignancies such melanoma, lung cancer, and colorectal cancer. RNA sequencing can identify differential expression of genes(DEG's), mutated genes, fusion genes, and gene isoforms in disease states. RNA sequencing has been used in the investigation of several colorectal diseases such as colorectal cancer, inflammatory bowel disease(ulcerative colitis and Crohn's disease), and irritable bowel syndrome.展开更多
In order to reveal the influence of different plant configurations on the microbial community structure and diversity in rhizosphere soil of Cotinus coggygria in Fragrant Hills park,the ITS+5.8S rDNA gene and 16S rDNA...In order to reveal the influence of different plant configurations on the microbial community structure and diversity in rhizosphere soil of Cotinus coggygria in Fragrant Hills park,the ITS+5.8S rDNA gene and 16S rDNA gene V3-V4 region sequencing analysis for fungi and bacteria,respectively,were conducted by high throughput sequencing(Illumina MiSeq).The results showed that the fungal diversity in the rhizosphere soil samples of C.coggygria in Fragrant Hills park in 2018 was significantly higher than that in 2016,and it was higher in the rhizosphere soil of healthy C.coggygria in Xunlupo than that in diseased ones in 2018.Verticillium dahliae,which is the causal agent of C.coggygria wilt,was detected in five soil samples.In 2018,the bacterial diversity in the rhizosphere soil of diseased C.coggygria in Xunlupo was the lowest,while it was the highest in the rhizosphere soil of healthy C.coggygria under Platycladus orientalis in Langfengting.展开更多
High-throughput satellite (HTS) systems usually make use of Multibeam coverage at high frequency bands in order to offer broadband access of large areas. Multibeam coverage increases the available capacity through fre...High-throughput satellite (HTS) systems usually make use of Multibeam coverage at high frequency bands in order to offer broadband access of large areas. Multibeam coverage increases the available capacity through frequency reuse and spatial separation. However, one of its major drawbacks is inter- spot interference which considered the motivation to propose a new approach using a coding technique to distinguish between beams that will be employed to mitigate this interference without the need of frequency reuse. This approach makes the use of orthogonal codes to identify beams and allow using the total satellite bandwidth per beam. Proposed system double the bandwidth used in each beam and save the usage of antenna polarization resource used in former designs, which may be used as a multiple accessing resource inside the coded beams. The objective of this paper is to provide a comprehensive performance assessment methodology for the proposed approach. Result validation is introduced by comparing the proposed system performance with conventional systems that relay on the DVB standards.展开更多
Xenobiotic drugs and chemicals directly interact with DNA,proteins,or other biomolecules in cells. These direct interactions with molecular targets may trigger a series of downstream effects on metabolic-biochemical a...Xenobiotic drugs and chemicals directly interact with DNA,proteins,or other biomolecules in cells. These direct interactions with molecular targets may trigger a series of downstream effects on metabolic-biochemical and regulatory-signaling networks that can invoke cellular consequences leading to adaptive homeostatic or adverse pathological responses. Regulators for drug and chemicals safety have therefore since long required the testing of toxicity in animal models before drugs and pesticides can enter the market. The US National Research Council of the National Academy of Sciences,in its report,Toxicity Testing in the 21st Century: a Vision and a Strategy [1] ,proposed that toxicity testing should become less reliant on apical endpoints from whole animal tests and eventually rely instead on quantitative,doseresponse models based on information from in vitro assays and in vivo biomarkers,which can be used to screen large numbers of chemicals. The present paper reports about a combination of HTS in vitro assays that can be used to study the potential tumorigenic effect of xenobiotics ( drug targets,environmental chemicals) via a set of"sentinel"genes [2] that are functionally interrelated based on evidence weighted functional linkage network ( FLN ) log-likelihood scores ( Linghu et al [3] ) .展开更多
Skin lightening and tanning are two major areas dominating the market of skincare and cosmetic products. Though the demands are originated from two different communities, the two areas share a same goal—skin colour t...Skin lightening and tanning are two major areas dominating the market of skincare and cosmetic products. Though the demands are originated from two different communities, the two areas share a same goal—skin colour tuning. The known safe compounds with skin colour tuning activities are limited. In contrary, Chinese medicinal herb provides a pool of natural bioactive compounds, which have been used in Asian countries for long time and have been tested for its toxicity. Here, we demonstrate a high throughput screening platform for potential compounds usable for skin colour tuning. From 147 natural compounds, 26 of them showed potential in skin tanning functions by using the high throughput melanogenesis platform based on the melanogenesis assay on B16 melanocytes. Five of them promoted melanogenesis by over 50%. Moreover, apart from 1, 8-dihydroxyanthraquinone, the other four compounds showed enhancement effect on tyrosinase activity. From the result, the compounds increased the Vmax of tyrosinase without changing the Km in a dose-dependent manner. Thus, there should be no irreversible structural change of the enzyme. Definitely, this report contributes to the development of personalization in skincare and cosmetic products.展开更多
Highly toxic phosgene,diethyl chlorophosphate(DCP)and volatile acyl chlorides endanger our life and public security.To achieve facile sensing and discrimination of multiple target analytes,herein,we presented a single...Highly toxic phosgene,diethyl chlorophosphate(DCP)and volatile acyl chlorides endanger our life and public security.To achieve facile sensing and discrimination of multiple target analytes,herein,we presented a single fluorescent probe(BDP-CHD)for high-throughput screening of phosgene,DCP and volatile acyl chlorides.The probe underwent a covalent cascade reaction with phosgene to form boron dipyrromethene(BODIPY)with bright green fluorescence.By contrast,DCP,diphosgene and acyl chlorides can covalently assembled with the probe,giving rise to strong blue fluorescence.The probe has demonstrated high-throughput detection capability,high sensitivity,fast response(within 3 s)and parts per trillion(ppt)level detection limit.Furthermore,a portable platform based on BDP-CHD was constructed,which has achieved high-throughput discrimination of 16 analytes through linear discriminant analysis(LDA).Moreover,a smartphone adaptable RGB recognition pattern was established for the quantitative detection of multi-analytes.Therefore,this portable fluorescence sensing platform can serve as a versatile tool for rapid and high-throughput detection of toxic phosgene,DCP and volatile acyl chlorides.The proposed“one for more”strategy simplifies multi-target discrimination procedures and holds great promise for various sensing applications.展开更多
The utilization of phosphorescent metal complexes as emissive dopants for organic light-emitting diodes(OLEDs)has been the subject of intense research.Cyclometalated Pt(Ⅱ)complexes are particularly popular triplet em...The utilization of phosphorescent metal complexes as emissive dopants for organic light-emitting diodes(OLEDs)has been the subject of intense research.Cyclometalated Pt(Ⅱ)complexes are particularly popular triplet emitters due to their color-tunable emissions.To make them viable for practical applications as OLED emitters,it is essential to develop Pt(Ⅱ)complexes with high radiative decay rate constants(k_(r))and photoluminescence quantum yields(PLQY).To this end,an efficient and accurate prediction tool is highly desirable.In this work,we propose a general yet powerful protocol achieving metal complex generation,high throughput virtual screening(HTVS),and fast predictions with high accuracy.More than 3600 potential structures are generated in a synthesis-friendly manner.Moreover,three HTVS-machine learning(ML)models are established using different algorithms with carefully designed features that are suitable for metal complexes.Specifically,30 potential candidates are filtered out by HTVS-ML models with a three-tier screening rule and put into accurate predictions with experimental calibrationΔ-learning method.The highly accurate prediction approach further reduces the stress of experiments and inspires greater confidence in identifying the most promising complexes as excellent emitters.As a result,12 promising complexes(k_(r)>10^(5) s^(−1) and PLQY>0.6)with the same superior core structures are confirmed from over 3600 Pt-complexes.Experiments revealed that two very close complexes have excellent emission properties and are consistent with the prediction results,providing strong evidence for the efficacy of the proposed protocol.We expect this protocol will become a valuable tool,expediting the rational design and rapid development of novel OLED materials with desired properties.展开更多
基金sponsored by the National Key Research and Development Program of China(No.2023YFB4604800,2021YFA1202300)the Natural and Science Foundation of China(Grant Nos.52201041,52275331,52205358)+1 种基金the Key Research and Development Program of Hubei Province(Nos.2024BCB091,2022CFA031)the Hong Kong Scholars Program(No.XJ2022014)。
文摘Metal 3D printing holds great promise for future digitalized manufacturing.However,the intricate interplay between laser and metal powders poses a significant challenge for conventional trial-and-error optimization.Meanwhile,the“optimized”yet fixed parameters largely limit possible extensions to new designs and materials.Herein,we report a high throughput design coupled with machine learning(ML)guidance to eliminate the notorious cracks and porosities in metal 3D printing for improved corrosion resistance and overall performance.The high throughput methodologies are mostly on obtaining the printed samples and their structural and physical properties,while ML is used for data analysis by model building for prediction(optimization),and understanding.For 316L stainless steel,we concurrently printed 54 samples with different parameters and subjected them to parallel tests to generate an extensive dataset for ML analysis.An ensemble learning model outperformed the other five single learners while Bayesian active learning recommended optimal parameters that could reduce porosity from 0.57%to below 0.1%.Accordingly,the ML-recommended samples showed higher tensile strength(609.28 MPa)and elongation(50.67%),superior anti-corrosion(I_(corr)=4.17×10^(-8) A·cm^(-2)),and stable alkaline oxygen evolution for>100 hours(at 500 mA·cm^(-2)).Remarkably,through the correlation analysis of printing parameters and targeted properties,we find that the influence of hardness on corrosion resistance is second only to porosity.We then expedited optimization in AlSi7Mg using the learned knowledge and feed hardness and relative density,thus demonstrating the method’s general extensibility and efficiency.Our strategy can significantly accelerate the optimization of metal 3D printing and facilitate adaptable design to accommodate diverse materials and requirements.
基金Selected from Proceedings of the 7th International Conference on Frontiers of Design and Manufacturing (ICFDM’2006).
文摘The experiments of high throughput drilling of Ti-6Al-4V at 183 m/min cutting speed and 156 mm^3/s material removal rate using a 4 mm diameter WC-Co spiral point drill are conducted. At this material removal rate, it took only 0.57 s to drill a hole in a 6.35 mm thick Ti plate. Supplying the cutting fluid via through-the-drill holes and the balance of cutting speed and feed have proven to be critical for drill life. An inverse heat transfer model is developed to predict the heat flux and the drill temperature distribution in drilling. A three-dimensional finite element modeling of drilling is con-ducted to predict the thrust force and torque. Experimental result demonstrates that, using proper machining process parameters, tool geometry, and fine-grained WC-Co tool material, the high throughput machining of Ti alloy is technically feasible.
基金funding from National Natural Science Foundation of China (Grant No. 31601745)Natural Science Foundation of Jiangsu Province (Grant No. BK20160579)Aarhus University Research Foundation (Grant No. 30379)
文摘Our aim is to study the roles of a new emerging group of non-coding RNAs, circRNAs, in tomato(Solanum lycopersicum L.) plants grown at the combination of drought and heat, two of the most usual stress conditions known to frequently happen in field. Tomato seedlings from cultivar‘Jinling Meiyu’ were treated without stresses(control), at water shortage, high temperature and subjected the multiple stresses. In total, 467 circRNAs were identified with 87.82% from exon using high throughput sequencing technology. Among the circRNAs, 70 were from chr1 with the range from 23 to 49 from the other chromosomes. In detail, 156 circRNAs were shared in the four libraries, while 21, 17 and 36 circRNAs were only shown in drought, heat and multiple stresses libraries, respectively. Through a differential expression analysis, four, seven and nine circRNAs were differentially regulated in tomato at drought, heat and multiple stresses as compared with control. These circRNAs played roles on photosynthesis, starch and sucrose metabolism, RNA transport, RNA degradation, spliceosome, ribosome, etc. Our study underlined the potential role of circRNAs involved in the abiotic stress response in tomato, which might pave the way for studying biological roles of circRNAs responding to multiple stresses in plants.
基金supported by the National Natural Science Foundation of China(31972576)the Beijing Natural Science Foundation(6202004)+2 种基金the Special Program on Science and Technology Innovation Capacity Building of BAAFS(KJCX20180414 and KJCX201914)the USDA National Institute of Food and Agriculture(2018-68003-27462 and 2018-33610-28252)the Oklahoma Center for the Advancement of Science and Technology(AR19-27)。
文摘Background:In-feed antibiotics are being phased out in livestock production worldwide.Alternatives to antibiotics are urgently needed to maintain animal health and production performance.Host defense peptides(HDPs)are known for their broad-spectrum antimicrobial and immunomodulatory capabilities.Enhancing the synthesis of endogenous HDPs represents a promising antibiotic alternative strategy to disease control and prevention.Methods:To identify natural products with an ability to stimulate the synthesis of endogenous HDPs,we performed a high-throughput screening of 1261 natural products using a newly-established stable luciferase reporter cell line known as IPEC-J2/pBD3-luc.The ability of the hit compounds to induce HDP genes in porcine IPEC-J2 intestinal epithelial cells,3D4/31 macrophages,and jejunal explants were verified using RT-qPCR.Augmentation of the antibacterial activity of porcine 3D4/31 macrophages against a Gram-negative bacterium(enterotoxigenic E.coli)and a Gram-positive bacterium(Staphylococcus aureus)were further confirmed with four selected HDP-inducing compounds.Results:A total of 48 natural products with a minimum Z-score of 2.0 were identified after high-throughput screening,with 21 compounds giving at least 2-fold increase in luciferase activity in a follow-up dose-response experiment.Xanthohumol and deoxyshikonin were further found to be the most potent in inducing pBD3 mRNA expression,showing a minimum 10-fold increase in IPEC-J2,3D4/31 cells,and jejunal explants.Other compounds such as isorhapontigenin and calycosin also enhanced pBD3 mRNA expression by at least 10-fold in both IPEC-J2 cells and jejunal explants,but not 3D4/31 cells.In addition to pBD3,other porcine HDP genes such as pBD2,PG1-5,and pEP2C were induced to different magnitudes by xanthohumol,deoxyshikonin,isorhapontigenin,and calycosin,although clear gene-and cell type-specific patterns of regulation were observed.Desirably,these four compounds had a minimum effect on the expression of several representative inflammatory cytokine genes.Furthermore,when used at HDP-inducing concentrations,these compounds showed no obvious direct antibacterial activity,but significantly augmented the antibacterial activity of 3D4/31 macrophages(P<0.05)against both Gram-negative and Gram-positive bacteria.Conclusions:Our results indicate that these newly-identified natural HDP-inducing compounds have the potential to be developed as novel alternatives to antibiotics for prophylactic and therapeutic treatment of infectious diseases in livestock production.
基金the Start- up Fund for Returned Overseas Scholars from Northeast Normal U niversity,National ScienceFund for Distinguished Young Scholars (No. 30 32 5 0 11) ,Distinguished Young Scholars Fund of Jilin Province(No.2 0 0 30 112 ) ,Excellent Young Teachers
文摘A stably transfected CHO cell line coexpressing G551D-CFTR and iodide-sensitive yellow fluorescent protein mutant EYFP-H148Q-I152L was successfully established and used as assay model to identify small-molecule activators of G551D-CFTR chloride channel from 100000 diverse combinatorial compounds by high throughput screening on a customized Beckman robotic system. A bicyclooctane compound was identified to activate G551D-CFTR chloride channel with high-affinity(K d=1.8 μmol/L). The activity of the bicyclooctane compound is G551D-CFTR-specific, reversible and non-toxic. The G551D-CFTR activator may be useful as a tool to study the mutant G551D-CFTR chloride channel structure and transport properties and as a candidate drug to cure cystic fibrosis caused by G551D-CFTR mutation.
基金financially supported by the National Key Research and Development Program of China (2018YFA0702002)the Beijing Natural Science Foundation (Z210016)the National Natural Science Foundation of China (21935001)。
文摘Single atomic catalysts(SACs),especially metal-nitrogen doped carbon(M-NC)catalysts,have been extensively explored for the electrochemical oxygen reduction reaction(ORR),owing to their high activity and atomic utilization efficiency.However,there is still a lack of systematic screening and optimization of local structures surrounding active centers of SACs for ORR as the local coordination has an essential impact on their electronic structures and catalytic performance.Herein,we systematic study the ORR catalytic performance of M-NC SACs with different central metals and environmental atoms in the first and second coordination sphere by using density functional theory(DFT)calculation and machine learning(ML).The geometric and electronic informed overpotential model(GEIOM)based on random forest algorithm showed the highest accuracy,and its R^(2) and root mean square errors(RMSE)were 0.96 and 0.21,respectively.30 potential high-performance catalysts were screened out by GEIOM,and the RMSE of the predicted result was only 0.12 V.This work not only helps us fast screen high-performance catalysts,but also provides a low-cost way to improve the accuracy of ML models.
基金supported by the National Natural Science Foun-dation of China under Grant Nos.U21A2063,52002376National Key R&D Program of China under Grant No.2021YFB3702300+1 种基金Key Research Program of the Chinese Academy of Sciences under Grant No.ZDRW-CN-2021-2-2LiaoNing Revitalization Talents Pro-gram under Grant No.XLYC2002018,Natural Science Foundation of Liaoning Province under Grant No.2020-MS-006.
文摘High throughput experimentation is employed to establish a ternary system with the compositional range of 30.8 mol.%-75.7 mol.%SiO_(2),16.6 mol.%-61.7 mol.%Yb_(2)O_(3),and 6.3 mol.%-4.1 moll.%Ho_(2)O_(3) through co-sputtering deposition on one combinatorial material chip.Considering their application in advanced SiC_(f)/SiC CMC,the phase composition and mechanical properties of samples with various RE/Si ratios and Yb/Ho ratios are comprehensively investigated.Chemical stability and thermal expansion compatibility between SiC and RE silicates with different compositions are also validated.Optimized materials for the application of environmental barrier coating and interphase for SiC_(f)/SiC CMC are screened respectively according to the above trends and data.This work is a case study to establish a composition-property library for RE_(2)O_(3)-SiO_(2) compounds.It is inspired more complicated multicomponent RE silicates could be prepared and characterized by high throughput experimentation,accelerating the design and screening of promising optimal candidates.
文摘A novel solid phase organic synthesis resin was synthesized for combinatorial high-throughput screening,which based on FTIR spectra self-encoding functional resin technology. A new deconvolution strategy termed position encoding deconvolution had illustrated and was compared with some popular combinatorial deconvolution strategies in efficiency and information content. The mimic high throughput screening of hexapeptide library successfully proved the applying of the self-encoding functional resin technology and the position encoding deconvolution strategy.
基金the Start- up Fund for Returned Overseas Scholars from Northeast Normal U niversity,National ScienceFund for Distinguished Young Scholars(No.30 32 5 0 11) ,Distinguished Young Scholars Fund of Jilin Province(No.2 0 0 30 112 ) ,Excellent Young Teachers Pr
文摘The glycine-to-aspartic acid missense mutation at the codon 551(G551D) of the cystic fibrosis transmembrane conductance regulator(CFTR) is one of the five most frequent cystic fibrosis(CF) mutations associated with a severe CF phenotype. To explore the feasibility of pharmacological correction of disrupted activation of CFTR chloride channel caused by G551D mutation, we developed a halide-sensitive fluorescence miniassay for G551D-CFTR in Fisher rat thyroid(FRT) epithelial cells for the discovery of novel activators of G551D-CFTR. A class of bicyclooctane small molecule compounds that efficiently stimulate G551D-CFTR chloride channel activity was identified by high throughput screening via the FRT cell-based assay. This class of compounds selectively activates G551D-CFTR with a high affinity, whereas little effect of the compounds on wildtype CFTR can be seen. The discovery of a class of bicyclooctane G551D-CFTR activators will permit the analysis of structure-activity relationship of the compounds to identify ideal leads for in vivo therapeutic studies.
基金supported by the Creative Research Group Program of Natural Science Foundation of Hubei Province (2022CFA021)National Natural Science Foundation of China (81702005).
文摘Alphaviruses,which contain a variety of mosquito-borne pathogens,are important pathogens of emerging/reemerging infectious diseases and potential biological weapons.Currently,no specific antiviral drugs are available for the treatment of alphaviruses infection.For most highly pathogenic alphaviruses are classified as risk group-3 agents,the requirement of biosafety level 3(BSL-3)facilities limits the live virus-based antiviral study.To facilitate the antiviral development of alphaviruses,we developed a high throughput screening(HTS)platform based on a recombinant Semliki Forest virus(SFV)which can be manipulated in BSL-2 laboratory.Using the reverse genetics approach,the recombinant SFV and SFV reporter virus expressing eGFP(SFV-eGFP)were successfully rescued.The SFV-eGFP reporter virus exhibited robust eGFP expression and remained relatively stable after four passages in BHK-21 cells.Using a broad-spectrum alphavirus inhibitor ribavirin,we demonstrated that the SFV-eGFP can be used as an effective tool for antiviral study.The SFV-eGFP reporter virus-based HTS assay in a 96-well format was then established and optimized with a robust Z0 score.A section of reference compounds that inhibit highly pathogenic alphaviruses were used to validate that the SFV-eGFP reporter virus-based HTS assay enables rapid screening of potent broad-spectrum inhibitors of alphaviruses.This assay provides a safe and convenient platform for antiviral study of alphaviruses.
基金Project supported by the National Natural Science Foundation of China(Grant No.91833302).
文摘Two-dimensional(2D)semiconducting tin disulfide(SnS_(2))has been widely used for optoelectronic applications.To functionalize SnS_(2) for extending its application,we investigate the stability,electronic and magnetic properties of substitutional doping by high throughput first-principles calculations.There are a lot of elements that can be doped in monolayer SnS_(2).Nonmetal in group A can introduce p-type and n-type carriers,while most metals in group A can only lead to p-type doping.Not only 3d,but also 4d and 5d transition metals in groups VB to VⅢB9 can introduce magnetism in SnS_(2),which is potentially applicable for spintronics.This study provides a comprehensive view of functionalization of SnS_(2) by substitutional doping,which will guide further experimental realization.
文摘In this article, we introduce the system of high throughput screening (HTS). Its role in new drug study and current development is described. The relationship between research achievements of genome study and new type screening model of new drugs is emphasized. The personal opinions of current problems about HTS study in China are raised.
基金supported in part by ZTE Industry-University-Institute Coop⁃eration funds under Grant No.2020ZTE01-03.
文摘This paper proposes a raptor-like low-density parity-check(RL-LDPC)code design together with the corresponding decoder hardware architecture aiming at next-generation mobile communication.A new kind of protograph different from the 5G new radio(NR)LDPC basic matrix is presented,and a code construction algorithm is proposed to improve the error-correcting performance.A multi-core layered decoder architecture that supports up to 100 Gbit/s throughput is designed based on the special protograph structure.
文摘RNA sequencing is the use of hight hroughput next generation sequencing technology to survey, characterize, and quantify the transcriptome of a genome. RNA sequencing has been used to analyze the pathogenesis of several malignancies such melanoma, lung cancer, and colorectal cancer. RNA sequencing can identify differential expression of genes(DEG's), mutated genes, fusion genes, and gene isoforms in disease states. RNA sequencing has been used in the investigation of several colorectal diseases such as colorectal cancer, inflammatory bowel disease(ulcerative colitis and Crohn's disease), and irritable bowel syndrome.
基金Supported by Science and Technology Project from the Beijing Municipal Administration Center of Parks(ZX2018016).
文摘In order to reveal the influence of different plant configurations on the microbial community structure and diversity in rhizosphere soil of Cotinus coggygria in Fragrant Hills park,the ITS+5.8S rDNA gene and 16S rDNA gene V3-V4 region sequencing analysis for fungi and bacteria,respectively,were conducted by high throughput sequencing(Illumina MiSeq).The results showed that the fungal diversity in the rhizosphere soil samples of C.coggygria in Fragrant Hills park in 2018 was significantly higher than that in 2016,and it was higher in the rhizosphere soil of healthy C.coggygria in Xunlupo than that in diseased ones in 2018.Verticillium dahliae,which is the causal agent of C.coggygria wilt,was detected in five soil samples.In 2018,the bacterial diversity in the rhizosphere soil of diseased C.coggygria in Xunlupo was the lowest,while it was the highest in the rhizosphere soil of healthy C.coggygria under Platycladus orientalis in Langfengting.
文摘High-throughput satellite (HTS) systems usually make use of Multibeam coverage at high frequency bands in order to offer broadband access of large areas. Multibeam coverage increases the available capacity through frequency reuse and spatial separation. However, one of its major drawbacks is inter- spot interference which considered the motivation to propose a new approach using a coding technique to distinguish between beams that will be employed to mitigate this interference without the need of frequency reuse. This approach makes the use of orthogonal codes to identify beams and allow using the total satellite bandwidth per beam. Proposed system double the bandwidth used in each beam and save the usage of antenna polarization resource used in former designs, which may be used as a multiple accessing resource inside the coded beams. The objective of this paper is to provide a comprehensive performance assessment methodology for the proposed approach. Result validation is introduced by comparing the proposed system performance with conventional systems that relay on the DVB standards.
文摘Xenobiotic drugs and chemicals directly interact with DNA,proteins,or other biomolecules in cells. These direct interactions with molecular targets may trigger a series of downstream effects on metabolic-biochemical and regulatory-signaling networks that can invoke cellular consequences leading to adaptive homeostatic or adverse pathological responses. Regulators for drug and chemicals safety have therefore since long required the testing of toxicity in animal models before drugs and pesticides can enter the market. The US National Research Council of the National Academy of Sciences,in its report,Toxicity Testing in the 21st Century: a Vision and a Strategy [1] ,proposed that toxicity testing should become less reliant on apical endpoints from whole animal tests and eventually rely instead on quantitative,doseresponse models based on information from in vitro assays and in vivo biomarkers,which can be used to screen large numbers of chemicals. The present paper reports about a combination of HTS in vitro assays that can be used to study the potential tumorigenic effect of xenobiotics ( drug targets,environmental chemicals) via a set of"sentinel"genes [2] that are functionally interrelated based on evidence weighted functional linkage network ( FLN ) log-likelihood scores ( Linghu et al [3] ) .
文摘Skin lightening and tanning are two major areas dominating the market of skincare and cosmetic products. Though the demands are originated from two different communities, the two areas share a same goal—skin colour tuning. The known safe compounds with skin colour tuning activities are limited. In contrary, Chinese medicinal herb provides a pool of natural bioactive compounds, which have been used in Asian countries for long time and have been tested for its toxicity. Here, we demonstrate a high throughput screening platform for potential compounds usable for skin colour tuning. From 147 natural compounds, 26 of them showed potential in skin tanning functions by using the high throughput melanogenesis platform based on the melanogenesis assay on B16 melanocytes. Five of them promoted melanogenesis by over 50%. Moreover, apart from 1, 8-dihydroxyanthraquinone, the other four compounds showed enhancement effect on tyrosinase activity. From the result, the compounds increased the Vmax of tyrosinase without changing the Km in a dose-dependent manner. Thus, there should be no irreversible structural change of the enzyme. Definitely, this report contributes to the development of personalization in skincare and cosmetic products.
基金the financial support of the National Natural Science Foundation of China(No.22168009)。
文摘Highly toxic phosgene,diethyl chlorophosphate(DCP)and volatile acyl chlorides endanger our life and public security.To achieve facile sensing and discrimination of multiple target analytes,herein,we presented a single fluorescent probe(BDP-CHD)for high-throughput screening of phosgene,DCP and volatile acyl chlorides.The probe underwent a covalent cascade reaction with phosgene to form boron dipyrromethene(BODIPY)with bright green fluorescence.By contrast,DCP,diphosgene and acyl chlorides can covalently assembled with the probe,giving rise to strong blue fluorescence.The probe has demonstrated high-throughput detection capability,high sensitivity,fast response(within 3 s)and parts per trillion(ppt)level detection limit.Furthermore,a portable platform based on BDP-CHD was constructed,which has achieved high-throughput discrimination of 16 analytes through linear discriminant analysis(LDA).Moreover,a smartphone adaptable RGB recognition pattern was established for the quantitative detection of multi-analytes.Therefore,this portable fluorescence sensing platform can serve as a versatile tool for rapid and high-throughput detection of toxic phosgene,DCP and volatile acyl chlorides.The proposed“one for more”strategy simplifies multi-target discrimination procedures and holds great promise for various sensing applications.
基金supported by the RGC General Research Fund under Grant No.17309620Hong Kong Quantum AI Lab Limited and Air@InnoHK of Hong Kong Government+4 种基金the support from National Natural Science Foundation of China(Grant Nos.22073007 and 22473022)Shenzhen Basic Research Key Project Fund(Grant No.JCYJ20220818103200001)National Natural Science Foundation of China(No.22273010)Department of Science and Technology of Jilin Province(20210402075GH)C-M C and F-F H acknowledge Guangdong Major Project of Basic and Applied Basic Research(Grant No.2019B030302009).
文摘The utilization of phosphorescent metal complexes as emissive dopants for organic light-emitting diodes(OLEDs)has been the subject of intense research.Cyclometalated Pt(Ⅱ)complexes are particularly popular triplet emitters due to their color-tunable emissions.To make them viable for practical applications as OLED emitters,it is essential to develop Pt(Ⅱ)complexes with high radiative decay rate constants(k_(r))and photoluminescence quantum yields(PLQY).To this end,an efficient and accurate prediction tool is highly desirable.In this work,we propose a general yet powerful protocol achieving metal complex generation,high throughput virtual screening(HTVS),and fast predictions with high accuracy.More than 3600 potential structures are generated in a synthesis-friendly manner.Moreover,three HTVS-machine learning(ML)models are established using different algorithms with carefully designed features that are suitable for metal complexes.Specifically,30 potential candidates are filtered out by HTVS-ML models with a three-tier screening rule and put into accurate predictions with experimental calibrationΔ-learning method.The highly accurate prediction approach further reduces the stress of experiments and inspires greater confidence in identifying the most promising complexes as excellent emitters.As a result,12 promising complexes(k_(r)>10^(5) s^(−1) and PLQY>0.6)with the same superior core structures are confirmed from over 3600 Pt-complexes.Experiments revealed that two very close complexes have excellent emission properties and are consistent with the prediction results,providing strong evidence for the efficacy of the proposed protocol.We expect this protocol will become a valuable tool,expediting the rational design and rapid development of novel OLED materials with desired properties.
