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P450-mediated dehydrotyrosine formation during WS9326 biosynthesis proceeds via dehydrogenation of a specific acylated dipeptide substrate

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Acta Pharmaceutica Sinica B 2023年第8期13卷 3561-3574页

作者： Songya Zhang Lin Zhang Anja Greule Julien Tailhades edward marschall Panward Prasongpholchai Daniel J.Leng Jingfan Zhang Jing Zhu Joe A.Kaczmarski Ralf B.Schittenhelm Oliver Einsle Colin J.Jackson Fabrizio Alberti Andreas Bechthold Youming Zhang Manuela Tosin Tong Si Max J.Cryle CAS Key Laboratory of Quantitative Engineering Biology Shenzhen Institute of Synthetic BiologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Institut für Biochemie Albert-Ludwigs-Universitat FreiburgFreiburg 79104Germany Department of Biochemistry and Molecular Biology the Monash Biomedicine Discovery InstituteMonash UniversityClayton 3800VICAustralia EMBL Australia Monash UniversityClayton 3800VICAustralia ARC Centre of Excellence for Innovations in Peptide and Protein Science Clayton 3800VICAustralia Department of Chemistry University of WarwickGibbet Hill RoadCoventry CV47ALUK School of Life Sciences University of WarwickGibbet Hill CampusCoventry CV47ALUK Research School of Chemistry the Australian National UniversityActon 2601ACTAustralia Monash Proteomics and Metabolomics Facility Monash UniversityClayton 3800VICAustralia Institute of Pharmaceutical Sciences Albert-Ludwigs-Universitat Freiburg79104Germany

WS9326A is a peptide antibiotic containing a highly unusual N-methyl-E-2-3-dehydrotyrosine(NMet-Dht)residue that is incorporated during peptide assembly on a non-ribosomal peptide synthetase(NRPS).The cytochrome P450 encoded by sas16(P450Sas)has been shown to be essential for the formation of the alkene moiety in NMet-Dht,but the timing and mechanism of the P450Sas-mediatedα,β-dehydrogenation of Dht remained ***,we show that the substrate of P450Sas is the NRPS-associated peptidyl carrier protein(PCP)-bound dipeptide intermediate(Z)-2-pent-1′-*** demonstrate that P450Sas-mediated incorporation of the double bond follows N-methylation of the Tyr by the N-methyl transferase domain found within the NRPS,and further that P450Sas appears to be specific for substrates containing the(Z)-2-pent-1’-enyl-cinnamoyl group.A crystal structure of P450Sas reveals differences between P450Sas and other P450s involved in the modification of NRPS-associated substrates,including the substitution of the canonical active site alcohol residue with a phenylalanine(F250),which in turn is critical to P450Sas activity and WS9326A ***,our results suggest that P450Sas catalyses the direct dehydrogenation of the NRPS-bound dipeptide substrate,thus expanding the repertoire of P450 enzymes that can be used to produce biologically active peptides.

关键词： Cytochrome P450 Non-ribosomal peptide synthetase Protein crystal structure Enzyme mechanism Natural products Peptideantibiotic

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Blast waveform tailoring using controlled venting in blast simulators and shock tubes

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Defence Technology（防务技术） 2024年第7期37卷 14-26页

作者： edward Chern Jinn Gan Alex Remennikov David Ritzel Faculty of Engineering and Information Sciences University of WollongongWollongongNSW2522Australia Dyn-FX Consulting Ltd 19 Laird Ave NorthAmherstburgONN9V 2T5Canada

A critical challenge of any blast simulation facility is in producing the widest possible pressure-impulse range for matching against equivalent high-explosive *** tubes and blast simulators are often constrained with the lack of effective ways to control blast wave profiles and as a result have a limited performance *** wave shaping techniques employed in some facilities are reviewed but often necessitate extensive geometric modifications,inadvertently cause flow anomalies,and/or are only applicable under very specific *** paper investigates controlled venting as an expedient way for waveforms to be tuned without requiring extensive modifications to the driver or existing geometry and could be widely applied by existing and future blast simulation and shock tube *** use of controlled venting is demonstrated experimentally using the Advanced Blast Simulator(shock tube)at the Australian National Facility of Physical Blast Simulation and via numerical flow simulations with Computational Fluid *** venting is determined as an effective method for mitigating the impact of re-reflected waves within the blast *** control method also allows for the adjustment of parameters such as tuning the peak overpressure,the positive phase duration,and modifying the magnitude of the negative phase and the secondary shock of the blast *** paper is concluded with an illustration of the potential expanded performance range of the Australian blast simulation facility when controlled venting for blast waveform tailoring as presented in this paper is applied.

关键词： Advanced blast simulator Shock wave propagation Far-field explosion Blast loads Blast waves Computational fluid dynamics

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Historic preservation theory:an anthology—readings from the 18th to the 21st Century,edited by Jorge *** books,***9780578547145

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Built Heritage 2024年第2期8卷 122-125页

作者： edward Denison The Bartlett School of Architecture UCL22 Gordon StreetWC1H 0QBLondonUK

As the world confronts a confluence of existential crises at the start of the new millennium,an anthology of theories concerned with historic preservation makes an important and timely contribution in and beyond the *** the early 21st century increasingly feeling like an age of reckoning,the hangover after centuries of profligacy,this collection of writings helps us to not only reassess our collective built pasts.

关键词： collective concerned preservation

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Reflections on Studying Huang Di Nei Jing in the West

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Chinese Medicine and Culture 2024年第1期7卷 72-76页

作者： edward Neal Apricot Grove Educational Services Portland 97213the United States of America Xinglin Institute for Early East Asian Medicine Portland 97213the United States of America

Huang Di Nei Jing(《黄帝内经》The Yellow Emperor’s Inner Classic) has been the source text of Chinese medicine knowledge and innovation for over two thousand years. Despite this key relevance, many of its ideas and practices have proven difficult to understand and implement fully into clinical practice. Cultural and language differences can be compounded with these challenges but may also present new opportunities for advancement and insight when studied by researchers outside of the originating culture. This article introduces the method of Classical-Text Archaeology and delves into the author’s two-decade journey of researching this text, with a discussion on cultural differences and issues of medical scholarship.

关键词： Huang Di Nei Jing Chinese medicine Nei Jing nature-based medicine Classical text research Global health Medical anthropology Classical-Text Archaeology

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Emerging glacier forelands alter carbon dynamics on the Tibetan Plateau

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Journal of Mountain Science 2024年第9期21卷 2871-2875页

作者： GAO Tanguang ZHANG Yulan MEADOWS Michael edward College of Earth and Environmental Sciences Lanzhou UniversityLanzhou 730000China Key Laboratory of Cryospheric Science and Frozen Soil Engineering Northwest Institute of Eco-Environment and ResourcesChinese Academy of SciencesLanzhou 730000China School of Geography and Ocean Sciences Nanjing UniversityNanjing 210023China Department of Environmental&Geographical Science University of Cape TownRondebosch 7701South Africa

The critical challenge of ongoing climate warming is resulting in glacier melting globally,a process accompanied by the formation of substantial glacier *** phenomenon emerges as a pivotal area of study,especially in the Tibetan Plateau(TP),known as the Third Pole and the Asian Water *** particular,the rapid retreat of temperate glaciers in the southeastern TP has led to the formation of expansive glacier *** forelands are not merely evidence of climate shifts but are also key areas for transformative carbon ***,the newly exposed land surface actively adjusts the balance of dissolved organic carbon,especially in meltwater,and influences the release of greenhouse gases from a range of sources including glacial lakes,subglacial sediments,and supraglacial/proglacial *** processes play a crucial role in the dynamics of atmospheric carbon *** from our intensive and detailed observations over several years,this perspective not only emphasizes the importance of the underexplored impact of glacier forelands on carbon cycles but also opens a window into understanding potential future trajectories in a warming world.

关键词： Glacier Climate warming Carbon release Tibetan Plateau

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DEM analysis of the influence of stirrer design on die filling with forced powder feeding

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Particuology 2024年第5期88卷 107-115页

作者： Chao Zheng edward Yost Ariel R.Muliadi Nicolin Govender Ling Zhang Chuan-Yu Wu School of Chemistry and Chemical Engineering University of SurreyGuildfordGU2 7XHUnited Kingdom Small Molecule Pharmaceutics GenentechInc.One DNA WaySouth San FranciscoCA94080USA

Die filling is a critical stage during powder compaction,which can significantly affect the product quality and *** this paper,a forced feeder is introduced attempting to improve the filling performance of a lab-scale die filling *** die filling process is analysed with a graphics processing units(GPU)enhanced discrete element method(DEM).Various stirrer designs are assessed for a wide range of process settings(i.e.,stirrer speed,filling speed)to explore their influence on the die filling performance of free-flowing *** results show that die filing with the novel helical-ribbon(i.e.,type D)stirrer design exhibits the highest filling ratio,implying that it is the most robust stirrer design for the feeder configuration ***,die filling performance with the type D stirrer design is a function of the stirrer speed and the filling speed.A positive variation of filling ratio(ηf>0%)can be ensured over the whole range of filling speed by adjusting the stirrer speed(i.e.,increasing the stirrer speed).The approach used in this study can not only help understand how the stirrer design affects the die filling performance but also guide the optimization of feeder system and process settings.

关键词： Discrete element method Die filling Forced feeding Stirrer design GPU computing

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Assimilation of GOES-R Geostationary Lightning Mapper Flash Extent Density Data in GSI 3DVar, EnKF, and Hybrid En3DVar for the Analysis and Short-Term Forecast of a Supercell Storm Case

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Advances in Atmospheric Sciences 2024年第2期41卷 263-277页

作者： Rong KONG Ming XUE edward R.MANSELL Chengsi LIU Alexandre O.FIERRO Center for Analysis and Prediction of Storms Norman Oklahoma 73072U.S.A University of Oklahoma Norman Oklahoma 73072U.S.A NOAA/National Severe Storms Laboratory NormanOklahoma 73072U.S A.4Zentralanstalt für Meteorologie und Geodynamik Department of Forecasting Models-ZAMGVienna 1190Austria

Capabilities to assimilate Geostationary Operational Environmental Satellite “R-series ”(GOES-R) Geostationary Lightning Mapper(GLM) flash extent density(FED) data within the operational Gridpoint Statistical Interpolation ensemble Kalman filter(GSI-EnKF) framework were previously developed and tested with a mesoscale convective system(MCS) case. In this study, such capabilities are further developed to assimilate GOES GLM FED data within the GSI ensemble-variational(EnVar) hybrid data assimilation(DA) framework. The results of assimilating the GLM FED data using 3DVar, and pure En3DVar(PEn3DVar, using 100% ensemble covariance and no static covariance) are compared with those of EnKF/DfEnKF for a supercell storm case. The focus of this study is to validate the correctness and evaluate the performance of the new implementation rather than comparing the performance of FED DA among different DA schemes. Only the results of 3DVar and pEn3DVar are examined and compared with EnKF/DfEnKF. Assimilation of a single FED observation shows that the magnitude and horizontal extent of the analysis increments from PEn3DVar are generally larger than from EnKF, which is mainly caused by using different localization strategies in EnFK/DfEnKF and PEn3DVar as well as the integration limits of the graupel mass in the observation operator. Overall, the forecast performance of PEn3DVar is comparable to EnKF/DfEnKF, suggesting correct implementation.

关键词： GOES-R lightning data assimilation EnKF EnVar

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Z-Score in Fetal Echocardiography–Is there Still Room for New Studies?

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Congenital Heart Disease 2024年第3期19卷 305-314页

作者： Marcio Fragoso Vieira Nathalie Jeanne Bravo-Valenzuela edward Araujo Júnior Department of Obstetrics Paulista School of MedicineFederal University of São Paulo(EPM-UNIFESP)São Paulo-SP04023-062Brazil Department of Obstetrics Federal University of Ceará(UFC)Sobral-CE60020-181Brazil Department of Pediatrics Pediatric CardiologySchool of MedicineFederal University of Rio de Janeiro(UFRJ)Rio de Janeiro-RJ21941-853Brazil

Congenital heart disease(CHD)is the most common type of birth defect,representing a significant cause of peri-natal morbidity and *** diagnosis of such anomalies is crucial for improving *** pro-tocols recommend a qualitative assessment of cardiac structures using two-dimensional ultrasound(2DUS)and color Doppler *** cases of suspected abnormalities,quantitative assessments through cardiac structure measurements and reference curves can aid in accurate *** to centiles widely employed in obste-trics,Z-scores provide more precise quantification of various cardiac structures,particularly at the extremes of the *** the development of reference curves and Z-scores has progressed over the past two decades,a lack of standardization in measurements and statistical methodology for their determination is *** reference curves requires adherence to specific recommendations to improve their *** purpose of this study is to provide a narrative review of the major studies that have generated reference values for cardiac struc-tures using 2DUS and Z-scores,to evaluate their methodology,and to provide a summary of the results.

关键词： Z-scores reference ranges fetal echocardiography

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CHINESE FLYING TAXI

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今日民航 2024年第1期 126-129页

作者： edward White 不详

A Shanghai flying taxi company says that China's"low altitude"industry is edging ahead of western rivals,thanks to more supportive regulators,technological breakthroughs and cut-throat competition in the Chinese logistics *** total market created by electric vertical takeoff and landing,or eVTOL,aircraft is forecast to be worth$1.5tn a year by 2040 in a base-case assessment by Morgan Stanley analysts,with potential customers across airlines,logistics,emergency services,agriculture,tourism and securityoperations.

关键词： breakthrough operations tourism

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Contraceptive behaviors and awareness in an urban slum community of south India

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Asian pacific Journal of Reproduction 2024年第4期13卷 160-168页

作者： Monica Albert Sekhar Shanthi edward Angeline Grace Sushmitha G Shirley Esther Priscilla Department of Community Medicine Sree Balaji Medical College and Hospital(SBMCH)ChennaiIndia

Objective:To assess the factors associated with knowledge,attitude and behavior of contraception use among urban slum population in ***:A cross-sectional study was conducted in the urban slum of Anakaputhur,*** couples between ages of 19-49 years and living in slum areas were taken up for the study by simple random *** women,postnatal and postmenopausal women were excluded from the *** collection was done using a pretested structured questionnaire focusing on details regarding contraception knowledge,attitude,and *** analysis was done using IBM SPSS version *** test like Chi square and odds ratio(OR)were used to identify association between knowledge,attitude,and behavior of contraception with the associated variables and enter method of logistic regression analysis was ***:Out of the 360 respondents,228 were females,with a mean age of(34±5)*** 43%demonstrated adequate knowledge of contraception use,and 91%were aware of at least one contraceptive ***,72%exhibited a positive attitude towards contraceptive ***,43%(155 individuals)did not utilize any contraceptive *** contraceptive users,intrauterine devices were the most commonly adopted,followed by barrier methods and female *** was significant association between knowledge of contraception and education(aOR 7.29,95%CI 2.93-18.10,P<0.05),age(aOR 2.04,95%CI 1.19-3.50,P<0.05)and socioeconomic class(aOR 3.66,95%CI 1.71-7.85,P<0.05;aOR 3.97,95%CI 2.12-7.49,P<0.05).Regarding attitude towards contraception use,education(aOR 8.54,95%CI 2.35-31.03,P<0.05),sex(aOR 0.15,95%CI 0.06-0.37,P<0.05),age(aOR 0.53,95%CI 0.28-0.99,P<0.05),socio-economic class(aOR 4.42,95%CI 1.97-9.92,P<0.05;aOR 9.83,95%CI 3.63-26.58,P<0.05)and number of children(aOR 10.04,95%CI 4.26-23.66,P<0.05)were the variables that had a significant ***:These findings underscore the imperative for enhanced d

关键词： Family planning Unmet need Sterilization Knowledge Practice Urban slum

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