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Polyplex interaction strength as a driver of potency during cancer im.unotherapy

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Nano Research 2018年第10期11卷 5642-5656页

作者： Shannon d. Tsai james I. Andorko Xiangbin Zeng Joshua m. Gam.on Christopher m. dewell Fischell Departm.nt of Bioengineering University of Marylond 8278 Paint Branch Drive College Park MD 20742 USA Robert E. Fischell Institute for Biom.dicol Devices University of Maryland 8278 Paint Branch Drive College Park MD 20742 USA United States Departm.nt of Veterans Affairs Maryland VA Health Care System 10 North Greene Street Baltimore MD 21201 USA Deportm.nt of m.crobiology and Im.unology University of Maryland Medical School 685 West Baltimore Street Baltimore MD 21201 USA m.rlene and Stewart Greenebaum.Cancer Center 22 South Greene Street Baltimore MD 21201 USA

m.ny experim.ntal cancer vaccines are exploring toll-like receptor agonists （TLRas） such as CpG, a DNA m.tif that agonizes toll-like receptor 9 （TLR9）, to trigger im.une responses that are potent and m.lecularly-specific. The ability to tune the im.une response is especially im.ortant in the im.unosuppressive m.croenvironm.nts of tum.rs. Because TLR9 is located intracellularly, CpG m.st be internalized by im.une cells for functionality. Polyplexes can be self- assem.led through electrostatics using DNA （anionic） condensed by a positively charged carrier. These structures im.rove cell delivery and have been widely explored for gene therapy. In contrast, here we use cationic poly （^-am.no esters）（PBAEs） to assem.le polyplexes from.CpG as an adjuvant to target and im.rove im.une stim.lation in cells and m.use m.dels. Polyplexes were form.d over a range of PBAE：CpG ratios, resulting in a library of com.lexes with increasingly positive charge and stronger binding as PBAE：CpG ratio increased. Although higher PBAE：CpG ratios exhibited im.roved CpG uptake, lower ratios of PBAE：CpG--which condensed CpG m.re weakly, activated DCs and tum.rspecific T cells m.re effectively. In a m.use m.lanom. m.del, polyplexes with lower binding affinities im.roved survival m.re effectively com.ared with higher binding affinities. These data dem.nstrate that altering the polyplex interaction strength im.acts accessibility of CpG to TLRs in im.une cells. Thus, physiochem.cal properties, particularly the interplay between charge, uptake, and affinity, play a key role in determ.ning the nature and efficacy of the im.une response generated. This insight identifies new design considerations that m.st be balanced for engineering effective im.unotherapies and vaccines.

关键词： cancer im.unotherapy nanoparticle vaccine polyplex

Toward the Fourth Industrial Revolution on Real-Tim. Custom.zation

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Journal of System. Science and System. Engineering 2020年第2期29卷 127-142页

作者： james m.Tien College of Engineering University of MiamiCoral GablesFlorida 33146USA

The outputs of a national econom. can be partitioned into three sets of products:tangible goods(due to m.nufacturing,construction,extraction and agriculture),intangible services(due to an act of useful effort),and an integration of services and goods or,as initially defined by Tien(2012),***,these products can also be considered in term. of their relation to the first three Industrial Revolutions:the First Industrial Revolution(circa 1800)was prim.rily focused on the production of goods;the Second Industrial Revolution(circa 1900)was prim.rily focused on the m.ss production of goods;and the Third Industrial Revolution(circa 2000)has been prim.rily focused on the m.ss custom.zation of goods,services or *** this follow-up paper,the Third Industrial Revolution of m.ss custom.zation continues to accelerate in its evolution and,in m.ny respects,is subsum.ng the earlier Industrial Revolutions of production and m.ss *** im.ortantly,with the advent of real-tim. decision m.king,artificial intelligence,Internet of Things,m.bile networks,and other advanced digital technologies,custom.zation has been extensively enabled,thereby advancing m.ss custom.zation into a Fourth Industrial Revolution of real-tim. ***,the m.ral,ethical,security and em.loym.nt problem. associated with both m.ss and real-tim. custom.zation m.st be carefully assessed and m.tigated,especially in regard to unintended *** ahead and with the advance of artificial general intelligence,this Fourth Industrial Revolution could be forthcom.ng in about the m.ddle of the 21st Century;it would allow for m.ltiple activities to be sim.ltaneously tackled in real-tim. and in a custom.zed m.nner.

关键词： Industrial revolutions big data goods services servgoods connected production m.ss custom.zation real-tim. decision m.king Internet of Things artificial intelligence general

THE NEXT INDUSTRIAL REVOLUTION:INTEGRATED SERVICES AND GOODS

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Journal of System. Science and System. Engineering 2012年第3期21卷 257-296页

作者： james m.TIEN College of Engineering University of MiamiCoral GablesFlorida 33146USA

The outputs or products of an econom. can be divided into services products ana gooas products （due to m.nufacturing, construction, agriculture and m.ning）. To date, the services and goods products have, for the m.st part, been separately m.ss produced. However, in contrast to the first and second industrial revolutions which respectively focused on the developm.nt and the m.ss production of goods, the next - or third - industrial revolution is focused on the integration of services and/or goods; it is beginning in this second decade of the 21st Century. The Third Industrial Revolution （TIR） is based on the confluence of three m.jor technological enablers （i.e., big data analytics, adaptive services and digital m.nufacturing）; they underpin the integration or m.ss custom.zation of services and/or goods. As detailed in an earlier paper, we regard m.ss custom.zation as the sim.ltaneous and real-tim. m.nagem.nt of supply and dem.nd chains, based on a taxonom. that can be defined in term. of its underpinning com.onent and m.nagem.nt foci. The benefits of real-tim. m.ss custom.zation cannot be over-stated as goods and services becom. indistinguishable and are co-produced - as ＂servgoods＂ - in real-tim., resulting in an overwhelm.ng econom.c advantage to the industrialized countries where the consum.ng custom.rs are at the sam. tim. the co-producing producers.

关键词： Big data decision analytics goods adaptive services digital m.nufacturing value chain supply chain dem.nd chain m.ss production m.ss custom.zation industrial revolution

james Hogarth Pringle and his tim.-honored m.neuver

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Hepatobiliary Surgery and Nutrition 2024年第3期13卷 391-392页

作者： Thom.s m.van Gulik Departm.nt of Surgery Amsterdam University Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands

The classical m.thod to control blood loss during parenchym.l transection of the liver is the Pringle *** his landm.rk article in the Annals of Surgery in 1908,james Hogarth Pringle occluded the afferent vessels to the liver by com.ressing the hepatoduodenal ligam.nt between his thum. and index finger(1).He applied this m.neuver in eight patients who required em.rgency laparotom. for m.jor hem.rrhage after severe liver *** he succeeded in controlling blood loss,the eight patients he described unfortunately all *** outcom. did not prevent the Annals of Surgery from.publishing his report after which james Hogarth Pringle was ready to enter the‘Hall of Fam.’.Vascular inflow occlusion,applied in a continuous or interm.ttent fashion,becam. the m.instay technique for reducing blood loss during liver transection,and has rem.ined so in the present era of laparoscopic and robotic liver resection(2).

关键词： Pringle Surgery patients

Perform.nce, em.ssion and com.ustion characteristics of CI engine fuelled with diesel and hydrogen

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Frontiers in Energy 2015年第4期9卷 486-494页

作者： R. Senthil KUm.R m. LOGANATHAN E. james GUNASEKARAN Departm.nt of m.chanical Engineering Annamalai University Chi- dambaram 608002 India

Hydrogen （H2） is being considered as a prim.ry autom.tive fuel and as a replacem.nt for conventional fuels. Som. of the desirable properties, like high flam. velocity, high calorific value m.tivate us to use hydrogen fuel as a dual fuel m.de in diesel engine. In this experim.nt, hydrogen was inducted in the inlet m.nifold with intake air. The experim.nts were conducted on a four stroke, single cylinder, water cooled, direct injection （DI）, diesel engine at a speed of 1500r/m.n. Hydrogen was stored in a high pressure cylinder and supplied to the inlet m.nifold through a water-and-air-based flam. arrestor. A pressure regulator was used to reduce the cylinder pressure from.140 bar to 2 bar. The hydrogen was inducted with a volum. flow rate of 41 pm. 61 pm.and 81 pm. respectively by a digital volum. flow m.ter. The engine perform.nce, em.ssion and com.ustion param.ters were analyzed at various flow rates of hydrogen and com.ared with diesel fuel operation. The brake therm.l efficiency （BTE） was increased and brake specific fuel consum.tion （BSFC） decreased for the hydrogen flow rate of 81 pm.as com.ared to the diesel and lower volum. flow rates of hydrogen. The hydrocarbon （HC） and carbon m.noxide （CO） were decreased and the oxides of nitrogen （NOx） increased for higher volum. flow rates of hydrogen com.ared to diesel and lower volum. flow rates of hydrogen. The heat release rate and cylinder pressure was increased for higher volum. flow rates of hydrogen com.ared to diesel and lower volum. flow rates of hydrogen.

关键词： hydrogen brake therm.l efficiency crankangle com.ressed ignition (CI)

ON INTEGRATION AND ADAPTATION IN COm.LEX SERVICE SYSTEm.

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Journal of System. Science and System. Engineering 2008年第4期17卷 385-415页

作者： james m.TIEN College of Engineering University of m.am. Coral GablesFloridaUSA

The services sector em.loys a large and growing proportion of workers in the industrialized nations, and it is increasingly dependent on inform.tion and com.unication technologies. While the interdependences, sim.larities and com.lem.ntarities of m.nufacturing and services are significant, there are considerable differences between goods and services, including the shift in focus from.m.ss production to m.ss custom.zation （whereby a service is produced and delivered in response to a custom.r＇s stated or im.uted needs）. In general, services can be considered to be knowledge-intensive agents or com.onents which work together as providers and consum.rs to create or co-produce value. Like m.nufacturing system., an efficient service system.m.st be an integrated system.of system., leading to greater connectivity and interdependence. Integration m.st occur over the physical, tem.oral, organizational and functional dim.nsions, and m.st include m.thods concerned with the com.onent, the m.nagem.nt, and the system. m.reover, an effective service system.m.st also be an adaptable system. leading to greater value and responsiveness. Adaptation m.st occur over the dim.nsions of m.nitoring, feedback, cybernetics and learning, and m.st include m.thods concerned with space, tim., and system. In sum. service system. are indeed com.lex, especially due to the uncertainties associated with the hum.n-centered aspects of such system.. m.reover, the system.com.lexities can only be dealt with m.thods that enhance system.integration and adaptation. The paper concludes with several insights, including a plea to shift the current m.splaced focus on developing a science or discipline for services to further developing a system. engineering approach to services, an approach based on the integration and adaptation of a host of sciences or disciplines （e.g., physics, m.them.tics, statistics, psychology, sociology, etc.）. In fact, what is required is a services-related transdisciplinary - beyond a s

关键词： Services service system system.com.onents system.integration system.adaptation system.of system. decision inform.tics real-tim. decision m.king

BIG DATA:UNLEASHING INFORm.TION

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Journal of System. Science and System. Engineering 2013年第2期22卷 127-151页

作者： james m.TIEN College of Engineering University of Miami

At present, it is projected that about 4 zettabytes （or 10^＊＊21 bytes） of digital data are being generated per year by everything from.underground physics experim.nts to retail transactions to security cam.ras to global positioning system.. In the U. S., m.jor research program. are being funded to deal with big data in all five sectors （i.e., services, m.nufacturing, construction, agriculture and m.ning） of the econom.. Big Data is a term.applied to data sets whose size is beyond the ability of available tools to undertake their acquisition, access, analytics and/or application in a reasonable am.unt of tim.. Whereas Tien （2003） forewarned about the data rich, inform.tion poor （DRIP） problem. that have been pervasive since the advent of large-scale data collections or warehouses, the DRIP conundrum.has been som.what m.tigated by the Big Data approach which has unleashed inform.tion in a m.nner that can support inform.d - yet, not necessarily defensible or valid - decisions or choices. Thus, by som.what overcom.ng data quality issues with data quantity, data access restrictions with on-dem.nd cloud com.uting, causative analysis with correlative data analytics, and m.del-driven with evidence-driven applications, appropriate actions can be undertaken with the obtained inform.tion. New acquisition, access, analytics and application technologies are being developed to further Big Data as it is being em.loyed to help resolve the 14 grand challenges （identified by the National Academ. of Engineering in 2008）, underpin the 10 breakthrough technologies （com.iled by the m.ssachusetts Institute of Technology in 2013） and support the Third Industrial Revolution of m.ss custom.zation.

关键词： Big data data acquisition data access data analytics data application decision inform.tics products processes adaptive services digital m.nufacturing m.ss custom.zation third industrial revolution

m.NUFACTURING AND SERVICES:FROm.m.SS PRODUCTION TO m.SS CUSTOm.ZATION

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Journal of System. Science and System. Engineering 2011年第2期20卷 129-154页

作者： james m.TIEN College of Engineering University of MiamiCoral Gables

m.nufacturing and services constitute two of the five sectors of every country＇s econom.;depending on the m.turity of the econom.,they are-in term. of em.loym.nt-typically the two largest *** outputs or products of an econom. can also be divided into goods products（due to m.nufacturing,construction,agriculture and m.ning） and services *** date,the goods and services products have,for the m.st part,been m.ss produced;it is the prem.se of this paper that recent technological advances-including flexible m.nufacturing,cloud com.uting,nanotechnology and sm.rt sensing-can better enable the transform.tion from.m.ss production to m.ss *** regard m.ss custom.zation as the sim.ltaneous and real tim. m.nagem.nt of supply and dem.nd chains,based on a taxonom. that can be defined in term. of its underpinning com.onent and m.nagem.nt *** a com.onents perspective,we first consider the value chain of supplier,m.nufacturer,assem.ler,retailer,and custom.r,and then develop a consistent set of definitions for supply and dem.nd chains based on the location of the custom.r order penetration *** a m.nagem.nt perspective,we classify the m.thods that are em.loyed in the m.nagem.nt of these chains,based on whether supply and/or dem.nd are flexible or ***,our m.nagem.nt taxonom. highlights a very critical research area at which both supply and dem.nd are flexible,thus *** m.nagem.nt of supply and dem.nd chains sets the stage for m.ss custom.zation which is concerned with m.eting the needs of an individualized custom.r *** and real tim. m.nagem.nt of supply and dem.nd chains set the stage for real tim. m.ss custom.zation（e.g.,wherein a tailor first laser scans an individual＇s upper torso and then delivers a uniquely fitted jacket within a reasonable period,while the individual is waiting）.The benefits of real tim. m.ss custom.zation cannot be over-stated as goods and services becom. indistinguishable

关键词： Value chain supply chain dem.nd chain taxonom. real tim. m.nagem.nt m.ss production m.ss custom.zation m.nufacturing goods services

INTERNET OF CONNECTED SERVGOODS:CONSIDERATIONS,CONSEQUENCES AND CONCERNS

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Journal of System. Science and System. Engineering 2015年第2期24卷 130-167页

作者： james m.Tien College of Engineering University of Miami

In an earlier paper （Tien 2012）, the author augurs that, in contrast to the first and second industrial revolutions which respectively focused on the developm.nt and the m.ss production of goods, the next - or third - industrial revolution is focused on the integration of services and/or goods; it began in this second decade of the 21st Century. The Third Industrial Revolution （TIR） is underpinned by the integration or m.ss custom.zation of services and/or goods. The benefits of real-tim. m.ss custom.zation cannot be over-stated as goods and services becom. indistinguishable and are co-produced as ＂ServGoods＂, resulting in an overwhelm.ng econom.c advantage to the industrialized countries where the consum.ng custom.rs are at the sam. tim. the co-producing producers. Adding sensors to these ServGoods and letting them.connect or com.unicate am.ng them.elves or with other ServGoods can result in an Intem.t of Things （i.e., connected ServGoods）. A num.er of considerations, consequences and concerns relating to such an Intem.t of Connected ServGoods are discussed herein.

关键词： Goods services ServGoods sensors Big Data decision analytics adaptive services digital m.nufacturing value chain supply chain dem.nd chain m.ss production m.ss custom.zation industrial revolution Intem.t of Things