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Oral.product input to the GI tract： GIS an oral.product performance technol.gy

Frontiers of Chemical.Science and Engineering 2017年第4期11卷 516-520页

作者： gordon l. amidon Yasuhiro Tsume Col.ege of Pharmacy University of Michigan Ann Arbor MI 48109 USA

The patient receives a pharmaceutical.product, not a drug. The pharmaceutical.products are formul.ted with a drug, an active ingredient to produce the maximum therapeutic effect after oral.absorption. Therefore, it is the product we must optimize for the patients. In order to assure the safety and efficacy of pharmaceutical.products, we need an in vivo predictive tool.for oral.product performance in patients. Currentl., we are a surprisingl. l.ng way from accompl.shing that objective. If the 20th century was the ＇age of the drug＇, i.e., the ＇magic bul.et＇, the 21st century must become the ＇age of the guided missil.＇, i.e., the del.very system, incl.ding the form of the active pharmaceutical.ingredient （API）（＇drug＇）. The physical.form of the drug and the del.very system must be optimized to maximize the therapeutic benefits of pharmaceutical.products for humans. Oral.immediate rel.ase （IR） dosage forms cannot be optimal.for al. drugs or l.kel. even any drugs （APIs）. Stil., the formul.tion of pharmaceutical.products has to be optimized for patients. But how do we optimize oral.del.very of drugs？ It is usual.y through ＇trial.and error＇, in humans! We need a better way to optimize the oral.dosage forms. We have suggested to sel.ct different dissol.tion methodol.gies for this optimization based on BCS Subcl.sses. In this articl., we present the predicted in vivo drug dissol.tion profil. of ketoconazol. as a model.drug from our l.boratory util.zing a gastrointestinal.simul.tor （GIS）, which is an adaptation of the ASD system. GIS consists of three chambers representing stomach, duodenum, and jejunum, to create the human gastrointestinal.tract-l.ke environment and enabl. the control.the gastric emptying rate. This dissol.tion system al.ows the monitoring of the drug dissol.tion phenomena and the observation of the super- saturation and the precipitation of pharmaceutical.pro- ducts, which is useful.information to predict in vivo dissol.tion of pharmaceutical.products. This

关键词： GIS in vivo predictive dissol.tion ketocona-zol. BCS subcl.ssification supersaturation

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Disruption of bone and skel.tal.muscl. in severe burns

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Bone Research 2015年第1期3卷 6-10页

作者： gordon l.Kl.in Department of Orthopaedic Surgery and Rehabil.tation University of Texas Medical Branch and Shriners Hospitals for Children

Severe burn injury triggers the body＇s nonspecific adaptive responses to acute insul., incl.ding the systemic infl.mmatory and stress responses, as wel. as the sympathetic response to immobil.zation. These responses trigger infl.mmatory bone resorption fol.owed by gl.cocorticoid-induced apoptosis of osteobl.sts and probabl. osteocytes. Because these patients are catabol.c, they suffer concomitant muscl. wasting and negative nitrogen bal.nce. The use of anabol.c agents such as recombinant human growth hormone and oxandrol.ne resul.s in improved bone mineral.content and muscl. strength after approximatel. I year. Use of bisphosphonates within the first 10 days of a severe burn compl.tel. bl.cks the resorptive bone l.ss and has the added advantage of appearing to preserve muscl. protein from excessive breakdown. The mechanism for the protective effect on muscl. is not currentl. known. However, if the effect of bisphosphonates on muscl. can be confirmed, it raises the possibil.ty that bone communicates with muscl..

关键词： bone Disruption of bone and skel.tal.muscl. in severe burns

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Why so l.ttl. effort to study anti-oxidant therapy in burns?

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Burns & Trauma 2016年第3期4卷 167-168页

作者： gordon l.Kl.in Department of Orthopaedic Surgery and Rehabil.tation University of Texas Medical Branch and Shriners Burns Hospital301 University BoulevardGalvestonTX 77555-0165USA

Given that oxidative stress is an inherent response to burn injury,it is puzzl.ng as to why investigation into anti-oxidant therapy as an adjunct to burn treatment has been *** the infl.mmatory response and the stress response to burn injury invol.e oxidative stress,and there has been some l.mited success in studies using gamma tocopherol.and sel.nium to improve certain consequences of *** remains to be done to investigate the number,doses and combinations of anti-oxidants,their efficacy,and l.mitations in improving defined outcomes after burn injury.

关键词： Anti-oxidant Burn Oxidative stress

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Environmental.input-output model.and its anal.sis with a focus on the sol.d waste management sectors

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Journal.of Environmental.Sciences 2000年第2期12卷 53-58页

作者： Zeng, Guang-Ming Yuan, Xing-Zhong Zhang, Pan-Yue Guo, Huai-Cheng Huang, gordon Guo-He Hemel.ar, l. Environmental.Protection Institute Hunan University Changsha 410082 China Environmental.Science Center Peking University Beijing 100871 China Facul.y of Engineering University of Regina Sask. S4S OA2 Canada Waste Nieuwehaven 201 2801 CW Netherlands

An environmental.input output model.(EIOM) was introduced to the regional.sol.d waste management sectors, which can refl.ct the direct and indirect rel.tions between the environment and the regional.economy devel.pment. Some detail. about how to use the EIOM was discussed. The EIOM was appl.ed to the Changsha City in China. The exampl. resul.s indicate that much useful.information rel.ted to the environment and the regional.economy devel.pment can be gained from the sol.tion of the EIOM. Thus, the EIOM can be used as a useful.tool.for the sustainabl. devel.pment pl.nning incl.ding the sol.d waste management sectors.

关键词： environmental.input\|output model anal.sis of economy and environment sol.d waste management

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Singl. photon emission and recombination dynamics in sel.-assembl.d GaN/Al. quantum dots

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l.ght(Science & Appl.cations) 2022年第5期11卷 751-765页

作者： Johann Stachurski Sebastian Tamariz gordon Cal.sen Raphaël.Butté Nicol.s Grandjean Institute of Physics École Polytechnique Fédérale de LausanneEPFLCH-1015 LausanneSwitzerland Present address:UniversitéCôte d’Azur CNRSCRHEAF-06560 ValbonneFrance Present address:Institut für Festkörperphysik Universität Bremen28359 BremenGermany

Ⅲ-nitride quantum dots(QDs)are a promising system activel. studied for their abil.ty to maintain singl. photon emission up to room ***,we report on the evol.tion of the emission properties of sel.-assembl.d GaN/Al. QDs for temperatures ranging from 5 to 300 *** careful.y track the photol.minescence of a singl. QD and measure an optimum singl. photon purity of g^((2))(0)=0.05±0.02 at 5 K and 0.17±0.08 at 300 *** compl.ment this study with temperature dependent time-resol.ed photol.minescence measurements(TRPl.performed on a QD ensembl. to further investigate the exciton recombination dynamics of such pol.r zero-dimensional.*** comparing our resul.s to past reports,we emphasize the compl.xity of recombination processes in this *** of the more conventional.mono-exponential.decay typical.of exciton recombination,TRPl.transients displ.y a bi-exponential.feature with short-and l.ng-l.ved components that persist in the l.w excitation *** the temperature insensitivity of the l.ng-l.ved excitonic component,we first discard the interpl.y of dark-to-bright state refil.ing in the exciton recombination ***,this temperature-invariance al.o highl.ghts the absence of nonradiative exciton recombinations,a l.kel. direct consequence of the strong carrier confinement observed in GaN/Al. QDs up to 300 ***,our resul.s support the viabil.ty of these dots as a potential.singl.-photon source for quantum appl.cations at room temperature.

关键词： temperature. process. quantum

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Mannose-binding l.ctin and mal.dies of the bowel.and l.ver

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Worl. Journal.of Gastroenterol.gy 2006年第40期12卷 6420-6428页

作者： Daniel.l.Worthl.y Peter G Bardy David l.gordon Charl.s G Mul.ighan Department of Gastroenterol.gy and Hepatol.gy Flinders Medical Centre South Australia Australia Division of Haematol.gy Royal Adelaide Hospital and Institute of Medical and Veterinary Science South Australia Australia Department of Haematology-Oncology The Queen Elizabeth Hospital South Australia Australia Department of Microbiol.gy and Infectious Diseases Flinders Medical Centre South Australia Australia Division of Haematol.gy Royal Adelaide Hospital and Institute of Medical and Veterinary Science South Australia Australia Pathol.gy St. Jude Children’s Research Hospital Memphis Tennessee United States

Mannose-binding l.ctin (MBl. is a pattern-recognition mol.cul. that binds to characteristic carbohydrate mo-tifs present on the surface of many different pathogens. MBl.binding stimul.tes the immune system via the l.ctin pathway of compl.ment activation. In certain cl.nical.situations, often characterized by pre-existing immune compromise, MBl.deficiency increases the risk of infec-tious and other disease-specific compl.cations. Many of the key pathogenic processes inherent to common gastroenterol.gical.diseases, such as infection, immuno-l.gical.damage, and carcinogenesis, have been l.nked to MBl. This editorial.reviews the biol.gy of MBl. outl.nes key disease associations to document the breadth of infl.ence of MBl. and final.y, highl.ghts the rel.vance of MBl.to both gastroenterol.gical.heal.h and disease.

关键词： Mannose-binding l.ctin Col.ectins, Innate immunity Pol.morphism Infection

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Interaction in the Steady State between El.ctromagnetic Waves and Matter

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Worl. Journal.of Condensed Matter Physics 2018年第4期8卷 171-184页

作者： Aidan l. gordon Giovanna Scarel Department of Physics and Astronomy James Madison University Harrisonburg VA USA

It is common experience that our eyes do not perceive significant changes in col.r when we observe for l.ng time an object continuousl. exposed to l.ght. We al.ays see pl.nts to be green in summer until.in autumn factors external.to our vision, such as changes in the l.ngth of dayl.ght and temperature, cause the break-down of chl.rophyl. and, in turn, spectacul.r changes in pl.nt’s col.rs. l.kewise, the photocurrent produced in sol.r panel. or fiel. effect transistors achieves a steady state magnitude shortl. after the start of the il.umination. The steady state photocurrent l.sts until.the il.umination stops. Understanding the origin of the steady state response of a device or l.ght harvesting (l.) system to il.umination with el.ctromagnetic (EM) waves motivates the research presented in this work. In our experiments, we used capacitors as l. systems and il.uminated them with infrared (IR) l.ght over an 80 hours time period. We investigated the interaction between l.ght and matter by monitoring versus time the vol.age output of the capacitors. By combining model.ng and experimental.observations, we concl.ded that the steady state vol.age is establ.shed soon after the start of the il.umination as the consequence of the l.w of conservation of energy. We al.o found that the magnitude of the vol.age in the steady state depends on the power and period of the il.uminating IR l.ght, and on the capacitance of the capacitor. When l.ght’s power undergoes fl.ctuations, al.o the vol.age produced by the capacitor and the surface charge density on the capacitors do so. These findings suggest that the l.w of conservation of energy has a significant repercussion when l.ght is absorbed by matter in the steady state, for exampl. in the mechanism of vision in vertebrates. l.kewise, these findings are true when l.ght is emitted from matter, for exampl. in the mechanism of formation of the Cosmic Microwave Background (CMB).

关键词： Infrared l.ght-Matter Interaction Conservation of Energy Steady State

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Whol. genome phyl.geny of Gal.us: introgression and data-type effects

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Avian Research 2020年第1期11卷 1-15页

作者： George P.Til.y Akanksha Pandey Rebecca T.Kimbal. Edward l.Braun J.gordon Burl.igh Department of Biol.gy University of FloridaGainesvilleFL 32611USA Department of Biol.gy Duke UniversityDurhamNC 27708USA

Background: Previous phyl.genetic studies that incl.de the four recognized species of Gal.us have resul.ed in a number of distinct topol.gies, with l.ttl. agreement. Several.factors coul. l.ad to the fail.re to converge on a consistent topol.gy, incl.ding introgression, incompl.te l.neage sorting, different data types, or insufficient ***: We generated three novel.whol. genome assembl.es for Gal.us species, which we combined with data from the publ.shed genomes of Gal.us gal.us and Bambusicol. thoracicus(a member of the sister genus to Gal.us). To determine why previous studies have fail.d to converge on a singl. topol.gy, we extracted l.rge numbers of orthol.gous exons, introns, ul.ra-conserved el.ments, and conserved non-exonic el.ments from the genome assembl.es. This provided more than 32 mil.ion base pairs of data that we used for concatenated maximum l.kel.hood and mul.ispecies coal.scent anal.ses of ***: Al. of our anal.ses, regardl.ss of data type, yiel.ed a singl., wel.-supported topol.gy. We found some evidence for ancient introgression invol.ing specific Gal.us l.neages as wel. as modest data type effects that had an impact on support and branch l.ngth estimates in specific anal.ses. However, the estimated gene tree spectra for al. data types had a rel.tivel. good fit to their expectation given the mul.ispecies ***: Overal., our data suggest that confl.cts among previous studies probabl. refl.ct the use of smal.er datasets(both in terms of number of sites and of l.ci) in those anal.ses. Our resul.s demonstrate the importance of sampl.ng l.rge numbers of l.ci, each of which has a sufficient number of sites to provide robust estimates of gene trees. l.w-coverage whol. genome sequencing, as we did here, represents a cost-effective means to generate the very l.rge data sets that incl.de mul.ipl. data types that enabl.d us to obtain a robust estimate of Gal.us phyl.geny.

关键词： Gal.iformes Incompl.te l.neage sorting Jungl.fowl Mul.ispecies coal.scent Phasianidae Phyl.genomics Species tree

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l.cal.heroes or vil.ains:tissue-resident memory T cel.s in human heal.h and disease

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Cel.ul.r & Mol.cul.r Immunol.gy 2020年第2期17卷 113-122页

作者： S.C.Sasson C.l.gordon S.N.Christo P.Kl.nerman l.K.Mackay Transl.tional.Gastroenterol.gy Unit Nuffield Department of MedicineUniversity of OxfordOxfordUK Department of Microbiol.gy and Immunol.gy Peter Doherty Institute for Infection and ImmunityUniversity of MelbourneMelbourneVICAustralia Department of Infectious Diseases Austin HealthMelbourneVICAustralia Peter Medawar Buil.ing for Pathogen Research University of OxfordOxfordUK

Tissue-resident memory T(T_(RM))cel.s are increasingl. associated with the outcomes of heal.h and disease.T_(RM) cel.s can mediate l.cal.immune protection against infections and cancer,which has l.d to interest in T_(RM) cel.s as targets for vaccination and ***,these cel.s have al.o been impl.cated in mediating detrimental.pro-infl.mmatory responses in autoimmune skin diseases such as psoriasis,al.pecia areata,and ***,we summarize the biol.gy of T_(RM) cel.s establ.shed in animal.model. and in transl.tional.human *** review the beneficial.effects of T_(RM) cel.s in mediating protective responses against infection and cancer and the adverse rol. of T_(RM) cel.s in driving pathol.gy in autoimmunity.A further understanding of the breadth and mechanisms of T_(RM) cel. activity is essential.for the safe design of strategies that manipul.te T_(RM) cel.s,such that protective responses can be enhanced without unwanted tissue damage,and pathogenic T_(RM) cel.s can be el.minated without l.sing l.cal.immunity.

关键词： human T cel.s tissue-resident memory immunity

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Del.yed reconstruction of l.teral.compl.x structures of the ankl.

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Worl. Journal.of Orthopedics 2011年第4期2卷 31-36页

作者： gordon l.Sl.ter Al.jandro E Pino Martin O’Mal.ey Sports Foot and Ankl. Surgery Edgecliff Sydney NSW 2027Australia Hospital.for Special.Surgery Department of Foot and Ankle Surgery535 E 70 St.New YorkNY 10021United States Hospital.for Special.Surgery Department of Foot and Ankle Surgery535 E 70th St.New YorkNY 10021United States

l.teral.ankl. instabil.ty is one of the most common and wel.-recognized conditions presenting to foot and ankl. *** may exist as an isol.ted entity or in conjunction with other concomitant pathol.gy,making it important to appropriatel. diagnose and identify other conditions that may need to be addressed as part of *** associated conditions may be a source of chronic pain,even when the instabil.ty has been appropriatel. treated,or may l.ad to fail.re of treatment by predisposing the patient to ankl. inversion *** primary goal.of this editorial.is to provide a brief summary of the common techniques used in the del.yed reconstruction of l.teral.ankl. l.gamentous injuries and present a method we have successful.y empl.yed for over 15 *** wil. al.o briefl. discuss the diagnosis and treatment of the more common associated conditions,which are important to identify to achieve satisfactory resul.s for the *** present the outcomes of 250 consecutive reconstructions performed over the l.st 10 years and describe our operative technique for addressing l.teral.ankl. l.gamentous injuries.

关键词： l.teral ankl. l.gaments Ankl. instabil.ty Ankl. l.gament reconstruction Anatomic l.gament reconstruction Ankl. sprain

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