bifurcations for the pH-regulated oscillations in a semibatch reactor (H2O2-Cu2+-S2O32-)
Scientia Horticulturae
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doi:10.1016/0304-4238(93)90047-T | How to Cite or Link Using DOICopyright © 1993 Published by Elsevier Science B.V.Permissions & ReprintsCPPU control of fruit morphogenesis in appleThis article is not included in your organization's subscription. However, you may be able to access this article under your organization's agreement with Elsevier.S. Tartarini, S. Sansavini and M. VenturaDipartimento di Colture Arboree, University of Bologna, Via Filippo Re 6, 40126, Bologna, ItalyAccepted 3 November 1992. ;Available online 14 October 2003.AbstractCPPU, a cytokinin-like substance derived from phenylurea, was applied to shoots, fruits, and to shoots + fruits of mature trees of apple cultivars ‘Golden Delicious’ clone B and ‘Red Delicious’ clone Clear Red 25 days after full bloom. While no influence on fruit morphogenesis was detected for the shoot only treatment, the fruit only and shoot + fruit applications enhanced fruit size and weight, though often inducing irregular elongation, a slight delay in colouring and a lower sugarcontent. No differences were recorded in the contents and degradation of pectic substances.Author Keywords: CPPU; cytokinin-like substance; Fruit morphogenesis; Malus domestica BorkhArticle OutlineStimulation of fruit growth of kiwifruit, Actinidia chinensis Planch., by N-(2-chloro-4-pyridyl)-N'-phenylurea, a diphenylurea-derivative cytokinin Original Research ArticleScientia Horticulturae, V olume 35, Issues 1-2, April 1988, Pages 109-115。
ijbc_2003国外混沌资料
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Hopf bifurcation
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Hopf bifurcationFrom Wikipedia, the free encyclopedia (Redirected from Andronov-Hopf bifurcation )Jump to: navigation , search In the mathematical theory of bifurcations , a Hopf or Poincaré–Andronov–Hopf bifurcation, named after Henri Poincaré, Eberhard Hopf , and Aleksandr Andronov , is a local bifurcation in which a fixed point of a dynamical system loses stability as a pair of complex conjugate eigenvalues of the linearization around the fixed point cross the imaginary axis of the complex plane . Under reasonably generic assumptions about the dynamical system, we can expect to see a small-amplitude limit cycle branching from the fixed point.For a more general survey on Hopf bifurcation and dynamical systems in general, see [1][2][3][4][5].Contents[hide ]● 1 Overview r 1.1 Supercritical / subcritical Hopf bifurcationsr 1.2 Remarks r1.3 Example ● 2 Definition of a Hopf bifurcation ● 3 Routh–Hurwitz criterionr 3.1 Sturm seriesr 3.2 Propositions ● 4 Example● 5 References●6 External links [edit ] Overview[edit ] Supercritical / subcritical Hopf bifurcationsThe limit cycle is orbitally stable if a certain quantity called the first Lyapunov coefficient is negative, and the bifurcation is supercritical. Otherwise it isunstable and the bifurcation is subcritical.The normal form of a Hopf bifurcation is:where z , b are both complex and λ is a parameter. WriteThe number α is called the first Lyapunov coefficient.●If α is negative then there is a stable limit cycle for λ > 0:whereThe bifurcation is then called supercritical.●If α is positive then there is an unstable limit cycle for λ < 0. The bifurcation is called subcritical.[edit ] Remarks The "smallest chemical reaction with Hopf bifurcation" was found in 1995 in Berlin, Germany [6]. The same biochemical system has been used in order to investigate how the existence of a Hopf bifurcation influences our ability to reverse-engineer dynamical systems [7].Under some general hypothesis, in the neighborhood of a Hopf bifurcation, a stable steady point of the system gives birth to a small stable limit cycle . Remark that looking for Hopf bifurcation is not equivalent to looking for stable limit cycles. First, some Hopf bifurcations (e.g. subcritical ones) do not imply the existence of stable limit cycles; second, there may exist limit cycles not related to Hopf bifurcations.[edit ] ExampleThe Hopf bifurcation in the Selkov system(see article). As the parameters change, a limitcycle (in blue) appears out of an unstableequilibrium.Hopf bifurcations occur in the Hodgkin–Huxley model for nerve membrane, the Selkov model of glycolysis , the Belousov–Zhabotinsky reaction , the Lorenz attractor and in the following simpler chemical system called the Brusselator as the parameter B changes:The Selkov model isThe phase portrait illustrating the Hopf bifurcation in the Selkov model is shown on the right. See Strogatz, Steven H. (1994). "Nonlinear Dynamics and Chaos" [1], page 205 for detailed derivation.[edit ] Definition of a Hopf bifurcationThe appearance or the disappearance of a periodic orbit through a local change in the stability properties of a steady point is known as the Hopf bifurcation. The following theorem works with steady points with one pair of conjugate nonzero purely imaginary eigenvalues . It tells the conditions under which this bifurcation phenomenon occurs.Theorem (see section 11.2 of [3]). Let J 0 be the Jacobian of a continuous parametric dynamical system evaluated at a steady point Z eof it. Suppose that all eigenvalues of J 0 have negative real parts except one conjugate nonzero purely imaginary pair. A Hopf bifurcation arises when these two eigenvalues cross the imaginary axis because of a variation of the system parameters.[edit ] Routh–Hurwitz criterionRouth–Hurwitz criterion (section I.13 of [5]) gives necessary conditions so that a Hopf bifurcation occurs. Let us see how one can use concretely this idea [8].[edit ] Sturm series Let be Sturm series associated to a characteristic polynomial P . They can be written in the form:The coefficients c i,0 for i in correspond to what is called Hurwitz determinants [8]. Their definition is related to the associated Hurwitz matrix .[edit ] PropositionsProposition 1. If all the Hurwitz determinants c i ,0 are positive, apart perhaps c k,0 then the associated Jacobian has no pure imaginary eigenvalues.Proposition 2. If all Hurwitz determinants c i ,0 (for all i in are positive, c k " 1,0 = 0 and c k" 2,1 < 0 then all the eigenvalues of the associated Jacobian have negative real parts except a purely imaginary conjugate pair.The conditions that we are looking for so that a Hopf bifurcation occurs (see theorem above) for a parametric continuous dynamical system are given by this last proposition.[edit ] Example Let us consider the classical Van der Pol oscillator written with ordinary differential equations:The Jacobian matrix associated to this system follows:The characteristic polynomial (in λ) of the linearization at (0,0) is equal to:P (λ) = λ2 " μλ + 1.The coefficients are: a 0 = 1,a 1 = " μ,a 2 = 1 The associated Sturm series is:The Sturm polynomials can be written as (here i = 0,1):The above proposition 2 tells that one must have:c 0,0 = 1 > 0,c 1,0 = " μ = 0,c 0,1 = " 1 < 0.Because 1 > 0 and 1 < 0 are obvious, one can conclude that a Hopf bifurcation may occur for Van der Pol oscillator if μ = 0.[edit ] References1. ^ a b Strogatz, Steven H. (1994). Nonlinear Dynamics and Chaos . Addison Wesley publishing company.2. ^ Kuznetsov, Yuri A. (2004). Elements of Applied Bifurcation Theory . New York: Springer-Verlag. ISBN 0-387-21906-4.3. ^ a b Hale, J.; Ko ak, H. (1991). Dynamics and Bifurcations . Texts in Applied Mathematics. 3. New York: Springer-Verlag.4. ^ Guckenheimer, J.; Myers, M.; Sturmfels, B. (1997). "Computing Hopf Bifurcations I". SIAM Journal on Numerical Analysis .5. ^ a b Hairer, E.; Norsett, S. P.; Wanner, G. (1993). Solving ordinary differential equations I: nonstiff problems (Second ed.). New York: Springer-Verlag.6. ^ Wilhelm, T.; Heinrich, R. (1995). "Smallest chemical reaction system with Hopf bifurcation". Journal of Mathematical Chemistry 17 (1): 1–14.doi :10.1007/BF01165134. http://www.fli-leibniz.de/~wilhelm/JMC1995.pdf .7. ^ Kirk, P. D. W.; Toni, T.; Stumpf, MP (2008). "Parameter inference for biochemical systems that undergo a Hopf bifurcation". Biophysical Journal 95 (2):540–549. doi :10.1529/biophysj.107.126086. PMC 2440454. PMID 18456830. /biophysj/pdf/PIIS0006349508702315.pdf .8. ^ a bKahoui, M. E.; Weber, A. (2000). "Deciding Hopf bifurcations by quantifier elimination in a software component architecture". Journal of SymbolicComputation 30 (2): 161–179. doi:10.1006/jsco.1999.0353. [edit] External links● Reaction-diffusion systems● The Hopf Bifurcation● Andronov–Hopf bifurcation page at ScholarpediaCategories: Bifurcation theoryPersonal tools● Log in / create accountNamespaces● Article● DiscussionVariantsViews● Read● Edit● View historyActionsSearchInteractionToolboxPrint/exportLanguages● This page was last modified on 25 May 2011 at 02:56.● Text is available under the Creative Commons Attribution-ShareAlike License; additional terms may apply. See Terms of use for details. Wikipedia is a registered trademark of the W ikimedia Foundation, Inc., a non-profit organization.● Contact us● Privacy policy● About Wikipedia● Disclaimers●●。
Substituted amides
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专利名称:Substituted amides发明人:William K. Hagmann,Linus S. Lin,Shrenik K.Shah,Ravindra N. Guthikonda,HongboQi,Linda L. Chang,Ping Liu,Helen M.Armstrong,James P. Jewell,Thomas J. Lanza 申请号:US11109076申请日:20050419公开号:US20050234061A1公开日:20051020专利内容由知识产权出版社提供摘要:Novel compounds of the structural formula (I) are antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. The compounds of the present invention are useful as centrally acting drugs in the treatment of psychosis, memory deficits, cognitive disorders, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson's disease, movement disorders, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, the treatment of obesity or eating disorders, as well as the treatment of asthma, constipation, chronic intestinal pseudo-obstruction, and cirrhosis of the liver.申请人:William K. Hagmann,Linus S. Lin,Shrenik K. Shah,Ravindra N.Guthikonda,Hongbo Qi,Linda L. Chang,Ping Liu,Helen M. Armstrong,James P.Jewell,Thomas J. Lanza地址:Westfield NJ US,Westfield NJ US,Metuchen NJ US,Edison NJ US,Edison NJ US,Wayne NJ US,Edison NJ US,Westfield NJ US,Jersey City NJ US,Edison NJ US 国籍:US,US,US,US,US,US,US,US,US,US更多信息请下载全文后查看。
缩阴球英语表达
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缩阴球英语表达The Cervical Dilator Ball is an innovative health device designed to be effectively used for cervical dilatation,toning and strengthening of the pelvic floor muscles in women. It is a vaginal ball made with medical silicone and specially designed for vaginal and cervical care.The Cervical Dilator Ball comes in three different sizes- small, medium and large, each one delivering different intensity levels of pressure, depending on what suits theuser best. This device can be used in multiple ways, such asby manually changing its position inside the vagina topromote further muscle stimulation and connection or using it while lying on your back or sitting in a chair.The Cervical Dilator Ball has multiple benefitsassociated with its use, such as increased elasticity and lubrication of the cervix, better libido and sexual pleasure, improved tone and strength of the pelvic floor muscles that support the uterus, bladder and other pelvic organs, improved digestion and elimination, better relaxation and stressrelief and improved post-coital recovery.It can also help with toning and strengthening of the uterus and other organs which are important for optimal reproductive health. Regular use of the Cervical Dilator Ball can also relieve common discomforts such as menstrual cramps, irregular menstruation, heavy bleeding, pre-menstrual syndrome, etc. It can also be used for postpartum recovery,as it helps in the restoration of the vaginal wall after the childbirth process.The Cervical Dilator Ball is a safe and effective tool that can be used in the privacy of your own home. It comes with detailed instructions and recommendations for use, making it easy and convenient to use. With regular use and proper guidance, it can help women improve their vaginal and cervical health and lead an enjoyable and active life.。
民族药理学作者须知
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JOURNAL OF ETHNOPHARMACOLOGYAn Interdisciplinary Journal Devoted to Indigenous DrugsAUTHOR INFORMATION PACK TABLE OF CONTENTS• Description• Audience• Impact Factor• Abstracting and Indexing • Editorial Board• Guide for Authors p.1p.2p.2p.2p.2p.4ISSN: 0378-8741DESCRIPTIONThe Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people's use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.In recent years the preservation of local knowledge, the promotion of indigenous medical systems in primary health care, and the conservation of biodiversity have become even more of a concern to all scientists working at the interface of social and natural sciences but especially to ethnopharmacologists. Recognizing the sovereign rights of States over their natural resources, ethnopharmacologists are particularly concerned with local people's rights to further use and develop their autochthonous resources.Accordingly, today's ethnopharmacological research embraces the multidisciplinary effort in the:• documentation of indigenous medical knowledge,• scientific study of indigenous medicines in order to contribute in the long-run to improved health care in the regions of study, as well as• search for pharmacologically unique principles from existing indigenous remedies.The Journal of Ethnopharmacology publishes original articles concerned with the observation and experimental investigation of the biological activities of plant and animal substances used in the traditional medicine of past and present cultures. The journal will particularly welcome interdisciplinary papers with an ethnopharmacological, an ethnobotanical or an ethnochemical approach to the study of indigenous drugs. Reports of anthropological and ethnobotanical field studies fall within the journal's scope. Studies involving pharmacological and toxicological mechanisms of action are especially welcome. Clinical studies on efficacy will be considered if contributing to the understanding of specific ethnopharmacological problems. The journal welcomes review articles in the above mentioned fields especially those highlighting the multi-disciplinary nature of ethnopharmacology. Commentaries are by invitation only.AUDIENCEEthnopharmacologists, Medicinal Chemists, Pharmacologists, Toxicologists, Anthropologists, Pharmacognosists, Ethnobotanists, Economic Botanists, EthnobiologistsIMPACT FACTOR2014: 2.998 © Thomson Reuters Journal Citation Reports 2015ABSTRACTING AND INDEXINGAGRICOLABIOSISCambridge Scientific AbstractsChemical AbstractsCurrent Contents/Life SciencesMEDLINE®International Pharmaceutical AbstractsEMBASENAPRALERT (Natural Products Alert)Science Citation IndexCAB AbstractsScopusEMBiologyEDITORIAL BOARDEditor-in-Chief:R. Verpoorte, Gorlaeus Lab., Universiteit Leiden, Einsteinweg 55, 2333 CC, Leiden, NetherlandsDeputy Editor-in-ChiefA.M. Viljoen, Tshwane University of Technology, Pretoria, South AfricaAssociate Editor:D. Guo, Chinese Academy of Sciences (CAS), Shanghai, ChinaA.K. Jäger, University of Copenhagen, Copenhagen O, DenmarkG. Lin, Chinese University of Hong Kong, Hong Kong, Hong KongP.K. Mukherjee, Jadavpur University, Kolkata, IndiaG. Schmeda Hirschmann, Universidad de Talca, Talca, ChileA. Shikov, Saint Petersburg Institute of Pharmacy, Kuzmolovo P 245, Russian FederationE. Yesilada, Yeditepe University, Erenkoy-Istanbul, TurkeyReviews Editor (including Commentaries and Book Reviews):M. Heinrich, The School of Pharmacy, University of London, 29-39 Brunswick Square, London, WC1N 1AX, UK If you want to suggest a review, please provide a structured abstract and include an annotated table of contents and a short CV of the lead author(s).Managing Editor:B. Pomahacova, Leiden University, Leiden, NetherlandsI. Vermaak, Tshwane University of Technology, Pretoria, South AfricaM. Sandasi, Tshwane University of Technology, Pretoria, South AfricaL.J. McGaw, University of Pretoria, Pretoria, South AfricaEditorial Board:S. Alban, Kiel, GermanyM.J. Balick, Bronx, New York, USAR. BauerG. Bourdy, Cayenne, French GuianaJ.B. Calixto, Florianópolis, BrazilC-T. Che, Hong Kong, Hong KongG.A. Cordell, Evanston, Illinois, USAV.S. da Silva Bolzani, Araraquara, BrazilJ. Ding, Shanghai, ChinaV.M. Dirsch, Vienna, AustriaE. Elisabetsky, Porto Alegre, BrazilJ. Fleurentin, Metz, FranceB.L. Furman, Glasgow, UKM.P. Germano, Messina, ItalyJ. Gertsch, Bern, SwitzerlandA.H. Gilani, Karachi, PakistanM.P. Gupta, Panama City, PanamaA. Hensel, Münster, GermanyP.J. Houghton, London, UKZ. Ismail, Penang, MalaysiaW. Jia, Kannapolis, North Carolina, USAT. Johns, Ste. Anne de Bellevue, Quebec, Canada A.K. Jäger, Copenhagen O, DenmarkG. Kavalali, Istanbul, TurkeyH-S. Kim, Cheongju, South KoreaJ. Kim, Seoul, South KoreaY. Kimura, Ehime, JapanM.A. Lacaille-Dubois, Dijon, FranceM. Leonti, Cagliari, ItalyE. Matteucci, Pisa, ItalyI. Merfort, Freiburg, GermanyJ.J.M. Meyer, Pretoria, South AfricaD.E. MoermanD.A. Mulholland, Guildford, England, UKA. Panthong, Chiang Mai, ThailandX. Peigen, Beijing, ChinaA. Pieroni, Pollenzo/Bra, ItalyD.D. Soejarto, Chicago, Illinois, USAE. Speroni, Bologna, ItalyA.J. Vlietinck, Antwerpen, BelgiumH. Wagner, München, GermanyC.S. Weckerle, Zurich, SwitzerlandC.W. Wright, Bradford, UKS. Zacchino, Rosario, ArgentinaFounding Editors:J.G. BruhnL. Rivier, Lausanne, SwitzerlandGUIDE FOR AUTHORSINTRODUCTIONThe Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people's use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people, confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.Please note that figures and tables should be embedded in the text as close as possible to where they are initially cited. It is also mandatory to upload separate graphic and table files as these will be required if your manuscript is accepted for publication.Classification of your paperPlease note that upon submitting your article you will have to select at least one classification and at least three of the given keywords. You can preview the list of classifications and keywords (here). This information is needed by the Editors to more quickly process your article. In addition to this, you can submit free keywords as described below under "Keywords".The "rules of 5"The Editors and Editorial Board have developed the "Rules of 5" for publishing in JEP. 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Peters (2010) Episodic Future Thinking Reduces Reward Delay Discounting
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NeuronArticleEpisodic Future Thinking ReducesReward Delay Discounting through an Enhancement of Prefrontal-Mediotemporal InteractionsJan Peters1,*and Christian Bu¨chel11NeuroimageNord,Department of Systems Neuroscience,University Medical Center Hamburg-Eppendorf,Hamburg20246,Germany*Correspondence:j.peters@uke.uni-hamburg.deDOI10.1016/j.neuron.2010.03.026SUMMARYHumans discount the value of future rewards over time.Here we show using functional magnetic reso-nance imaging(fMRI)and neural coupling analyses that episodic future thinking reduces the rate of delay discounting through a modulation of neural decision-making and episodic future thinking networks.In addition to a standard control condition,real subject-specific episodic event cues were presented during a delay discounting task.Spontaneous episodic imagery during cue processing predicted how much subjects changed their preferences toward more future-minded choice behavior.Neural valuation signals in the anterior cingulate cortex and functional coupling of this region with hippo-campus and amygdala predicted the degree to which future thinking modulated individual preference functions.A second experiment replicated the behavioral effects and ruled out alternative explana-tions such as date-based processing and temporal focus.The present data reveal a mechanism through which neural decision-making and prospection networks can interact to generate future-minded choice behavior.INTRODUCTIONThe consequences of choices are often delayed in time,and in many cases it pays off to wait.While agents normally prefer larger over smaller rewards,this situation changes when rewards are associated with costs,such as delays,uncertainties,or effort requirements.Agents integrate such costs into a value function in an individual manner.In the hyperbolic model of delay dis-counting(also referred to as intertemporal choice),for example, a subject-specific discount parameter accurately describes how individuals discount delayed rewards in value(Green and Myer-son,2004;Mazur,1987).Although the degree of delay discount-ing varies considerably between individuals,humans in general have a particularly pronounced ability to delay gratification, and many of our choices only pay off after months or even years. It has been speculated that the capacity for episodic future thought(also referred to as mental time travel or prospective thinking)(Bar,2009;Schacter et al.,2007;Szpunar et al.,2007) may underlie the human ability to make choices with high long-term benefits(Boyer,2008),yielding higher evolutionaryfitness of our species.At the neural level,a number of models have been proposed for intertemporal decision-making in humans.In the so-called b-d model(McClure et al.,2004,2007),a limbic system(b)is thought to place special weight on immediate rewards,whereas a more cognitive,prefrontal-cortex-based system(d)is more involved in patient choices.In an alternative model,the values of both immediate and delayed rewards are thought to be repre-sented in a unitary system encompassing medial prefrontal cortex(mPFC),posterior cingulate cortex(PCC),and ventral striatum(VS)(Kable and Glimcher,2007;Kable and Glimcher, 2010;Peters and Bu¨chel,2009).Finally,in the self-control model, values are assumed to be represented in structures such as the ventromedial prefrontal cortex(vmPFC)but are subject to top-down modulation by prefrontal control regions such as the lateral PFC(Figner et al.,2010;Hare et al.,2009).Both the b-d model and the self-control model predict that reduced impulsivity in in-tertemporal choice,induced for example by episodic future thought,would involve prefrontal cortex regions implicated in cognitive control,such as the lateral PFC or the anterior cingulate cortex(ACC).Lesion studies,on the other hand,also implicated medial temporal lobe regions in decision-making and delay discounting. In rodents,damage to the basolateral amygdala(BLA)increases delay discounting(Winstanley et al.,2004),effort discounting (Floresco and Ghods-Sharifi,2007;Ghods-Sharifiet al.,2009), and probability discounting(Ghods-Sharifiet al.,2009).Interac-tions between the ACC and the BLA in particular have been proposed to regulate behavior in order to allow organisms to overcome a variety of different decision costs,including delays (Floresco and Ghods-Sharifi,2007).In line with thesefindings, impairments in decision-making are also observed in humans with damage to the ACC or amygdala(Bechara et al.,1994, 1999;Manes et al.,2002;Naccache et al.,2005).Along similar lines,hippocampal damage affects decision-making.Disadvantageous choice behavior has recently been documented in patients suffering from amnesia due to hippo-campal lesions(Gupta et al.,2009),and rats with hippocampal damage show increased delay discounting(Cheung and Cardinal,2005;Mariano et al.,2009;Rawlins et al.,1985).These observations are of particular interest given that hippocampal138Neuron66,138–148,April15,2010ª2010Elsevier Inc.damage impairs the ability to imagine novel experiences (Hassa-bis et al.,2007).Based on this and a range of other studies,it has recently been proposed that hippocampus and parahippocam-pal cortex play a crucial role in the formation of vivid event repre-sentations,regardless of whether they lie in the past,present,or future (Schacter and Addis,2009).The hippocampus may thus contribute to decision-making through its role in self-projection into the future (Bar,2009;Schacter et al.,2007),allowing an organism to evaluate future payoffs through mental simulation (Johnson and Redish,2007;Johnson et al.,2007).Future thinking may thus affect intertemporal choice through hippo-campal involvement.Here we used model-based fMRI,analyses of functional coupling,and extensive behavioral procedures to investigate how episodic future thinking affects delay discounting.In Exper-iment 1,subjects performed a classical delay discounting task(Kable and Glimcher,2007;Peters and Bu¨chel,2009)that involved a series of choices between smaller immediate and larger delayed rewards,while brain activity was measured using fMRI.Critically,we introduced a novel episodic condition that involved the presentation of episodic cue words (tags )obtained during an extensive prescan interview,referring to real,subject-specific future events planned for the respective day of reward delivery.This design allowed us to assess individual discount rates separately for the two experimental conditions,allowing us to investigate neural mechanisms mediating changes in delay discounting associated with episodic thinking.In a second behavioral study,we replicated the behavioral effects of Exper-iment 1and addressed a number of alternative explanations for the observed effects of episodic tags on discount rates.RESULTSExperiment 1:Prescan InterviewOn day 1,healthy young volunteers (n =30,mean age =25,15male)completed a computer-based delay discounting proce-dure to estimate their individual discount rate (Peters and Bu ¨-chel,2009).This discount rate was used solely for the purpose of constructing subject-specific trials for the fMRI session (see Experimental Procedures ).Furthermore,participants compiled a list of events that they had planned in the next 7months (e.g.,vacations,weddings,parties,courses,and so forth)andrated them on scales from 1to 6with respect to personal rele-vance,arousal,and valence.For each participant,seven subject-specific events were selected such that the spacing between events increased with increasing delay to the episode,and that events were roughly matched based on personal rele-vance,arousal,and valence.Multiple regression analysis of these ratings across the different delays showed no linear effects (relevance:p =0.867,arousal:p =0.120,valence:p =0.977,see Figure S1available online).For each subject,a separate set of seven delays was computed that was later used as delays in the control condition.Median and range for the delays used in each condition are listed in Table S1(available online).For each event,a label was selected that would serve as a verbal tag for the fMRI session.Experiment 1:fMRI Behavioral ResultsOn day 2,volunteers performed two sessions of a delay dis-counting procedure while fMRI was measured using a 3T Siemens Scanner with a 32-channel head-coil.In each session,subjects made a total of 118choices between 20V available immediately and larger but delayed amounts.Subjects were told that one of their choices would be randomly selected and paid out following scanning,with the respective delay.Critically,in half the trials,an additional subject-specific episodic tag (see above,e.g.,‘‘vacation paris’’or ‘‘birthday john’’)was displayed based on the prescan interview (see Figure 1)indicating which event they had planned on the particular day (episodic condi-tion),whereas in the remaining trials,no episodic tag was pre-sented (control condition).Amount and waiting time were thus displayed in both conditions,but only the episodic condition involved the presentation of an additional subject-specific event tag.Importantly,nonoverlapping sets of delays were used in the two conditions.Following scanning,subjects rated for each episodic tag how often it evoked episodic associations during scanning (frequency of associations:1,never;to 6,always)and how vivid these associations were (vividness of associa-tions:1,not vivid at all;to 6,highly vivid;see Figure S1).Addition-ally,written reports were obtained (see Supplemental Informa-tion ).Multiple regression revealed no significant linear effects of delay on postscan ratings (frequency:p =0.224,vividness:p =0.770).We averaged the postscan ratings acrosseventsFigure 1.Behavioral TaskDuring fMRI,subjects made repeated choices between a fixed immediate reward of 20V and larger but delayed amounts.In the control condi-tion,amounts were paired with a waiting time only,whereas in the episodic condition,amounts were paired with a waiting time and a subject-specific verbal episodic tag indicating to the subjects which event they had planned at the respective day of reward delivery.Events were real and collected in a separate testing session prior to the day of scanning.NeuronEpisodic Modulation of Delay DiscountingNeuron 66,138–148,April 15,2010ª2010Elsevier Inc.139and the frequency/vividness dimensions,yielding an‘‘imagery score’’for each subject.Individual participants’choice data from the fMRI session were then analyzed byfitting hyperbolic discount functions to subject-specific indifference points to obtain discount rates (k-parameters),separately for the episodic and control condi-tions(see Experimental Procedures).Subjective preferences were well-characterized by hyperbolic functions(median R2 episodic condition=0.81,control condition=0.85).Discount functions of four exemplary subjects are shown in Figure2A. For both conditions,considerable variability in the discount rate was observed(median[range]of discount rates:control condition=0.014[0.003–0.19],episodic condition=0.013 [0.002–0.18]).To account for the skewed distribution of discount rates,all further analyses were conducted on the log-trans-formed k-parameters.Across subjects,log-transformed discount rates were significantly lower in the episodic condition compared with the control condition(t(29)=2.27,p=0.016),indi-cating that participants’choice behavior was less impulsive in the episodic condition.The difference in log-discount rates between conditions is henceforth referred to as the episodic tag effect.Fitting hyperbolic functions to the median indifference points across subjects also showed reduced discounting in the episodic condition(discount rate control condition=0.0099, episodic condition=0.0077).The size of the tag effect was not related to the discount rate in the control condition(p=0.56). We next hypothesized that the tag effect would be positively correlated with postscan ratings of episodic thought(imagery scores,see above).Robust regression revealed an increase in the size of the tag effect with increasing imagery scores (t=2.08,p=0.023,see Figure2B),suggesting that the effect of the tags on preferences was stronger the more vividly subjects imagined the episodes.Examples of written postscan reports are provided in the Supplemental Results for participants from the entire range of imagination ratings.We also correlated the tag effect with standard neuropsychological measures,the Sensation Seeking Scale(SSS)V(Beauducel et al.,2003;Zuck-erman,1996)and the Behavioral Inhibition Scale/Behavioral Approach Scale(BIS/BAS)(Carver and White,1994).The tag effect was positively correlated with the experience-seeking subscale of the SSS(p=0.026)and inversely correlated with the reward-responsiveness subscale of the BIS/BAS scales (p<0.005).Repeated-measures ANOVA of reaction times(RTs)as a func-tion of option value(lower,similar,or higher relative to the refer-ence option;see Experimental Procedures and Figure2C)did not show a main effect of condition(p=0.712)or a condition 3value interaction(p=0.220),but revealed a main effect of value(F(1.8,53.9)=16.740,p<0.001).Post hoc comparisons revealed faster RTs for higher-valued options relative to similarly (p=0.002)or lower valued options(p<0.001)but no difference between lower and similarly valued options(p=0.081).FMRI DataFMRI data were modeled using the general linear model(GLM) as implemented in SPM5.Subjective value of each decision option was calculated by multiplying the objective amount of each delayed reward with the discount fraction estimated behaviorally based on the choices during scanning,and included as a parametric regressor in the GLM.Note that discount rates were estimated separately for the control and episodic conditions(see above and Figure2),and we thus used condition-specific k-parameters for calculation of the subjective value regressor.Additional parametric regressors for inverse delay-to-reward and absolute reward magnitude, orthogonalized with respect to subjective value,were included in theGLM.Figure2.Behavioral Data from Experiment1Shown are experimentally derived discount func-tions from the fMRI session for four exemplaryparticipants(A),correlation with imagery scores(B),and reaction times(RTs)(C).(A)Hyperbolicfunctions werefit to the indifference points sepa-rately for the control(dashed lines)and episodic(solid lines,filled circles)conditions,and thebest-fitting k-parameters(discount rates)and R2values are shown for each subject.The log-trans-formed difference between discount rates wastaken as a measure of the effect of the episodictags on choice preferences.(B)Robust regressionrevealed an association between log-differences indiscount rates and imagery scores obtained frompostscan ratings(see text).(C)RTs were signifi-cantly modulated by option value(main effectvalue p<0.001)with faster responses in trialswith a value of the delayed reward higher thanthe20V reference amount.Note that althoughseven delays were used for each condition,somedata points are missing,e.g.,onlyfive delay indif-ference points for the episodic condition areplotted for sub20.This indicates that,for the twolongest delays,this subject never chose the de-layed reward.***p<0.005.Error bars=SEM.Neuron Episodic Modulation of Delay Discounting140Neuron66,138–148,April15,2010ª2010Elsevier Inc.Episodic Tags Activate the Future Thinking NetworkWe first analyzed differences in the condition regressors without parametric pared to those of the control condi-tion,BOLD responses to the presentation of the delayed reward in the episodic condition yielded highly significant activations (corrected for whole-brain volume)in an extensive network of brain regions previously implicated in episodic future thinking (Addis et al.,2007;Schacter et al.,2007;Szpunar et al.,2007)(see Figure 3and Table S2),including retrosplenial cortex (RSC)/PCC (peak MNI coordinates:À6,À54,14,peak z value =6.26),left lateral parietal cortex (LPC,À44,À66,32,z value =5.35),and vmPFC (À8,34,À12,z value =5.50).Distributed Neural Coding of Subjective ValueWe then replicated previous findings (Kable and Glimcher,2007;Kable and Glimcher,2010;Peters and Bu¨chel,2009)using a conjunction analysis (Nichols et al.,2005)searching for regions showing a positive correlation between the height of the BOLD response and subjective value in the control and episodic condi-tions in a parametric analysis (Figure 4A and Table S3).Note that this is a conservative analysis that requires that a given voxel exceed the statistical threshold in both contrasts separately.This analysis revealed clusters in the lateral orbitofrontal cortex (OFC,À36,50,À10,z value =4.50)and central OFC (À18,12,À14,z value =4.05),bilateral VS (right:10,8,0,z value =4.22;left:À10,8,À6,z value =3.51),mPFC (6,26,16,z value =3.72),and PCC (À2,À28,24,z value =4.09),representing subjective (discounted)value in both conditions.We next analyzed the neural tag effect,i.e.,regions in which the subjective value correlation was greater for the episodic condi-tion as compared with the control condition (Figure 4B and Table S4).This analysis revealed clusters in the left LPC (À66,À42,32,z value =4.96,),ACC (À2,16,36,z value =4.76),left dorsolateral prefrontal cortex (DLPFC,À38,36,36,z value =4.81),and right amygdala (24,2,À24,z value =3.75).Finally,we performed a triple-conjunction analysis,testing for regions that were correlated with subjective value in both conditions,but in which the value correlation increased in the episodic condition.Only left LPC showed this pattern (À66,À42,30,z value =3.55,see Figure 4C and Table S5),the same region that we previously identified as delay-specific in valuation (Petersand Bu¨chel,2009).There were no regions in which the subjective value correlation was greater in the control condition when compared with the episodic condition at p <0.001uncorrected.ACC Valuation Signals and Functional Connectivity Predict Interindividual Differences in Discount Function ShiftsWe next correlated differences in the neural tag effect with inter-individual differences in the size of the behavioral tag effect.To this end,we performed a simple regression analysis in SPM5on the single-subject contrast images of the neural tag effect (i.e.,subjective value correlation episodic >control)using the behavioral tag effect [log(k control )–log(k episodic )]as an explana-tory variable.This analysis revealed clusters in the bilateral ACC (right:18,34,18,z value =3.95,p =0.021corrected,left:À20,34,20,z value =3.52,Figure 5,see Table S6for a complete list).Coronal sections (Figure 5C)clearly show that both ACC clusters are located in gray matter of the cingulate sulcus.Because ACC-limbic interactions have previously been impli-cated in the control of choice behavior (Floresco and Ghods-Sharifi,2007;Roiser et al.,2009),we next analyzed functional coupling with the right ACC from the above regression contrast (coordinates 18,34,18,see Figure 6A)using a psychophysiolog-ical interaction analysis (PPI)(Friston et al.,1997).Note that this analysis was conducted on a separate first-level GLM in which control and episodic trials were modeled as 10s miniblocks (see Experimental Procedures for details).We first identified regions in which coupling with the ACC changed in the episodic condition compared with the control condition (see Table S7)and then performed a simple regression analysis on these coupling parameters using the behavioral tag effect as an explanatory variable.The tag effect was associated with increased coupling between ACC and hippocampus (À32,À18,À16,z value =3.18,p =0.031corrected,Figure 6B)and ACC and left amygdala (À26,À4,À26,z value =2.95,p =0.051corrected,Figure 6B,see Table S8for a complete list of activa-tions).The same regression analysis in a second PPI with the seed voxel placed in the contralateral ACC region from the same regression contrast (À20,34,22,see above)yielded qual-itatively similar,though subthreshold,results in these same structures (hippocampus:À28,À32,À6,z value =1.96,amyg-dala:À28,À6,À16,z value =1.97).Experiment 2We conducted an additional behavioral experiment to address a number of alternative explanations for the observed effects of tags on choice behavior.First,it could be argued thatepisodicFigure 3.Categorical Effect of Episodic Tags on Brain ActivityGreater activity in lateral parietal cortex (left)and posterior cingulate/retrosplenial and ventro-medial prefrontal cortex (right)was observed in the episodic condition compared with the control condition.p <0.05,FWE-corrected for whole-brain volume.NeuronEpisodic Modulation of Delay DiscountingNeuron 66,138–148,April 15,2010ª2010Elsevier Inc.141tags increase subjective certainty that a reward would be forth-coming.In Experiment 2,we therefore collected postscan ratings of reward confidence.Second,it could be argued that events,always being associated with a particular date,may have shifted temporal focus from delay-based to more date-based processing.This would represent a potential confound,because date-associated rewards are discounted less than delay-associated rewards (Read et al.,2005).We therefore now collected postscan ratings of temporal focus (date-based versus delay-based).Finally,Experiment 1left open the question of whether the tag effect depends on the temporal specificity of the episodic cues.We therefore introduced an additional exper-imental condition that involved the presentation of subject-specific temporally unspecific future event cues.These tags (henceforth referred to as unspecific tags)were obtained by asking subjects to imagine events that could realistically happen to them in the next couple of months,but that were not directly tied to a particular point in time (see Experimental Procedures ).Episodic Imagery,Not Temporal Specificity,Reward Confidence,or Temporal Focus,Predicts the Size of the Tag EffectIn total,data from 16participants (9female)are included.Anal-ysis of pretest ratings confirmed that temporally unspecific and specific tags were matched in terms of personal relevance,arousal,valence,and preexisting associations (all p >0.15).Choice preferences were again well described by hyperbolic functions (median R 2control =0.84,unspecific =0.81,specific =0.80).We replicated the parametric tag effect (i.e.,increasing effect of tags on discount rates with increasing posttest imagery scores)in this independent sample for both temporally specific (p =0.047,Figure 7A)and temporally unspecific (p =0.022,Figure 7A)tags,showing that the effect depends on future thinking,rather than being specifically tied to the temporal spec-ificity of the event cues.Following testing,subjects rated how certain they were that a particular reward would actually be forth-coming.Overall,confidence in the payment procedure washighFigure 4.Neural Representation of Subjective Value (Parametric Analysis)(A)Regions in which the correlation with subjective value (parametric analysis)was significant in both the control and the episodic conditions (conjunction analysis)included central and lateral orbitofrontal cortex (OFC),bilateral ventral striatum (VS),medial prefrontal cortex (mPFC),and posterior cingulate cortex(PCC),replicating previous studies (Kable and Glimcher,2007;Peters and Bu¨chel,2009).(B)Regions in which the subjective value correlation was greater for the episodic compared with the control condition included lateral parietal cortex (LPC),ante-rior cingulate cortex (ACC),dorsolateral prefrontal cortex (DLPFC),and the right amygdala (Amy).(C)A conjunction analysis revealed that only LPC activity was positively correlated with subjective value in both conditions,but showed a greater regression slope in the episodic condition.No regions showed a better correlation with subjective value in the control condition.Error bars =SEM.All peaks are significant at p <0.001,uncorrected;(A)and (B)are thresholded at p <0.001uncorrected and (C)is thresholded at p <0.005,uncorrected for display purposes.NeuronEpisodic Modulation of Delay Discounting142Neuron 66,138–148,April 15,2010ª2010Elsevier Inc.(Figure 7B),and neither unspecific nor specific tags altered these subjective certainty estimates (one-way ANOVA:F (2,45)=0.113,p =0.894).Subjects also rated their temporal focus as either delay-based or date-based (see Experimental Procedures ),i.e.,whether they based their decisions on the delay-to-reward that was actually displayed,or whether they attempted to convert delays into the corresponding dates and then made their choices based on these dates.There was no overall significant effect of condition on temporal focus (one-way ANOVA:F (2,45)=1.485,p =0.237,Figure 7C),but a direct comparison between the control and the temporally specific condition showed a significant difference (t (15)=3.18,p =0.006).We there-fore correlated the differences in temporal focus ratings between conditions (control:unspecific and control:specific)with the respective tag effects (Figure 7D).There were no correlations (unspecific:p =0.71,specific:p =0.94),suggesting that the observed differences in discounting cannot be attributed to differences in temporal focus.High-Imagery,but Not Low-Imagery,Subjects Adjust Their Discount Function in an Episodic ContextFor a final analysis,we pooled the samples of Experiments 1and 2(n =46subjects in total),using only the temporally specific tag data from Experiment 2.We performed a median split into low-and high-imagery participants according to posttest imagery scores (low-imagery subjects:n =23[15/8Exp1/Exp2],imagery range =1.5–3.4,high-imagery subjects:n =23[15/8Exp1/Exp2],imagery range =3.5–5).The tag effect was significantly greater than 0in the high-imagery group (t (22)=2.6,p =0.0085,see Figure 7D),where subjects reduced their discount rate by onaverage 16%in the presence of episodic tags.In the low-imagery group,on the other hand,the tag effect was not different from zero (t (22)=0.573,p =0.286),yielding a significant group difference (t (44)=2.40,p =0.011).DISCUSSIONWe investigated the interactions between episodic future thought and intertemporal decision-making using behavioral testing and fMRI.Experiment 1shows that reward delay dis-counting is modulated by episodic future event cues,and the extent of this modulation is predicted by the degree of sponta-neous episodic imagery during decision-making,an effect that we replicated in Experiment 2(episodic tag effect).The neuroi-maging data (Experiment 1)highlight two mechanisms that support this effect:(1)valuation signals in the lateral ACC and (2)neural coupling between ACC and hippocampus/amygdala,both predicting the size of the tag effect.The size of the tag effect was directly related to posttest imagery scores,strongly suggesting that future thinking signifi-cantly contributed to this effect.Pooling subjects across both experiments revealed that high-imagery subjects reduced their discount rate by on average 16%in the episodic condition,whereas low-imagery subjects did not.Experiment 2addressed a number of alternative accounts for this effect.First,reward confidence was comparable for all conditions,arguing against the possibility that the tags may have somehow altered subjec-tive certainty that a reward would be forthcoming.Second,differences in temporal focus between conditions(date-basedFigure 5.Correlation between the Neural and Behavioral Tag Effect(A)Glass brain and (B and C)anatomical projection of the correlation between the neural tag effect (subjective value correlation episodic >control)and the behav-ioral tag effect (log difference between discount rates)in the bilateral ACC (p =0.021,FWE-corrected across an anatomical mask of bilateral ACC).(C)Coronal sections of the same contrast at a liberal threshold of p <0.01show that both left and right ACC clusters encompass gray matter of the cingulate gyrus.(D)Scatter-plot depicting the linear relationship between the neural and the behavioral tag effect in the right ACC.(A)and (B)are thresholded at p <0.001with 10contiguous voxels,whereas (C)is thresholded at p <0.01with 10contiguousvoxels.Figure 6.Results of the Psychophysiolog-ical Interaction Analysis(A)The seed for the psychophysiological interac-tion (PPI)analysis was placed in the right ACC (18,34,18).(B)The tag effect was associated with increased ACC-hippocampal coupling (p =0.031,corrected across bilateral hippocampus)and ACC-amyg-dala coupling (p =0.051,corrected across bilateral amygdala).Maps are thresholded at p <0.005,uncorrected for display purposes and projected onto the mean structural scan of all participants;HC,hippocampus;Amy,Amygdala;rACC,right anterior cingulate cortex.NeuronEpisodic Modulation of Delay DiscountingNeuron 66,138–148,April 15,2010ª2010Elsevier Inc.143。
脯氨酸与植物的抗逆性
![脯氨酸与植物的抗逆性](https://img.taocdn.com/s3/m/ae90a72be2bd960590c67786.png)
脯氨酸与植物的抗逆性王宝增(河北省廊坊师范学院生命科学学院065000)摘要本文主要介绍了脯氨酸在植物体中的合成与分解以及脯氨酸与植物抗逆性的关系。
关键词脯氨酸逆境胁迫相容性溶质抗逆性植物一生中会受到多种不利环境的影响,在诸多逆境因素中,由干旱、盐渍等因素引起的渗透胁迫(os-motic stress)是限制植物生长发育和作物产量的主要原因。
许多植物在逆境胁迫中都会积累一些相容性溶质(compatible solute),如脯氨酸、甜菜碱、糖醇等,这些物质溶解度高,没有毒性,在细胞中积累不会干扰细胞内正常的生化反应,并且可以抵抗渗透胁迫[1]。
在已知的相容性溶质中,脯氨酸在植物中的分布最为广泛[2]。
1脯氨酸在植物体中的积累脯氨酸作为蛋白质氨基酸中的一员,在植物初生代谢中的作用尤为重要。
人们在萎蔫的黑麦中首先发现了脯氨酸积累这一现象[3]。
之后,在逆境胁迫下的其他植物中也发现了脯氨酸的积累。
植物在遭受干旱、盐渍、强光与重金属污染和其他生物胁迫过程中都会有脯氨酸的大量积累,少则十几倍,多则几十倍甚至上百倍。
许多研究表明,脯氨酸主要分布在细胞质中,调节胞质和液泡之间渗透势的平衡[4]。
在水分胁迫中,它优先在细胞质中积累。
例如马铃薯细胞在正常水分条件下,细胞内的脯氨酸有34%积累在液泡中;但当其处于水分亏缺条件下时,液泡中脯氨酸含量下降,细胞质中脯氨酸含量上升[5]。
2脯氨酸的合成与分解在植物中,脯氨酸的合成主要来自谷氨酸,合成反应主要在叶绿体中完成。
谷氨酸在吡咯啉-5-羧酸合成酶(P5CS)催化下还原成谷氨酸半缩醛,后者自发转变成吡咯啉-5-羧酸(P5C),吡咯啉-5-羧酸还原酶(P5CR)进一步将吡咯啉-5-羧酸还原成脯氨酸。
在大多数植物中,吡咯啉-5-羧酸合成酶由2个基因编码,吡咯啉-5-羧酸还原酶由1个基因编码。
脯氨酸的分解代谢在线粒体中完成,分别由脯氨酸脱氢酶(PDH)和吡咯啉-5-羧酸脱氢酶(P5CDH)催化完成,脯氨酸脱氢酶催化脯氨酸转变成吡咯啉-5-羧酸,吡咯啉-5-羧酸脱氢酶催化吡咯啉-5-羧酸氧化成谷氨酸。
在燃烧室燃烧振荡的反馈控制
![在燃烧室燃烧振荡的反馈控制](https://img.taocdn.com/s3/m/0a5cf5e581c758f5f61f679c.png)
Short communicationFeedback control of combustion oscillations in combustion chambersWei Wei a,*,Jing Wang a ,Dong-hai Li b ,Min Zhu b ,Ya-li Xue ba School of Information Engineering,University of Science and Technology Beijing,ChinabState Key Lab of Power Systems,Department of Thermal Engineering,Tsinghua University,Beijing,Chinaa r t i c l e i n f o Article history:Received 14November 2009Received in revised form 17December 2009Accepted 18December 2009Available online 28December 2009Keywords:Active control Model freeThermoacoustic instabilities Active compensation Longitudinal oscillationsa b s t r a c tModel-based algorithms are generally employed in active control of combustion oscilla-tions.Since practical combustion processes consist of complex thermal and acoustic cou-plings,their accurate models and parameters may not be obtained in advance economically,a model free controller is necessary for the control of thermoacoustic insta-bilities.Active compensation based control algorithm is applied in the suppression of com-bustion instabilities.Tuning the controller parameters on line,the amplitudes of the acoustic waves can be modulated to desired values.Simulations performed on a control oriented,typical longitudinal oscillations combustor model illustrate the controllers’capa-bility to attenuate combustion oscillations.Ó2009Elsevier B.V.All rights reserved.1.IntroductionCombustion oscillations have been plaguing designers of the propulsion and power generation systems,and oscillations arise more frequent when the combustors are under the operating condition of lean premixed to reduce the nitrous oxide emissions.Oscillations in combustion chambers occur as a result of couplings between the unsteady heat release rate and acoustic pressure.Their self-excited feedback loop can be diagrammed in Fig.1.Unsteady heat release is an efficient acoustic source,and combustor may be high resonant systems [1].In most cases,such oscillations are unwanted since they can cause structural damage.Due to the oscillations’severity,a significant multitude of efforts have made to prevent or alleviate them.Traditionally,two approaches are adopted to interrupt the couplings.Passive approaches,such as changing the combustors geometry or installing baffles and acoustic dampers,resort to reduce the sensibility of the combustion process to the acoustic excitation [2–4].The problem is that they may be ineffective when the operating conditions are changed,and the changes of design involved are costly and time consuming.That is,the passive approaches have bad robustness.Active feedback control provides another way of suppressing oscillations in combustors.At first,controllers are designed as a way of trial-and-error [5–7],which are empirical and unsuitable for practical instable combustion processes.Such ap-proaches can not provide guarantees of the stability and may excite the amplitude of the thermoacoustic oscillations.A con-troller,which can offer suitable gains and phases in real time,is desirable.Control theories are applied in interrupting the couplings between acoustic waves and unsteady combustion.Consequently,systematic approaches to controllers design are utilized.Model-based control algorithms are designed to decouple the physical processes leading to thermoacoustic instabilities.Adaptive control [8–11],robust control [12–14],LQR control [15,16],State-feedback [17]and PID [18–20]con-trol etc are intensively studied,all of which demonstrate the valid of active feedback control approaches in suppressing com-bustion oscillations.A summary of active control designs for combustion oscillations can be found in Ref.[1].However,the1007-5704/$-see front matter Ó2009Elsevier B.V.All rights reserved.doi:10.1016/sns.2009.12.020*Corresponding author.Address:Mailbox 136,University of Science and Technology Beijing,Beijing 100083,China.E-mail address:weiweiustb@ (W.Wei).Commun Nonlinear Sci Numer Simulat 15(2010)3274–3283Contents lists available at ScienceDirectCommun Nonlinear Sci Numer Simulatjournal homepage:www.else v i e r.c o m /l o c a t e /c n s n sexact models of the combustion processes needed in model-based algorithms are not practical or economical.A control algo-rithm,which does not depend on the precise mathematical models of the physical processes,is of significance.In this paper,a controller,based on active compensation,is designed for the control-oriented model of unsteady motions in a combustor [17].The control technology employed here is model free and its parameters can be tuned easily to suppress the instabilities.In what follows,a control-oriented theoretical model of an unsteady combustion chamber is stated in Sec-tion 2.Control algorithm,stability analysis of the closed-loop system and the analysis of ability to suppress oscillations are given in Section 3.In Section 4,simulations are performed on the model stated in Section 2to demonstrate the controller.Section 5concludes the paper.2.Controlled dynamic models of combustion chambersYang et al.[17]developed control-oriented models for combustion processes,a set of linear ordinary differential equa-tions governing the dynamics of the combustor is given for the time-dependent amplitude of each mode [17]€g n þx 2n g n þXK i ¼1ðD ni _g i þE ni g i ÞþF NL n ðg 1;g 2;...;_g 1;_g 2;...Þ¼w n ðt ÞþU n ðt Þ;n ¼1;2;...;K ð1Þwhere w n ðt Þis the noise,D ni and E ni are linear coefficients associated with growth rate and frequency shift,respectively.F NL nrepresents all nonlinear processes.K ,the number of the modes,should be infinite to describe the combustion dynamics com-pletely.As a matter of fact,however,the unsteady motions can be represented by a truncated mode,i.e.K may be large but finite.The distributed control of the secondary fuel may be provided by M point actuators,each actuator supplies an exci-tation u i ðt Þat a position r i as shown in Fig.2.The control input to the n th mode can be written asU n ðt Þ¼a2 p E 2n X Mi ¼1u i ðt Þw n ðr i Þð2Þwhere E 2n ¼R R R w 2n dV is the Euclidean norm of the mode function,w n ¼cos n p L z is normal mode function,and a is the speed of sound in mixture.The unsteady pressure field is measured by P point sensors,the sensor output measured at the position r j ,with the mea-surement noise modeled by a random function v j ðt Þ,in the chamber can be written as followsy j ¼c j pX K n ¼1g n ðt Þw n ðr j Þþv j ðt Þ;j ¼1;2;...;Pð3ÞThe controlled dynamics of combustion chambers are described in Eqs.(1)–(3).We consider the deterministic and linearsystems,i.e.w n ðt Þ¼v j ðt Þ¼0and F NL n ¼0.Nonlinear problems are considered in Ref.[19].According to Ref.[17],the first N modes (N <K )are controlled,the state variables can be classified into controlled and uncontrolled (residual)parts as follows.x ¼½x N ;x R TFig.2.Scheme of active control system with distributed actuators.Fig.1.Thermoacoustic instabilities loop.W.Wei et al./Commun Nonlinear Sci Numer Simulat 15(2010)3274–32833275where,x N ¼½g 1;_g1;g 2;_g 2;...;g N ;_g N T ;x R ¼½g N þ1;_g N þ1;g N þ2;_g N þ2;...;g K ;_g K T .Thus,Eqs.(1)–(3)can be written as following state-space form_x N _x R ¼A N A NRA RN A Rx N x R þB N B R uy ¼C N x N þC R x R8<:ð4Þwhere,A N ;A NR and A R ;A RN are system matrices associated with controlled and uncontrolled modes.Input and output matri-ces are expressed by B N ;B R and C N ;C R ,respectively.u ¼½u 1;u 2;...;u M T 2R M ;y ¼½y 1;y 2;...;y P T 2R P .Similar to Ref.[17],two controlled and two residual modes of longitudinal oscillations are considered.We use one actu-ator and one sensor.Thus,the state variables,system matrices,input matrices,and the output matrices are shown below,respectively.x N ¼½g 1;_g1;g 2;_g 2 T ;x R ¼½g 3;_g 3;g 4;_g 4 T ;u 2R ;y 2R ;A N ¼0100Àðx 21þE 11ÞÀD11ÀE 12ÀD 12001ÀE 21ÀD 21Àðx 22þE 22ÞÀD 22B B B@1C CC A ;A R ¼0100Àðx 23þE 33ÞÀD33ÀE 34ÀD 34001ÀE 43ÀD 43Àðx 24þE 44ÞÀD 44B B B@1C CC AA NR¼0000ÀE 13ÀD 13ÀE 14ÀD 140000ÀE 23ÀD 23ÀE 24ÀD 240B B B @1C CC A ;A RN¼0000ÀE 31ÀD 31ÀE 32ÀD 320000ÀE 41ÀD 41ÀE 42ÀD 42B B B @1C CC A ð5ÞB N ¼0a 2w 1ðr Þ pE 210 a2w 2ðr Þp E 2B B B B B @1CC C C CA ;B R ¼0a 2w 3ðr Þ pE 230 a2w 4ðr Þp E 4B B B B B @1CC C C CA ;C N ¼ðc pw 10c pw 20Þ;C R ¼ðc p w 30c pw 40Þ3.Controller designIn this section,an active compensation based controller is designed to suppress the oscillations in combustion chambers,i.e.to make the amplitudes of the pressure oscillation g n approach zero.3.1.Control law and closed-loop block diagramAn active compensation based controller,proposed by Tornambe and Valigi [21],is employed here.We may call it TC con-troller in this paper.The control law,when relative degree is 1,has the formu ¼Àh 0ðy Ày r ÞÀ^d^d ¼n þk 0ðy Ày r Þ_n ¼Àk 0n Àk 20ðy Ày r ÞÀk 0u8>><>>:ð6Þwhere ^d is the extended state observer,which estimates the uncertainties.y is the output of the system.y ris the desired tra-jectory.n is the intermediate variable.h 0;k 0are tunable variables,and h 0determines,the response speed of the system.The control block diagram is shown in Fig.3.In the diagram,u c is the control output of the controller,u p is the control input of the combustion process.3276W.Wei et al./Commun Nonlinear Sci Numer Simulat 15(2010)3274–32833.2.Stability analysisControl law Eq.(6)can be rewritten as e¼yrÀyu¼ðh0þk0ÞeÀn_n¼Àh0k0e8><>:ð7ÞTo simplify the notation,we have c1¼Àðh0þk0Þ;c2¼h0k0.Under the function of TC controller,the closed-loop state-space description of the system Eq.(5)is given belowx¼½g1;_g1;g2;_g2;g3;_g3;g4;_g4;n T;_x¼Aclxwhere A cl¼010000000Àðx21þE11Þþ a2w1ðrÞp E21c p w1ðrÞc1ÀD11ÀE12þ a2w1ðrÞp E21c p w2ðrÞc1ÀD12ÀE13ÀD13ÀE14ÀD14À a2w1ðrÞp E21000100000ÀE21þ a2w2ðrÞp E22c p w1ðrÞc1ÀD21Àðx22þE22Þþ a2w2ðrÞp E22c p w2ðrÞc1ÀD22ÀE23ÀD23ÀE24ÀD24À a2w2ðrÞp E22000001000ÀE31þ a2w3ðrÞp E23c p w1ðrÞc1ÀD31ÀE32þ a2w3ðrÞp E23c p w2ðrÞc1ÀD32Àðx23þE33ÞÀD33ÀE34ÀD34À a2w3ðrÞp E23000000010ÀE41þ a2w4ðrÞp E24c p w1ðrÞc1ÀD41ÀE42þ a2w4ðrÞp E24c p w2ðrÞc1ÀD42ÀE43ÀD43Àðx24þE44ÞÀD44À a2w4ðrÞp E24c p w1ðrÞc20c p w2ðrÞ20000000 B B B B B B B B B B B B B B B B B B @1 C C C C C C C C C C C C C C C C C C Að8ÞCorollary1.If A cl is Hurwitz,the closed-loop system is asymptotically stable.We note that the characteristic polynomial of closed-loop system Eq.(8)is j k IÀA cl j¼k9þa8k8þÁÁÁþa1kþa0.If all the roots of j k IÀA cl j¼0have negative real parts,the closed-loop system is asymptotically stable.Note that the matrixQ¼a8a6a4a2a000001a7a5a3a100000a8a6a4a2a000001a7a5a3a100000a8a6a4a2a000001a7a5a3a100000a8a6a4a2a000001a7a5a3a100000a8a6a4a2a0B BB BB BB BB BB BB BB B@1C CC CC CC CC CC CC CC CAAccording to the Hurwitz criterion[22],fðkÞis Hurwitz if and only if the matrix Q’s leading principal minors are positive:detq11q12...q1kq21...q2k.........qk1qk2...qkkB BB BB@1C CC CC A>0;k¼1;2;...;9:ð9Þthat is,D1¼a8>0;D2¼a8a61a7>0;D3¼a8a6a41a7a50a8a6>0;D4¼a8a6a4a21a7a5a30a8a6a401a7a5>0;D5¼a8a6a4a2a01a7a5a3a10a8a6a4a201a7a5a300a8a6a4>0;W.Wei et al./Commun Nonlinear Sci Numer Simulat15(2010)3274–32833277D 6¼a 8a 6a 4a 2a 001a 7a 5a 3a 100a 8a 6a 4a 2a 001a 7a 5a 3a 100a 8a 6a 4a 2001a 7a 5a 3>0;D 7¼a 8a 6a 4a 2a 0001a 7a 5a 3a 1000a 8a 6a 4a 2a 0001a 7a 5a 3a 1000a 8a 6a 4a 2a 0001a 7a 5a 3a 100a 8a 6a 4a 2>0;D 8¼a 8a 6a 4a 2a 00001a 7a 5a 3a 10000a 8a 6a 4a 2a 00001a 7a 5a 3a 10000a 8a 6a 4a 2a 00001a 7a 5a 3a 10000a 8a 6a 4a 2a 001a 7a 5a 3a 1>0;D 9¼a 8a 6a 4a 2a 000001a 7a 5a 3a 100000a 8a 6a 4a 2a 000001a 7a 5a 3a 100000a 8a 6a 4a 2a 000001a 7a 5a 3a 100000a 8a 6a 4a 2a 000001a 7a 5a 3a 100a 8a 6a 4a 2a 0>0:are satisfied.Thus,the A cl is Hurwitz,or the closed-loop system is asymptotically stable.3.3.Analysis of the ability to suppress oscillationsIn order to illustrate the capable of suppressing oscillations,we make an assumption that y ¼sin ðX t Þ.Substituting y intoEq.(7),we have e ¼Àsin ðX t Þand u ¼c 1sin ðX t Þþc 2cosðX t ÞXþC ,where C is the integral constant.It is obvious that the phase-shift resulting from the control input depends on the term c 1sin ðX t Þþc 2cosðX t Þ.As a matter of fact,c 1sin ðX t Þþc 2cos ðX t ÞX¼1X ½c 1X sin ðX t Þþc 2cos ðX t Þ ¼1X ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffic 21X 2þc 22q sin X t þarctan c21Xh i ¼1ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiðh 0þk 0Þ2X 2þh 20k 20q sin X t Àarctan h 0k 000 h iHence,the phase-shift made by control input is arctan h 0k 0h 0X þk 0X,in other words the time delay on account of the control in-put is 1X arctan h 0k 00X 0X.This explains why the TC controller is capable of suppressing the combustion instabilities in combustors.4.Simulations for the modelTo demonstrate the TC controller,we performed simulations for the four modes of longitudinal pressure oscillations.The normalized natural radian frequency of the fundamental mode and the amplification factor (c )of the pressure signal are both taken to be unity.The linear parameters D ni and E ni in Eq.(1)are given in Table 1.According to Ref.[17],the optimal locations of actuators and sensors are selected to be at z o ¼L =7:5.L is taken as 76.2cm as in Ref.[18].In this paper,we define e as the ratio of u cmax to y max .Simulations are performed on system Eq.(5),the results are shown below,respectively (see Figs.4–9).Table 1System parameters.i =1i =2i =3i =4D ni n =1À0.010.007À0.0010.007n =20.010.10.007À0.001n =3À0.010.010.750.008n =40.02À0.0050.01 1.50E ni n =1À0.005À0.0050.00250.016n =2À0.0025À0.0150.010.01n =3À0.0050.0À0.020.02n =40.010.020.02À0.00253278W.Wei et al./Commun Nonlinear Sci Numer Simulat 15(2010)3274–3283W.Wei et al./Commun Nonlinear Sci Numer Simulat15(2010)3274–328332794.1.Simulation results for TCThe parameters and performance indexes of TC controllers are given in Table2.To check whether the closed-loop system is asymptotically stable under the function of TC controller,we verify the Eq.(9)for each system.3280W.Wei et al./Commun Nonlinear Sci Numer Simulat15(2010)3274–3283(1)Under the function of TC1,the characteristic polynomial of closed-loop system Eq.(8)is j k IÀA cl j¼k9þ2:34k8þ8165:7k7þ18846:2k6þ234295:1k5þ264215:2k4þ1714489:6k3þ576571:9k2þ2933414:7kþ12191:5, and D1¼2:34,D2¼261:5,D3¼4264354:8,D4¼5:1079Â1011,D5¼1:7429Â1016,D6¼1:8386Â1022,D7¼4:2955Â1026,D8¼1:0029Â1033,D9¼1:2227Â1037.Eq.(9)is satisfied,the closed-loop system is asymptotically stable.W.Wei et al./Commun Nonlinear Sci Numer Simulat15(2010)3274–32833281Table2Parameters and performance indexes of TC.TC k0h0u cmax y max e IAE10.020.00530.00170.06830.0247 3.278620.040.00640.00310.06830.0454 2.553230.050.00450.00360.06830.0533 2.39573282W.Wei et al./Commun Nonlinear Sci Numer Simulat15(2010)3274–3283Table3Parameters and performance indexes of phase-shift control.Phase-shift s c k p u cmax y max e IAE10.3À0.02530.00170.06830.0247 3.398920.2À0.04640.00310.06830.0454 2.606630.3À0.05450.00360.06830.0533 2.4872Table4Comparison of TC and phase-shift controller.e IAETC controller Phase-shift controller0.0247 3.2786 3.39890.0454 2.5532 2.60660.0533 2.3957 2.4872(2)Under the function of TC2,the characteristic polynomial of closed-loop system Eq.(8)is j k IÀA cl j¼k9þ2:34k8þ14949:8k7þ34551k6þ429514:8k5þ484984:4k4þ3144421:4k3þ1061213:2k2þ5381370:2kþ29447, and D1¼2:34,D2¼431:5,D3¼13692874:4,D4¼3:0075Â1012D5¼1:8922Â1017,D6¼3:6443Â1023, D7¼1:6566Â1028,D8¼6:6567Â1034,D9¼1:9602Â1039.Eq.(9)is satisfied,the closed-loop system is asymptoti-cally stable.(3)Under the function of TC3,the characteristic polynomial of closed-loop system Eq.(8)is j k IÀA cl j¼k9þ2:34k8þ17554:1k7þ40551:4k6þ504393:7k5þ568912:4k4þ3692469:9k3þ1241233:6k2þ6319299:4kþ25882:3, and D1¼2:34,D2¼525:2,D3¼19866748:8,D4¼5:127Â1012,D5¼3:7695Â1017,D6¼8:5727Â1023, D7¼4:28Â1028,D8¼2:1563Â1035,D9¼5:5811Â1039.According to Eq.(9),the closed-loop system is also asymp-totically stable.The time traces of closed-loop systems are shown in Figs.4–6,respectively.A popular control algorithm utilized for suppressing the combustion oscillations in experimental devices is phase-shift control,and it is independent of exact models of the physical processes.For the reasons above,we choose the standard con-trol algorithm,i.e.phase-shift control,as the benchmark,and make some comparison with TC controller.Simulations are performed on the same system with the same parameters.The results are given in Figs.7–9,respectively.4.2.Simulation results for phase-shiftThe parameters and performance indexes of phase-shift controllers are shown in Table3.The time traces of closed-loop systems are given in Figs.7–9,respectively.From Figs.4-9and IAE values given in Tables2and3,we can see that the TC controller,under the same control cost,is superior to the phase-shift controller.To show the advantages of TC controller over the phase-shift controller more distinct, we have Table4.From Table4,we may see clearly that the IAE values of TC controller,at the same price of control input,is minimal.In contrast to the phase-shift controller,the TC controller parameters has obvious physical interpretation,therefore the param-eter adjustments are more practicable.5.ConclusionIn this paper,a combustor model,which takes account of the influences of acoustic andflame dynamics,is considered and active compensation based controllers are adopted in the suppression of combustion oscillations.Controller employed,by comparison,does not need the prior knowledge of the process models.Tuning the parameters on line,the control action can suppress the amplitudes of oscillations to prespecified values,which may provide a realistic solution.However,the work in this paper is a necessary preparation for practical applications.With the purpose of verifying the control algorithm employed in this paper,the higher order and nonlinear models describing the combustion dynamics more exactly will be taken into account.Furthermore,the experimental verification is of importance in the forthcoming research as well.AcknowledgementThis work is supported by National Basic Research Program of China Grant No.2007CB210106.W.Wei et al./Commun Nonlinear Sci Numer Simulat15(2010)3274–32833283 References[1]Dowling AP,Morgans AS.Feedback control of combustion oscillations.Annu Rev Fluid Mech2005;37:151–82.[2]Culick F.,Combustion instabilities in liquid-fueled propulsion systems:an overview.In:AGA-RD conference on combustion instabilities in liquid-fueled propulsion systems;1988.[3]Steele RC,Cowell LH,Cannon SM,Smith CE.Passive control of combustion instability in lean premixed combustors.J Eng Gas Turbines Power2000;122(3):412–9.[4]Richards GA,Straub DL,Robey EH.Passive control of combustion dynamics in stationary gas turbines.J Prop Power2003;19(5):795–810.[5]Ffowcs Williams JE.Antisound.Proc Roy Soc London1984;A395:63–88.[6]Langhorne PJ,Dowling AP,Hooper N.A practical active control system for combustion oscillations.J Prop Power1990;6:324–33.[7]Seume J,Vortmeyer N,Krause W,Hermann J,Hantschk C,Zangl P.Application of active combustion instability control to a heavy duty gas turbine.J EngGas Turbines Power1998;120:721–6.[8]Billoud G,Galland MA,Huynh Huu C,Candel S.Adaptive active control of combustion bus Sci Technol1992;81:257–83.[9]Himani Jain,Ananthkrishnan N,Fred EC.Culick,Feedback-linearization-based adaptive control and estimation of a nonlinear combustion instabilitymodel.In:AIAA guidance,navigation,and control conference and exhibit;2005.p.5847–56.[10]Morgans AS,Annaswamy AM.Adaptive control of combustion instabilities for combustion systems with right-half plane bus Sci Technol2008;180:1549–71.[11]Kopasakis George,Delaat John C,Chang Clarence T.Adaptive instability suppression controls method for aircraft gas turbine engine combustors.J PropPower2009;25(3):618–27.[12]Chu Yun Chung,Dowling AP,Glover Keith.Robust control of combustion oscillations.In:Proceedings of IEEE international conference on controlapplications;1998.p.1165–69.[13]Hong Boe Shong,Yang Vigor,Ray Asok.Robust feedback control of combustion instability with modeling bus Flame2000;120:91–106.[14]Chu Yun Chung,Glover Keith,Dowling AP.Control of combustion oscillations via H1loop-shaping,l-analysis and integral quadratic constraints.Automatica2003;39:219–31.[15]Annaswamy AM,Ghoniem AF.Active control in combustion systems.IEEE Control Syst1995:49–63.[16]Annaswamy AM,Fleifil Mahmoud,Rumsey JW,Prasanth Ravi,Hathout Jean-Pierre,Ghoniem AF.Thermoacoustic instability:model-based optimalcontrol designs and experimental validation.IEEE Trans Control Syst Technol2000;8(6):905–18.[17]Yang Vigor,Sinha Alok,Fung YT.State-feedback control of longitudinal combustion instabilities.J Prop Power1992;8(1):66–73.[18]Fung YT,Yang Vigor,Sinha Alok.Active control of combustion instabilities with distributed bus Sci Technol1991;78:217–45.[19]Fung YT,Yang Vigor.Active control of nonlinear pressure oscillations in combustion chambers.J Prop Power1992;8(6):1282–9.[20]Krstic Miroslav,Krupadanam Ashish,Jacobson Clas.Self-tuning control of a nonlinear model of combustion instabilities.IEEE Trans Control SystTechnol1999;7(4):424–35.[21]Tornambe A,Valigi PA.Decentralized controller for the robust stabilization of a class of MIMO dynamical systems.J Dynam Syst,Measure,Control1994;116:293–304.[22]Wuqi.Principle of automatic control.Beijing:Tsinghua University Press;1990.。
艾氟康唑(英文说明书)
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__________________ ______________HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use JUBLIA safely and effectively. See full prescribing information for JUBLIA. JUBLIA® (efinaconazole) topical solution, 10%For topical useInitial U.S. Approval: 2014INDICATIONS AND USAGEJUBLIA is an azole antifungal indicated for the topical treatment of onychomycosis of the toenails due to Trichophyton rubrum and Trichophyton mentagrophytes. (1)_______________DOSAGE AND ADMINISTRATION• Apply JUBLIA to affected toenails once daily for 48 weeks using the integrated flow-through brush applicator. (2)• When applying JUBLIA, ensure the toenail, the toenail folds, toenail bed, hyponychium, and the undersurface of the toenail plate, are completely covered. (2)• For topical use only. (2) • Not for oral, ophthalmic, or intravaginal use. (2)DOSAGE FORMS AND STRENGTHSSolution: 10%. (3)___________________ CONTRAINDICATIONS ___________________ None. (4)___________________ ADVERSE REACTIONS ___________________ The most common adverse reactions (incidence >1%) were ingrown toenails, application site dermatitis, application site vesicles, and application site pain.(6.1)To report SUSPECTED ADVERSE REACTIONS, contact Valeant Pharmaceuticals North America LLC at 1-800-321-4576 or FDA at 1-800FDA-1088 or /medwatch.See 17 for PATIENT COUNSELING INFORMATION and FDA-Approved Patient LabelingRevised: 06/2014FULL PRESCRIBING INFORMATION: CONTENTS*12 CLINICAL PHARMACOLOGY 1 INDICATIONS AND USAGE 12.1 Mechanism of Action2 3 DOSAGE AND ADMINISTRATIONDOSAGE FORMS AND STRENGTHS12.2 Pharmacodynamics12.3 Pharmacokinetics4 6 CONTRAINDICATIONSADVERSE REACTIONS 1312.4 MicrobiologyNONCLINICAL TOXICOLOGY7 6.1 Clinical Trials ExperienceDRUG INTERACTIONS 1413.1 Carcinogenesis, Mutagenesis, Impairment of FertilityCLINICAL STUDIES8 USE IN SPECIFIC POPULATIONS8.1 Pregnancy8.3 Nursing Mothers8.4 Pediatric Use8.5 Geriatric Use 1617*SeareHOW SUPPLIED/STORAGE AND HANDLINGPATIENT COUNSELING INFORMATIONctions or subsections omitted from the full prescribing information not listed.11 DESCRIPTION 1FULL PRESCRIBING INFORMATION1 INDICATIONS AND USAGEJUBLIA (efinaconazole) topical solution, 10% is an azole antifungal indicated for the topical treatment of onychomycosis of the toenail(s) due to Trichophyton rubrum and Trichophyton mentagrophytes.2 DOSAGE AND ADMINISTRATIONApply JUBLIA to affected toenails once daily for 48 weeks, using the integrated flow-through brush applicator. When applying JUBLIA, ensure the toenail, the toenail folds, toenail bed, hyponychium, and the undersurface of the toenail plate, are completely covered.JUBLIA is for topical use only and not for oral, ophthalmic, or intravaginal use.3 DOSAGE FORMS AND STRENGTHSJUBLIA (efinaconazole) topical solution, 10% contains 100 mg of efinaconazole in each gram of clear, colorless to pale yellow solution.4 CONTRAINDICATIONSNone.6 ADVERSE REACTIONS6.1 Clinical Trials ExperienceBecause clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.In two clinical trials, 1227 subjects were treated with JUBLIA, 1161 for at least 24 weeks and 780 for 48 weeks. Adverse reactions reported within 48 weeks of treatment and in at least 1% of subjects treated with JUBLIA and those reported in subjects treated with the vehicle are presented in Table 1.Table 1: Adverse Reactions Reported by at Least 1% of Subjects Treated for up to 48 WeeksAdverse Event, n (%) JUBLIAN = 1227 Vehicle N = 413Ingrown toenail 28 (2.3%) 3 (0.7%) Application site dermatitis 27 (2.2%) 1 (0.2%) Application site vesicles 20 (1.6%) 0 (0.0%) Application site pain 13 (1.1%) 1 (0.2%)7 DRUG INTERACTIONSIn vitro studies have shown that JUBLIA, at therapeutic concentrations, neither inhibits nor induces cytochrome P450 (CYP450) enzymes.8 USE IN SPECIFIC POPULATIONS8.1 PregnancyPregnancy Category CThere are no adequate and well-controlled studies with JUBLIA in pregnant women. JUBLIA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.Systemic embryofetal development studies were conducted in rats and rabbits. Subcutaneous doses of 2, 10 and 50 mg/kg/day efinaconazole were administered during the period of organogenesis (gestational days 6-16) to pregnant female rats. In the presence of maternal toxicity, embryofetal toxicity (increased embryofetal deaths, decreased number of live fetuses, and placental effects) was noted at 50 mg/kg/day [559 times the Maximum Recommended Human Dose (MRHD) based on Area Under the Curve (AUC) comparisons]. No embryofetal toxicity was noted at 10 mg/kg/day (112 times the MRHD based on AUC comparisons). No malformations were observed at 50 mg/kg/day (559 times the MRHD based on AUC comparisons).Subcutaneous doses of 1, 5, and 10 mg/kg/day efinaconazole were administered during the period of organogenesis (gestational days 6-19) to pregnant female rabbits. In the presence of maternal toxicity, there was no embryofetal toxicity or malformations at 10 mg/kg/day (154 times the MRHD based on AUC comparisons).In a pre-and post-natal development study in rats, subcutaneous doses of 1, 5 and 25 mg/kg/day efinaconazole were administered from the beginning of organogenesis (gestation day 6) through the end of lactation (lactation day 20). In the presence of maternal toxicity, embryofetal toxicity (increased prenatal pup mortality, reduced live litter sizes and increased postnatal pup mortality) was noted at 25 mg/kg/day. No embryofetal toxicity was noted at 5 mg/kg/day (17 times the MRHD based on AUC comparisons). No effects on postnatal development were noted at25 mg/kg/day (89 times the MRHD based on AUC comparisons).8.3 Nursing MothersIt is not known whether efinaconazole is excreted in human milk. After repeated subcutaneous administration, efinaconazole was detected in milk of nursing rats. Because many drugs are excreted in human milk, caution should be exercised when JUBLIA is administered to nursing women.8.4 Pediatric UseSafety and effectiveness of JUBLIA in pediatric subjects have not been established.8.5 Geriatric UseOf the total number of subjects in clinical trials of JUBLIA, 11.3% were 65 and over, while none were 75 and over. No overall differences in safety and effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and the younger subjects, but greater sensitivity of some older individuals cannot be ruled out.11 DESCRIPTIONJUBLIA (efinaconazole) topical solution, 10% is a clear colorless to pale yellow solution for topical use. Each gram of JUBLIA contains 100 mg of efinaconazole. Efinaconazole is an azole antifungal with a chemical name of ((2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidin-1yl)-1-(1H-1,2,4-triazol-1-yl) butan-2-ol). The structural formula for efinaconazole is represented below:Molecular Formula: C18H22F2N4O Molecular Weight: 348.39JUBLIA contains the following inactive ingredients: alcohol, anhydrous citric acid, butylated hydroxytoluene, C12-15 alkyl lactate, cyclomethicone, diisopropyl adipate, disodium edetate, and purified water.12 CLINICAL PHARMACOLOGY12.1 Mechanism of ActionJUBLIA topical solution is an azole antifungal [see Clinical Pharmacology (12.4)].12.2 PharmacodynamicsThe pharmacodynamics of JUBLIA is unknown.12.3 PharmacokineticsSystemic absorption of efinaconazole in 18 adult subjects with severe onychomycosis was determined after application of JUBLIA once daily for 28 days to patients 10 toenails and 0.5 cm adjacent skin. The concentration of efinaconazole in plasma was determined at multiple time points over the course of 24-hour periods on days 1, 14, and 28. Efinaconazole mean ± SD plasma C max on Day 28 was 0.67 ± 0.37 ng/mL and the mean ± SD AUC was 12.15 ± 6.91ng*h/mL. The plasma concentration versus time profile at steady state was generally flat over a 24-hour dosing interval. In a separate study of healthy volunteers, the plasma half-life of efinaconazole following daily applications when applied to all 10 toenails for 7 days was 29.9 hours.Drug InteractionsJUBLIA is considered a non-inhibitor of the CYP450 enzyme family. In in vitro studies using human liver microsomes, efinaconazole did not inhibit CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2PE1 and CYP3A4 enzyme activities at expected clinical systemicconcentrations. In vitro studies in human primary hepatocytes showed that efinaconazole did not induce CYP1A2 or CYP3A4 activities.12.4 MicrobiologyMechanism of ActionEfinaconazole is an azole antifungal. Efinaconazole inhibits fungal lanosterol 14α-demethylase involved in the biosynthesis of ergosterol, a constituent of fungal cell membranes.Activity In Vitro and In VivoEfinaconazole has been shown to be active against isolates of the following microorganisms, both in vitro and in clinical infections. Efinaconazole exhibits in vitro minimum inhibitory concentrations (MICs) of 0.06 μg/mL or less against most (≥90%) isolates of the following microorganisms:Trichophyton rubrumTrichophyton mentagrophytesMechanism of ResistanceEfinaconazole drug resistance development was studied in vitro against T. mentagrophytes, T. rubrum and C. albicans. Serial passage of fungal cultures in the presence of sub-growth inhibitory concentrations of efinaconazole increased the MIC by up to 4-fold. The clinical significance of these in vitro results is unknown.13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of FertilityA 2-year dermal carcinogenicity study in mice was conducted with daily topical administration of 3%, 10% and 30% efinaconazole solution. Severe irritation was noted at the treatment site in all dose groups, which was attributed to the vehicle and confounded the interpretation of skin effects by efinaconazole. The high dose group was terminated at week 34 due to severe skin reactions. No drug-related neoplasms were noted at doses up to 10% efinaconazole solution (248 times the MRHD based on AUC comparisons).Efinaconazole revealed no evidence of mutagenic or clastogenic potential based on the results of two in vitro genotoxicity tests (Ames assay and Chinese hamster lung cell chromosome aberration assay) and one in vivo genotoxicity test (mouse peripheral reticulocyte micronucleus assay).No effects on fertility were observed in male and female rats that were administered subcutaneous doses up to 25 mg/kg/day efinaconzole (279 times the MRHD based on AUC comparisons) prior to and during early pregnancy. Efinaconazole delayed the estrous cycle in females at 25 mg/kg/day but not at 5 mg/kg/day (56 times MRHD based on AUC comparisons).14 CLINICAL STUDIESThe safety and efficacy of once daily use of JUBLIA for the treatment of onychomycosis of the toenail were assessed in two 52-week prospective, multi-center, randomized, double-blind clinical trials in patients 18 years and older (18 to 70 years of age) with 20% to 50% clinical involvement of the target toenail, without dermatophytomas or lunula (matrix) involvement. The trials compared 48-weeks of treatment with JUBLIA to the vehicle solution. The Complete Cure rate was assessed at Week 52 (4-weeks after completion of therapy). Complete cure was defined as 0% involvement of the target toenail (no clinical evidence of onychomycosis of the target toenail) in addition to Mycologic Cure, defined as both negative fungal culture and negative KOH. Table 2 lists the efficacy results for trials 1 and 2.Table 2: Efficacy EndpointsTrial 1 Trial 2JUBLIA Vehicle JUBLIA VehicleN = 656 N = 214 N = 580 N = 201Complete Cure a11717.8%73.3%8815.2%115.5%Complete or Almost Complete Cure b17326.4%157.0%13623.4%157.5%Mycologic Cure c 362 36 310 3455.2% 16.8% 53.4% 16.9%a Complete cure defined as 0% clinical involvement of the target toenail plus negative KOH and negative culture.b Complete or almost complete cure defined as ≤5% affected target toenail area involved and negative KOH and culture.c Mycologic cure defined as negative KOH and negative culture.16 HOW SUPPLIED/STORAGE AND HANDLINGJUBLIA (efinaconazole) topical solution, 10% is a clear, colorless to pale yellow solution supplied in a white plastic bottle with an integrated flow-through brush applicator as follows:• 4 mL (NDC 0187-5400-04)•8 mL (NDC 0187-5400-08)Storage and Handling Conditions:Store at 20°C -25°C (68°F -77°F); excursions permitted to 15°C -30°C (59°F -86°F) [see USP Controlled Room Temperature].• Solution is flammable; keep away from heat or flame• Protect from freezing• Keep out of the reach of children• Keep bottle tightly closed• Store in upright position17 PATIENT COUNSELING INFORMATIONSee FDA-Approved Patient Labeling (Patient Information)• JUBLIA is for external use only and is not for ophthalmic, oral, or intravaginal use. It is for use on toenails and immediately adjacent skin only.• Apply JUBLIA once daily to clean dry toenails. Wait for at least 10 minutes after showering, bathing, or washing before applying.• Use JUBLIA only on the affected toenails, as directed by your healthcare provider.• Inform a health care professional if the area of application shows signs of persistent irritation (for example, redness, itching, swelling).• Avoid pedicures, the use of nail polish, and cosmetic nail products while using JUBLIA.• Flammable, avoid use near heat or open flame.Manufactured for: Valeant Pharmaceuticals North America LLC, Bridgewater, NJ 08807 USA Manufactured by: Kaken Pharmaceutical Co. Ltd, Shizuoka, JapanProduct of JapanU.S. Patents 8,039,494; 7,214,5069391900 Issued: 06/2014PATIENT INFORMATIONJUBLIA (joo-blee-uh)(efinaconazole) topical solution, 10%Important information: JUBLIA is for use on toenails and surrounding skin only. Do not use JUBLIA in your mouth, eyes, or vagina.What is JUBLIA?JUBLIA is a prescription medicine used to treat fungal infections of the toenails.It is not known if JUBLIA is safe and effective in children.What should I tell my healthcare provider before using JUBLIA?Before you use JUBLIA, tell your healthcare provider about all your medical conditions, including if you:•are pregnant or plan to become pregnant. It is not known if JUBLIA can harm your unborn baby.•are breastfeeding or plan to breastfeed. It is not known if JUBLIA passes into your breast milk. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.How should I use JUBLIA?See the “Instructions for Use” at the end of this Patient Information leaflet for detailed information about the right way to use JUBLIA.•Use JUBLIA exactly as your healthcare provider tells you to use it. Apply JUBLIA to your affected toenails 1 time each day. Wait for at least 10 minutes after showering, bathing, or washing before applying JUBLIA. JUBLIA is used for 48 weeks.What should I avoid while using JUBLIA?•JUBLIA is flammable. Avoid heat and flame while applying JUBLIA to your toenail.•Avoid pedicures, use of nail polish, or cosmetic nail products, while using JUBLIA.What are the possible side effects of JUBLIA?JUBLIA may cause irritation at the treated site. The most common side effects include: ingrown toenail, redness, itching, swelling, burning or stinging, blisters, and pain. Tell your healthcare provider if you have any side effects that bother you or that does not go away.These are not all the possible side effects of JUBLIA.Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1800-FDA-1088.How should I store JUBLIA?•Store JUBLIA at room temperature, between 68°F to 77°F (20°C to 25°C). Do not freeze JUBLIA.•Keep the bottle tightly closed and store in an upright position.•JUBLIA is flammable. Keep away from heat and flame.Keep JUBLIA and all medicines out of the reach of children.General information about the safe and effective use of JUBLIAMedicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask your pharmacist or healthcare provider for information about JUBLIA that is written for health professionals. Do not use JUBLIA for a condition for which it was not prescribed. Do not give JUBLIA to other people, even if they have the same condition you have. It may harm them.What are the ingredients in JUBLIA?Active ingredients: efinaconazoleInactive ingredients: alcohol, anhydrous citric acid, butylated hydroxytoluene, C12-15 alkyl lactate, cyclomethicone, diisopropyl adipate, disodium edetate, and purified water. Manufactured for: Valeant Pharmaceuticals North America LLC, Bridgewater, NJ 08807 Manufactured by: Kaken Pharmaceutical Co. Ltd, Shizuoka, Japan. Product of JapanFor more information, call 1-800-321-4576.This Patient Information has been approved by the U.S. Food and Drug Administration. Issued: 06/2014Instructions for UseJUBLIA® (joo-blee-uh)(efinaconazole) topical solution, 10%Important information: JUBLIA is for use on toenails and surrounding skin only. Do not use JUBLIA in your mouth, eyes or vagina.Read the Instructions for Use that comes with JUBLIA before you start using it. Talk to your healthcare provider if you have any questions.How to apply JUBLIA:Your toenails should be clean and dry before you apply JUBLIA.Step 1: Before you apply JUBLIA to your affected toenail, remove the cap from the JUBLIA bottle (See Figure A).Step 2: Hold the bottle directly over the affected toenail and gently squeeze the bottle to apply one drop of JUBLIA onto the toenail (See Figure B).Step 3: For the big toenail, also apply a second drop to the end of the toenail (See FigureC).Step 4: Use the brush attached to the bottle to gently spread JUBLIA around the entire toenail including: the cuticle, folds of the skin next to the sides of the toenail, andunderneath the nail (See Figure D). Do not squeeze the bottle while spreadingJUBLIA with the brush.Step 5: Repeat Steps 2 to 4 to apply JUBLIA to each affected toenail.Step 6: Let JUBLIA dry completely.Step 7: After applying JUBLIA to your affected toenails, place the cap on the bottle and screw it on tightly.Step 8: Wash your hands with soap and water after applying JUBLIA.This Patient Information and Instructions for Use has been approved by the U.S. Food and Drug Administration.Manufactured for: Valeant Pharmaceuticals North America LLC, Bridgewater, NJ 08807 USA Manufactured by: Kaken Pharmaceutical Co. Ltd, Shizuoka, Japan.Product of JapanIssued: 06/2014。
CRRT的几个基本概念
![CRRT的几个基本概念](https://img.taocdn.com/s3/m/5db688f3dc3383c4bb4cf7ec4afe04a1b171b063.png)
Return Pressure Positive +50 to +150 mmHg
Effluent Pressure Negative or Positive >+50 to -150 mmHg
高通量旳滤器 面积 1.6-2.2平方米
HVHF
总之,对重症脓毒血症或合并休克患者, CRRT极难设定上限计量,尚需研究,超滤
率至少应≥35ml/kg/h。
Access Pressure Negative -50 to -150 mmHg
Filter Pressure Positive +100 to +250 mmHg
凝措施) 局部肝素抗凝法 局部枸橼酸盐抗凝法 低分子肝素抗凝法 无肝素抗凝法 前列腺素抗凝法
前列腺素抗凝法
原理:阻断血小板粘附功能和汇集功能 有人以为比肝素安全,半衰期极短(2min) 缺陷:停用后抗血小板活性时间长(24H) 无中和制剂 调整需依赖血小板汇集试验 药物剂量依赖性低血压发生率高 应用
技术构成三
滤器 聚砜膜(AV400及AV600)滤器 聚丙烯腈膜(AN69)滤器
AN 69
AV600
血液滤过器旳构造
血液入口
透析液和滤 出液出口
横断面
空心纤维 膜
透析液入 口
血液出口
空心纤维外面 (滤出液) 空心纤维里面 (血液)
血滤器
种类
聚砜膜
聚丙烯晴膜
聚酰胺
膜通透性
低通量滤器 <10000D
治疗中旳经典压力
治疗中旳经典压力
动脉压Access Pressure
测量当血液离开病人血液通路(例如双腔导管)时 旳压力(体外旳)
法布里珀罗基模共振英文
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法布里珀罗基模共振英文The Fabryperot ResonanceOptics, the study of light and its properties, has been a subject of fascination for scientists and researchers for centuries. One of the fundamental phenomena in optics is the Fabry-Perot resonance, named after the French physicists Charles Fabry and Alfred Perot, who first described it in the late 19th century. This resonance effect has numerous applications in various fields, ranging from telecommunications to quantum physics, and its understanding is crucial in the development of advanced optical technologies.The Fabry-Perot resonance occurs when light is reflected multiple times between two parallel, partially reflective surfaces, known as mirrors. This creates a standing wave pattern within the cavity formed by the mirrors, where the light waves interfere constructively and destructively to produce a series of sharp peaks and valleys in the transmitted and reflected light intensity. The specific wavelengths at which the constructive interference occurs are known as the resonant wavelengths of the Fabry-Perot cavity.The resonant wavelengths of a Fabry-Perot cavity are determined bythe distance between the mirrors, the refractive index of the material within the cavity, and the wavelength of the incident light. When the optical path length, which is the product of the refractive index and the physical distance between the mirrors, is an integer multiple of the wavelength of the incident light, the light waves interfere constructively, resulting in a high-intensity transmission through the cavity. Conversely, when the optical path length is not an integer multiple of the wavelength, the light waves interfere destructively, leading to a low-intensity transmission.The sharpness of the resonant peaks in a Fabry-Perot cavity is determined by the reflectivity of the mirrors. Highly reflective mirrors result in a higher finesse, which is a measure of the ratio of the spacing between the resonant peaks to their width. This high finesse allows for the creation of narrow-linewidth, high-resolution optical filters and laser cavities, which are essential components in various optical systems.One of the key applications of the Fabry-Perot resonance is in the field of optical telecommunications. Fiber-optic communication systems often utilize Fabry-Perot filters to select specific wavelength channels for data transmission, enabling the efficient use of the available bandwidth in fiber-optic networks. These filters can be tuned by adjusting the mirror separation or the refractive index of the cavity, allowing for dynamic wavelength selection andreconfiguration of the communication system.Another important application of the Fabry-Perot resonance is in the field of laser technology. Fabry-Perot cavities are commonly used as the optical resonator in various types of lasers, providing the necessary feedback to sustain the lasing process. The high finesse of the Fabry-Perot cavity allows for the generation of highly monochromatic and coherent light, which is crucial for applications such as spectroscopy, interferometry, and precision metrology.In the realm of quantum physics, the Fabry-Perot resonance plays a crucial role in the study of cavity quantum electrodynamics (cQED). In cQED, atoms or other quantum systems are placed inside a Fabry-Perot cavity, where the strong interaction between the atoms and the confined electromagnetic field can lead to the observation of fascinating quantum phenomena, such as the Purcell effect, vacuum Rabi oscillations, and the generation of nonclassical states of light.Furthermore, the Fabry-Perot resonance has found applications in the field of optical sensing, where it is used to detect small changes in physical parameters, such as displacement, pressure, or temperature. The high sensitivity and stability of Fabry-Perot interferometers make them valuable tools in various sensing and measurement applications, ranging from seismic monitoring to the detection of gravitational waves.The Fabry-Perot resonance is a fundamental concept in optics that has enabled the development of numerous advanced optical technologies. Its versatility and importance in various fields of science and engineering have made it a subject of continuous research and innovation. As the field of optics continues to advance, the Fabry-Perot resonance will undoubtedly play an increasingly crucial role in shaping the future of optical systems and applications.。
英文原文-超声波辅助提取大豆异黄酮
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1. Introduction Isoflavones are a flavanoid subgroup found in several plants. In soybeans, they are present in 12 main forms: genistin, glycitin, daidzin and their respective acetyl, malonyl and aglucon forms [1]. There is an increasing interest in these compounds due to their biological effects, including estrogenic and fungitoxic activities. Isoflavones have been associated with a decreased risk of breast, prostate and colon cancers and are being studied for the prevention of menopausal symptoms and osteoporosis (see Ref. [2] for a review). They may be
Abstract Efficiency in extracting four isoflavone derivatives (daidzin, glycitin, genistin and malonyl genistin) from freeze–dried ground soybeans was compared for mix-stirring extraction and ultrasound-assisted extraction, using different solvents and extraction temperatures with both. The efficiency of the extraction of soy isoflavones was improved by ultrasound but was dependent on the solvent employed. Optimization of the ratios of sample quantity to solvent volume and length of extraction time was also performed. Isoflavones can be quantitatively extracted from soybeans with 50% ethanol at 60 8C using ultrasound-assisted extraction in 20 min. 2003 Elsevier B.V. All rights reserved. Keywords: Ultrasound-assisted extraction; Extraction methods; Soybean; Isoflavones
国际上著名的从事药剂学研究的专家
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Intra Oral Delivery (口腔内传递)直接由口腔黏膜吸收,瞬间进入血液循环,有效成分不流失。
Universities, Departments,FacultiesResearchersButler University College of Pharmacy and Health Sciences Health Sciences USA Associate Professor Nandita G. DasMain focus on her research facilities are about peformulation, biopharmaceutics, drug targeting, anticancer drug delivery.Purdue University School of Pharmacy and Pharmacal Sciences Department of Industrial and Physical Pharmacy (IPPH) USA Professor Kinam ParkControlled Drug Delivery, Glucose-Sensitive Hydrogels for Self-Regulated Insulin Delivery, Superporous Hydrogel Composites, Oral Vaccination using Hydrogel Microparticles, Fractal Analysis of Pharmaceutical Solid Materials.St. John's University School of Pharmacy and Allied Health ProfessionsUSA Professor Parshotam L. MadanControlled and targeted drug delivery systems; Bio-erodible polymers as drug delivery systemsThe University of Iowa College of Dentistry Department of Oral Pathology, Radiology, and Medicine USA Professor Christopher A. Squierpermeability of skin, and oral mucosa to exogenous substances, including alcohol and tobacco, and drug deliveryThe University of Iowa College of Pharmacy Department of Pharmaceutics USA Associate Professor Maureen D. DonovanMucosal drug delivery especially via the nasal, gastrointestinal and vaginal epithelia; and mechanisms of drug absorption and disposition.The University of Texas at San Antonio College of Engineering Department of Biomedical Engineering USA Professor Jeffrey Y. ThompsonDental restorative materials and implantsThe University of Utah Pharmaceutics & Pharmaceutical Chemistry USA Professor John W. MaugerDr. Maugner is mainly focused on dissolution testing and coating technology of orally administered drug products with bitter taste about which he is one of the inventors of a filed patent.University of Kentucky College of Pharmacy Pharmaceutical Sciences USA Professor Peter CrooksDr. Crooks is internationally known for his research work in drug discovery, delivery, and development, which includes drug design and synthesis, pharmacophore development, drug biotransformation studies, prodrug design, and medicinal plant natural product research. His research also focuses on preclinical drug development, including drug metabolism and pharmacokinetics in animal models, dosage form development, and drug delivery assessment using both conventional and non-conventional routes, and preformulation/formulation studies.Associate Professor Russell MumperDr. Mumper's main research areas are thin-films and mucoadhesive gels for (trans)mucosal delivery of drugs, microbicides, and mucosal vaccines, and nanotemplate engineering of nano-based detection devices and cell-specific nanoparticles for tumor and brain targeting, gene therapy and vaccines.West Virginia University School of Pharmacy Department of Basic Pharmaceutical Sciences USA Associate Professor Paula Jo Meyer StoutDr. Stout's research areas are composed of dispersed pharmaceutical systems, sterile product formulation DDS for dental diseases and coating of sustained release formulations.Monash University Victorian College of Pharmacy Department of Pharmaceutics Australia Professor Barrie C. FinninTransdermal Drug Delivery. Physicochemical Characterisation of Drug Candidates. Topical Drug Delivery. Drug uptake by the buccal mucosaProfessor Barry L. ReedTransdermal Drug Delivery. Topical Drug Delivery. Formulation of Dental Pharmaceuticals.University of Gent Faculty of Pharmaceutical Sciences Department of Pharmaceutics Belgium Professor Chris Vervaet-Extrusion/spheronisation - Bioadhesion - Controlled release based on hot stage extrusion technology - Freeze-drying - Tabletting and - GranulationPh.D. Els AdriaensMucosal drug delivery (Vaginal and ocular) Nasal BioadhesionUniversity of Gent Faculty of Pharmaceutical SciencesLaboratory of Pharmaceutical Technology Belgium Professor Jean Paul Remonbioadhesive carriers, mucosal delivery, Ocular bioerodible minitablets, Compaction of enteric-coated pellets; matrix-in-cylinder system for sustained drug delivery; formulation of solid dosage forms; In-line monitoring of a pharmaceutical blending process using FT-Raman spectroscopy; hot-melt extruded mini-matricesDanish University of Pharmaceutical Sciences Department of Pharmaceutics Denmark Associate Professor Jette JacobsenLow soluble drugs ?in vitro lymphatic absorption Drug delivery to the oral cavity ?in vitro models (cell culture, diffusion chamber) for permeatbility and toxicity of drugs, in vivo human perfusion model, different formulation approaces, e.g. iontophoresis.。
开启片剂完整性的窗户(中英文对照)
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开启片剂完整性的窗户日本东芝公司,剑桥大学摘要:由日本东芝公司和剑桥大学合作成立的公司向《医药技术》解释了FDA支持的技术如何在不损坏片剂的情况下测定其完整性。
太赫脉冲成像的一个应用是检查肠溶制剂的完整性,以确保它们在到达肠溶之前不会溶解。
关键词:片剂完整性,太赫脉冲成像。
能够检测片剂的结构完整性和化学成分而无需将它们打碎的一种技术,已经通过了概念验证阶段,正在进行法规申请。
由英国私募Teraview公司研发并且以太赫光(介于无线电波和光波之间)为基础。
该成像技术为配方研发和质量控制中的湿溶出试验提供了一个更好的选择。
该技术还可以缩短新产品的研发时间,并且根据厂商的情况,随时间推移甚至可能发展成为一个用于制药生产线的实时片剂检测系统。
TPI技术通过发射太赫射线绘制出片剂和涂层厚度的三维差异图谱,在有结构或化学变化时太赫射线被反射回。
反射脉冲的时间延迟累加成该片剂的三维图像。
该系统使用太赫发射极,采用一个机器臂捡起片剂并且使其通过太赫光束,用一个扫描仪收集反射光并且建成三维图像(见图)。
技术研发太赫技术发源于二十世纪九十年代中期13本东芝公司位于英国的东芝欧洲研究中心,该中心与剑桥大学的物理学系有着密切的联系。
日本东芝公司当时正在研究新一代的半导体,研究的副产品是发现了这些半导体实际上是太赫光非常好的发射源和检测器。
二十世纪九十年代后期,日本东芝公司授权研究小组寻求该技术可能的应用,包括成像和化学传感光谱学,并与葛兰素史克和辉瑞以及其它公司建立了关系,以探讨其在制药业的应用。
虽然早期的结果表明该技术有前景,但日本东芝公司却不愿深入研究下去,原因是此应用与日本东芝公司在消费电子行业的任何业务兴趣都没有交叉。
这一决定的结果是研究中心的首席执行官DonArnone和剑桥桥大学物理学系的教授Michael Pepper先生于2001年成立了Teraview公司一作为研究中心的子公司。
TPI imaga 2000是第一个商品化太赫成像系统,该系统经优化用于成品片剂及其核心完整性和性能的无破坏检测。
Analysis of compliance between the cutting tool and the workpiece on
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E-mail addresses: vela@ciateq.mx (L. Vela-Martı´ nez), ´ uregui-Correa), eduardo.ruateq.mx (J.C. Ja (E. Rubio-Cerda), gherrera@uaq.mx (G. Herrera-Ruiz), ´ n). concyteq@.mx (A. Lozano-Guzma 0890-6955/$ - see front matter r 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.ijmachtools.2007.10.016
ARTICLE IN PRESS
´nez et al. / International Journal of Machine Tools & Manufacture 48 (2008) 1054–1062 L. Vela-Martı 1055
Nomenclature € 1 ðtÞ, x _ 1 ðtÞ, x1 ðtÞ acceleration, velocity and displacex ment of the cutting tool in the present time € 2 ðtÞ, x _ 2 ðtÞ, x2 ðtÞ acceleration, velocity and displacex ment of the workpiece in the current time z1, on1, m1 damping ratio; natural frequency (Hz), and modal mass (kg) of the cutting tool z2, on2, m2 damping ratio; natural frequency (Hz), and modal mass (kg) of the workpiece Fx(t) force in feed direction (N) Kc, Kf cutting coefficients (N/m2) b depth of cut (m) f0 nominal feed (rpm) x1 (tÀt), x2 (tÀt) displacement of the cutting tool and the workpiece in the previous time f(t) dynamic feed in terms of relative motion Fc(t), Ff(t) cutting and feed forces (N) t time delay (s) [I] unit matrix [C] damping coefficients matrix [K] stiffness coefficients matrix {f(t)} dynamic feed vector ff^g static feed vector {F(t)} dynamic force vector € ðtÞg, fx _ ðtÞg, fxðtÞg acceleration, velocity and displacefx ment vectors ^ b specific depth of cut [A] coupling matrix {x(t)}, {xt(t)} displacement vector in present time and time delay, respectively
国内中国期刊的英文缩写
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Abstr. Papers Am. Chem. Soc. Abstracts of Papers. American Chemical Society Acta Academiae Aboensis Acta Academiae AboensisActa Chem. Scand. Acta Chemica ScandinavicaActa Crystallograph. Acta CrystallographicaActa Hydrobiol. Sinica Acta Hydrobiolica SinicaActa Hydrochim. Hydrobiol. Acta Hydrochimica et HydrobiologicaActa Med. Scand. Acta Medica ScandinavicaActa Pharmaceutica Fennica Acta Pharmaceutica FennicaAmbio AmbioAnalyst AnalystAnalyt. Bioanalyt. Chem. Analytical and Bioanalytical Chemistry Analyt. Biochem. Analytical BiochemistryAnalyt. Chem. Analytical ChemistryAnalyt. Chim. Acta Analytica Chimica ActaAnalyt. Lett. Analytical LettersAnalyt. Sci. Analytical Sciences——仅供参考Angew. Chem. Int. Ed. Angewandte Chemie–International EditionAnn. Allergy Annals of AllergyAnn. Internal Med. Annals of Internal MedicineAnn. Limnol. Annales de Limnologie–International Journal ofLimnologyAnn. N.Y. Acad. Sci. Annals. New York Academy of SciencesAnn. Rev. Microbiol. 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Nippon Suisan GakkaishiNorsk Veterinaertidsskrift Norsk VeterinaertidsskriftNZ. J. Mar. Freshwater Res. New Zealand Journal of Marine and Freshwater Research NZ. Vet. J. New Zealand Veterinary JournalOecologiaOpheliaOrg. Lett.PathologyPest. Sci.Pharmacol. Therapeut. Pharmacology & TherapeuticsPharmacol. Toxicol. Pharmacology & ToxicologyPharmacology PharmacologyPharmazie PharmaziePhilosoph. Trans. Roy. Soc. London Ser. B.Biol. Sci. Philisophical Transactions of the Royal Society of London Series B–Biological SciencesPhotosyn. Res. Photosynthesis Research Phycol. Res. Phycological ResearchPhycol. Soc. Am. News Bull. Phycological Society of American News Bulletin Phycologia PhycologiaPhykos PhykosPhysiol. Plant. Physiologica PlantarumPhysiol. Rev. Physicological ReviewsPhytochem. PhytochemistryPhytomedicine PhytomedicinePhyton–Int. J. Exp. Bot. Phyton. International Journal of Experimental BotanyPlant Sci.PlantaPlasmidProtein Sci. Protein ScienceProtist ProtistPub. Health Lab. Serv. 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Transplantation ProceedingsTrends Biochem. Sci. Trends in Biochemical SciencesTrends Plant Sci. Trends in Plant ScienceUmschauUrtVandVet. Med.Vet. Res.Water Environ. Res. Water Environment ResearchWater Poll. Control Water Pollution ControlWater Poll. Control Fed. J. Water Pollution Control Federation. JournalWater Quality Res. J. Canada Water Quality Research Journal of CanadaWater Res. Water ResearchWater Res. Action Water Research in ActionWater Resources Manage. Water Resources ManagementWater S. Afr. Water South AfricaWater Sci. Technol. Water Science & TechnologyWater Sci. Technol. Water Supply Water Science & Technology: Water Supply Water Sewage Works Water and Sewage WorksWater Treat. Exam. Water Treatment and ExaminationWeed Sci. Weed ScienceWildlife Soc. Bull. Wildlife Society. BulletinWissen. Z. Wilhelm-Pieck Uni. Rostock Wissenschaftliche Zeitschrift derWilhelm-Pieck-Universitaet Rostock。
211188541_基于体外发酵的双孢菇膳食纤维及双孢菇粉对人体肠道菌群的调节作用
![211188541_基于体外发酵的双孢菇膳食纤维及双孢菇粉对人体肠道菌群的调节作用](https://img.taocdn.com/s3/m/25f29f822dc58bd63186bceb19e8b8f67c1cefb2.png)
向情儒,李文远,冯涛. 基于体外发酵的双孢菇膳食纤维及双孢菇粉对人体肠道菌群的调节作用[J]. 食品工业科技,2023,44(10):130−137. doi: 10.13386/j.issn1002-0306.2022080226XIANG Qingru, LI Wenyuan, FENG Tao. Regulating Effects of Dietary Fiber and Powder of Agaricus bisporus Based on in Vitro Fermentation on Human Gut Microbiota[J]. Science and Technology of Food Industry, 2023, 44(10): 130−137. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2022080226· 生物工程 ·基于体外发酵的双孢菇膳食纤维及双孢菇粉对人体肠道菌群的调节作用向情儒1,李文远2,冯 涛2,*(1.新疆大学生命科学与技术学院,新疆乌鲁木齐 830017;2.上海应用技术大学香料学院,上海 201418)摘 要:目的:探究双胞菇膳食纤维以及双胞菇粉对肠道菌群的调节功能。
方法:通过水提醇沉的方法提取双胞菇膳食纤维和双胞菇粉末进行肠道微生物体外发酵,测定代谢产物中pH 、产气量、短链脂肪酸的含量,采用IlluminaPE250测序平台对粪便微生物V4区进行富集测序,探究双胞菇膳食纤维和双胞菇粉对于肠道菌群中短链脂肪酸产生菌相对丰度的影响。
结果:以低聚果糖为阳性对照组,不加膳食纤维为空白对照组,体外发酵过程中,随着时间的增加,双胞菇膳食纤维组pH 从6.93下降到4.48,双胞菇粉末pH 从6.93下降至4.86;随着时间的增加,与空白组相比,双胞菇膳食纤维组和双胞菇粉末组的产气量分别增加了3.4和1.9 mL ;在体外发酵24 h 后发现,与阳性对照组相比,双胞菇膳食纤维组和双胞菇粉末组的肠道菌群丰富度和多样性更高;双胞菇膳食纤维组和双胞菇粉末组均能被肠道微生物利用产生短链脂肪酸,与空白组相比,双胞菇膳食纤维组更有利于被肠道微生物利用产生乙酸(34.3 mmol/L )和丙酸(7.6 mmol/L ),促进有益菌属双歧杆菌属的生长,双胞菇粉末组更有利于产生乙酸(39.4 mmol/L ),促进肠杆菌属的生长;与阳性对照组相比,双胞菇膳食纤维组和双胞菇粉末组的丙酸产量更高。
USP 干燥失重法中英文对照
![USP 干燥失重法中英文对照](https://img.taocdn.com/s3/m/429a7edb49649b6648d7472e.png)
<731>LOSS ON DRYINGThe procedure set forth in this chapter determines the amount of volatile matter of any kind that is driven off under the conditions specified.For substances appearing to contain water as the only volatile constituent, the procedure given in the chapter,Water Determination921,is appropriate,and is specified in the individual monograph.Mix and accurately weigh the substance to be tested,and,unless otherwise directed in the individual monograph,conduct the determination on1to 2g.If the test specimen is in the form of large crystals,reduce the particle size to about2mm by quickly crushing.Tare a glass-stoppered, shallow weighing bottle that has been dried for30minutes under the same conditions to be employed in the determination.Put the test specimen in the bottle,replace the cover,and accurately weigh the bottle and the contents.By gentle,sidewise shaking,distribute the test specimen as evenly as practicable to a depth of about5mm generally,and not more than10mm in the case of bulky materials.Place the loaded bottle in the drying chamber,removing the stopper and leaving it also in the chamber. Dry the test specimen at the temperature and for the time specified in the monograph.[NOTE—The temperature specified in the monograph is to be regarded as being within the range of±2of the stated figure.]Upon opening the chamber,close the bottle promptly,and allow it to come to room temperature in a desiccator before weighing.If the substance melts at a lower temperature than that specified for the determination of Loss on drying,maintain the bottle with its contents for1to2hours at a temperature5to10below the melting temperature, then dry at the specified temperature.Where the specimen under test is Capsules,use a portion of the mixed contents of not fewer than4capsules.Where the specimen under test is Tablets,use powder from not fewer than 4tablets ground to a fine powder.Where the individual monograph directs that loss on drying be determined by thermogravimetric analysis,a sensitive electrobalance is to be used.Where drying in vacuum over a desiccant is directed in the individual monograph,a vacuum desiccator or a vacuum drying pistol,or other suitable vacuum drying apparatus,is to be used.Where drying in a desiccator is specified,exercise particular care to ensure that the desiccant is kept fully effective by frequent replacement.Where drying in a capillary-stoppered bottle*in vacuum is directed in the individual monograph,use a bottle or tube fitted with a stopper having a225±25µm diameter capillary,and maintain the heating chamber at a pressure of5mm or less of mercury.At the end of the heating period, admit dry air to the heating chamber,remove the bottle,and with the capillary stopper still in place allow it to cool in a desiccator before weighing.本章中给出的方法阐述了在特定的条件下物质中的挥发性成分的测定。
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Infinite period and Hopf bifurcations for the p H-regulated oscillations in a semibatch reactor(H2O2–Cu2؉–S2O32؊–NaOH system) Peter E.StrizhakL.V.Pisarzhevskii Institute of Physical Chemistry,National Academy of Sciences of Ukraine,Prospect Nauki31,Kiev252028,UkraineJohn A.PojmanDepartment of Chemistry and Biochemistry,University of Southern Mississippi,Hattiesburg,Mississippi39406-5043͑Received22January1996;accepted for publication1May1996͒Dynamic behavior of the p H-regulated oscillations has been studied for the hydrogen peroxideoxidation of thiosulfate ions in the presence of trace amounts of copper͑II͒ions in a semibatchreactor.A solution of0.08M Na2S2O3and0.112M NaOH wasflowed at0.160mL/min into300mL of solution containing the H2O2and Cu2ϩin a vessel.There exists a critical value of the H2O2or Cu2ϩconcentrations below which the system does not oscillate.The oscillations appear due to aninfinite period bifurcation at low initial concentrations of the H2O2.The initial concentration ofCu2ϩmay be considered as a bifurcation parameter in this case.Increase of the initial hydrogenperoxide concentration causes the p H-regulated oscillations through a nondegenerate supercriticalHopf bifurcation.The classification of bifurcations is based on the analysis of the behavior ofoscillation amplitude and period at different initial concentrations of the H2O2and Cu2ϩ.Our resultsshow a possibility to distinguish different scenarios for the appearance of transient oscillations insemibatch experiments.©1996American Institute of Physics.͓S1054-1500͑96͒00203-0͔We have studied p H-regulated oscillations in the hydro-gen peroxide oxidation of thiosulfate ions in the presenceof trace amounts of copper…II…in a semibatch reactor.There exists a critical value of the H2O2or Cu2؉concen-tration below which the system does not oscillate.At lowinitial concentrations of H2O2,the oscillations arise viaan infinite period bifurcation with the initial concentra-tion of Cu2؉as the bifurcation parameter.Atfixed †Cu2؉‡,increasing the initial hydrogen peroxide concen-tration leads to oscillations through a nondegenerate su-percritical Hopf bifurcation.Our classification of bifur-cations is based on an analysis of the amplitude ofoscillation and the period as functions of†H2O2‡and †Cu2؉‡.Our results demonstrate that it is possible to dis-tinguish different bifurcations that lead to the birth of oscillations in semibatch experiments,in which the sys-tem naturally moves through the parametric space as time increases,and all phenomena are transient.I.INTRODUCTIONSemibatch experiments are a modern tool to investigate nonlinear phenomena in chemical reactions.1–3This tech-nique possesses a middle place between CSTR͑continuous flow stirred tank reactor͒and batch͑closed reactor͒experi-ments.In a semibatch experiment reactants areflowed into a vessel containing other reagents.The oscillatory behavior has been found for different chemical systems under semi-batch conditions.Periodic pulsating phenomena were ob-served during the reaction of certain molten polymers with oxygen.4The catalyzed oxidation of benzaldehyde by oxygen,5the oxidation of NADH by O2,6the reduction of bromate by H2,7and the gas-phase reaction between H2and Cl2show oscillations in semibatch experiments.2Recently, nonlinear phenomena have been studied for oscillating reac-tions in homogeneous solutions in a semibatch reactor,spe-cifically,p H-regulated oscillations.1,8The experiments performed in a semibatch reactor show that this technique should be considered as a tool to investi-gate nonlinear phenomena in chemical systems.The semi-batch experiments can be easier to perform than CSTR ex-periments.However,there is a question about the lack of the well-controlled conditions for the semibatch experiments. The oscillations appear after a pseudoinduction period and disappear owing to the dilution of the solution.Of course, there is no true induction period because its length depends not only on the chemistry but also on the applied physical ually theflow rate is sufficiently low in a semibatch experiment that oscillations exist during a long time interval.During this time interval the dynamic behavior is very similar to that in a CSTR.This idea shows that semi-batch experiments can be useful tofind new systems that oscillate in a CSTR at lowflow rate.The similarity between semibatch and CSTR experiments leads to the question whether it is possible to check the origin of oscillations in a semibatch experiment using bifurcation theory.Our results show a possibility to distinguish different bifurcations for the birth of oscillations in semibatch experi-ments,in which the system naturally moves through the parametric space,and all phenomena are transient.We present evidence that it is possible in this case to apply bi-furcation analysis,with some special considerations.In this paper we apply bifurcation theory to the analysis of oscillations obtained from the semibatch experiment.We investigated the influence of the initial concentrations of cop-per͑II͒and hydrogen peroxide in a vessel with a solution461CHAOS6(3),19961054-1500/96/6(3)/461/5/$10.00©1996American Institute of Physicscontaining thiosulfate and hydroxide ionsflowed in at a con-stant rate.This system has been reported by Rabai and Ep-stein in a semibatch reactor1and has been studied previously in a CSTR by Orban and Epstein.9We found that p H-regulated oscillations appeared through an infinite period bi-furcation or Hopf bifurcation.We present evidence that the initial concentration of copper͑II͒in a vessel may be consid-ered as a bifurcation parameter.These results are of interest not only from the dynamical point of view but also because they show what bifurcations must be realized in a realistic chemical scheme for the H2O2–Cu2ϩ–S2O32Ϫ–NaOH oscil-lating system.II.EXPERIMENTAL SECTIONThe major reagents used without additional purification were CuSO4•5H2O͑Aldrich͒,Na2S2O3͑Fisher,certified͒, NaOH͑Aldrich͒,and hydrogen peroxide water solution ͓50%,about14.6M,͑Aldrich͔͒.Solutions were prepared us-ing deionized water.The stock concentration of hydrogen peroxide solution was determined by titration with the Ce4ϩ͓͑NH4͒2Ce͑NO3͒6,͑Aldrich͔͒in0.5M H2SO4͑Aldrich͒us-ing ferrion͑Fisher,aqueous solution͒as an indicator.10 The semibatch experiments were performed in a600mL reactor at constant temperature26Ϯ0.5°C.The behavior of the system was followed by measuring the p H͑Corning Ion analyzer250,combined glass p H electrode͒and the Pt elec-trode potential versus Hg͉Hg2SO4͉K2SO4reference͑Radiom-eter K601͒.The signals were digitized with a Macintosh IIcx.A four-channel peristaltic pump͑Rainin Instruments, model Rabbit-Plus͒was used to feed the input solution into the reactor.Experiments were performed at a constantflow rate of0.160mL/min.The concentrations of reagents in the inflow solution were the same in all experiments:0.08M Na2S2O3and0.112M NaOH.The initial volume of solution containing copper͑II͒ions and hydrogen peroxide was300 mL.The dynamical states of the system were determined by measuring the responses of p H and Pt electrodes as functions of the initial concentration of the reagents͑Cu2ϩand H2O2͒in a vessel.III.RESULTS AND DISCUSSIONFigure1shows the time evolution of the p H at differentinitial concentrations of copper͑II͒and hydrogen peroxide in a vessel.The systems start their evolution at p Hϳ6.The oscillations appear after long times͑1–7h͒and exist during 2–10h in the p H range between5.5and9.The oscillations disappear when the p H increases over9due to dilution of the reaction mixture by the inflow of solution.The amplitude of the p H-regulated oscillations and their shape depend in a complex manner on the initial concentrations of the Cu2ϩand H2O2in the reactor.Our experiments show that there exists a critical value of the initial concentration for both reagents below which the p H-regulated oscillations do not rge amplitude p H-regulated oscillations exist if the reaction starts at low initial concentrations of hydrogen per-oxide.In Fig.1͑a͒we show the case when large amplitude p H oscillations appear just after the pseudoinduction period. The amplitudes of these oscillations do not vary signifi-cantly.The increase of the initial concentration of the H2O2 leads to the appearance of the p H oscillations of another kind that are shown in Figs.1͑b͒and1͑c͒.In this case the p H goes through few peaks during the pseudoinduction period before almost regular oscillations appear.Figure1͑c͒shows the existence of a broad peak at250min.The oscillation period is much smaller when the oscillations appear at340 min.We propose that the oscillations appear from the pseu-dosteady state that undergoes complicated changes.After the onset of oscillations,their amplitude grows monotonically.The different behavior of p H-regulated oscillationsde-pending on the initial concentrations of reagents allows us to suggest that transient oscillations in this system may appear through different bifurcations.Our further steps to show that the appearance of oscillations at low initial concentration of H2O2may be associated with an infinite period bifurcation, whereas oscillations appear through a Hopf bifurcation at high initial concentration of H2O2.To understand the origin of oscillations in both cases we will attempt to apply bifur-cation theory to the experimental data.Bifurcation theory in its classical presentation describes the qualitative change of the asymptotic dynamics of the system as a control param-eter is varied.11–13The asymptotic state of a semibatch reac-tor is identical to that of the feedstream.Therefore,the ap-plication of bifurcation theory to nonlinear phenomena in a semibatch reactor can be performed using some restrictions because the oscillations do not correspond to the asymptotic regime.The oscillations exist during afinite time interval after their onset.They can appear through the birth of a limit cycle or be caused by a damped oscillating decay to a pseu-dosteady state,which is not the case presented in Fig.1because the oscillation amplitude does not decay during the reaction.From this point of view the appearance of oscilla-tions may be considered as a result of the birth of a limit cycle whose properties depend on time.Before the onset of oscillations the pseudosteady state varies slowly in time and loses its stability at a moment of time that corresponds to the appearance of oscillations.One may introduce a bifurcation parameter whose value is time dependent.Its value depends on the initial concentration of reagents in a vessel,concen-tration of reagents in inflow,andflow rate.We performed experiments at constantflow rate and concentration of re-agents in the feedstream.Therefore,the value of the time-dependent bifurcation parameter depends also on the initial concentration of reagents in a vessel:ϭ͑t,͓H2O2͔0,͓Cu2ϩ͔0͒.͑1͒Investigation of the dependencies of oscillation period (T)and amplitude(A)on the control parameter near the bifurcation point͑*͒is a useful tool to describe the nature of bifurcation.11,13Such analysis can answer the question whether the control parameter is a real bifurcation parameter. The oscillation period and amplitude depend in a different manner on the value of⌬ϭϪ*for different bifurca-tions.In the simplest case these dependencies correspond to those obtained from theoretical consideration.Theory pro-vides that for a nondegenerate supercritical Hopf bifurcation, the oscillation amplitude has a square root dependence on, and the oscillation frequency is linearly proportional to this value near the bifurcation point.12In another case,the oscil-lation period decreases from infinity as the system moves away from the bifurcation point;the oscillation period satis-fies the following scaling law near the bifurcation point:14–16 Tϰ͉⌬͉Ϫ␥.͑2͒The value of␥is positive indicating the possibility of infinite period bifurcation.Some theoretical predictions of this value have been discussed in the literature for period lengthening near the critical value of the control parameter.14Notice that in the general case there is no theory that predicts the scaling law for oscillation amplitude.In many cases its value is con-stant and does not depend on.These results are valid for the true bifurcations if the system reaches an asymptotic regime.One should expect that it is possible to apply these results in the case if the bifurca-tion parameter changes sufficiently slowly in time,and the system moves through the bifurcation point.Bifurcations of pseudostationary states in closed systems have been treated by Gray and Scott.17To apply this concept to the bifurcation analysis of the p H-regulated oscillations in a semibatch,we consider two cases that correspond to low and high initial concentration of hydrogen peroxide in a vessel.Low initial concentration of hydrogen peroxide.In this case the oscillation amplitude and period do not change sig-nificantly during the time interval when oscillations exist. The oscillations appear suddenly after the pseudoinduction period.The pseudoinduction period does not depend on the copper͑II͒concentration but is determined solely by the ini-tial hydrogen peroxide concentration.Therefore the value of the bifurcation parameter,at the moment of time that corre-sponds to the appearance of oscillations,depends on the ini-tial concentration of copper͑II͒only if the initial concentra-tion of hydrogen peroxide is constant:ϭ͑t i,͓H2O2͔0,͓Cu2ϩ͔0͒ϭ͓͑Cu2ϩ͔0͒,͑3͒where t i is the value of the pseudoinduction period.We investigated this situation at͓H2O2͔0ϭ0.056M.We found that there exists a critical value of the initial copper͑II͒concentration͑C*ϭ2.55ϫ10Ϫ6M͒below which oscilla-tions do not appear.Figure2shows the dependence of the average period on the initial copper͑II͒concentration in a vessel.The oscillation period decreases monotonically if the initial concentration of copper͑II͒is increased in a narrow range above its critical value.Further increase of the Cu2ϩconcentration does not change the oscillation period.Theseobservations allow us to suggest that oscillations appear be-cause of an infinite period bifurcation at low initial concen-tration of hydrogen peroxide if the initial concentration of copper͑II͒may be associated with the value of the bifurca-tion parameter.To show the direct correspondence between these two values one should linearize the dependence͑3͒in a narrow region where oscillation period depends strongly on the initial concentration of copper͑II͒:ϭ͓͑Cu2ϩ͔0͒ϭ͑C Cu*͒ϩ␣͑C CuϪC Cu*͒,͑4͒where C Cu*is a critical value of the initial copper͑II͒concen-tration.It follows from this equation that⌬ϭ͓͑Cu2ϩ͔0͒Ϫ͑C Cu*͒Ϸ⌬C Cu*ϭC CuϪC Cu*.͑5͒Equations͑2͒and͑5͒give us a possibility to expect the existence of a scaling between the oscillation period and the initial concentration of copper͑II͒:TϷ͉⌬C Cu͉Ϫ␥.͑6͒We used the experimental data shown in Fig.2tofindthe scaling parameter from the log–log plot of period versusthe distance from the critical point in units of the Cu2ϩcon-centration.The scaling law is valid in a sufficiently wideinterval of initial concentrations of copper ͑2.55–14.7͒ϫ10Ϫ6M.The correlation coefficient equals 0.957,which indicates a good approximation of oscillationperiod dependencies by scaling law͑6͒.The scaling param-eter equals␥ϭ0.14Ϯ0.02.This value of scaling parameter does not give a direct possibility to classify the infinite pe-riod bifurcation in this case as saddle-loop͑␥ϭ1͒or saddle-node͑␥ϭ0.5͒.Analysis of the dynamical behavior of p H-regulated os-cillations at low concentration of hydrogen peroxide showsthat the increase of copper͑II͒concentration near its criticalvalue leads to the appearance of oscillations through the in-finite period bifurcation.Moreover we showed that it is thecase when the initial concentration of copper͑II͒may be con-sidered as a bifurcation parameter.The type of bifurcation depends on the hydrogen perox-ide concentration.The other bifurcation is realized at highinitial concentration of hydrogen peroxide.High initial concentration of hydrogen peroxide.Our ex-periments show that the amplitude and period of oscillationsvary significantly during a reaction started at high initial con-centration of hydrogen peroxide.The pseudoinduction periodvaries if either of the initial concentrations of reagents in avessel are changed,as can be seen from data presented inFigs.1͑b͒and1͑c͒.Therefore,it is not evident how to obtaina simple relationship between the time-dependent bifurcationparameter and the initial concentrations of reagents in thiscase.Moreover,it is crucial in this case that the oscillationamplitude depends on time.It means that transient oscilla-tions are characterized by a departure of the system from abifurcation point.The monotonic growth of the oscillationamplitude in time is clearly visible from data shown in Figs.1͑b͒and1͑c͒.This suggests that oscillations appear due tothe supercritical Hopf bifurcation when the bifurcation pa-rameter varies slowly in time.In this case the equations for the oscillation amplitude and phase can be written in the following form:dAdtϭ͑t͒AϪ␣1A3,͑7͒ddtϭ⍀0Ϫ␣2A2,where͑͒is a time-dependent bifurcation parameter and values of␣1,␣2,⍀0are approximately constant.Here the bifurcation parameter depends on time.This is the difference between these equations and those written for the true supercritical Hopf bifurcation when the bifurcation parameter does not change in time.11–13This difference leads to the absence of the scaling law between oscillation ampli-tude and the value of the time-dependent bifurcation param-eter.Equations͑7͒illustrate the delay of the Hopf bifurcation in time.The system does not oscillate when the bifurcation parameter corresponds to its critical value for the time-independent case.The system does start to oscillate when the bifurcation parameter exceeds its critical value.Nevertheless it is possible to extract the quantitative relation from these equations in the case of time-dependent bifurcation.The fol-lowing relation between oscillation frequency and amplitude follows from Eqs.͑7͒:⍀ϭ2/Tϭ⍀͑0͒Ϫ␣2A2.͑8͒This relationship gives a quantitative tool to check the possibility of a time-dependent supercritical Hopf bifurca-tion.Figure3shows the dependence of frequency on the square of the amplitude for the oscillations shown in Fig. 1͑c͒.The oscillation frequency is linearly proportional to the square of the amplitude.͑The correlation coefficient of linear dependence is0.983.͒The oscillation frequency grows monotonically if the oscillation amplitude is increased.The linear dependence presented in Fig.3suggests that the p H-regulated oscillations appear due to a nondegenerate supercritical Hopf bifurcation.We found that oscillations ap-pear through a Hopf bifurcation if the initial concentrationofhydrogen peroxide is0.131M and the initial concentration of copper͑II͒is varied.The same situation is realized at the highest values of initial hydrogen peroxide concentrations. IV.CONCLUSIONSThe analysis of dynamic behavior of p H-regulated oscil-lations performed in this paper shows that the initial concen-trations of copper͑II͒ions and hydrogen peroxide determine the type of bifurcation that is responsible for the appearance of p H-regulated oscillations in a semibatch reactor.These observations are in good agreement with experiments in a CSTR.9The p H-regulated oscillations may appear due to an infinite period bifurcation or a time-dependent supercritical Hopf bifurcation.These observations should be taken into account in the construction of the realistic kinetic scheme for the p H-regulated oscillations in the H2O2–Cu2ϩ–S2O32Ϫ–NaOH system.We showed that the initial concen-tration of copper͑II͒in a vessel may be considered as a real bifurcation parameter if oscillations appear because of an infinite period bifurcation.The time dependence of the con-trol parameter is crucial if oscillations appear owing to a supercritical Hopf bifurcation,and there is no possibility to associate the value of bifurcation parameter with the initial concentrations of reagents.Our results show an example of where it is possible to apply bifurcation theory to semibatch experiments.These ex-periments can be used as a tool to investigate the nature of nonlinear chemical systems only under some restrictions.To check the nature of bifurcation one must consider the time dependence of the control parameter. 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