Large deviations for Langevin spin glass dynamics

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到9月9日

到9月9日，社保基金正式进入股市整整3个月，按照有关规定，社保基金必须通过基金管理公司在三个月内完成建仓，并且其持仓市值要达到投资组合总市值80%的水平。

与此前大受追捧的QFII概念相比，社保基金及其所持有的股票显然低调得多，但是在西南证券分析师田磊看来，至少就目前来看，社保基金无论是在资金规模，还是在持股数量上明显都强于境外投资者，其投资理念和行为更可能给市场带来影响。

基金操作的社保基金的选股思路并不侧重某个行业，而更看重企业本身的发展和成长性，并且现阶段的企业经营业绩和走势也不是基金重点考虑的方面。

目前入市的社保基金都是委托南方、博时、华夏、鹏华、长盛、嘉实6家基金管理公司管理。

社保基金大致是被分为14个组合由以上6家管理公司分别管理，每个组合都有一个三位数的代码，第一位代表投资方向，其中“1”指股票投资、“2”指债券投资；第三位数字则代表基金公司名称，其中“1”为南方、“2”为博时、“3”为华夏、“4”为鹏华、“5”为长盛、“6”为嘉实；另有107、108组合主要运作社保基金此前一直持有的中石化股票，分别由博时与华夏基金公司管理。

在许多社保基金介入的股票中经常可以看到开放式基金的身影，例如在被社保基金大量持有的安阳钢铁(600569)的前10大股东中，其第2、6、7、8、9大股东均为开放式基金，而社保基金则以持股500多万股位列第3大股东。

类似的情况也出现在社保基金103组合所持有的华菱管线(000932)上，其第二大股东即为鹏华行业成长证券投资基金，社保基金则以200多万股的持仓量位列第7大股东，此外，在其前10大股东中还有5家是封闭式基金。

对此，某基金公司人士解释说，在获得社保基金管理人资格后，6家基金公司成立了专门的机构理财部门负责社保基金的投资管理，但是其研究、交易系统等则与公募基金共用一个平台，因此社保基金和开放式基金在选股时才会如此一致。

针对“社保概念股”的走势，国盛证券的分析师王剑认为，虽然社保基金此次委托入市资金超过百亿元，但大部分投向是债券，而且由于社保基金的特殊地位，因此基金管理公司对社保基金的操纵策略应该是以“集中持股，稳定股价”为主，不大可能博取太高的收益。

氢键的应用

© XXXX American Chemical Society
how the standard perception of halogen substituents, which assumes an isotropic negative electron density around the halogen, was replaced by a description that takes the σ-hole into account. Halogen bonds have been found to occur in a multitude of inorganic, organic, and biological systems.4,5 In an early study from the 1950s, Hassel and Hvoslef solved the crystal structure of the equimolar Br2:dioxane adduct and found Br···O contacts featuring distances substantially below the sum of the van der Waals radii of both atoms, indicating a strong attractive interaction between both atoms.6,7 In 1984, a search of the Cambridge crystallographic data ﬁles for short iodine···N/O/S contacts revealed that these interactions are also formed in biologically relevant systems, being employed by nature for the molecular recognition of thyroid hormones at their target proteins such as transthyretin.8 In protein−ligand environments, halogen bonds can be formed between a halogenated ligand and any accessible Lewis base in the binding pocket.9 Probably because of its presence in every amino acid, the backbone carbonyl oxygen function is the most prominent Lewis base involved in halogen bonds in protein binding sites, as found from an analysis of the Protein Data Bank (PDB).10,11 Additionally, halogen bonds can be formed involving side chain groups, such as hydroxyls in serine, threonine, and tyrosine, carboxylate groups in aspartate and glutamate, sulfurs in cysteine and methionine, nitrogens in histidine, and the π surfaces of phenylalanine, tyrosine, histidine, and tryptophan. Several examples for these contacts are given in Figure 2.

Role of oxidative stress in alcohol-induced liver injury

REVIEW ARTICLERole of oxidative stress in alcohol-induced liver injuryArthur I.Cederbaum ÆYongke Lu ÆDefeng WuReceived:9March 2009/Accepted:28April 2009/Published online:16May 2009ÓSpringer-Verlag 2009Abstract Reactive oxygen species (ROS)are highly reactive molecules that are naturally generated in small amounts during the body’s metabolic reactions and can react with and damage complex cellular molecules such as lipids,proteins,or DNA.Acute and chronic ethanol treat-ments increase the production of ROS,lower cellular antioxidant levels,and enhance oxidative stress in many tissues,especially the liver.Ethanol-induced oxidative stress plays a major role in the mechanisms by which ethanol produces liver injury.Many pathways play a key role in how ethanol induces oxidative stress.This review summarizes some of the leading pathways and discusses the evidence for their contribution to alcohol-induced liver injury.Special emphasis is placed on CYP2E1,which is induced by alcohol and is reactive in metabolizing and activating many hepatotoxins,including ethanol,to reac-tive products,and in generating ROS.Keywords Oxidative stress ÁAlcoholic liver injury ÁReactive oxygen species ÁAntioxidants ÁCYP2E1ÁTNF aIntroductionUnder certain conditions,such as acute or chronic alcohol exposure,production of reactive oxygen species (ROS)is enhanced and/or the level or activity of antioxidants is reduced.The resulting state,which is characterized by a disturbance in the balance between ROS production,on one hand and ROS removal and repair of damaged com-plex molecules,on the other is called oxidative stress.ROS have been implicated in many of the major dis-eases that plague mankind,including the toxicity of O 2itself;hyperbaric O 2;ischemia–reperfusion injury;cardio-vascular diseases;atherosclerosis;carcinogenesis;diabetes;neurodegenerative diseases,including Parkinson’s disease and Alzheimer’s disease;toxicity of heavy metals,e.g.,iron;asbestos injury;radiation injury;vitamin deﬁciency;drug (e.g.,redox cycling agents)toxicity;aging;inﬂam-mation;smoke toxicity;emphysema;and toxicity of acute and chronic ethanol treatment (Knight 1998;Kehrer 1993;Bondy 1992;Nordman et al.1992;Cederbaum 2001).ROS can be produced from many systems in cells including the mitochondrial respiratory chain (Chance et al.1979);the cytochrome P450s (White 1991;Blanck et al.1991);oxi-dative enzymes such as xanthine oxidase,aldehyde oxi-dase,cyclooxygenase,monoamine oxidase,the NADPH oxidase complex (Toykuni 1999;De Groot 1994);auto-oxidation of heme proteins such as ferrohemoglobin or myoglobin or biochemicals such as catecholamines,qui-nones or tetrahydrobiopterins.In addition to these cellular sources of ROS,environmental sources of ROS include radiation,UV light,smoke and certain drugs which are metabolized to radical intermediates or which can redox cycle.ROS are toxic to cells because they can react with most cellular macromolecules inactivating enzymes or denaturing proteins,causing DNA damage such as strandA.I.Cederbaum (&)ÁY.Lu ÁD.WuDepartment of Pharmacology and Systems Therapeutics,Mount Sinai School of Medicine,Box 1603,One Gustave L Levy Place,New York,NY 10029,USA e-mail:Arthur.cederbaum@ Y.Lue-mail:Yongke.lu@ D.Wue-mail:Defeng.wu@Arch Toxicol (2009)83:519–548DOI 10.1007/s00204-009-0432-0breaks,base removal or base modiﬁcations which can result in mutation,peroxidation of lipids which can result in destruction of biological membranes and produce reac-tive aldehydic products such as malondialdehyde or4-hy-droxynonenal(Nakazawa et al.1996;McCord1998).A variety of enzymatic and non-enzymatic mechanisms have evolved to protect cells against ROS,including the super-oxide dismutases(SODs),which remove O2-Á;catalase and the glutathione(GSH)peroxidase system which remove H2O2;glutathione transferases which can remove reactive intermediates and lipid aldehydes,metallothioneins,heme oxygenase,thioredoxin which remove various ROS;ceru-loplasmin and ferritin which help remove metals such as iron which promote oxidative reactions;non-enzymatic, low molecular weight antioxidants such as GSH itself, vitamin E,ascorbate(vitamin C),vitamin A,ubiquinone, uric acid,bilirubin(Halliwell1999;Yu1994).Oxidative stress or toxicity by ROS reﬂects a balance between the rates of production of ROS compared to the rates of removal of ROS plus repair of damaged cellular macro-molecules.While excess ROS can cause toxicity,macro-phages and neutrophils contain an NADPH oxidase which produces ROS to destroy foreign organisms(Rosen et al. 1995),and the enzyme myeloperoxidase catalyzes a reac-tion between H2O2and chloride to produce the powerful oxidant hypochlorite(bleach)to help destroy foreign invaders.In addition,ROS at low concentrations,espe-cially H2O2,may be important in signal transduction mechanisms in cells,and thus be involved in cellular physiology and metabolism(Lander1997).Alcohol,oxidative stress and cell injuryThe ability of acute and chronic ethanol treatment to increase production of ROS and enhance peroxidation of lipids,protein,and DNA has been demonstrated in a variety of systems,cells,and species,including humans. Much has been learned about alcohol metabolism,the various enzymes and pathways involved,and how alcohol, directly via its metabolism,or indirectly via its solvent-like action affecting cellular membranes impacts on cell func-tion.Yet,despite this tremendous growth in understanding alcohol metabolism and actions,the mechanism(s)by which alcohol causes cell injury are still not clear.A variety of leading mechanisms have been brieﬂy summa-rized(Cederbaum2001;Bondy1992;Nordman et al. 1992),and it is likely that many of them ultimately con-verge as they reﬂect a spectrum of the organism’s response to the myriad of direct and indirect actions of alcohol.A major mechanism that is a focus of considerable research is the role of lipid peroxidation and oxidative stress in alcohol toxicity.Many pathways have been suggested to play a key role in how ethanol induces‘‘oxidative stress’’.Some of these include redox state changes(decrease in the NAD?/ NADH redox ratio)produced as a result of ethanol oxi-dation by alcohol and aldehyde dehydrogenases;produc-tion of the reactive product acetaldehyde as a consequence of ethanol oxidation by all major oxidative pathways; damage to mitochondria which results in decreased ATP production;direct or membrane effects caused by hydro-phobic ethanol interaction with either phospholipids or protein components or enzymes;ethanol-induced hypoxia, especially in the pericentral zone of the liver acinus as oxygen is consumed in order for the liver to detoxify eth-anol via oxidation;ethanol effects on the immune system, and altered cytokine production;ethanol-induced increase in bacterial-derived endotoxin with subsequent activation of Kupffer cells;ethanol induction of CYP2E1;ethanol mobilization of iron which results in enhanced levels of low molecular weight non-heme iron;effects on antioxi-dant enzymes and chemicals,particularly mitochondrial and cytosolic glutathione;one electron oxidation of ethanol to the1-hydroxyethyl radical;conversion of xanthine dehydrogenase to the xanthine oxidase form.Again,many of these pathways are not exclusive of one another and it is likely that several,indeed many,systems contribute to the ability of ethanol to induce a state of oxidative stress.What is the evidence that ethanol-induced oxidative stress plays a role in cell injury?While many studies have shown increases in lipid peroxidation or protein carbonyl formation by alcohol,it is not always clear if these are causes of or consequences of the alcohol-induced tissue injury.Nevertheless,there are many studies which show that administration of antioxidants or iron chelators or GSH-replenishing agents can prevent or ameliorate the toxic actions of alcohol.The most convincing data that oxidative stress contributes to alcohol-induced liver injury comes from the studies using the intragastric infusion model of alcohol administration.In these studies,alcohol-induced liver injury was associated with enhanced lipid peroxidation,protein carbonyl formation,formation of the 1-hydroxyethyl radical,formation of lipid radicals, decreases in hepatic antioxidant defense especially GSH (Knecht et al.1995;Tsukamoto and Lu2001;Iimuro et al. 2000;Nanji et al.1994a,b;Morimoto et al.1994). Replacement of polyunsaturated fat(required for lipid peroxidation to occur)with saturated fat or medium chain triglycerides in the diets fed to rats intragastrically,lowered or prevented the lipid peroxidation,and the alcohol-induced liver injury.Thus,alcohol plus polyunsaturated fat was required for the injury to occur.Addition of iron, known to generate OH•and promote oxidative stress,to these diets exacerbated the liver injury(Tsukamoto et al. 1995).Importantly,addition of antioxidants such as vita-min E,ebselen,superoxide dismutase,GSH precursors,prevented the alcohol-induced liver injury.Because alco-hol-induced liver injury has been linked to oxidative stress, we investigated the effect of a compromised antioxidant defense system,copper–zinc superoxide dismutase(SOD1) deﬁciency on alcohol-induced liver injury(Kessova et al. 2003).C57BL/SV129wild type and SOD1knockout mice were fed dextrose or ethanol(10%total calories)liquid diets for3weeks.Absence of SOD1in the knockouts was conﬁrmed by immunoblot.Histological evaluation of the liver showed the development of liver injury ranging from mild to extensive centrilobular necrosis and inﬂammation (Fig.1a,b).Alanine aminotransferase levels were elevated only in the SOD1knockouts fed ethanol and not in the other three groups(Fig.1).Hepatic ATP levels were lowered only in the SOD1knockout mice fed ethanol (Fig.1),and oxidative and nitrosative stress was found in their livers.Wild type mice fed ethanol showed mild ste-atosis(Fig.1d)while wild type or knockout mice fed the dextrose diet showed normal histology(Fig.1c,e).Thus,a rather moderate ethanol consumption promoted oxidative stress and liver injury in Sod1knockout mice indicating that compromised antioxidant defense promotes alcohol liver injury.In addition to these in vivo studies,in vitro studies with hepatocytes also showed that ethanol can produce oxida-tive stress and hepatocyte toxicity.Studies with isolated hepatocytes from control rats or chronic ethanol-fed rats indicated that ethanol metabolism via alcohol dehydroge-nase results in an increase in ROS production,hepatocyte injury,and apoptosis,reactions blocked by antioxidants (Adachi and Ishii2002;Bailey and Cunningham2002). Studies in our laboratory with HepG2cell lines expressing CYP2E1showed that addition of ethanol or polyunsatu-rated fatty acids(PUFA)or iron,or depletion of GSH, resulted in cell toxicity,increased oxidative stress and mitochondrial damage,reactions prevented by antioxidants (Wu and Cederbaum1999).HepG2cells expressing both CYP2E1and alcohol dehydrogenase have been very valuable in studies on ethanol-induced oxidative stress and cell injury(Osna et al.2003;Donohue et al.2006).The sections below explore in more detail some of the major mechanisms which are believed to play an important role in pathways contributing to alcohol-induced oxidative stress.Kupffer cells and alcoholic liver diseaseKupffer cells are stimulated by chronic ethanol treatment to produce free radicals and cytokines,including tumor necrosis factor alpha(TNF a),which plays a role in ALD (Adachi et al.1994;Iimuro et al.1997).This stimulation is mediated by bacterial-derived endotoxin,and ALD is decreased when gram-negative bacteria are depleted from the gut by treatment with lactobacillus or antibiotics(Nanji et al.1994a,b).Destruction of Kupffer cells with gado-linium chloride attenuated ALD(Adachi et al.1994).A major advance was theﬁnding that anti-TNF a antibodies protect against ALD(Iimuro et al.1997).NADPH oxidase was identiﬁed as a key enzyme for generating ROS in Kupffer cells after ethanol treatment(Kono et al.2001). Moreover,in mice deﬁcient in a subunit of NADPH oxi-dase,p47phox,the ethanol-induced increase in ROS and TNF a and liver injury was decreased(Kono et al.2000). The role of TNF a in ALD was further validated by the ﬁndings that the ethanol-induced pathology was nearly completely blocked in TNF a receptor1knockout mice(Yin et al.1999).The transcription factor nuclear factor-kappaB(NF-kB) regulates activation of many inﬂammatory genes,including TNF a.Endotoxin activates NF-kB,leading to the hypoth-esis that inhibition of NF-kB would prevent ALD(Uesugi et al.2001).Administration of an adenovirus encoding for the IkB superrepressor to rats chronically infused with ethanol blunted the ethanol-induced activation of NF-kB, TNF a production and pathological changes.A general scheme to explain these results is that chronic ethanol treatment elevates endotoxin levels,endotoxin activates Kupffer cells to produce free radicals via NADPH oxidase, the free radicals activate NF-kB,leading to an increase in production of TNF a,followed eventually by tissue damage (Thurman1998;Wheeler and Thurman2001;Takei et al. 2005).Iron-and alcohol-induced oxidative stressMost of the systems for the production of ROS described above produce superoxide radicals or hydrogen peroxide. In the presence of certain metals,particularly free iron or copper ions,hydroxyl radical,the most powerful ROS,can be produced via the Fenton or the metal-catalyzed Haber–Weiss reaction(McCord1998).These two chemical reac-tions appear to account for most of the hydroxyl radical production in biological systems and explain,at least in part,why metals such as iron and copper produce oxidative stress and ROS-induced injury in cells.As discussed above,iron promotes oxidative stress by catalyzing the conversion of less reactive oxidants such as superoxide or H2O2to more powerful oxidants such as hydroxyl radical or perferryl-type oxidants.An increase in hepatic iron concentrations occurs in alcohol-dependent individuals and elevated hepatic iron uptake is seen in patients with alcohol-induced cirrhosis(Chapman et al. 1983).An increase in the cellular pool of low-molecular weight iron occurs during ethanol metabolism in rathepatocyte cultures (Sergent et al.1995).In rats,chronic ethanol feeding for 8weeks elevated iron content in the hepatocytes and Kupffer cells (Valerio et al.1996).Treatment of rats with ethanol plus carbonyl iron strikingly elevated liver iron levels and produced signiﬁcant liver injury (Valerio et al.1996;Stal et al.1996).In the intra-gastric infusion model,addition of a small amount of iron,which only elevated hepatic iron levels twofold to three-fold,enhanced lipid peroxidation,serum transaminase levels,and induced ﬁbrosis (Tsukamoto et al.1995).Ethanol administration elevated the iron content of Kupffer cells,and this was suggested to prime Kupffer cells for NF-kB activation and ultimately for TNF a production and ALD (Tsukamoto et al.1999).Addition of Fe 2?butnotFig.1Chronic ethanolconsumption causes liver injury and a decrease in hepatic ATP levels in SOD 1knockout mice as compared to wild type mice.Arrows in a and b indicate necrosisFe3?increased TNF a release by rat Kupffer cells in an NF-kB—dependent manner(She et al.2002).Oral iron chelators attenuated these effects,reducing the elevations in non-heme iron,lipid peroxidation,and liver fat accu-mulation and injury(Tsukamoto et al.1999;Sadrzadeh et al.1994).ROS production,lipid peroxidation,and interaction with iron chelates were enhanced with microsomes from etha-nol-treated rats(Cederbaum2003).This was associated with elevated levels of CYP2E1and blocked by inhibitors of CYP2E1or by anti-CYP2E1immunoglobulin.In HepG2cells expressing CYP2E1,an iron chelator,ferric-nitrilotriacetate,produced greater toxicity than that found with control HepG2cells(Cederbaum2003).Damage to the mitochondria played a critical role in the CYP2E1plus iron-dependent toxicity.In the CYP2E1-expressing HepG2 cells,synergistic interactions between iron and PUFA were observed.1-Hydroxyethyl radical(HER)Ethanol is a hydroxyl radical scavenger;the product of the interaction of ethanol with hydroxyl radical is HER.Liver microsomes can oxidize ethanol to HER in an NADPH dependent manner(Albano et al.1987).The mechanism involves production of superoxide and H2O2by cyto-chrome P450,followed by an iron-catalyzed generation of hydroxyl radical like—oxidants,which interact with etha-nol to yield HER(Knecht et al.1993;Rashba-Step and Cederbaum1994).Microsomes isolated from rats treated chronically with ethanol were more reactive in producing HER from ethanol than control microsomes(Albano et al. 1991).This was due to induction of CYP2E1.HER pro-duction from ethanol has been demonstrated in vivo,as a spin-trapped HER adduct was detected in bile from mice or rats treated with ethanol(Knecht et al.1990).The role of HER adducts in ALD is not known.HER binds readily to proteins to produce ethanol-derived protein adducts,which are immunogenic,and production of antibodies that spe-ciﬁcally recognize HER protein adducts was found after chronic ethanol consumption(Moncada et al.1994),as well as in patients with alcohol-induced cirrhosis(Clot et al.1995).Interaction of HER with cellular antioxidants could contribute to mechanisms by which ethanol produces a state of oxidative stress(Reinke2002).Protection against ROS toxicity/GSHBecause ROS production is a naturally occurring process,a variety of enzymatic and nonenzymatic mechanisms have evolved to protect cells against ROS(Halliwell1999;Yu 1994).At least some of these mechanisms are impaired after long-term alcohol consumption.Antioxidant enzymes involved in the elimination of ROS include SODs,catalase,and glutathione peroxidase. SODs catalyze removal of superoxide radicals.A copper–zinc SOD is present in the cytosol and in the space between the two membranes surrounding the mitochondria,while a manganese-containing SOD is present in the mitochondrial matrix.Both of these enzymes are critical for prevention of ROS-induced toxicity(Fridovich1997).The effects of chronic alcohol exposure on the cellular content or activity of SODs are controversial,with reports of increases,no changes,or decreases,depending on the model,diet, amount,and time of alcohol feeding.Studies employing the intragastric infusion model,found decreases in SOD activity in the liver(Polavarapu et al.1998).Catalase and the glutathione peroxidase system both help to remove hydrogen peroxide.Catalase is found pri-marily in peroxisomes;it catalyzes a reaction between two hydrogen peroxide molecules,resulting in the formation of water and O2.In addition,catalase can promote the inter-action of hydrogen peroxide with hydrogen donors so that the hydrogen peroxide can be converted to one molecule of water,and the reduced donor becomes oxidized(peroxid-atic activity of catalase).Compounds that can provide these hydrogen atoms include ethanol and methanol,which are oxidized to acetaldehyde and formaldehyde,respectively. The glutathione peroxidase system consists of several components,including the enzymes glutathione peroxidase and glutathione reductase and the cofactors GSH and NADPH.Together,these molecules effectively remove hydrogen peroxide.GSH is an essential component of this system and serves as a cofactor for glutathione transferase, which helps remove certain drugs and chemicals as well as other reactive molecules from the cells.Because of all its functions,GSH is probably the most important nonenzymatic antioxidant present in cells. Therefore,enzymes that help generate GSH are critical to the body’s ability to protect itself against oxidative stress. Alcohol has been shown to deplete GSH levels,particularly in the mitochondria,which normally are characterized by high levels of GSH needed to eliminate the ROS generated during activity of the respiratory chain(Fernandez-Checa et al.1997).Numerous other nonenzymatic antioxidants are present in the cells,most prominently vitamin E (a-tocopherol)and vitamin C(ascorbate).Vitamin E is a major antioxidant found in the lipid phase of membranes and,acts as a powerful terminator of lipid peroxidation. During the reaction between vitamin E and a lipid radical, the vitamin E radical is formed,from which vitamin E can be regenerated in a reaction involving GSH and ascorbate. Alcohol also appears to interfere with the body’s normal vitamin E content because patients with ALD commonlyexhibit reduced vitamin E levels(Nanji and Hiller-Sturmho¨fel1997).The effects of ethanol on total hepatic GSH levels are variable,with reports of decreases,no effects,or even an increase(Fernandez-Checa et al.1989;Iimuro et al.2000; Oh et al.1998).Lowering of mitochondrial GSH by chronic ethanol treatment has been a more consistent observation and appears to be a key lesion contributing to ALD.Because liver mitochondria lack catalase,mito-chondrial GSH in association with glutathione peroxidase is the major mechanism by which H2O2is detoxiﬁed by mitochondria.Chronic ethanol intake either in the Lieber–DeCarli model or the intragastric infusion model selec-tively lowers levels of mitochondrial GSH in hepatocytes (Fernandez-Checa et al.1989,1997).Depletion of mito-chondrial GSH by chronic ethanol feeding occurs prefer-entially in pericentral hepatocytes,where most of the liver injury originates(Garcia-Ruiz et al.1995).This depletion by ethanol is attributable to defective transport of GSH from the cytosol into the mitochondria and can be pre-vented byﬂuidization of the mitochondrial membrane by S-adenosylmethionine(Colell et al.1998).Lowering of mitochondrial GSH by ethanol has been suggested to sensitize hepatocytes to TNF a-induced cell death,and replenishment of mitochondrial GSH with S-adenosylme-thionine protects hepatocytes from alcohol-treated rats to TNF toxicity(Colell et al.1998).Bailey et al.(2001), however,found that mitochondrial GSH levels were increased after chronic ethanol feeding in the Lieber–DeCarli model by approximately25%.Thisﬁnding was suggested to reﬂect an adaptive response to counteract ethanol-related increases in mitochondrial production of ROS.Deaciuc et al.(1999)reported no change in mito-chondrial GSH levels after7weeks of ethanol intake. Thus,the effects of ethanol on mitochondrial GSH,as with total GSH,remain controversial.S-Adenosyl-L-methionineS-Adenosyl-L-methionine(SAM)is the principal biological methyl donor,the precursor of aminopropyl groups utilized in polyamine biosynthesis and,in the liver,SAM is also a precursor of glutathione(GSH)through its conversion to cysteine via the transsulfuration pathway(Avila et al.2002; Lieber2002).SAM is particularly important in opposing the toxicity of free radicals generated by various toxins, including alcohol.Abnormalities in SAM metabolism have been well recognized in liver diseases and in various neurological disorders.Methionine adenosyltransferase (MAT)is the enzyme responsible for the synthesis of SAM using methionine and ATP.Liver injury causes a decrease in SAM concentration largely because of decreased MAT1A activity(Cabrero et al.1988;Avila et al.2000). Impairment of SAM synthesis is believed to play an important role in hepatic injury induced by various agents, and indeed there is a considerable literature,which shows that exogenous administration of SAM can protect against injury induced by CCl4,acetaminophen,galactosamine, cytokines,thioacetamide,ischemia–reperfusion(Chawla et al.1998;Bray et al.1992;Wu et al.1996;Song et al. 2004).The effects of ethanol on SAM concentrations are somewhat variable.Baboons fed ethanol chronically had decreased hepatic levels of SAM and GSH,and adminis-tration of SAM elevated these and protected against liver injury(Lieber et al.1990).Rats fed the Lieber–DeCarli diet showed no or a small decrease in SAM after4weeks but a more substantial decrease in8weeks on the diet(Barak et al.1987;Trimble et al.1993).Mini pigs fed ethanol for 1year had no change in SAM levels(Halsted et al.1996). Rats fed ethanol in the intragastric infusion model for 9weeks had an increase in MAT1A and MAT2A mRNA but only MAT2A protein was elevated(Lu et al.2000); these changes were associated with a40%fall in SAM levels.Depletion of mitochondrial GSH appears to be an important sensitizing factor for susceptibility to TNF a toxicity after chronic ethanol feeding(Fernandez-Checa et al.1997).This depletion is due to a decrease in transport of GSH into the mitochondria and can be corrected by administration of SAM(Garcia-Ruiz et al.1995).In iso-lated hepatocytes,SAM prevented the decrease in GSH caused by ethanol(Gigliozzi et al.1998)and in perfused rat liver studies,SAM prevented the decline in GSH and oxygen consumption and liver damage produced by etha-nol(Bosch-Morell et al.1998).Kharbanda et al.(2005) compared the effects of betaine and SAM,on ethanol-induced changes of methionine metabolism and hepatic steatosis.Wistar rats were fed ethanol or control Lieber–Decarli liquid diet for4weeks and metabolites of the methionine cycle were measured in isolated hepatocytes. Hepatocytes from ethanol-fed rats had a50%lower intra-cellular SAM/SAH ratio and almost twofold greater homocysteine release into the media compared with con-trols.Supplementation of betaine or SAM in the incubation media increased the SAM/SAH ratio in hepatocytes from both control and ethanol-fed rats and attenuated the etha-nol-induced increased hepatocellular triglyceride levels by approximately20%.SAM protects against alcohol-dependent toxicity in vivo Chronic ethanol consumption by baboons(50%of energy from a liquid diet)for18–36months resulted in signiﬁcant depletion of hepatic SAM concentration and levels of GSH (Lieber et al.1990).These depletions were corrected withSAM administration.There was a signiﬁcant correlation between hepatic SAM and GSH level.Esfandiari et al. (2007)reported that feeding micropigs with ethanol at40% of total calories with folate-deﬁcient diets for14weeks increased and supplemental SAM maintained control levels of liver and plasma triglyceride.Serum adiponectin,liver transcripts of adiponectin receptor-1,and phosphorylated adenosine monophosphate kinase-beta were each reduced by ethanol feeding and were sustained at normal levels by SAM supplementation of the ethanol diets.Ethanol feeding activated and SAM supplementation maintained control levels of ER stress-induced transcription factor sterol regulatory element-binding protein-1c and its targeted transcripts of lipid synthesizing enzymes acetyl-CoA car-boxylase,fatty acid synthase,and glycerol-3-phosphate acyltransferase(Esfandiari et al.2007).The protective effect of SAM against rat liver steatosis induced by chronic ethanol ingestion was investigated by Feo et al.(1986).SAM given during ethanol treatment prevented steatosis and accelerated recovery from steatosis when given after ethanol withdrawal.Bailey et al.(2006) found that alcohol feeding to rats caused a signiﬁcant decrease in mitochondrial state three respiration and the respiratory control ratio in5weeks,whereas SAM administration prevented these alcohol-mediated defects and preserved hepatic SAM levels.SAM treatment pre-vented alcohol-associated increases in mitochondrial superoxide production,mitochondrial DNA damage,and inducible nitric oxide synthase induction,without a sig-niﬁcant lessening of steatosis.Although SAM supplemen-tation did not alleviate steatosis by itself,SAM prevented several key alcohol-mediated defects to the mitochondrial genome and proteome that contribute to the bioenergetic defect in the liver after alcohol consumption(Bailey et al. 2006).Acute ethanol administration caused prominent micro-vesicular steatosis with mild necrosis and an elevation of serum L-alanine:2-oxoglutarate aminotransferase activity. SAM treatment signiﬁcantly attenuated the liver injury. SAM treatment attenuated hepatic SAM and mitochondrial GSH depletion and lipid peroxidation following acute alcohol exposure(Song et al.2003).SAM protects against CYP2E1-dependent toxicityin vivoWe recently reported that induction of CYP2E1in mice by treatment with pyrazole increased the hepatotoxicity caused by Fas agonistic Jo2antibody(Wang et al.2005). Increased hepatotoxicity in the pyrazole/Jo2-treated mice was associated with increased oxidative and nitrosative stress in association with decreased GSH and other antioxidant levels.Exogenous administration of SAM (50mg/kg body weight i.p.every12h for3days)signif-icantly decreased serum transaminases and ameliorated morphological changes of the liver(Wang and Cederbaum 2006).Addition of SAM elevated hepatic SAM and total reduced glutathione levels and inhibited CYP2E1activity. SAM also lowered the elevated oxidative stress(lipid peroxidation,protein carbonyls,and superoxide produc-tion)and nitrosative stress(induction of inducible nitric oxide synthase and3-nitrotyrosine adducts)and increases in caspase-8and-3activation produced by the pyrazole plus Jo2treatment.These results indicate that SAM can have an important hepatoprotective role as an effective reagent against Fas plus CYP2E1-induced hepatotoxicity by lowering oxidative and nitrosative stress.Obese mice have been used extensively as animal models to study human obesity.We have recently observed that pyrazole-induced CYP2E1promotes liver injury in ob/ ob mice,compared with saline-treated ob/ob mice or with lean controls treated with pyrazole(Dey and Cederbaum 2007).Administration of SAM(50mg/kg body weight i.p. every12h for3days)prevented the observed pathological changes as well as the increase of apoptotic hepatocytes, caspase3activity,and serum TNF a levels.SAM admin-istration inhibited CYP2E1activity but not CYP2E1con-tent.The pyrazole treatment increased lipid peroxidation, 4-hydroxynonenal and3-nitrotyrosine protein adducts,and protein carbonyls.These increases in oxidative and nitro-sative stress were prevented by SAM(Dey et al.2007). SAM is effective in protecting against pyrazole-induced oxidative and nitrosative stress and liver injury in obese mice by lowering CYP2E1-generated oxidative/nitrosative stress in the liver and in the mitochondrial compartment.As mentioned above,a model of chronic alcohol-induced liver injury using Cu,Zn-superoxide dismutase deﬁcient mice(SOD-/-)was developed(Kessova et al. 2003).Feeding the homozygous SOD-/-mice ethanol resulted in liver injury characterized by extensive centri-lobular necrosis and inﬂammation,and increased trans-aminase levels(but not the wild type SOD?/?mice).Liver injury in the SOD-/-mice was associated with induction of CYP2E1,and increased protein carbonyls,lipid perox-idation aldehydic products and3-nitrotyrosine protein adducts,indicative of enhanced oxidative and nitrosative stress.SAM protected SOD-/-mice from alcohol-induced liver injury.SAM lowered the serum L-alanine:2-oxoglu-tarate aminotransferase and aspartate aminotransferase levels,decreased steatosis,necrosis and inﬂammation upon histological evaluation as compared to alcohol treated alone mice(Fig.2).The ability of SAM in vitro to protect against CYP2E1-dependent toxicity was studied in pyrazole-treated rat hepatocytes,with high levels of CYP2E1(Wu and。

等离激元共振峰英文

等离激元共振峰英文全文共四篇示例，供读者参考第一篇示例：Plasmon Resonance PeakIntroductionPlasmon resonance is a collective oscillation of free electrons in a material that occurs when the frequency of incident light matches the natural frequency of the electrons in the material. This phenomenon is often observed in metallic nanoparticles, where the conduction electrons can be excited by incident electromagnetic radiation. One of the most prominent features of plasmon resonance is the appearance of a distinct peak in the absorption or scattering spectra of the material, known as the plasmon resonance peak or plasmon resonance band.第二篇示例：Plasmon resonance refers to the collective oscillation of free electrons in a metal when it is subjected to electromagnetic radiation. This phenomenon, also known as surface plasmon resonance (SPR), has been extensively studied and applied invarious fields such as sensing, imaging, and light manipulation. One of the key features of plasmon resonance is the emergence of a characteristic peak in the absorption or scattering spectrum, known as the plasmon resonance peak or plasmon resonance band. In this article, we will focus on a specific type of plasmon resonance peak – the localized surface plasmon resonance peak, which is commonly referred to as the plasmon resonance peak.第三篇示例：Plasmonic resonance peak, also known as localized surface plasmon resonance (LSPR) peak, is a phenomenon in which free electrons in a metal nanoparticle oscillate collectively in response to incident light. This oscillation creates a strong electromagnetic field enhancement around the nanoparticle, leading to enhanced light-matter interactions. The spectral position of the plasmonic resonance peak, known as the plasmon resonance wavelength, depends on the size, shape, composition, and surrounding environment of the nanoparticle.第四篇示例：One specific type of surface plasmon resonance that has attracted attention is the localized surface plasmon resonance (LSPR) peak. LSPR peaks manifest as sharp extinction peaks inthe absorption or scattering spectra of metal nanoparticles due to the resonance between incident light and the localized surface plasmons on the nanoparticle surface. These peaks are highly sensitive to the size, shape, and composition of the nanoparticle, making them an excellent candidate for various applications such as chemical sensing, biological detection, and single molecule analysis.。

Abstract

July 17, 2006
Technical Report 2Science 140 Governors Drive University of Massachusetts Amherst, Massachusetts 01003-9624
Abstract We present a novel hierarchical framework for solving Markov decision processes (MDPs) using a multiscale method called diﬀusion wavelets. Diﬀusion wavelet bases signiﬁcantly diﬀer from the Laplacian eigenfunctions studied in the companion paper (Mahadevan and Maggioni, 2006): the basis functions have compact support, and are inherently multi-scale both spectrally and spatially, and capture localized geometric features of the state space, and of functions on it, at diﬀerent granularities in spacefrequency. Classes of (value) functions that can be compactly represented in diﬀusion wavelets include piecewise smooth functions. Diﬀusion wavelets also provide a novel approach to approximate powers of transition matrices. Policy evaluation is usually the expensive step in policy iteration, requiring O(|S |3 ) time to directly solve the Bellman equation (where |S | is the number of states for discrete state spaces or sample size in continuous spaces). Diﬀusion wavelets compactly represent powers of transition matrices, yielding a direct policy evaluation method requiring only O(|S |) complexity in many cases, which is remarkable because the Green’s function (I − γP π )−1 is usually a full matrix requiring quadratic space just to store each entry. A range of illustrative examples and experiments, from simple discrete MDPs to classic continuous benchmark tasks like inverted pendulum and mountain car, are used to evaluate the proposed framework.

碳酸锰的几种漂亮结构

Yu Qiao, Si-Rong Li, Yan Yu and Chun-Hua Chen*
Yolk-structured microspheres of spinel LiMn2O4 are successfully prepared by a specially designed multi-step synthesis procedure involving precipitation, controlled oxidation, selective etching and chemical lithiation. Solid-structured and hollow-structured LiMn2O4 are also synthesized by a similar method for comparison. X-ray diﬀraction, scanning electron microscopy, transmission electron microscopy, Brunauer–Emmett–Teller method and IR spectroscopy are employed to study their structures and compositions. The electrochemical
case of large particle sizes. Although the nano-structured LiMn2O4 is very eﬀective in improving the rate capability, the low tap density of nano-sized powders directly leads to the low energy density of a cell. To achieve a high tap density, electrode materials are preferred to have micron-sized particles, especially with spherical shapes which can pack more densely.21–25 In our study, we want to nd a balance between high tap density and short diﬀusion distance. Inspired by the work of Qian et al. who have synthesized hollow structures of Mn2O3, MnO2 and Mn2O3 microspheres,26–28 we design and synthesize a special yolk-structured LiMn2O4 microsphere (Scheme 1b). In this structure model, the outer shell is porous and composed of many nanoparticles, which can enlarge the specic surface area of the electrode and provide more reaction sites for lithium insertion and extraction. The core is relatively dense to increase the volumetric energy density. The spacing between the shell and the core can buﬀer any volume change of the core during heating/cooling or charge/discharge. In the present work, we rst synthesize a yolk-structured Mn2O3 as a precursor and then follow a simple solid-state reaction or chemical lithiation to produce the yolk-structured LiMn2O4 microsphere (LMO-Y) (Scheme 1a). Moreover, we compare the electrochemical performance of LMO-Y with those of hollow LiMn2O4 microspheres (LMO-H) (Scheme 1c) and solid LiMn2O4 microspheres (LMO-S) (Scheme 1d).

Optimization of ultrasonic extraction of Flammulina velutipes polysaccharides and evaluation of its

Optimization of ultrasonic extraction of Flammulina velutipes polysaccharides and evaluation of its acetylcholinesterase inhibitory activityWenjian Yang a ,Yong Fang b ,Jin Liang a ,Qiuhui Hu a ,b ,⁎a College of Food Science and Technology,Nanjing Agricultural University,Weigang,Nanjing 210095,ChinabCollege of Food Science and Engineering,Nanjing University of Finance and Economics,Nanjing,210046,People's Republic of Chinaa b s t r a c ta r t i c l e i n f o Article history:Received 19September 2010Accepted 15November 2010Available online xxxxKeywords:Flammulina velutipes Polysaccharides OptimizationResponse surface methodology Ultrasonic extraction AcetylcholinesterasePolysaccharide was testi ﬁed to be the main component of Flammulina velutipes for inhibiting AChE activity in our preliminary study.Therefore,response surface methodology,based on Box –Behnken design,was used to optimize the ultrasonic extraction conditions of F.velutipes polysaccharides (FVP).Four independent variables (ratio of water to raw material,ultrasonic power,ultrasonic time,and ultrasonic temperature)were taken into consideration.A quadratic model,adequate for reasonably predicting the yield of FVP,was constructed between ultrasonic conditions and yield of FVP.A yield of FVP of 8.33%was obtained under a modi ﬁed condition (ratio of water to material of 25ml/g,ultrasonic power of 620W,ultrasonic time of 20min,and ultrasonic temperature of 45°C).Subsequently,acetylcholinesterase (AChE)inhibitory activity and 1,1-diphenyl-2-picryl hydrazine (DPPH)scavenging activity of FVP were determined.AChE inhibitory rate of 18.51%and DPPH scavenging rate of 61.24%were obtained at 0.6mg/ml of FVP,indicating a good potential of FVP to enhance learning and cognitive ability.©2010Elsevier Ltd.All rights reserved.1.IntroductionNowadays,edible mushrooms are distinguished as important natural resources of immunomodulating and anticancer agents and have been cultured on a large scale in Asia (Wasser,2002).Flammulina velutipes ,one of the most popular edible mushrooms,has attracted considerable attention in the ﬁelds of biochemistry and pharmacology due to its biological activities.Polysaccharides,as one of the important active components of F.velutipes ,have been proved to be bene ﬁcial in immunomodulating antitumor and anti-in ﬂammatory activities (Leung,Fung &Choy,1997).Therefore,much attention has been paid to the studies of F.velutipes polysaccharides (FVP).Although polysaccharides have been well known for their various pharmacological functions,their extraction is still mainly performed with conventional techniques,which are based on proper solvents,prolonging extraction time,heating process,and agitation to increase extraction yield (Wang,Cheng,Mao,Fan &Wu,2009).In these methods,the extraction process usually consumes a long time and a lot of energy,but the extraction ef ﬁciency is very low.Therefore,it is essential and desirable to ﬁnd out an economical and highly ef ﬁcient extraction method.Ultrasonic has been used to increase extraction yield of bioactive substances from natural products,which is mainly attributed to disruption of cell walls,particle-size reduction,and enhanced mass transfer to the cell contents as a result of cavitationbubble collapse (Li,Pordesimo,&Weiss,2004;Vinatoru et al.,1997;Wang et al.,2009).However,there is hardly any report that ultrasonic is applied to separate FVP.Therefore,ultrasonic was employed for the extraction of FVP in our study.Especially,temperature was controlled during the extraction process to prevent overheating-induced oxidation and degradation of polysaccharides.The worldwide population ageing has increased the incidence of cognitive de ﬁcits,such as the age-associated memory impairment and senile dementias and Alzheimer's disease (Hornick et al.,2008).Extensive evidence supports the view that cholinergic mechanisms modulate learning and memory formation.Neuropathological occur-rences of cognitive de ﬁcits are associated with the cholinergic de ﬁciency (Gold,2003;Roberson &Harrell,1997).Inhibitors of acetylcholinesterase (AChE)have been extensively used to increase the effectiveness of cholinergic transmissions and endogenous acetylcholine levels and thus overcome cognitive de ﬁcits (Hornick et al.,2008;Silman &Sussman,2005).F.velutipes is bene ﬁcial to human memory.FVP has been proven to improve learning and memory ability of scopolamine hydrobromid-induced model mice and rats using step-through test and Morris water test (Zou,Liao,Wu &Liu,2010).However,the effect of FVP on AChE activity has not been studied.In our preliminary study,crude polysaccharide solution was testi ﬁed to be the main fraction in F.velutipes for inhibiting AChE activity.In view of the above,it is necessary to research the AChE inhibitory activity of FVP.In addition,it is suggested that polysaccharides induced cognitive improvement owing to their antioxidant activity (Fan et al.,2005;Zhang,Zhang,Wang &Mao,2008),so antioxidant activity of FVP was also investigated.Food Research International xxx (2010)xxx –xxx⁎Corresponding author.Tel./fax:+862584399086.E-mail address:qiuhuihu@ (Q.Hu).FRIN-03416;No of Pages 70963-9969/$–see front matter ©2010Elsevier Ltd.All rights reserved.doi:10.1016/j.foodres.2010.11.027Contents lists available at ScienceDirectFood Research Internationalj o u r n a l h o me p a g e :w w w.e l s e v i e r.c om /l oc a te /fo o d r e sThe objective of this study was to optimize the ultrasonic-assisted extraction conditions of FVP using response surface methodology. Effects of ratio of water to raw material,ultrasonic power,ultrasonic time,and ultrasonic temperature on the extraction yield of FVP were fully examined.Moreover,AChE inhibitory activity of FVP was investigated to study its potential to improve memory impairment and cognitive deﬁcit.On account of the relationship between oxidative stress and cognitive deﬁcit,1,1-diphenyl-2-picryl hydrazine (DPPH)radicals scavenging assay was also conducted to evaluate the antioxidant ability of FVP.2.Materials and methods2.1.Materials and chemicalsF.velutipes was purchased from local market(Nanjing,China)and then dried at60°C and ground to pass through80mesh screen,the powder was stored at4°C until used.Glucose,phenol,and sulfuric acid were obtained from Shanghai Chemical Co.(Shanghai,China).1,1-Diphenyl-2-picryl hydrazine(DPPH),5,5′-dithio-bis-(2-nitrobenzoic) acid,acetylthiocholine iodide,ascorbic acid,acetylcholinesterase (AChE,type VI-S,EC3.1.1.7),and galanthamine were obtained from Sigma-Aldrich Chemical Co.(St.Louis,MO,USA).All other chemicals used in experiments were of analytical grade.2.2.AChE inhibitory activity of Flammulina velutipes extracts10g F.velutipes powder was extracted with200ml of different solvents(deionized water,ethanol,petroleum ether,and ethyl acetate),respectively,and AChE inhibitory activities of the extracts were compared.Subsequently,the water extract was mixed with quadruplicate anhydrous ethanol and then centrifuged.The precip-itate,crude polysaccharides,was lyophilized and redissolved in water as crude polysaccharide solution(CPS).The supernatant was concentrated under reduced pressure,lyophilized,and redissolved in water as water–ethanol solution(WES).The AChE inhibitory activities of CPS and WES were further investigated.2.3.Ultrasonic extraction and determination of polysaccharidesF.velutipes powder was weighed accurately(10.0g)and extracted with distilled water in ultrasonic cell disintegrator((DCTZ-2000, Beijing Hongxianglong Biotechnology Development Co.Ltd).Subse-quently,the treated mixture was air cooled to room temperature and centrifuged(10,000rpm/min,15min).The supernatant was concen-trated under reduced pressure at65°C.The polysaccharides extracts obtained above were then mixed with4-fold volume anhydrous ethanol(ethanolﬁnal concentration,80%)and kept at4°C for24h. After centrifugation at5000rpm/min for15min,the precipitate was washed three times with anhydrous ethanol and then dialyzed and lyophilized to yield FVP sample.The percentage polysaccharides yield(%)is calculated as follows:Yield of polysaccharideð%Þ¼weight of dried crude FVPðgÞ×1002.4.Experimental designA three-level-four-factor,Box–Behnken factorial design(BBD)was employed in this optimization study.Ratio of water to raw material (X1),ultrasonic power(X2),ultrasonic time(X3),and ultrasonic temperature(X4)were chosen for independent variables to be optimized for the extraction of FVP.Yield of polysaccharides(Y)was taken as the response of the design experiments.Twenty-nine experiments were carried out in BBD(Table1).Five replicates at the center point were used for estimation of a pure error sum of squares.Triplicate determinations were performed at all design points in randomized order.A quadratic polynomial model wasﬁtted to correlate the response variable(yield of polysaccharide)to the independent variables.The general form of quadratic polynomial equation is as follows:Y¼β0þ∑4i¼1βi X iþ∑4i¼1βii X i2þ∑i¼1∑4j¼iþ1βijXiXjwhere Y is the response variable,andβ0,βi,βii,andβij are the regression coefﬁcients for intercept,linearity,square,and interaction, respectively,while X i and X j are the independent variables.2.5.AChE inhibitory activityThe AChE inhibitory activity assay was performed according to the protocol described by Langjae,Bussarawit,Yuenyongsawad, Ingkaninan and Plubrukarn(2007)with slight modiﬁcations.Brieﬂy, 125μl of3mM5,5′-dithio-bis-(2-nitrobenzoic)acid,25μl of1.5mM acetylthiocholine iodide,50μl of50μM Tris–HCl buffer(pH8.0),25μl of sample,and25μl of0.25U/ml AChE were added consecutively into 96-well plate.Then the absorbance was measured immediately at 412nm using an ELISA plate reader(TECAN Inﬁnite F200, Switzerland).The potency of AChE inhibitory activity of FVP was expressed as the inhibition rate.Galanthamine was used as a positive control.Table1Experiment of ultrasonic extraction of polysaccharides from Flammulina velutipes.(Data presented are the mean of triplicate determinations.)Run X1-ratio(ml/g)X2-ultrasonicpower(W)X3-ultrasonictime(min)X4-ultrasonictemperature(°C)Yield of FVP(%)ActualvaluePredictedvalue 12060015508.218.08 2304001550 6.887.05 32060015507.998.08 4204001565 6.63 6.76 5208001565 6.46 6.38 6208002550 6.64 6.82 7206005357.577.30 820400550 6.45 6.25 9108001550 6.21 6.16 1010600550 6.33 6.57 11104001550 6.18 6.14 1220600565 6.897.09 132040025507.597.56 143060015657.797.48 152060015508.178.08 163080015507.467.61 173********.557.55 182******** 6.58 6.96 193060025508.398.03 202060015508.298.08 21106001565 6.28 5.94 222080015357.917.66 23204001535 6.75 6.70 242060025358.067.98 25106001535 6.63 6.92 26106002550 6.77 6.64 272060015507.788.08 283060015357.427.74 29208005507.577.58 Optimumconditions24.81618.9818.6444.73–8.32Modiﬁedconditions2562020458.338.302W.Yang et al./Food Research International xxx(2010)xxx–xxx2.6.DPPH radicals scavenging assayThe DPPH radicals scavenging assay was carried out as previously described by Yang et al (2009).Brie ﬂy,0.1ml of FVP in water was added directly to 3.9ml of a DPPH solution in ethanol (0.1mM).The mixture was immediately shaken for 10s using a vortex mixer,kept at 37°C for 30min,and then centrifuged at 5000rpm/min for 10min.Absorbance of the supernatant was measured at 517nm.Antioxidant capability (AA)was expressed as the percentage of DPPH radicals reduced,which was calculated with the following formula:AA DPPH =A B −A S ðÞ=A B ðÞ×100;where A S is the absorbance of the DPPH solution after reacting with FVP sample at a given concentration and A B is the absorbance of the DPPH solution after reacting with distilled water instead of sample.Ascorbic acid was measured as a positive control.2.7.Statistical analysesData were expressed as means of three replicated determinations.Design Expert (Trial Version 7.0.3)was employed for experimental design,analysis of variance (ANOVA),and model building.SPSS 12.0software was used for statistical calculations and correlation analysis.Values of p b 0.05were considered to be statistically signi ﬁcant.3.Result and discussion3.1.AChE inhibitory activities of Flammulina velutipes extracts In order to study the AChE inhibitory activity of F.velutipes ,four solvent extracts of F.velutipes were prepared for AChE inhibitory activities assay.Results showed that the AChE inhibitory activity of water extract was signi ﬁcantly better than the other solvents extracts (ethanol,petroleum ether,and ethyl acetate).Subsequently,water extract of F.velutipes was separated into two parts (CPS and WES).The results of CPS and WES inhibiting AChE activities suggested that polysaccharides were the principal effective fraction of water extract (Fig.1).Therefore,FVP was selected for further study.3.2.Fitting the model and evaluation of the model predictability In order to obtain more polysaccharides,ratio of water to raw material (10–30ml/g),ultrasonic power (400–800W),ultrasonictime (5–25min),and ultrasonic temperature (35–65°C)was adopted to research their effects on the yield of FVP.The experiments were designed to evaluate the effects of four factors on the yield of FVP using ultrasonic extraction method (Table 1).The mathematical model representing the yield of polysaccharides as a function of the independent variables within the region under investigation was expressed as follows:Y =−11:94+0:18d X 1+0:03d X 2+0:30d X 3+0:25d X 4+6:88×10−5d X 1X 2+1:0×10−3d X 1X 3+1:2×10−3d X 1X 4−2:59×10−4d X 2X 3−1:11×10−4d X 2X 4−1:33×10−3d X 3X 4−5:99×10−3d X 21−1:86×10−5d X 22−2:87×10−3d X 23−2:06×10−3d X 24where Y is the yield of polysaccharides,and X 1,X 2,X 3,and X 4represent ratio of water to raw material,ultrasonic power,ultrasonic time,and ultrasonic temperature,respectively.Predicted response values for the yield of polysaccharides could be obtained using this quadratic polynomial equation in terms of independent variables values.ANOVA for the ﬁtted quadratic polynomial model was given to check the model adequacy (Table 2).F -test suggested that model had a high F -value (F =10.627)and a very low p -value (p b 0.0001),indicating that the ﬁtness of this model was highly signi ﬁck of ﬁt is the variation of the data around the ﬁtted model.The F -value and p -value of the lack of ﬁt were 2.576and 0.188,respectively,which implied an insigni ﬁcant difference relative to the pure error and a good ﬁtness of the model.Coef ﬁcient of determination (R 2)is de ﬁned as the ratio of the explained variation to the total variation,and R 2=0.914approaching unity suggested a good relevance of the dependent variables in the model (Yang,Zhao,Shi,Yang &Jiang,2008).The adjusted determination coef ﬁcient of the model (R 2adj =0.828)con ﬁrmed that the model was signi ﬁcant,indicating a good degree of correlation between the actual values and the predicted values of FVP yield.Adeq precision measures the signal to noise ratio,and a ratio greater than 4is desirable (Zhu,Heo,&Row,2010).An adequate ratio (Adeq precision =10.00)of this ﬁtted model indicated that it can be used to navigate the design space.Coef ﬁcient of variation (CV)is a standard deviation expressed as a percentage of the mean.The lower the CV,the smaller the residuals relative to the predicted value (Zhong &Wang,2010).A low CV of the model (CV=4.12)suggested a good precision and higher reliability oftheFig. 1.AChE inhibitory activity of Flammulina velutipes extracts.CPS:crude polysaccharide solution,WES:water –ethanol solution.Values are means ±SD.Values with same superscript letters are statistically not signi ﬁcantly different at p b 0.05(analysis of variance).Table 2Analysis of variance for the ﬁtted quadratic polynomial model of extraction of polysaccharides.Source Sum of squares dfMean Square F Value p -value Prob N F X 1 4.1891 4.18947.237b 0.0001X 20.26110.261 2.9440.1082X 30.23210.232 2.6210.1278X 41.1471 1.14712.9340.0029X 1X 20.07610.0760.8530.3714X 1X 30.0410.040.4510.5128X 1X 40.13010.130 1.4610.2467X 2X 3 1.0711 1.07112.0800.0037X 2X 40.44210.442 4.9870.0424X 3X 40.16010.16 1.8040.2006X 12 2.3271 2.32726.2440.0002X 223.5911 3.59140.488b 0.0001X 320.53210.532 6.0040.0280X 42 1.3971 1.39715.7480.0014Model 13.194140.94210.627b 0.0001Residual 1.242140.0887Lack of ﬁt 1.07100.107 2.5760.188Pure error 0.1740.042Cor total14.4428R 2=0.914R 2Adj =0.828CV =4.12Adeq precision =10.003W.Yang et al./Food Research International xxx (2010)xxx –xxxexperiments carried out(Gangadharan,Nampoothir,Sivaramakrishnan, &Pandey,2009).These results suggested that the model equation was adequate for reasonably predicting the yield of polysaccharides under any combination of values of the variables.The correlation between the predicted values and the actual values of FVP yield was analyzed according previous reports(Gan,Abdul Manaf&Latiff,2010).The closer the value of correlation coefﬁcient to 1,the better the correlation between the observed and predicted values(Banik&Pandey,2009).As shown in Fig.2,the Pearson's correlation coefﬁcient R=0.962approaching unity indicated a good agreement between the predicted values and the actual values and a good suitability of theﬁtted model equation for reﬂecting the expected optimization.3.3.Effects of extraction conditions on the yield of FVPThe effects of ratio of water to raw material,ultrasonic power, ultrasonic time,and ultrasonic temperature on the yield of poly-saccharides as well as their interactions were analyzed.Three-dimensional response surface plots for the response(the yield of polysaccharides)were plotted in Fig.3.Fig.3a shows the effects of ratio of water to raw material(X1)and ultrasonic power(X2)on the yield of FVP.With the increase of ultrasonic power,the yield of polysaccharides increased to a value and then declined when ratio of water to raw material was low but constantly increased when ratio of water to raw material was high.The yield of polysaccharides increased with increasing of ratio of water to raw material when ultrasonic power,as well as ultrasonic time(Fig.3b)and ultrasonic temperature(Fig.3c)was kept at a constant value.Fig.3b shows the effects of ratio of water to raw material(X1)and ultrasonic time(X3) on the yield of FVP.The yield of polysaccharides increased with the extension of ultrasonic time.Fig.3c shows the effects of ratio of water to raw material(X1)and ultrasonic temperature(X4)on the yield of FVP.The yield of polysaccharides decreased with the elevation of ultrasonic temperature.Fig.3d shows the effects of ultrasonic power (X2)and ultrasonic time(X3)on the yield of FVP.The yield of polysaccharides increased with the increasing of ultrasonic power when extraction bearing a short ultrasonic time,while a contrary result was obtained when extraction bearing a long ultrasonic time. Similarly,the yield of polysaccharides increased with the extension of ultrasonic time when ultrasonic power was low but decreased when ultrasonic power was high.Fig.3e shows the effects of ultrasonic power(X2)and ultrasonic temperature(X4)on the yield of FVP.The extraction yield of polysaccharides decreased with the elevation of ultrasonic temperature when ultrasonic power was high,butﬁrstly increased to a value and then declined when ultrasonic power was low.The possible mechanism was due to the degradation effect of ultrasonic wave and too high temperature(Yang,Zhao&Jiang,2008). The extraction yield of polysaccharides increased with the increase of ultrasonic power at low ultrasonic temperature,butﬁrst increased to a value and then declined at high ultrasonic temperature.Fig.3f shows the effects of ultrasonic time(X3)and ultrasonic temperature (X4)on the yield of FVP.The longer ultrasonic time and lower ultrasonic temperature,the higher polysaccharides yield.Taken altogether,the augment of all the four factors in a certain extent could increase the yield of polysaccharides,but higher ultrasonic power,if accompanied with higher ultrasonic temperature or longer ultrasonic time,would lower the yield of the yield of polysaccharides.The signiﬁcance of each coefﬁcient was checked by F-test and p-value(Table2).Values of“prob N F”less than0.05indicate model terms are signiﬁcant.It can be seen that the variables with the largest effect on the yield of FVP were X1,X4,X2X3,X2X4,X12,X22,X32,and X42,which suggested that ratio of water to raw material and ultrasonic temperature signiﬁcantly inﬂuenced the yield of FVP.Meanwhile,signiﬁcant interactions between ultrasonic power and ultrasonic time,and ultrasonic power and ultrasonic temperature were observed.This indicated that high ultrasonic power could reduce extraction time and temperature to avoid oxidation induced by high temperature.3.4.The optimal conditions and validation of the modelBy prediction of computing program,the optimal conditions for the highest yield of polysaccharides were as follows:ratio of water to material of24.81ml/g,ultrasonic power of618.98W,ultrasonic time of18.64min,and ultrasonic temperature of44.73°C.A predicted value of8.32%was obtained for yield of polysaccharides under the optimal conditions.In order to facilitate the practical extraction process of FVP,the optimal conditions were modiﬁed as follows:ratio of water to material of25ml/g,ultrasonic power of620W,ultrasonic time of20min,and ultrasonic temperature of45°C.A predicted value of8.30%was obtained under the modiﬁed conditions.The modiﬁed conditions were used to validate the suitability of theﬁtted model equation for accurately predicting the responses values.The results showed that the actual values of polysaccharides yield were8.29% under the modiﬁed conditions(Table1),which were in agreement with the predict values signiﬁcantly(p N0.05).Furthermore,FVP was extracted with a conventional method (ratio of water to material of25ml/g,extraction in80°C water bath for4h),and a yield of5.12%was obtained,which is signiﬁcantly less than that obtained with the ultrasonic extraction method.The results suggested that ultrasonic assistant extraction of FVP was a time and energy saving and high yielding method.3.5.AChE inhibitory activity of FVPAlzheimer's disease,a disorder associated with progressive degeneration of memory and cognitive function,results from a deﬁcit of cholinergic function in brain.The most important changes observed in brain are a decrease in hippocampal and cortical levels of the neurotransmitter acetylcholine and associated choline transferase (López,Bastida,Viladomat&Codina,2002;Perry,1986).Inhibiting AChE activity is considered as one of the most important methods to improve cognitive deﬁcit and learning and memory impairment by restoring the level of acetylcholine.In this study,concentration-dependent inhibition of AChE was observed for galanthamine.FVP exhibited moderate AChE inhibitory activity(up to20%)that was not dose-dependent(Fig.4).It is reported that polyphenol-rich extract of Vaccinium angustifolium exhibited moderate AChE inhibitory activity in vitro(up to30%),but the polyphenol treated mice exhibited a signiﬁcant improvement in learning and memory(Papandreou et al.,2009).Theseﬁndings indicated that FVP may be having a potential application value in improving cognitive deﬁcit and memory impairment.It has been reported that FVP improved the learning and memory ability of dysmnesia model animals effectively evaluated bystep-Fig.2.Correlation between the predicted values and actual values of FVP yield.4W.Yang et al./Food Research International xxx(2010)xxx–xxxthrough test and Morris water test (Zou et al.,2010).In the present study,the results of AChE inhibitory activity in vitro suggest a potential application of FVP to improve cognitive de ﬁcit.This may be one of the most important pharmacological mechanisms of enhancing the learning and memory capability of dysmnesia mice,which need our furtherinvestigation.Fig.3.(a)Response surface plots showing the effects of ratio of water to raw material (X 1)and ultrasonic power (X 2)on the yield of FVP (Y ).(b)Response surface plots showing the effects of ratio of water to raw material (X 1)and ultrasonic time (X 3)on the yield of FVP (Y ).(c)Response surface plots showing the effects of ratio of water to raw material (X 1)and ultrasonic temperature (X 4)on the yield of FVP (Y ).(d)Response surface plots showing the effects of ultrasonic power (X 2)and ultrasonic time (X 3)on the yield of FVP (Y ).(e)Response surface plots showing the effects of ultrasonic power (X 2)and ultrasonic temperature (X 4)on the yield of FVP (Y ).(f)Response surface plots showing the effects of ultrasonic time (X 3)and ultrasonic temperature (X 4)on the yield of FVP (Y ).5W.Yang et al./Food Research International xxx (2010)xxx –xxx3.6.DPPH radicals scavenging activity of FVPFree radical species have been reported to contribute to cellular ageing and neuronal damage (Sastre,Pallardo &Vina,2000).Excess amount of reactive oxygen species,which causes oxidative stress,is associated with pathology of memory de ﬁcits and associated diseases including Alzheimer's disease (Silva et al.,2004;Soholm,1998).DPPH radicals have been widely used as model systems to investigate the antioxidant ability of compounds.In this study,the DPPH scavengingactivity of FVP was concentration-dependent and the scavenging rate was up to 61.24%at concentration of 0.6mg/ml (Fig.5).Good antioxidant ability of FVP implies a potential of FVP to protect cognitive impairment.Moreover,polysaccharides have been proved to exhibit indirect antioxidant ability in vivo by increasing glutathione peroxidase and superoxide dismutase activities (Zhang et al.,2003).Therefore,in order to have a thorough knowledge of pharmacological mechanisms of improving cognitive de ﬁcit,the effect of FVP on antioxidant enzymes in vivo needs to be further studied.4.ConclusionExtraction conditions of FVP were optimized using BBD in response surface methodology,and a quadratic model was ﬁtted for the extraction conditions of FVP.Results of ANOVA and validation experiments suggested that the ﬁtted model was adequate for reasonably predicting the yield of FVP.A FVP yield of 8.33%was obtained under the modi ﬁed conditions (ratio of water to material of 25ml/g,ultrasonic power of 620W,ultrasonic time of 20min,and ultrasonic temperature of 45°C).A good potential of FVP to enhance cognitive ability was testi ﬁed by DPPH scavenging activity assay and AChE inhibitory activity test,which indicate that consummation of F.velutipes is bene ﬁcial to improve learning and memory de ﬁcit.AcknowledgmentThis work is ﬁnancially supported by the earmarked fund for Modern Agro-industry Technology Research System of China.ReferencesBanik,R.M.,&Pandey,S.K.(2009).Selection of metal salts for alkaline phosphataseproduction using response surface methodology.Food Research International ,42,470−475.Fan,Y.,Hu,J.,Li,J.,Yang,Z.,Xin,X.,Wang,J.,Ding,J.,&Geng,M.(2005).Effect of acidicoligosaccharide sugar chain on scopolamine-induced memory impairment in rats and its related mechanisms.Neuroscience Letters ,374,222−226.Gan,C.-Y.,Abdul Manaf,N.H.,&Latiff,A.A.(2010).Optimization of alcohol insolublepolysaccharides (AIPS)extraction from the Parkia speciosa pod using response surface methodology (RSM).Carbohydrate Polymers ,79,825−831.Gangadharan, D.,Nampoothiri,K.M.,Sivaramakrishnan,S.,&Pandey, A.(2009).Immobilized bacterial α-amylase for effective hydrolysis of raw and soluble starch.Food Research International ,42,436−442.Gold,P.E.(2003).Acetylcholine modulation of neural systems involved in learning andmemory.Neurobiology of Learning and Memory ,80,194−210.Hornick,A.,Schwaiger,S.,Rollinger,J.M.,Vo,N.P.,Prast,H.,&Stuppner,H.(2008).Extracts and constituents of Leontopodium alpinum enhance cholinergic transmis-sion:Brain ACh increasing and memory improving properties.Biochemical Pharmacology ,76,236−248.Langjae,R.,Bussarawit,S.,Yuenyongsawad,S.,Ingkaninan,K.,&Plubrukarn,A.(2007).Acetylcholinesterase-inhibiting steroidal alkaloid from the sponge Corticium sp.Steroids ,72,682−685.Leung,M.Y.K.,Fung,K.P.,&Choy,Y.M.(1997).The isolation and characterization of animmunomodulatory and anti-tumor polysaccharide preparation from Flammulina velutipes .Immunopharmacology ,35,255−263.Li,H.,Pordesimo,L.,&Weiss,J.(2004).High intensity ultrasound-assisted extraction ofoil from soybeans.Food Research International ,37(7),731−738.López,S.,Bastida,J.,Viladomat,F.,&Codina,C.(2002).Acetylcholinesterase inhibitoryactivity of some Amaryllidaceae alkaloids and Narcissus extracts.Life Sciences ,71,2521−2529.Papandreou,M.A.,Dimakopoulou,A.,Linardaki,Z.I.,Cordopatis,P.,Klimis-Zacas,D.,Margarity,M.,&Lamari,F.N.(2009).Effect of a polyphenol-rich wild blueberry extract on cognitive performance of mice,brain antioxidant markers and acetylcholinesterase activity.Behavioural Brain Research ,198,352−358.Perry,E.K.(1986).The cholinergic hypothesis —ten years on.British Medical Bulletin ,42,63−69.Roberson,M.R.,&Harrell,L.E.(1997).Cholinergic activity and amyloid precursorprotein metabolism.Brain Research.Brain Research Reviews ,25,50−69.Sastre,J.,Pallardo,F.V.,&Vina,J.(2000).Mitochondrial oxidative stress plays a key rolein aging and apoptosis.IUBMB Life ,49,427−435.Silman,I.,&Sussman,J.L.(2005).Acetylcholinesterase:‘Classical ’and 'non-classical'functions and pharmacology.Current Opinion in Pharmacology ,5,293−302.Silva,R.H.,Abilio,V.C.,Takatsu,A.L.,Kameda,S.R.,Grassl,C.,Chehin,A.B.,Medrano,W.A.,Calzavara,M.B.,Registro,S.,Andersen,M.L.,Machado,R.B.,Carvalho,R.C.,Ribeiro,R.d.A.,Tu ﬁk,S.,&Frussa-Filho,R.(2004).Role of hippocampal oxidative stress in memory de ﬁcits induced by sleep deprivation in mice.Neuropharmacology ,46,895−903.Fig.4.AChE inhibitory activity of galanthamine and FVP with various concentrations (data are in mean ±SD,n =3).Fig. 5.DPPH radicals scavenging activity of FVP and ascorbic acid with various concentrations (data are in mean±SD,n =3).6W.Yang et al./Food Research International xxx (2010)xxx –xxx。

Principles of Plasma Discharges and Materials Processing9

CHAPTER8MOLECULAR COLLISIONS8.1INTRODUCTIONBasic concepts of gas-phase collisions were introduced in Chapter3,where we described only those processes needed to model the simplest noble gas discharges: electron–atom ionization,excitation,and elastic scattering;and ion–atom elastic scattering and resonant charge transfer.In this chapter we introduce other collisional processes that are central to the description of chemically reactive discharges.These include the dissociation of molecules,the generation and destruction of negative ions,and gas-phase chemical reactions.Whereas the cross sections have been measured reasonably well for the noble gases,with measurements in reasonable agreement with theory,this is not the case for collisions in molecular gases.Hundreds of potentially signiﬁcant collisional reactions must be examined in simple diatomic gas discharges such as oxygen.For feedstocks such as CF4/O2,SiH4/O2,etc.,the complexity can be overwhelming.Furthermore,even when the signiﬁcant processes have been identiﬁed,most of the cross sections have been neither measured nor calculated. Hence,one must often rely on estimates based on semiempirical or semiclassical methods,or on measurements made on molecules analogous to those of interest. As might be expected,data are most readily available for simple diatomic and polyatomic gases.Principles of Plasma Discharges and Materials Processing,by M.A.Lieberman and A.J.Lichtenberg. ISBN0-471-72001-1Copyright#2005John Wiley&Sons,Inc.235236MOLECULAR COLLISIONS8.2MOLECULAR STRUCTUREThe energy levels for the electronic states of a single atom were described in Chapter3.The energy levels of molecules are more complicated for two reasons. First,molecules have additional vibrational and rotational degrees of freedom due to the motions of their nuclei,with corresponding quantized energies E v and E J. Second,the energy E e of each electronic state depends on the instantaneous con-ﬁguration of the nuclei.For a diatomic molecule,E e depends on a single coordinate R,the spacing between the two nuclei.Since the nuclear motions are slow compared to the electronic motions,the electronic state can be determined for anyﬁxed spacing.We can therefore represent each quantized electronic level for a frozen set of nuclear positions as a graph of E e versus R,as shown in Figure8.1.For a mole-cule to be stable,the ground(minimum energy)electronic state must have a minimum at some value R1corresponding to the mean intermolecular separation (curve1).In this case,energy must be supplied in order to separate the atoms (R!1).An excited electronic state can either have a minimum( R2for curve2) or not(curve3).Note that R2and R1do not generally coincide.As for atoms, excited states may be short lived(unstable to electric dipole radiation)or may be metastable.Various electronic levels may tend to the same energy in the unbound (R!1)limit. Array FIGURE8.1.Potential energy curves for the electronic states of a diatomic molecule.For diatomic molecules,the electronic states are speciﬁedﬁrst by the component (in units of hÀ)L of the total orbital angular momentum along the internuclear axis, with the symbols S,P,D,and F corresponding to L¼0,+1,+2,and+3,in analogy with atomic nomenclature.All but the S states are doubly degenerate in L.For S states,þandÀsuperscripts are often used to denote whether the wave function is symmetric or antisymmetric with respect to reﬂection at any plane through the internuclear axis.The total electron spin angular momentum S (in units of hÀ)is also speciﬁed,with the multiplicity2Sþ1written as a preﬁxed superscript,as for atomic states.Finally,for homonuclear molecules(H2,N2,O2, etc.)the subscripts g or u are written to denote whether the wave function is sym-metric or antisymmetric with respect to interchange of the nuclei.In this notation, the ground states of H2and N2are both singlets,1Sþg,and that of O2is a triplet,3SÀg .For polyatomic molecules,the electronic energy levels depend on more thanone nuclear coordinate,so Figure8.1must be generalized.Furthermore,since there is generally no axis of symmetry,the states cannot be characterized by the quantum number L,and other naming conventions are used.Such states are often speciﬁed empirically through characterization of measured optical emission spectra.Typical spacings of low-lying electronic energy levels range from a few to tens of volts,as for atoms.Vibrational and Rotational MotionsUnfreezing the nuclear vibrational and rotational motions leads to additional quan-tized structure on smaller energy scales,as illustrated in Figure8.2.The simplest (harmonic oscillator)model for the vibration of diatomic molecules leads to equally spaced quantized,nondegenerate energy levelse E v¼hÀv vib vþ1 2(8:2:1)where v¼0,1,2,...is the vibrational quantum number and v vib is the linearized vibration frequency.Fitting a quadratic functione E v¼12k vib(RÀ R)2(8:2:2)near the minimum of a stable energy level curve such as those shown in Figure8.1, we can estimatev vib%k vibm Rmol1=2(8:2:3)where k vib is the“spring constant”and m Rmol is the reduced mass of the AB molecule.The spacing hÀv vib between vibrational energy levels for a low-lying8.2MOLECULAR STRUCTURE237stable electronic state is typically a few tenths of a volt.Hence for molecules in equi-librium at room temperature (0.026V),only the v ¼0level is signiﬁcantly popula-ted.However,collisional processes can excite strongly nonequilibrium vibrational energy levels.We indicate by the short horizontal line segments in Figure 8.1a few of the vibrational energy levels for the stable electronic states.The length of each segment gives the range of classically allowed vibrational motions.Note that even the ground state (v ¼0)has a ﬁnite width D R 1as shown,because from(8.2.1),the v ¼0state has a nonzero vibrational energy 1h Àv vib .The actual separ-ation D R about Rfor the ground state has a Gaussian distribution,and tends toward a distribution peaked at the classical turning points for the vibrational motion as v !1.The vibrational motion becomes anharmonic and the level spa-cings tend to zero as the unbound vibrational energy is approached (E v !D E 1).FIGURE 8.2.Vibrational and rotational levels of two electronic states A and B of a molecule;the three double arrows indicate examples of transitions in the pure rotation spectrum,the rotation–vibration spectrum,and the electronic spectrum (after Herzberg,1971).238MOLECULAR COLLISIONSFor E v.D E1,the vibrational states form a continuum,corresponding to unbound classical motion of the nuclei(breakup of the molecule).For a polyatomic molecule there are many degrees of freedom for vibrational motion,leading to a very compli-cated structure for the vibrational levels.The simplest(dumbbell)model for the rotation of diatomic molecules leads to the nonuniform quantized energy levelse E J¼hÀ22I molJ(Jþ1)(8:2:4)where I mol¼m Rmol R2is the moment of inertia and J¼0,1,2,...is the rotational quantum number.The levels are degenerate,with2Jþ1states for the J th level. The spacing between rotational levels increases with J(see Figure8.2).The spacing between the lowest(J¼0to J¼1)levels typically corresponds to an energy of0.001–0.01V;hence,many low-lying levels are populated in thermal equilibrium at room temperature.Optical EmissionAn excited molecular state can decay to a lower energy state by emission of a photon or by breakup of the molecule.As shown in Figure8.2,the radiation can be emitted by a transition between electronic levels,between vibrational levels of the same electronic state,or between rotational levels of the same electronic and vibrational state;the radiation typically lies within the optical,infrared,or microwave frequency range,respectively.Electric dipole radiation is the strongest mechanism for photon emission,having typical transition times of t rad 10À9s,as obtained in (3.4.13).The selection rules for electric dipole radiation areDL¼0,+1(8:2:5a)D S¼0(8:2:5b) In addition,for transitions between S states the only allowed transitions areSþÀ!Sþand SÀÀ!SÀ(8:2:6) and for homonuclear molecules,the only allowed transitions aregÀ!u and uÀ!g(8:2:7) Hence homonuclear diatomic molecules do not have a pure vibrational or rotational spectrum.Radiative transitions between electronic levels having many different vibrational and rotational initial andﬁnal states give rise to a structure of emission and absorption bands within which a set of closely spaced frequencies appear.These give rise to characteristic molecular emission and absorption bands when observed8.2MOLECULAR STRUCTURE239using low-resolution optical spectrometers.As for atoms,metastable molecular states having no electric dipole transitions to lower levels also exist.These have life-times much exceeding10À6s;they can give rise to weak optical band structures due to magnetic dipole or electric quadrupole radiation.Electric dipole radiation between vibrational levels of the same electronic state is permitted for molecules having permanent dipole moments.In the harmonic oscillator approximation,the selection rule is D v¼+1;weaker transitions D v¼+2,+3,...are permitted for anharmonic vibrational motion.The preceding description of molecular structure applies to molecules having arbi-trary electronic charge.This includes neutral molecules AB,positive molecular ions ABþ,AB2þ,etc.and negative molecular ions ABÀ.The potential energy curves for the various electronic states,regardless of molecular charge,are commonly plotted on the same diagram.Figures8.3and8.4give these for some important electronic statesof HÀ2,H2,and Hþ2,and of OÀ2,O2,and Oþ2,respectively.Examples of both attractive(having a potential energy minimum)and repulsive(having no minimum)states can be seen.The vibrational levels are labeled with the quantum number v for the attrac-tive levels.The ground states of both Hþ2and Oþ2are attractive;hence these molecular ions are stable against autodissociation(ABþ!AþBþor AþþB).Similarly,the ground states of H2and O2are attractive and lie below those of Hþ2and Oþ2;hence they are stable against autodissociation and autoionization(AB!ABþþe).For some molecules,for example,diatomic argon,the ABþion is stable but the AB neutral is not stable.For all molecules,the AB ground state lies below the ABþground state and is stable against autoionization.Excited states can be attractive or repulsive.A few of the attractive states may be metastable;some examples are the 3P u state of H2and the1D g,1Sþgand3D u states of O2.Negative IonsRecall from Section7.2that many neutral atoms have a positive electron afﬁnity E aff;that is,the reactionAþeÀ!AÀis exothermic with energy E aff(in volts).If E aff is negative,then AÀis unstable to autodetachment,AÀ!Aþe.A similar phenomenon is found for negative molecular ions.A stable ABÀion exists if its ground(lowest energy)state has a potential minimum that lies below the ground state of AB.This is generally true only for strongly electronegative gases having large electron afﬁnities,such as O2 (E aff%1:463V for O atoms)and the halogens(E aff.3V for the atoms).For example,Figure8.4shows that the2P g ground state of OÀ2is stable,with E aff% 0:43V for O2.For weakly electronegative or for electropositive gases,the minimum of the ground state of ABÀgenerally lies above the ground state of AB,and ABÀis unstable to autodetachment.An example is hydrogen,which is weakly electronegative(E aff%0:754V for H atoms).Figure8.3shows that the2Sþu ground state of HÀ2is unstable,although the HÀion itself is stable.In an elec-tropositive gas such as N2(E aff.0),both NÀ2and NÀare unstable. 240MOLECULAR COLLISIONS8.3ELECTRON COLLISIONS WITH MOLECULESThe interaction time for the collision of a typical (1–10V)electron with a molecule is short,t c 2a 0=v e 10À16–10À15s,compared to the typical time for a molecule to vibrate,t vib 10À14–10À13s.Hence for electron collisional excitation of a mole-cule to an excited electronic state,the new vibrational (and rotational)state canbeFIGURE 8.3.Potential energy curves for H À2,H 2,and H þ2.(From Jeffery I.Steinfeld,Molecules and Radiation:An Introduction to Modern Molecular Spectroscopy ,2d ed.#MIT Press,1985.)8.3ELECTRON COLLISIONS WITH MOLECULES 241FIGURE 8.4.Potential energy curves for O À2,O 2,and O þ2.(From Jeffery I.Steinfeld,Molecules and Radiation:An Introduction to Modern Molecular Spectroscopy ,2d ed.#MIT Press,1985.)242MOLECULAR COLLISIONS8.3ELECTRON COLLISIONS WITH MOLECULES243 determined by freezing the nuclear motions during the collision.This is known as the Franck–Condon principle and is illustrated in Figure8.1by the vertical line a,showing the collisional excitation atﬁxed R to a high quantum number bound vibrational state and by the vertical line b,showing excitation atﬁxed R to a vibra-tionally unbound state,in which breakup of the molecule is energetically permitted. Since the typical transition time for electric dipole radiation(t rad 10À9–10À8s)is long compared to the dissociation( vibrational)time t diss,excitation to an excited state will generally lead to dissociation when it is energetically permitted.Finally, we note that the time between collisions t c)t rad in typical low-pressure processing discharges.Summarizing the ordering of timescales for electron–molecule collisions,we havet at t c(t vib t diss(t rad(t cDissociationElectron impact dissociation,eþABÀ!AþBþeof feedstock gases plays a central role in the chemistry of low-pressure reactive discharges.The variety of possible dissociation processes is illustrated in Figure8.5.In collisions a or a0,the v¼0ground state of AB is excited to a repulsive state of AB.The required threshold energy E thr is E a for collision a and E a0for Array FIGURE8.5.Illustrating the variety of dissociation processes for electron collisions with molecules.collision a0,and it leads to an energy after dissociation lying between E aÀE diss and E a0ÀE diss that is shared among the dissociation products(here,A and B). Typically,E aÀE diss few volts;consequently,hot neutral fragments are typically generated by dissociation processes.If these hot fragments hit the substrate surface, they can profoundly affect the process chemistry.In collision b,the ground state AB is excited to an attractive state of AB at an energy E b that exceeds the binding energy E diss of the AB molecule,resulting in dissociation of AB with frag-ment energy E bÀE diss.In collision b0,the excitation energy E b0¼E diss,and the fragments have low energies;hence this process creates fragments having energies ranging from essentially thermal energies up to E bÀE diss few volts.In collision c,the AB atom is excited to the bound excited state ABÃ(labeled5),which sub-sequently radiates to the unbound AB state(labeled3),which then dissociates.The threshold energy required is large,and the fragments are hot.Collision c can also lead to dissociation of an excited state by a radiationless transfer from state5to state4near the point where the two states cross:ABÃðboundÞÀ!ABÃðunboundÞÀ!AþBÃThe fragments can be both hot and in excited states.We discuss such radiationless electronic transitions in the next section.This phenomenon is known as predisso-ciation.Finally,a collision(not labeled in theﬁgure)to state4can lead to dis-sociation of ABÃ,again resulting in hot excited fragments.The process of electron impact excitation of a molecule is similar to that of an atom,and,consequently,the cross sections have a similar form.A simple classical estimate of the dissociation cross section for a level having excitation energy U1can be found by requiring that an incident electron having energy W transfer an energy W L lying between U1and U2to a valence electron.Here,U2is the energy of the next higher level.Then integrating the differential cross section d s[given in(3.4.20)and repeated here],d s¼pe24021Wd W LW2L(3:4:20)over W L,we obtains diss¼0W,U1pe24pe021W1U1À1WU1,W,U2pe24021W1U1À1U2W.U28>>>>>><>>>>>>:(8:3:1)244MOLECULAR COLLISIONSLetting U2ÀU1(U1and introducing voltage units W¼e E,U1¼e E1and U2¼e E2,we haves diss¼0E,E1s0EÀE11E1,E,E2s0E2ÀE1EE.E28>>>><>>>>:(8:3:2)wheres0¼pe4pe0E12(8:3:3)We see that the dissociation cross section rises linearly from the threshold energy E thr%E1to a maximum value s0(E2ÀE1)=E thr at E2and then falls off as1=E. Actually,E1and E2can depend on the nuclear separation R.In this case,(8.3.2) should be averaged over the range of R s corresponding to the ground-state vibrational energy,leading to a broadened dependence of the average cross section on energy E.The maximum cross section is typically of order10À15cm2. Typical rate constants for a single dissociation process with E thr&T e have an Arrhenius formK diss/K diss0expÀE thr T e(8:3:4)where K diss0 10À7cm3=s.However,in some cases E thr.T e.For excitation to an attractive state,an appropriate average over the fraction of the ground-state vibration that leads to dissociation must be taken.Dissociative IonizationIn addition to normal ionization,eþABÀ!ABþþ2eelectron–molecule collisions can lead to dissociative ionizationeþABÀ!AþBþþ2eThese processes,common for polyatomic molecules,are illustrated in Figure8.6.In collision a having threshold energy E iz,the molecular ion ABþis formed.Collisionsb andc occur at higher threshold energies E diz and result in dissociative ionization,8.3ELECTRON COLLISIONS WITH MOLECULES245leading to the formation of fast,positively charged ions and neutrals.These cross sections have a similar form to the Thompson ionization cross section for atoms.Dissociative RecombinationThe electron collision,e þAB þÀ!A þB Ãillustrated as d and d 0in Figure 8.6,destroys an electron–ion pair and leads to the production of fast excited neutral fragments.Since the electron is captured,it is not available to carry away a part of the reaction energy.Consequently,the collision cross section has a resonant character,falling to very low values for E ,E d and E .E d 0.However,a large number of excited states A Ãand B Ãhaving increasing principal quantum numbers n and energies can be among the reaction products.Consequently,the rate constants can be large,of order 10À7–10À6cm 3=s.Dissocia-tive recombination to the ground states of A and B cannot occur because the potential energy curve for AB þis always greater than the potential energycurveFIGURE 8.6.Illustration of dissociative ionization and dissociative recombination for electron collisions with molecules.246MOLECULAR COLLISIONSfor the repulsive state of AB.Two-body recombination for atomic ions or for mol-ecular ions that do not subsequently dissociate can only occur with emission of a photon:eþAþÀ!Aþh n:As shown in Section9.2,the rate constants are typically three toﬁve orders of magnitude lower than for dissociative recombination.Example of HydrogenThe example of H2illustrates some of the inelastic electron collision phenomena we have discussed.In order of increasing electron impact energy,at a threshold energy of 8:8V,there is excitation to the repulsive3Sþu state followed by dissociation into two fast H fragments carrying 2:2V/atom.At11.5V,the1Sþu bound state is excited,with subsequent electric dipole radiation in the ultraviolet region to the1Sþg ground state.At11.8V,there is excitation to the3Sþg bound state,followedby electric dipole radiation to the3Sþu repulsive state,followed by dissociation with 2:2V/atom.At12.6V,the1P u bound state is excited,with UV emission tothe ground state.At15.4V,the2Sþg ground state of Hþ2is excited,leading to the pro-duction of Hþ2ions.At28V,excitation of the repulsive2Sþu state of Hþ2leads to thedissociative ionization of H2,with 5V each for the H and Hþfragments.Dissociative Electron AttachmentThe processes,eþABÀ!AþBÀproduce negative ion fragments as well as neutrals.They are important in discharges containing atoms having positive electron afﬁnities,not only because of the pro-duction of negative ions,but because the threshold energy for production of negative ion fragments is usually lower than for pure dissociation processes.A variety of pro-cesses are possible,as shown in Figure8.7.Since the impacting electron is captured and is not available to carry excess collision energy away,dissociative attachment is a resonant process that is important only within a narrow energy range.The maximum cross sections are generally much smaller than the hard-sphere cross section of the molecule.Attachment generally proceeds by collisional excitation from the ground AB state to a repulsive ABÀstate,which subsequently either auto-detaches or dissociates.The attachment cross section is determined by the balance between these processes.For most molecules,the dissociation energy E diss of AB is greater than the electron afﬁnity E affB of B,leading to the potential energy curves shown in Figure8.7a.In this case,the cross section is large only for impact energies lying between a minimum value E thr,for collision a,and a maximum value E0thr for8.3ELECTRON COLLISIONS WITH MOLECULES247FIGURE 8.7.Illustration of a variety of electron attachment processes for electron collisions with molecules:(a )capture into a repulsive state;(b )capture into an attractive state;(c )capture of slow electrons into a repulsive state;(d )polar dissociation.248MOLECULAR COLLISIONScollision a 0.The fragments are hot,having energies lying between minimum and maximum values E min ¼E thr þE affB ÀE diss and E max ¼E 0thr þE af fB ÀE diss .Since the AB Àstate lies above the AB state for R ,R x ,autodetachment can occur as the mol-ecules begin to separate:AB À!AB þe.Hence the cross section for production of negative ions can be much smaller than that for excitation of the AB Àrepulsive state.As a crude estimate,for the same energy,the autodetachment rate is ﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃM R =m p 100times the dissociation rate of the repulsive AB Àmolecule,where M R is the reduced mass.Hence only one out of 100excitations lead to dissociative attachment.Excitation to the AB Àbound state can also lead to dissociative attachment,as shown in Figure 8.7b .Here the cross section is signiﬁcant only for E thr ,E ,E 0thr ,but the fragments can have low energies,with a minimum energy of zero and a maximum energy of E 0thr þE affB ÀE diss .Collision b,e þAB À!AB ÀÃdoes not lead to production of AB Àions because energy and momentum are not gen-erally conserved when two bodies collide elastically to form one body (see Problem3.12).Hence the excited AB ÀÃion separates,AB ÀÃÀ!e þABunless vibrational radiation or collision with a third body carries off the excess energy.These processes are both slow in low-pressure discharges (see Section 9.2).At high pressures (say,atmospheric),three-body attachment to form AB Àcan be very important.For a few molecules,such as some halogens,the electron afﬁnity of the atom exceeds the dissociation energy of the neutral molecule,leading to the potential energy curves shown in Figure 8.7c .In this case the range of electron impact ener-gies E for excitation of the AB Àrepulsive state includes E ¼0.Consequently,there is no threshold energy,and very slow electrons can produce dissociative attachment,resulting in hot neutral and negative ion fragments.The range of R s over which auto-detachment can occur is small;hence the maximum cross sections for dissociative attachment can be as high as 10À16cm 2.A simple classical estimate of electron capture can be made using the differential scattering cross section for energy loss (3.4.20),in a manner similar to that done for dissociation.For electron capture to an energy level E 1that is unstable to autode-tachment,and with the additional constraint for capture that the incident electron energy lie within E 1and E 2¼E 1þD E ,where D E is a small energy difference characteristic of the dissociative attachment timescale,we obtain,in place of (8.3.2),s att¼0E ,E 1s 0E ÀE 1E 1E 1,E ,E 20E .E 28>><>>:(8:3:5)8.3ELECTRON COLLISIONS WITH MOLECULES 249wheres 0%p m M R 1=2e 4pe 0E 1 2(8:3:6)The factor of (m =M R )1=2roughly gives the fraction of excited states that do not auto-detach.We see that the dissociative attachment cross section rises linearly at E 1to a maximum value s 0D E =E 1and then falls abruptly to zero.As for dissociation,E 1can depend strongly on the nuclear separation R ,and (8.3.5)must be averaged over the range of E 1s corresponding to the ground state vibrational motion;e.g.,from E thr to E 0thr in Figure 8.7a .Because generally D E (E 0thr ÀE thr ,we can write (8.3.5)in the forms att %p m M R 1=2e 4pe 0 2(D E )22E 1d (E ÀE 1)(8:3:7)where d is the Dirac delta ing (8.3.7),the average over the vibrational motion can be performed,leading to a cross section that is strongly peaked lying between E thr and E 0thr .We leave the details of the calculation to a problem.Polar DissociationThe process,e þAB À!A þþB Àþeproduces negative ions without electron capture.As shown in Figure 8.7d ,the process proceeds by excitation of a polar state A þand B Àof AB Ãthat has a separ-ated atom limit of A þand B À.Hence at large R ,this state lies above the A þB ground state by the difference between the ionization potential of A and the electron afﬁnity of B.The polar state is weakly bound at large R by the Coulomb attraction force,but is repulsive at small R .The maximum cross section and the dependence of the cross section on electron impact energy are similar to that of pure dissociation.The threshold energy E thr for polar dissociation is generally large.The measured cross section for negative ion production by electron impact in O 2is shown in Figure 8.8.The sharp peak at 6.5V is due to dissociative attachment.The variation of the cross section with energy is typical of a resonant capture process.The maximum cross section of 10À18cm 2is quite low because autode-tachment from the repulsive O À2state is strong,inhibiting dissociative attachment.The second gradual maximum near 35V is due to polar dissociation;the variation of the cross section with energy is typical of a nonresonant process.250MOLECULAR COLLISIONS。

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E COLE NORMALE SUPERIEURE
_____e Deviations for Langevin Spin Glass Dynamics G. BEN AROUS A. GUIONNET
LMENS - 95 - 3
________________________
G. Ben Arous, A. Guionnet y
Abstract: We study the asymptotic behavior of asymmetrical spin glass dynamics in a
Sherrington-Kirkpatrick model as proposed by Sompolinsky-Zippelius. We prove that the annealed law of the empirical measure on path space of these dynamics satisfy a large deviation principle in the high temperature regime. We study the rate function of this large deviation principle and prove that it achieves its minimum value at a unique probability measure Q which is not markovian.We deduce that the quenched law of the empirical measure converges to Q. Extending then the preceeding results to replicated dynamics, we investigate the quenched behavior of a single spin. We get quenched convergence to Q in the case of a symmetric initial law and even potential for the free spin. dynamics.
Laboratoire de Mathematiques de l'Ecole Normale Superieure 45 rue d'Ulm 75230 PARIS Cedex 05
Tel : (33)(1) 44 32 00 00 Adresse electronique : .. @dmi.ens.fr
code A.M.S : 60F10, 60H10, 60K35, 82C44, 82C31, 82C22
1
1 Introduction
The Sherrington Kirkpatrick model is a mean eld simpli cation of the spin glass model of Edwards-Anderson. The behavior of its static characteristics such as its partition function has been intensively studied by physicists (see 9] for a broad survey). There are few mathematical results available ( except for 1], 3] and 17]). In 9], it is argued that studying dynamics might be simpler since it avoids using the "replica trick" and the Parisi ansatz for symmetry-breaking which are yet to be put on rm ground. It seems that, in the physics litterature, the rst attempt to study the dynamics of Sherrington-Kirkpatrick is due to Sompolinsky and Zippelius (see 16]), who chose a Langevin dynamics scheme. We follow here this stategy with some technical restrictions explained below. Our aim was to understand chapter V of 9] from a mathematical point of view. Roughly speaking, the rst conclusion to be drawn from 9] is that the limiting dynamics are not markovian and seem rather mysterious. One of our goals is to derive the law of those dynamics by means of a large deviation principle . Our approach builds upon the strategy developped for a much simpler mean- eld dynamics problem ; i.e the large deviation approach to study propagation of chaos for mean eld interacting di usions, and subsequently convergence to Mac Kean-Vlasov dynamics ( see 2], 4], 15], 18] ). To be more speci c, let us recall that the Sherrington- Kirckpatrick hamiltonian is given X by HJ (x) = p1 J x x , for x = (x1; ; xN ) 2 f?1; 1gN , where the randomness in the N i;j ij i j spin glass is here modelled by the (Jij )i j which are i.i.d standard centered gaussian random variables, and where Jij = Jji. The Gibbs measure one would like to study ( for N large) is given by : e? HJ (x) N (dx) Z (J )
N
Where = 1 ( ?1 + 1) and is the inverse of temperature. 2 ZN (J ) is the partition function : X ? HJ (x) e ZN (J ) = 21 N N x2f?1;1g
2 ( )
If one replaces the hard spins f?1; +1g by continuous spins, i.e by spins taking values in IR, or 1 as we shall see in a bounded interval of IR, and if one replaces the measure = 2 ( ?1 + 1) e? U x by = R e? U x dx dx, where U is, for instance, a double well potential on IR, then, the Langevin dynamics for this problem are given by : X Jjixitdt (1) dxjt = dBtj ? rU (xjt )dt ? p N1 i N Where B is a N-dimensional brownian motion.
y
Keywords : Large deviations, Interacting random processes, Statistical mechanics, Langevin
URA 762, CNRS, DMI, Ecole Normale Superieure, 75230 Paris, France URA 743, CNRS, Bat. 425, Universite de Paris Sud, 91405 Orsay, France
Laboratoire de Modelisation Stochastique et Statistique, URA 743 Universite Paris-Sud (B^t 425) 91405 ORSAY Cedex a
Large deviations for Langevin spin glass dynamics
2 ( )
2
We want to understand the limiting behavior ( for large N ) of this system of randomly interacting di usions. We will need two simplifying features : First, we will study only bounded spins, i.e we will assume that U (x) is de ned on a bounded interval ?A; A] and tends to in nity when jxj ! A su ciently fast to insure our spins xj stay in the interval ?A; A]. The