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A review of advanced and practical lithium battery materialsRotem Marom,*S.Francis Amalraj,Nicole Leifer,David Jacob and Doron AurbachReceived 3rd December 2010,Accepted 31st January 2011DOI:10.1039/c0jm04225kPresented herein is a discussion of the forefront in research and development of advanced electrode materials and electrolyte solutions for the next generation of lithium ion batteries.The main challenge of the ﬁeld today is in meeting the demands necessary to make the electric vehicle fully commercially viable.This requires high energy and power densities with no compromise in safety.Three families of advanced cathode materials (the limiting factor for energy density in the Li battery systems)are discussed in detail:LiMn 1.5Ni 0.5O 4high voltage spinel compounds,Li 2MnO 3–LiMO 2high capacity composite layered compounds,and LiMPO 4,where M ¼Fe,Mn.Graphite,Si,Li x TO y ,and MO (conversion reactions)are discussed as anode materials.The electrolyte is a key component that determines the ability to use high voltage cathodes and low voltage anodes in the same system.Electrode–solution interactions and passivation phenomena on both electrodes in Li-ion batteries also play signiﬁcant roles in determining stability,cycle life and safety features.This presentation is aimed at providing an overall picture of the road map necessary for the future development of advanced high energy density Li-ion batteries for EV applications.IntroductionOne of the greatest challenges of modern society is to stabilize a consistent energy supply that will meet our growing energy demands.A consideration of the facts at hand related to the energy sources on earth reveals that we are not encountering an energy crisis related to a shortage in total resources.For instancethe earth’s crust contains enough coal for the production of electricity for hundreds of years.1However the continued unbridled usage of this resource as it is currently employed may potentially bring about catastrophic climatological effects.As far as the availability of crude oil,however,it in fact appears that we are already beyond ‘peak’production.2As a result,increasing oil shortages in the near future seem inevitable.Therefore it is of critical importance to considerably decrease our use of oil for propulsion by developing effective electric vehicles (EVs).EV applications require high energy density energy storage devices that can enable a reasonable driving range betweenDepartment of Chemistry,Bar-Ilan University,Ramat-Gan,52900,Israel;Web:http://www.ch.biu.ac.il/people/aurbach.E-mail:rotem.marom@live.biu.ac.il;aurbach@mail.biu.ac.ilRotem MaromRotem Marom received her BS degree in organic chemistry (2005)and MS degree in poly-mer chemistry (2007)from Bar-Ilan University,Ramat Gan,Israel.She started a PhD in electrochemistry under the supervision of Prof.D.Aurbach in 2010.She is currently con-ducting research on a variety of lithium ion battery materials for electric vehicles,with a focus on electrolyte solutions,salts andadditives.S :Francis AmalrajFrancis Amalraj hails from Tamil Nadu,India.He received his MSc in Applied Chemistry from Anna University.He then carried out his doctoral studies at National Chemical Laboratory,Pune and obtained his PhD in Chemistry from Pune University (2008).He is currently a postdoctoral fellow in Prof.Doron Aurbach’s group at Bar-Ilan University,Israel.His current research interest focuses on the synthesis,electrochemical and transport properties of high ener-getic electrode materials for energy conversion and storage systems.Dynamic Article Links CJournal ofMaterials ChemistryCite this:DOI:10.1039/c0jm04225k /materialsFEATURE ARTICLED o w n l o a d e d b y B e i j i n g U n i v e r s i t y o f C h e m i c a l T e c h n o l o g y o n 24 F e b r u a r y 2011P u b l i s h e d o n 23 F e b r u a r y 2011 o n h t t p ://p u b s .r s c .o r g | d o i :10.1039/C 0J M 04225KView Onlinecharges and maintain acceptable speeds.3Other important requirements are high power density and acceptable safety features.The energy storage ﬁeld faces a second critical chal-lenge:namely,the development of rechargeable systems for load leveling applications (e.g.storing solar and wind energy,and reducing the massive wasted electricity from conventional fossil fuel combustion plants).4Here the main requirements are a very prolonged cycle life,components (i.e.,relevant elements)abun-dant in high quantities in the earth’s crust,and environmentally friendly systems.Since it is not clear whether Li-ion battery technology can contribute signiﬁcantly to this application,battery-centered solutions for this application are not discussedherein.In fact,even for electrical propulsion,the non-petroleum power source with the highest energy density is the H 2/O 2fuel cell (FC).5However,despite impressive developments in recent years in the ﬁeld,there are intrinsic problems related to electrocatalysis in the FCs and the storage of hydrogen 6that will need many years of R&D to solve.Hence,for the foreseeable future,rechargeable batteries appear to be the most practically viable power source for EVs.Among the available battery technologies to date,only Li-ion batteries may possess the power and energy densities necessary for EV applications.The commonly used Li-ion batteries that power almost all portable electronic equipment today are comprised of a graphite anode and a LiCoO 2cathode (3.6V system)and can reach a practical energy density of 150W h kg À1in single cells.This battery technology is not very useful for EV application due to its limited cycle life (especially at elevated temperatures)and prob-lematic safety features (especially for large,multi-cell modules).7While there are ongoing developments in the hybrid EV ﬁeld,including practical ones in which only part of the propulsion of the car is driven by an electrical motor and batteries,8the main goal of the battery community is to be able to develop full EV applications.This necessitates the development of Li-ion batteries with much higher energy densities compared to the practical state-of-the-art.The biggest challenge is that Li-ion batteries are complicated devices whose components never reach thermodynamic stability.The surface chemistry that occurs within these systems is very complicated,as described brieﬂy below,and continues to be the main factor that determines their performance.9Nicole Leifer Nicole Leifer received a BS degree in chemistry from MIT in 1998.After teaching high school chemistry and physics for several years at Stuyvesant High School in New York City,she began work towards her PhD in solid state physics from the City University of New York Grad-uate Center.Her research con-sisted primarily of employing solid state NMR in the study of lithium ion electrode materialsand electrode surfacephenomena with Prof.Green-baum at Hunter College andProf.Grey at Stony Brook University.After completing her PhD she joined Prof.Doron Aurbach for a postdoctorate at Bar-Ilan University to continue work in lithium ion battery research.There she continues her work in using NMR to study lithium materials in addition to new forays into carbon materials’research for super-capacitor applications with a focus on enhancement of electro-chemical performance through the incorporation of carbonnanotubes.David Jacob David Jacob earned a BSc from Amravati University in 1998,an MSc from Pune University in 2000,and completed his PhD at Bar-Ilan University in 2007under the tutelage of Professor Aharon Gedanken.As part of his PhD research,he developed novel methods of synthesizing metal ﬂuoride nano-material structures in ionic liquids.Upon ﬁnishing his PhD he joined Prof.Doron Aurbach’s lithium ionbattery group at Bar-Ilan in2007as a post-doctorate and during that time developed newformulations of electrolyte solutions for Li-ion batteries.He has a great interest in nanotechnology and as of 2011,has become the CEO of IsraZion Ltd.,a company dedicated to the manufacturing of novelnano-materials.Doron Aurbach Dr Doron Aurbach is a full Professor in the Department of Chemistry at Bar-Ilan Univer-sity (BIU)in Ramat Gan,Israel and a senate member at BIU since 1996.He chaired the chemistry department there during the years 2001–2005.He is also the chairman of the Israeli Labs Accreditation Authority.He founded the elec-trochemistry group at BIU at the end of 1985.His groupconducts research in thefollowing ﬁelds:Li ion batteries for electric vehicles and for otherportable uses (new cathodes,anodes,electrolyte solutions,elec-trodes–solution interactions,practical systems),rechargeable magnesium batteries,electronically conducting polymers,super-capacitors,engineering of new carbonaceous materials,develop-ment of devices for storage and conversion of sustainable energy (solar,wind)sensors and water desalination.The group currently collaborates with several prominent research groups in Europe and the US and with several commercial companies in Israel and abroad.He is also a fellow of the ECS and ISE as well as an associate editor of Electrochemical and Solid State Letters and the Journal of Solid State Electrochemistry.Prof.Aurbach has more than 350journals publications.D o w n l o a d e d b y B e i j i n g U n i v e r s i t y o f C h e m i c a l T e c h n o l o g y o n 24 F e b r u a r y 2011P u b l i s h e d o n 23 F e b r u a r y 2011 o n h t t p ://p u b s .r s c .o r g | d o i :10.1039/C 0J M 04225KAll electrodes,excluding 1.5V systems such as LiTiO x anodes,are surface-ﬁlm controlled (SFC)systems.At the anode side,all conventional electrolyte systems can be reduced in the presence of Li ions below 1.5V,thus forming insoluble Li-ion salts that comprise a passivating surface layer of particles referred to as the solid electrolyte interphase (SEI).10The cathode side is less trivial.Alkyl carbonates can be oxidized at potentials below 4V.11These reactions are inhibited on the passivated aluminium current collectors (Al CC)and on the composite cathodes.There is a rich surface chemistry on the cathode surface as well.In their lithiated state,nucleophilic oxygen anions in the surface layer of the cathode particles attack electrophilic RO(CO)OR solvents,forming different combinations of surface components (e.g.ROCO 2Li,ROCO 2M,ROLi,ROM etc.)depending on the electrolytes used.12The polymerization of solvent molecules such as EC by cationic stimulation results in the formation of poly-carbonates.13The dissolution of transition metal cations forms surface inactive Li x MO y phases.14Their precipitation on the anode side destroys the passivation of the negative electrodes.15Red-ox reactions with solution species form inactive LiMO y with the transition metal M at a lower oxidation state.14LiMO y compounds are spontaneously delithiated in air due to reactions with CO 2.16Acid–base reactions occur in the LiPF 6solutions (trace HF,water)that are commonly used in Li-ion batteries.Finally,LiCoO 2itself has a rich surface chemistry that inﬂuences its performance:4LiCo III O 2 !Co IV O 2þCo II Co III 2O 4þ2Li 2O !4HF4LiF þ2H 2O Co III compounds oxidize alkyl carbonates;CO 2is one of the products,Co III /Co II /Co 2+dissolution.14Interestingly,this process seems to be self-limiting,as the presence of Co 2+ions in solution itself stabilizes the LiCoO 2electrodes,17However,Co metal in turn appears to deposit on the negative electrodes,destroying their passivation.Hence the performance of many types of electrodes depends on their surface chemistry.Unfortunately surface studies provide more ambiguous results than bulk studies,therefore there are still many open questions related to the surface chemistry of Li-ion battery systems.It is for these reasons that proper R&D of advanced materials for Li-ion batteries has to include bulk structural and perfor-mance studies,electrode–solution interactions,and possible reﬂections between the anode and cathode.These studies require the use of the most advanced electrochemical,18structural (XRD,HR microscopy),spectroscopic and surface sensitive analytical techniques (SS NMR,19FTIR,20XPS,21Raman,22X-ray based spectroscopies 23).This presentation provides a review of the forefront of the study of advanced materials—electrolyte systems,current collectors,anode materials,and ﬁnally advanced cathodes materials used in Li-ion batteries,with the emphasis on contributions from the authors’group.ExperimentalMany of the materials reviewed were studied in this laboratory,therefore the experimental details have been provided as follows.The LiMO 2compounds studied were prepared via self-combus-tion reactions (SCRs).24Li[MnNiCo]O 2and Li 2MnO 3$Li/MnNiCo]O 2materials were produced in nano-andsubmicrometric particles both produced by SCR with different annealing stages (700 C for 1hour in air,900 C or 1000 C for 22hours in air,respectively).LiMn 1.5Ni 0.5O 4spinel particles were also synthesized using SCR.Li 4T 5O 12nanoparticles were obtained from NEI Inc.,USA.Graphitic material was obtained from Superior Graphite (USA),Timcal (Switzerland),and Conoco-Philips.LiMn 0.8Fe 0.2PO 4was obtained from HPL Switzerland.Standard electrolyte solutions (alkyl carbonates/LiPF 6),ready to use,were obtained from UBE,Japan.Ionic liquids were obtained from Merck KGaA (Germany and Toyo Gosie Ltd.,(Japan)).The surface chemistry of the various electrodes was charac-terized by the following techniques:Fourier transform infrared (FTIR)spectroscopy using a Magna 860Spectrometer from Nicolet Inc.,placed in a homemade glove box purged with H 2O and CO 2(Balson Inc.air puriﬁcation system)and carried out in diffuse reﬂectance mode;high-resolution transmission electron microscopy (HR-TEM)and scanning electron microscopy (SEM),using a JEOL-JEM-2011(200kV)and JEOL-JSM-7000F electron microscopes,respectively,both equipped with an energy dispersive X-ray microanalysis system from Oxford Inc.;X-ray photoelectron spectroscopy (XPS)using an HX Axis spectrom-eter from Kratos,Inc.(England)with monochromic Al K a (1486.6eV)X-ray beam radiation;solid state 7Li magic angle spinning (MAS)NMR performed at 194.34MHz on a Bruker Avance 500MHz spectrometer in 3.2mm rotors at spinning speeds of 18–22kHz;single pulse and rotor synchronized Hahn echo sequences were used,and the spectra were referenced to 1M LiCl at 0ppm;MicroRaman spectroscopy with a spectrometerfrom Jobin-Yvon Inc.,France.We also used M €ossbauer spec-troscopy for studying the stability of LiMPO 4compounds (conventional constant-acceleration spectrometer,room temperature,50mC:57Co:Rh source,the absorbers were put in Perspex holders.In situ AFM measurements were carried out using the system described in ref.25.The following electrochemical measurements were posite electrodes were prepared by spreading slurries comprising the active mass,carbon powder and poly-vinylidene diﬂuoride (PVdF)binder (ratio of 75%:15%:10%by weight,mixed into N -methyl pyrrolidone (NMP),and deposited onto aluminium foil current collectors,followed by drying in a vacuum oven.The average load was around 2.5mg active mass per cm 2.These electrodes were tested in two-electrode,coin-type cells (Model 2032from NRC Canada)with Li foil serving as the counter electrode,and various electrolyte puter-ized multi-channel battery analyzers from Maccor Inc.(USA)and Arbin Inc.were used for galvanostatic measurements (voltage vs.time/capacity,measured at constant currents).Results and discussionOur road map for materials developmentFig.1indicates a suggested road map for the direction of Li-ion research.The axes are voltage and capacity,and a variety of electrode materials are marked therein according to their respective values.As is clear,the main limiting factor is the cathode material (in voltage and capacity).The electrode mate-rials currently used in today’s practical batteries allow forD o w n l o a d e d b y B e i j i n g U n i v e r s i t y o f C h e m i c a l T e c h n o l o g y o n 24 F e b r u a r y 2011P u b l i s h e d o n 23 F e b r u a r y 2011 o n h t t p ://p u b s .r s c .o r g | d o i :10.1039/C 0J M 04225Ka nominal voltage of below 4V.The lower limit of the electro-chemical window of the currently used electrolyte solutions (alkyl carbonates/LiPF 6)is approximately 1.5V vs.Li 26(see later discussion about the passivation phenomena that allow for the operation of lower voltage electrodes,such as Li and Li–graphite).The anodic limit of the electrochemical window of the alkyl carbonate/LiPF 6solutions has not been speciﬁcally determined but practical accepted values are between 4.2and 5V vs.Li 26(see further discussion).With some systems which will be discussed later,meta-stability up to 4.9V can be achieved in these standard electrolyte solutions.Electrolyte solutionsThe anodic stability limits of electrolyte solutions for Li-ion batteries (and those of polar aprotic solutions in general)demand ongoing research in this subﬁeld as well.It is hard to deﬁne the onset of oxidation reactions of nonaqueous electrolyte solutions because these strongly depend on the level of purity,the presence of contaminants,and the types of electrodes used.Alkyl carbonates are still the solutions of choice with little competition (except by ionic liquids,as discussed below)because of the high oxidation state of their central carbon (+4).Within this class of compounds EC and DMC have the highest anodic stability,due to their small alkyl groups.An additional beneﬁt is that,as discussed above,all kinds of negative electrodes,Li,Li–graphite,Li–Si,etc.,develop excellent passivation in these solutions at low potentials.The potentiodynamic behavior of polar aprotic solutions based on alkyl carbonates and inert electrodes (Pt,glassy carbon,Au)shows an impressive anodic stability and an irreversible cathodic wave whose onset is $1.5vs.Li,which does not appear in consequent cycles due to passivation of the anode surface bythe SEI.The onset of these oxidation reactions is not well deﬁned (>4/5V vs.Li).An important discovery was the fact that in the presence of Li salts,EC,one of the most reactive alkyl carbonates (in terms of reduction),forms a variety of semi-organic Li-con-taining salts that serve as passivation agents on Li,Li–carbon,Li–Si,and inert metal electrodes polarized to low potentials.Fig.2and Scheme 1indicates the most signiﬁcant reduction schemes for EC,as elucidated through spectroscopic measure-ments (FTIR,XPS,NMR,Raman).27–29It is important to note (as reﬂected in Scheme 1)that the nature of the Li salts present greatly affects the electrode surface chemistry.When the pres-ence of the salt does not induce the formation of acidic species in solutions (e.g.,LiClO 4,LiN(SO 2CF 3)2),alkyl carbonates are reduced to ROCO 2Li and ROLi compounds,as presented in Fig. 2.In LiPF 6solutions acidic species are formed:LiPF 6decomposes thermally to LiF and PF 5.The latter moiety is a Lewis acid which further reacts with any protic contaminants (e.g.unavoidably present traces of water)to form HF.The presence of such acidic species in solution strongly affects the surface chemistry in two ways.One way is that PF 5interactswithFig.1The road map for R&D of new electrode materials,compared to today’s state-of-the-art.The y and x axes are voltage and speciﬁc capacity,respectively.Fig.2A schematic presentation of the CV behavior of inert (Pt)elec-trodes in various families of polar aprotic solvents with Li salts.26D o w n l o a d e d b y B e i j i n g U n i v e r s i t y o f C h e m i c a l T e c h n o l o g y o n 24 F e b r u a r y 2011P u b l i s h e d o n 23 F e b r u a r y 2011 o n h t t p ://p u b s .r s c .o r g | d o i :10.1039/C 0J M 04225Kthe carbonyl group and channels the reduction process of EC to form ethylene di-alkoxide species along with more complicated alkoxy compounds such as binary and tertiary ethers,rather than Li-ethylene dicarbonates (see schemes in Fig.2);the other way is that HF reacts with ROLi and ROCO 2Li to form ROH,ROCO 2H (which further decomposes to ROH and CO 2),and surface LiF.Other species formed from the reduction of EC are Li-oxalate and moieties with Li–C and C–F bonds (see Scheme 1).27–31Efforts have been made to enhance the formation of the passivation layer (on graphite electrodes in particular)in the presence of these solutions through the use of surface-active additives such as vinylene carbonate (VC)and lithium bi-oxalato borate (LiBOB).27At this point there are hundreds of publica-tions and patents on various passivating agents,particularly for graphite electrodes;their further discussion is beyond the scope of this paper.Readers may instead be referred to the excellent review by Xu 32on this subject.Ionic liquids (ILs)have excellent qualities that could render them very relevant for use in advanced Li-ion batteries,including high anodic stability,low volatility and low ﬂammability.Their main drawbacks are their high viscosities,problems in wetting particle pores in composite structures,and low ionic conductivity at low temperatures.Recent years have seen increasing efforts to test ILs as solvents or additives in Li-ion battery systems.33Fig.3shows the cyclic voltammetric response (Pt working electrodes)of imidazolium-,piperidinium-,and pyrrolidinium-based ILs with N(SO 2CF 3)2Àanions containing LiN(SO 2CF 3)2salt.34This ﬁgure reﬂects the very wide electrochemical window and impressive anodic stability (>5V)of piperidium-and pyr-rolidium-based ILs.Imidazolium-based IL solutions have a much lower cathodic stability than the above cyclic quaternary ammonium cation-based IL solutions,as demonstrated in Fig.3.The cyclic voltammograms of several common electrode mate-rials measured in IL-based solutions are also included in the ﬁgure.It is clearly demonstrated that the Li,Li–Si,LiCoO 2,andLiMn 1.5Ni 0.5O 4electrodes behave reversibly in piperidium-and pyrrolidium-based ILs with N(SO 2CF 3)2Àand LiN(SO 2CF 3)2salts.This ﬁgure demonstrates the main advantage of the above IL systems:namely,the wide electrochemical window with exceptionally high anodic stability.It was demonstrated that aluminium electrodes are fully passivated in solutions based on derivatives of pyrrolidium with a N(SO 2CF 3)2Àanion and LiN(SO 2CF 3)2.35Hence,in contrast to alkyl carbonate-based solutions in which LiN(SO 2CF 3)2has limited usefulness as a salt due to the poor passivation of aluminium in its solutions in the above IL-based systems,the use of N(SO 2CF 3)2Àas the anion doesn’t limit their anodic stability at all.In fact it was possible to demonstrate prototype graphite/LiMn 1.5Ni 0.5O 4and Li/L-iMn 1.5Ni 0.5O 4cells operating even at 60 C insolutionsScheme 1A reaction scheme for all possible reduction paths of EC that form passivating surface species (detected by FTIR,XPS,Raman,and SSNMR 28–31,49).Fig.3Steady-state CV response of a Pt electrode in three IL solutions,as indicated.(See structure formulae presented therein.)The CV presentations include insets of steady-state CVs of four electrodes,as indicated:Li,Li–Si,LiCoO 2,and LiMn 1.5Ni 0.5O 4.34D o w n l o a d e d b y B e i j i n g U n i v e r s i t y o f C h e m i c a l T e c h n o l o g y o n 24 F e b r u a r y 2011P u b l i s h e d o n 23 F e b r u a r y 2011 o n h t t p ://p u b s .r s c .o r g | d o i :10.1039/C 0J M 04225Kcomprising alkyl piperidium-N(SO2CF3)2as the IL solvent and Li(SO2CF3)2as the electrolyte.34Challenges remain in as far as the use of these IL-based solutions with graphite electrodes.22Fig.4shows the typical steady state of the CV of graphite electrodes in the IL without Li salts.The response in this graph reﬂects the reversible behavior of these electrodes which involves the insertion of the IL cations into the graphite lattice and their subsequent reduction at very low potentials.However when the IL contains Li salt,the nature of the reduction processes drastically changes.It was recently found that in the presence of Li ions the N(SO2CF3)2Àanion is reduced to insoluble ionic compounds such as LiF,LiCF3, LiSO2CF3,Li2S2O4etc.,which passivate graphite electrodes to different extents,depending on their morphology(Fig.4).22 Fig.4b shows a typical SEM image of a natural graphite(NG) particle with a schematic view of its edge planes.Fig.4c shows theﬁrst CVs of composite electrodes comprising NG particles in the Li(SO2CF3)2/IL solution.These voltammograms reﬂect an irreversible cathodic wave at theﬁrst cycle that belongs to the reduction and passivation processes and their highly reversible repeated Li insertion into the electrodes comprising NG. Reversible capacities close to the theoretical ones have been measured.Fig.4d and e reﬂect the structure and behavior of synthetic graphiteﬂakes.The edge planes of these particles are assumed to be much rougher than those of the NG particles,and so their passivation in the same IL solutions is not reached easily. Their voltammetric response reﬂects the co-insertion of the IL cations(peaks at0.5V vs.Li)together with Li insertion at the lower potentials(<0.3V vs.Li).Passivation of this type of graphite is obtained gradually upon repeated cycling(Fig.4e), and the steady-state capacity that can be obtained is much lower than the theoretical one(372mA h gÀ1).Hence it seems that using graphite particles with suitable morphologies can enable their highly reversible and stable operation in cyclic ammonium-based ILs.This would make it possible to operate high voltage Li-ion batteries even at elevated temperatures(e.g. 4.7–4.8V graphite/LiMn1.5Ni0.5O4cells).34 The main challenge in thisﬁeld is to demonstrate the reasonable performance of cells with IL-based electrolytes at high rates and low temperatures.To this end,the use of different blends of ILs may lead to future breakthroughs.Current collectorsThe current collectors used in Li-ion systems for the cathodes can also affect the anodic stability of the electrolyte solutions.Many common metals will dissolve in aprotic solutions in the potential ranges used with advanced cathode materials(up to5V vs.Li). Inert metals such as Pt and Au are also irrelevant due to cost considerations.Aluminium,however,is both abundantand Fig.4A collection of data related to the behavior of graphite electrodes in butyl,methyl piperidinium IL solutions.22(a)The behavior of natural graphite electrodes in pure IL without Li salt(steady-state CV is presented).(b)The schematic morphology and a SEM image of natural graphite(NG)ﬂakes.(c)The CV response(3ﬁrst consecutive cycles)of NG electrodes in IL/0.5lithium triﬂuoromethanesulfonimide(LiTFSI)solution.(d and e)Same as(b and c)but for synthetic graphiteﬂakes.DownloadedbyBeijingUniversityofChemicalTechnologyon24February211Publishedon23February211onhttp://pubs.rsc.org|doi:1.139/CJM4225Kcheap and functions very well as a current collector due to its excellent passivation properties which allow it a high anodic stability.The question remains as to what extent Al surfaces can maintain the stability required for advanced cathode materials (up to 5V vs.Li),especially at elevated temperatures.Fig.5presents the potentiodynamic response of Al electrodes in various EC–DMC solutions,considered the alkyl carbonate solvent mixture with the highest anodic stability,at 30and 60 C.37The inset to this picture shows several images in which it is demonstrated that Al surfaces are indeed active and develop unique morphologies in the various solutions due to their obvious anodic processes in solutions,some of which lead to their effective passivation.The electrolyte used has a critical impact on the anodic stability of the Al.In general,LiPF 6solutions demonstrate the highest stability even at elevated temperatures due to the formation of surface AlF 3and even Al(PF 6)3.Al CCs in EC–DMC/LiPF 6solutions provide the highest anodic stability possible for conventional electrode/solution systems.This was demonstrated for Li/LiMn 1.5Ni 0.5O 4spinel (4.8V)cells,even at 60 C.36This was also conﬁrmed using bare Al electrodes polarized up to 5V at 60 C;the anodic currents were seen to decay to negligible values due to passivation,mostly by surface AlF 3.37Passivation can also be reached in Li(SO 2CF 3),LiClO 4and LiBOB solutions (Fig.5).Above 4V (vs.Li),the formation of a successful passivation layer on Al CCs is highly dependent on the electrolyte formula used.The anodic stability of EC–DMC/LiPF 6solutions and Al current collectors may be further enhanced by the use of additives,but a review of additives in itself deserves an article of its own and for this readers are again referred to the review by Xu.32When discussing the topic of current collectors for Li ion battery electrodes,it is important to note the highly innovative work on (particularly anodic)current collectors by Taberna et al.on nano-architectured Cu CCs 47and Hu et al.who assembled CCs based on carbon nano-tubes for ﬂexible paper-like batteries,38both of whom demonstrated suberb rate capabilities.39AnodesThe anode section in Fig.1indicates four of the most promising groups of materials whose Li-ion chemistry is elaborated as follows:1.Carbonaceous materials/graphite:Li ++e À+C 6#LiC 62.Sn and Si-based alloys and composites:40,41Si(Sn)+x Li ++x e À#Li x Si(Sn),X max ¼4.4.3.Metal oxides (i.e.conversion reactions):nano-MO +2Li ++2e À#nano-MO +Li 2O(in a composite structure).424.Li x TiO y electrodes (most importantly,the Li 4Ti 5O 12spinel structure).43Li 4Ti 5O 12+x Li ++x e À#Li 4+x Ti 5O 12(where x is between 2and 3).Conversion reactions,while they demonstrate capacities much higher than that of graphite,are,practically speaking,not very well-suited for use as anodes in Li-ion batteries as they generally take place below the thermodynamic limit of most developed electrolyte solutions.42In addition,as the reactions require a nanostructuring of the materials,their stability at elevated temperatures will necessarily be an issue because of the higher reactivity (due to the 1000-fold increase in surface area).As per the published research on this topic,only a limited meta-stability has been demonstrated.Practically speaking,it does not seem likely that Li batteries comprising nano-MO anodes will ever reach the prolonged cycle life and stability required for EV applications.Tin and silicon behave similarly upon alloying with Li,with similar stoichiometries and >300%volume changes upon lith-iation,44but the latter remain more popular,as Si is much more abundant than Sn,and Li–Si electrodes indicate a 4-fold higher capacity.The main approaches for attaining a workable revers-ibility in the Si(Sn)–Li alloying reactions have been through the use of both nanoparticles (e.g.,a Si–C nanocomposites 45)and composite structures (Si/Sn–M1–M2inter-metalliccompounds 44),both of which can better accommodate these huge volume changes.The type of binder used in composite electrodes containing Si particles is very important.Extensive work has been conducted to determine suitable binders for these systems that can improve the stability and cycle life of composite silicon electrodes.46As the practical usage of these systems for EV applications is far from maturity,these electrodes are not dis-cussed in depth in this paper.However it is important to note that there have been several recent demonstrations of how silica wires and carpets of Si nano-rods can act as much improved anode materials for Li battery systems in that they can serveasFig.5The potentiodynamic behavior of Al electrodes (current density measured vs.E during linear potential scanning)in various solutions at 30and 60 C,as indicated.The inset shows SEM micrographs of passivated Al surfaces by the anodic polarization to 5V in the solutions indicated therein.37D o w n l o a d e d b y B e i j i n g U n i v e r s i t y o f C h e m i c a l T e c h n o l o g y o n 24 F e b r u a r y 2011P u b l i s h e d o n 23 F e b r u a r y 2011 o n h t t p ://p u b s .r s c .o r g | d o i :10.1039/C 0J M 04225K。

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Q1126pis Rev 01/221Product InformationQ Sepharose ® Fast FlowQ1126Product DescriptionQ Sepharose ® Fast Flow is an ion exchangechromatography resin with a quaternary amine (Q) functional group [-CH 2-N +(CH 3)3] attached to Sepharose ® Fast Flow. The Q group serves as astrong anion exchanger, which is completely ionized over a broad pH range. The terms “s trong" and"weak" in ion exchange chromatography refer to the extent of ionization with pH, and not to the binding strength of the functional group to the target species. The parent Sepharose ® Fast Flow is a cross-linked derivative of Sepharose ®. The particle size range is 45-165 µm. The average bead diameter is ~90 µm. The counterion in the product is sulfate (SO 4-2). Recommended cation buffers to use with Q Sepharose ® Fast Flow include alkylamines,ammonium, ethylenediamine, imidazole, pyridine, or Tris. In terms of pH, it is suggested to operate within 0.5 pH unit of the buffer's pK a . With proteins, it is suggested to operate at least 1 pH unit above the pI of the protein, to facilitate binding. Oxidizing agents, and anionic detergents and buffers, should not be used with Q Sepharose ® Fast Flow. Likewise,extended exposure of Q1126 to pH < 4 should be avoided. Several publications 1,2 and dissertations 3-5 cite use of product Q1126 in their research.ReagentQ Sepharose ® Fast Flow is offered as a suspension in 20% ethanol.Approximate Exclusion Limit: average molecular mass of ~4 × 106 DaltonsIonic Capacity: 0.18-0.24 mmol Cl -/mL gel Binding Capacity: ~42 mg BSA per mL gel pH Stability: 2-12Working temperature: 4-40 °CPrecautions and DisclaimerFor R&D use only. Not for drug, household, or other uses. Please consult the Safety Data Sheet for information regarding hazards and safe handling practices. General Resin Preparation Procedure1. Allow the ion exchange medium and ~10 columnvolumes (CV) of buffer to equilibrate to thetemperature chosen for the chromatographic run. 2. Mix the pre-swollen suspension with startingbuffer to form a moderately thick slurry, which consists of ~75% settled gel and 25% liquid. 3. Degas the gel under vacuum at the temperatureof column operation.4. Mount the column vertically on a suitable stand,out of the way of direct sunlight or drafts, which may cause temperature fluctuations.5. Pour a small amount of buffer into the emptycolumn. Allow the buffer to flow through spaces to eliminate air pockets.6. Pour the suspension of ion exchange mediumprepared in Step 3 into the column by allowing it to flow gently down the side of the tube, to avoid bubble formation.7. For consistent flow rates and reproducibleseparations, connect a pump to the column. 8. Fill the remainder of the column to the top withbuffer. Allow ~5 CV of buffer to drain through the bed at a flow rate at least 133% of the flow rate to be used in the procedure. The bed height should have settled to a constant height.9. Using a syringe or similar instrument, apply thesample dissolved in starting buffer to the column. For isocratic separations, the sample volumeshould range from 1-5% of the column volume. If the chromatographic run involves elution with a gradient, the applied sample mass is of much greater importance than the sample volume, and the sample should be applied in a low ionicstrength medium. Ion exchange is used both to concentrate and to fractionate the sample. 10. Elution:• If only unwanted substances in the sample areadsorbed, or if sample components aredifferentially retarded under isocratic conditions, the starting buffer can also be used as the eluent.The life science business of Merck operates as MilliporeSigma in the U.S. and Canada.Merck and Sigma-Aldrich are trademarks of Merck KGaA, Darmstadt, Germany or its affiliates. All other trademarks are the property of their respective owners. Detailed information on trademarks is available via publicly accessible resources.© 2022 Merck KGaA, Darmstadt, Germany and/or its affiliates. All Rights Reserved. Q1126pis Rev 01/22 JJJ,MAM,GCY2•Normally, however, separation and elution are achieved by selectively decreasing the affinity of the molecules for the charged groups on the resin by changing the pH and/or ionic strength of the eluent. This procedure is termed gradient elution. 11. Regeneration: •Either (a) washing the column with a high ionic strength salt solution, such as 1 M NaCl, or (b) changing the pH to the tolerable low and high pH extremes, is usually sufficient to remove reversibly bound material.• When needed, lipids and precipitated proteins canbe removed by washing with 1 CV of 1-2 M NaCl, followed by 1 CV of 0.1 M NaOH in 0.5 M NaCl. • Rinse with several CV of water. Thenre-equilibrate the resin with starting buffer.• If base such as NaOH was used, adjust the pH ofthe resin to neutral before storing or using.12. Storage: Q Sepharose ® Fast Flow may be storedat 2-8 °C in water with 20% ethanol added as an antibacterial agent.General NotesCation versus Anion Exchanger• If sample components are most stable below their pI values, a cation exchanger should be used. • If sample components are most stable above their pI values, an anion exchanger should be used. •If stability is good over a wide pH range on both sides of the pI, either or both types of ion exchanger may be used.Strong versus Weak Ion Exchanger•Most proteins have pI values within the range 5.5-7.5, and can thus be separated on both strong and weak ion exchangers.•When maximum resolution occurs at an extreme pH and the molecules of interest are stable at that pH, a strong ion exchanger should be used. Choice of Buffer, pH, and Ionic Strength• The highest ionic strength which permits binding should normally be used.•The required buffer concentration varies fromsubstance to substance. Usually, an ionic strength of at least 10 mM is required to ensure adequate buffering capacity.•As salts (such as buffers) help to stabilize proteins in solution, their concentration should be highenough to prevent denaturation and precipitation.References1. López, G. et al ., Eukaryot. Cell , 14(6), 564-577(2015).2. Bhargava, V. et al ., Dev. Cell., 52(1), 38-52.e10(2020).3. Fu , Yinan, “Structure and dynamics ofPseudomonas aeruginosa ICP”. University ofGlasgow, Ph.D. dissertation, p. 126 (April 2009). 4. Redmond, Miranda , “The Role of N-TerminalAcidic Inserts on the Dynamics of the Tau Protein ”. University of Vermont, Ph.D. dissertation, p. 22 (May 2017).5. Taylor-Whiteley, Teresa Rachel , “RecapitulatingParkinson’s disease pathology in athree-dimensional neural cell culture mode ”. Sheffield Hallam University, Ph.D. dissertation, p. 58 (September 2019).NoticeWe provide information and advice to our customers on application technologies and regulatory matters to the best of our knowledge and ability, but without obligation or liability. Existing laws and regulations are to be observed in all cases by our customers. This also applies in respect to any rights of third parties. Our information and advice do not relieve ourcustomers of their own responsibility for checking the suitability of our products for the envisaged purpose. The information in this document is subject to change without notice and should not be construed as acommitment by the manufacturing or selling entity, or an affiliate. 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chemicalreactionengineering3ededition作者octavelevenspiel课后习题答案

Corresponding Solutions for Chemical Reaction EngineeringCHAPTER 1 OVERVIEW OF CHEMICAL REACTION ENGINEERING .......................................... 错误!未定义书签。

CHAPTER 2 KINETICS OF HOMOGENEOUS REACTIONS ........................................................ 错误!未定义书签。

CHAPTER 3 INTERPRETATION OF BATCH REACTOR DATA ..................................................... 错误!未定义书签。

CHAPTER 4 INTRODUCTION TO REACTOR DESIGN ............................................................... 错误!未定义书签。

CHAPTER 5 IDEAL REACTOR FOR A SINGLE REACTOR........................................................... 错误!未定义书签。

CHAPTER 6 DESIGN FOR SINGLE REACTIONS ....................................................................... 错误!未定义书签。

CHAPTER 10 CHOOSING THE RIGHT KIND OF REACTOR ....................................................... 错误!未定义书签。

Histone Methylation by PRC2 Is Inhibited by Active Chromatin Marks

Molecular CellArticleHistone Methylation by PRC2Is Inhibitedby Active Chromatin MarksFrank W.Schmitges,1,6Archana B.Prusty,2,6Mahamadou Faty,1Alexandra Stu¨tzer,3Gondichatnahalli M.Lingaraju,1 Jonathan Aiwazian,1Ragna Sack,1Daniel Hess,1Ling Li,4Shaolian Zhou,4Richard D.Bunker,1Urs Wirth,5Tewis Bouwmeester,5Andreas Bauer,5Nga Ly-Hartig,2Kehao Zhao,4Homan Chan,4Justin Gu,4Heinz Gut,1 Wolfgang Fischle,3Ju¨rg Mu¨ller,2,7,*and Nicolas H.Thoma¨1,*1Friedrich Miescher Institute for Biomedical Research,Maulbeerstrasse66,CH-4058Basel,Switzerland2Genome Biology Unit,EMBL Heidelberg,Meyerhofstrasse1,D-69117Heidelberg,Germany3Laboratory of Chromatin Biochemistry,Max Planck Institute for Biophysical Chemistry,Am Fassberg11,D-37077Go¨ttingen,Germany4China Novartis Institutes for Biomedical Research,Lane898Halei Road,Zhangjiang,Shanghai,China5Novartis Institutes for Biomedical Research,CH-4002Basel,Switzerland6These authors contributed equally to this work7Present address:Max Planck Institute of Biochemistry,Am Klopferspitz18,D-82152Martinsried,Germany*Correspondence:muellerj@biochem.mpg.de(J.M.),nicolas.thoma@fmi.ch(N.H.T.)DOI10.1016/j.molcel.2011.03.025SUMMARYThe Polycomb repressive complex2(PRC2)confers transcriptional repression through histone H3lysine 27trimethylation(H3K27me3).Here,we examined how PRC2is modulated by histone modiﬁcations associated with transcriptionally active chromatin. We provide the molecular basis of histone H3 N terminus recognition by the PRC2Nurf55-Su(z)12 submodule.Binding of H3is lost if lysine4in H3is trimethylated.Weﬁnd that H3K4me3inhibits PRC2 activity in an allosteric fashion assisted by the Su(z)12C terminus.In addition to H3K4me3,PRC2 is inhibited by H3K36me2/3(i.e.,both H3K36me2 and H3K36me3).Direct PRC2inhibition by H3K4me3and H3K36me2/3active marks is con-served in humans,mouse,andﬂy,rendering tran-scriptionally active chromatin refractory to PRC2 H3K27trimethylation.While inhibition is present in plant PRC2,it can be modulated through exchange of the Su(z)12subunit.Inhibition by active chromatin marks,coupled to stimulation by transcriptionally repressive H3K27me3,enables PRC2to autono-mously template repressive H3K27me3without over-writing active chromatin domains.INTRODUCTIONPolycomb(PcG)and trithorax group(trxG)proteins form distinct multiprotein complexes that modify chromatin.These com-plexes are conserved in animals and plants and are required to maintain spatially restricted transcription of HOX and other cell fate determination genes(Henderson and Dean,2004; Pietersen and van Lohuizen,2008;Schuettengruber et al., 2007;Schwartz and Pirrotta,2007).PcG proteins act to repress their target genes while trxG protein complexes are required to keep the same genes active in cells where they must be expressed.Among the PcG protein complexes,Polycomb repressive complex2(PRC2)is a histone methyl-transferase(HMTase) that methylates Lys27of H3(H3K27)(Cao et al.,2002;Czermin et al.,2002;Kuzmichev et al.,2004;Mu¨ller et al.,2002).High levels of H3K27trimethylation(H3K27me3)in the coding region generally correlate with transcription repression(Cao et al., 2008;Nekrasov et al.,2007;Sarma et al.,2008).PRC2contains four core subunits:Enhancer of zeste[E(z),EZH2in mammals], Suppressor of zeste12[Su(z)12,SUZ12in mammals],Extra-sex combs[ESC,EED in mammals]and Nurf55[Rbbp4/ RbAp48and Rbbp7/RbAp46in mammals](reviewed in Schuet-tengruber et al.,2007;Wu et al.,2009).E(z)is the catalytic subunit;it requires Nurf55and Su(z)12for nucleosome associa-tion,whereas ESC is required to boost the catalytic activity of E(z)(Nekrasov et al.,2005).Recent studies reported that ESC binds to H3K27me3and that this interaction stimulates the HMTase activity of the complex(Hansen et al.,2008;Margueron et al.,2009;Xu et al.,2010).The observation that PRC2is able to bind to the same modiﬁcation that it deposits led to a model for propagation of H3K27me3during replication.In this model, recognition of H3K27me3on previously modiﬁed nucleosomes promotes methylation of neighboring nucleosomes that contain newly incorporated unmodiﬁed histone H3(Hansen et al.,2008; Margueron et al.,2009).However,it is unclear how such a positive feedback loop ensures that H3K27trimethylation remains localized to repressed target genes and does not invade the chromatin of nearby active genes.In organisms ranging from yeast to humans,chromatin of actively transcribed genes is marked by H3K4me3, H3K36me2,and H3K36me3modiﬁcations:while H3K4me3is tightly localized at and immediately downstream of the transcrip-tion start site,H3K36me2peaks adjacently in the50coding region and H3K36me3is speciﬁcally enriched in the30coding region(Bell et al.,2008;Santos-Rosa et al.,2002).Among the trxG proteins that keep PcG target genes active are the HMTases Trx and Ash1,which methylate H3K4and H3K36, respectively(Milne et al.,2002;Nakamura et al.,2002;Tanaka330Molecular Cell42,330–341,May6,2011ª2011Elsevier Inc.et al.,2007).Studies in Drosophila showed that Trx and Ash1 play a critical role in antagonizing H3K27trimethylation by PRC2,suggesting a crosstalk between repressive and activating marks(Papp and Mu¨ller,2006;Srinivasan et al.,2008).In this study we investigated how PRC2activity is modulated by chromatin marks typically associated with active transcrip-tion.We found that the Nurf55WD40propeller binds the N terminus of unmodiﬁed histone H3and that H3K4me3 prevents this binding.In the context of the tetrameric PRC2 complex,weﬁnd that H3K4me3and H3K36me2/3(i.e.,both H3-K36me2and H3-K36me3)inhibit histone methylation by PRC2in vitro.Dissection of this process by usingﬂy,human, and plant PRC2complexes suggests that the Su(z)12subunit is important for mediating this inhibition.PRC2thus not only contains the enzymatic activity for H3K27methylation and a recognition site for binding to this modiﬁcation,but it also harbors a control module that triggers inhibition of this activity to prevent deposition of H3K27trimethylation on transcription-ally active genes.PRC2can thus integrate information provided by pre-existing histone modiﬁcations to accurately tune its enzymatic activity within a particular chromatin context.RESULTSStructure of Nurf55Bound to the N Terminusof Histone H3Previous studies reported that Nurf55alone is able to bind to histone H3(Beisel et al.,2002;Hansen et al.,2008;Song et al., 2008;Wysocka et al.,2006)but not to a GST-H3fusion protein (Verreault et al.,1998).By usingﬂuorescence polarization(FP) measurements,we found that Nurf55binds the very N terminus of unmodiﬁed histone H3encompassing residues1–15(H31–15) with a K D of$0.8±0.1m M but does not bind to a histone H319–38 peptide(Figure1A).Crystallographic screening resulted in the successful cocrystallization of Nurf55in complex with an H31–19peptide.After molecular replacement with the known structure of Nurf55(Song et al.,2008),the initial mF oÀDF c differ-ence map showed density for H3residues1–14in bothNurf55molecules in the crystallographic asymmetric unit. Figures1B–1E show the structure of H31–19bound to Drosophila Nurf55,reﬁned to2.7A˚resolution(R/R free=20.1%and25.0%, Table1;Figure S1A,available online).The H3peptide binds to theﬂat surface of the Nurf55WD40propeller(Figure1B),subse-quently referred to as the canonical binding site(c-site)(Gaudet et al.,1996).The H3peptide is held in an acidic pocket(Figures 1C and1E)and traverses the central WD40cavity in a straight line across the propeller(Figure1B).Nurf55binds the H3peptide by contacting H3residues Ala1, Arg2,Lys4,Ala7,and Lys9.Each of these residues forms side-chain speciﬁc contacts with the Nurf55propeller(Figures 1D and1E).The bulk of the molecular recognition is directed toward H3Arg2and Lys4.Ala1sits in a buried pocket with its a-amino group hydrogen bonding to Nurf55Asp252,which recognizes andﬁxes the very N terminus of histone H3.The neighboring Arg2is buried deeper within the WD40propeller fold,with its guanidinium group sandwiched by Nurf55residues Phe325and Tyr185(Figure1D).H3Lys4binds to a well-deﬁned surface pocket on Nurf55located on blade2,near the central cavity of the propeller.Its3-amino group is speciﬁcally coordi-nated by the carboxyl groups of Nurf55residues Glu183andGlu130and through the amide oxygen of Asn132(Figure1E).Lys9is stabilized by hydrophobic interactions on the WD40surface while having its3-amino group held in solvent-exposedfashion(Figure1D).Ser10of histone H3marks the beginningof a turn that inverses the peptide directionality.Histone H3residues Thr11–Lys14become progressively disordered andare no longer speciﬁcally recognized.No interpretable densitywas observed beyond Lys14.Taken together,Nurf55speciﬁcallyrecognizes an extended region of the extreme N terminus ofhistone H3(11residues long,700A˚2buried surface area)in thecanonical ligand binding location of WD40propeller domains. Structure of the Nurf55-Su(z)12Subcomplex of PRC2 The H3-Nurf55structure prompted us to investigate how Nurf55might bind histone tails in the presence of Su(z)12,its interactionpartner in PRC2(Nekrasov et al.,2005;Pasini et al.,2004).Asaﬁrst step we mapped the Nurf55-Su(z)12interaction in detailby carrying out limited proteolysis experiments on reconstitutedDrosophila PRC2,followed by isolation of a Nurf55-Su(z)12subcomplex.Mass spectrometric analysis and pull-down exper-iments with recombinant protein identiﬁed Su(z)12residues73–143[hereafter referred to as Su(z)1273–143]as sufﬁcient forNurf55binding(Figures S1C and S1D).Crystals were obtained when Drosophila Nurf55and Su(z)12residues64–359were set up in the presence of0.01%subtilisinprotease(Dong et al.,2007).After data collection,the structurewas reﬁned to a maximal resolution of2.3A˚(Table1).Molecularreplacement with Nurf55as search model provided clear initialmF oÀDF c difference density for a13amino acid-long Su(z)12 fragment spanning Su(z)12residues79–91(Figures2A–2C).Theﬁnal model was reﬁned to2.3A˚(R/R free=17.5%/20.9%)and veriﬁed by simulated annealing composite-omit maps(Fig-ure S1B).The portion of Su(z)12involved in Nurf55binding willhenceforth be referred to as the Nurf55binding epitope(NBE).The Su(z)12binding site on Nurf55is located on the side of thepropeller between the stem of the N-terminal a helix(a1)andthe PP loop(Figures2A and2B).Binding between Su(z)12andNurf55occurs mostly through hydrophobic interactions in anextended conformation.The interaction surface betweenNurf55and the NBE is large for a peptide,spanning around800A˚2.Sequence alignment between Su(z)12orthologs revealsthat the NBE is highly conserved(53%identity and84%similarity)in animals and in plants(Figure2E).With the exceptionof Su(z)12Arg85,the majority of the conserved Su(z)12NBEresidues engage in hydrophobic packing with Nurf55(Figures2B and2C).Together with the Su(z)12VEFS domain and theC2H2zincﬁnger(C5domain)(Birve et al.,2001),the NBE consti-tutes the only identiﬁable motif in Su(z)12found conserved in allSu(z)12orthologs.The NBE binding site on Nurf55has previously been shown tobe occupied by helix1of histone H4(Figure2D)(Murzina et al.,2008;Song et al.,2008),an epitope not accessible in assemblednucleosomes(Luger et al.,1997).Nurf55binds H4and theSu(z)12NBE epitope in a different mode,and importantly,withopposite directionality(Figure2D).The detailed comparison ofthe Nurf55-Su(z)12structure with that of H4bound to Nurf55Molecular CellAllosteric PRC2Inhibition by H3K4me3/H3K36me3Molecular Cell42,330–341,May6,2011ª2011Elsevier Inc.331strongly suggests that binding of Su(z)12(NBE)and of H4(helix 1)are mutually exclusive (Figure 2D).We therefore refer to the Su(z)12and H4binding site on Nurf55as the S/H -site.Su(z)12fragments that include the NBE have poor solubility by themselves and generally require Nurf55coexpression for solu-bilization.However,we were able to measure binding of a chem-ically synthesized Su(z)1275–93peptide to Nurf55by isothermal titration calorimetry (ITC)and found that the peptide was bound with a K D value of 6.7±0.3m M in a 1:1stoichiometry (Fig-ure 2F).Pull-down experiments with recombinant proteinandFigure 1.Crystal Structure of Nurf55in Complex with a Histone H31–19Peptide(A)Nurf55binds to an H31–15peptide with an afﬁnity of $0.8±0.1m M as measured by FP.It has similar afﬁnity for an H31–31peptide (2.2±0.2m M)but no binding can be detected to an H319–38peptide.(B)Ribbon representation of Nurf55-H31–19.Nurf55is shown in rainbow colors and H31–19is depicted in green.The peptide is bound to the c -site of the WD40propeller.(C)Electrostatic surface potential representation (À10to 10kT/e)of the c -site with the H3peptide shown as a stick model in green.(D)Close-up of the c -site detailing the interactions between Nurf55(yellow)and the H31–19peptide (green),with a water molecule shown as a red sphere.(E)Schematic representation of interactions between the H31–19peptide (green)and Nurf55(yellow).Molecular CellAllosteric PRC2Inhibition by H3K4me3/H3K36me3332Molecular Cell 42,330–341,May 6,2011ª2011Elsevier Inc.streptavidin beads suggest that Su(z)12residues 94–143harbor an additional Nurf55binding site not visible in the structure (Figure S1E).Su(z)12144–359,lacking the N-terminal 143residues,no longer binds to Nurf55.The NBE (residues 79–93)and the region adjacent to the NBE (residues 94–143)are thus required for stable interaction with Nurf55.The extended NBE was found enriched after limited proteolysis and in subsequent gel ﬁltration runs coupled with quantitative mass spectrometry (Figure S1C).As the NBE was the only fragment visible after structure determi-nation,we conclude that it represents the major Su(z)12interac-tion epitope for Nurf55binding.The Nurf55-Su(z)12Complex Binds to Histone H3In order to study the potential interdependence of the identiﬁed Nurf55binding sites we compared binding of Nurf55and Nurf55-Su(z)12to the histone H3N terminus.FP experiments showed similar afﬁnities for binding of a histone H31–15peptide to Nurf55(K D $0.8±0.1m M;Figure 1A)and a Nurf55-Su(z)1273–143complex (K D $0.6±0.1m M;Figure 2G).Importantly,mutation of Nurf55resi-dues contacting H3via its c -site drastically reduced binding to an H31–15peptide (Figure S2A),demonstrating that the Nurf55-Su(z)1273–143complex indeed binds the H31–15peptide through the c -site.We conclude that the presence of Su(z)12is compatible with Nurf55binding to H3via its c -site and that the two binding interactions are not interdependent.The observation that the Su(z)12NBE occupies the same Nurf55pocket that was previously shown to bind to helix 1of histone H4prompted us to test whether the Su(z)1273–143-Nurf55complex could still bind to histone H4.We performed pull-down experiments with a glutathione S-transferase (GST)fusion protein containing histone H41–48(Murzina et al.,2008)and found that H4stably interacted with isolated Nurf55but not with Su(z)1273–143-Nurf55(Figure 2H).In PRC2,the presence of Su(z)12in the Nurf55S/H -site therefore precludes binding to helix 1of histone H4.H3Binding by Nurf55-Su(z)12Is Sensitive to the Methylation Status of Lysine 4We next investigated how posttranslational modiﬁcations of the H3tail affect binding to the Nurf55-Su(z)1273–143complex.Modi-ﬁcations on H3Arg2,Lys9,and Lys14did not change afﬁnity of Nurf55-Su(z)12for the modiﬁed H31–15peptide (Figures S2B and S2D).In contrast,peptides that were mono-,di-,or trimethylated on Lys4were bound with signiﬁcantly reduced afﬁnity exhibiting K D values of 17±3m M (H3K4me1),24±3m M (H3K4me2),and >70m M (H3K4me3),respectively (Figure 2I).The FP binding data were independently conﬁrmed by ITC measurements (Figures S2C–S2F).Together,these ﬁndings are in accord with the structural data,which show that H3K9and H3K14are being held with their 3-amino moiety solvent-exposed,while the H3K4side chain is tightly coordinated (Figure 1E).The additional methyl groups on the H3K43-amino group are expected to progressively decrease afﬁnity because of increased steric clashes within the H3K4binding pocket.H3K27Methylation by PRC2Is Inhibited by Histone H3K4me3MarksWe then examined the effect of H3K4me3modiﬁcations,which are no longer retained by Nurf55-Su(z)12,on the catalytic activity of PRC2.In a ﬁrst set of experiments,we determined PRC2steady-state parameters on histone H31–45peptide substrates that were either unmodiﬁed or methylated at Lys 4.We observed similar K M values for H3and H3K4me3peptides of 0.84±0.21m M and 0.36±0.07m M,respectively (Figure 3A),and similar K M values for SAM (5.42±0.65m M for H3and 10.04±1.56m M for H3K4me3).The turnover rate constant k cat ,however,was 8-fold reduced in the presence of H3K4me3:2.53±0.21min -1for unmodiﬁed H3and 0.32±0.08min -1in the presence of H3K4me3(Figure 3A).While substrate binding is largely unaf-fected,turnover is thus severely inhibited in the presence of H3K4me3.This behavior,which results in a k cat /K M speciﬁcity constant of 7.83103M -1s -1(unmodiﬁed H3)compared to 0.533103M -1s -1(H3K4me3),is consistent with heterotrophic allosteric inhibition of the PRC2HMTase triggered by the pres-ence of the H3K4me3.To investigate the effect of the H3K4me3modiﬁcation on PRC2activity in the context of nucleosomes,we reconstituted mononucleosomes with a trimethyllysine analog (MLA)at Lys4in H3(referred to as H3Kc4me3;Figure S3A)(Simon et al.,2007).We found that total H3K27methylation (measured by incorporation of 14C-labeled methyl groups)was substantially impaired on H3Kc4me3-containing nucleosomes compared to wild-type nucleosomes (Figures S3B and S3C).We used western blot analysis to monitor how levels of H3K27mono-,di-,and trimethylation were affected by the H3Kc4me3modiﬁca-tion.While H3K27me1formation was reduced by more than 50%on H3Kc4me3nucleosomes compared to unmodiﬁed nucleosomes (Figures 3B and 3C),H3K27dimethylationandTable 1.Crystallographic Data and Reﬁnement StatisticsNurf55–Su(z)12Nurf55–H31–19Space Group P212121P212121theses.Molecular CellAllosteric PRC2Inhibition by H3K4me3/H3K36me3Molecular Cell 42,330–341,May 6,2011ª2011Elsevier Inc.333titrant H3:S/H-siteN CNCSu(z)12 79-91Histone H4 31-41PP-loophelix α10.00.51.0 1.52.0 2.5-16.00-14.00-12.00-10.00-8.00-6.00-4.00-2.000.00-2.00-1.50-1.00-0.500.00020406080100120Time (min)µc a l /s e cMolar RatioK C a l /M o l e o f I n j e c t a n tK D = 6.7 ± 0.3 µMtitrant: H31-15DEFGH ICA B protein concentration [µM]Nurf55-Su(z)12protein concentration [µM]00.20.40.60.81.000.20.40.60.81.00.010.11101000.010.1110100Nurf55Nurf55-Su(z)12unmod K4me1K4me2K4me3f r a c t i o n b o u n df r a c t i o n b o u n d G ST -H 41-48 + N u r f 55G S T -H 41-48 + N u r f 55-S u (z )1273-143N u r f 55(m o c k c o n t r o l )N u r f 55-S u (z )1273-143(m o c k c o n t r o l )Nurf55GST-H41-48Su(z)1273-143i np ut i n p u t i n p u t i n p u t G S T -p u l l d o w n G S T -p u l l d o w n G S T -p u l l d o w n G S T -p u l l d o w n Figure 2.Crystal Structure and Characterization of Nurf55in Complex with the Su(z)12Binding Epitope for Nurf55(A)Ribbon representation of Nurf55-Su(z)12.Nurf55(rainbow colors)depicts the WD40domain nomenclature and Su(z)12is shown in magenta.The S/H -site is marked by a dashed box.(B)Detailed interactions of Su(z)12(magenta)with the S/H -site (yellow).Water molecules are depicted as red spheres.(C)Schematic representation of interactions between Su(z)12(magenta)and Nurf55(yellow).(D)Overlay of the backbone trace of Su(z)12(magenta)and the H4helix a 1(orange)(Song et al.,2008)in the S/H -site.(E)Alignment of the Su(z)12NBE with sequences from Drosophila melanogaster (dm,Q9NJG9),mouse (mm,NP_954666),human (hs,AAH15704),Xenopus tropicalis (xt,BC121323),zebraﬁsh (dr,BC078293),and the three Arabidopsis thaliana (at)homologs Fis2(ABB84250),EMF2(NP_199936),and VRN2(NP_567517).Identical residues are highlighted in yellow.(F)ITC proﬁle for binding of a Su(z)1275–93peptide to Nurf55.Data were ﬁtted to a one-site model with stoichiometry of 1:1.The derived K D value is 6.7±0.3m M.(G)Binding of H31–15to Nurf55(0.8±0.1m M)and Nurf55-Su(z)1273–143(0.6±0.1m M)measured by FP.Molecular CellAllosteric PRC2Inhibition by H3K4me3/H3K36me3334Molecular Cell 42,330–341,May 6,2011ª2011Elsevier Inc.trimethylation were impaired by more than 80%by using H3Kc4me3nucleosomes (Figure 3C).In order to ascertain that inhibition of PRC2is indeed due to trimethylation of the aminogroup in the lysine side chain,and not due to the use of the MLA,we performed HMTase assays on H3K4me3-containing nucleosomes generated by native peptide ligation (Shogren-Knaak et al.,2003)and on H3Kc4me0and H3K4A nucleosomes.H3K27mono-,di-,and trimethylation was comparably inhibited on H3K4me3and on H3Kc4me3-containing nucleosomes,but was not affected by H3Kc4me0and H3K4A (Figures S3D and S3E).We conclude that H3K4me3speciﬁcally inhibits PRC2-mediated H3K27methylation with the most pronounced inhibi-tory effects observed for H3K27di-and trimethylation.We next tested whether the H3K4me3modiﬁcation affects PRC2nucleosome binding.In electrophoretic mobility shift assays (EMSA),we found that PRC2binds unmodiﬁed or H3Kc4me3-modiﬁed nucleosomes with comparable afﬁnity (Fig-ure S4A).Even though binding of Nurf55to the N terminus of ABC571141712290286571141712290286unmodified H3Kc4me3H3K27me3H4dmPRC2 [nM]H3K27me2H4H3K27me1H4H3K27me1H3K27me3H3K27me2dmPRC2 + unmod H3dmPRC2 + H3Kc4me3r e l a t i v e H M T a s e a c t i v i t ySubstrate Apparent Km of SAM (µM)Apparent Km of peptide (nM)k cat (min )-1k cat /Km (M S )-1-1H31-45 -biotin H3K4me31-45 -biotin5.42 ± 0.6510.04 ± 1.56355 ± 74.60.32 ± 0.080.53 x 10836 ± 207 2.53 ± 0.217.8 x 1033Figure 3.HMTase Activity of PRC2Is In-hibited by H3K4me3Marks(A)HMTase assay with PRC2and H31–45-biotin peptides measuring the concentration of SAH produced by the enzymatic reaction.When an H3K4me3-modiﬁed peptide is used,the speciﬁcity constant (k cat /K M )is drastically reduced,indicative of heterotrophic allosteric inhibition.(B)Western blot-based HMTase assay by using recombinant Drosophila mononucleosomes (571nM)and increasing amounts of PRC2.HMTase activity was monitored with antibodies against H3K27me1,H3K27me2,or H3K27me3as indicated;in each case the membrane was also probed with an antibody against unmodiﬁed histone H4to control for equal loading and western blot processing.Deposition of K27di-and trime-thylation is drastically reduced when nucleosomes are used that carry a H3Kc4me3modiﬁcation.(C)Quantiﬁcation of HMTase activity of Drosophila PRC2(286nM)on unmodiﬁed and H3Kc4me3-modiﬁed nucleosomes by quantitative western blotting.histone H3is almost 100-fold reduced byH3K4me3(Figure 2I and Figure S2F),inter-action of the Nurf55c -site with H3K4does not seem to make a detectable con-tribution to nucleosome binding by PRC2in this assay.Consistent with the allosteric mechanism of H3K4me3inhibition that we had observed in the peptide assays (Figure 3A),inhibition of the PRC2HMTase activity by H3K4me3-containingnucleosomes is not caused by impaired nucleosome binding,but is rather the consequence of reduced catalytic turnover.H3K4me3Needs to Be Present on the Same Tail as K27to Inhibit PRC2We then assessed whether inhibition of the PRC2HMTase activity by H3K4me3requires the K4me3mark to be located on the substrate nucleosome (in cis ),or whether it could also be trig-gered if the H3K4me3modiﬁcation was provided on a separate peptide (in trans ).We performed HMTase assays on unmodiﬁed oligonucleosomes in the presence of increasing amounts of a histone H31–15peptide trimethylated at K4(H31–15-K4me3)(Figure 4A).Addition of the H31–15-K4me3peptide did not affect PRC2HMTase activity at peptide concentrations as high as $200m M.When testing H31–19-unmodiﬁed peptide in controls at comparable concentrations,we did observe concentration-dependent PRC2inhibition (Figure 4A),probably because of substrate competition at large peptide excess.As H3K4me3-(H)GST pull-down assay with recombinant GST-H41–48and Nurf55and Nurf55-Su(z)1273–143proteins.GST-H41–48is able to bind Nurf55alone but in the Nurf55-Su(z)1273–143complex the binding site is occupied by Su(z)12(left panel).Control pull-downs with GST beads and either Nurf55or Nurf55-Su(z)1273–143alone showed no unspeciﬁc binding (right panel).(I)Binding of different H31–15peptides to Nurf55-Su(z)1273–143measured by FP.While unmodiﬁed H3is bound with 0.8±0.1m M afﬁnity,methylation of Lys 4drastically reduces binding afﬁnity (17±3m M for K4me1,24±3m M for K4me2,and >70m M for K4me3).Molecular CellAllosteric PRC2Inhibition by H3K4me3/H3K36me3Molecular Cell 42,330–341,May 6,2011ª2011Elsevier Inc.335modiﬁed peptides did not show this competitive behavior,we conclude that PRC2is not inhibited by H3K4me3in trans and that H3K4me3and unmodiﬁed H3peptides are probably bound to PRC2in a different fashion.Analogously,we saw no inhibition when testing the effect of H3K4me3in trans by using peptides as substrates (Figure S4B ).Taken together,our ﬁndings strongly argue that H3K4me3only inhibits PRC2if present on the same tail that contains the H3K27target lysine (in cis ).Previous studies reported that addition of H3K27me3peptides in trans enhances H3K27methylation of oligonucleosomes by human PRC2through binding to the EED WD40domain (Margueron et al.,2009;Xu et al.,2010).We tested whether addition of H3K27me3peptides in trans would stimulate H3K27methylation by PRC2on H3Kc4me3-modiﬁed nucleosomes.We observed that the inhibitory effect of H3Kc4me3-containing nucleosomes can,at least in part,be overcome through addition of high concentrations of H3K27me3peptides (Figure 4B and Figure S4C).PRC2is therefore able to simultaneously integrate inhibitory (H3K4me3)and activating (H3K27me3)chromatin signatures and adjust its enzymatic activity in response to the surrounding epigenetic environment.PRC2Inhibition of H3K4me3Is Conserved in Mammalian PRC2Our results with Drosophila PRC2prompted us to investigate to what extent inhibition by H3K4me3is an evolutionarily conserved mechanism.H3K27methylation by human and mouse PRC2on nucleosome substrates carrying H3Kc4me3modiﬁcations was also strongly inhibited,comparable to the inhibition observed for Drosophila PRC2(Figure 5A and Figure S5A).The Su(z)12Subunit Codetermines Whether PRC2Is Inhibited by H3K4me3In Arabidopsis thaliana ,three different E(z)homologs combined with three Su(z)12homologs have been described.The distinct PRC2complexes in plants harboring the different E(z)or Su(z)12subunits are implicated in the control of distinct developmental processes during Arabidopsis development (He,2009).In this study we focused on PRC2complexes con-taining the E(z)homolog CURLY LEAF (CLF).We expressed and reconstituted the Arabidopsis PRC2complex comprising CLF,FERTILIZATION INDEPENDENT ENDOSPERM (FIE,a homolog of ESC),EMBRYONIC FLOWER 2(EMF2,a homolog of Su(z)12),and MULTICOPY SUPPRESSOR OF IRA (MSI1,a homolog of Nurf55).We found that CLF indeed functions as a H3K27me3HMTase (Figure 5B).Moreover,H3K27methylation by the CLF-FIE-EMF2-MSI1complex on nucleosome arrays containing H3Kc4me3was inhibited (Figure 5B)in a manner comparable to human or Drosophila PRC2.We next tested a related Arabidopsis PRC2complex again composed of CLF,FIE,and MSI1but containing the Su(z)12homolog vernalization 2(VRN2)instead of EMF2.The VRN2protein is speciﬁcally implicated as a repressor of the FLC locus,thereby controlling ﬂowering time in response to vernalization (reviewed in Henderson and Dean,2004).The CLF-FIE-MSI1-VRN2complex was active on unmodiﬁed nucleosomes but,strikingly,it was not inhibited on H3Kc4me3-modiﬁed nucle-osomes (Figure 5C).Substitution of a single subunit (i.e.,EMF2by VRN2)thus renders the complex nonresponsive to the H3K4methylation state.While PRC2inhibition by H3K4me3appears hardwired in mammals and ﬂies,in which only a single-Su(z)12ortholog is present,Arabidopsis inhibition can be enabled or disabled through exchange of the Su(z)12homolog.The Su(z)12C Terminus Harboring the VEFS Domain Is the Minimal Su(z)12Domain Required for Activation and Active Mark InhibitionThe importance of the Su(z)12subunit in active mark H3K4me3inhibition prompted us to map the Su(z)12domains required for inhibition.Previous ﬁndings showed that E(z)or E(z)-ESC in the absence of Su(z)12is enzymatically inactive (Nekrasov et al.,2005).Moreover,the VEFS domain (Birve et al.,2001)was found to be the major E(z)binding domain (Ketel et al.,2005).We reconstituted mouse PRC2complexes containing EZH2,EED,and either SUZ12C 2H 2domain +VEFS (residues 439–741)or SUZ12VEFS alone (residues 552–741).Both of these minimal complexes were active in HMTase assays on nucleosomes (Figure 5D)but with lower activity than that of the full PRC2complex.We therefore focused on formation ofAB26511030206H3K27me3H4peptides in trans[µM]H3K27me2H4H3K27me1H4H3 unmod H3K4me3H3K36me326511032062651103206n o e n z ym e26511030H3K27me3H4peptides in trans[µM]H3K27me2H4H3K27me1H4H3K27me3n oe n z y m eFigure 4.PRC2Activity Is Not Inhibited by H3K4me3Peptides in trans(A)Western blot-based HMTase assay by using unmodiﬁed 4-mer oligonu-cleosomes (36nM)and increasing amounts of H3peptides added in trans .Enzyme concentration was kept constant at 86nM.Western blots were pro-cessed as described in Figure 3B.HMTase activity is inhibited by an unmodiﬁed H31–19peptide (left),but not by H3K4me3-or H3K36me3-modiﬁed peptides.(B)HMTase assay with H3Kc4me3-modiﬁed oligonucleosomes (36nM),86nM PRC2,and H3K27me3peptide in trans .Western blots were processed as described in Figure 3B.HMTase activity of PRC2can be stimulated by the H3K27me3peptide even on inhibiting substrate leading to increased levels of H3K27di-and trimethylation.Molecular CellAllosteric PRC2Inhibition by H3K4me3/H3K36me3336Molecular Cell 42,330–341,May 6,2011ª2011Elsevier Inc.。

应用地球化学元素丰度数据手册-原版

应用地球化学元素丰度数据手册迟清华鄢明才编著地质出版社·北京·1内容提要本书汇编了国内外不同研究者提出的火成岩、沉积岩、变质岩、土壤、水系沉积物、泛滥平原沉积物、浅海沉积物和大陆地壳的化学组成与元素丰度，同时列出了勘查地球化学和环境地球化学研究中常用的中国主要地球化学标准物质的标准值，所提供内容均为地球化学工作者所必须了解的各种重要地质介质的地球化学基础数据。

本书供从事地球化学、岩石学、勘查地球化学、生态环境与农业地球化学、地质样品分析测试、矿产勘查、基础地质等领域的研究者阅读，也可供地球科学其它领域的研究者使用。

图书在版编目（CIP）数据应用地球化学元素丰度数据手册/迟清华，鄢明才编著. －北京：地质出版社，2007.12ISBN 978－7－116－05536－0Ⅰ. 应… Ⅱ. ①迟…②鄢…Ⅲ. 地球化学丰度－化学元素－数据－手册Ⅳ. P595－62中国版本图书馆CIP数据核字（2007）第185917号责任编辑：王永奉陈军中责任校对：李玫出版发行：地质出版社社址邮编：北京市海淀区学院路31号，100083电话：（010）82324508（邮购部）网址：电子邮箱：zbs@传真：（010）82310759印刷：北京地大彩印厂开本：889mm×1194mm 1/16印张：10.25字数：260千字印数：1－3000册版次：2007年12月北京第1版•第1次印刷定价：28.00元书号：ISBN 978－7－116－05536－0（如对本书有建议或意见，敬请致电本社；如本社有印装问题，本社负责调换）2关于应用地球化学元素丰度数据手册（代序）地球化学元素丰度数据，即地壳五个圈内多种元素在各种介质、各种尺度内含量的统计数据。

它是应用地球化学研究解决资源与环境问题上重要的资料。

将这些数据资料汇编在一起将使研究人员节省不少查找文献的劳动与时间。

这本小册子就是按照这样的想法编汇的。

基于Swin_Transformer的岩石岩性智能识别研究

现代电子技术Modern Electronics Technique2024年4月1日第47卷第7期Apr. 2024Vol. 47 No. 70 引言岩石识别是地质调查的基础性工作。

在野外地质调查中，地质工作者会根据岩石的颜色、结构构造、矿物成分等辨识岩石的岩性。

随着计算机视觉和深度学习技术的飞速发展，岩石纹理图像的自动识别和分类已经成为地质学中一个热门的研究方向。

近年来，许多国际和国内的研究团队都投入大量的精力进行此类研究，以期获得更高的识别精度和更稳健的分类效果[1]。

自AlexNet [2]在ImageNet [3]上取得重大突破后，卷积神经网络（Convolutional Neural Network, CNN ）[4]便一直引领着计算机视觉领域的研究。

随着深度学习的发展，各种卷积神经网络在岩石识别分类方面取得显著进展。

卷积运算可以有效地替代人工提取特征的方法，从而更准确地获取图像纹理与色彩中的岩石图像信息，精准识别岩石类型。

文献[5]基于Iception⁃v3深度卷积神经网基于Swin Transformer 的岩石岩性智能识别研究韩鑫豪1，2，何月顺1，陈杰1，2，熊凌龙1，2，钟海龙1，杜萍1，田鸣3（1.东华理工大学信息工程学院，江西南昌 330013；2.江西省放射性地学大数据技术工程实验室，江西南昌 330013；3.郑州市公安局网监支队，河南郑州 450000）摘要：常规卷积神经网络在识别纹理多变的岩石图像时，由于感受野和局部处理方式的局限性，识别精度不高，为解决上述问题，在复杂情况下准确识别岩石岩性，提高地质调查的效率，文中提出一种基于改进Swin Transformer 的岩石识别方法。

该方法增加了空间局部感知模块，并结合Transformer 的自注意力结构来增强对局部相关性的提取。

为增强泛化，模型中添加了Dropout 层，减少对单神经元的依赖。

WRFChem Users Guide

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The following institutions were instrumental in the development of the WRF-Chem model and its documentation. Department of Commerce/National Oceanic and Atmospheric Administration The Cooperative Institute for Research in Environmental Sciences The University Corporation for Atmospheric Research (UCAR) The National Center for Atmospheric Research (NCAR) The Max Plank Institute The University of Chile Centro de Previsão de Tempo e Estudos Climáticos This document does not constitute endorsement of the information, products or services contained herein by the contributing institutions previously named or unnamed. For other than authorized activities, the contributing institutions do not exercise any editorial control over the information contained herein. Any opinions, findings, conclusions or recommendations expressed in this document are those of the authors and do not necessarily reflect those of the contributing institutions. In no event shall these institutions, or any unmentioned institution associated with WRF-Chem development, be liable for any damages, whatsoever, whether direct, indirect, consequential or special, that arise out of or in connection with the access, use or performance of WRF-Chem, including infringement actions. The Weather Research and Forecasting model (WRF hereafter) was developed at the National Center for Atmospheric Research (NCAR) that is operated by the University Corporation for Atmospheric Research (UCAR). NCAR and UCAR make no proprietary claims, either statutory or otherwise, to this version and release of WRF and consider WRF to be in the public domain for use by any person or entity for any purpose without any fee or charge. UCAR requests that any WRF user include this notice on any partial or full copies of WRF. WRF is provided on an “AS IS” basis and any warranties, either express or implied, including but not limited to implied warranties of non-infringement, originality, merchantability and fitness for a particular purpose, are disclaimed. In no event shall UCAR be liable for any damages, whatsoever, whether direct, indirect, consequential or special, which arise out of or in connection with the access, use or performance of WRF, including infringement actions.

Clariom D solutions 产品说明书

DATA SHEET Clariom D solutionsClariom D solutions for human, mouse, and ratDeep and broad transcriptome-level expression profiling solutions for a faster path to biomarker discoveryRobust results even from precious samples• Generate robust expression profiles from as little as 100 pg of total RNA—as few as 10 cells• Use RNA from various sample types, including whole blood, cultured cells, and fresh/fresh-frozen or formalin-fixed, paraffin-embedded (FFPE) tissues• Preserve sample integrity and reduce data variability with an assay that does not require a globin or rRNA removal stepClariom D solutions are available in a single-sample(cartridge array) format for use on the Applied Biosystems ™ GeneChip ™ 3000 instrument system and comewith reagents and fast, simple Applied Biosystems ™Transcriptome Analysis Console (TAC) Software to analyze and visualize global expression patterns of genes, exons, pathways, and alternative splicing events.Accelerate your biomarker research withApplied Biosystems ™ Clariom ™ D solutions—the nextgeneration of transcriptome-level profiling tools—providing a highly detailed view of the transcriptome for a faster path to biomarker discovery. Available for human,mouse, and rat, Clariom D solutions allow translational scientists to generate high-fidelity biomarker signatures quickly and easily with a design that provides intricate transcriptome-wide, gene- and exon-level expression profiles, including the ability to detect alternative splicing events of coding and long noncoding RNA, in a single three-day experiment.Get all the data you need• Rapidly identify complex disease signatures from as many as 540,000 transcripts, the most comprehensive coverage available, helping to ensure that biomarkers are not missed• Confidently detect genes, exons, and alternative splicing events that give rise to coding and long noncoding RNA isoforms• Detect rare and low-expressing transcripts otherwise missed by common sequencing practices• Go from data to insight in minutes with intuitive, highly visual, free analysis softwareTranscripts*>542,500>214,900>495,200 Exons*>948,300>498,500>320,400 Exon-exonsplice junctions*>484,900>282,500>293,700 Total probes*>6,765,500>6,022,300>5,946,400 Probes targeting exons*>4,781,200>4,895,600>4,780,700 Probes targeting exon-exon splice junctions*>1,984,300>1,126,700>1,165,700 Probe length (bases)252525 Probe feature size 5 μm 5 μm 5 μmBackground probes AntigenomicsetAntigenomicsetAntigenomicsetPerformance specifications Human, mouse, ratTotal RNA input required**100 pg–500 ngSensitivity ≥1.5 pMDetectable 2-fold change1:100,000 vs. 1:50,000Dynamic range~3 logarithmic unitsTechnical replicate signal correlation≥0.90Correlation coefficient (intra-lot)≥0.99cRNA yield≥20 μgcDNA yield≥6 μgControls†• 92 ERCC transcripts• poly(A) (dap, lys, phe, thr)Target orientation‡Sense targetFluidics script FS450_0001* Numbers are representative of annotations as of April 2016. All numbers have been rounded down to the nearest hundred.** Total RNA input requirements depend on assay selection. The assay types offered require different total RNA input amounts based on sample sources.† P robe sets interrogating external RNA controls present in the Applied Biosystems™ ERCC RNA Spike-In Control Mixes (Cat. No. 4456740 and 4456739).‡ The probes tiled on the array are designed in the antisense orientation, requiring sense-strand, labeled targets to be hybridized to the array.* Numbers are representative of annotations as of April 2016. All numbers have been rounded down to the nearest hundred.** 1. Luo H, et al. (2013) Comprehensive characterization of 10,571 mouse large intergenic noncoding RNAs from whole transcriptome sequencing. PLoS One 8(8):e70835.2. Chalmel F, et al. (2014) High-resolution profiling of novel transcribed regions during rat spermatogenesis. Biol Reprod 91(1):5.3. Williams WP, et al. (2004) Increased levels of B1 and B2 SINE transcripts in mouse fibroblast cells due to minute virus of mice infection. Virology 327(2):233–241.4. Guo JU, et al. (2014) Expanded identification and characterization of mammalian circular RNAs. Genome Biol 15(7):409.Find out more at /microarraysFor Research Use Only. Not for use in diagnostic procedures. © 2017 Thermo Fisher Scientific Inc. All rights reserved. All trademarks are the property of Thermo Fisher Scientific and its subsidiaries unless otherwise specified. COL13238 0417Clariom D Assay, human10 reactions 90292230 reactions 902923Clariom D Assay, mouse(previously named GeneChip Mouse Transcriptome Assay 1.0)10 reactions 90251330 reactions 902514Clariom D Assay, rat(previously named GeneChip Rat Transcriptome Assay 1.0)10 reactions 90263330 reactions 902634GeneChip Hybridization, Wash, and Stain Kit30 reactions900720。

隐马尔可夫模型(hmm)的matlab实现

隐马尔可夫模型(HMM)是一种用于对时序数据进行建模和分析的概率模型，特别适用于具有一定的隐含结构和状态转移概率的数据。

在自然语言处理、语音识别、生物信息学等领域中，HMM都有着广泛的应用。

在本文中，我将向您介绍HMM的基本概念和原理，并共享如何使用Matlab来实现HMM模型。

1. HMM基本概念和原理隐马尔可夫模型是由隐含状态和可见观测两部分组成的，其中隐含状态是不可见的，而可见观测是可以被观测到的。

在HMM中，隐含状态和可见观测之间存在转移概率和发射概率。

通过这些概率，HMM可以描述一个系统在不同隐含状态下观测到不同可见观测的概率分布。

HMM可以用状态转移矩阵A和发射矩阵B来表示，同时也需要一个初始状态分布π来描述系统的初始状态。

2. Matlab实现HMM模型在Matlab中，我们可以使用HMM工具箱（HMM Toolbox）来实现隐马尔可夫模型。

我们需要定义系统的隐含状态数目、可见观测的数目以及状态转移概率矩阵A和发射概率矩阵B。

利用Matlab提供的函数，可以方便地计算出系统在给定观测下的概率分布，以及通过学习的方法来调整参数以适应实际数据。

3. 在Matlab中实现HMM模型需要注意的问题在实现HMM模型时，需要注意参数的初始化和调整，以及对于不同类型的数据如何选择合适的模型和算法。

在使用HMM模型对实际问题进行建模时，需要考虑到过拟合和欠拟合等问题，以及如何有效地利用HMM模型进行预测和决策。

总结通过本文的介绍，我们可以了解到隐马尔可夫模型在时序数据建模中的重要性，以及如何使用Matlab来实现HMM模型。

对于HMM的进一步学习和实践，我个人认为需要多实践、多探索，并结合具体应用场景来深入理解HMM模型的原理和方法。

在今后的学习和工作中，我相信掌握HMM模型的实现和应用将对我具有重要的帮助。

我会继续深入学习HMM模型，并将其运用到实际问题中，以提升自己的能力和水平。

以上是我对隐马尔可夫模型的个人理解和观点，希望对您有所帮助。

欧洲药典7.5版

EUROPEAN PHARMACOPOEIA 7.5
INDEX
To aid users the index includes a reference to the supplement in which the latest version of a text can be found. For example : Amikacin sulfate...............................................7.5-4579 means the monograph Amikacin sulfate can be found on page 4579 of Supplement 7.5. Note that where no reference to a supplement is made, the text can be found in the principal volume.
English index ........................................................................ 4707
Latin index ................................................................................. 4739
EUROPEAN PHARMACOPபைடு நூலகம்EIA 7.5
Index
Numerics 1. General notices ................................................................... 7.5-4453 2.1.1. Droppers...................

英语国际会议PPT课件

6
Materials and Methods
Patients
Materials and Methods
Cytokine assessment by ELISA
Western blot
Cell isolation and culture
Statistical analysis
7
Methods
IFN-c-induced protein of 10-kDa (IP-10)/CXCL10
we studied the effects of α-toxin on Th1- and Th2related chemokines in macrophages from patients with AD and psoriasis where the intrinsic abnormal and different chemokines production profile is well defined.
13
Figure 3 Punch biopsies (3 mm) from healthy individuals were left either unstimulated (A) or stimulated with a-toxin (100 ng/ ml) (B) or IFN-c (100 ng/ml) (C) for 24 h at 37C. 5-lm parafﬁn sections were stained for CXCL10 along with appropriate isotype as well as CD68.
16
Low effect of a-toxin on CXCL10 induction (Th1-related chemokine) in macrophages from patients with AD

C8051F060_07中文资料

• Programmable hysteresis/response time - Voltage Reference - Precision VDD Monitor/Brown-Out Detector On-Chip JTAG Debug & Boundary Scan - On-chip debug circuitry facilitates full-speed, nonintrusive in-circuit/in-system debugging Provides breakpoints, single-stepping, watchpoints, stack monitor; inspect/modify memory and registers Superior performance to emulation systems using ICE-chips, target pods, and sockets IEEE1149.1 compliant boundary scan Complete development kit
Clock Sources - Internal calibrated precision oscillator: 24.5 MHz - External oscillator: Crystal, RC, C, or clock Supply Voltage .......................... 2.7 to 3.6 V - Multiple power saving sleep and shutdown modes 100-Pin and 64-Pin TQFP Packages Available Temperature Range: -40 to +85 °C

ccs chemistry awaiting reviewer selection

ccs chemistry awaiting reviewer selection "CCS Chemistry awaiting reviewer selection" 表示你的论文已经提交给CCS Chemistry（中国化学会会刊）期刊，并且正在等待编辑选择合适的审稿人来评审你的论文。

在这个阶段，编辑会根据你的论文主题和领域，选择具有相关专业知识和经验的审稿人来对你的论文进行评审。

这可能需要一些时间，因为编辑需要仔细考虑每个候选人的资格和可用性。

一旦编辑选择了审稿人，他们将开始评审你的论文，并在一段时间后向编辑提供反馈意见。

编辑会根据这些意见决定是否接受你的论文、要求修改或拒绝。

packmol 配体与蛋白质改坐标

packmol 配体与蛋白质改坐标packmol是一种用于分子动力学模拟中构建复杂分子系统的软件工具。

它能够将不同的分子类型组装在一起，并生成最终的系统坐标文件。

在生物科学领域中，packmol被广泛用于配体与蛋白质的研究中，因其灵活性和高效性而备受青睐。

通过改变蛋白质与配体的坐标，可以探索它们之间的相互作用，从而揭示出生物分子的结构和功能。

在配体与蛋白质的研究中，packmol的使用流程通常包括以下几个主要步骤：准备配体、准备蛋白质、准备包含水分子的溶剂盒子、将配体和蛋白质放入溶剂盒子中、生成系统坐标。

1. 准备配体配体通常是小分子化合物，且能够与蛋白质发生特定的相互作用。

准备配体时，需要确定其结构、电荷和拓扑信息。

可以通过结构数据库（如PDB）或化学绘图软件（如ChemDraw）来获得配体的结构。

使用分子力学软件（如GROMACS）来为配体生成拓扑文件和参数。

2. 准备蛋白质准备蛋白质的步骤与准备配体类似，但更为复杂。

需要确定蛋白质的序列、结构和电荷信息。

通常，可以通过结构数据库（如PDB）或蛋白质建模软件（如MODELLER）来获得蛋白质的结构。

使用相应的工具（如GROMACS）来生成蛋白质的拓扑文件和参数。

3. 准备包含水分子的溶剂盒子生物分子通常处于水溶液中，因此在模拟过程中需要考虑溶剂的存在。

使用packmol时，可以通过定义一个有一定体积的盒子来模拟溶液环境。

可以使用packmol内置的几何体来生成溶剂盒子，也可以根据需要自定义盒子的尺寸。

4. 将配体和蛋白质放入溶剂盒子中将配体和蛋白质放入溶剂盒子中是建立配体蛋白系统的关键步骤。

在packmol中，可以通过设置每种分子的个数和位置来实现这一目标。

通常，可以根据实验数据或文献中的信息确定配体和蛋白质的最佳浓度和比例。

5. 生成系统坐标在完成溶剂盒子的构建后，packmol会自动生成一个包含所有分子的坐标文件。

该文件可以用于后续的分子动力学模拟和结构分析。

HISTORYMARKINGSCHEMEPAPER22013ZIMSEC

Download: HISTORY MARKING SCHEME PAPER2 2013 ZIMSEC PDFHISTORY MARKING SCHEME PAPER2 2013 ZIMSEC PDF - Are you looking for Ebook History Marking Scheme Paper2 2013 Zimsec Pdf? You will be glad to know that right now History Marking Scheme Paper2 2013 Zimsec Pdf is available on our online library. With our online resources, you can find Applied Numerical Methods With Matlab Solution Manual 3rd Edition or just about any type of ebooks, for any type of product.Best of all, they are entirely free to find, use and download, so there is no cost or stress at all. History Marking Scheme Paper2 2013 Zimsec Pdf may not make exciting reading, but Applied Numerical Methods With Matlab Solution Manual 3rd Edition is packed with valuable instructions, information and warnings. We also have many ebooks and user guide is also related with History Marking Scheme Paper2 2013 Zimsec Pdf and many other ebooks.We have made it easy for you to find a PDF Ebooks without any digging. 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AuthorChecklist-Elsevier

Systematic Review of MOOSE Meta-analysis of Observational Studies in Epidemiology
Obs ervational
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BMP-2对肺癌细胞上皮-间质转化的影响及其作用机制

BMP-2对肺癌细胞上皮-间质转化的影响及其作用机制王福琴【摘要】目的:探讨骨形态发生蛋白-2(BMP-2)对肺癌细胞上皮-间质转化的影响及作用机制。

方法:经免疫组织化学SP法检测BMP-2作用下肺癌A549细胞内E-钙黏蛋白(E-cad)表达强度,蛋白质印迹法检测E-cad、波形蛋白(vimentin)表达水平,并进行细胞侵袭、凋亡实验;经p38丝裂原活化蛋白激酶(MAPK)信号通路抑制剂SB203580联合BMP-2作用于A549细胞,评估p38 MAPK信号通路抑制剂SB203580在BMP-2促进A549细胞上皮-间质转化、凋亡中的作用。

结果:细胞质内E-cad表达强度呈浓度依赖性降低,vimentin表达水平呈浓度依赖性增加;B、C、D组穿过滤泡细胞数多于A组,早期凋亡率低于A组(P<0.05);F组E-cad表达高于E组,vimentin表达低于E组,穿过滤泡细胞数少于E组,早期凋亡率高于E组(P <0.05)。

结论:BMP-2可能经由激活p38 MAPK信号通路促进肺癌A549细胞出现上皮-间质转化,影响细胞侵袭、凋亡。

【期刊名称】《生物化工》【年(卷),期】2019(005)001【总页数】4页(P77-80)【关键词】肺癌细胞;上皮-间质转化;BMP-2;作用机制【作者】王福琴【作者单位】[1]山西医科大学晋祠学院,山西太原030025;【正文语种】中文【中图分类】R734.2目前，肺癌发病机制仍未明确，临床多经手术、放化疗治疗，但术后癌细胞侵袭性转移、复发仍是影响肺癌患者死亡的重要原因[1]。

因此，探寻肺癌细胞侵袭、转移发生机制至关重要。

而包括肺癌在内的多种肿瘤细胞侵袭、转移与上皮-间质转化有较大关联。

研究发现，肺癌组织中BMP-2特异性升高，可判断预后[2]。

骨形态发生蛋白（BMPs）是转化生长因子-β超家族成员，可刺激骨细胞分化。

骨形态发生蛋白-2（BMP-2）为BMPs最具代表性因子，可促进骨修复，抑制肿瘤细胞生长。