Cellular Automata Generalized to an Inferential System：元胞自动机广义推理系统
cellular automata文献
cellular automata文献Cellular Automata: A Comprehensive Review - 细胞自动机：综述1. Introduction - 引言1.1 Background - 背景Cellular automata (CA) is a computational model that is widely used in various scientific disciplines, including physics, biology, computer science, and mathematics. Initially introduced by John von Neumann and Stanislaw Ulam in the 1940s, CA has gained significant attention due to its ability to generate complex and emergent behaviors from simple local rules.1.2 Objective - 目标The objective of this comprehensive review is to provide an overview of the fundamental concepts, applications, and current research trends in CA. The review aims to serve as a helpful resource for researchers and practitioners in understanding the potential of CA in simulating and analyzing complex systems. 2. Fundamental Concepts - 基础概念2.1 Cellular Structure - 细胞结构A cellular automaton consists of a grid of cells, each of which can have a certain state. The state of a cell can be represented by a finite set of values, such as "on/off" or "1/0". The grid is often visualized as a two-dimensional lattice, although CA can also be defined in higher dimensions.2.2 Neighbourhood - 邻域In a CA, each cell is influenced by its neighboring cells. The neighborhood of a cell is defined as the set of cells that directly influence its state. The neighborhood can be defined in various ways, such as the Moore neighborhood or the von Neumann neighborhood.2.3 Transition Rules - 转换规则The behavior of a CA is determined by transition rules, which specify how the state of a cell changes based on the states of its neighbors. The transition rules can be deterministic, where the next state is uniquely determined, or probabilistic, where the next state is determined by a probability distribution.2.4 Time - 时间CA operate in discrete time steps, where each time step corresponds to an update of the cell states based on the transition rules. The order in which the cells are updated can vary, such as synchronous updates or asynchronous updates.2.5 Boundary Conditions - 边界条件Boundary conditions define the behavior of cells at the edges of the grid. Different boundary conditions can lead to different global behaviors of the CA. Commonly used boundary conditions include periodic boundary conditions, reflecting boundaries, and absorbing boundaries.3. Applications - 应用3.1 Physics - 物理学CA has been extensively used in physics to model various physical phenomena, such as fluid dynamics, crystal growth, andmagnetism. For example, the Ising model, which is a lattice-based CA, has been used to study phase transitions in magnetic materials.3.2 Biology - 生物学CA has also found applications in biology, particularly in the study of pattern formation and biological morphogenesis. CA models have been used to simulate the growth of plants, the behavior of animal populations, and the development of biological tissues.3.3 Computer Science - 计算机科学In computer science, CA has been used for various purposes, including image processing, cryptography, and parallel computing. The cellular automaton known as Conway's Game of Life has gained popularity due to its ability to simulate complex patterns and behaviors.3.4 Mathematics - 数学CA has been extensively studied in the field of mathematics, particularly in the study of dynamical systems and complexity theory. The behavior of CA has been found to exhibit rich and often unpredictable patterns, leading to connections with chaos theory and fractal geometry.4. Current Research Trends - 当前研究趋势4.1 Hybrid Models - 混合模型Current research in CA is focused on integrating CA with other modeling techniques, such as differential equations, agent-based models, and network models. These hybrid models allow for a more comprehensive and accurate representation of complex systems.4.2 Machine Learning - 机器学习Recent developments in machine learning have led to the use of CA as a tool for training and evaluating neural networks. CA-based neural networks, known as cellular neural networks, have shown promising results in various applications, including image recognition and pattern classification.4.3 Complex Systems - 复杂系统CA continues to be a valuable tool for studying complex systems, such as social networks, ecological systems, and traffic flow. The ability of CA to capture emergent behaviors and self-organization makes it well-suited for modeling and analyzing complex systems.5. Conclusion - 结论Cellular automata have proven to be a powerful computational model with a wide range of applications in various scientific disciplines. The fundamental concepts, applications, and current research trends in CA have been discussed in this comprehensive review. As research in complex systems continues to advance, CA is expected to play an increasingly important role in understanding and simulating the behavior of complex systems.。
Cellular automata
Cellular automata:From a theoretical parallel computational model to its application to complex systemsS.Bandini a,*,G.Mauri a ,R.Serra ba Department of Computer Science,Systems and Communication (DISCo),University of Milano-Bicocca,Via Bicocca degli Arcimboldi,8-20134Milan,Italyb Centro Ricerche Ambientali Montecatini,Via Ciro Menotti,48-48023Marina di Ravenna,ItalyReceived 12October 2000AbstractThis introductory paper gives a short survey of cellular automata (CAs),from di erent points of view.It starts with the main de®nitions and theoretical results about CAs as an abstract model of computation or as discrete dynamical systems.Then,the main applications of CAs in di erent ®elds (biology,physics,etc.)as a model of complex systems are illustrated.Finally,implementations of the CA model on parallel computing platforms are sur-veyed.Ó2001Elsevier Science B.V.All rights reserved.Keywords:Cellular automata;Applications;Complex systems1.Introduction and basic de®nitionsThis issue of Parallel Computing collects the best papers presented at the con-ference on ``Cellular Automata for Research and Industry'',held in Trieste (Italy)in September 1998.The selection includes papers containing the theoretical research results about cellular automata (CAs),as well as more application-oriented contri-butions that illustrate a growing scenario of interests in the ®eld of CAs./locate/parcoParallel Computing 27(2001)539±553*Corresponding author.Present address:rmatica-Sistemistica e Comunicazione,Univ.Degli Studi di Milano-Bicocca,20126Milano,Italy.Tel.:+39-02-64487835;fax:+39-02-64487839.E-mail addresses:bandini@disco.unimib.it (S.Bandini),giancarlo.mauri@disco.unimib.it (G.Mauri),rserra@cramont.it (R.Serra).0167-8191/01/$-see front matter Ó2001Elsevier Science B.V.All rights reserved.PII:S 0167-8191(00)00076-4This introductory paper aims at giving a short overview of the di erent aspects of CAs.In Section 1,the main theoretical results about CAs are presented.Section 2illustrates the main applications of CAs in di erent ®elds.Finally,Section 3concerns implementations of the CA model on parallel computing platforms.For a more detailed presentation of CAs,see [30,36,73].The theory of CAs as models of self-reproducing systems was conceived and ®rstly developed by John Von Neumann during the 1950s,and was exposed in [72]In the same years,other researchers like Thatcher [68],Code [24]and Burks [16±18]contributed to completing and improving the model.Following these seminal pa-pers,the interest in CAs grew in di erent directions,and they were studied from di erent rmally,a CA is a set of identical elements,called cells ,each one of which oc-cupies a node of a regular,discrete,in®nite spatial network.Each cell can assume a state from a ®nite set,and the automaton evolves in discrete time steps,changing the states of all its cells according to a local rule ,homogeneously applied at every step.The new state of a cell depends on the previous states of a set of cells,which can include the cell itself,and constitutes its neighborhood .More formally,we can give the following de®nition,assuming Z d as the underlying spatial network of the automaton.De®nition 1.1.A d-dimensional cellular automaton (or d-CA)is a structure A Z d ;S ;N ;d where:(a)Z d is the (discrete)lattice of d -tuples of integer numbers.(b)S is a ®nite set of states .(c)N f n j x 1j ;...;x dj =j P f 1;...;n gg is a ®nite ordered subset of Z d called the neighborhood of A .(d)d :S n 13S is the local transition function or local rule of A .It is useful to have a special state,called quiescent and denoted by 0,such that d 0;...;0 0.Let x P Z d be a cell,and s P S its state at time t .Then at time t 1,x will assume the state S H d x n 1;...;x n n .Hence,the elements of N give the vector of displacements along each one of the d possible directions that allow reaching the cells that in¯uence the state change of the cell at hand.Two important neighbor-hoods are as follows:(a)Von Neumann neighborhood:n VN n j ( x 1j ;...;x dj =x kj P f À1;0;1g for k 1;...;d and X d k 1j x kj j 61):In this case,a cell x is connected to all the cells at a distance 1along exactly one of the d coordinates,and with itself (distance 0):see Fig.1(a).(b)Moore neighborhood:n M f n j x 1j ;...;x dj =x kj P fÀ1;0;1g for k 1;...;d gIn this case,a cell x is connected to cells at distance at most 1in each direction (i.e.,diagonal connections are allowed:see Fig.1(b)for the 2D case).540S.Bandini et al./Parallel Computing 27(2001)539±553It appears clear from the above de®nition that the main characteristics of CAs are discreteness and locality .From the repeated synchronous application of the simple local evolution rules,a global behavior emerges which can be very complex.Let us now formalize the notion of evolution or behavior of CAs,starting with the de®nition of con®guration.De®nition 1.2.A configuration or instantaneous description or global state of a cel-lular automaton A Z d ;S ;n ;d is a map C :Z d 3S that associates a state with every cell.We will denote by C A ,or simply C ,the set of con®gurations of A .The synchronous application of the local rule to every cell allows transforming a con®guration into a new one.De®nition 1.3.The global function of a cellular automaton A Z d ;S ;n ;d is a map F A :C 3C de®ned by F A c x d x n 1;...;x n n for every x P Z d .De®nition 1.4.The behavior or evolution of a cellular automaton A from a given initial con®guration c 0P C is a sequence of con®gurations f c t g t P 0,such that for t P n ;c t 1 F A c t .The sequence f c t g t P 0is often designated as the orbit of c 0when CAs are con-sidered as dynamical systems,or as a computation on c 0when they are seen as computation models.2.Dynamical behavior of CAsDespite their apparently simple de®nition,based on local rules,CAs can show very complex dynamical behaviors,even in the case of the so-calledelementary S.Bandini et al./Parallel Computing 27(2001)539±553541542S.Bandini et al./Parallel Computing27(2001)539±553CAs,i.e.1D cellular automata with two neighbors and two states.To de®ne a precise criterium which captures the notion of complexity,concepts like chaos or non-ergodicity,taken from the theory of dynamical systems,have been used [46,47,50].An important work on CAs as dynamical systems was done by Wolfram[73],with the interpretation of the1D cellular automata dynamics in the framework of sta-tistical physics.Wolfram proposes a classi®cation of1D CAs in four complexity classes,according to the asymptotic pattern generated by the synchronous dynamics starting from random initial con®gurations:1.Any initial con®guration converges to a®xed homogeneous state(i.e.,all the cells are in the same state).2.The limits of initial con®gurations are cycles,with separated simple stable or pe-riodic structures.3.``Chaotic''or fractal patterns,with arbitrary periods,appear.4.Breaking symmetry con®gurations(as gliders)and long-lived localized patterns appear.This classi®cation is empirical and di cult to apply.For example,it has been shown that the membership of a given CA even in the simpler class(1)is undecidable. However,this classi®cation is the basis for more rigorous classi®cation attempts. An attempt in the formalization of Wolfram's classi®cation scheme has been done by Culik and Yu(28)who split CA into three classes of increasing complexity. Unfortunately,membership in each of these classes is shown to be undecidable.A complete and e ective classi®cation of elementary cellular automata was given by Braga[15].The dynamical properties of CAs are essentially related to the properties of the global functions,such as surjectivity,injectivity and bijectivity.Another im-portant property,in particular when CAs are considered as models of physical systems,is reversibility.Before considering these properties,let us de®ne some classes of con®gurations of particular interest:(a)Finite con®gurations:For every con®guration c P C we de®ne its support as the set of cells whose state is not the quiescent onesupp c f x P Z d:c x 0g:We say c is®nite if j supp c j<I,and will denote by c fin the set of®nite con®gu-rations.Since we are interested in using CAs to represent and manipulate®nite data, these con®gurations are essential in the computation or language recognition areas. Since d 0;...;0 0,the global function maps®nite con®gurations into®nite con®gurations:F A:C fin3C fin: 1 (b)Periodic con®gurations:A periodic con®guration is a con®guration c for which there exists x P Z d such that c x Z c x for every x P Z d.(c)Garden of Eden:Since the global function is not in general surjective,there are con®gurations that cannot be obtained during the evolution of the CA,but can only be taken as initial con®gurations,or given as``input''.They are called Garden ofS.Bandini et al./Parallel Computing27(2001)539±553543 Eden con®gurations,and originated the systematic study of global functions [29,52,53].The principal result is as follows[52,53].Theorem2.1.A cellular automaton with a quiescent state is surjective iff its restriction to finite configurations is injective.Another important problem is to characterize the set of global functions F,which come from local functions.This problem was solved by Hedlund[39]and Rich-ardson[56].Theorem2.2.An application F:C3C that commutes with the shift r,i.e.satisfies F r r F,is continuous with respect to the product topology on Z d iff it is the global function of a CA.Let us recall that r is de®ned by r c x c x 1 ;this means that every cell x is mapped by r in the state assumed by the cell x 1in the current con®guration, where1is the vector of all ones.We also have:Theorem2.3.A cellular automaton is bijective iff it is reversible iff it is injective. Let us now introduce another important concept,the phase space of the cellular automaton A,that is a graph whose nodes are the con®gurations,and in which there is an arc from cÁto c H i c H F A c .The orbit generated by a given initial con®gu-ration c will correspond to a path in this graph.Some of these orbits,after an initial subpath without cycles,called transient,enter a cycle,called period of c.Periodic orbits of some classes of CAs,like additive or linear automata,have been completely characterized.An important role,in order to®nd signi®cant classi®cations,is played by to-pologies or metrics de®ned on the phase space,and by related notions of topological chaos.Various notions of topological chaos for iterated discrete time dynamical systems,with applications to cellular automata dynamics,are introduced and compared in[21].The study of the dynamics of CAs has played an important role in the develop-ment of concepts and conjectures in the®eld of complex systems,in particular those concerning the notion of the``edge of chaos''[41±43]and``self-organized criticality'' [4,5].Langton[43]observed that,by de®ning a suitable order parameter on a set of CA rules,it was possible to observe a transition between an interval of values of the order parameter where the automata displayed ordered behaviors(Wolfram's classes 1or2),and an interval corresponding to chaotic behaviors(class3).The transition region,corresponding to class4behavior,was a sort of boundary between ordered and chaotic regimes,and was called the``edge of chaos''.Packard[54]observed that a population of CA rules,which evolved under selective pressure trying to perform a544S.Bandini et al./Parallel Computing27(2001)539±553 computational task,tended to reach the boundary region,which seemed favored with respect to other regions.Mitchell et al.[51]investigating a di erent case,ob-tained very di erent results,where the evolution towards the boundary region is not observed.Kau man[42]provided heuristic arguments,as well as examples from other dynamical systems,in favor of the notion that complex adaptive systems tend to evolve under fairly general conditions towards the``edge of chaos''which sepa-rates the ordered and the chaotic regions.Self-organized criticality[4,5]is a theory of the evolution of dynamical systems, which emphasizes the role of the so-called critical states,which are ubiquitous in nature and which are characterized by the presence of perturbations of every size, following a power-law distribution.This theory aims at a great generality and has generated an animated debate on complex systems'theoretical research.It is worth recalling here that the basic example upon which the whole theory was built,namely the celebrated sandpile,has been modeled by Bak and co-workers with a simple CA rule.It should also be recalled that the work by Mitchell,Crutch®eld and co-workers on emergent computation,who developed CAs to be able to perform various computational tasks and a theoretical framework to analyze them,called compu-tational mechanics(see e.g.[27]);an interesting example concerning density classi-®cation can be found in this volume(see the paper by Jimenez Morales et al.). These examples show how the availability of CA models has allowed the birth and the development of deep concepts for the investigation of the theoretical bases of complex systems behavior.puting capabilities of CAsCellular automata can be considered as an abstract model of computation,which transforms a given®nite con®guration,representing the input data,in an output con®guration.The computational capabilities of CAs have been extensively studied since the beginning,for example by Thatcher[68],Codd[24],Banks[11]and Burks[18]. They proved that there exist CAs that have the capabilities of an universal Turing machine,hence could be used as general-purpose computers.The notion of uni-versality was de®ned both in a direct way and by simulation of Turing machines. In the above-quoted papers,2D cellular automata were considered,and the main e ort was to®nd the simpler(i.e.,with less states)universal automaton.In par-ticular,starting from a universal automaton with von Neumann neighborhood and 29states,shown by von Neumann,Codd reduced the number of states to8and Banks to4.If we consider the Moore neighborhood,only two states su ce to obtain uni-versality.This was shown by Conway[13,26].Its universal automaton has been presented as a solitaire computer game,the well-known``Game of Life''.It is natural to ask whether universality may be obtained even with1D automata.A positive answer was given by Smith[62],who proved the following theorem.S.Bandini et al./Parallel Computing27(2001)539±553545 Theorem3.1.Given a Turing machine with n internal states and m alphabetic symbols, there exists a1D cellular automaton with six neighbors and max n;m 1states which simulates it.4.Applications of CAsThe primitive concept of CAs dates back to the late1940s,but during their fol-lowing existence,CAs models and applications have been created,developed,and used in many di erent®elds.In spite of the large amount of work made throughout these di erent®elds,in this section the focus will be on applications,letting to the solid literature on CA the task of satisfying other interests of the readers about this topic.1In general,it is possible to distinguish two main approaches in the creation of CA models:forward and backward[73].The forward(theoretical)approach concerns the study of transition rules of a given cellular space in order to establish its intrinsic properties(dynamical behavior,patterns growth,and so on[74].The backward (practical)approach regards the design of transition rule sets of a designed cellular space in order to match the``right''behavior of the CA system of a given complex system(physical,biological,social,urban,and so on).Many actual applications of CA directly derive from the theoretical results(as in the case of the dialectics between physics and engineering sciences,for example).In several cases,sets of backward rules show a successful behavior matching on the behavior of a given system,and the theoretical properties of such rules have to be investigated.Looking around in the world of applications of CA,it is possible to hazard the observation of a mirroring situation between the CA world and the world of the hard/soft sciences:where formal models can be de®ned,a synergic cycle among theoretical and application aspects rises.The example of physics is an evident case of this cycle.Moreover,in many cases of scienti®c discovery,the cycle is very complex,and the exact role of theoretical and application/experimental contribution is fuzzy.In the case of not-hard sciences(e.g.urbanistics,sociology,and so on),the question is controversial,but the lack of formal models due to the intrinsic very complex nature of phenomena often does not allow the above-mentioned cycle to be evident.The application of CA to physical systems has been the®rst successful case.In particular,the case of the so-called HPP(from the name of the authors)lattice gas model[38]signed an important milestone in the evolution of CA models.As well described in[23],the HPP dynamics was initially planned as a theoretical model to study the fundamental statistical properties of a gas of interacting particles.Sim-plifying,since it is well known that the¯ows of a real system of particle(like a¯uid or a gas),a fully discrete and simpli®ed molecular dynamics could simulate a¯uid-dynamic phenomenon at an appropriated observation scale.This principle is the1ftp:///pub/topics/cas/ca-faq.bib546S.Bandini et al./Parallel Computing27(2001)539±553basis of many applications of¯uid-dynamic CA models to simulate real physical phenomena.It should also be stressed that the so-called lattice Boltzmann automata[64]have been successful in simulating¯uid dynamics,by resorting to a state space which is continuous.This departure from the original CA paradigm improves however their simulation capabilities,and it has been taken also in the so-called macroscopic cellular automata[33].A case of industrial application of a CA(HPP)is the simulation of water per-colation processes occurring in a porous medium:ground and toasted co ee[20]. This work has been developed within the cellular automata for percolation processes (CAPPs)transfer technology project,supported by European Union[8].Within this project,also the applications of CA to the simulation of visco-elastic properties in rubber compounds[10]and of reaction±di usion phenomena in polluted soil[9]have been developed in collaboration with three companies.They gave the real experi-mental data of the investigated phenomena in order to verify the goodness of the models and of the simulations results.All the three applications of the CAPP pro-jects have been developed on parallel platforms(CRAY3TE and Origin2000)at CINECA(Bologna),showing good performances[8].In the framework of projects supported by UE another interesting industrial application must be mentioned:the CABOTO,and its successor COLOMBO pro-jects dedicated to the modeling of the problem of bioremediation of contaminated soils.They regard a CA-based model which describes the interaction among phys-ical,chemical and biological phenomena which take place during in situ bioreme-diation,and which can be used to forecast the results of interventions in the®eld, starting from laboratory and pilot plant data[31,59].Biology is one of the®rst disciplines involved in the application of CA.The main purpose of von Neumann when he created the core de®nition of CAs[17]was the development of a formal computational model for the description and the simulation of self-reproduction in a biological sense.Today it is possible to roughly divide the research and the application of CA in biology into two main branches.The®rst falls in the general topic of Arti®cial Life (Alife)models[44,45],and the second regards models and systems that have been developed for studying dynamical properties of biological phenomena.The boundaries of these two sets are fuzzy.This fact depends on the discipline where researchers belong to,on the speci®c biological phenomena to be studied using computational supports,and of the possible interactions occurring in interdisci-plinary environments(i.e.,computer scientists involved in some biological research). For instance,the creation of a CA-based system for the simulation of the cellular interaction in the immune system[22]has been possible thanks to the positive col-laboration between an immunologist and a theoretical physicist at the Watson Re-search Center of IBM(USA).A nested CA-based model has been developed from this original devoted to the immune system and adopted also for the simulation of the calcium ions di usion in living cells[7].Models and simulations of vegetal growth is a very interesting case of application of CA.In[3]a CA model for the simulation of emergent spatial structure in vege-S.Bandini et al./Parallel Computing27(2001)539±553547 tation successions is presented.It allows the examination of the response of the boreal treeline of northern Qu e bec to various environmental forcing factors,such as climate amelioration in the post-glacial period.Moreover,a CA-based model and the related parallel simulation concerning growth patterns of botanical colonies is presented in[40]This simulation shows graceful features visualizing the structural dynamics of the growing colonies.Other interesting applications can be found in [6,25,37].The importance of the dynamics of gene expression in a cell is becoming in-creasingly clear for the study,e.g.of cell di erentiation,switching among di erent metabolic regimes and tumor growth.A simpli®ed model of random boolean net-works,proposed by Kau man[41],which can be regarded as a CA-like model,has provided valuable theoretical insights into the generic behavior of these networks.A generalization of this model,designed to describe the bacterial degradation of or-ganic compounds by bacterial consortia,has been proposed[57,59],which allows for the presence of exogenous chemicals and for continuous activation values.By adopting a simpli®ed version of this model as the rule for cell dynamics,it has also been possible to develop a CA model which describes the growth of a population of cells in a tissue,simulating the development of tumors in in vitro cell cultures[60]. Another topic that is becoming a challenging application®eld for CA regards the simulation of population dynamics.Research contributions(e.g.[14,61])de®ned the basis of this approach,and constituted a side important milestone also in the ap-plication of CA to the simulation of the dynamics of populations organization. For instance,change within an organization is a complex phenomenon that in-volves the interaction of many individuals and can be studied by CA in the area of Arti®cial Societies[34].This interaction among independent entities makes CA useful in modeling the di usion of change processes in populations.Other disciplines that are introducing CA-based models and applications are those involved in geography and economic geography.Cellular geography has been introduced by W.Tobler[69]more than20years ago,and today is a central issue in the application of models and computer-based simulation systems[12].In economic geography several models concerning competition and coordination dynamics in the formation of social clusters have been successfully applied on several cases[35,48]. Tra c control is another application area that involves CA models and systems. An overview of the main results in this area can be found in[63].The main appli-cations in this area regard both urban and extra-urban tra c,and the CA approach allows the knowledge of the tra c state to be explicitly represented in the model in order to simulate crucial situations(i.e.,tra c jams).Also Arti®cial Vision has been approached by CA models[49].The most mean-ingful application area is edge detection of images in automotive[1].Another sug-gestive application®eld of CA concerns graphics applications.Examples of this novel CA topic are etherogeneous.Virtual clay modeling[2]and the texture gen-eration by CA[66]have been performed.In the late example,arti®cial evolution of RD textures,maze formation and zebra formation examples have been simulated.In [65]parallel particle systems are applied to the cases of¯ames,¯ames in the wind, trickle of water(steps and slope),collision and scatter,aggregation of particles.548S.Bandini et al./Parallel Computing27(2001)539±5535.Parallel implementation of CAsAlthough CAs have been conceived at a time when the computing tools which were available to the majority of researchers were pen and pencil,they seem to be ``born for computers'',as the use of discrete time and discrete state space perfectly ®ts the features of digital computers.Actually,CA and computers were born at about the same time,and one might speculate upon the fact that the inventor of the CAs approach,John von Neumann,has been also deeply involved in the develop-ment of digital computers,so the relationship might not be due to chance. Unknown at the time of their conception,there is another feature of CA which makes them well suited also for simulation on parallel computers,which do not conform to the von Neumann architecture,namely locality of interactions.More-over,the regular topologies that are used in CA allow the use of straightforward parallelization methods.It is trivial to observe that some global information is also needed for simulating a CA,for example the parameters of the transition function that must be uniform over the entire grid.While in classical,textbook cases these parameters are®xed once and for all,there may be cases where they may change in time,and must do so in a globally coherent way.There is of course some fuzziness concerning the de®nition of a CA;while the classical``basic case''is that of a fully homogeneous automaton with a discrete state space,the requirements related to the application of a CA approach to real problems have led many researchers to``enlarge the paradigm''.Among the most important extensions,let us recall the introduction of inhomogeneous automata,where dif-ferent cells may be ruled by di erent transition functions,and of continuous state spaces(for a discussion see[32,33,75].Inhomogeneous automata are necessary to deal with systems with physical boundaries,whose behavior di ers from that of the bulk cells;continuous state spaces are necessary,e.g.in lattice Boltzmann or in macroscopic CA,in order to deal with a coarser graining of physical systems than that which is typical of lattice gases.For the sake of de®niteness,let us consider the case of macroscopic CAs[33], where the state variables refer to macroscopic quantities like,for example,concen-trations of chemicals in a given¯uid phase.In this case,the transition function of every cell might require the knowledge of phenomenological parameters,e.g.par-tition coe cients of a given chemical among di erent phases,which may depend upon physical parameters like the temperature.If the system is not held at®xed temperature,this parameter may change in time,and there is a need to make available the corresponding information to each cell.It is possible,in principle,to introduce(local)heat transport mechanisms into the model,but this may be inconvenient,or computationally heavy,so a macroscopic description might require global variables which are determined from``outside''the system itself.And it is of course necessary to provide each cell which the necessary information.Moreover,there may be cases where a CA model is coupled with a parameter estimation algorithm,like e.g.genetic algorithms[31].The whole procedure which。
Embedding cellular automata into reversible ones
Peter Hertling
Department of Computer Science University of Auckland
CDMTCS-065crete Mathematics and Theoretical Computer Science
Embedding Cellular Automata into Reversible Ones
Peter Hertling Department of Computer Science, University of Auckland Private Bag 92019, Auckland, New Zealand email: hertling@
The
author was supported by the DFG Research Grant No. HE 2489/2-1.
1
is negative. This question was restated by Culik, Hurd, and Yu [4] in the context of computational aspects of cellular automata. We show that this is in general impossible, thus proving To oli's conjecture. Only when one does not impose any e ectivity condition on an embedding, one can embed an arbitrary cellular automaton into a reversible cellular automaton of the same dimension, and in fact, then even into a reversible cellular automaton of dimension one. But as soon as one demands that the embedding respects the uniform structure of cellular automata in at least a weak sense | which leads to the notion of a weak embedding | one obtains a negative answer. We recall that a con guration c in the con guration space of a cellular automaton with global map F is called a Garden of Eden con guration if there is no con guration from which c can be reached via F . Hence, a cellular automaton has a Garden of Eden con guration if and only if it is not surjective. Starting with Moore's paper [10], in which the notion of a Garden of Eden con guration was introduced, a series of papers by Myhill [11], Richardson [12], Maruoka and Kimura [9], and others have led to interesting other characterizations of surjective cellular automata and the relations between injectivity and surjectivity for cellular automata. The following two results will be derived in the last section from the technical main result, which is stated in terms of spatially periodic con gurations. A cellular automaton which possesses a Garden of Eden con guration cannot be weakly embedded into a reversible cellular automaton of the same dimension. For one-dimensional cellular automata we obtain a slightly stronger result. An irreversible cellular automaton of dimension one cannot be weakly embedded into a reversible cellular automaton of dimension one. In the following section we provide precise de nitions of a cellular automaton and of the embedding notions which we consider. Then, in the section about positive results we restate To oli's [14] result and give a complete and simpli ed proof. Furthermore we show that every cellular automaton can be embedded in an ine ective, purely set-theoretic way into a very simple, reversible, one-dimensional cellular automaton. Since this embedding does not make much sense, in Section 4 we consider weak embeddings, which respect the basic structure of cellular automata in a weak sense. First, we show that no cellular automaton can be weakly embedded into any cellular automaton of smaller dimension. Then the main result is proved. A cellular automaton which is not injective on all spatially periodic con gurations cannot be weakly embedded into a cellular automaton of the same dimension which is injective on all spatially periodic con gurations. From this result the two statements above are deduced. We conclude the paper with some remarks about reversible computation by cellular automata.
多重微珠免疫法 英文缩写
多重微珠免疫法英文缩写英文回答：Multiplex bead immunoassay (MBIA) is a high-throughput technique used for the simultaneous quantification of multiple analytes in a single sample. It is based on the principle of flow cytometry, where beads coated with specific antibodies are incubated with the sample. The beads are then washed and analyzed using a flow cytometer, which measures the fluorescence intensity of each bead. The fluorescence intensity is proportional to the amount of analyte bound to the bead.MBIA has several advantages over traditional immunoassays. First, it is highly multiplexed, allowing for the simultaneous quantification of up to 100 analytes in a single sample. Second, it is sensitive, with a lower limit of detection in the picomolar range. Third, it is fast and efficient, with results available in less than an hour.MBIA is used in a wide variety of applications, including:Clinical diagnostics.Drug discovery.Food safety testing.Environmental monitoring.中文回答：多重微珠免疫法（MBIA）是一种高通量技术，用于在单个样品中同时定量分析多种分析物。
前列腺不典型小腺泡增生
ASAP与前列腺微小癌 (m inimal volume p rostatic adeno2 carcinoma,癌占活检组织总量的 5%以下 )之间的鉴别标准 中 ,腺泡数目和病灶大小是最主要的一条 , ASAP腺泡的数目 是癌腺泡数目的 2 /3 (11、17) , ASAP病灶比癌性病灶小一半 (014 mm、018 mm ) 。核增大 、明显的核仁 、核分裂象 、腔内蓝 色黏液及并存 P IN等形态特征在前列腺微小癌中更明显 ,但 核深染及中 ～重度萎缩在 ASAP 比癌中更为常见 (分别为 44%、9%和 59%、35% ) 。 100%前列腺微小癌呈浸润性生 长 ,但浸润性的生长方式也存在于 75%的 ASAP病例中 。嗜 酸性颗粒性分泌物与类晶体在两者无明显差异 [12 ] 。
前列腺癌占男性恶性肿瘤的第 2位 ,在发达国家 ,前列 腺癌占全部恶性肿瘤的 19% ,在发展中国家为 513% [1 ] 。前 列腺穿刺活检是发现和确诊前列腺癌的重要手段 ,但穿刺标 本中经常会遇到少量不典型腺泡 ,疑似癌却又不能确定为 癌 ,这便是前列腺不典型小腺泡增生 ( atyp ical small acinar p roliferation, ASAP) 。现将 ASAP形态特征 、诊断标准 、发病 率 、临床意义以及对发现前列腺癌的预测价值等作一综述 。
1 A SA P的病理特征及应用现状
ASAP也称不典型腺体 ( atyp ia / atyp ical glands) [2 ] ,是由 Bostw ick等 [3 ]于 1993年首次提出的一个描述不典型腺样前 列腺增生的诊断术语 。4 年后这一诊断的临床意义得到首 次阐述 [4 ] 。
ASAP为不典型腺泡病变 ,表现为排列紧密的灶性增生 的小腺泡集落 。这些小腺泡被覆一层几近透明的分泌细胞 上皮 ,而基底细胞呈断片状或消失 (可经 34βE12 免疫组化 证实 ) 。组织特点为 : ①有限数量的腺体 ; ② 极少腺体出现 细胞不典型性 ,包括核增大 、核仁增大 ; ③ 组织异型 :缺乏核 异型的小腺泡杂乱无章地排列 ; ④ 腔内可见蓝色黏液 、结晶 体或粉红色蛋白样分泌物 [5 ] 。这些腺泡的结构形态和 /或细 胞形态类似于分化较好的前列腺癌 ,但数量太少 ,只是怀疑 为癌但不能明确诊断 。不足以诊断为癌而做出 ASAP这一 诊断主要见于两种情况 [6 ] : ①质的方面 ,缺乏足够的前列腺 癌细胞和组织结构特点 。例如一个病灶可能包括 12 个腺 泡 ,腺泡缺乏基底细胞层 ,呈浸润性生长 ,但细胞形态和组织 结构上尚未达到癌的诊断标准 (如缺少明显的核仁和明显 的核增大 ) ; ②量的方面 ,包含的腺泡数量太少 ,腺泡的细胞 和组织结构方面已经达到癌的诊断标准 ,但病灶的大小是其 主要限制 (如 1～3个腺泡 ) 。
典型跟驰模型的特征与性能分析
典型跟驰模型的特征与性能分析陈征;闫冬梅;刘钊;郭建华【摘要】为对比分析传统的跟驰模型在描述车辆行驶特性中的应用特征,从模型形式和基本特征两方面对典型的刺激-反应类GM模型、安全距离类Gipps模型、优化速度类FVD模型进行了对比分析.为验证以上理论分析结果,对3种跟驰模型分别进行了数值仿真分析,并分别对前后车之间的速度变化关系以及位置变化关系进行了对比分析.实验结果表明,相较于GM模型与Gipps模型,FVD模型在应用中更符合实际情况,能够较为准确地描述单一车辆加速或减速的行驶特性.【期刊名称】《交通科技》【年(卷),期】2018(000)003【总页数】5页(P98-102)【关键词】跟驰模型;微观交通仿真;GM模型;Gipps模型;FVD模型【作者】陈征;闫冬梅;刘钊;郭建华【作者单位】南京理工大学自动化学院南京 210094;东南大学智能运输系统研究中心南京 210018;东南大学智能运输系统研究中心南京 210018;东南大学智能运输系统研究中心南京 210018【正文语种】中文车辆跟驰(Car Following，CF)模型主要研究前车行驶过程中状态改变所引起的后车相应的变化行为，通过车辆逐一跟驰的方式描述单一车道上的交通流特性，建立驾驶员微观行为与交通流宏观现象之间的联系。
在过去60多年的发展过程中，学者们相继提出了许多不同形式的跟驰模型，取得了丰富的研究成果[1]。
车辆跟驰模型在微观交通仿真、交通安全评价和通行能力分析等领域得到了广泛应用。
因此，对跟驰模型进行充分研究，从而揭示交通流运行的内在机理，完善微观仿真系统，提高交通仿真的现实性，具有重要的理论价值和现实意义。
本文首先阐述跟驰模型的发展背景，然后分析典型模型GM模型、Gipps模型和全速度差模型的基本形式、假设条件和基本特性。
最后，通过实例研究，对比分析不同跟驰模型下车辆跟驰过程中的位置、速度和加速度等参数的变化，分析车辆行驶状态的变化。
调制线粒体钙作为阿尔茨海默氏症的药物靶老龄化住宅
Ageing Research Reviews 9 (2010) 447–456Contents lists available at ScienceDirectAgeing ResearchReviewsj o u r n a l h o m e p a g e :w w w.e l s e v i e r.c o m /l o c a t e /a rrReviewModulation of mitochondrial calcium as a pharmacological target for Alzheimer’s diseaseClara Hiu-Ling Hung a ,Yuen-Shan Ho a ,Raymond Chuen-Chung Chang a ,b ,c ,∗aLaboratory of Neurodegenerative Diseases,Department of Anatomy,LKS Faculty of Medicine,The University of Hong Kong,Pokfulam,Hong Kong,China bResearch Centre of Heart,Brain,Hormone and Healthy Aging,LKS Faculty of Medicine,The University of Hong Kong,Pokfulam,Hong Kong,China cState Key Laboratory of Brain and Cognitive Sciences,The University of Hong Kong,Pokfulam,Hong Kong,Chinaa r t i c l e i n f o Article history:Received 8February 2010Received in revised form 14May 2010Accepted 19May 2010Keywords:Mitochondria CalciumAlzheimer’s diseaseVoltage dependent anion channel Mitochondrial membrane potentiala b s t r a c tPerturbed neuronal calcium homeostasis is a prominent feature in Alzheimer’s disease (AD).Mito-chondria accumulate calcium ions (Ca 2+)for cellular bioenergetic metabolism and suppression of mitochondrial motility within the cell.Excessive Ca 2+uptake into mitochondria often leads to mitochon-drial membrane permeabilization and induction of apoptosis.Ca 2+is an interesting second messenger which can initiate both cellular life and death pathways in mitochondria.This review critically discusses the potential of manipulating mitochondrial Ca 2+concentrations as a novel therapeutic opportunity for treating AD.This review also highlights the neuroprotective role of a number of currently available agents that modulate different mitochondrial Ca 2+transport pathways.It is reasoned that these mitochondrial Ca 2+modulators are most effective in combination with agents that increase the Ca 2+buffering capacity of mitochondria.Modulation of mitochondrial Ca 2+handling is a potential pharmacological target for future development of AD treatments.© 2010 Elsevier B.V. All rights reserved.1.IntroductionAs the average life span of human population gradually increases,the prevalence of age-related diseases has significantly increased.Alzheimer’s disease (AD)is a fatal neurodegenerative disorder,affecting approximately 35.6million people worldwide (Prince and Jackson,2009).AD is the most common form of dementia.The disease is characterized by progressive synaptic dys-function and neuronal loss in various brain regions,especially in the cortex and hippocampus.Severe neurodegeneration in these brain regions results in cognitive,emotion,social and motor impair-ments.With more than a 100years of research,the underlying mechanism of this incurable disease still remains elusive.Per-turbed neuronal calcium (Ca 2+)homeostasis is a common feature in many neurodegenerative diseases including AD,amyotrophic lat-eral sclerosis (ALS),ischemic stroke and Parkinson’s disease (PD)(Mattson and Chan,2003).Increasing lines of evidence support the idea that Ca 2+dysregulation plays a key role in AD pathogenesis∗Corresponding author at:Rm.L1-49,Laboratory Block,Faculty of Medicine Building,Department of Anatomy,LKS Faculty of Medicine,21Sassoon Road,Pok-fulam,Hong Kong SAR,China.Tel.:+852********;fax:+852********.E-mail address:rccchang@hku.hk (R.C.-C.Chang).(Bezprozvanny,2009;Bojarski et al.,2008;LaFerla,2002;Mattson and Chan,2003;Yu et al.,2009).2.Neuronal Ca 2+dysregulation and Alzheimer’s disease Ca 2+signaling is essential for life and death processes includ-ing neuronal excitability,synaptic plasticity,gene transcription and apoptosis (Berridge,1998;Berridge et al.,1998).The Ca 2+dysregulation hypothesis postulates that sustained increase in cytosolic Ca 2+concentrations can lead to neurodegeneration in AD (Khachaturian,1994;Toescu and Verkhratsky,2007).Disturbances in Ca 2+signaling have been found in both sporadic and familial cases of AD (LaFerla,2002).Several age-related perturbations in pathways regulating Ca 2+homeostasis have been reported,sug-gesting a possible linkage between aging and the development of sporadic AD (Bezprozvanny,2009).A small proportion of AD patients (∼5%)suffer from an early-onset familial form that occurs under age of 65(Hardy,2006).The genes involved in familial AD include presenilins (presenilin 1and 2)and amyloid precursor pro-tein (APP)(Hardy and Gwinn-Hardy,1998).Both have been shown to play important roles in Ca 2+signaling (LaFerla,2002).The mech-anisms of how Ca 2+homeostasis is disrupted in AD have been extensively reviewed (Bezprozvanny,2009;Bojarski et al.,2008;LaFerla,2002;Mattson and Chan,2003;Yu et al.,2009).In the fol-1568-1637/$–see front matter © 2010 Elsevier B.V. All rights reserved.doi:10.1016/j.arr.2010.05.003448 C.H.-L.Hung et al./Ageing Research Reviews9 (2010) 447–456lowing sections,we will briefly discuss this issue for readers to understand how Ca2+dyshomeostasis is linked with AD.2.1.APP mutation induces Ca2+influx and elevates cytosolic Ca2+ concentrationsAccumulation of senile plaques and neurofibrillary tangles are two important pathological hallmarks in AD brains.Senile plaques are made of beta-amyloid(A)peptides which are derived from APP.Mutations associated with familial AD result in increased pro-duction of the amyloidogenic Afragments(Mattson,1997).APP derivatives such as secreted forms of APP(sAPP),A-containing fragments,and APP intracellular domain(AICD)have been shown to modulate cellular Ca2+signaling(Leissring et al.,2002;Mattson et al.,1993,1992).Aaggregates have been found to form cation-selective ion channels in the plasma membrane,resulting in increased cytosolic Ca2+concentrations(Arispe et al.,1993a,b; Kagan et al.,2002).Nevertheless,how A-induced membrane pores are related to human AD is still unclear.Oxidative dam-age is another mechanism by which Acauses disruption in Ca2+ homeostasis and neurotoxicity(Hensley et al.,1994;LaFerla,2002). Accumulation of Aleads to formation of reactive oxygen species (ROS),which promotes DNA damage,lipid peroxidation,protein carbonylation and nitrosylation.Lipid peroxidation modifies func-tions of membrane transporters and ion channels(Mark et al., 1995),which in turn further elevates basal cytosolic Ca2+concen-trations,forming a vicious cycle(LaFerla,2002;Mattson and Chan, 2003).2.2.Presenilins modulate ER Ca2+signaling and enhance ER Ca2+ releasePresenilins(PS1and PS2)are components of the␥-secretase complex which are involved in the proteolytic cleavage of APP.PS1 and PS2are located in various intracellular compartments such as the endoplasmic reticulum(ER)(Annaert et al.,1999),Golgi apparatus(Annaert et al.,1999),and mitochondria(Ankarcrona and Hultenby,2002).Notably,presenilins are highly enriched in a specific region where the ER membranes are in close contact with mitochondria namely the ER-mitochondrial-associated mem-branes(MAM)(Area-Gomez et al.,2009).FAD-linked presenilin mutations are believed to alter the activ-ity of␥-secretase such that more Aare produced,especially the fibrillogenic A1–42peptides(Xia et al.,1997).FAD-related mutant presenilins can also affect ER Ca2+handling independent of Aby exaggerating Ca2+release from the ER in response to agonist stim-ulation.FAD mutant PS1and PS2have been shown to interact with the inositol1,4,5-triphosphate receptor(InsP3R)Ca2+-releasing channels and enhance their gating activity by a gain-of-function effect(Cheung et al.,2010,2008).InsP3Rs are more likely to be in a high-probability burst mode,resulting in enhanced ER Ca2+release (Cheung et al.,2010).However the molecular mechanism of this modulation remains elusive.Depletion of ER Ca2+store triggers Ca2+influx from extracellu-lar space via store-operated Ca2+channels(Putney,1986).This is known as capacitive Ca2+entry(CCE or store-operated Ca2+entry). Stromal interacting molecule1(STIM1)protein acts as Ca2+-sensors on the ER which interacts with Orai1/TRPC channels in the plasma membrane and activates store-operated channels for Ca2+entry (Ong et al.,2007;Zhang et al.,2005).CCE has been shown to be attenuated by presenilin mutants,possibly due to increased Ca2+ in the ER store(Herms et al.,2003;Leissring et al.,2000;Yoo et al.,2000).Moreover,increased levels of STIM1have been found in mouse embryonicfibroblasts lacking presenilins,implicating that expression of STIM1may be presenilin-dependent(Bojarski et al., 2009).2.3.Ca2+-dependent tau phosphorylation and dephosphorylationNeurofibrillary tangles formed by hyperphosphorylation of the microtubule-associated protein tau are another hallmark in AD.The phosphorylation state of tau is highly Ca2+-dependent. Tau phosphorylation is regulated by Ca2+-dependent calmodulin-dependent protein kinase II(CaMKII)and calpain(Litersky et al., 1996;Maccioni et al.,2001).Activation of cyclin-dependent pro-tein kinase5(Cdk5)by calpain via p25has been suggested to play a role in tau hyperphosphorylation(Maccioni et al.,2001). On the other hand,calcineurin,a Ca2+/calmodulin-dependent pro-tein phosphatase is involved in tau dephosphorylation(Fleming and Johnson,1995).Tau dephosphorylation was completely atten-uated in rat cerebral-cortical slice pre-treated with the calcineurin inhibitor Cyclosporin A(Fleming and Johnson,1995).Injection of FK506(a calcineurin inhibitor)has been reported to enhance tau phosphorylation at various phosphorylation sites in mouse brain (Luo et al.,2008).On the other hand,calcineurin inhibitors have also been shown to increase phosphorylation of glycogen synthase kinase-3beta(GSK-3)at serine-9(Kim et al.,2009).Phosphoryla-tion of GSK-3at serine-9inhibits tau phosphorylation by GSK-3(Hughes et al.,1993).Hence,both increase and decrease cytosolic Ca2+concentrations contribute to tau phosphorylation,therefore perturbed Ca2+homeostasis may associate with the tau pathology in AD.2.4.Sporadic AD:ApoE4and CALHM1Apolipoprotein E is involved in transporting cholesterol from the blood to the cells.Individuals with the allele for the E4isoform of apolipoprotein E(ApoE4)have an increased risk of sporadic AD (Mahley et al.,2006).ApoE4was found to disrupt Ca2+homeosta-sis by triggering extracellular Ca2+influx and amplifying neuronal Ca2+responses(Hartmann et al.,1994;Tolar et al.,1999).Recent research has identified polymorphism of a gene called calcium homeostasis modulator1(CALHM1)that may link with sporadic AD.CALHM1encodes for a protein which forms a Ca2+channel on the plasma membrane and controls Alevels(Dreses-Werringloer et al.,2008).Since then several studies have shown that the P86L polymorphism of CALHM1is associated with AD(Boada et al.,2010; Cui et al.,2010),whilst other studies failed tofind a link between CALHM1and risk of AD(Bertram et al.,2008;Minster et al.,2009; Nacmias et al.,2010;Sleegers et al.,2009).The relevance of CALHM1 in AD remains unclear.2.5.Current“Ca2+-targeted”drugsAs illustrated above,it is clear that Ca2+signaling pathways are highly involved in AD pathogenesis.Several FAD-approved drugs and drugs tested in clinical trials therefore aim to tar-get different Ca2+signaling pathways in order to re-establish the cytosolic Ca2+homeostasis.Memantine(Namenda)is the most common drug for moderate to severe AD.Memantine is a non-competitive N-methyl D-aspartate(NMDA)antagonist.It inhibits Ca2+entry into neurons through the NMDA receptors and therefore reduces excitotoxicity(Bezprozvanny,2009).How-ever,currently it only provides limited benefits for AD patients. Hu et al.(2009)found that specific antagonists targeting at NMDA receptors containing the GluN2B subunit e.g.ifenprodil and Ro25–6981,might be effective in protecting neurons from A-induced inhibition of synaptic plasticity in vivo.EVT-101 (Evotec AG,Hamburg,Germany;/)is a newly developed NMDA receptor subunit2B specific antagonist. Phase I trial of EVT-101is completed and cognitive performance of patients was improved(NCT00526968).This specific NMDA receptor antagonist is believed to greatly reduce the chance ofC.H.-L.Hung et al./Ageing Research Reviews9 (2010) 447–456449Fig.1.Life and death pathways of mitochondrial Ca2+accumulation.Left:Under normal conditions,Ca2+influx from extracellular matrix or Ca2+release from the ER causes increase in cytosolic Ca2+concentration([Ca2+]i).Mitochondria rapidly take up cytosolic Ca2+,which is crucial for life processes such as mitochondrial movement,Ca2+ homeostasis and bioenergetic metabolism.Right:When mitochondria are overloaded with Ca2+,mitochondrial permeability transition pores will be triggered to open. Several pro-apoptotic factors will be released to the cytosol,thereby inducing apoptosis.side effects caused by the unspecific NMDAR antagonist meman-tine.Nimodipine is an isopropyl Ca2+channel blocker which has been shown to improve cognitive performance of dementia patients including AD(Lopez-Arrieta and Birks,2002).MEM-1003(Memory Pharmaceuticals,Montvale,New Jersey,USA; /)is a nimodipine-related neu-ronal L-type Ca2+channel antagonist.Phase IIa clinical trial has recently been completed(NCT00257673),but failed to show sig-nificant improvements in patients(Hareyan,2007).Evidence from NMDA receptor antagonists and Ca2+channel blockers indicates that decreased Ca2+flux into neurons may benefit AD patients.Indeed,classic therapies which aim to compensate the level of acetylcholine in AD patients also cause alteration in Ca2+home-ostasis.FAD-approved acetylcholinesterase(AChE)inhibitors e.g. Donepezil,Galatamine,and Rivastigmine inhibit degradation of acetylcholine and therefore increase acetylcholine concentrations in the brain which is believed to associate with improvement in cognitive functions.In fact,the AChE inhibitors will cause an increase opening of acetylcholine receptors,which are receptor-activated Ca2+channels themselves.The two major classes of FAD-approved AD drugs(NMDA receptor antagonists and AChE inhibitors)apparently will have opposite effects on cytosolic Ca2+ concentration,implying that there is evidence for both increased and decreased cytosolic Ca2+in AD.Dimebon(Latrepirdine)(Medivation Inc.,San Francisco,CA)is an antihistamine drug used in Russia(Bachurin et al.,2001).Recent studies have discovered the novel role of Dimebon as a neuropro-tective agent as well as a cognition-enhancing agent(Bachurin et al.,2001).As an antagonist of NMDAR and Ca2+channels,Dimebon protects neurons by preventing NMDA and Ca2+-induced neurotox-icity(Bachurin et al.,2001).On the other hand,it also increases the level of acetylcholine by inhibiting the AChE(Bachurin et al.,2001). Phase II clinical trial reported that Dimebon is well tolerated and exhibit significant improvements in patients with mild to moder-ate AD(Doody et al.,2008).However,a recent Phase III clinical trial failed to show the same promising results(Neale,2010).Additional Phase III clinical trials of Dimebon are still on-going at the moment; therefore the effectiveness of Dimebon in AD remains debatable.Most of the current AD treatments such as AChE inhibitors can provide a one-time elevation of cognitive performance.How-ever,the decline of cognitive ability from this elevated level will occur with the same speed as in non-treated patients.This urges researchers to seek for disease-modifying drugs.3.Mitochondrial Ca2+governs neuronal life and death pathwaysMitochondria are important in maintaining neuronal Ca2+ homeostasis.Normal mitochondrial functions are extremely important for neurons,as neuronal activities such as synaptic transmission and axonal transport require high level of energy. In particular,mitochondrial Ca2+levels are crucial for maintaining cellular functions including bioenergetic metabolism.On the other hand,excessive Ca2+uptake into mitochondria results in rupture of the outer mitochondria membrane,which may then lead to ini-tiation of apoptosis.However,this phenomenon is likely to occur only in vitro.The regulatory systems maintaining the mitochondrial Ca2+homeostasis thus provide an attractive therapeutic target in treating AD.In the following sections we will explain how mito-chondrial Ca2+is involved in life and death pathways in the cell (Fig.1),and how mitochondrial Ca2+is linked to AD.3.1.The cell life pathway:physiological roles of mitochondrialCa2+uptakeCa2+uptake into mitochondria plays a key role in cellular ATP production and mitochondrial motility.Bioenergetic metabolism in mitochondria highly relies upon Ca2+.In the mitochondrial matrix,activity of the metabolic enzymes involved in the Krebs450 C.H.-L.Hung et al./Ageing Research Reviews9 (2010) 447–456cycle(pyruvate,␣-ketoglutarate,and isocitrate dehydrogenases) is all Ca2+-dependent(Rizzuto et al.,2000).Ca2+directly regulates ␣-ketoglutarate and isocitrate dehydrogenases,whilst pyruvate dehydrogenases are activated by Ca2+-dependent phosphatases (Rizzuto et al.,2000).Ca2+concentration in mitochondria therefore determines the rate of ATP synthesis for the cell.Mitochondria are mobile organelles which travel along the axons to regions of increased energy need in the cell,such as synapses(Chang et al.,2006;Hollenbeck and Saxton,2005). Microtubules-dependent mitochondrial motility is regulated by the kinesin1/Miro/Milton complex(Glater et al.,2006;Guo et al., 2005;Stowers et al.,2002).Miro(mitochondrial Rho GTPase)is a mitochondrial outer membrane protein.The activity of Miro is Ca2+-dependent due to the presence of a pair of Ca2+-binding EF hand motifs(Frederick et al.,2004).Milton is a cytoplasmic protein which binds with Miro to form a protein complex that links kinesin-1to mitochondria for anterograde transport(Glater et al.,2006;Guo et al.,2005;Stowers et al.,2002).The Ca2+-binding EF-hand domain of Miro is essential for Ca2+-dependent mitochondrial movement. Elevated Ca2+causes kinesin heavy chain to dissociate with micro-tubules,suppressing mitochondrial motility(Wang and Schwarz, 2009).Ca2+-dependent mitochondrial motility is crucial for dis-tribution of mitochondria in neurons.It recruits mitochondria to cellular regions with the need of ATP supply and Ca2+buffering e.g. activated synapses(Macaskill et al.,2009).In addition,Miro is essential for regulation of mitochondrial morphology.At resting low cytosolic Ca2+levels,Miro facil-itates the formation of elongated mitochondria by inhibiting dynamin-related protein1(Drp-1or dynamin-like protein1,DLP-1)-mediatedfission(Saotome et al.,2008).On the other hand, high cytosolic Ca2+triggers fragmentation and shortening of mito-chondria(Saotome et al.,2008).Miro-mediated redistribution of mitochondria has also been shown to increase their ability to accumulate Ca2+(Saotome et al.,2008).Evidence from the above studies demonstrates that Miro acts as a cytosolic Ca2+-dependent regulator of mitochondrial dynamics.Meanwhile,calcineurin,a Ca2+-dependent phosphatases,has been shown to regulate the translocation of cytosolic Drp-1via dephosphorylation duringfis-sion(Cereghetti et al.,2008).Clearly,Ca2+regulates motility,distribution,morphology and functions of mitochondria in physiological conditions.It is there-fore crucial to maintain mitochondrial Ca2+homeostasis for normal cellular functioning.If this homeostasis is disrupted,a death signal can be resulted.3.2.The cell death pathway:mitochondrial Ca2+overload triggers intrinsic apoptosisThe physiological Ca2+signal can switch to a death signal when the Ca2+level is beyond the threshold.Hence,excessive Ca2+ uptake into mitochondria can be lethal to neurons.The intrinsic (mitochondrial)pathway of apoptosis is triggered by intracellu-lar stress,such as Ca2+overload and oxidative stress(Galluzzi et al.,2009).Mitochondria integrate pro-and anti-apoptotic signals and determine the fate of the cell.If death signals predomi-nate,mitochondrial-membrane-permeabilization(MMP)occurs, and large conductance permeability-transition-pores(PTP)opens (Galluzzi et al.,2009).PTP opening allows uncontrolled entry of solutes and water into the mitochondrial matrix by osmotic forces (Galluzzi et al.,2009).This causes mitochondria to swell and leads to rupture of the outer mitochondria membrane,releasing proteins from the intramembrane space e.g.cytochrome c into the cytosol (Galluzzi et al.,2009).MMP results in mitochondrial depolariza-tion,uncoupling of oxidative phosphorylation,overproduction of ROS and release of pro-apoptotic proteins to the cytosol,eventually leading to cell death.When MMP is permanent and numerous mito-chondria are continuously affected,neurons can no longer cope with the stress and apoptosis is initiated(Galluzzi et al.,2009). Physiological mitochondrial Ca2+concentrations do not induce PTP opening,but will work in synergy with pro-apoptotic stim-uli(Rizzuto et al.,2009).The“double hit”hypothesis proposes that apoptotic stimuli have dual targets(Pinton et al.,2008).On one hand,it causes Ca2+release from the ER and subsequent Ca2+uptake by mitochondria.On the other hand,it makes mitochondria more sensitive to potential Ca2+damaging effects(Pinton et al.,2008).The above pathways are summarized in Fig.1.Given the dual roles of mitochondria Ca2+in neurons,we will critically discuss the possibility of modulating Ca2+in mitochondria as a potential pharmacological target for AD in this review.4.Mitochondrial Ca2+handling and ADMitochondrial dysfunction is a prominent feature in AD.Ahas been found in mitochondria of AD brain and transgenic mouse model of AD overexpressing A.Apeptides accumulate in mito-chondria and are associated with oxidative stress,disrupted Ca2+ homeostasis,impaired energy metabolism and induction of apop-tosis(Mattson et al.,2008).Mitochondria from aged cerebellar granular neurons are depolarized and less efficient in handling Ca2+ load(Toescu and Verkhratsky,2007).Cortical mitochondria from 12-month-old mice also show a reduced capacity for Ca2+uptake when challenged with CaCl2pulses,compared to that of6-month-old mice(Du et al.,2008).Mitochondria isolated fromfibroblasts of AD patients exhibit reduced Ca2+uptake compared to age-matched control,suggesting that Ca2+buffering ability may be impaired in the mitochondria of ADfibroblasts(Kumar et al.,1994).Follow-ing oxidative stress,the increase in Ca2+uptake in mitochondria of ADfibroblasts is much greater than that in control,implicat-ing that mitochondria from ADfibroblasts have a higher sensitivity towards oxidative stress(Kumar et al.,1994).Mitochondria with over-expression of human APP also show a lower Ca2+capacity compared to non-transgenic mitochondria(Du et al.,2008).A1–42 oligomer induces Ca2+overload in mitochondria in both cortical and cerebellar granular neurons(Sanz-Blasco et al.,2008).The increase is limited to a pool of mitochondria close to the sites of Ca2+entry and release(Sanz-Blasco et al.,2008).Ca2+overload in mitochondria causes increased ROS production and impairment of bioenergetic metabolism which eventually leads to cell death. Mutations in presenilins may promote mitochondrial dysfunction by perturbing ER Ca2+handling,which promotes synaptic mito-chondrial Ca2+overload and in turn triggers apoptosis.A recent study has also shown that mutated CALHM1may cause slower kinetics of mitochondrial Ca2+uptake and release,increasing the risk of mitochondrial Ca2+overload(Moreno-Ortega et al.,2010).The importance of mitochondrial Ca2+in apoptosis has been emphasized in neuronal death in AD.However,mitochondrial Ca2+ is also important in earlier stages of the disease.The rupture of mitochondrial membrane caused by Ca2+overload reduces the number of“healthy”mitochondria,and this will affect crucial neu-ronal functions including synaptic transmission and axonal trans-port.This could perhaps account for some of the early symptoms of the disease e.g.memory impairment.In this notion,the main-tenance of mitochondrial Ca2+homeostasis is important for both early and later stages of the disease.In the following paragraphs, we will illustrate different influx and efflux pathways regulating the mitochondrial Ca2+homeostasis,and how different agents tar-geting these pathways can provide neuroprotection in AD.5.Mitochondria in neuronal Ca2+signalingCa2+signaling causes transient changes in cytosolic Ca2+con-centration.Mitochondria rapidly take up Ca2+when a physiologicalC.H.-L.Hung et al./Ageing Research Reviews 9 (2010) 447–456451Table 1Current agents showing neuroprotective effect via modulation of mitochondrial Ca 2+concentrations. «(mitochondrial membrane potential);Ca 2+(calcium ions);FCCP [carbonyl cyanide-p-(trifluoromethoxy)phenylhydrazone];mAPP (mutant amyloid precursor protein);mPTP (mitochondrial permeability transition pore);NMDA (N-methyl D-aspartate);NSAIDs (non-steroid anti-inflammatory drugs),TAB (Tournefolic acid B);VDAC (voltage-dependent anion channel).Agent/Drug Site of action EffectModelNeurotoxicity model ReferenceFCCP DepolarizationReduce Ca 2+uptake Rat cerebellar granule neurons Rat cortical neuronsA 1–42oligomer Sanz-Blasco et al.(2008)NSAIDS DepolarizationReduce Ca 2+uptake Rat cerebellar granule neurons A 1–42oligomer Sanz-Blasco et al.(2008)Minocycline VDACDepolarizationReduce Ca 2+uptake Rat cerebellar granule neurons NMDAGarcia-Martinez et al.(2010)KB-R7943Na +/Ca 2+exchanger Reduce Ca 2+uptake Rat cerebellar granule neurons Glutamate Storozhevykh et al.(2009)TABUnknown Reduce Ca 2+uptake Rat cortical neurons A 25–35Chi et al.(2008)DimebonmPTPInhibit mPTP opening Rat liver mitochondriaA 25–35Bachurin et al.(2003)Cyclosporin ACyclophilin DInhibit mPTP opening Increase Ca 2+buffering capacityMouse cortical mitochondriamAPPTrangenic miceDu et al.(2008)stimulus elicits an increase in cytosolic Ca 2+concentrations.This uptake machinery allows mitochondria to act as “Ca 2+buffers”to maintain the normal homeostasis.At the same time,it also provides Ca 2+for various mitochondrial functions.Mitochondrial Ca 2+sig-naling therefore plays an important role in determining the fate of neurons.Mitochondria possess various Ca 2+influx and efflux path-ways (Fig.2),which provide attractive targets for manipulation of Ca 2+concentrations within the organelle (Table 1).5.1.Pathways for Ca 2+uptake5.1.1.Voltage-gated anion channel regulates Ca 2+uptake in theouter mitochondrial membraneThe outer mitochondrial membrane (OMM)is relatively per-meable to Ca 2+due to the high conductance voltage dependent anion channel (VDAC)located in this membrane.Over-expression of VDAC has been shown to promote Ca 2+uptake into mitochon-dria (Rapizzi et al.,2002).Closure of VDAC enhances Ca 2+influx into mitochondria,thereby promoting mitochondrial permeabil-ity transition and subsequent cell death (Rizzuto et al.,2009;Rostovtseva et al.,2005;Tan and Colombini,2007).5.1.2.Mitochondrial membrane potential regulates Ca 2+entry via the uniporter in the inner mitochondrial membraneIn the inner mitochondrial membrane (IMM),the mitochon-drial Ca 2+uniporter regulates Ca 2+entry into mitochondria.The uniporter is a highly selective divalent cation channel (Kirichok et al.,2004).The electron transport chain (ETC)in the IMM con-Fig.2.Mitochondrial Ca 2+signaling pathways. «m (mitochondrial membrane potential);[Ca 2+]m (mitochondrial Ca 2+concentration);[Ca 2+]c ,(cytosolic Ca 2+con-centration);H +(hydrogen ions);PTP (mitochondria permeability transition pore);Na +(sodium ions),VDAC (voltage-dependent anion channel);CypD (cyclophilin D);ANT (adenine nucleotide translocase).sists of five protein complexes for the production of ATP.The ETC maintains an electrochemical gradient of −180mV across the IMM,and is known as the mitochondrial membrane potential ( «m ). «m provides a driving force for Ca 2+to enter the mitochondria via the uniporter.Given that mitochondrial Ca 2+overload can lead to cell death,depolarization of «m (hence reduced driving force for Ca 2+entry)can be a drug target for stopping excessive Ca 2+from entering mitochondria.5.2.Pathways for calcium efflux5.2.1.Antiporters and permeability transition pores for mitochondrial calcium sequestrationBesides various Ca 2+uptake systems mentioned,there are also a few pathways for Ca 2+efflux.The Na +/Ca 2+and H +/Ca 2+antiporters are two main routes for Ca 2+release from mitochondria.Generally,3Na +and 3H +enter mitochondria via the respective antiporters when a Ca 2+is extruded (Fig.2).Hence,concentrations of Na +and H +can affect Ca 2+concentration in the mitochondria.These efflux pathways can become saturated when there is high Ca 2+concentration in the matrix,which can lead to mitochondrial Ca 2+overload (Rizzuto et al.,2009).As mentioned earlier,mitochon-drial Ca 2+overload triggers opening of PTP which locates across the OMM and IMM.The molecular identity of PTP is still uncer-tain,but it is suggested to be a multimeric complex composed of the VDAC,an integral protein called adenine nucleotide translo-case (ANT)on the IMM,and a matrix protein called cyclophilin D (CypD).However,mitochondria lacking VDAC (Szalai et al.,2000)and ANT (Kokoszka et al.,2004)have been shown to undergo Ca 2+-induced PTP opening,implying that the two components may not be prerequisite for MPT (Rizzuto et al.,2009).PTP is a non-selective channel of which operation is dependent on the mitochondrial matrix Ca 2+.High Ca 2+levels in the mitochondrial matrix activate translocation of CypD to the IMM.CypD binds to ANT and inhibits ATP/ADP binding,thereby inducing opening of PTP (Rizzuto et al.,2009).5.3.ER/mitochondria calcium crosstalk is important for efficient mitochondrial calcium signalingMitochondria rapidly take up Ca 2+released from the ER.The proximate juxtaposition between these two organelles ensures efficient Ca 2+transfer (Rizzuto et al.,1993,1998).In fact,the contact between the ER and mitochondria is estimated to be 5–20%of the total mitochondrial surface (Rizzuto et al.,1998).MAM is a region between the ER and mitochondria enriched with enzymes and proteins involved in lipid biosythesis and Ca 2+sig-naling between the organelles (Vance,1990).Indeed,VDAC on the OMM is located in the interface between the ER and mitochon-。
翻译——精选推荐
细胞分子生物学文章第十卷（2005），711-719 pl2005.7.15寄出200510.6收到脂质体：一项先进制造技术的概述新西兰，北帕默斯顿，专用邮袋11222，梅西大学Riddet中心，M.REZA MOZAFARI摘要：近几十年来，脂质体作为生物膜的理想模型，也是药物、诊断、疫苗、营养物和其他生物活性剂的有效载体，引起了广泛关注。
在不同背景下研究者们对脂质体学领域的文献报道广泛地不断地增加，这表明这一领域引人入胜。
自从大约40年前脂质体被介绍到科学界，许多技术和方法在或大或小的脂质体制造规模上得到发展。
这篇文章将在大体上提供脂质体制备方法优缺点的概览，特别强调在我们实验室开发的加热法，作为一种脂质囊泡快速生产的模式技术。
关键词：载体系统，加热法，脂质囊泡，脂质体学，制造技术引言脂质体科学技术是一个正在飞速发展的科学，举几个例子，它用于诸如药物递送，化妆品，生物膜的结构和功能，探索生命起源等领域。
这是由于脂质体有一些有利的特性，例如，它不仅能包含水溶性药物也能包含脂溶性药物，在体内识别特定靶向位点，在流动性、大小、电荷、层数的方面具有多样性。
脂质体作为生物膜模型的应用限于在实验室中研究，它们在生物活性剂的包载和递送的成功应用不仅取决于脂质体载体可以达到预期目的的优越性的示范，还取决于技术和经济可行性的规划。
对于递送应用，脂质体配方应该具有高包封率，窄粒度分布，持久稳定性和理想的释放特性（根据预期的应用）。
这些要求制备方法有产生脂质体的可能性，且脂质体可采用多种成分分子，例如：脂质/磷脂可提高脂质体稳定性。
除了上述特性，对于蛋白质、核酸之类敏感的分子/化合物的递送，脂质体也应该能保护复合制剂，防止其退化。
尽管在脂质体上进行了大量的研究开发工作，但只有少数脂质体产品已被批准为人类使用至今。
这也许有许多原因：一些脂质体配方的毒性，分子和化合物在脂质体中的低包封，脂质体载体的不稳定性，脂质载体的不稳定性，特别是大尺度的脂质体生产成本高。
线粒体自噬的英语
线粒体自噬的英语Mitochondrial Autophagy: A Vital Process for Cellular HomeostasisMitochondria, often referred to as the "powerhouses" of cells, play a crucial role in cellular metabolism and energy production. These organelles are responsible for generating the majority of the cell's supply of adenosine triphosphate (ATP), the primary energy currency of the cell. However, mitochondria are not just passive energy producers; they are dynamic structures that undergo constant remodeling and maintenance to ensure optimal function. One of the key mechanisms involved in this process is mitochondrial autophagy, also known as mitophagy.Autophagy is a fundamental cellular process in which damaged or unwanted components are engulfed and degraded within the cell. This process serves as a quality control mechanism, removing dysfunctional organelles, misfolded proteins, and other cellular debris to maintain cellular homeostasis. Mitophagy, a specialized form of autophagy, specifically targets and removes damaged or dysfunctional mitochondria, ensuring the overall health and efficiency of the cellular energy production system.The importance of mitophagy cannot be overstated. Impaired mitophagy has been linked to a variety of disease states, including neurodegenerative disorders, cardiovascular diseases, and metabolic disorders. When mitochondria become damaged or dysfunctional, they can release reactive oxygen species (ROS) and pro-apoptotic factors, leading to cellular stress and potentially triggering programmed cell death (apoptosis). Mitophagy serves as a protective mechanism, selectively removing these damaged mitochondria and preventing the propagation of cellular damage.The process of mitophagy is a highly regulated and complex event, involving a series of coordinated steps. The initial step involves the identification of damaged or dysfunctional mitochondria. This is typically achieved through the detection of specific molecular signals, such as the loss of membrane potential or the accumulation of misfolded proteins within the mitochondria. These signals trigger the recruitment of specialized proteins, known as mitophagy receptors, which act as the "tags" that mark the damaged mitochondria for removal.Once the mitochondria have been identified, the next step is the formation of the autophagosome, a double-membrane vesicle that engulfs the targeted mitochondria. This process is facilitated by a group of proteins known as the autophagy-related (Atg) proteins, which coordinate the assembly and maturation of theautophagosome. The autophagosome then fuses with the lysosome, an organelle rich in digestive enzymes, resulting in the degradation of the mitochondrial contents.The regulation of mitophagy is a delicate balance, as the process must be precisely controlled to ensure the appropriate removal of damaged mitochondria without compromising the overall cellular function. This regulation is achieved through a complex network of signaling pathways and transcriptional programs that respond to various cellular cues, such as oxidative stress, nutrient availability, and energy status.One of the key regulators of mitophagy is the PINK1/Parkin pathway, which has been extensively studied in the context of Parkinson's disease. In this pathway, the PINK1 protein acts as a sensor, detecting the loss of mitochondrial membrane potential and recruiting the E3 ubiquitin ligase Parkin to the damaged mitochondria. Parkin then ubiquitinates specific mitochondrial proteins, marking them for degradation and triggering the mitophagy process.In addition to the PINK1/Parkin pathway, other signaling cascades, such as the AMPK (AMP-activated protein kinase) and mTOR (mechanistic target of rapamycin) pathways, also play crucial roles in the regulation of mitophagy. These pathways respond to changes incellular energy status and nutrient availability, respectively, and modulate the activity of mitophagy-related proteins to maintain cellular homeostasis.The importance of mitophagy extends beyond its role in maintaining cellular health. Emerging evidence suggests that mitophagy may also be involved in various physiological processes, such as development, aging, and adaptation to environmental stressors. For instance, during embryonic development, mitophagy is crucial for the elimination of paternal mitochondria, ensuring the exclusive inheritance of maternal mitochondrial DNA.Furthermore, the dysregulation of mitophagy has been implicated in the pathogenesis of various age-related diseases, including neurodegenerative disorders, cardiovascular diseases, and cancer. Understanding the mechanisms underlying mitophagy and its role in these disease states has become a major focus of research in the field of cellular and molecular biology.In conclusion, mitochondrial autophagy, or mitophagy, is a vital process that ensures the proper maintenance and function of mitochondria within the cell. By selectively removing damaged or dysfunctional mitochondria, mitophagy plays a crucial role in maintaining cellular homeostasis and preventing the propagation of cellular damage. The regulation of mitophagy is a complex anddynamic process, involving a network of signaling pathways and transcriptional programs that respond to various cellular cues. Ongoing research in this field continues to shed light on the importance of mitophagy in both physiological and pathological conditions, paving the way for the development of potential therapeutic interventions targeting this crucial cellular process.。
细胞自动机cellularautomata
Von Neumann 對應用數學的興趣，從流體力學始，並對非線性偏微分方程產生莫大的興趣。而對他而言，數值計算是最可能的「實驗」方法，這也使 Von Neumann 成為今日電腦之奠基者，並因此發展 cellular automata 的理論。
1926年 Von Neumann 以一篇集合論的論文獲得布達佩斯大學的博士學位，然後以 Rockefeller 獎學金前往哥廷根大學跟隨 Hilbert 作博士後研究，並在柏林，漢堡講學。Von Neumann 在廿餘歲時已經是數學圈中公認的年輕天才。
1930年 Von Neumann 應 Veblen 之邀，到普林斯頓大學客座，1931年普林斯頓大學即授予教授職位，1933年他成為新成立的普林斯頓高等研究院終身職院士。Von Neumann 的家庭宴會在普林斯頓非常熱鬧知名，這在數學家中是很少見的。
Sierpinski's Triangle
細胞自動機 (cellular automata; CA )
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細胞自動機的特點
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細胞自動機的定義與組成
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細胞自動機的發展歷史
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細胞自動機的運作
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細胞自動機的發展
細胞自動機的定義與組成
一種十分新穎的數學演算法。在網格資料結構上（將每一個網格視為一個細胞），利用其空間近鄰性，模擬其空間的自動演化過程。
If the random number is less then 1/3, then the following equations should be applied to X and Y. xn = 0.5 * (xn-1 + 1) yn = 0.5 * yn-1 If the random number is between 1/3 and 2/3, then these equations should be used. xn = xn-1 * 0.5 yn = yn-1 * 0.5 If the number is greater than 2/3, the the following equations should be applied. xn = 0.5 * (xn-1 + 0.5) yn = 0.5 * (yn-1 + 1) Now that X and Y have changed, the point should be plotted on the screen. Finally, loop back to the random number generation and start over again. Only a few hundred iterations are needed to begin to see the triangles. A few thousand pixels will produce a good image.
开启片剂完整性的窗户(中英文对照)
开启片剂完整性的窗户日本东芝公司，剑桥大学摘要：由日本东芝公司和剑桥大学合作成立的公司向《医药技术》解释了FDA支持的技术如何在不损坏片剂的情况下测定其完整性。
太赫脉冲成像的一个应用是检查肠溶制剂的完整性，以确保它们在到达肠溶之前不会溶解。
关键词：片剂完整性，太赫脉冲成像。
能够检测片剂的结构完整性和化学成分而无需将它们打碎的一种技术，已经通过了概念验证阶段，正在进行法规申请。
由英国私募Teraview公司研发并且以太赫光（介于无线电波和光波之间）为基础。
该成像技术为配方研发和质量控制中的湿溶出试验提供了一个更好的选择。
该技术还可以缩短新产品的研发时间，并且根据厂商的情况，随时间推移甚至可能发展成为一个用于制药生产线的实时片剂检测系统。
TPI技术通过发射太赫射线绘制出片剂和涂层厚度的三维差异图谱，在有结构或化学变化时太赫射线被反射回。
反射脉冲的时间延迟累加成该片剂的三维图像。
该系统使用太赫发射极，采用一个机器臂捡起片剂并且使其通过太赫光束，用一个扫描仪收集反射光并且建成三维图像(见图)。
技术研发太赫技术发源于二十世纪九十年代中期13本东芝公司位于英国的东芝欧洲研究中心，该中心与剑桥大学的物理学系有着密切的联系。
日本东芝公司当时正在研究新一代的半导体，研究的副产品是发现了这些半导体实际上是太赫光非常好的发射源和检测器。
二十世纪九十年代后期，日本东芝公司授权研究小组寻求该技术可能的应用，包括成像和化学传感光谱学，并与葛兰素史克和辉瑞以及其它公司建立了关系，以探讨其在制药业的应用。
虽然早期的结果表明该技术有前景，但日本东芝公司却不愿深入研究下去，原因是此应用与日本东芝公司在消费电子行业的任何业务兴趣都没有交叉。
这一决定的结果是研究中心的首席执行官DonArnone和剑桥桥大学物理学系的教授Michael Pepper先生于2001年成立了Teraview公司一作为研究中心的子公司。
TPI imaga 2000是第一个商品化太赫成像系统，该系统经优化用于成品片剂及其核心完整性和性能的无破坏检测。
Remarks on permutive cellular automata
Remarks on permutive cellular automataJ.-P.AlloucheCNRS,LRIBˆa timent490F-91405Orsay CedexFrance allouche@lri.frG.SkordevCEVIS,Universit¨a t BremenUniversit¨a tsallee29D-28359BremenGermanyskordev@cevis.uni-bremen.de AbstractWe prove that every n-dimensional permutive cellular automaton is conjugate to a one-sided shift with compact set of states.This is a generalization of a theorem of R.Gilman.Keywords:cellular automata;permutivity;permutativity;one-sided shift;chaotic cellular au-tomata.AMS classification:37B15,68Q80.1Preliminaries1.1Cellular automata onfinitely generated abelian groupIn this section we recall the definition of a cellular automaton A with set of states S on an abelian group G offinite rank,and we give some notations(see[2,3]for example).We denote by Z the set of integers and by N the set of nonnegative integers.Let G be afinitely generated abelian group of rank n,(see for example[12,chapter3]).Wefix a representation of G as a direct sum G=Z n⊕T,where T is afinite abelian group.Then an element g∈G is an (n+1)-tuple:g=(m1,...,m n,h),m1,...,m n∈Z,h∈T.The set of states S of the cellular automaton A is afinite set with cardinality|S|≥1.A configuration of A is a map x:G−→S.The set of all configurations is denoted by S G or by M(G,S).The shift mapsσg:S−→S are defined on the set of configurations as follows.For a given element g∈G the shiftσg is defined byσg(x)(a):=x(a+g),∀a∈G.The cellular automaton A is a map A:S G−→S G which is local and homogeneous.This means that the map A is defined by a given local(generating)function(or local rule)l:S N k−→S,where N k=[−k,k]n×T,k∈N(S N k is the set of all configurations/blocks on N k with values in S).For a given x∈S G we denote by x|k the restriction of the configuration x to N k.Then the map A is defined byA(x(g))=l(σ−g(x|k)).1There is an elegant topological definition of cellular automata in [10,Theorem 3.4].To recall it we introduce a metric on the space of configurations S G :d (x,y )= 0if x =y 1k +1if x =ywhere k is the least nonnegative integer such that there exists g =(m 1,...,m n ,h )∈G with •x (g )=y (g ),•|m j |=k for some j =1,...,n .The space S G with this metric is compact and totally disconnected,and therefore homeomor-phic to the triadic Cantor set (see for example [14,p.165–166]).The shifts σg :S G −→S G are homeomorphisms.The set S G is a G -space,i.e.,the group G acts on it as a group of transforma-tions.The action is given by the embedding of G into the group of homeomorphims of the space S G to itself:g −→σg (see for example [11,p.112–113]).The natural maps B :S G −→S G of the G -space S G are the G -maps,i.e.,the continuous maps which commute with all shifts σg :Bσg (x )=σg B (x ),∀g ∈G,∀x ∈S G .In [10,Theorem 3.4],it is proved that the cellular automata on S G are exactly the G -maps .The proof of Hedlund is given in the case where G =Z ,but the same proof works in general (see [17]).1.2Cellular automata on finitely generated abelian groups of rank n and onthe n -dimensional lattice Z nIn this section we give a representation of any cellular automaton on an abelian group G =Z n ⊕T as a cellular automaton on Z n .For this purpose we will use the classical identificationi 1:M (Z n ⊕T,S )−→M (Z n ,M (T,S )),defined as follows.Let x :Z n ⊕T −→S be a configuration.Theni 1(x ):Z n −→M (T,S )is given byi 1(x )(m 1,...,m n )(h )=x (m 1,...,m n ,h )for (m 1,...,m n )∈Z n and h ∈T ,(see for example [11,p.23–24]).The map i 1is a homeomorphism.Now with a given cellular automaton A :S G −→S G we associate a cellular automatonA 1:S Z n 1−→S Z n1with state space S 1=S T such that the following diagram commutesS GA −→S G i 1↓↓i 1S Z n 1A 1−→S Z n 1i.e.,A 1=i 1A i −11.Remark 1This means that the dynamical systems (A,S G )and (A 1,S Z n 1)are conjugate and there-fore they have the same dynamics,see for example [7,p.47].21.3Representation of multi-dimensional cellular automata as one-dimensionalcellular automataA cellular automaton A:S Z n−→S Z n will be called an n-dimensional cellular automaton.Let n≥2.We will use the identification i2i2:M(Z n,S)−→M(Z,M(Z n−1,S)),given byi2(x)(m1)(m2,...,m n)=x(m1,...,m n)for x∈M(Z n,S),(see for example[11,p.23–24]).The map i2is bijective and bicontinuous.The elements z of the set M(Z,M(Z n−1,S))are configurations on Z with values in the compact(totally disconnected)space M(Z n−1,S).The state space for these configurations is not afinite set but an infinite(compact)space.On the space M(Z,M(Z n−1,S))we consider the metric defined byρ(α,β)=∞n=0d(α(n),β(n))2nforα,β∈M(Z,M(Z n−1,S)).Thenα(n),β(n)∈M(Z n−1,S)and d(.,.)is the metric on M(Z n−1,S) we introduced before.With the cellular automaton A:S Z n−→S Z n we associate the map A2:S Z2−→S Z2,where S2=M(Z n−1,S)such that the following diagram commutesS Z n A−→S Z ni2↓↓i2S Z2A2−→S Z2i.e.,A2=i2A i−12.Remark21.The(topological)dynamical systems(A,S Z n)and(A2,S Z2)are conjugate and therefore have the same dynamics.2.The map A2is local,since the map A is local,i.e.,induced by a local generating function.3.On the space M(Z,M(Z n−1,S))there are two types of shift maps:σm and s(m1,...,m n−1)form,m1,...,m n−1∈Z.They are defined as follows:σm(α)( )=α(m+ ),∀ ∈Z,s(m1,...,m n−1)(α)( )(u1,...,u n−1)=α( )(u1+m1,...,u n−1+m n−1),∀ ,u1,...,u n−1∈Z.The map A2is continuous and commutes with the shiftsσm and s(m1,...,m n−1).It is worth notingthat not all continuous mapsϕ:M(Z,M(Z n−1,S))−→M(Z,M(Z n−1,S))which commute with all shiftsσm and s(m1,...,m n−1)are local.For example take n=2and considerthe mapϕ:M(Z,M(Z,S))−→M(Z,M(Z,S))defined byϕ(α)(k)( )=α(k− )(0).This map is continuous,it commutes with all shiftsσm and s m,but it is easy to check that it is not local,i.e.,ϕ=i2A i−12for every cellular automaton A(hint:an“infinite memory”is needed).31.4One-sided shifts with compact state spaceLet K be a compact set.On the set K N=M(N,K)we define the metricd1(u,v)=0if u=v1k+1if u=vwhere k is the smallest nonnegative integer with u(j)=v(j),0≤j≤k−1and u(k)=v(k).The mapσK:K N−→K N defined byσK(u)(m)=u(m+1),∀m∈Nis called the shift map on K N.The dynamical system(σK,K N)is called the one-sided shift(shift on N)with state space K(see[6]for example).1.5Chaotic dynamical systemsLet X be a compact metric space and let f:X−→X be a continuous map.The dynamical system (f,X)is called chaotic[7,4]if and only if•the set of periodic points of the map f is dense in X;•(f,X)is mixing,i.e.,for any two(nonempty)open sets U,V⊂X there exists k∈N withf k(U)∩V=∅.Note that the one-sided shift is a chaotic dynamical system.Remark3The dynamical system(f,X)is called expanding if there exists a numberδ>0such that for any two different points x,y∈X there exists n∈N withρX(f n(x),f n(y))>δ(here ρX(.,.)is the metric on the space X).The one-sided shift with state space K is expanding if and only if the set K isfinite.For an expanding map f on a compact metric space X the dynamical system(f,X)is conjugate to a one-sided subshift withfinite state space,[10,Theorem2.1].A one-sided subshift is a closed subset of the one-sided shift dynamical system invariant under the shift.2Multidimensional cellular automata conjugated to one-sided shifts with compact state spaceUsing the notion of permutive cellular automata,that was introduced in[10],Gilman proved in [9]that(bi)permutive one-dimensional cellular automata are topologically conjugate to one-sided shifts with appropriatefinite state space.(Note that Gilman uses the expression“linear automata”for“one-dimensional automata”.Usually“linear automata”are automata whose local rule is lin-ear.)This implies that(bi)permutive cellular automata are chaotic as dynamical systems.This theorem was rediscovered several times,e.g.,see[1,19,15,8,5].We will generalize this result to n-dimensional cellular automata.For simplicity of notations we will only consider the case n=2.Let usfirst recall the definition of permutivity in the one-dimensional case[10,Definition6.3]: a one-dimensional cellular automaton is called permutive if and only if the local function has the property that,when all its variables but the leftmost(resp.the rightmost)take anyfixed values, then the resulting one-variable function is a bijection.Note that permutivity is sometimes called permutativity in the literature;it is also called the class M property in[1].4We now introduce an appropriate notion of permutive2-dimensional cellular automaton.Let A:S Z2−→S Z2be a2-dimensional cellular automaton with states in afinite set S,induced by a local generating functionλ:S U k,l−→S,where U k,l=[−k,k]×[−l,l]for k,l∈N.For(a,b)∈U k,l denote by M(a,b)the set U k,l\{(a,b)}.For any configuration c∈S M(a,b)we define the mapi c:S−→S U k,lbyi c(s)(x,y)=c(x,y)if(x,y)=(a,b) s if(x,y)=(a,b).For every c∈S M(a,b)we define the mapµc:S−→S,byµc(s)=λ(i c(s)).Definition1The local generating functionλis permutive at(a,b)if the mapµc is bijective for all c∈S M(a,b).The point(a,b)∈U k,l is called not essential forλifµc≡Constant for all c∈S M(a,b). Definition2The cellular automaton A with local generating functionλ:S U k,l−→S is calledpermutive if and only if•there exist u,v≥1and a1,...,a u,b1,...,b v with−k≤a1<...<a u≤k and−k≤b1<...<b v≤ksuch that the set of essential points ofλof the form(α,l)or(β,−l)is equal to the set{(a1,l),...,(a u,l),(b1,−l),...,(b v,−l)};•the inequalities a1<0<a u,b1<0<b v hold;•the mapλis permutive at the four points(a1,l),(a u,l),(b1,−l),(b v,−l).Example1Let S=GF(q)be thefinitefield with q elements.Then S U k,l is a vector space over GF(q).The cellular automaton A with local generating functionλis called a linear cellular automaton if the mapλ:S U k,l−→S is linear(over GF(q)).The linear cellular automaton A is permutive ifλhas essential points(a1,l),(a u,l),(b1,−l),(b v,−l)with a1<0<a u,b1<0<b v. Remark4Permutivity was defined only for cellular automata on the grid Z n.It can be defined in a similar way for a cellular automaton on afinitely generated abelian group of rank n,either directly,or by using the conjugation of such cellular automata with appropriate cellular automata on the grid Z n.Proposition1Let A be a2-dimensional permutive cellular automaton with state space S.Then, the dynamical system(A,S Z2)is congugate to a one-sided shift(σK,K N)with appropriate compact state space K.5Proof.We use an idea of Gilman in[9]and consider the maph:S Z2−→K Nwhere K=S M and M=(Z×[−l+1,l])∪([a1,a u−1]×[l+1,∞))∪([b1,b v−1]×[−l,−∞))(in the above notations),defined byh(x)(n)=A n(c)|M,∀n∈Nfor x:Z2−→S(here A n is the n-th iteration of the cellular automaton A).The map h is continuous and the diagramS Z2A−→S Z2h↓↓hK NσK−→K Ncommutes.Note that if the map h is defined from a continuous map that is not a cellular automaton (i.e.,that does not commute with the shifts),then the map h is not necessarily surjective or bijective. But here we prove that h is bijective.Step1.The map h is injectiveAssume that h(x1)=h(x2)for x1,x2∈S Z2.We will prove that x1=x2.The proof is by induction and we will only give thefirst two steps.Since h(x1)=h(x2),we have h(x1)(0)=h(x2)(0). This is equivalent to x1(m,n)=x2(m,n)for(m,n)∈M.We will prove by induction on m that x1(m,−l)=x2(m,−l)for all m≥b v.For m=b v:the assumption implies h(x1)(1)=h(x2)(1). Therefore h(x1)(1)(0,0)=h(x2)(1)(0,0)or A(x1)(0,0)=A(x2)(0,0).From the definition of the cellular automaton A we have A(x j)(0,0)=λ(x j|U k,l).Since x1(a,b)=x2(a,b)for(a,b)∈U k,l\ {(b v,−l)},the permutivity ofλat(b v,−l)implies x1(b v,−l)=x2(b v,−l).The next steps of the induction are similar.Having x1|M=x2|M and x1(m,n)=x2(m,n)for m∈Z,−l≤n≤l we prove as above that x1(m,n)=x2(m,n)for m∈Z,−∞<n≤−l.In the same way we prove that x1(m,−l)=x2(m,−l)for m≤b1.In the same manner,using the permutivity ofλat(a1,l)and(a u,l),we prove that x1(m,n)= x2(m,n)for m∈Z,l≤n<∞.Step2.The map h is surjectiveLet c:N−→S M.We have tofind an extension˜c:Z2−→S of c(0)with h(˜c)=c.This is done in several steps by induction,using the permutivity of the cellular automaton A.First we extend c(0)on M∪(Z×{l+1}).For all(m,l),with m≥a u,the procedure is the same as for(a u,l).We show only this step.The permutivity ofλat(a u,l)implies that there exists only one s∈S such that for c1:U k,l−→S defined byc1(a,b)=c(0)(a,b)if(a,b)=(a u,l) s if(a,b)=(a u,l)we have c(1)(0,0)=λ(c1).Then we define˜c(a u,l)=s.Using the permutivity ofλat(a1,l)we define˜c for(m,l),m≤a1.In the same way the extension ˜c is defined for(m,n),m∈Z,n≥ing the permutivity ofλat(b1,−l),(b v,−l)we define the extension˜c for(m,n),m∈Z,n≤−l.6Remark51.A consequence of our Proposition1above is that,for any permutive cellular automaton A:S Z2−→S Z2,the dynamical system(A,S Z2)is chaotic(in the sense of Devaney).This assertion can be compared to[21,Theorem A,p.137]and to[20,Theorem3.4,p.604].2.As we mentioned before the one-sided shift with infinite compact state space is not expanding. The n-dimensional cellular automata,n≥2,are conjugate to one-dimensional cellular automata with a Cantor set as state space.This is at least an intuitive reason for the result in[18]that n-dimensional cellular automata are not expanding for n≥2.3Continous maps commuting with some powers of the shiftHere we consider a continuous map B:S Z−→S Z for which there exists an integer l∈N,l≥2 such that Bσl=σl B.We call such maps l-cellular automata;they are also called place-dependent cellular automata[16].In the case where the cellular automaton is linear,the reader can look at [13].Example2Let f0:S2u+1−→S and f1:S2v+1−→S be two local generating functions.They generate a map B:S Z−→S Z as follows:for x∈S ZB(x)(2n):=f0(x(2n−u),···,x(2n+u)),B(x)(2n+1):=f1(x(2n+1−v),···,x(2n+1+v)),The map B is continuous and satisfiesσ2B=Bσ2,i.e.,it is a2-cellular automaton.We say that the map B is generated by two local generating functions.In a similar way we define maps induced by l generating functions.With a small modification of the proof of[10,Theorem3.4]we obtainProposition2The l-cellular automata B:S Z−→S Z are exactly the maps induced by l generating functions.The theorem of Gilman[9]that we generalized above also holds for l-cellular automata.Consider an l-cellular automaton B induced by the generating functions f0,...,f l−1:S2k+1−→S.We say that the l-cellular automaton B is permutive if f0,...,f l−1are permutive at the leftmost and the rightmost arguments.Proposition3Every permutive l-cellular automaton is conjugate to an appropriate one-dimen-sional shift withfinite state space.The proof is similar to the proof of Gilman[9].Acknowledgments.This paper was written during a stay of GS in Orsay and a stay of JPA in Bremen.Both authors want to thank heartily D.Gouyou-Beauchamps and H.-O.Peitgen for their warm support and for their interest.7References[1]V.S.Afra˘ımovich,M.A.Shereshevsky,Cellular automata as dynamical systems,NonlinearWaves3.Physics and astrophysics,Proc.9th All-Union Sch.Nonlinear Phys.,Gorky/USSR 1989, A.V.Gaponov-Grekhov,M.I.Rabinovich,J.Engelbrecht,Eds.,Res.Rep.Phys., Springer,Berlin,1990,pp.296–300.[2]J.-P.Allouche,M.Courbage,G.Skordev,Notes on cellular automata,Preprint,Report458,Institut f¨u r Dynamische Systeme,Universit¨a t Bremen,2000.[3]H.Aso,N.Honda,Dynamical characteristics of linear cellular automata,put.SystemSci.30(1985)291–317.[4]J.Banks,J.Brooks,J.G.Cairns,G.Davis,P.Stacey,On Devaney’s definition of chaos,Amer.Math.Monthly99(1992)332–334.[5]G.Cattaneo,M.Finelli,L.Margara,Investigating topological chaos by elementary cellularautomata dynamics,put.Sci.244(2000)219–241.[6]M.Denker,C.Grillenberger,K.Sigmund,Ergodic Theory on Compact Spaces,Lecture Notesin Mathematics,527,Springer,New York,1976.[7]R.L.Devaney,An Introduction to Chaotic Dynamical Systems,Second Edition,Addison-Wesley,Reading,1989.[8]F.Fagnani,L.Margara,Expansivity,permutivity,and chaos for cellular automata,TheoryComput.Syst.31(1998)663–677.[9]R.Gilman,Periodic behavior of linear automata,in Dynamical Systems,Lecture Notes inMathematics1342,Springer,New York,1988,pp.216–219.[10]G.Hedlund,Endomorphisms and automorphisms of the shift dynamical systems,Math.Sys-tems Theory3(1969)320–375.[11]I.M.James,General Topology and Homotopy Theory,Springer,New York,1984.[12]M.I.Kargapolov,Ju.I.Merzljakov,Fundamentals of the Theory of Groups,Springer,NewYork,1979.[13]J.Kari,Linear cellular automata with multiple state variables,in Stacs2000,H.Reichel,S.Tison,Eds.,Lecture Notes in Computer Science1770,Springer,New York,2000,pp.110–121.[14]J.L.Kelley,General Topology,Reprint of the1955edition,Springer,New York,1975.[15]R.Kleveland,Mixing properties of one-dimensional cellular automata,Proc.Amer.Math.Soc.125(1997)1755–1766.[16]nge,H.-O.Peitgen,G.Skordev,Fractal patterns in Gaussian and Stirling number tables,Ars Combin.48(1998)3–26.[17]D.Richardson,Tessellation with local transformations,put.System Sci.6(1972)373–388.8[18]M.Shereshevsky,Expansiveness,entropy and polynomial growth for groups acting on subshiftsby automorphisms,Indag.Math.4(1993)203–210.[19]M.A.Shereshevsky,V.S.Afra˘ımovich,Bipermutative cellular automata are topologicallyconjugate to the one-sided Bernoulli shift,Random Comput.Dynam.1(1992)91–98. [20]M.Shirvani,T.D.Rogers,On ergodic one-dimensional cellular automata,Commun.Math.Phys.136(1991)599–605.[21]S.J.Willson,On the ergodic theory of cellular automata,Math.Systems Theory9(1975)132–141.9。
yeastautolysis1[1]
![yeastautolysis1[1]](https://img.taocdn.com/s3/m/ce7af30202020740be1e9b59.png)
Yeast AutolysisBy Murli DharmadhikariThe term autolysis literally means 'self-destruction'. It represents self-degradation of the cellular constituents of a cell by its own enzymes following the death of the cell. In the process of autolysis, the medium (wine) is enriched by the compounds released as a result of the degradation of intracellular constituents. These yeast constituents have an important influence on the sensory properties and biological stability of wine.Yeast autolysis is very important to the food industry. Yeast extract is used as an additive in the production of meat paste, meat pie filling, soups, sauces, and snacks. Yeast autolysate is a good source of nutrients such as proteins, vitamins, fiber, and micronutrients. It is also used to enhance the color and flavor of food products. The process (autolysis) is of great value to biochemical researchers, since it is used in the extraction and purification of enzymes and coenzymes. In the wine industry, yeast autolysis is important in the production of sparkling wines, sherry, and white wines produced with prolonged yeast contact, such as the "sur lie" method.The process of autolysisThe process of autolysis begins with the death of the cell. At first, disorganization of membranous systems (cytoplasmic membrane and other organelles) of the cell occurs. This permits the enzymes to come in contact with cellular constituents which are degraded and rendered soluble. The proteolytic enzyme, protease, attacks proteins and breaks them down into smaller constituent units, such as peptides and amino acids. Likewise, enzyme nuclease degrades RNA and DNA yielding compounds such as nucleosides, mononucleotides, and polynucleotides.The enzymes glucanase and proteinase degrade the cell wall constituents such as glucans and mannoproteins, which causes the cell wall to become porous. The autolysate (the mixture of degraded cellular components) leaks through the cell wall into the surrounding medium. The process of degradation of the cellular components continues to occur in the surrounding medium.Yeast autolysis is strongly influenced by temperature and pH. In wine, the process occurs at low pHs (3 to 4), and at relatively low temperatures, e.g., 15 to 18°C, and also in the presence of ethanol. These conditions are less than ideal for autolysis, and the autolytic process is likely to occur at a much slower rate. By permitting the wine to be in contact with the yeast for a longer period, a wine maker can secure the beneficial effects of autolysis.The two important aspects of yeast autolysis are (i) degradation and solubilization of cellular components, and (ii) degradation of the cell wall. The concentrated form of solubilized cell constituents resulting from autolysis is referred to as yeast extract. The breakdown product of the whole cell, i.e., the cell wall and the cytoplasm, are referred to as yeast autolysate.The process of yeast autolysis can be divided into two parts:1. Degradation of cellular constituents which is predominantly the breakdown ofproteinaceous substances also known as proteolysis.2. Degradation of the cell wall, which is a rigid structure that is responsible for theshape of the yeast cell.ProteolysisThe yeast cell contains a wide array of protein degrading enzymes. These enzymes are mostly located in a vacuole. Upon cell death, the cellular matrix becomes disorganized and the enzymes come in contact with their substrate. The proteolytic enzymes hydrolyze peptide bonds and yield protein breakdown products such as peptides and amino acids.It should be noted that an increase in amino acid content in the medium (wine) does not necessarily mean the beginning of the autolytic processes. It has been observed that at the end of alcoholic fermentation, when the sugars are used up, amino acids located within the cells are passively released into the wine. This leads to an increase in amino acid content, but does not involve enzymatic action.With the beginning of the autolytic process, there is a significant increase in amino acids and other nitrogenous compounds. The concentration of various nitrogenous compounds released during autolysis was studied by Freyssinet (1988). In the experiment, the autolysis was conducted at pH 3.0 and 40°C to expedite the process. The results showed that about 42% of the total nitrogen was released within the first 24 hours of the experiment; the remaining 58% was released during the following 14 days. The nitrogenous compounds released at the beginning consisted mostly of large protein fractions. At a later state, the protein fragments were further degraded, and an increase in amino acid concentration was noted.Degradation of cellThe cell wall is a rigid outer layer of the cell. It envelops the protoplast and confers specific shape to the cell. Many enzymatic activities are associated with the cell wall. These enzymes participate in the degradation of extracellular constituents, and also in the breakdown of cell wall components.On a dry weight basis, the cell wall constitutes 15 to 20% of the cell's weight. It (the cell wall) consists of 80 to 90% polysaccharides and a small amount of proteins and lipids. The main polysaccharides include glucans and mannans, and a small amount ofchitin. The glucan polymer exists in both alkali insoluble, acid insoluble, and alkali soluble forms. The insoluble glucan fraction helps the cell to retain its shape. In the cell wall, the mannans are linked to protein. They are commonly described as mannoproteins and are important structural components of the cell wall. The enzymes glucanase and protease play a significant role in the degradation of cell wall constituents. As a result of their action, the cell wall becomes porous and a mixture of glucan, mannan, protein, and 6-(1-3) linked oligosaccharides is released into the surrounding medium.Importance of yeast autolysisThe phenomenon of autolysis is of great importance to the producers of sparkling wine (methode champenoise) and white wine by "sur lie" method.Sparkling wine - In the case of sparkling wine produced by methode champenoise, the wine in the bottle (cuvee) is kept in contact with the yeast lees for a long period (1 to 3 years). following secondary fermentation in the bottle. During this prolonged yeast contact, the yeast undergoes autolysis and consequently, the sparkling wine is enriched by the components of the autolysate. It should be noted that many factors influence the quality and quantity of yeast autolysate (released in the wine during the course of autolysis). The important factors include the yeast strain, its conditions of growth and population, storage temperature, ethanol content, wine pH, and the duration of yeast contact.The major constituents formed during autolysis include: nitrogenous compounds, polysaccharides, nucleic acid components, fatty acids, various vitamins, and aroma compounds. These and other components of autolysate play an important role in the aroma and quality of sparkling wine.Nitrogenous compoundsAn increase in the concentration of protein degradation products such as amino acids has usually been considered characteristic of yeast autolysis. It has been mentioned earlier that an increase in amino acid content in wine can occur in the absence of the autolytic process.During the course of secondary fermentation in the bottle, the yeasts utilize the amino acids present in the wine. Following the end of the secondary fermentation, when all the sugar is used up, the yeasts release amino acids back into the wine. This movement of amino acid from the intracellular pool to the surrounding medium occurs passively and results in higher amino acid levels in the wine. This new amino acid level in the wine stays relatively stable, usually for a 3 to 4 month period. Following this phase, the amino acid concentration in the wine begins to increase. This increase is attributed to the autolytic process, where cell proteins are degraded, solubilized, and released into the wine. With the continuation of the autolytic process, the wine becomes richer in aminoacid content. Some of these amino acids undergo a transformation due to decarboxylation and deamination reactions. The net amount of amino acid present at a given point represents the difference between the amino acids formed during autolysis (plus passive release) and the amount utilized in other reactions. In addition to amino acids, other nitrogenous compounds obtained during autolysis include polypeptides, peptides, and nucleic acid components.PolysaccharidesThe polysaccharides found in yeast autolysate originate from the breakdown of cell wall components. It has been mentioned earlier that the main polysaccharides in the cell wall are B1->3-glucans and mannoproteins, with some chitin. The degradation products of these polysaccharides are glucose and man nose. Several studies have reported an increase in these sugars and other polysaccharide fragments in sparkling wine following secondary fermentation and subsequent aging of wine on lees in the bottle. Following autolysis, changes in the concentrations of these constituents may occur due to other chemical reactions such as hydrolysis by B-(1->3)-glucanase. It is important to note that mannoproteins formed during autolysis contribute significantly to the quality of sparkling wine, such as fineness and persistence of bubbles.One reason for methode champenoise wine to be considered superior to the bulk process sparkling wine is the fact that the former is enriched by yeast autolysate.Fatty acidsIn yeast cells, the lipids are mostly associated with plasma membrane and cell wall. A small amount is also found in cytoplasm. During autolysis the lipids are degraded to fatty acids. These fatty acids are saturated and consist of 8 to 16 carbon atoms. Once released, these fatty acids can be involved in the formation of esters, aldehydes, and other volatile compounds. Fatty acids and other fatty acid-derived volatile compounds can have a significant impact on the flavor of sparkling wine.Volatile compoundsMany aromatic compounds released during yeast autolysis have been reported to influence the aroma profile of sparkling wines. These substances include heavy esters, terpenes, higher alcohols, and other volatile substances. A list of some of the important aroma contributing compounds is given in Table 1.________________________________________________________________________ Table 1. Compounds contributing to thearoma of sparkling wine.________________________________________________________________________ 1. Heavy estersisoamylcaproateoctylacetatephenylethylacetate phenylethylcaproateethyllinoleatediethylsuccinate2. Terpene compoundslinaloola-terpenolnerolidolfarnesol3. Higher alcoholsisoamyl alcoholphenylethyl alcohol4. Other volatile compoundsmethyl- 2-ethoxy-2-furanedimethyl-4,5-tetrahydrofu rane-2-3-dione vitispirane________________________________________________________________________ Maturing white wine on lees or “sur lie.”In the "sur lie" wine production technique, the wine is matured in contact with yeast lees following the alcoholic fermentation. This method has traditionally been used in Burgundy for Chardonnay production. However, the method is now used by many winemakers for white wine production in many parts of the world.In the traditional approach, the must is fermented in the barrel. Following alcoholic fermentation, malolactic fermentation is encouraged and the wine is kept on lees, usually for a period of 6 to 12 months. In some cases, the wine is matured on lees for an even longer duration. While on lees, the wine is stirred periodically to resuspend the sediment. Wine kept on lees for a long period shows an increased concentration of nitrogenous compounds (such as amino acids and peptides) as well as polysaccharide breakdown products, such as mannoproteins. The enrichment of wine by these compounds is considered to be due to yeast autolysis.There are several reasons as to why a winemaker may choose the "sur lie" method of wine production. The most important reason being the influence of yeast lees on the organoleptic properties of wine. The wine is often described to have enhanced body,creamier, richer, mouth feel, greater complexity and depth of flavor, and a better integration of fruit-and-wood-derived components. The other reasons for choosing prolonged yeast contact are:1. To encourage malolactic fermentation. As mentioned earlier, during lees contact,the wine becomes richer with yeast autolysate which serves as a source of nutrients for bacterial growth.2. Use of S02 can be minimized. Sulfur dioxide is often added to a wine to protect itfrom oxidation. Yeasts are good scavengers of oxygen and yeast lees contribute to the reductive atmosphere (when it is retained during maturation.) Because of this, the need to add S02 is minimized.3. To soften the effect of aggressive oak tannins. This point is discussed later.There are two ways in which lees contact affects the quality of wines matured in oak barrels:1. During extended lees contact, yeast autolysis occurs and many constituents arereleased into the wine. These substances affect the body (mouthfeel) and thearoma of wine.2. Yeast as well as products of autolysis interacts with oak-derived componentsand this interaction leads to the changes in wine composition and its organoleptic character.The effect of lees contact (yeast autolysate) on wine has been mentioned earlier. The influence of lees on oak extractives warrants some discussion.Influence of yeast lees on the composition and quality of wine matured in oak barrels.Yeast lees ("sur lie" aging) exerts a great influence on the composition of wine. During barrel fermentation and aging, many components are extracted from the oak. The important constituents include: furan derivatives, oak lactones, volatile phenols, and phenolic aldehydes (see Table 2). The yeast lees affects the concentration of many oak constituents and thus influences the organoleptic character of the wine.________________________________________________________________________ Table 2. Important oak-derived compounds.__________________________________________________________________ Furansfurfural5-methylfurfuralalcoholfurfuralMethyloctalactonesmethyloctalactonecismethyloctalactonetransVolatile phenolsguaiacol4-methylguaiacol4-ethylguaiacol4-vi nylguaiacoleugenolphenol + o-cresol4-vi nylphenolPhenolic aldehydesvanillinsyringaldehyde__________________________________________________________________ Influence of lees contact on oak-derived aromatic compounds.When the wine is stored in wooden barrels, the components of the wood are extracted into the wine. The concentration of some of the compounds is altered when a wine is matured in contact with lees for a long period. Observations indicate that contact with yeast lees results in the reduction of the woody aroma in wine. Such a reduction in the intensity of woody aroma can be explained on the basis of two possible reasons.First is the fixation of certain volatile compounds, such as volatile phenols and lactones, by the yeast cell wall. Another is the conversion of aroma compounds to less aromatic forms by the yeast enzyme. For example, vanillin could be converted to vanillyl alcohol.Effect of lees contact on phenolic compoundsProlonged maturation on lees with periodic stirring causes a reduction in the concentration of polyphenols in wine. The wood tannins (polyphenols) are adsorbed onto yeast cell walls and mannoproteins released during autolysis, and are removed with the lees. In this manner yeast lees acts as a fining agent that lowers the tannin content of the wine.Effect of lees contact on varietal aromaMany reports indicate that varietal or fruity aroma is enhanced when a wine is matured on the lees. The reason for such an effect is not clear. However, the role of yeast enzymes in the development of fruity compounds is suspected. In this context, the results of an Australian study are worth considering. In an experiment, Chardonnay wine was matured on the lees for five months, with and without periodic stirring. The judges were asked to evaluate wine aroma using aroma descriptors such as fruity, woody, and yeasty. The results of the sensory analysis showed that in the control treatment (no lees contact),fruit and wood aromas were dominant. In wine with lees contact, but no stirring, the fruit aroma was enhanced, the wood component was subdued, and the yeasty character was a little more noticeable as compared to the control. In samples where the lees was stirred, the yeast component increased and both fruit and wood aromas were reduced.It seems that lees contact, in general, causes a reduction in the aggressive wood characters. However, its effect on fruity aroma is less clear. In certain cases it may enhance, while in others it may not. The important influence of lees contact should be viewed in terms of flavor complexity and how well the various flavors (fruit, wood, and yeast) are balanced and integrated.The "sur lie" method can sometimes have a negative effect on wine quality. Higher amounts of acetic acid and acetaldehyde can result. But more importantly, reduced sulfur compounds, such as hydrogen sulfide and mercaptans with unpleasant odors can be formed. It is important to exercise great care when wine is sitting on lees, and appropriate action should be quickly taken if off odors from reduced sulfur compounds are noticed. Stirring the lees can be helpful in removing the odors, but sometimes that is not enough. In this regard, it should be mentioned that certain phenolic compounds from the barrel can help in minimizing the problem of off sulfide odors. Gallic acid can be formed in the wine from the hydrolysis of wood ellagitannins. Oxidation of gallic acid yields hydrogen peroxide (a highly reactive oxydizing agent) which can oxidize the sulfide compounds, and thus prevent or reduce the occurrence of off sulfide odors. It should be noted that the new barrels would have greater amounts of hydrolyzable tannins than the old barrels; consequently, the chance of these unpleasant sulfide odors would be greater in old barrels.。
sat阅读理解的高频词汇
sat阅读理解的高频词汇sat阅读理解部分必备的高频词汇：A开头Autotroph(自养生物)An organism that can produce the organic molecules and energy necessary for life through the processes of photosynthesis or chemosynthesis. Autotrophs do not rely on other organisms for food. In a food web, autotrophs are producers.Auxin(茁长素) ：一种植物激素，刺激细胞伸长One in a class of plant hormones that stimulates (among other things) cell elongation, secondary tissue growth, and fruit development.amino acid(氨基酸)The monomer of a protein. A central carbon attached to an amino group (–NH2), a carboxyl group (–COOH), and a hydrogen atom (–H). The fourth group is variable and defines the amino acid’s chemical identity.amnion(羊膜) ：位于最内侧直接覆蓄胚体的膜The extraembryonic membrane in birds, reptiles, and mammals that surrounds the embryo, forming an amniotic sac.anaerobic respiration(无氧呼吸)A form of cell respiration that does not use oxygen (as opposed to aerobic cell respiration). Anaerobic respiration is less efficient than the aerobic variety and produces just 2 ATP per molecule of glucose. Anaerobic respiration has two stages: glycolysis and fermentation(发酵).analogous trait (相似特征)：来源于相同祖先，与其他生物种功能、形态上相似的结构A trait that is morphologically and functionally similar to that of a different species but that arose from a distinct, ancestral condition.anaphase (分裂后期)The stage of mitosis in which sister chromosomes are separated and pulled to opposite ends of the cell by microtubules; the fourth stage of the first meiotic division (meiosis I), during which maternal and paternal homologous pairs are separated on microtubules; the fourth stage of the second meiotic division (meiosis II), during which either maternal or paternal sister chromatids are separated on microtubules.androgen(雄性激素)A male sex hormone. (e.g. testosterone【睾酮】)Angiosperm(被子植物)A vascular flowering plant in which seeds are enclosed inside protective ovaries, such as fruit or flowers. Angiosperms can be monocots(单子叶) or dicots(双子叶).Anther(花粉囊，花药)Pollen-producing structure at the top of the stamen, the male reproductive organ of flowers.Anticodon(反密码子) ：位于tRNA上，和mRNA的'密码子相反配对The sequence of three nucleotides on tRNA that pairs with a codon of mRNA at the A site of a ribosome during translation.Antigen(抗原)A protein coat on the surface of red blood cells; a red blood cell may have a protein coat of type A, B, or AB. If the cell has no antigens, it is called type O. The presence of a foreign antigen in a body will cause blood to clot.Aorta(大动脉)The largest artery in the body; carries oxygenated blood from the left ventricle of the heart.aphotic zone(无光带)Literally, zone without light. The aphotic zone is part of the marine pelagic zone and begins 600 feet below the surface of the ocean.Only chemosynthetic organisms, scavengers, and predators are able to survive in this habitat.sat阅读理解部分必备的高频词汇：T开头taste buds(味蕾)Structures on the tongue that contain chemoreceptors, which respond to four main sensations—sour, salty, bitter, and sweet—to create the sense of taste.Taxonomy(分类法)The study of biological classification.Telophase(末期)The final stage of mitosis before cytokinesis. In telophase, the nuclear envelope re-forms around separated sister chromatids and kinetochore microtubules disappear. Cell elongation also occurs during this phase. The final stage of the first meiotic division (meiosis I), during which chromosomes arrive at the poles of the cell and begin to recondense; the final stage of the second meiotic division (meiosis II), during which chromosomes arrive at the poles of the cell, the nuclear envelope begins to re-form, and the chromosomes begin to recondense.Tendon(腱)Connective tissue between bones and muscles.Testes(睾丸)The male gonads; sperm and testosterone are produced here.Testosterone(睾酮)A hormone necessary for sperm production in men. Also responsible for developing and maintaining the secondary sex characteristics of males, starting at puberty.Thyroid(甲状腺)Gland that produces the hormone thyroxine, which increases the metabolism of most of the cells in the body. Located in the neck.Tissue(组织)A group of closely connected and similar cells that cooperate to generate a specific structure or specialized function within an organism.Tracheophyte(维管植物)A terrestrial plant with a vascular system.Trait(特征)Any observable feature or characteristic of an organism.transfer RNA (Trna/翻译RNA)An RNA molecule used in protein synthesis as a link helping to convert messenger RNA into amino acids.Transpiration(蒸发作用)The process by which a plant loses water to its environment through evaporation.trophic level(营养级)Steps on a food/biomass pyramid that are defined by organisms within a community that are the same distance from the primary producers in a food web.Tropism(向性)Long-term growth of a plant toward or away from a stimulus.Tuber(块茎)Fleshy underground storage structure composed of an enlarged portion of the stem that has on its surface buds capable of producing new plants.sat阅读理解部分必备的高频词汇：F开头flame calorimeter 火焰量热计flammable 易燃的flare 照明弹flow rate 流速Fluid 流体fluidised bed 流化床fluorescent screen 荧光屏fluoride controversyfluoride 氟化物fluorine is pale yellow gas 氟是淡黄绿色气体foaming agent 起泡剂formation of ions 离子的形成fertiliser 肥料fertility 肥(沃)度fibre 纤维fibrous 纤维状的filament 灯丝filtration 过滤fire extinguisher 灭火器firework 焰火first ionisation energy 一级电离能。
中国大陆首例XOFT术中放疗在上海交通大学医学院附属瑞金医院北部院区成功实施
2021,41（5）上海交通大学学报（医学版）Vol.41No.5May 2021JOURNAL OF SHANGHAI JIAO TONG UNIVERSITY (MEDICAL SCIENCE)[20]Aksu B,Ayvaz S,Aksu F,et al.Effects of sphingosylphosphorylcholineagainst oxidative stress and acute lung injury ınduced by pulmonary contusion in rats[J].J Pediatr Surg,2015,50(4):591-597.[21]Smith S,McCully B,Bommiasamy A,et al.A combat relevant model forthe creation of acute lung injury in swine[J].J Trauma Acute Care Surg,2018,85(1S Suppl 2):S39-S43.[22]Dhar SM,Breite MD,Barnes SL,et al.Pulmonary contusion inmechanically ventilated subjects after severe trauma[J].Respir Care,2018,63(8):950-954.[23]López-Alonso I,Blázquez-Prieto J,Amado-Rodríguez L,et al.Preventingloss of mechanosensation by the nuclear membranes of alveolar cells reduces lung injury in mice during mechanical ventilation[J].Sci Transl Med,2018,10(456):eaam7598.[24]Neudecker V,Brodsky KS,Clambey ET,et al.Neutrophil transfer of miR-223to lung epithelial cells dampens acute lung injury in mice[J].Sci Transl Med,2017,9(408):eaah5360.[25]Kreyer S,Scaravilli V,Linden K,et al.Early utilization of extracorporealCO 2removal for treatment of acute respiratory distress syndrome due to smoke inhalation and burns in sheep[J].Shock,2016,45(1):65-72.[26]Chen K,Xu ZC,Liu YK,et al.Irisin protects mitochondria function duringpulmonary ischemia/reperfusion injury[J].Sci Transl Med,2017,9(418):eaao6298.[27]Jia Y,Chen K,Lin P,et al.Treatment of acute lung injury by targetingMG53-mediated cell membrane repair[J].Nat Commun,2014,5:4387.[28]Grimm JC,Zhang F,Magruder JT,et al.Accumulation and cellular localizationof nanoparticles in an ex vivo model of acute lung injury[J].J Surg Res,2017,210:78-85.[29]Patel BV,Wilson MR,Takata M.Resolution of acute lung injury andinflammation:a translational mouse model[J].Eur Respir J,2012,39(5):1162-1170.[30]Liu Y ,Tao T,Li WZ,et al.Regulating autonomic nervous system homeostasis improves pulmonary function in rabbits with acute lung injury[J].BMC Pulm Med,2017,17(1):98.[31]Allard B,Panariti A,Pernet E,et al.Tolerogenic signaling of alveolar macrophages induces lung adaptation to oxidative injury[J].J Allergy Clin Immunol,2019,144(4):945-961.e9.[32]Carnesecchi S,Deffert C,Pagano A,et al.NADPH oxidase-1plays a crucial role in hyperoxia-induced acute lung injury in mice[J].Am J Respir Crit Care Med,2009,180(10):972-981.[33]Rangarajan S,Bone NB,Zmijewska AA,et al.Metformin reverses established lung fibrosis in a bleomycin model[J].Nat Med,2018,24(8):1121-1127.[34]Sherman MA,Suresh MV,Dolgachev VA,et al.Molecular characterization of hypoxic alveolar epithelial cells after lung contusion indicates an important role for HIF-1α[J].Ann Surg,2018,267(2):382-391.[35]Aires ID,Boia R,Rodrigues-Neves AC,et al.Blockade of microglial adenosine A2A receptor suppresses elevated pressure-induced inflammation,oxidative stress,and cell death in retinal cells[J].Glia,2019,67(5):896-914.[36]Grzanka R,Damasiewicz-Bodzek A,Kasperska-Zajac A.Tumor necrosis factor-αand Fas/Fas ligand signaling pathways in chronic spontaneous urticaria[J].Allergy Asthma Clin Immunol,2019,15:15.[37]Voicu S,Balas M,Stan M,et al.Amorphous silica nanoparticles obtained by laser ablation induce inflammatory response in human lung fibroblasts[J].Materials,2019,12(7):1026.[38]de Langhe E,Vande Velde G,Hostens J,et al.Quantification of lung fibrosis and emphysema in mice using automated micro-computed tomography[J].PLoS One,2012,7(8):e43123.[39]Langheinrich AC,Leithäuser B,Greschus S,et al.Acute rat lung injury:feasibility of assessment with micro-CT[J].Radiology,2004,233(1):165-171.［收稿日期］2020-06-25［本文编辑］徐敏694。
元胞自动机在地理学中的应用综述
总633期第三期2018年3月河南科技Henan Science and Technology元胞自动机在地理学中的应用综述郭珂1，2（1.洛阳师范学院国土与旅游学院，河南洛阳471934；2.中原经济区智慧旅游河南省协同创新中心，河南洛阳471934）摘要：由于元胞自动机在模拟空间复杂系统的时空演变方面具有巨大的优势，因此，经常被用于复杂系统的建模与模拟。
元胞自动机与地理学结合有较强的优势，通过分析元胞自动机在地理学各领域的应用现状，提出了现阶段元胞自动机存在的不足之处。
关键词：元胞自动机；地理学；研究综述中图分类号：P208文献标识码：A文章编号：1003-5168（2018）07-0024-02Application of Cellular Automata in GeographyGUO Ke1,2（1.College of Land and Tourism,Luoyang Normal University，Luoyang Henan471934；2.Collaborative Innovation Center of Smarter Tourism of Central-China Economic Region in Henan Province，Luoyang Henan471934）Abstract:Cellular automata are often used to model and simulate complex systems due to their great ad⁃vantages in space-time evolution of complex systems.Cellular automata and geography combine quite strong advantages.By analyzing the current status of cellular automaton in all aspects of geography,this paper put forward the shortcomings of cellular automata at the present stage.Keywords:cellular automaton；geography；research review1元胞自动机概述1.1元胞自动机的定义元胞自动机是由冯·诺依曼在20世纪40年代首先提出的一种离散模型，其采用“自底而上”的方式，将地理空间划分为一个一个的元胞单元，通过元胞单元之间的相互作用，利用循环的方式达到了元胞演化的目的。
FDA术语词汇
[Top] [Laws & Regulations] [FDA Organization] [SFDA][Top] [Laws & Regulations] [FDA Organization] [SFDA]FDA Organization Charts[Top] [Laws & Regulations] [FDA Organization] [SFDA]SFDA State Food and Drug Administration国家食品药品监督管理局[Top] [Laws & Regulations] [FDA Organization] [SFDA]1 of the Bureau of Customs and Border Protection (CBP)2 a biologic response modifier, is a single-chain polypeptide containing 140 amino acids3 An unwanted effect caused by the administration of drugs. Onset may be sudden or develop over time4 Organizations and groups that actively support participants and their families with valuable resources, including self-empowerment and survival tools.5 A negative experience encountered by an individual during the course of a clinical trial that is associated with the drug.6The basic premise of AIP is: If FDA determines that a company’s applications are not reliable, the agency will not perform substantive review of any of the company’s applications until confidence in the data is restored.7 An alanine aminotransferase (ALT) test measures the amount of this enzyme in the blood. ALT is measured to see if the liver is damaged or diseased.8 to check for liver disease or damage to the liver. Symptoms of liver disease can include jaundice, belly pain, nausea, and vomiting. An ALP test may also be used to check the liver when medicines that can damage the liver are taken or to check bone problems (sometimes found on X-rays), such as rickets, osteomalacia, bone tumors, Paget's disease, or too much of the hormone that controls bone growth (parathyroid hormone).9 An allograft is a transplanted organ or tissue from a genetically non-identical member of the same species10 is a general linear model with a continuous outcome variable (quantitative) and two or more predictor variables where at least one is continuous (quantitative) and at least one is categorical (qualitative). ANCOVA is a merger of ANOVA and regression for continuous variables. ANCOVA tests whether certain factors have an effect on the outcome variable after removing the variance for which quantitative predictors (covariates) account. The inclusion of covariates can increase statistical power because it accounts for some of the variability11 Any of the treatment groups in a randomized trial.12 Low levels of AST are normally found in the blood. When body tissue or an organ such as the heart or liver is diseased or damaged, additional AST is released into the bloodstream. The amount of AST in the blood is directly related to the extent of the tissue damage.13 A renewable permit granted by the federal government to an institution or research center to conduct clinical trials.14 in an "as treated" (or "observed data") analysis only those patients still taking the assigned treatment are analyzed; those who drop out are "censored."15指由不直接涉及试验的人员所进行的一种系统性检查，以评价试验的实施、数据的记录和分析是否与试验方案、标准操作规程以及药物临床试验相关法规要求相符16一种批准用于治疗2型糖尿病的药物17 Benzodiazepines have also been used as a "date rape" drug because they can markedly impair and even abolish functions that normally allow a person to resist or even want to resist sexual aggression or assault18本类药物也称弱安定药，包括氯氮卓(利眠宁，chlordiazepoxide，商品名Librium)、地西泮(安定，diazepam，商品名valium)、硝西泮(硝基安定，nitrazepam)、氟西泮(氟安定，flurazepam)及奥沙西泮(去甲羟基安定，舒宁，oxazepam)。
改进的OVM交通流模型及数值模拟研究
改进的OVM交通流模型及数值模拟研究张立东;贾磊;朱文兴【摘要】传统的最优速度模型(OVM)中驾驶员灵敏度系数均取常数,这与实际情况不完全相符,为此,提出一种基于驾驶员灵敏度系数概率分布的最优速度模型(PDDS-OVM).该模型根据概率统计理论,将驾驶员的灵敏度系数归纳为按一定概率分布的函数,交通流队列中的每辆车对应该分布的一个值.在Matlab7.0仿真平台上,对驾驶员灵敏度系数在定值、均匀分布、正态分布3种情况下,分别进行反复数值模拟仿真,结果表明PDDS-OVM模型能更好地描述交通流的波动特性.%The driver's sensitivity factor in former Optimal Velocity Model(OVM) is always constant, which does not fully comply with realistic traffic flow characteristics. To gain a more realistic and objective model, a kind of probability distribution driver sensitivity OVM, i.e. PDDS-OVM is studied. In the model, the constant driver's sensitivity is substituted with probability distribution function, and each car driver in the queue matches a probability value. With Matlab7.0 platform, three kinds of simulations are made, in which the driver's sensitivity is fixed value, mean distribution value, and normal distribution value. The simulation after many times shows that the PDDS-OVM model is more realistic than traditional ones, and can better describe the dynamics and complexity of traffic flow.【期刊名称】《计算机工程》【年(卷),期】2012(038)016【总页数】4页(P161-163,166)【关键词】交通流理论;跟驰模型;最优速度模型;驾驶员灵敏度;均匀分布;正态分布;数值模拟【作者】张立东;贾磊;朱文兴【作者单位】山东大学控制科学与工程学院,济南250061;山东省计算中心,济南250014;山东大学控制科学与工程学院,济南250061;山东大学控制科学与工程学院,济南250061【正文语种】中文【中图分类】TP391 概述交通流理论领域的研究大致可以分为交通流预测和交通流建模理论2 大方向。
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The “Invalid” Logical Argument Solved by Probability Theory
Use the numerical assignments from the joint probability table.
Probability theory as a generalization of logic returns an answer, while classical logic refuses to address the issue calling it “undecidable.”
Placement of 0s in JPT
Perfect choice for discussing formal manipulation rules of probability theory where the actual numerical assignments are not the issue.
Boolean Algebra
Formal Rules, Boolean Algebra, and Probability Theory
Boolean Algebra on a finite carrier set is a “closed” system, that is, there is always an answer. Moreover, neither numbers nor arithmetic operations are required to find that answer.
Two statements A and B each take on only two values. There are four cells in the joint probability table. The model assigning these numerical values is the implication function AB.
Example of Boolean Function
Function Table Boolean Formula
Substitute specific arguments
Boole’s Expansion Theorem
Any Boolean function can be expanded in the following manner. Applying this theorem in a recursive manner yields the disjunctive normal form (DNF).
Cell 3 indexes joint statement: A is TRUE and B is FALSE. f13 (A, B) has functional assignment of FALSE if A is TRUE and B is FALSE by very definition of operator. Therefore, cell 3 MUST HAVE a numerical assignment of 0 under this model.
Disjunctive Normal Form
For example, here is the expansion of any Boolean
function
f(x,y) with n = 2 arguments.
These are called the discriminants.
Disjunctive Normal Form
Cellular Automata Generalized To An Inferential System
27th International Workshop on Bayesian Inference and Maximum Entropy Methods in Science and Engineering,
The Motivating Question
But isn’t the quintessential feature of probability theory and inferential systems the ability to predict future events?
Proposed Solution
Probability Theory Generalizes Classical Logic
Here is an “invalid’’ logical argument, but one that is easily solved using probability theory in exactly the same manner as before.
Boolean Algebra
An example of a carrier set with four elements
All 16 ordered pairs from the carrier set
A mapping from an element of B x B into an element of B
cellular automata).
Some Basic Boolean Questions
1.How are Boolean functions defined? 2.How are syntactically correct Boolean
formulas produced? 3.What is a good canonical expression for
Logic Functions
A special case of Boolean Algebra
Different Notation
Functions with two arguments written in generic Boolean Algebra notation and then in Classical Logic notation.
Modus Ponens
Substitute the shortened DNF expansion for the implication function in Bayes’s Theorem
Bayes’s Theorem now looks like this
Modus Ponens
Boolean operations on denominator
Joint Probability Table
Cell 1
Cell 1
Cell 3
The same answer as before.
The model Mk assigns legitimate numerical values to the joint statements in the four cells of the jpt. The model is the implication function.
Boolean functions?
Why Is It Helpful?
eful for both logic functions and cellular automata
2.Axioms of Boolean Algebra used in Bayes’s Theorem
3.Canonical expressions substituted for complicated logic and CA rules
Saratoga Springs, New York, 11 July 2019
David J. Blower Cogon Systems Pensacola FL
Motivation
Why is it impossible to predict the behaviour of a cellular automaton?
Why Start with Boolean Algebra?
The following few slides on Boolean Algebra are solely to set the stage for analogous operations with classical logic functions (and
Classical Syllogism
Recapitulate Jaynes’s demonstration generalizing classical logic with probability theory (but here I emphasize the Boolean Algebra aspects). *
Jaynes used probability theory to generalize classical logic functions.
Treat CA from an inferential and informational point of view.
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Why Examine Cellular Automata?
Boolean operations on numerator
Bayes’s Theorem
Different Approach
Now solve modus ponens using a
joint probability table.
The answer should be the same.
Joint Probability Table
The logic function that returns B when arguments A and B given. f10 (A,B) on next slide.