TY - CONF AB - We introduce the notion of permissiveness in transactional memories (TM). Intuitively, a TM is permissive if it never aborts a transaction when it need not. More specifically, a TM is permissive with respect to a safety property p if the TM accepts every history that satisfies p. Permissiveness, like safety and liveness, can be used as a metric to compare TMs. We illustrate that it is impractical to achieve permissiveness deterministically, and then show how randomization can be used to achieve permissiveness efficiently. We introduce Adaptive Validation STM (AVSTM), which is probabilistically permissive with respect to opacity; that is, every opaque history is accepted by AVSTM with positive probability. Moreover, AVSTM guarantees lock freedom. Owing to its permissiveness, AVSTM outperforms other STMs by up to 40% in read dominated workloads in high contention scenarios. But, in low contention scenarios, the book-keeping done by AVSTM to achieve permissiveness makes AVSTM, on average, 20-30% worse than existing STMs. AU - Guerraoui, Rachid AU - Thomas Henzinger AU - Vasu Singh ID - 4386 TI - Permissiveness in transactional memories VL - 5218 ER - TY - CONF AB - Software transactional memory (STM) offers a disciplined concurrent programming model for exploiting the parallelism of modern processor architectures. This paper presents the first deterministic specification automata for strict serializability and opacity in STMs. Using an antichain-based tool, we show our deterministic specifications to be equivalent to more intuitive, nondeterministic specification automata (which are too large to be determinized automatically). Using deterministic specification automata, we obtain a complete verification tool for STMs. We also show how to model and verify contention management within STMs. We automatically check the opacity of popular STM algorithms, such as TL2 and DSTM, with a universal contention manager. The universal contention manager is nondeterministic and establishes correctness for all possible contention management schemes. AU - Guerraoui, Rachid AU - Thomas Henzinger AU - Vasu Singh ID - 4387 TI - Completeness and nondeterminism in model checking transactional memories VL - 5201 ER - TY - CONF AU - Beyer, Dirk AU - Damien Zufferey AU - Majumdar, Ritankar S ID - 4397 TI - CSIsat: Interpolation for LA+EUF ER - TY - CONF AU - Aviv,Adam J. AU - Pavol Cerny AU - Clark,Sandy AU - Cronin,Eric AU - Shah,Gaurav AU - Sherr,Micah AU - Blaze,Matt ID - 4400 TI - Security Evaluation of ES&S Voting Machines and Election Management System ER - TY - THES AB - Models of timed systems must incorporate not only the sequence of system events, but the timings of these events as well to capture the real-time aspects of physical systems. Timed automata are models of real-time systems in which states consist of discrete locations and values for real-time clocks. The presence of real-time clocks leads to an uncountable state space. This thesis studies verification problems on timed automata in a game theoretic framework. For untimed systems, two systems are close if every sequence of events of one system is also observable in the second system. For timed systems, the difference in timings of the two corresponding sequences is also of importance. We propose the notion of bisimulation distance which quantifies timing differences; if the bisimulation distance between two systems is epsilon, then (a) every sequence of events of one system has a corresponding matching sequence in the other, and (b) the timings of matching events in between the two corresponding traces do not differ by more than epsilon. We show that we can compute the bisimulation distance between two timed automata to within any desired degree of accuracy. We also show that the timed verification logic TCTL is robust with respect to our notion of quantitative bisimilarity, in particular, if a system satisfies a formula, then every close system satisfies a close formula. Timed games are used for distinguishing between the actions of several agents, typically a controller and an environment. The controller must achieve its objective against all possible choices of the environment. The modeling of the passage of time leads to the presence of zeno executions, and corresponding unrealizable strategies of the controller which may achieve objectives by blocking time. We disallow such unreasonable strategies by restricting all agents to use only receptive strategies --strategies which while not being required to ensure time divergence by any agent, are such that no agent is responsible for blocking time. Time divergence is guaranteed when all players use receptive strategies. We show that timed automaton games with receptive strategies can be solved by a reduction to finite state turn based game graphs. We define the logic timed alternating-time temporal logic for verification of timed automaton games and show that the logic can be model checked in EXPTIME. We also show that the minimum time required by an agent to reach a desired location, and the maximum time an agent can stay safe within a set of locations, against all possible actions of its adversaries are both computable. We next study the memory requirements of winning strategies for timed automaton games. We prove that finite memory strategies suffice for safety objectives, and that winning strategies for reachability objectives may require infinite memory in general. We introduce randomized strategies in which an agent can propose a probabilistic distribution of moves and show that finite memory randomized strategies suffice for all omega-regular objectives. We also show that while randomization helps in simplifying winning strategies, and thus allows the construction of simpler controllers, it does not help a player in winning at more states, and thus does not allow the construction of more powerful controllers. Finally we study robust winning strategies in timed games. In a physical system, a controller may propose an action together with a time delay, but the action cannot be assumed to be executed at the exact proposed time delay. We present robust strategies which incorporate such jitters and show that the set of states from which an agent can win robustly is computable. AU - Prabhu, Vinayak ID - 4409 TI - Games for the verification of timed systems ER - TY - THES AB - Many computing applications, especially those in safety critical embedded systems, require highly predictable timing properties. However, time is often not present in the prevailing computing and networking abstractions. In fact, most advances in computer architecture, software, and networking favor average-case performance over timing predictability. This thesis studies several methods for the design of concurrent and/or distributed embedded systems with precise timing guarantees. The focus is on flexible and compositional methods for programming and verification of the timing properties. The presented methods together with related formalisms cover two levels of design: (1) Programming language/model level. We propose the distributed variant of Giotto, a coordination programming language with an explicit temporal semantics—the logical execution time (LET) semantics. The LET of a task is an interval of time that specifies the time instants at which task inputs and outputs become available (task release and termination instants). The LET of a task is always non-zero. This allows us to communicate values across the network without changing the timing information of the task, and without introducing nondeterminism. We show how this methodology supports distributed code generation for distributed real-time systems. The method gives up some performance in favor of composability and predictability. We characterize the tradeoff by comparing the LET semantics with the semantics used in Simulink. (2) Abstract task graph level. We study interface-based design and verification of applications represented with task graphs. We consider task sequence graphs with general event models, and cyclic graphs with periodic event models with jitter and phase. Here an interface of a component exposes time and resource constraints of the component. Together with interfaces we formally define interface composition operations and the refinement relation. For efficient and flexible composability checking two properties are important: incremental design and independent refinement. According to the incremental design property the composition of interfaces can be performed in any order, even if interfaces for some components are not known. The refinement relation is defined such that in a design we can always substitute a refined interface for an abstract one. We show that the framework supports independent refinement, i.e., the refinement relation is preserved under composition operations. AU - Matic, Slobodan ID - 4415 TI - Compositionality in deterministic real-time embedded systems ER - TY - CONF AB - We describe Valigator, a software tool for imperative program verification that efficiently combines symbolic computation and automated reasoning in a uniform framework. The system offers support for automatically generating and proving verification conditions and, most importantly, for automatically inferring loop invariants and bound assertions by means of symbolic summation, Gröbner basis computation, and quantifier elimination. We present general principles of the implementation and illustrate them on examples. AU - Thomas Henzinger AU - Hottelier, Thibaud AU - Kovács, Laura ID - 4452 TI - Valigator: A verification tool with bound and invariant generation VL - 5330 ER - TY - JOUR AB - I discuss two main challenges in embedded systems design: the challenge to build predictable systems, and that to build robust systems. I suggest how predictability can be formalized as a form of determinism, and robustness as a form of continuity. AU - Thomas Henzinger ID - 4509 IS - 1881 JF - Philosophical Transactions of the Royal Society A Mathematical Physical and Engineering Sciences TI - Two challenges in embedded systems design: Predictability and robustness VL - 366 ER - TY - THES AB - Complex requirements, time-to-market pressure and regulatory constraints have made the designing of embedded systems extremely challenging. This is evident by the increase in effort and expenditure for design of safety-driven real-time control-dominated applications like automotive and avionic controllers. Design processes are often challenged by lack of proper programming tools for specifying and verifying critical requirements (e.g. timing and reliability) of such applications. Platform based design, an approach for designing embedded systems, addresses the above concerns by separating requirement from architecture. The requirement specifies the intended behavior of an application while the architecture specifies the guarantees (e.g. execution speed, failure rate etc). An implementation, a mapping of the requirement on the architecture, is then analyzed for correctness. The orthogonalization of concerns makes the specification and analyses simpler. An effective use of such design methodology has been proposed in Logical Execution Time (LET) model of real-time tasks. The model separates the timing requirements (specified by release and termination instances of a task) from the architecture guarantees (specified by worst-case execution time of the task). This dissertation proposes a coordination language, Hierarchical Timing Language (HTL), that captures the timing and reliability requirements of real-time applications. An implementation of the program on an architecture is then analyzed to check whether desired timing and reliability requirements are met or not. The core framework extends the LET model by accounting for reliability and refinement. The reliability model separates the reliability requirements of tasks from the reliability guarantees of the architecture. The requirement expresses the desired long-term reliability while the architecture provides a short-term reliability guarantee (e.g. failure rate for each iteration). The analysis checks if the short-term guarantee ensures the desired long-term reliability. The refinement model allows replacing a task by another task during program execution. Refinement preserves schedulability and reliability, i.e., if a refined task is schedulable and reliable for an implementation, then the refining task is also schedulable and reliable for the implementation. Refinement helps in concise specification without overloading analysis. The work presents the formal model, the analyses (both with and without refinement), and a compiler for HTL programs. The compiler checks composition and refinement constraints, performs schedulability and reliability analyses, and generates code for implementation of an HTL program on a virtual machine. Three real-time controllers, one each from automatic control, automotive control and avionic control, are used to illustrate the steps in modeling and analyzing HTL programs. AU - Ghosal, Arkadeb ID - 4524 TI - A hierarchical coordination language for reliable real-time tasks ER - TY - CONF AB - The search for proof and the search for counterexamples (bugs) are complementary activities that need to be pursued concurrently in order to maximize the practical success rate of verification tools.While this is well-understood in safety verification, the current focus of liveness verification has been almost exclusively on the search for termination proofs. A counterexample to termination is an infinite programexecution. In this paper, we propose a method to search for such counterexamples. The search proceeds in two phases. We first dynamically enumerate lasso-shaped candidate paths for counterexamples, and then statically prove their feasibility. We illustrate the utility of our nontermination prover, called TNT, on several nontrivial examples, some of which require bit-level reasoning about integer representations. AU - Ashutosh Gupta AU - Thomas Henzinger AU - Majumdar, Ritankar S AU - Rybalchenko, Andrey AU - Xu, Ru-Gang ID - 4521 TI - Proving non-termination ER - TY - CONF AB - We introduce bounded asynchrony, a notion of concurrency tailored to the modeling of biological cell-cell interactions. Bounded asynchrony is the result of a scheduler that bounds the number of steps that one process gets ahead of other processes; this allows the components of a system to move independently while keeping them coupled. Bounded asynchrony accurately reproduces the experimental observations made about certain cell-cell interactions: its constrained nondeterminism captures the variability observed in cells that, although equally potent, assume distinct fates. Real-life cells are not “scheduled”, but we show that distributed real-time behavior can lead to component interactions that are observationally equivalent to bounded asynchrony; this provides a possible mechanistic explanation for the phenomena observed during cell fate specification. We use model checking to determine cell fates. The nondeterminism of bounded asynchrony causes state explosion during model checking, but partial-order methods are not directly applicable. We present a new algorithm that reduces the number of states that need to be explored: our optimization takes advantage of the bounded-asynchronous progress and the spatially local interactions of components that model cells. We compare our own communication-based reduction with partial-order reduction (on a restricted form of bounded asynchrony) and experiments illustrate that our algorithm leads to significant savings. AU - Fisher, Jasmin AU - Thomas Henzinger AU - Maria Mateescu AU - Piterman, Nir ID - 4527 TI - Bounded asynchrony: Concurrency for modeling cell-cell interactions VL - 5054 ER - TY - JOUR AB - We consider the equivalence problem for labeled Markov chains (LMCs), where each state is labeled with an observation. Two LMCs are equivalent if every finite sequence of observations has the same probability of occurrence in the two LMCs. We show that equivalence can be decided in polynomial time, using a reduction to the equivalence problem for probabilistic automata, which is known to be solvable in polynomial time. We provide an alternative algorithm to solve the equivalence problem, which is based on a new definition of bisimulation for probabilistic automata. We also extend the technique to decide the equivalence of weighted probabilistic automata. AU - Doyen, Laurent AU - Thomas Henzinger AU - Raskin, Jean-François ID - 4532 IS - 3 JF - International Journal of Foundations of Computer Science TI - Equivalence of labeled Markov chains VL - 19 ER - TY - CONF AB - Interface theories have been proposed to support incremental design and independent implementability. Incremental design means that the compatibility checking of interfaces can proceed for partial system descriptions, without knowing the interfaces of all components. Independent implementability means that compatible interfaces can be refined separately, maintaining compatibility. We show that these interface theories provide no formal support for component reuse, meaning that the same component cannot be used to implement several different interfaces in a design. We add a new operation to interface theories in order to support such reuse. For example, different interfaces for the same component may refer to different aspects such as functionality, timing, and power consumption. We give both stateless and stateful examples for interface theories with component reuse. To illustrate component reuse in interface-based design, we show how the stateful theory provides a natural framework for specifying and refining PCI bus clients. AU - Doyen, Laurent AU - Thomas Henzinger AU - Jobstmann, Barbara AU - Tatjana Petrov ID - 4533 TI - Interface theories with component reuse ER - TY - JOUR AB - A stochastic graph game is played by two players on a game graph with probabilistic transitions. We consider stochastic graph games with ω-regular winning conditions specified as parity objectives, and mean-payoff (or limit-average) objectives. These games lie in NP ∩ coNP. We present a polynomial-time Turing reduction of stochastic parity games to stochastic mean-payoff games. AU - Krishnendu Chatterjee AU - Thomas Henzinger ID - 4534 IS - 1 JF - Information Processing Letters TI - Reduction of stochastic parity to stochastic mean-payoff games VL - 106 ER - TY - CONF AB - We propose the notion of logical reliability for real-time program tasks that interact through periodically updated program variables. We describe a reliability analysis that checks if the given short-term (e.g., single-period) reliability of a program variable update in an implementation is sufficient to meet the logical reliability requirement (of the program variable) in the long run. We then present a notion of design by refinement where a task can be refined by another task that writes to program variables with less logical reliability. The resulting analysis can be combined with an incremental schedulability analysis for interacting real-time tasks proposed earlier for the Hierarchical Timing Language (HTL), a coordination language for distributed real-time systems. We implemented a logical-reliability-enhanced prototype of the compiler and runtime infrastructure for HTL. AU - Krishnendu Chatterjee AU - Ghosal, Arkadeb AU - Thomas Henzinger AU - Iercan, Daniel AU - Kirsch, Christoph M AU - Pinello, Claudio AU - Sangiovanni-Vincentelli, Alberto ID - 4546 TI - Logical reliability of interacting real-time tasks ER - TY - JOUR AB - The value of a finite-state two-player zero-sum stochastic game with limit-average payoff can be approximated to within ε in time exponential in a polynomial in the size of the game times polynomial in logarithmic in 1/ε, for all ε > 0. AU - Krishnendu Chatterjee AU - Majumdar, Ritankar S AU - Thomas Henzinger ID - 4548 IS - 2 JF - International Journal of Game Theory TI - Stochastic limit-average games are in EXPTIME VL - 37 ER - TY - CONF AB - We present and evaluate a framework and tool for combining multiple program analyses which allows the dynamic (on-line) adjustment of the precision of each analysis depending on the accumulated results. For example, the explicit tracking of the values of a variable may be switched off in favor of a predicate abstraction when and where the number of different variable values that have been encountered has exceeded a specified threshold. The method is evaluated on verifying the SSH client/server software and shows significant gains compared with predicate abstraction-based model checking. AU - Beyer, Dirk AU - Thomas Henzinger AU - Théoduloz, Grégory ID - 4568 TI - Program analysis with dynamic change of precision ER - TY - JOUR AB - We have detected a spin-dependent displacement perpendicular to the refractive index gradient for photons passing through an air-glass interface. The effect is the photonic version of the spin Hall effect in electronic systems, indicating the universality of the effect for particles of different nature. Treating the effect as a weak measurement of the spin projection of the photons, we used a preselection and postselection technique on the spin state to enhance the original displacement by nearly four orders of magnitude, attaining sensitivity to displacements of ∼1 angstrom. The spin Hall effect can be used for manipulating photonic angular momentum states, and the measurement technique holds promise for precision metrology. AU - Onur Hosten AU - Kwiat, Paul ID - 581 IS - 5864 JF - Science TI - Observation of the spin hall effect of light via weak measurements VL - 319 ER - TY - CONF AB - Using “quantum weak-measurements” as a coherent enhancement technique for small signals, we have measured the recently proposed “spin Hall effect” of light at an air-glass interface, and are working on the smoothly varying refractive-index case. AU - Hosten, Onur AU - Kwiat, Paul ID - 584 SN - 21622701 TI - Spin hall effect of light via weak measurements: Sharp and smooth index variations ER - TY - JOUR AB - Homeostasis of internal carbon dioxide (CO2) and oxygen (O2) levels is fundamental to all animals. Here we examine the CO2 response of the nematode Caenorhabditis elegans. This species inhabits rotting material, which typically has a broad CO2 concentration range. We show that well fed C. elegans avoid CO2 levels above 0.5%. Animals can respond to both absolute CO2 concentrations and changes in CO2 levels within seconds. Responses to CO2 do not reflect avoidance of acid pH but appear to define a new sensory response. Sensation of CO2 is promoted by the cGMP-gated ion channel subunits TAX-2 and TAX-4, but other pathways are also important. Robust CO2 avoidance in well fed animals requires inhibition of the DAF-16 forkhead transcription factor by the insulin-like receptor DAF-2. Starvation, which activates DAF-16, strongly suppresses CO2 avoidance. Exposure to hypoxia (<1% O2) also suppresses CO2 avoidance via activation of the hypoxia-inducible transcription factor HIF-1. The npr-1 215V allele of the naturally polymorphic neuropeptide receptor npr-1, besides inhibiting avoidance of high ambient O2 in feeding C. elegans, also promotes avoidance of high CO2. C. elegans integrates competing O2 and CO2 sensory inputs so that one response dominates. Food and allelic variation at NPR-1 regulate which response prevails. Our results suggest that multiple sensory inputs are coordinated by C. elegans to generate different coherent foraging strategies. AU - Bretscher, A. J. AU - Busch, K. E. AU - de Bono, Mario ID - 6146 IS - 23 JF - Proceedings of the National Academy of Sciences SN - 0027-8424 TI - A carbon dioxide avoidance behavior is integrated with responses to ambient oxygen and food in Caenorhabditis elegans VL - 105 ER - TY - JOUR AU - Kammenga, Jan E. AU - Phillips, Patrick C. AU - de Bono, Mario AU - Doroszuk, Agnieszka ID - 6148 IS - 4 JF - Trends in Genetics SN - 0168-9525 TI - Beyond induced mutants: using worms to study natural variation in genetic pathways VL - 24 ER - TY - JOUR AU - Olofsson, Birgitta AU - de Bono, Mario ID - 6149 IS - 5 JF - Current Biology SN - 0960-9822 TI - Sleep: dozy worms and sleepy flies VL - 18 ER - TY - JOUR AB - Cell interaction phenomena in polymer electrolyte fuel cell stacks that arise from imbalance between adjacent cells are investigated in detail experimentally and theoretically. A specialized two-cell stack with advanced localized diagnostics was developed and used to analyze the mechanism and effect of cell-to-cell coupling as a result of operationally relevant variations in reactant feed flow. Contributions to overall and local voltage changes with respect to uniformly operated cells are scrutinized. Unequal operation of the cells causes in-plane current in the bipolar plate to redistribute current and result in inhomogeneous polarization. Both increasing and decreasing polarization along the air-flow path reduces cell power as compared to isopotential operation. A two-dimensional model based on a commercial computational fluid dynamics code is used to back and extend the experimental results to more general cases. Furthermore, the experimental setup presented allowed for the first time to perform simultaneous localized electrochemical impedance spectroscopy beyond the single-cell level. The mechanism of mutual cell interaction on local and integral spectra is revealed. Results show that virtually identical operation of the cells is essential to obtain meaningful integral spectra. AU - Freunberger, Stefan Alexander AU - Schneider, Ingo A. AU - Sui, Pang-Chieh AU - Wokaun, Alexander AU - Djilali, Nedjib AU - Büchi, Felix N. ID - 7321 IS - 7 JF - Journal of The Electrochemical Society SN - 0013-4651 TI - Cell interaction phenomena in polymer electrolyte fuel cell stacks VL - 155 ER - TY - JOUR AB - A comparative, experimental diffusivity study of gas diffusion layer (GDL) materials for polymer electrolyte fuel cells (PEFC) is presented for the first time. The GDL plays an important role for electrochemical losses due to gas transport limitations at high current densities. Characterization and optimization of these layers is therefore essential to improve power density. A recently developed method which allows for fast diffusimetry is applied and data compared to the literature values. Measurements are made as a function of direction and compression and the effect of different binder structures and hydrophobic treatments on effective diffusivities are discussed. A better understanding of the results is gained by including novel GDL cross-section images and a meaningful unit cell model for the interpretation of the data. The diffusivity data is valuable for GDL manufacturers and future PEFC models. The study reveals that a binder–fiber ratio larger than 50% has a negative impact on the effective diffusion properties. The hydrophobic treatment which is necessary to improve the water management can impede diffusion and thus reduce the power density. Furthermore binder has an isotropic effect while compression pronounces the in-plane orientation of the fibers. AU - Flückiger, Reto AU - Freunberger, Stefan Alexander AU - Kramer, Denis AU - Wokaun, Alexander AU - Scherer, Günther G. AU - Büchi, Felix N. ID - 7320 IS - 2 JF - Electrochimica Acta SN - 0013-4686 TI - Anisotropic, effective diffusivity of porous gas diffusion layer materials for PEFC VL - 54 ER - TY - JOUR AB - The gas diffusion layers (GDLs) of a membrane electrode assembly (MEA) serve as link between flow field and porous electrode within a polymer electrolyte fuel cell. Beside ensuring sufficient electrical and thermal contact between the whole electrode area and the flow field, these typically 200–400 μm thick porous structures enable the access of educts to the electrode area which would be occluded by the flow field lands if the flow field is directly attached to the electrode. Hence, the characterisation of properties pertaining to mass transport of educts and products through these structures is indispensable whilst examining the contribution of the GDLs to the overall electrochemical characteristics of a MEA. A fast and cost effective method to measure the effective diffusivity of a GDL is presented. Electrochemical impedance spectroscopy is applied to measure the effective ionic conductivity of an electrolyte-soaked GDL. Taking advantage of the analogy between Ficks and Ohms law, this provides a measure for the effective diffusivity. The method is described in detail, including experimental as well as theoretical aspects, and selected results, highlighting the anisotropy and dependence on the degree of compression, are shown. Moreover, a two-dimensional model consisting of regularly spaced ellipses is developed to represent the porous structure of the GDL, and by using conformal maps, the agreement between this model and experiment with respect to the sensitivity of the effective diffusivity towards compression is shown. AU - Kramer, Denis AU - Freunberger, Stefan Alexander AU - Flückiger, Reto AU - Schneider, Ingo A. AU - Wokaun, Alexander AU - Büchi, Felix N. AU - Scherer, Günther G. ID - 7322 IS - 1 JF - Journal of Electroanalytical Chemistry SN - 1572-6657 TI - Electrochemical diffusimetry of fuel cell gas diffusion layers VL - 612 ER - TY - CONF AB - The propagation of single cell performance losses to adjacent cells in a polymer electrolyte fuel cell stack is studied by means of local current density measurements in a two cell stack. In this stack, the working conditions of adjacent cells can be controlled independently in order to deliberately change the performance of one cell (inducing cell) and study the coupling effects to the adjacent cell (response cell), while keeping the working conditions of the later one unchanged. The experiments have shown that changes in the current density distribution caused by lowering of the air stoichiometry in the inducing cell cause changes in the current density distribution of the response cell in the order of 60% of the change of the inducing cell, even when the air stoichiometry of the response cell is kept constant. The losses in cell voltage of the inducing cell cause losses in cell voltage of the response cell in a magnitude between 30 and 50%. AU - Santis, Marco AU - Freunberger, Stefan Alexander AU - Papra, Matthias AU - Büchi, Felix N. ID - 7425 SN - 0791837645 T2 - 3rd International Conference on Fuel Cell Science, Engineering and Technology TI - Experimental investigation of the propagation of local current density variations to adjacent cells in PEFC stacks ER - TY - CONF AB - This paper addresses the following question: what is the minimum-sized synchronous window needed to solve consensus in an otherwise asynchronous system? In answer to this question, we present the first optimally-resilient algorithm ASAP that solves consensus as soon as possible in an eventually synchronous system, i.e., a system that from some time GST onwards, delivers messages in a timely fashion. ASAP guarantees that, in an execution with at most f failures, every process decides no later than round GST + f + 2, which is optimal. AU - Alistarh, Dan-Adrian AU - Gilbert, Seth AU - Guerraoui, Rachid AU - Travers, Corentin ID - 753 TI - How to solve consensus in the smallest window of synchrony VL - 5218 LNCS ER - TY - JOUR AU - Robinson, Matthew Richard AU - Pilkington, Jill G. AU - Clutton-Brock, Tim H. AU - Pemberton, Josephine M. AU - Kruuk, Loeske. E.B. ID - 7752 IS - 10 JF - Current Biology SN - 0960-9822 TI - Environmental heterogeneity generates fluctuating selection on a secondary sexual trait VL - 18 ER - TY - JOUR AB - Mutation rate varies greatly between nucleotide sites of the human genome and depends both on the global genomic location and the local sequence context of a site. In particular, CpG context elevates the mutation rate by an order of magnitude. Mutations also vary widely in their effect on the molecular function, phenotype, and fitness. Independence of the probability of occurrence of a new mutation's effect has been a fundamental premise in genetics. However, highly mutable contexts may be preserved by negative selection at important sites but destroyed by mutation at sites under no selection. Thus, there may be a positive correlation between the rate of mutations at a nucleotide site and the magnitude of their effect on fitness. We studied the impact of CpG context on the rate of human-chimpanzee divergence and on intrahuman nucleotide diversity at non-synonymous coding sites. We compared nucleotides that occupy identical positions within codons of identical amino acids and only differ by being within versus outside CpG context. Nucleotides within CpG context are under a stronger negative selection, as revealed by their lower, proportionally to the mutation rate, rate of evolution and nucleotide diversity. In particular, the probability of fixation of a non-synonymous transition at a CpG site is two times lower than at a CpG site. Thus, sites with different mutation rates are not necessarily selectively equivalent. This suggests that the mutation rate may complement sequence conservation as a characteristic predictive of functional importance of nucleotide sites. AU - Schmidt, Steffen AU - Gerasimova, Anna AU - Fyodor Kondrashov AU - Adzuhbei, Ivan A AU - Kondrashov, Alexey S AU - Sunyaev, Shamil R ID - 844 IS - 11 JF - PLoS Genetics TI - Hypermutable non-synonymous sites are under stronger negative selection VL - 4 ER - TY - JOUR AB - The copK gene is localized on the pMOL30 plasmid of Cupriavidus metallidurans CH34 within the complex cop cluster of genes, for which 21 genes have been identified. The expression of the corresponding periplasmic CopK protein is strongly upregulated in the presence of copper, leading to a high periplasmic accumulation. The structure and metal-binding properties of CopK were investigated by NMR and mass spectrometry. The protein is dimeric in the apo state with a dissociation constant in the range of 10- 5 M estimated from analytical ultracentrifugation. Mass spectrometry revealed that CopK has two high-affinity Cu(I)-binding sites per monomer with different Cu(I) affinities. Binding of Cu(II) was observed but appeared to be non-specific. The solution structure of apo-CopK revealed an all-β fold formed of two β-sheets in perpendicular orientation with an unstructured C-terminal tail. The dimer interface is formed by the surface of the C-terminal β-sheet. Binding of the first Cu(I)-ion induces a major structural modification involving dissociation of the dimeric apo-protein. Backbone chemical shifts determined for the 1Cu(I)-bound form confirm the conservation of the N-terminal β-sheet, while the last strand of the C-terminal sheet appears in slow conformational exchange. We hypothesize that the partial disruption of the C-terminal β-sheet is related to dimer dissociation. NH-exchange data acquired on the apo-protein are consistent with a lower thermodynamic stability of the C-terminal sheet. CopK contains seven methionine residues, five of which appear highly conserved. Chemical shift data suggest implication of two or three methionines (Met54, Met38, Met28) in the first Cu(I) site. Addition of a second Cu(I) ion further increases protein plasticity. Comparison of the structural and metal-binding properties of CopK with other periplasmic copper-binding proteins reveals two conserved features within these functionally related proteins: the all-β fold and the methionine-rich Cu(I)-binding site. AU - Bersch, Beate AU - Favier, Adrien AU - Schanda, Paul AU - van Aelst, Sébastien AU - Vallaeys, Tatiana AU - Covès, Jacques AU - Mergeay, Max AU - Wattiez, Ruddy ID - 8481 IS - 2 JF - Journal of Molecular Biology KW - Molecular Biology SN - 0022-2836 TI - Molecular structure and metal-binding properties of the periplasmic CopK protein expressed in Cupriavidus metallidurans CH34 during copper challenge VL - 380 ER - TY - JOUR AB - The KIX domain of the transcription co-activator CBP is a three-helix bundle protein that folds via rapid accumulation of an intermediate state, followed by a slower folding phase. Recent NMR relaxation dispersion studies revealed the presence of a low-populated (excited) state of KIX that exists in equilibrium with the natively folded form under non-denaturing conditions, and likely represents the equilibrium analog of the folding intermediate. Here, we combine amide hydrogen/deuterium exchange measurements using rapid NMR data acquisition techniques with backbone 15N and 13C relaxation dispersion experiments to further investigate the equilibrium folding of the KIX domain. Residual structure within the folding intermediate is detected by both methods, and their combination enables reliable quantification of the amount of persistent residual structure. Three well-defined folding subunits are found, which display variable stability and correspond closely to the individual helices in the native state. While two of the three helices (α2 and α3) are partially formed in the folding intermediate (to ∼ 50% and ∼ 80%, respectively, at 20 °C), the third helix is disordered. The observed helical content within the excited state exceeds the helical propensities predicted for the corresponding peptide regions, suggesting that the two helices are weakly mutually stabilized, while methyl 13C relaxation dispersion data indicate that a defined packing arrangement is unlikely. Temperature-dependent experiments reveal that the largest enthalpy and entropy changes along the folding reaction occur during the final transition from the intermediate to the native state. Our experimental data are consistent with a folding mechanism where helices α2 and α3 form rapidly, although to different extents, while helix α1 consolidates only as folding proceeds to complete the native state-structure. AU - Schanda, Paul AU - Brutscher, Bernhard AU - Konrat, Robert AU - Tollinger, Martin ID - 8480 IS - 4 JF - Journal of Molecular Biology KW - Molecular Biology SN - 0022-2836 TI - Folding of the KIX domain: Characterization of the equilibrium analog of a folding intermediate using 15N/13C relaxation dispersion and fast 1H/2H amide exchange NMR spectroscopy VL - 380 ER - TY - JOUR AB - The SOFAST-HMQC experiment [P. Schanda, B. Brutscher, Very fast two-dimensional NMR spectroscopy for real-time investigation of dynamic events in proteins on the time scale of seconds, J. Am. Chem. Soc. 127 (2005) 8014–8015] allows recording two-dimensional correlation spectra of macromolecules such as proteins in only a few seconds acquisition time. To achieve the highest possible sensitivity, SOFAST-HMQC experiments are preferably performed on high-field NMR spectrometers equipped with cryogenically cooled probes. The duty cycle of over 80% in fast-pulsing SOFAST-HMQC experiments, however, may cause problems when using a cryogenic probe. Here we introduce SE-IPAP-SOFAST-HMQC, a new pulse sequence that provides comparable sensitivity to standard SOFAST-HMQC, while avoiding heteronuclear decoupling during 1H detection, and thus significantly reducing the radiofrequency load of the probe during the experiment. The experiment is also attractive for fast and sensitive measurement of heteronuclear one-bond spin coupling constants. AU - Kern, Thomas AU - Schanda, Paul AU - Brutscher, Bernhard ID - 8482 IS - 2 JF - Journal of Magnetic Resonance KW - Nuclear and High Energy Physics KW - Biophysics KW - Biochemistry KW - Condensed Matter Physics SN - 1090-7807 TI - Sensitivity-enhanced IPAP-SOFAST-HMQC for fast-pulsing 2D NMR with reduced radiofrequency load VL - 190 ER - TY - JOUR AB - DNA methylation is an ancient process found in all domains of life. Although the enzymes that mediate methylation have remained highly conserved, DNA methylation has been adapted for a variety of uses throughout evolution, including defense against transposable elements and control of gene expression. Defects in DNA methylation are linked to human diseases, including cancer. Methylation has been lost several times in the course of animal and fungal evolution, thus limiting the opportunity for study in common model organisms. In the past decade, plants have emerged as a premier model system for genetic dissection of DNA methylation. A recent combination of plant genetics with powerful genomic approaches has led to a number of exciting discoveries and promises many more. AU - Zilberman, Daniel ID - 9537 IS - 5 JF - Current Opinion in Plant Biology SN - 1369-5266 TI - The evolving functions of DNA methylation VL - 11 ER - TY - JOUR AB - We give many examples of applying Bogoliubov's forest formula to iterative solutions of various nonlinear equations. The same formula describes an extremely wide class of objects, from an ordinary quadratic equation to renormalization in quantum field theory. AU - Morozov, Alexei Y AU - Maksym Serbyn ID - 965 IS - 2 JF - Theoretical and Mathematical Physics TI - Nonlinear algebra and Bogoliubov's recursion VL - 154 ER - TY - JOUR AB - In this paper, using the ideas of Bessi and Mather, we present a simple mechanical system exhibiting Arnold diffusion. This system of a particle in a small periodic potential can be also interpreted as ray propagation in a periodic optical medium with a near-constant index of refraction. Arnold diffusion in this context manifests itself as an arbitrary finite change of direction for nearly constant index of refraction. AU - Kaloshin, Vadim AU - Levi, Mark ID - 8510 IS - 3 JF - Bulletin of the American Mathematical Society KW - Applied Mathematics KW - General Mathematics SN - 0273-0979 TI - An example of Arnold diffusion for near-integrable Hamiltonians VL - 45 ER - TY - JOUR AB - The goal of this paper is to present to nonspecialists what is perhaps the simplest possible geometrical picture explaining the mechanism of Arnold diffusion. We choose to speak of a specific model—that of geometric rays in a periodic optical medium. This model is equivalent to that of a particle in a periodic potential in ${\mathbb R}^{n}$ with energy prescribed and to the geodesic flow in a Riemannian metric on ${\mathbb R}^{n} $. AU - Kaloshin, Vadim AU - Levi, Mark ID - 8509 IS - 4 JF - SIAM Review KW - Theoretical Computer Science KW - Applied Mathematics KW - Computational Mathematics SN - 0036-1445 TI - Geometry of Arnold diffusion VL - 50 ER - TY - JOUR AB - Background. The arginine vasopressin V1a receptor (V1aR) modulates social cognition and behavior in a wide variety of species. Variation in a repetitive microsatellite element in the 5′ flanking region of the V1aR gene (AVPR1A) in rodents has been associated with variation in brain V1aR expression and in social behavior. In humans, the 5′ flanking region of AVPR1A contains a tandem duplication of two ∼350 bp, microsatellite-containing elements located approximately 3.5 kb upstream of the transcription start site. The first block, referred to as DupA, contains a polymorphic (GT) 25microsatellite; the second block, DupB, has a complex (CT) 4-(TT)-(CT)8-(GT)24polymorphic motif, known as RS3. Polymorphisms in RS3 have been associated with variation in sociobehavioral traits in humans, including autism spectrum disorders. Thus, evolution of these regions may have contributed to variation in social behavior in primates. We examined the structure of these regions in six ape, six monkey, and one prosimian species. Results. Both tandem repeat blocks are present upstream of the AVPR1A coding region in five of the ape species we investigated, while monkeys have only one copy of this region. As in humans, the microsatellites within DupA and DupB are polymorphic in many primate species. Furthermore, both single (lacking DupB) and duplicated alleles (containing both DupA and DupB) are present in chimpanzee (Pan troglodytes) populations with allele frequencies of 0.795 and 0.205 for the single and duplicated alleles, respectively, based on the analysis of 47 wild-caught individuals. Finally, a phylogenetic reconstruction suggests two alternate evolutionary histories for this locus. Conclusion. There is no obvious relationship between the presence of the RS3 duplication and social organization in primates. However, polymorphisms identified in some species may be useful in future genetic association studies. In particular, the presence of both single and duplicated alleles in chimpanzees provides a unique opportunity to assess the functional role of this duplication in contributing to variation in social behavior in primates. While our initial studies show no signs of directional selection on this locus in chimps, pharmacological and genetic association studies support a potential role for this region in influencing V1aR expression and social behavior. AU - Donaldson, Zoe R AU - Fyodor Kondrashov AU - Putnam, Andrea S AU - Bai, Yaohui AU - Stoinski, Tara S AU - Hammock, Elizabeth A AU - Young, Larry ID - 895 IS - 1 JF - BMC Evolutionary Biology TI - Evolution of a behavior-linked microsatellite-containing element in the 5′ flanking region of the primate AVPR1A gene VL - 8 ER - TY - JOUR AB - The most common form of protein-coding gene overlap in eukaryotes is a simple nested structure, whereby one gene is embedded in an intron of another. Analysis of nested protein-coding genes in vertebrates, fruit flies and nematodes revealed substantially higher rates of evolutionary gains than losses. The accumulation of nested gene structures could not be attributed to any obvious functional relationships between the genes involved and represents an increase of the organizational complexity of animal genomes via a neutral process. AU - Assis, Raquel AU - Kondrashov, Alexey S AU - Koonin, Eugene V AU - Fyodor Kondrashov ID - 907 IS - 10 JF - Trends in Genetics TI - Nested genes and increasing organizational complexity of metazoan genomes VL - 24 ER - TY - JOUR AB - Eukaryotic chromatin is separated into functional domains differentiated by posttranslational histone modifications, histone variants, and DNA methylation1–6. Methylation is associated with repression of transcriptional initiation in plants and animals, and is frequently found in transposable elements. Proper methylation patterns are critical for eukaryotic development4,5, and aberrant methylation-induced silencing of tumor suppressor genes is a common feature of human cancer7. In contrast to methylation, the histone variant H2A.Z is preferentially deposited by the Swr1 ATPase complex near 5′ ends of genes where it promotes transcriptional competence8–20. How DNA methylation and H2A.Z influence transcription remains largely unknown. Here we show that in the plant Arabidopsis thaliana, regions of DNA methylation are quantitatively deficient in H2A.Z. Exclusion of H2A.Z is seen at sites of DNA methylation in the bodies of actively transcribed genes and in methylated transposons. Mutation of the MET1 DNA methyltransferase, which causes both losses and gains of DNA methylation4,5, engenders opposite changes in H2A.Z deposition, while mutation of the PIE1 subunit of the Swr1 complex that deposits H2A.Z17 leads to genome-wide hypermethylation. Our findings indicate that DNA methylation can influence chromatin structure and effect gene silencing by excluding H2A.Z, and that H2A.Z protects genes from DNA methylation. AU - Zilberman, Daniel AU - Coleman-Derr, Devin AU - Ballinger, Tracy AU - Henikoff, Steven ID - 9457 IS - 7218 JF - Nature KW - Multidisciplinary SN - 0028-0836 TI - Histone H2A.Z and DNA methylation are mutually antagonistic chromatin marks VL - 456 ER - TY - JOUR AB - Supraspheres (SS) composed of hundreds to thousands of metal nanoparticles (NPs) and crosslinked by dithiol linkers are assembled into larger structures, which are subsequently converted into nanoporous metals (NMs). Conversion is achieved by heating which removes organic molecules stabilizing the NPs and allows for NP fusion. Heating of SS solutions leads to NMs of overall macroscopic dimensions; localized radiation using collimated electron beam is used to prepare metallized surface micropatterns. Depending on the composition of supraspherical precursors, nanoporous materials composed of up to three metals can be obtained. Strategies for controlling pore size and nanoscale surface roughness of these materials are discussed. AU - Klajn, Rafal AU - Gray, Timothy P. AU - Wesson, Paul J. AU - Myers, Benjamin D. AU - Dravid, Vinayak P. AU - Smoukov, Stoyan K. AU - Grzybowski, Bartosz A. ID - 13423 IS - 18 JF - Advanced Functional Materials KW - Electrochemistry KW - Condensed Matter Physics KW - Biomaterials KW - Electronic KW - Optical and Magnetic Materials SN - 1616-301X TI - Bulk synthesis and surface patterning of nanoporous metals and alloys from supraspherical nanoparticle aggregates VL - 18 ER - TY - JOUR AB - Make like a leaf: The synthesis and characterization of a family of “flowerlike” Au/Fe3O4 nanoparticles is described, whereby Fe3O4 “leaves” adhere to a gold core (see image). The size and numbers of iron oxide domains can be adjusted flexibly by changing the proportion of the starting materials and the reaction time. AU - Wei, Yanhu AU - Klajn, Rafal AU - Pinchuk, Anatoliy O. AU - Grzybowski, Bartosz A. ID - 13422 IS - 10 JF - Small KW - Biomaterials KW - Biotechnology KW - General Materials Science KW - General Chemistry SN - 1613-6810 TI - Synthesis, shape control, and optical properties of hybrid Au/Fe3O4 “nanoflowers” VL - 4 ER - TY - JOUR AU - Barton, Nicholas H ID - 517 IS - 5-6 JF - Genetics Research TI - Identity and coalescence in structured populations: A commentary on 'Inbreeding coefficients and coalescence times' by Montgomery Slatkin VL - 89 ER - TY - JOUR AB - We explore the rich internal structure of Cs2 Feshbach molecules. Pure ultracold molecular samples are prepared in a CO2 -laser trap, and a multitude of weakly bound states is populated by elaborate magnetic-field ramping techniques. Our methods use different Feshbach resonances as input ports and various internal level crossings for controlled state transfer. We populate higher partial-wave states of up to eight units of rotational angular momentum (l -wave states). We investigate the molecular structure by measurements of the magnetic moments for various states. Avoided level crossings between different molecular states are characterized through the changes in magnetic moment and by a Landau-Zener tunneling method. Based on microwave spectroscopy, we present a precise measurement of the magnetic-field-dependent binding energy of the weakly bound s -wave state that is responsible for the large background scattering length of Cs. This state is of particular interest because of its quantum-halo character. AU - Mark, Michael AU - Ferlaino, Francesca AU - Knoop, Steven AU - Danzl, Johann G AU - Kraemer, Tobias AU - Chin, Cheng AU - Nägerl, Hanns AU - Grimm, Rudolf ID - 1035 IS - 4 JF - Physical Review A - Atomic, Molecular, and Optical Physics TI - Spectroscopy of ultracold trapped cesium Feshbach molecules VL - 76 ER - TY - JOUR AB - The metazoan nuclear envelope (NE) breaks down and re-forms during each cell cycle. Nuclear pore complexes (NPCs), which allow nucleocytoplasmic transport during interphase, assemble into the re-forming NE at the end of mitosis. Using in vitro NE assembly, we show that the vertebrate homologue of MEL-28 (maternal effect lethal), a recently discovered NE component in Caenorhabditis elegans, functions in postmitotic NPC assembly. MEL-28 interacts with the Nup107–160 complex (Nup for nucleoporin), an important building block of the NPC, and is essential for the recruitment of the Nup107–160 complex to chromatin. We suggest that MEL-28 acts as a seeding point for NPC assembly. AU - Franz, Cerstin AU - Walczak, Rudolf AU - Yavuz, Sevil AU - Santarella, Rachel AU - Gentzel, Marc AU - Askjaer, Peter AU - Galy, Vincent AU - HETZER, Martin W AU - Mattaj, Iain W AU - Antonin, Wolfram ID - 11116 IS - 2 JF - EMBO reports KW - Genetics KW - Molecular Biology KW - Biochemistry SN - 1469-221X TI - MEL‐28/ELYS is required for the recruitment of nucleoporins to chromatin and postmitotic nuclear pore complex assembly VL - 8 ER - TY - JOUR AB - The formation of the nuclear envelope (NE) around chromatin is a major membrane-remodelling event that occurs during cell division of metazoa. It is unclear whether the nuclear membrane reforms by the fusion of NE fragments or if it re-emerges from an intact tubular network of the endoplasmic reticulum (ER). Here, we show that NE formation and expansion requires a tubular ER network and occurs efficiently in the presence of the membrane fusion inhibitor GTPγS. Chromatin recruitment of membranes, which is initiated by tubule-end binding, followed by the formation, expansion and sealing of flat membrane sheets, is mediated by DNA-binding proteins residing in the ER. Thus, chromatin plays an active role in reshaping of the ER during NE formation. AU - Anderson, Daniel J. AU - HETZER, Martin W ID - 11115 IS - 10 JF - Nature Cell Biology KW - Cell Biology SN - 1465-7392 TI - Nuclear envelope formation by chromatin-mediated reorganization of the endoplasmic reticulum VL - 9 ER - TY - JOUR AB - About 20% of the world's population uses the Web, and a large majority thereof uses Web search engines to find information. As a result, many Web researchers are devoting much effort to improving the speed and capability of search technology. AU - Henzinger, Monika H ID - 11884 IS - 5837 JF - Science SN - 0036-8075 TI - Search technologies for the internet VL - 317 ER - TY - CONF AB - How much can smart combinatorial algorithms improve web search engines? To address this question we will describe three algorithms that have had a positive impact on web search engines: The PageRank algorithm, algorithms for finding near-duplicate web pages, and algorithms for index server loadbalancing. AU - Henzinger, Monika H ID - 11924 SN - 9780898716245 T2 - 18th Annual ACM-SIAM Symposium on Discrete Algorithms TI - Combinatorial algorithms for web search engines: three success stories ER - TY - JOUR AB - A 671 nm diode laser with a mode-hop-free tuning range of 40 GHz is described. This long tuning range is achieved by simultaneously ramping the external cavity length with the laser injection current. The laser output pointing remains fixed, independent of its frequency because of the cover slip cavity design. This system is simple, economical, robust, and easy to use for spectroscopy, as we demonstrate with lithium vapor and lithium atom beam experiments. AU - Carr, Adra AU - Serchest, Yancey AU - Waitukaitis, Scott R AU - Perreault, John AU - Lonij, Vincent AU - Cronin, Alexander ID - 128 IS - 10 JF - Review of Scientific Instruments TI - Cover slip external cavity diode laser VL - 78 ER - TY - JOUR AB - In flies, the large tangential cells of the lobula plate represent an important processing center for visual navigation based on optic flow. Although the visual response properties of these cells have been well studied in blowflies, information on their synaptic organization is mostly lacking. Here we study the distribution of presynaptic release and postsynaptic inhibitory sites in the same set of cells in Drosophila melanogaster. By making use of transgenic tools and immunohistochemistry, our results suggest that HS and VS cells of Drosophila express γ-aminobutyric acid (GABA) receptors in their dendritic region within the lobula plate, thus being postsynaptic to inhibitory input there. At their axon terminals in the protocerebrum, both cell types express synaptobrevin, suggesting the presence of presynaptic specializations there. HS- and VS-cell terminals additionally show evidence for postsynaptic GABAergic input, superimposed on this synaptic polarity. Our findings are in line with the general circuit for visual motion detection and receptive field properties as postulated from electrophysiological and optical recordings in blowflies, suggesting a similar functional organization of lobula plate tangential cells in the two species. AU - Raghu, Shamprasad V AU - Maximilian Jösch AU - Borst, Alexander AU - Reiff, Dierk F ID - 1297 IS - 4 JF - Journal of Comparative Neurology TI - Synaptic organization of lobula plate tangential cells in Drosophila: γ-aminobutyric acid receptors and chemical release sites VL - 502 ER - TY - CHAP AB - This book contains research articles on Diophantine Geometry, written by participants of a research program held at the Ennio De Giorgi Mathematical Research Center in Pisa, Italy, during the period April – July 2005. The authors are eminent experts in the field. Several subfields of the main topic are presented; the volume thus is particularly useful to get a broad overview of recent research developments. AU - Browning, Timothy D AU - Heath Brown, Roger ED - Zannier, Umberto ID - 167 T2 - Diophantine Geometry TI - Simultaneous equal sums of three powers VL - 4 ER - TY - JOUR AB - The authors investigate the composition profile of SiGe islands after capping with Si to form quantum dots, using a two step etching procedure and atomic force microscopy. Initially, the Si capping layers are removed by etching selectively Si over Ge and then the composition of the disclosed islands is addressed by selectively etching Ge over Si. For samples grown at 580 °C the authors show that even when overgrowth leads to a flat Si surface and the islands undergo strong morphological changes, a Ge-rich core region is still preserved in the dot. At high growth and overgrowth temperatures (740 °C), the experiments show that the newly formed base of the buried islands is more Si rich than their top. Furthermore, the authors find that for the growth conditions used, no lateral motion takes place during capping. AU - Georgios Katsaros AU - Stoffel, Mathieu AU - Rastelli, Armando AU - Schmidt, Oliver G AU - Kern, Klaus AU - Tersoff, Jerry ID - 1750 IS - 1 JF - Applied Physics Letters TI - Three-dimensional isocompositional profiles of buried SiGeSi (001) islands VL - 91 ER - TY - JOUR AB - In quantum information science, the phase of a wave function plays an important role in encoding information. Although most experiments in this field rely on dynamic effects to manipulate this information, an alternative approach is to use geometric phase, which has been argued to have potential fault tolerance. We demonstrated the controlled accumulation of a geometric phase, Berry's phase, in a superconducting qubit; we manipulated the qubit geometrically by means of microwave radiation and observed the accumulated phase in an interference experiment. We found excellent agreement with Berry's predictions and also observed a geometry-dependent contribution to dephasing. AU - Leek, Peter J AU - Johannes Fink AU - Blais, Alexandre AU - Bianchetti, R AU - Göppl, M AU - Gambetta, Jay M AU - Schuster, David I AU - Frunzio, Luigi AU - Schoelkopf, Robert J AU - Wallraff, Andreas ID - 1762 IS - 5858 JF - Science TI - Observation of Berry's phase in a solid-state qubit VL - 318 ER - TY - JOUR AB - Intrinsically photosensitive melanopsin-containing retinal ganglion cells (ipRGCs) control important physiological processes, including the circadian rhythm, the pupillary reflex, and the suppression of locomotor behavior (reviewed in [1]). ipRGCs are also activated by classical photoreceptors, the rods and cones, through local retinal circuits [2, 3]. ipRGCs can be transsynaptically labeled through the pupillary-reflex circuit with the derivatives of the Bartha strain of the alphaherpesvirus pseudorabies virus(PRV) [4, 5] that express GFP [6-12]. Bartha-strain derivatives spread only in the retrograde direction [13]. There is evidence that infected cells function normally for a while during GFP expression [7]. Here we combine transsynaptic PRV labeling, two-photon laser microscopy, and electrophysiological techniques to trace the local circuit of different ipRGC subtypes in the mouse retina and record light-evoked activity from the transsynaptically labeled ganglion cells. First, we show that ipRGCs are connected by monostratified amacrine cells that provide strong inhibition from classical-photoreceptor-driven circuits. Second, we show evidence that dopaminergic interplexiform cells are synaptically connected to ipRGCs. The latter finding provides a circuitry link between light-dark adaptation and ipRGC function. AU - Viney, Tim J AU - Bálint, Kamill AU - Hillier, Dániel AU - Sandra Siegert AU - Boldogköi, Zsolt S AU - Enquist, Lynn W AU - Meister, Markus AU - Cepko, Constance L AU - Roska, Botond M ID - 1797 IS - 11 JF - Current Biology TI - Local retinal circuits of melanopsin-containing ganglion cells identified by transsynaptic viral tracing VL - 17 ER - TY - JOUR AB - Respiratory complex I (NADH:ubiquinone oxidoreductase) is an L-shaped multisubunit protein assembly consisting of a hydrophobic membrane arm and a hydrophilic peripheral arm. It catalyses the transfer of two electrons from NADH to quinone coupled to the translocation of four protons across the membrane. Although we have solved recently the crystal structure of the peripheral arm, the structure of the complete enzyme and the coupling mechanism are not yet known. The membrane domain of Escherichia coli complex I consists of seven different subunits with total molecular mass of 258 kDa. It is significantly more stable than the whole enzyme, which allowed us to obtain well-ordered two-dimensional crystals of the domain, belonging to the space group p22121. Comparison of the projection map of negatively stained crystals with previously published low-resolution structures indicated that the characteristic curved shape of the membrane domain is remarkably well conserved between bacterial and mitochondrial enzymes, helping us to interpret projection maps in the context of the intact complex. Two pronounced stain-excluding densities at the distal end of the membrane domain are likely to represent the two large antiporter-like subunits NuoL and NuoM. Cryo-electron microscopy on frozen-hydrated crystals allowed us to calculate a projection map at 8 Å resolution. About 60 transmembrane α-helices, both perpendicular to the membrane plane and tilted, are present within one membrane domain, which is consistent with secondary structure predictions. A possible binding site and access channel for quinone are found at the interface with the peripheral arm. Tentative assignment of individual subunits to the features of the map has been made. The location of subunits NuoL and NuoM at substantial distance from the peripheral arm, which contains all the redox centres of the complex, indicates that conformational changes are likely to play a role in the mechanism of coupling between electron transfer and proton pumping. AU - Baranova, Ekaterina A AU - Holt, Peter J AU - Leonid Sazanov ID - 1965 IS - 1 JF - Journal of Molecular Biology TI - Projection structure of the membrane domain of Escherichia coli respiratory Complex I at 8 Å resolution VL - 366 ER - TY - JOUR AB - Respiratory complex I catalyses the transfer of electrons from NADH to quinone coupled to the translocation of protons across the membrane. The mechanism of coupling and the structure of the complete enzyme are not known. The membrane domain of the complex contains three similar antiporter-like subunits NuoL/M/N, probably involved in proton pumping. We have previously shown that subunits NuoL/M can be removed from the rest of the complex, suggesting their location at the distal end of the membrane domain. Here, using electron microscopy and single particle analysis, we show that subunits NuoL and M jointly occupy a distal half of the membrane domain, separated by about 10 nm from the interface with the peripheral arm. This indicates that coupling mechanism of complex I is likely to involve long range conformational changes. AU - Baranova, Ekaterina A AU - Morgan, David J AU - Leonid Sazanov ID - 1969 IS - 2 SPEC. ISS. JF - Journal of Structural Biology TI - Single particle analysis confirms distal location of subunits NuoL and NuoM in Escherichia coli complex I VL - 159 ER - TY - JOUR AB - Complex I of respiratory chains plays a central role in cellular energy production. Mutations in its subunits lead to many human neurodegenerative diseases. Recently, a first atomic structure of the hydrophilic domain of complex I from Thermus thermophilus was determined. This domain represents a catalytic core of the enzyme. It consists of eight different subunits, contains all the redox centers, and comprises more than half of the entire complex. In this review, novel mechanistic implications of the structure are discussed, and the effects of many known mutations of complex I subunits are interpreted in a structural context. AU - Leonid Sazanov ID - 1964 IS - 9 JF - Biochemistry TI - Respiratory complex I: Mechanistic and structural insights provided by the crystal structure of the hydrophilic domain VL - 46 ER - TY - CONF AB - We present a novel multi-scale representation and acquisition method for the animation of high-resolution facial geometry and wrinkles. We first acquire a static scan of the face including reflectance data at the highest possible quality. We then augment a traditional marker-based facial motion-capture system by two synchronized video cameras to track expression wrinkles. The resulting model consists of high-resolution geometry, motion-capture data, and expression wrinkles in 2D parametric form. This combination represents the facial shape and its salient features at multiple scales. During motion synthesis the motion-capture data deforms the high-resolution geometry using a linear shell-based mesh-deformation method. The wrinkle geometry is added to the facial base mesh using nonlinear energy optimization. We present the results of our approach for performance replay as well as for wrinkle editing. AU - Bernd Bickel AU - Botsch, Mario AU - Angst, Roland AU - Matusik, Wojciech AU - Otaduy, Miguel A AU - Pfister, Hanspeter AU - Groß, Markus S ID - 2091 TI - Multi scale capture of facial geometry and motion ER - TY - JOUR AB - We present a novel multi-scale representation and acquisition method for the animation of high-resolution facial geometry and wrinkles. We first acquire a static scan of the face including reflectance data at the highest possible quality. We then augment a traditional marker-based facial motion-capture system by two synchronized video cameras to track expression wrinkles. The resulting model consists of high-resolution geometry, motion-capture data, and expression wrinkles in 2D parametric form. This combination represents the facial shape and its salient features at multiple scales. During motion synthesis the motion-capture data deforms the high-resolution geometry using a linear shell-based mesh-deformation method. The wrinkle geometry is added to the facial base mesh using nonlinear energy optimization. We present the results of our approach for performance replay as well as for wrinkle editing. AU - Bernd Bickel AU - Botsch, Mario AU - Angst, Roland AU - Matusik, Wojciech AU - Otaduy, Miguel A AU - Pfister, Hanspeter AU - Groß, Markus S ID - 2093 IS - 3 JF - ACM Transactions on Graphics TI - Multi scale capture of facial geometry and motion VL - 26 ER - TY - JOUR AB - We introduce a new appearance-modeling paradigm for synthesizing the internal structure of a 3D model from photographs of a few cross-sections of a real object. When the internal surfaces of the 3D model are revealed as it is cut, carved, or simply clipped, we synthesize their texture from the input photographs. Our texture synthesis algorithm is best classified as a morphing technique, which efficiently outputs the texture attributes of each surface point on demand. For determining source points and their weights in the morphing algorithm, we propose an interpolation domain based on BSP trees that naturally resembles planar splitting of real objects. In the context of the interpolation domain, we define efficient warping and morphing operations that allow for real-time synthesis of textures. Overall, our modeling paradigm, together with its realization through our texture morphing algorithm, allow users to author 3D models that reveal highly realistic internal surfaces in a variety of artistic flavors. AU - Pietroni, Nico AU - Otaduy, Miguel A AU - Bernd Bickel AU - Ganovelli, Fabio AU - Groß, Markus S ID - 2092 IS - 3 JF - Computer Graphics Forum TI - Texturing internal surfaces from a few cross-sections VL - 26 ER - TY - JOUR AB - We extend to infinite dimensions an explicit formula of Chill, Fašangová, Metafune, and Pallara for the optimal angle of analyticity of analytic Ornstein-Uhlenbeck semigroups. The main ingredient is an abstract representation of the Ornstein-Uhlenbeck operator in divergence form. AU - Jan Maas AU - van Neerven, Jan M ID - 2118 IS - 3 JF - Archiv der Mathematik TI - On analytic Ornstein-Uhlenbeck semigroups in infinite dimensions VL - 89 ER - TY - JOUR AB - We use the x-ray absorption fine structure spectroscopy at Nb K edge to reveal the local atomic structure of KxNa1−xNbO3 (PSN) solid solutions. The study is performed over the temperature range 10–1023K for six different x values. We show that only the combined analysis of extended x-ray absorption fine structure and preedge fine structure provides complete and reliable information about the local structure of NbO6 octahedra. Such extensive treatment of the experimental data shows that the local structure of PSN could be described within the spherical model proposed earlier as a hypothesis for perovskite-type ferroelectric zirconates. We reveal that the Nb atoms are localized near their average positions on the sphere surfaces for all temperatures and x values. With regard to previous results we point out the features of microscopic structure common for PSN and perovskite-type zirconates. AU - Mikhail Lemeshko AU - Nazarenko, Elena S AU - Gonchar, A.A AU - Reznichenko, Larisa A AU - Nedoseykina, Tatiana I AU - Novakovich, Alexander A AU - Mathon, Olivier AU - Joly, Yves AU - Vedrinskiǐ, Rostislav V ID - 2135 JF - Physical Review B - Condensed Matter and Materials Physics TI - EXAFS studies of the local atomic structure of the lead-free piezoelectric ceramics KxNa1−xNbO3 over the temperature range 10–1023K VL - 76 ER - TY - JOUR AB - Local atomic structure of the piezoelectric ceramics KxNa 1-xNbO3 (x≤0.00, 0.05, 0.30, 0.40, 0.50 and 0.65) is studied in all phase regions (10 K-1023 K) using Nb K-edge extended X-ray absorption fine-structure (EXAFS) spectroscopy. We have shown the validity of a new spherical model for phase transitions on the basis of both fitting of EXAFS signal in the R-space and differential EXAFS analysis. Within this model the Nb atoms are located on the surfaces of small spheres of constant radii surrounding centers of NbO6 octahedrons in all phases. The distribution of the Nb atom on this surface changes during phase transitions. Besides, the analysis of local structure reveals that the geometry of NbO6 octahedra does not depend on the x value at each temperature, whereas the octahedra rotation angles do. AU - Mikhail Lemeshko AU - Nazarenko, Elena S AU - Gonchar, Anastasia A AU - Reznichenko, Larisa A AU - Mathon, Olivier AU - Joly, Yves AU - Vedrinskiǐ, Rostislav V ID - 2143 IS - 2 JF - EPL TI - Phase transitions in lead-free piezoelectric ceramics: Study of local atomic structure VL - 77 ER - TY - JOUR AB - We use the x-ray absorption fine structure spectroscopy at Nb K edge to reveal the local atomic structure of Kx Na1-x Nb O3 (PSN) solid solutions. The study is performed over the temperature range 10-1023 K for six different x values. We show that only the combined analysis of extended x-ray absorption fine structure and preedge fine structure provides complete and reliable information about the local structure of Nb O6 octahedra. Such extensive treatment of the experimental data shows that the local structure of PSN could be described within the spherical model proposed earlier as a hypothesis for perovskite-type ferroelectric zirconates. We reveal that the Nb atoms are localized near their average positions on the sphere surfaces for all temperatures and x values. With regard to previous results we point out the features of microscopic structure common for PSN and perovskite-type zirconates. AU - Mikhail Lemeshko AU - Nazarenko, Elena S AU - Gonchar, Anastasia A AU - Reznichenko, Larisa A AU - Nedoseykina, Tatiana I AU - Novakovich, Alexander A AU - Mathon, Olivier AU - Joly, Yves AU - Vedrinskiǐ, Rostislav V ID - 2145 IS - 13 JF - Physical Review B - Condensed Matter and Materials Physics TI - EXAFS studies of the local atomic structure of the lead free piezoelectric ceramics Kx Na1-x Nb O3 over the temperature range 10-1023 K VL - 76 ER - TY - JOUR AB - This paper contains a proof of the Manin conjecture for the singular cubic surface S ⊂ P3 that is defined by the equation x1 x22 + x2 x02 + x33 = 0. In fact if U ⊂ S is the Zariski open subset obtained by deleting the unique line from S, and H is the usual exponential height on P3 (Q), then the height zeta function ∑x ∈ U (Q) H (x)- s is analytically continued to the half-plane R e (s) > 9 / 10. AU - De La Bretèche, Régis AU - Browning, Timothy D AU - Derenthal, Ulrich ID - 219 IS - 1 JF - Annales Scientifiques de l'Ecole Normale Superieure TI - On Manin's conjecture for a certain singular cubic surface VL - 40 ER - TY - JOUR AB - Let X ⊂ ℙN be a geometrically integral cubic hypersurface defined over ℚ, with singular locus of dimension at most dim X - 4. The main result in this paper is a proof of the fact that X(ℚ) contains OεX,(BdimX+ε) points of height at most B. AU - Timothy Browning ID - 220 IS - 1-2 JF - Mathematika TI - Counting rational points on cubic hypersurfaces VL - 54 ER - TY - JOUR AU - De La Bretèche, Régis AU - Browning, Timothy D ID - 221 IS - 1 JF - Michigan Mathematical Journal TI - On Manin's conjecture for singular del Pezzo surfaces of degree four, I VL - 55 ER - TY - JOUR AB - Acknowledgements. The authors are grateful to Ulrich Derenthal and Brendan Hassett for several useful conversations relating to universal torsors for singular del Pezzo surfaces. Special thanks are due to Roger Heath–Brown whose ideas led us to the proof of Lemma 6. The paper was finalised while the first author was at the École Normale Supérieure, and the second author was at Oxford University supported by EPSRC grant number GR/R93155/01. The hospitality and financial support of these institutions is gratefully acknowledged. Finally, the authors would like to thank the anonymous referee for his careful reading of the manuscript and numerous useful suggestions. AU - de la Bretèche, Régis AU - Timothy Browning ID - 222 IS - 3 JF - Mathematical Proceedings of the Cambridge Philosophical Society TI - On Manin's conjecture for singular del Pezzo surfaces of degree four, II VL - 143 ER - TY - JOUR AB - Let Q be a non-singular diagonal quadratic form in at least four variables. We provide upper bounds for the number of integer solutions to the equation Q = 0, which lie in a box with sides of length 2B, as B → ∞. The estimates obtained are completely uniform in the coefficients of the form, and become sharper as they grow larger in modulus. AU - Timothy Browning ID - 223 IS - 1 JF - Monatshefte fur Mathematik TI - Density of integer solutions to diagonal quadratic forms VL - 152 ER - TY - JOUR AB - It was recently shown by Hansen that the Wigner-Yanase entropy is, for general states of quantum systems, not subadditive with respect to decomposition into two subsystems, although this property is known to hold for pure states. We investigate the question whether the weaker property of subadditivity for pure states with respect to decomposition into more than two subsystems holds. This property would have interesting applications in quantum chemistry. We show, however, that it does not hold in general, and provide a counterexample. AU - Robert Seiringer ID - 2367 IS - 3 JF - Letters in Mathematical Physics TI - On the failure of subadditivity of the Wigner-Yanase entropy VL - 80 ER - TY - JOUR AB - The increasing interest in the Müller density-matrix-functional theory has led us to a systematic mathematical investigation of its properties. This functional is similar to the Hartree-Fock (HF) functional, but with a modified exchange term in which the square of the density matrix γ(x, x′) is replaced by the square of γ1 2 (x, x′). After an extensive introductory discussion of density-matrix-functional theory we show, among other things, that this functional is convex (unlike the HF functional) and that energy minimizing γ 's have unique densities ρ(r), which is a physically desirable property often absent in HF theory. We show that minimizers exist if N≤Z, and derive various properties of the minimal energy and the corresponding minimizers. We also give a precise statement about the equation for the orbitals of γ, which is more complex than for HF theory. We state some open mathematical questions about the theory together with conjectured solutions. AU - Frank, Rupert L AU - Lieb, Élliott H AU - Robert Seiringer AU - Siedentop, Heinz K ID - 2372 IS - 5 JF - Physical Review A - Atomic, Molecular, and Optical Physics TI - Müller's exchange-correlation energy in density-matrix-functional theory VL - 76 ER - TY - JOUR AB - After recalling briefly the connection between spontaneous symmetry breaking and off-diagonal long-range order for models of magnets a general proof of spontaneous breaking of gauge symmetry as a consequence of Bose-Einstein condensation is presented. The proof is based on a rigorous validation of Bogoliubov's c-number substitution for the k = 0 mode operator α0. AU - Lieb, Élliott H AU - Robert Seiringer AU - Yngvason, Jakob ID - 2370 IS - 3 JF - Reports on Mathematical Physics TI - Bose-Einstein condensation and spontaneous symmetry breaking VL - 59 ER - TY - JOUR AB - We give a Cwikel-Lieb-Rozenblum type bound on the number of bound states of Schrödinger operators with matrix-valued potentials using the functional integral method of Lieb. This significantly improves the constant in this inequality obtained earlier by Hundertmark. AU - Frank, Rupert L AU - Lieb, Élliott H AU - Robert Seiringer ID - 2375 IS - 2-3 JF - Letters in Mathematical Physics TI - Number of bound states of Schrödinger operators with matrix-valued potentials VL - 82 ER - TY - JOUR AB - For the BCS equation with local two-body interaction λV(x), we give a rigorous analysis of the asymptotic behavior of the critical temperature as γ"0. We derive necessary and sufficient conditions onV(x) for the existence of a nontrivial solution for all values of γ>0. AU - Frank, Rupert L AU - Hainzl, Christian AU - Naboko, Serguei N AU - Robert Seiringer ID - 2373 IS - 4 JF - Journal of Geometric Analysis TI - The critical temperature for the BCS equation at weak coupling VL - 17 ER - TY - JOUR AB - We give a proof of stability of relativistic matter with magnetic fields all the way up to the critical value of the nuclear charge Zα = 2/π. AU - Frank, Rupert L AU - Lieb, Élliott H AU - Robert Seiringer ID - 2371 IS - 2 JF - Communications in Mathematical Physics TI - Stability of relativistic matter with magnetic fields for nuclear charges up to the critical value VL - 275 ER - TY - JOUR AB - Signal molecules known as phytohormones play a decisive role in processing signals coming to plants from the surrounding environment. They include auxin — a simple compound with a large range of effects. Auxin is irregularly deposited in plant tissues, it accumulates in certain cellules and through activation of a signal cascade it causes changes in the development programme of these cellules. This article forms a part of the series prepared in honour of the anniversary of the important plant physiologist — Bohumil Němec. AU - Friml, Jirí ID - 2451 JF - Živa TI - Auxin - Universal development signal in plant life VL - 1 ER - TY - JOUR AU - Michniewicz, Marta AU - Brewer, Philip B AU - Jirí Friml ID - 2462 JF - The Arabidopsis Book TI - Polar auxin transport and asymmetric auxin distribution VL - 5 ER - TY - JOUR AB - Metabotropic glutamate receptor 4 (mGluR4) is localized mainly to presynaptic membranes in the brain. Rat neostriatum has been reported to contain two types of mGluR4-immunoreactive axon varicosities: small, weakly immunoreactive varicosities that were distributed randomly (type 1) and large, intensely immunoreactive ones that were often aligned linearly (type 2). In the present study, most type 1 terminals formed asymmetric synapses on dendritic spines, whereas type 2 terminals made symmetric synapses on dendritic shafts, showing immunoreactivity for GABAergic markers. After depletion of neostriatal neurons, type 2 but not type 1 varicosities were largely decreased in the damaged region. When medium-sized spiny neurons (MSNs) were labeled with Sindbis virus expressing membrane-targeted green fluorescent protein, mGluR4 immunoreactivity was observed on some varicosities of their axon collaterals in immunofluorescence and immunoelectron microscopies. Furthermore, type 2 varicosities were often positive for substance P but mostly negative for striatal interneuron markers and preproenkephalin. Thus, striatonigral/striato- entopeduncular MSNs are likely to be the largest source of type 2 mGluR4-immunopositive axon terminals in the neostriatum. Next, in the double-immunofluorescence study, almost all choline acetyltransferase (ChAT)-immunopositive and 41% of NK1 receptor-positive dendrites were heavily associated with type 2 mGluR4-immunoreactive varicosities. Neuronal nitric oxide synthase (nNOS)-positive dendrites, in contrast, seemed associated with only a few type 2 varicosities. Conversely, almost all type 2 varicosities were closely apposed to NK1 receptor-positive dendrites that were known to be derived from cholinergic and nNOS-producing interneurons. These findings indicate that the mGluR4-positive terminals of MSN axon collaterals selectively form synapses with neostriatal cholinergic interneurons. AU - Kuramoto, Eriko AU - Fujiyama, Fumino AU - Unzai, Tomo AU - Nakamura, Kouichi AU - Hioki, Hiroyuki AU - Furuta, Takahiro AU - Ryuichi Shigemoto AU - Ferraguti, Francesco AU - Kaneko, Takeshi ID - 2495 IS - 5 JF - Journal of Comparative Neurology TI - Metabotropic glutamate receptor 4-immunopositive terminals of medium-sized spiny neurons selectively form synapses with cholinergic interneurons in the rat neostriatum VL - 500 ER - TY - JOUR AB - Glutamate is one candidate for the neurotransmitters and/or neuromodulators involved in taste signaling in taste buds. Group II metabotropic glutamate receptors (mGluRs: mGluR2 and mGluR3) are known to function as presynaptic receptors that regulate the release of glutamate and/or other neurotransmitters in the central nervous system. Group II mGluRs are negatively linked to adenylyl cyclase through Gαi subunits and thereby reduce the turnover of cAMP. In rat taste tissues, a subset of adenylyl-cyclase-8-expressing taste cells coexpress the Gαi subunits gustducin and Gαi2. However, the expression patterns of group II mGluRs in rat taste tissues have not yet been elucidated. We have therefore examined the expression patterns of mGluR2, mGluR3, and gustducin in rat gustatory tissues. Reverse transcription/polymerase chain reaction assays have revealed that mGluR2 and mGluR3 mRNAs are expressed in the circumvallate papillae. In situ hybridization analyses have detected positive signals for mGluR2 and mGluR3 mRNAs only in the circumvallate taste buds. Among the fungiform, foliate, and circumvallate papillae, an antibody against mGluR2/3 labels a subset of taste bud cells and nerve fibers immediately beneath the taste lingual epithelium. Double-labeling experiments have demonstrated that mGluR2/3-positive cells coexpress gustducin. These results indicate that mGluR2 and mGluR3 are coupled to Gαi subunits and play roles in glutamate-mediated signaling in taste transductions. AU - Toyono, Takashi AU - Kataoka, Shinji AU - Seta, Yuji AU - Ryuichi Shigemoto AU - Toyoshima, Kuniaki ID - 2496 IS - 1 JF - Cell and Tissue Research TI - Expression of group II metabotropic glutamate receptors in rat gustatory papillae VL - 328 ER - TY - JOUR AB - Substance P (SP) is known to be a peptide that facilitates epileptic activity of principal cells in the hippocampus. Paradoxically, in other models, it was found to be protective against seizures by activating substance P receptor (SPR)-expressing interneurons. Thus, these cells appear to play an important role in the generation and regulation of epileptic seizures. The number, distribution, morphological features and input characteristics of SPR-immunoreactive cells were analyzed in surgically removed hippocampi of 28 temporal lobe epileptic patients and eight control hippocampi in order to examine their changes in epileptic tissues. SPR is expressed in a subset of inhibitory cells in the control human hippocampus, they are multipolar interneurons with smooth dendrites, present in all hippocampal subfields. This cell population is considerably different from SPR-positive cells of the rat hippocampus. The CA1 (cornu Ammonis subfield 1) region was chosen for the detailed morphological analysis of the SPR-immunoreactive cells because of its extreme vulnerability in epilepsy. The presence of various neurochemical markers identifies functionally distinct interneuron types, such as those responsible for perisomatic, dendritic or interneuron-selective inhibition. We found considerable colocalization of SPR with calbindin but not with parvalbumin, calretinin, cholecystokinin and somatostatin, therefore we suppose that SPR-positive cells participate mainly in dendritic inhibition. In the non-sclerotic CA1 region they are mainly preserved, whereas their number is decreased in the sclerotic cases. In the epileptic samples their morphology is considerably altered, they possessed more dendritic branches, which often became beaded. Analyses of synaptic coverage revealed that the ratio of symmetric synaptic input of SPR-immunoreactive cells has increased in epileptic samples. Our results suggest that SPR-positive cells are preserved while principal cells are present in the CA1 region, but show reactive changes in epilepsy including intense branching and growth of their dendritic arborization. AU - Tóth, Kinga AU - Wittner, Lucia AU - Urbán, Z AU - Doyle, Werner K AU - Buzsáki, György AU - Ryuichi Shigemoto AU - Freund, Tamás F AU - Maglóczky, Zsófia ID - 2665 IS - 2 JF - Neuroscience TI - Morphology and synaptic input of substance P receptor-immunoreactive interneurons in control and epileptic human hippocampus VL - 144 ER - TY - JOUR AB - GABAB receptors (GABABRs) are involved in early events during neuronal development. The presence of GABABRs in developing oligodendrocytes has not been established. Using immunofluorescent co-localization, we have identified GABABR proteins in O4 marker-positive oligodendrocyte precursor cells (OPCs) in 4-day-old mouse brain periventricular white matter. In culture, OPCs, differentiated oligodendrocytes (DOs) and type 2 astrocytes (ASTs) express both the GABAB1abcdf and GABAB2 subunits of the GABABR. Using semiquantitative PCR analysis with GABABR isoform-selective primers we found that the expression level of GABAB1abd was substantially higher in OPCs or ASTs than in DOs. In contrast, the GABAB2 isoform showed a similar level of expression in OPCs and DOs, and a significantly higher level in ASTs. This indicates that the expression of GABAB1 and GABAB2 subunits are under independent control during oligodendroglial development. Activation of GABABRs using the selective agonist baclofen demonstrated that these receptors are functionally active and negatively coupled to adenylyl cyclase. Manipulation of GABABR activity had no effect on OPC migration in a conventional agarose drop assay, whereas baclofen significantly increased OPC migration in a more sensitive transwell microchamber-based assay. Exposure of cultured OPCs to baclofen increased their proliferation, providing evidence for a functional role of GABABRs in oligodendrocyte development. The presence of GABABRs in developing oligodendrocytes provides a new mechanism for neuronal-glial interactions during development and may offer a novel target for promoting remyelination following white matter injury. AU - Luyt, Karen AU - Slade, Timothy P AU - Dorward, Jienchi J AU - Durant, Claire F AU - Wu, Yue AU - Ryuichi Shigemoto AU - Mundell, Stuart J AU - Váradi, Anikó AU - Molnár, Elek ID - 2666 IS - 3 JF - Journal of Neurochemistry TI - Developing oligodendrocytes express functional GABAB receptors that stimulate cell proliferation and migration VL - 100 ER - TY - JOUR AB - Hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channels are expressed postsynaptically in the rodent globus pallidus (GP), where they play several important roles in controlling GP neuronal activity. To further elucidate the role of HCN channels in the GP, immunocytochemical and electrophysiological approaches were used to test the hypothesis that HCN channels are also expressed presynaptically on the local axon collaterals of GP neurons. At the electron microscopic level, immunoperoxidase labelling for HCN1 and HCN2 was localized in GP somata and dendritic processes, myelinated and unmyelinated axons, and axon terminals. One population of labelled terminals formed symmetric synapses with somata and proximal dendrites and were immunoreactive for parvalbumin, consistent with the axon collaterals of GABAergic GP projection neurons. In addition, labelling for HCN2 and, to a lesser degree, HCN1 was observed in axon terminals that formed asymmetric synapses and were immunoreactive for the vesicular glutamate transporter 2. Immunogold labelling demonstrated that HCN1 and HCN2 were located predominantly at extrasynaptic sites along the plasma membrane of both types of terminal. To determine the function of presynaptic HCN channels in the GP, we performed whole-cell recordings from GP neurons in vitro. Bath application of the HCN channel blocker ZD7288 resulted in an increase in the frequency of mIPSCs but had no effect on their amplitude, implying that HCN channels tonically regulate the release of GABA. Their presence, and predicted role in modulating transmitter release, represents a hitherto unidentified mechanism whereby HCN channels influence the activity of GP neurons. AU - Boyes, Justin AU - Bolam, John P AU - Ryuichi Shigemoto AU - Stanford, Ian M ID - 2668 IS - 7 JF - European Journal of Neuroscience TI - Functional presynaptic HCN channels in the rat globus pallidus VL - 25 ER - TY - JOUR AB - The number of AMPA receptor (AMPAR) is the major determinant of synaptic strength at glutamatergic synapses, but little is known about the absolute number and density of AMPARs in individual synapses. Using SDS-digested freeze-fracture replica labeling, which has high detection efficiency comparable with electrophysiological noise analysis for functional AMPAR, we analyzed three kinds of excitatory synapses in the molecular layer of the adult rat cerebellum. In parallel fiber (PF)-Purkinje cell (PC) synapses, we found large variability in the number (38.1 ± 34.4 particles per synapse, mean ± SD; range, 2-178 particles per synapse) and density (437 ± 277 particles/μm2; range, 48-1210 particles/μm2) of immunogold-labeled AMPARs. Two-dimensional view and high sensitivity of this method revealed irregular-shaped small AMPAR clusters within synapses. Climbing fiber (CF)-PC synapses had higher number of AMPAR labeling (68.6 ± 34.5 particles per synapse) than PF-PC and PF-interneuron synapses (36.8 ± 14.4 particles per synapse). Furthermore, AMPAR density at CF-PC and PF-interneuron synapses was approximately five times higher and more uniform than that at PF-PC synapses. These results suggest input- and target-dependent regulation of AMPAR-mediated synaptic strength. AU - Masugi-Tokita, Miwako AU - Tarusawa, Etsuko AU - Watanabe, Masahiko AU - Molnár, Elek AU - Fujimoto, Kazushi AU - Ryuichi Shigemoto ID - 2667 IS - 8 JF - Journal of Neuroscience TI - Number and density of AMPA receptors in individual synapses in the rat cerebellum as revealed by SDS-digested freeze-fracture replica labeling VL - 27 ER - TY - JOUR AB - The properties of the hyperpolarization-activated current (Ih) and its roles in hippocampal network function evolve radically during development. Because Ih is conducted by the hyperpolarization- activated cyclic nucleotide-gated (HCN) cation channels, we tested the hypothesis that understanding the quantitative developmental profiles of HCN1, HCN2, and HCN4 expression, and the isoform- and age-specific progression of their subcellular distribution, should shed light on the established modifications of the properties of Ih throughout development. Combined quantitative in situ hybridization, regional western blots, and high-resolution, dual-label immunocytochemistry revealed striking and novel information about the expression and distribution of the HCN channel isoforms in the developing hippocampal formation. In cornus ammon 1 (CA) pyramidal cell layer, a robust increase of HCN1 mRNA and protein expression occurred with age, with reciprocal reduction of HCN4 and relatively stable HCN2 levels. These distinct expression patterns raised the contribution of HCN1 to the total HCN channel pool from 33% to 65% consonant with acceleration and reduced cyclic adenosine mono phosphate (cAMP) sensitivity of Ih in this region with age. In CA3, strong expression of HCN1 already neonatally supports the recently established role of this conductance in neonatal, age-specific, hippocampal oscillations (giant depolarizing potentials). Notably, HCN1 channels were present and probably transported to dendritic compartments already on postnatal day (P) 2, whereas HCN2 channel protein was not evident in dendrites for the first 2 weeks of life. HCN2 mRNA and protein expression remained fairly constant subsequent to the first week of life in all hippocampal subfields examined, whereas HCN4 mRNA and protein expression declined after maximal neonatal expression, so that the contribution of this isoform to the total HCN channel pool dropped from 43% (CA1) and 34% (CA3) on P11 to 8% (CA1) and 19% (CA3) on P90. Interneuronal expression of all HCN channel isoforms in stratum pyramidale was robust in parvalbumin-but not in cholecystokinin-expressing populations and with a subunit-specific subcellular distribution. Taken together, these data suggest that early in life, HCN4 may contribute significantly to the functions of Ih in specific hippocampal regions. In addition, these evolving, differential quantitative, and subcellular expression patterns of the HCN channel isoforms support age-specific properties and functions of Ih within the developing hippocampal formation. AU - Brewster, Amy L AU - Chen, Yuncai AU - Bender, Roland A AU - Yeh, Amy AU - Ryuichi Shigemoto AU - Baram, Tallie Z ID - 2669 IS - 3 JF - Cerebral Cortex TI - Quantitative analysis and subcellular distribution of mRNA and protein expression of the hyperpolarization-activated cyclic nucleotide-gated channels throughout development in rat hippocampus VL - 17 ER - TY - JOUR AB - Excitatory synaptic transmission is inhibited by G protein coupled receptors, including the adenosine A1, GABAB, and metabotropic glutamate receptor 7. These receptors are present in nerve terminals where they reduce the release of glutamate through activating signaling pathways negatively coupled to Ca2+ channels and adenylyl cyclase. However, it is not clear whether these receptors operate in distinct subpopulations of nerve terminals or if they are co-expressed in the same nerve terminals, despite the functional consequences that such distributions may have on synaptic transmission. Applying Ca2+ imaging and immunocytochemistry, we show that these three G protein coupled receptors coexist in a subpopulation of cerebrocortical nerve terminals. The three receptors share an intracellular signaling pathway through which their inhibitory responses are integrated and coactivation of these receptors produced an integrated response. Indeed, this response was highly variable, from a synergistic response at subthreshold agonist concentrations to an occluded response at high agonist concentrations. The presence of multiple receptors in a nerve terminal could be responsible for the physiological effects of neurotransmitter spillover from neighboring synapses or alternatively, the co-release of transmitters by the same nerve terminal. AU - Ladera, Carolina AU - Godino, María D AU - Martín, Ricardo J AU - Luján, Rafael AU - Ryuichi Shigemoto AU - Ciruela, Francisco AU - Torres, Magdalena AU - Sánchez-Prieto, José ID - 2673 IS - 6 JF - Journal of Neurochemistry TI - The coexistence of multiple receptors in a single nerve terminal provides evidence for pre-synaptic integration VL - 103 ER - TY - JOUR AB - Increasing evidence supports roles for the current mediated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, I h, in hippocampal maturation and specifically in the evolving changes of intrinsic properties as well as network responses of hippocampal neurons. Here, we describe a novel developmental plasticity of HCN channel expression in axonal and presynaptic compartments: HCN1 channels were localized to axon terminals of the perforant path (the major hippocampal afferent pathway) of immature rats, where they modulated synaptic efficacy. However, presynaptic expression and functions of the channels disappeared with maturation. This was a result of altered channel transport to the axons, because HCN1 mRNA and protein levels in entorhinal cortex neurons, where the perforant path axons originate, were stable through adulthood. Blocking action potential firing in vitro increased presynaptic expression of HCN1 channels in the perforant path, suggesting that network activity contributed to regulating this expression. These findings support a novel developmentally regulated axonal transport of functional ion channels and suggest a role for HCN1 channel-mediated presynaptic I h in hippocampal maturation. AU - Bender, Roland A AU - Kirschstein, Timo AU - Kretz, Oliver AU - Brewster, Amy L AU - Richichi, Cristina AU - Rüschenschmidt, Christiane AU - Ryuichi Shigemoto AU - Beck,Heinz AU - Frotscher, Michael AU - Baram, Tallie Z ID - 2671 IS - 17 JF - Journal of Neuroscience TI - Localization of HCN1 channels to presynaptic compartments: Novel plasticity that may contribute to hippocampal maturation VL - 27 ER - TY - JOUR AB - Hyperpolarization-activated cyclic nucleotide-modulated (HCN) "pacemaker" channel subunits are integral membrane proteins that assemble as tetramers to form channels in cardiac conduction tissue and nerve cells. Previous studies have suggested that the HCN2 and HCN4 channel isoforms physically interact when overexpressed in mammalian cells, but whether they are able to co-assemble and form functional channels remains unclear. The extent to which co-assembly occurs over self-assembly and whether HCN2-HCN4 heteromeric channels are formed in native tissue are not known. In this study, we show co-assembly of HCN2 and HCN4 in live Chinese hamster ovary cells using bioluminescence resonance energy transfer (BRET2), a novel approach for studying tetramerization of ion channel subunits. Together with results from electrophysiological and imaging approaches, the BRET2 data show that HCN2 and HCN4 subunits self-assemble and co-assemble with equal preference. We also demonstrate colocalization of HCN2 and HCN4 and a positive correlation of their intensities in the embryonic mouse heart using immunohistochemistry, as well as physical interactions between these isoforms in the rat thalamus by coimmunoprecipitation. Together, these data support the formation of HCN2-HCN4 heteromeric channels in native tissue. AU - Whitaker, Gina M AU - Angoli, Damiano AU - Nazzari, Hamed AU - Ryuichi Shigemoto AU - Accili, Eric A ID - 2672 IS - 31 JF - Journal of Biological Chemistry TI - HCN2 and HCN4 isoforms self-assemble and co-assemble with equal preference to form functional pacemaker channels VL - 282 ER - TY - GEN AB - Glutamate and GABA are the main transmitters in the central nervous system and their effects are mediated by ionotropic and metabotropic receptors. Immunogold electron microscopy has revealed the quantitative localization of these receptors at 20-30 nm resolution. SDS-digested freeze-fracture replica labeling (SDS-FRL), a newly developed immunogold method, provides an accurate estimate of molecule numbers. Here, we summarize the recent advances in quantitative receptor localization, including use of SDS-FRL analyses to determine numbers of AMPA-type glutamate receptors in the cerebellum. The two-dimensional view and high sensitivity of SDS-FRL have revealed small, irregularly shaped AMPA receptor clusters within cerebellar synapses. AU - Masugi-Tokita, Miwako AU - Ryuichi Shigemoto ID - 2670 IS - 3 T2 - Current Opinion in Neurobiology TI - High-resolution quantitative visualization of glutamate and GABA receptors at central synapses VL - 17 ER - TY - CHAP AU - László Erdös ED - Gesztesy, Fritz ED - Deift, Percy ED - Galvez, Percy ED - Perry, Peter ED - Schlag, Wilhelm ID - 2705 T2 - Spectral Theory and Mathematical Physics: a Festschrift in Honor of Barry Simon's 60th Birthday TI - Recent developments in quantum mechanics with magnetic fields VL - 76 ER - TY - JOUR AB - We consider random Schrödinger equations on ℝd for d ≥ 3 with a homogeneous Anderson-Poisson type random potential. Denote by λ the coupling constant and ψt the solution with initial data ψ0. The space and time variables scale as χ ≃λ-2-κ/2, t ≃λ-2-κ with 0 < kappa; < kappa;0(d). We prove that, in the limit λ → 0, the expectation of the Wigner distribution of ψt converges weakly to the solution of a heat equation in the space variable x for arbitrary L2 initial data. The proof is based on a rigorous analysis of Feynman diagrams. In the companion paper [10] the analysis of the non-repetition diagrams was presented. In this paper we complete the proof by estimating the recollision diagrams and showing that the main terms, i.e. the ladder diagrams with renormalized propagator, converge to the heat equation. AU - László Erdös AU - Salmhofer, Manfred AU - Yau, Horng-Tzer ID - 2750 IS - 1 JF - Communications in Mathematical Physics TI - Quantum diffusion of the random Schrödinger evolution in the scaling limit II. The recollision diagrams VL - 271 ER - TY - JOUR AB - We consider random Schrödinger equations on ℤd for d ≥ 3 with identically distributed random potential. Denote by λ the coupling constant and ψ t the solution with initial data ψ 0. The space and time variables scale as x ∼ λ -2-κ/2,t ∼ λ-2-κ with 0 < κ < κ0(d). We prove that, in the limit λ → 0, the expectation of the Wigner distribution of ψ t converges weakly to a solution of a heat equation in the space variable x for arbitrary L 2 initial data. The diffusion coefficient is uniquely determined by the kinetic energy associated to the momentum υ. This work is an extension to the lattice case of our previous result in the continuum [8,9]. Due to the non-convexity of the level surfaces of the dispersion relation, the estimates of several Feynman graphs are more involved. AU - László Erdös AU - Salmhofer, Manfred AU - Yau, Horng-Tzer ID - 2751 IS - 4 JF - Annales Henri Poincare TI - Quantum diffusion for the Anderson model in the scaling limit VL - 8 ER - TY - JOUR AB - We prove L p -bounds on the Fourier transform of measures μ supported on two dimensional surfaces. Our method allows to consider surfaces whose Gauss curvature vanishes on a one-dimensional submanifold. Under a certain non-degeneracy condition, we prove that μ ∧ ε L 4+β, β > 0, and we give a logarithmically divergent bound on the L 4-norm. We use this latter bound to estimate almost singular integrals involving the dispersion relation, e(p)= ∑13 [1-\cos p_j]} , of the discrete Laplace operator on the cubic lattice. We briefly explain our motivation for this bound originating in the theory of random Schrödinger operators. AU - László Erdös AU - Salmhofer, Manfred ID - 2752 IS - 2 JF - Mathematische Zeitschrift TI - Decay of the Fourier transform of surfaces with vanishing curvature VL - 257 ER - TY - GEN AB - We prove rigorously that the one-particle density matrix of three dimensional interacting Bose systems with a short-scale repulsive pair interaction converges to the solution of the cubic non-linear Schrödinger equation in a suitable scaling limit. The result is extended to k-particle density matrices for all positive integer k. AU - László Erdös AU - Schlein, Benjamin AU - Yau, Horng-Tzer ID - 2749 IS - 3 T2 - Inventiones Mathematicae TI - Derivation of the cubic non linear Schrödinger equation from quantum dynamics of many body systems VL - 167 ER - TY - JOUR AB - The time-dependent Gross-Pitaevskii equation describes the dynamics of initially trapped Bose-Einstein condensates. We present a rigorous proof of this fact starting from a many-body bosonic Schrödinger equation with a short-scale repulsive interaction in the dilute limit. Our proof shows the persistence of an explicit short-scale correlation structure in the condensate. AU - László Erdös AU - Schlein, Benjamin AU - Yau, Horng-Tzer ID - 2748 IS - 4 JF - Physical Review Letters TI - Rigorous derivation of the Gross-Pitaevskii equation VL - 98 ER - TY - GEN AB - Pipe flow is a prominent example among the shear flows that undergo transition to turbulence without mediation by a linear instability of the laminar profile. Experiments on pipe flow, as well as plane Couette and plane Poiseuille flow, show that triggering turbulence depends sensitively on initial conditions, that between the laminar and the turbulent states there exists no intermediate state with simple spatial or temporal characteristics, and that turbulence is not persistent, i.e., it can decay again, if the observation time is long enough. All these features can consistently be explained on the assumption that the turbulent state corresponds to a chaotic saddle in state space. The goal of this review is to explain this concept, summarize the numerical and experimental evidence for pipe flow, and outline the consequences for related flows. AU - Eckhardt, Bruno AU - Schneider, Tobias M AU - Björn Hof AU - Westerweel, Jerry ID - 2793 T2 - Annual Review of Fluid Mechanics TI - Turbulence transition in pipe flow VL - 39 ER - TY - CONF AU - Björn Hof AU - Tax, Wilco AU - Westerweel, Jerry ID - 2794 TI - Lifetime of turbulence in pipe flow VL - 117 ER - TY - JOUR AB - Summary: Regulatory CD4+ T cells, enriched in the CD25 pool of healthy individuals, mediate natural tolerance and prevent autoimmune diseases. Despite their fundamental and potential clinical significance, regulatory T (TR) cells have not yet been incorporated in a coherent theory of the immune system. This article reviews experimental evidence and theoretical arguments supporting a model of TR cell dynamics, uncovering some of its most relevant biological implications. According to this model, the persistence and expansion of TR cell populations depend strictly on specific interactions they make with antigen-presenting cells (APCs) and conventional effector T (TE) cells. This three-partner crossregulation imposes that TR cells feed on the specific autoimmune activities they suppress, with implications ranging from their interactions with other cells to their repertoire selection in the periphery and in the thymus, and to the relationship between these cells and the innate immune system. These implications stem from the basic prediction that the peripheral dynamics sort the CD4+ T-cell repertoire into two subsets: a less diverse set of small clones of autoreactive effector and regulatory cells that regulate each other’s growth, and a more diverse set of barely autoreactive TE cell clones, whose expansion is limited only by APC availability. It is argued that such partitioning of the repertoire sets the ground for self–non-self discrimination. AU - Carneiro, Jorge AU - Leon, Kalet AU - Caramalho, Íris AU - Van Den Dool, Carline AU - Gardner, Rui AU - Oliveira, Vanessa AU - Bergman, Marie L AU - Sepúlveda, Nuno AU - Tiago Paixao AU - Faro, Jose AU - Demengeot, Jocelyne ID - 2893 IS - 1 JF - Immunological Reviews TI - When three is not a crowd a Crossregulation Model of the dynamics and repertoire selection of regulatory CD4 T cells VL - 216 ER - TY - JOUR AB - Gene expression from both parental alleles is beneficial by masking the effects of deleterious recessive mutations and by reducing the noise in gene expression in diploid organisms. However, a class of genes are expressed preferentially or strictly from a single allele. The selective advantage of avoiding biallelic expression is clear for allelic-excluded antigen receptor and odorant receptor genes, genes undergoing X-chromosome inactivation in females and parental genomic imprinted genes. In contrast, there is no clear biological rationale for the predominant and stochastic monoallelic expression of cytokine genes in the immune system, and the underlying mechanism is elusive and controversial. A clarification of the mechanism of predominant monoallelic expression would be instrumental in better understanding its eventual biological functional. This prompted the development of a quantitative framework that could describe the dynamics of the pattern of allele expression of the IL-10 gene, from which general quantitative insights could be gained. We report that the experimental observations on these patterns of allelic expression cannot be easily reconciled with a simple model of stochastic transcriptional activation, in which the two alleles are, at any time, equally competent for transcription. Instead, these observations call into action a general model of eukaryotic transcriptional regulation according to which the locus competence for transcription is dynamic, involving multiple, cooperative and stochastic modification steps. In this model, the probability that an allele becomes transcriptionally active is a function of the number of chromatin modifications that it accumulated. On the basis of the properties of this model, we argue that predominant monoallelic expression might have had no adaptive role, and may have evolved under indirect selection for low frequency of expressing cells. AU - Tiago Paixao AU - Carvalho, Tiago P AU - Calado, Dinis P AU - Carneiro, Jorge ID - 2896 IS - 4 JF - Immunology and Cell Biology TI - Quantitative insights into stochastic monoallelic expression of cytokine genes VL - 85 ER - TY - CONF AU - Kumar, M Pawan AU - Vladimir Kolmogorov AU - Torr, Philip H ID - 2933 TI - An Analysis of Convex Relaxations for MAP Estimation ER - TY - JOUR AB - Directional transport of the phytohormone auxin is established primarily at the point of cellular afflux and is required for the establishment and maintenance of plant polarity. Studies in whole plants and heterologous systems indicate that PIN-FORMED (PIN) and P-glycoprotein (PGP) transport proteins mediate the cellular efflux of natural and synthetic auxins. However, aromatic anion transport resulting from PGP and PIN expression in nonplant systems was also found to lack tha high level of substrate specificity seen in planta. Furthermore, previous reports that PGP19 stabilizes PIN1 on the plasma membrane suggested that PIN-PGP interactions might regulate polar auxin efflux. Hare, we show that PGP1 and PGP19 colocalized with PIN1 in the shoot apax in Arabidopsis thaliana and with PIN1 and PIN2 in root tissues. Specific PGP-PIN interactions were seen in yeast two-hybrid and colmmunoprecipitation assays. PIN-PGP interactions appeared to enhance transport activity and, to a greater extent, substrate/inhibitor specificities when coexpressed in heterologous systems. By contrast, no interactions between PGPs and the AUXIN1 influx carrier were observed. Phenotypes of pin and pgp mutants suggest discrete functional roles in auxin transport, but pin pgp mutants exhibited phenotypes that are both additive and synergistic. These results suggest that PINs and PGPs characterize coordinated, Independent auxin transport mechanisms but also function interactively in a tissue-specific manner. AU - Blakeslee, Joshua AU - Bandyopadhyay, Anindita AU - Ok, Ran Lee AU - Mravec, Jozef AU - Titapiwatanakun, Boosaree AU - Sauer, Michael AU - Makam, Srinivas N AU - Cheng, Yan AU - Bouchard, Rodolphe AU - Adamec, Jiří AU - Geisler, Markus AU - Nagashima, Akitomo AU - Sakai, Tatsuya AU - Martinoia, Enrico AU - Jirí Friml AU - Peer, Wendy A AU - Murphy, Angus S ID - 3019 IS - 1 JF - Plant Cell TI - Interactions among PIN FORMED and P glycoprotein auxin transporters in Arabidopsis VL - 19 ER - TY - JOUR AB - Cytokinesis ensures proper partitioning of the nucleocytoplasmic contents into two daughter cells. It has generally been thought that cytokinesis is accomplished differently in animals and plants because of the differences in the preparatory phases, into the centrosomal or acentrosomal nature of the process, the presence or absence of rigid cell walls, and on the basis of ‘outside‐in’ or ‘inside‐out’ mechanism. However, this long‐standing paradigm needs further reevaluation based on new findings. Recent advances reveal that plant cells, similarly to animal cells, possess astral microtubules that regulate the cell division plane. Furthermore, endocytosis has been found to be important for cytokinesis in animal and plant cells: vesicles containing endocytosed cargo provide material for the cell plate formation in plants and for closure of the midbody channel in animals. Thus, although the preparatory phases of the cell division process differ between plant and animal cells, the later phases show similarities. We unify these findings in a model that suggests a conserved mode of cytokinesis. AU - Dhonukshe, Pankaj AU - Šamaj, Jozef AU - Baluška, František AU - Friml, Jirí ID - 3023 IS - 4 JF - Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology TI - A unifying new model of cytokinesis for the dividing plant and animal cells VL - 29 ER -