@inproceedings{3351,
abstract = {In two-player games on graph, the players construct an infinite path through the game graph and get a reward computed by a payoff function over infinite paths. Over weighted graphs, the typical and most studied payoff functions compute the limit-average or the discounted sum of the rewards along the path. Besides their simple definition, these two payoff functions enjoy the property that memoryless optimal strategies always exist. In an attempt to construct other simple payoff functions, we define a class of payoff functions which compute an (infinite) weighted average of the rewards. This new class contains both the limit-average and the discounted sum functions, and we show that they are the only members of this class which induce memoryless optimal strategies, showing that there is essentially no other simple payoff functions.},
author = {Chatterjee, Krishnendu and Doyen, Laurent and Singh, Rohit},
editor = {Owe, Olaf and Steffen, Martin and Telle, Jan Arne},
location = {Oslo, Norway},
pages = {148 -- 159},
publisher = {Springer},
title = {{On memoryless quantitative objectives}},
doi = {10.1007/978-3-642-22953-4_13},
volume = {6914},
year = {2011},
}
@article{3352,
abstract = {Exploring the connection of biology with reactive systems to better understand living systems.},
author = {Fisher, Jasmin and Harel, David and Henzinger, Thomas A},
journal = {Communications of the ACM},
number = {10},
pages = {72 -- 82},
publisher = {ACM},
title = {{Biology as reactivity}},
doi = {10.1145/2001269.2001289},
volume = {54},
year = {2011},
}
@article{3353,
abstract = {Compositional theories are crucial when designing large and complex systems from smaller components. In this work we propose such a theory for synchronous concurrent systems. Our approach follows so-called interface theories, which use game-theoretic interpretations of composition and refinement. These are appropriate for systems with distinct inputs and outputs, and explicit conditions on inputs that must be enforced during composition. Our interfaces model systems that execute in an infinite sequence of synchronous rounds. At each round, a contract must be satisfied. The contract is simply a relation specifying the set of valid input/output pairs. Interfaces can be composed by parallel, serial or feedback composition. A refinement relation between interfaces is defined, and shown to have two main properties: (1) it is preserved by composition, and (2) it is equivalent to substitutability, namely, the ability to replace an interface by another one in any context. Shared refinement and abstraction operators, corresponding to greatest lower and least upper bounds with respect to refinement, are also defined. Input-complete interfaces, that impose no restrictions on inputs, and deterministic interfaces, that produce a unique output for any legal input, are discussed as special cases, and an interesting duality between the two classes is exposed. A number of illustrative examples are provided, as well as algorithms to compute compositions, check refinement, and so on, for finite-state interfaces.},
author = {Tripakis, Stavros and Lickly, Ben and Henzinger, Thomas A and Lee, Edward},
journal = {ACM Transactions on Programming Languages and Systems (TOPLAS)},
number = {4},
publisher = {ACM},
title = {{A theory of synchronous relational interfaces}},
doi = {10.1145/1985342.1985345},
volume = {33},
year = {2011},
}
@article{3354,
abstract = {We consider two-player games played on a finite state space for an infinite number of rounds. The games are concurrent: in each round, the two players (player 1 and player 2) choose their moves independently and simultaneously; the current state and the two moves determine the successor state. We consider ω-regular winning conditions specified as parity objectives. Both players are allowed to use randomization when choosing their moves. We study the computation of the limit-winning set of states, consisting of the states where the sup-inf value of the game for player 1 is 1: in other words, a state is limit-winning if player 1 can ensure a probability of winning arbitrarily close to 1. We show that the limit-winning set can be computed in O(n2d+2) time, where n is the size of the game structure and 2d is the number of priorities (or colors). The membership problem of whether a state belongs to the limit-winning set can be decided in NP ∩ coNP. While this complexity is the same as for the simpler class of turn-based parity games, where in each state only one of the two players has a choice of moves, our algorithms are considerably more involved than those for turn-based games. This is because concurrent games do not satisfy two of the most fundamental properties of turn-based parity games. First, in concurrent games limit-winning strategies require randomization; and second, they require infinite memory.},
author = {Chatterjee, Krishnendu and De Alfaro, Luca and Henzinger, Thomas A},
journal = {ACM Transactions on Computational Logic (TOCL)},
number = {4},
publisher = {ACM},
title = {{Qualitative concurrent parity games}},
doi = {10.1145/1970398.1970404},
volume = {12},
year = {2011},
}
@inproceedings{3355,
abstract = {Byzantine Fault Tolerant (BFT) protocols aim to improve the reliability of distributed systems. They enable systems to tolerate arbitrary failures in a bounded number of nodes. BFT protocols are usually proven correct for certain safety and liveness properties. However, recent studies have shown that the performance of state-of-the-art BFT protocols decreases drastically in the presence of even a single malicious node. This motivates a formal quantitative analysis of BFT protocols to investigate their performance characteristics under different scenarios. We present HyPerf, a new hybrid methodology based on model checking and simulation techniques for evaluating the performance of BFT protocols. We build a transition system corresponding to a BFT protocol and systematically explore the set of behaviors allowed by the protocol. We associate certain timing information with different operations in the protocol, like cryptographic operations and message transmission. After an elaborate state exploration, we use the time information to evaluate the performance characteristics of the protocol using simulation techniques. We integrate our framework in Mace, a tool for building and verifying distributed systems. We evaluate the performance of PBFT using our framework. We describe two different use-cases of our methodology. For the benign operation of the protocol, we use the time information as random variables to compute the probability distribution of the execution times. In the presence of faults, we estimate the worst-case performance of the protocol for various attacks that can be employed by malicious nodes. Our results show the importance of hybrid techniques in systematically analyzing the performance of large-scale systems.},
author = {Halalai, Raluca and Henzinger, Thomas A and Singh, Vasu},
location = {Aachen, Germany},
pages = {255 -- 264},
publisher = {IEEE},
title = {{Quantitative evaluation of BFT protocols}},
doi = {10.1109/QEST.2011.40},
year = {2011},
}
@inproceedings{3356,
abstract = {There is recently a significant effort to add quantitative objectives to formal verification and synthesis. We introduce and investigate the extension of temporal logics with quantitative atomic assertions, aiming for a general and flexible framework for quantitative-oriented specifications. In the heart of quantitative objectives lies the accumulation of values along a computation. It is either the accumulated summation, as with the energy objectives, or the accumulated average, as with the mean-payoff objectives. We investigate the extension of temporal logics with the prefix-accumulation assertions Sum(v) ≥ c and Avg(v) ≥ c, where v is a numeric variable of the system, c is a constant rational number, and Sum(v) and Avg(v) denote the accumulated sum and average of the values of v from the beginning of the computation up to the current point of time. We also allow the path-accumulation assertions LimInfAvg(v) ≥ c and LimSupAvg(v) ≥ c, referring to the average value along an entire computation. We study the border of decidability for extensions of various temporal logics. In particular, we show that extending the fragment of CTL that has only the EX, EF, AX, and AG temporal modalities by prefix-accumulation assertions and extending LTL with path-accumulation assertions, result in temporal logics whose model-checking problem is decidable. The extended logics allow to significantly extend the currently known energy and mean-payoff objectives. Moreover, the prefix-accumulation assertions may be refined with "controlled-accumulation", allowing, for example, to specify constraints on the average waiting time between a request and a grant. On the negative side, we show that the fragment we point to is, in a sense, the maximal logic whose extension with prefix-accumulation assertions permits a decidable model-checking procedure. Extending a temporal logic that has the EG or EU modalities, and in particular CTL and LTL, makes the problem undecidable.},
author = {Boker, Udi and Chatterjee, Krishnendu and Henzinger, Thomas A and Kupferman, Orna},
location = {Toronto, Canada},
publisher = {IEEE},
title = {{Temporal specifications with accumulative values}},
doi = {10.1109/LICS.2011.33},
year = {2011},
}
@inproceedings{3357,
abstract = {We consider two-player graph games whose objectives are request-response condition, i.e conjunctions of conditions of the form "if a state with property Rq is visited, then later a state with property Rp is visited". The winner of such games can be decided in EXPTIME and the problem is known to be NP-hard. In this paper, we close this gap by showing that this problem is, in fact, EXPTIME-complete. We show that the problem becomes PSPACE-complete if we only consider games played on DAGs, and NP-complete or PTIME-complete if there is only one player (depending on whether he wants to enforce or spoil the request-response condition). We also present near-optimal bounds on the memory needed to design winning strategies for each player, in each case.},
author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Horn, Florian},
editor = {Dediu, Adrian-Horia and Inenaga, Shunsuke and Martín-Vide, Carlos},
location = {Tarragona, Spain},
pages = {227 -- 237},
publisher = {Springer},
title = {{The complexity of request-response games}},
doi = {10.1007/978-3-642-21254-3_17},
volume = {6638},
year = {2011},
}
@inproceedings{3358,
abstract = {The static scheduling problem often arises as a fundamental problem in real-time systems and grid computing. We consider the problem of statically scheduling a large job expressed as a task graph on a large number of computing nodes, such as a data center. This paper solves the large-scale static scheduling problem using abstraction refinement, a technique commonly used in formal verification to efficiently solve computationally hard problems. A scheduler based on abstraction refinement first attempts to solve the scheduling problem with abstract representations of the job and the computing resources. As abstract representations are generally small, the scheduling can be done reasonably fast. If the obtained schedule does not meet specified quality conditions (like data center utilization or schedule makespan) then the scheduler refines the job and data center abstractions and, again solves the scheduling problem. We develop different schedulers based on abstraction refinement. We implemented these schedulers and used them to schedule task graphs from various computing domains on simulated data centers with realistic topologies. We compared the speed of scheduling and the quality of the produced schedules with our abstraction refinement schedulers against a baseline scheduler that does not use any abstraction. We conclude that abstraction refinement techniques give a significant speed-up compared to traditional static scheduling heuristics, at a reasonable cost in the quality of the produced schedules. We further used our static schedulers in an actual system that we deployed on Amazon EC2 and compared it against the Hadoop dynamic scheduler for large MapReduce jobs. Our experiments indicate that there is great potential for static scheduling techniques.},
author = {Henzinger, Thomas A and Singh, Vasu and Wies, Thomas and Zufferey, Damien},
location = {Salzburg, Austria},
pages = {329 -- 342},
publisher = {ACM},
title = {{Scheduling large jobs by abstraction refinement}},
doi = {10.1145/1966445.1966476},
year = {2011},
}
@inproceedings{3359,
abstract = {Motivated by improvements in constraint-solving technology and by the increase of routinely available computational power, partial-program synthesis is emerging as an effective approach for increasing programmer productivity. The goal of the approach is to allow the programmer to specify a part of her intent imperatively (that is, give a partial program) and a part of her intent declaratively, by specifying which conditions need to be achieved or maintained. The task of the synthesizer is to construct a program that satisfies the specification. As an example, consider a partial program where threads access shared data without using any synchronization mechanism, and a declarative specification that excludes data races and deadlocks. The task of the synthesizer is then to place locks into the program code in order for the program to meet the specification.
In this paper, we argue that quantitative objectives are needed in partial-program synthesis in order to produce higher-quality programs, while enabling simpler specifications. Returning to the example, the synthesizer could construct a naive solution that uses one global lock for shared data. This can be prevented either by constraining the solution space further (which is error-prone and partly defeats the point of synthesis), or by optimizing a quantitative objective that models performance. Other quantitative notions useful in synthesis include fault tolerance, robustness, resource (memory, power) consumption, and information flow.},
author = {Cerny, Pavol and Henzinger, Thomas A},
location = {Taipei; Taiwan},
pages = {149 -- 154},
publisher = {ACM},
title = {{From boolean to quantitative synthesis}},
doi = {10.1145/2038642.2038666},
year = {2011},
}
@inproceedings{3360,
abstract = {A discounted-sum automaton (NDA) is a nondeterministic finite automaton with edge weights, which values a run by the discounted sum of visited edge weights. More precisely, the weight in the i-th position of the run is divided by lambda^i, where the discount factor lambda is a fixed rational number greater than 1. Discounted summation is a common and useful measuring scheme, especially for infinite sequences, which reflects the assumption that earlier weights are more important than later weights. Determinizing automata is often essential, for example, in formal verification, where there are polynomial algorithms for comparing two deterministic NDAs, while the equivalence problem for NDAs is not known to be decidable. Unfortunately, however, discounted-sum automata are, in general, not determinizable: it is currently known that for every rational discount factor 1 < lambda < 2, there is an NDA with lambda (denoted lambda-NDA) that cannot be determinized. We provide positive news, showing that every NDA with an integral factor is determinizable. We also complete the picture by proving that the integers characterize exactly the discount factors that guarantee determinizability: we show that for every non-integral rational factor lambda, there is a nondeterminizable lambda-NDA. Finally, we prove that the class of NDAs with integral discount factors enjoys closure under the algebraic operations min, max, addition, and subtraction, which is not the case for general NDAs nor for deterministic NDAs. This shows that for integral discount factors, the class of NDAs forms an attractive specification formalism in quantitative formal verification. All our results hold equally for automata over finite words and for automata over infinite words. },
author = {Boker, Udi and Henzinger, Thomas A},
location = {Bergen, Norway},
pages = {82 -- 96},
publisher = {Springer},
title = {{Determinizing discounted-sum automata}},
doi = {10.4230/LIPIcs.CSL.2011.82},
volume = {12},
year = {2011},
}
@inproceedings{3361,
abstract = {In this paper, we investigate the computational complexity of quantitative information flow (QIF) problems. Information-theoretic quantitative relaxations of noninterference (based on Shannon entropy)have been introduced to enable more fine-grained reasoning about programs in situations where limited information flow is acceptable. The QIF bounding problem asks whether the information flow in a given program is bounded by a constant $d$. Our first result is that the QIF bounding problem is PSPACE-complete. The QIF memoryless synthesis problem asks whether it is possible to resolve nondeterministic choices in a given partial program in such a way that in the resulting deterministic program, the quantitative information flow is bounded by a given constant $d$. Our second result is that the QIF memoryless synthesis problem is also EXPTIME-complete. The QIF memoryless synthesis problem generalizes to QIF general synthesis problem which does not impose the memoryless requirement (that is, by allowing the synthesized program to have more variables then the original partial program). Our third result is that the QIF general synthesis problem is EXPTIME-hard.},
author = {Cerny, Pavol and Chatterjee, Krishnendu and Henzinger, Thomas A},
location = {Cernay-la-Ville, France},
pages = {205 -- 217},
publisher = {IEEE},
title = {{The complexity of quantitative information flow problems}},
doi = {10.1109/CSF.2011.21},
year = {2011},
}
@inproceedings{3362,
abstract = {State-transition systems communicating by shared variables have been the underlying model of choice for applications of model checking. Such formalisms, however, have difficulty with modeling process creation or death and communication reconfigurability. Here, we introduce “dynamic reactive modules” (DRM), a state-transition modeling formalism that supports dynamic reconfiguration and creation/death of processes. The resulting formalism supports two types of variables, data variables and reference variables. Reference variables enable changing the connectivity between processes and referring to instances of processes. We show how this new formalism supports parallel composition and refinement through trace containment. DRM provide a natural language for modeling (and ultimately reasoning about) biological systems and multiple threads communicating through shared variables.},
author = {Fisher, Jasmin and Henzinger, Thomas A and Nickovic, Dejan and Piterman, Nir and Singh, Anmol and Vardi, Moshe},
location = {Aachen, Germany},
pages = {404 -- 418},
publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik},
title = {{Dynamic reactive modules}},
doi = {10.1007/978-3-642-23217-6_27},
volume = {6901},
year = {2011},
}
@unpublished{3363,
abstract = {We consider probabilistic automata on infinite words with acceptance defined by safety, reachability, Büchi, coBüchi, and limit-average conditions. We consider quantitative and qualitative decision problems. We present extensions and adaptations of proofs for probabilistic finite automata and present a complete characterization of the decidability and undecidability frontier of the quantitative and qualitative decision problems for probabilistic automata on infinite words.},
author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Tracol, Mathieu},
pages = {19},
publisher = {ArXiv},
title = {{The decidability frontier for probabilistic automata on infinite words}},
year = {2011},
}
@article{3364,
abstract = {Molecular noise, which arises from the randomness of the discrete events in the cell, significantly influences fundamental biological processes. Discrete-state continuous-time stochastic models (CTMC) can be used to describe such effects, but the calculation of the probabilities of certain events is computationally expensive. We present a comparison of two analysis approaches for CTMC. On one hand, we estimate the probabilities of interest using repeated Gillespie simulation and determine the statistical accuracy that we obtain. On the other hand, we apply a numerical reachability analysis that approximates the probability distributions of the system at several time instances. We use examples of cellular processes to demonstrate the superiority of the reachability analysis if accurate results are required.},
author = {Didier, Frédéric and Henzinger, Thomas A and Mateescu, Maria and Wolf, Verena},
journal = {Theoretical Computer Science},
number = {21},
pages = {2128 -- 2141},
publisher = {Elsevier},
title = {{Approximation of event probabilities in noisy cellular processes}},
doi = {10.1016/j.tcs.2010.10.022},
volume = {412},
year = {2011},
}
@inproceedings{3365,
abstract = {We present the tool Quasy, a quantitative synthesis tool. Quasy takes qualitative and quantitative specifications and automatically constructs a system that satisfies the qualitative specification and optimizes the quantitative specification, if such a system exists. The user can choose between a system that satisfies and optimizes the specifications (a) under all possible environment behaviors or (b) under the most-likely environment behaviors given as a probability distribution on the possible input sequences. Quasy solves these two quantitative synthesis problems by reduction to instances of 2-player games and Markov Decision Processes (MDPs) with quantitative winning objectives. Quasy can also be seen as a game solver for quantitative games. Most notable, it can solve lexicographic mean-payoff games with 2 players, MDPs with mean-payoff objectives, and ergodic MDPs with mean-payoff parity objectives.},
author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Jobstmann, Barbara and Singh, Rohit},
location = {Saarbrucken, Germany},
pages = {267 -- 271},
publisher = {Springer},
title = {{QUASY: quantitative synthesis tool}},
doi = {10.1007/978-3-642-19835-9_24},
volume = {6605},
year = {2011},
}
@inproceedings{3366,
abstract = {We present an algorithmic method for the quantitative, performance-aware synthesis of concurrent programs. The input consists of a nondeterministic partial program and of a parametric performance model. The nondeterminism allows the programmer to omit which (if any) synchronization construct is used at a particular program location. The performance model, specified as a weighted automaton, can capture system architectures by assigning different costs to actions such as locking, context switching, and memory and cache accesses. The quantitative synthesis problem is to automatically resolve the nondeterminism of the partial program so that both correctness is guaranteed and performance is optimal. As is standard for shared memory concurrency, correctness is formalized "specification free", in particular as race freedom or deadlock freedom. For worst-case (average-case) performance, we show that the problem can be reduced to 2-player graph games (with probabilistic transitions) with quantitative objectives. While we show, using game-theoretic methods, that the synthesis problem is Nexp-complete, we present an algorithmic method and an implementation that works efficiently for concurrent programs and performance models of practical interest. We have implemented a prototype tool and used it to synthesize finite-state concurrent programs that exhibit different programming patterns, for several performance models representing different architectures. },
author = {Cerny, Pavol and Chatterjee, Krishnendu and Henzinger, Thomas A and Radhakrishna, Arjun and Singh, Rohit},
editor = {Gopalakrishnan, Ganesh and Qadeer, Shaz},
location = {Snowbird, USA},
pages = {243 -- 259},
publisher = {Springer},
title = {{Quantitative synthesis for concurrent programs}},
doi = {10.1007/978-3-642-22110-1_20},
volume = {6806},
year = {2011},
}
@inproceedings{3367,
abstract = {In this paper, we present the first output-sensitive algorithm to compute the persistence diagram of a filtered simplicial complex. For any Γ>0, it returns only those homology classes with persistence at least Γ. Instead of the classical reduction via column operations, our algorithm performs rank computations on submatrices of the boundary matrix. For an arbitrary constant δ ∈ (0,1), the running time is O(C(1-δ)ΓR(n)log n), where C(1-δ)Γ is the number of homology classes with persistence at least (1-δ)Γ, n is the total number of simplices, and R(n) is the complexity of computing the rank of an n x n matrix with O(n) nonzero entries. Depending on the choice of the rank algorithm, this yields a deterministic O(C(1-δ)Γn2.376) algorithm, a O(C(1-δ)Γn2.28) Las-Vegas algorithm, or a O(C(1-δ)Γn2+ε) Monte-Carlo algorithm for an arbitrary ε>0.},
author = {Chen, Chao and Kerber, Michael},
location = {Paris, France},
pages = {207 -- 216},
publisher = {ACM},
title = {{An output sensitive algorithm for persistent homology}},
doi = {10.1145/1998196.1998228},
year = {2011},
}
@article{3368,
abstract = {Tissue surface tension (TST) is an important mechanical property influencing cell sorting and tissue envelopment. The study by Manning et al. (1) reported on a mathematical model describing TST on the basis of the balance between adhesive and tensile properties of the constituent cells. The model predicts that, in high-adhesion cell aggregates, surface cells will be stretched to maintain the same area of cell–cell contact as interior bulk cells, resulting in an elongated and flattened cell shape. The authors (1) observed flat and elongated cells at the surface of high-adhesion zebrafish germ-layer explants, which they argue are undifferentiated stretched germ-layer progenitor cells, and they use this observation as a validation of their model.},
author = {Krens, Gabriel and Möllmert, Stephanie and Heisenberg, Carl-Philipp J},
journal = {PNAS},
number = {3},
pages = {E9 -- E10},
publisher = {National Academy of Sciences},
title = {{Enveloping cell layer differentiation at the surface of zebrafish germ layer tissue explants}},
doi = {10.1073/pnas.1010767108},
volume = {108},
year = {2011},
}
@article{3369,
abstract = {Rab3 interacting molecules (RIMs) are highly enriched in the active zones of presynaptic terminals. It is generally thought that they operate as effectors of the small G protein Rab3. Three recent papers, by Han et al. (this issue of Neuron), Deng et al. (this issue of Neuron), and Kaeser et al. (a recent issue of Cell), shed new light on the functional role of RIM in presynaptic terminals. First, RIM tethers Ca2+ channels to active zones. Second, RIM contributes to priming of synaptic vesicles by interacting with another presynaptic protein, Munc13.},
author = {Pernia-Andrade, Alejandro and Jonas, Peter M},
journal = {Neuron},
number = {2},
pages = {185 -- 187},
publisher = {Elsevier},
title = {{The multiple faces of RIM}},
doi = {10.1016/j.neuron.2011.01.010},
volume = {69},
year = {2011},
}
@article{3370,
abstract = {Supertree methods are widely applied and give rise to new conclusions about phylogenies (e.g., Bininda-Emonds et al. 2007). Although several desiderata for supertree methods exist (Wilkinson, Thorley, et al. 2004), only few of them have been studied in greater detail, examples include shape bias (Wilkinson et al. 2005) or pareto properties (Wilkinson et al. 2007). Here I look more closely at two matrix representation methods, matrix representation with compatibility (MRC) and matrix representation with parsimony (MRP). Different null models of random data are studied and the resulting tree shapes are investigated. Thereby I consider unrooted trees and a bias in tree shape is determined by a tree balance measure. The measure for unrooted trees is a modification of a tree balance measure for rooted trees. I observe that depending on the underlying null model of random data, the methods may resolve conflict in favor of more balanced tree shapes. The analyses refer only to trees with the same taxon set, also known as the consensus setting (e.g., Wilkinson et al. 2007), but I will be able to draw conclusions on how to deal with missing data.},
author = {Kupczok, Anne},
journal = {Systematic Biology},
number = {2},
pages = {218 -- 225},
publisher = {Oxford University Press},
title = {{Consequences of different null models on the tree shape bias of supertree methods}},
doi = {10.1093/sysbio/syq086},
volume = {60},
year = {2011},
}
@article{3371,
abstract = {The Minisymposium “Cell Migration and Motility” was attended by approximately 500 visitors and covered a broad range of questions in the field using diverse model systems. Topics comprised actin dynamics, cell polarity, force transduction, signal transduction, bar- rier transmigration, and chemotactic guidance.},
author = {Sixt, Michael K and Parent, Carole},
journal = {Molecular Biology and Evolution},
number = {6},
pages = {724},
publisher = {Oxford University Press},
title = {{Cells on the move in Philadelphia}},
doi = {10.1091/mbc.E10-12-0958},
volume = {22},
year = {2011},
}
@article{3372,
abstract = {Nowak et al.1 argue that inclusive fitness theory has been of little value in explaining the natural world, and that it has led to negligible progress in explaining the evolution of eusociality. However, we believe that their arguments are based upon a misunderstanding of evolutionary theory and a misrepresentation of the empirical literature. We will focus our comments on three general issues.},
author = {Abbot, Patrick and Abe, Jun and Alcock, John and Alizon, Samuel and Alpedrinha, Joao and Andersson, Malte and Andre, Jean and Van Baalen, Minus and Balloux, Francois and Balshine, Sigal and Barton, Nicholas H and Beukeboom, Leo and Biernaskie, Jay and Bilde, Trine and Borgia, Gerald and Breed, Michael and Brown, Sam and Bshary, Redouan and Buckling, Angus and Burley, Nancy and Burton Chellew, Max and Cant, Michael and Chapuisat, Michel and Charnov, Eric and Clutton Brock, Tim and Cockburn, Andrew and Cole, Blaine and Colegrave, Nick and Cosmides, Leda and Couzin, Iain and Coyne, Jerry and Creel, Scott and Crespi, Bernard and Curry, Robert and Dall, Sasha and Day, Troy and Dickinson, Janis and Dugatkin, Lee and El Mouden, Claire and Emlen, Stephen and Evans, Jay and Ferriere, Regis and Field, Jeremy and Foitzik, Susanne and Foster, Kevin and Foster, William and Fox, Charles and Gadau, Juergen and Gandon, Sylvain and Gardner, Andy and Gardner, Michael and Getty, Thomas and Goodisman, Michael and Grafen, Alan and Grosberg, Rick and Grozinger, Christina and Gouyon, Pierre and Gwynne, Darryl and Harvey, Paul and Hatchwell, Ben and Heinze, Jürgen and Helantera, Heikki and Helms, Ken and Hill, Kim and Jiricny, Natalie and Johnstone, Rufus and Kacelnik, Alex and Kiers, E Toby and Kokko, Hanna and Komdeur, Jan and Korb, Judith and Kronauer, Daniel and Kümmerli, Rolf and Lehmann, Laurent and Linksvayer, Timothy and Lion, Sébastien and Lyon, Bruce and Marshall, James and Mcelreath, Richard and Michalakis, Yannis and Michod, Richard and Mock, Douglas and Monnin, Thibaud and Montgomerie, Robert and Moore, Allen and Mueller, Ulrich and Noë, Ronald and Okasha, Samir and Pamilo, Pekka and Parker, Geoff and Pedersen, Jes and Pen, Ido and Pfennig, David and Queller, David and Rankin, Daniel and Reece, Sarah and Reeve, Hudson and Reuter, Max and Roberts, Gilbert and Robson, Simon and Roze, Denis and Rousset, Francois and Rueppell, Olav and Sachs, Joel and Santorelli, Lorenzo and Schmid Hempel, Paul and Schwarz, Michael and Scott Phillips, Tom and Shellmann Sherman, Janet and Sherman, Paul and Shuker, David and Smith, Jeff and Spagna, Joseph and Strassmann, Beverly and Suarez, Andrew and Sundström, Liselotte and Taborsky, Michael and Taylor, Peter and Thompson, Graham and Tooby, John and Tsutsui, Neil and Tsuji, Kazuki and Turillazzi, Stefano and Úbeda, Francisco and Vargo, Edward and Voelkl, Bernard and Wenseleers, Tom and West, Stuart and West Eberhard, Mary and Westneat, David and Wiernasz, Diane and Wild, Geoff and Wrangham, Richard and Young, Andrew and Zeh, David and Zeh, Jeanne and Zink, Andrew},
journal = {Nature},
number = {7339},
pages = {E1 -- E4},
publisher = {Nature Publishing Group},
title = {{Inclusive fitness theory and eusociality}},
doi = {10.1038/nature09831},
volume = {471},
year = {2011},
}
@article{3373,
abstract = {The use of optical traps to measure or apply forces on the molecular level requires a precise knowledge of the trapping force field. Close to the trap center, this field is typically approximated as linear in the displacement of the trapped microsphere. However, applications demanding high forces at low laser intensities can probe the light-microsphere interaction beyond the linear regime. Here, we measured the full nonlinear force and displacement response of an optical trap in two dimensions using a dual-beam optical trap setup with back-focal-plane photodetection. We observed a substantial stiffening of the trap beyond the linear regime that depends on microsphere size, in agreement with Mie theory calculations. Surprisingly, we found that the linear detection range for forces exceeds the one for displacement by far. Our approach allows for a complete calibration of an optical trap.},
author = {Jahnel, Marcus and Behrndt, Martin and Jannasch, Anita and Schaeffer, Erik and Grill, Stephan},
journal = {Optics Letters},
number = {7},
pages = {1260 -- 1262},
publisher = {OSA},
title = {{Measuring the complete force field of an optical trap}},
doi = {10.1364/OL.36.001260},
volume = {36},
year = {2011},
}
@article{3374,
abstract = {Genetic regulatory networks enable cells to respond to changes in internal and external conditions by dynamically coordinating their gene expression profiles. Our ability to make quantitative measurements in these biochemical circuits has deepened our understanding of what kinds of computations genetic regulatory networks can perform, and with what reliability. These advances have motivated researchers to look for connections between the architecture and function of genetic regulatory networks. Transmitting information between a network's inputs and outputs has been proposed as one such possible measure of function, relevant in certain biological contexts. Here we summarize recent developments in the application of information theory to gene regulatory networks. We first review basic concepts in information theory necessary for understanding recent work. We then discuss the functional complexity of gene regulation, which arises from the molecular nature of the regulatory interactions. We end by reviewing some experiments that support the view that genetic networks responsible for early development of multicellular organisms might be maximizing transmitted 'positional information'.},
author = {Tkacik, Gasper and Walczak, Aleksandra},
journal = {Journal of Physics: Condensed Matter},
number = {15},
publisher = {IOP Publishing Ltd.},
title = {{Information transmission in genetic regulatory networks a review}},
doi = {10.1088/0953-8984/23/15/153102},
volume = {23},
year = {2011},
}
@article{3375,
abstract = {By exploiting an analogy between population genetics and statistical mechanics, we study the evolution of a polygenic trait under stabilizing selection, mutation and genetic drift. This requires us to track only four macroscopic variables, instead of the distribution of all the allele frequencies that influence the trait. These macroscopic variables are the expectations of: the trait mean and its square, the genetic variance, and of a measure of heterozygosity, and are derived from a generating function that is in turn derived by maximizing an entropy measure. These four macroscopics are enough to accurately describe the dynamics of the trait mean and of its genetic variance (and in principle of any other quantity). Unlike previous approaches that were based on an infinite series of moments or cumulants, which had to be truncated arbitrarily, our calculations provide a well-defined approximation procedure. We apply the framework to abrupt and gradual changes in the optimum, as well as to changes in the strength of stabilizing selection. Our approximations are surprisingly accurate, even for systems with as few as five loci. We find that when the effects of drift are included, the expected genetic variance is hardly altered by directional selection, even though it fluctuates in any particular instance. We also find hysteresis, showing that even after averaging over the microscopic variables, the macroscopic trajectories retain a memory of the underlying genetic states.},
author = {de Vladar, Harold and Barton, Nicholas H},
journal = {Journal of the Royal Society Interface},
number = {58},
pages = {720 -- 739},
publisher = {Royal Society of London},
title = {{The statistical mechanics of a polygenic character under stabilizing selection mutation and drift}},
doi = {10.1098/rsif.2010.0438},
volume = {8},
year = {2011},
}
@article{3376,
abstract = {Regulatory conflicts occur when two signals that individually trigger opposite cellular responses are present simultaneously. Here, we investigate regulatory conflicts in the bacterial response to antibiotic combinations. We use an Escherichia coli promoter-GFP library to study the transcriptional response of many promoters to either additive or antagonistic drug pairs at fine two-dimensional (2D) resolution of drug concentration. Surprisingly, we find that this data set can be characterized as a linear sum of only two principal components. Component one, accounting for over 70% of the response, represents the response to growth inhibition by the drugs. Component two describes how regulatory conflicts are resolved. For the additive drug pair, conflicts are resolved by linearly interpolating the single drug responses, while for the antagonistic drug pair, the growth-limiting drug dominates the response. Importantly, for a given drug pair, the same conflict resolution strategy applies to almost all genes. These results provide a recipe for predicting gene expression responses to antibiotic combinations.},
author = {Bollenbach, Mark Tobias and Kishony, Roy},
journal = {Molecular Cell},
number = {4},
pages = {413 -- 425},
publisher = {Cell Press},
title = {{Resolution of gene regulatory conflicts caused by combinations of antibiotics}},
doi = {10.1016/j.molcel.2011.04.016},
volume = {42},
year = {2011},
}
@article{3377,
abstract = {By definition, transverse intersections are stable under in- finitesimal perturbations. Using persistent homology, we ex- tend this notion to sizeable perturbations. Specifically, we assign to each homology class of the intersection its robust- ness, the magnitude of a perturbation necessary to kill it, and prove that robustness is stable. Among the applications of this result is a stable notion of robustness for fixed points of continuous mappings and a statement of stability for con- tours of smooth mappings.},
author = {Edelsbrunner, Herbert and Morozov, Dmitriy and Patel, Amit},
journal = {Foundations of Computational Mathematics},
number = {3},
pages = {345 -- 361},
publisher = {Springer},
title = {{Quantifying transversality by measuring the robustness of intersections}},
doi = {10.1007/s10208-011-9090-8},
volume = {11},
year = {2011},
}
@article{3378,
abstract = {The theory of intersection homology was developed to study the singularities of a topologically stratified space. This paper in- corporates this theory into the already developed framework of persistent homology. We demonstrate that persistent intersec- tion homology gives useful information about the relationship between an embedded stratified space and its singularities. We give, and prove the correctness of, an algorithm for the computa- tion of the persistent intersection homology groups of a filtered simplicial complex equipped with a stratification by subcom- plexes. We also derive, from Poincare ́ Duality, some structural results about persistent intersection homology.},
author = {Bendich, Paul and Harer, John},
journal = {Foundations of Computational Mathematics},
number = {3},
pages = {305 -- 336},
publisher = {Springer},
title = {{Persistent intersection homology}},
doi = {10.1007/s10208-010-9081-1},
volume = {11},
year = {2011},
}
@article{3379,
abstract = {The process of gastrulation is highly conserved across vertebrates on both the genetic and morphological levels, despite great variety in embryonic shape and speed of development. This mechanism spatially separates the germ layers and establishes the organizational foundation for future development. Mesodermal identity is specified in a superficial layer of cells, the epiblast, where cells maintain an epithelioid morphology. These cells involute to join the deeper hypoblast layer where they adopt a migratory, mesenchymal morphology. Expression of a cascade of related transcription factors orchestrates the parallel genetic transition from primitive to mature mesoderm. Although the early and late stages of this process are increasingly well understood, the transition between them has remained largely mysterious. We present here the first high resolution in vivo observations of the blebby transitional morphology of involuting mesodermal cells in a vertebrate embryo. We further demonstrate that the zebrafish spadetail mutation creates a reversible block in the maturation program, stalling cells in the transition state. This mutation creates an ideal system for dissecting the specific properties of cells undergoing the morphological transition of maturing mesoderm, as we demonstrate with a direct measurement of cell–cell adhesion.},
author = {Row, Richard and Maître, Jean-Léon and Martin, Benjamin and Stockinger, Petra and Heisenberg, Carl-Philipp J and Kimelman, David},
journal = {Developmental Biology},
number = {1},
pages = {102 -- 110},
publisher = {Elsevier},
title = {{Completion of the epithelial to mesenchymal transition in zebrafish mesoderm requires Spadetail}},
doi = {10.1016/j.ydbio.2011.03.025},
volume = {354},
year = {2011},
}
@article{3380,
abstract = {Linkage between markers and genes that affect a phenotype of interest may be determined by examining differences in marker allele frequency in the extreme progeny of a cross between two inbred lines. This strategy is usually employed when pooling is used to reduce genotyping costs. When the cross progeny are asexual, the extreme progeny may be selected by multiple generations of asexual reproduction and selection. We analyse this method of measuring phenotype in asexual progeny and examine the changes in marker allele frequency due to selection over many generations. Stochasticity in marker frequency in the selected population arises due to the finite initial population size. We derive the distribution of marker frequency as a result of selection at a single major locus, and show that in order to avoid spurious changes in marker allele frequency in the selected population, the initial population size should be in the low to mid hundreds.},
author = {Logeswaran, Sayanthan and Barton, Nicholas H},
journal = {Genetical Research},
number = {3},
pages = {221 -- 232},
publisher = {Cambridge University Press},
title = {{Mapping Mendelian traits in asexual progeny using changes in marker allele frequency}},
doi = {10.1017/S0016672311000115},
volume = {93},
year = {2011},
}
@article{3381,
abstract = {In this survey, we compare several languages for specifying Markovian population models such as queuing networks and chemical reaction networks. All these languages — matrix descriptions, stochastic Petri nets, stoichiometric equations, stochastic process algebras, and guarded command models — describe continuous-time Markov chains, but they differ according to important properties, such as compositionality, expressiveness and succinctness, executability, and ease of use. Moreover, they provide different support for checking the well-formedness of a model and for analyzing a model.},
author = {Henzinger, Thomas A and Jobstmann, Barbara and Wolf, Verena},
journal = {IJFCS: International Journal of Foundations of Computer Science},
number = {4},
pages = {823 -- 841},
publisher = {World Scientific Publishing},
title = {{Formalisms for specifying Markovian population models}},
doi = {10.1142/S0129054111008441},
volume = {22},
year = {2011},
}
@article{3382,
abstract = {Dynamic tactile sensing is a fundamental ability to recognize materials and objects. However, while humans are born with partially developed dynamic tactile sensing and quickly master this skill, today's robots remain in their infancy. The development of such a sense requires not only better sensors but the right algorithms to deal with these sensors' data as well. For example, when classifying a material based on touch, the data are noisy, high-dimensional, and contain irrelevant signals as well as essential ones. Few classification methods from machine learning can deal with such problems. In this paper, we propose an efficient approach to infer suitable lower dimensional representations of the tactile data. In order to classify materials based on only the sense of touch, these representations are autonomously discovered using visual information of the surfaces during training. However, accurately pairing vision and tactile samples in real-robot applications is a difficult problem. The proposed approach, therefore, works with weak pairings between the modalities. Experiments show that the resulting approach is very robust and yields significantly higher classification performance based on only dynamic tactile sensing.},
author = {Kroemer, Oliver and Lampert, Christoph and Peters, Jan},
journal = {IEEE Transactions on Robotics},
number = {3},
pages = {545 -- 557},
publisher = {IEEE},
title = {{Learning dynamic tactile sensing with robust vision based training}},
doi = {10.1109/TRO.2011.2121130},
volume = {27},
year = {2011},
}
@article{3383,
author = {Heisenberg, Carl-Philipp J},
journal = {FEBS Journal},
number = {S1},
pages = {24 -- 24},
publisher = {Wiley-Blackwell},
title = {{Invited Lectures ‐ Symposia Area}},
doi = {10.1111/j.1742-4658.2011.08136.x},
volume = {278},
year = {2011},
}
@article{3384,
abstract = {Here we introduce a database of calibrated natural images publicly available through an easy-to-use web interface. Using a Nikon D70 digital SLR camera, we acquired about six-megapixel images of Okavango Delta of Botswana, a tropical savanna habitat similar to where the human eye is thought to have evolved. Some sequences of images were captured unsystematically while following a baboon troop, while others were designed to vary a single parameter such as aperture, object distance, time of day or position on the horizon. Images are available in the raw RGB format and in grayscale. Images are also available in units relevant to the physiology of human cone photoreceptors, where pixel values represent the expected number of photoisomerizations per second for cones sensitive to long (L), medium (M) and short (S) wavelengths. This database is distributed under a Creative Commons Attribution-Noncommercial Unported license to facilitate research in computer vision, psychophysics of perception, and visual neuroscience.},
author = {Tkacik, Gasper and Garrigan, Patrick and Ratliff, Charles and Milcinski, Grega and Klein, Jennifer and Seyfarth, Lucia and Sterling, Peter and Brainard, David and Balasubramanian, Vijay},
journal = {PLoS One},
number = {6},
publisher = {Public Library of Science},
title = {{Natural images from the birthplace of the human eye}},
doi = {10.1371/journal.pone.0020409},
volume = {6},
year = {2011},
}
@article{3385,
author = {Sixt, Michael K},
journal = {Immunology Letters},
number = {1},
pages = {32 -- 34},
publisher = {Elsevier},
title = {{Interstitial locomotion of leukocytes}},
doi = {10.1016/j.imlet.2011.02.013},
volume = {138},
year = {2011},
}
@article{3386,
abstract = {Evolutionary theories of ageing predict that life span increases with decreasing extrinsic mortality, and life span variation among queens in ant species seems to corroborate this prediction: queens, which are the only reproductive in a colony, live much longer than queens in multi-queen colonies. The latter often inhabit ephemeral nest sites and accordingly are assumed to experience a higher mortality risk. Yet, all prior studies compared queens from different single- and multi-queen species. Here, we demonstrate an effect of queen number on longevity and fecundity within a single, socially plastic species, where queens experience the similar level of extrinsic mortality. Queens from single- and two-queen colonies had significantly longer lifespan and higher fecundity than queens living in associations of eight queens. As queens also differ neither in morphology nor the mode of colony foundation, our study shows that the social environment itself strongly affects ageing rate.},
author = {Schrempf, Alexandra and Cremer, Sylvia and Heinze, Jürgen},
journal = {Journal of Evolutionary Biology},
number = {7},
pages = {1455 -- 1461},
publisher = {Wiley-Blackwell},
title = {{Social influence on age and reproduction reduced lifespan and fecundity in multi queen ant colonies}},
doi = {10.1111/j.1420-9101.2011.02278.x},
volume = {24},
year = {2011},
}
@article{3387,
abstract = {Background: Supertree methods combine overlapping input trees into a larger supertree. Here, I consider split-based supertree methods that first extract the split information of the input trees and subsequently combine this split information into a phylogeny. Well known split-based supertree methods are matrix representation with parsimony and matrix representation with compatibility. Combining input trees on the same taxon set, as in the consensus setting, is a well-studied task and it is thus desirable to generalize consensus methods to supertree methods. Results: Here, three variants of majority-rule (MR) supertrees that generalize majority-rule consensus trees are investigated. I provide simple formulas for computing the respective score for bifurcating input- and supertrees. These score computations, together with a heuristic tree search minmizing the scores, were implemented in the python program PluMiST (Plus- and Minus SuperTrees) available from http://www.cibiv.at/software/ plumist. The different MR methods were tested by simulation and on real data sets. The search heuristic was successful in combining compatible input trees. When combining incompatible input trees, especially one variant, MR(-) supertrees, performed well. Conclusions: The presented framework allows for an efficient score computation of three majority-rule supertree variants and input trees. I combined the score computation with a heuristic search over the supertree space. The implementation was tested by simulation and on real data sets and showed promising results. Especially the MR(-) variant seems to be a reasonable score for supertree reconstruction. Generalizing these computations to multifurcating trees is an open problem, which may be tackled using this framework.},
author = {Kupczok, Anne},
journal = {BMC Evolutionary Biology},
number = {205},
publisher = {BioMed Central},
title = {{Split based computation of majority rule supertrees}},
doi = {10.1186/1471-2148-11-205},
volume = {11},
year = {2011},
}
@article{3388,
abstract = {Background: Fragmentation of terrestrial ecosystems has had detrimental effects on metapopulations of habitat specialists. Maculinea butterflies have been particularly affected because of their specialized lifecycles, requiring both specific food-plants and host-ants. However, the interaction between dispersal, effective population size, and long-term genetic erosion of these endangered butterflies remains unknown. Using non-destructive sampling, we investigated the genetic diversity of the last extant population of M. arion in Denmark, which experienced critically low numbers in the 1980s. Results: Using nine microsatellite markers, we show that the population is genetically impoverished compared to nearby populations in Sweden, but less so than monitoring programs suggested. Ten additional short repeat microsatellites were used to reconstruct changes in genetic diversity and population structure over the last 77 years from museum specimens. We also tested amplification efficiency in such historical samples as a function of repeat length and sample age. Low population numbers in the 1980s did not affect genetic diversity, but considerable turnover of alleles has characterized this population throughout the time-span of our analysis. Conclusions: Our results suggest that M. arion is less sensitive to genetic erosion via population bottlenecks than previously thought, and that managing clusters of high quality habitat may be key for long-term conservation.},
author = {Ugelvig, Line V and Nielsen, Per and Boomsma, Jacobus and Nash, David},
journal = {BMC Evolutionary Biology},
number = {201},
publisher = {BioMed Central},
title = {{Reconstructing eight decades of genetic variation in an isolated Danish population of the large blue butterfly Maculinea arion}},
doi = {10.1186/1471-2148-11-201},
volume = {11},
year = {2011},
}
@article{3389,
abstract = {Kernel canonical correlation analysis (KCCA) is a general technique for subspace learning that incorporates principal components analysis (PCA) and Fisher linear discriminant analysis (LDA) as special cases. By finding directions that maximize correlation, KCCA learns representations that are more closely tied to the underlying process that generates the data and can ignore high-variance noise directions. However, for data where acquisition in one or more modalities is expensive or otherwise limited, KCCA may suffer from small sample effects. We propose to use semi-supervised Laplacian regularization to utilize data that are present in only one modality. This approach is able to find highly correlated directions that also lie along the data manifold, resulting in a more robust estimate of correlated subspaces. Functional magnetic resonance imaging (fMRI) acquired data are naturally amenable to subspace techniques as data are well aligned. fMRI data of the human brain are a particularly interesting candidate. In this study we implemented various supervised and semi-supervised versions of KCCA on human fMRI data, with regression to single and multi-variate labels (corresponding to video content subjects viewed during the image acquisition). In each variate condition, the semi-supervised variants of KCCA performed better than the supervised variants, including a supervised variant with Laplacian regularization. We additionally analyze the weights learned by the regression in order to infer brain regions that are important to different types of visual processing.},
author = {Blaschko, Matthew and Shelton, Jacquelyn and Bartels, Andreas and Lampert, Christoph and Gretton, Arthur},
journal = {Pattern Recognition Letters},
number = {11},
pages = {1572 -- 1583},
publisher = {Elsevier},
title = {{Semi supervised kernel canonical correlation analysis with application to human fMRI}},
doi = {10.1016/j.patrec.2011.02.011},
volume = {32},
year = {2011},
}
@article{3390,
abstract = {What determines the genetic contribution that an individual makes to future generations? With biparental reproduction, each individual leaves a 'pedigree' of descendants, determined by the biparental relationships in the population. The pedigree of an individual constrains the lines of descent of each of its genes. An individual's reproductive value is the expected number of copies of each of its genes that is passed on to distant generations conditional on its pedigree. For the simplest model of biparental reproduction analogous to the Wright-Fisher model, an individual's reproductive value is determined within ~10 generations, independent of population size. Partial selfing and subdivision do not greatly slow this convergence. Our central result is that the probability that a gene will survive is proportional to the reproductive value of the individual that carries it, and that conditional on survival, after a few tens of generations, the distribution of the number of surviving copies is the same for all individuals, whatever their reproductive value. These results can be generalized to the joint distribution of surviving blocks of ancestral genome. Selection on unlinked loci in the genetic background may greatly increase the variance in reproductive value, but the above results nevertheless still hold. The almost linear relationship between survival probability and reproductive value also holds for weakly favored alleles. Thus, the influence of the complex pedigree of descendants on an individual's genetic contribution to the population can be summarized through a single number: its reproductive value.},
author = {Barton, Nicholas H and Etheridge, Alison},
journal = {Genetics},
number = {4},
pages = {953 -- 973},
publisher = {Genetics Society of America},
title = {{The relation between reproductive value and genetic contribution}},
doi = {10.1534/genetics.111.127555},
volume = {188},
year = {2011},
}
@article{3391,
abstract = {Evolutionary biology shares many concepts with statistical physics: both deal with populations, whether of molecules or organisms, and both seek to simplify evolution in very many dimensions. Often, methodologies have undergone parallel and independent development, as with stochastic methods in population genetics. Here, we discuss aspects of population genetics that have embraced methods from physics: non-equilibrium statistical mechanics, travelling waves and Monte-Carlo methods, among others, have been used to study polygenic evolution, rates of adaptation and range expansions. These applications indicate that evolutionary biology can further benefit from interactions with other areas of statistical physics; for example, by following the distribution of paths taken by a population through time},
author = {de Vladar, Harold and Barton, Nicholas H},
journal = {Trends in Ecology and Evolution},
number = {8},
pages = {424 -- 432},
publisher = {Cell Press},
title = {{The contribution of statistical physics to evolutionary biology}},
doi = {10.1016/j.tree.2011.04.002},
volume = {26},
year = {2011},
}
@article{3392,
abstract = {Migrating lymphocytes acquire a polarized phenotype with a leading and a trailing edge, or uropod. Although in vitro experiments in cell lines or activated primary cell cultures have established that Rho-p160 coiled-coil kinase (ROCK)-myosin II-mediated uropod contractility is required for integrin de-adhesion on two-dimensional surfaces and nuclear propulsion through narrow pores in three-dimensional matrices, less is known about the role of these two events during the recirculation of primary, nonactivated lymphocytes. Using pharmacological antagonists of ROCK and myosin II, we report that inhibition of uropod contractility blocked integrin-independent mouse T cell migration through narrow, but not large, pores in vitro. T cell crawling on chemokine-coated endothelial cells under shear was severely impaired by ROCK inhibition, whereas transendothelial migration was only reduced through endothelial cells with high, but not low, barrier properties. Using three-dimensional thick-tissue imaging and dynamic two-photon microscopy of T cell motility in lymphoid tissue, we demonstrated a significant role for uropod contractility in intraluminal crawling and transendothelial migration through lymph node, but not bone marrow, endothelial cells. Finally, we demonstrated that ICAM-1, but not anatomical constraints or integrin-independent interactions, reduced parenchymal motility of inhibitor-treated T cells within the dense lymphoid microenvironment, thus assigning context-dependent roles for uropod contraction during lymphocyte recirculation.},
author = {Soriano, Silvia and Hons, Miroslav and Schumann, Kathrin and Kumar, Varsha and Dennier, Timo and Lyck, Ruth and Sixt, Michael K and Stein, Jens},
journal = {Journal of Immunology},
number = {5},
pages = {2356 -- 2364},
publisher = {American Association of Immunologists},
title = {{In vivo analysis of uropod function during physiological T cell trafficking}},
doi = {10.4049/jimmunol.1100935},
volume = {187},
year = {2011},
}
@article{3393,
abstract = {Unlike unconditionally advantageous “Fisherian” variants that tend to spread throughout a species range once introduced anywhere, “bistable” variants, such as chromosome translocations, have two alternative stable frequencies, absence and (near) fixation. Analogous to populations with Allee effects, bistable variants tend to increase locally only once they become sufficiently common, and their spread depends on their rate of increase averaged over all frequencies. Several proposed manipulations of insect populations, such as using Wolbachia or “engineered underdominance” to suppress vector-borne diseases, produce bistable rather than Fisherian dynamics. We synthesize and extend theoretical analyses concerning three features of their spatial behavior: rate of spread, conditions to initiate spread from a localized introduction, and wave stopping caused by variation in population densities or dispersal rates. Unlike Fisherian variants, bistable variants tend to spread spatially only for particular parameter combinations and initial conditions. Wave initiation requires introduction over an extended region, while subsequent spatial spread is slower than for Fisherian waves and can easily be halted by local spatial inhomogeneities. We present several new results, including robust sufficient conditions to initiate (and stop) spread, using a one-parameter cubic approximation applicable to several models. The results have both basic and applied implications.},
author = {Barton, Nicholas H and Turelli, Michael},
journal = {American Naturalist},
number = {3},
pages = {E48 -- E75},
publisher = {University of Chicago Press},
title = {{Spatial waves of advance with bistable dynamics: Cytoplasmic and genetic analogues of Allee effects}},
doi = {10.1086/661246},
volume = {178},
year = {2011},
}
@article{3394,
abstract = {Random genetic drift shifts clines in space, alters their width, and distorts their shape. Such random fluctuations complicate inferences from cline width and position. Notably, the effect of genetic drift on the expected shape of the cline is opposite to the naive (but quite common) misinterpretation of classic results on the expected cline. While random drift on average broadens the overall cline in expected allele frequency, it narrows the width of any particular cline. The opposing effects arise because locally, drift drives alleles to fixation—but fluctuations in position widen the expected cline. The effect of genetic drift can be predicted from standardized variance in allele frequencies, averaged across the habitat: 〈F〉. A cline maintained by spatially varying selection (step change) is expected to be narrower by a factor of relative to the cline in the absence of drift. The expected cline is broader by the inverse of this factor. In a tension zone maintained by underdominance, the expected cline width is narrower by about 1 – 〈F〉relative to the width in the absence of drift. Individual clines can differ substantially from the expectation, and we give quantitative predictions for the variance in cline position and width. The predictions apply to clines in almost one-dimensional circumstances such as hybrid zones in rivers, deep valleys, or along a coast line and give a guide to what patterns to expect in two dimensions.},
author = {Polechova, Jitka and Barton, Nicholas H},
journal = {Genetics},
number = {1},
pages = {227 -- 235},
publisher = {Genetics Society of America},
title = {{Genetic drift widens the expected cline but narrows the expected cline width}},
doi = {10.1534/genetics.111.129817},
volume = {189},
year = {2011},
}
@article{3395,
abstract = {Defining population structure and genetic diversity levels is of the utmost importance for developing efficient conservation strategies. Overfishing has caused mean annual catches of the European spiny lobster (Palinurus elephas) to decrease alarmingly along its distribution area. In this context, there is a need for comprehensive studies aiming to evaluate the genetic health of the exploited populations. The present study is based on a set of ten nuclear markers amplified in 331 individuals from ten different localities covering most of P. elephas distribution area. Samples from Atlantic and Mediterranean basins showed small but significant differences, indicating that P. elephas populations do not behave as a single panmictic unit but form two partially-overlapping groups. Despite intense overfishing, our dataset did not recover a recent bottleneck signal, and instead showed a large and stable historical effective size. This result could be accounted for by specific life-history traits (reproduction and longevity) and the limitations of molecular markers in covering recent timescales for nontemporal samples. The findings of the present study emphasize the need to integrate information on effective population sizes and life-history parameters when evaluating population connectivity levels from genetic data.},
author = {Palero, Ferran and Abello, Pere and Macpherson, Enrique and Beaumont, Mark and Pascual, Marta},
journal = {Biological Journal of the Linnean Society},
number = {2},
pages = {407 -- 418},
publisher = {Wiley-Blackwell},
title = {{Effect of oceanographic barriers and overfishing on the population genetic structure of the European spiny lobster Palinurus elephas }},
doi = {10.1111/j.1095-8312.2011.01728.x},
volume = {104},
year = {2011},
}
@article{3396,
abstract = {Facial branchiomotor neurons (FBMNs) in zebrafish and mouse embryonic hindbrain undergo a characteristic tangential migration from rhombomere (r) 4, where they are born, to r6/7. Cohesion among neuroepithelial cells (NCs) has been suggested to function in FBMN migration by inhibiting FBMNs positioned in the basal neuroepithelium such that they move apically between NCs towards the midline of the neuroepithelium instead of tangentially along the basal side of the neuroepithelium towards r6/7. However, direct experimental evaluation of this hypothesis is still lacking. Here, we have used a combination of biophysical cell adhesion measurements and high-resolution time-lapse microscopy to determine the role of NC cohesion in FBMN migration. We show that reducing NC cohesion by interfering with Cadherin 2 (Cdh2) activity results in FBMNs positioned at the basal side of the neuroepithelium moving apically towards the neural tube midline instead of tangentially towards r6/7. In embryos with strongly reduced NC cohesion, ectopic apical FBMN movement frequently results in fusion of the bilateral FBMN clusters over the apical midline of the neural tube. By contrast, reducing cohesion among FBMNs by interfering with Contactin 2 (Cntn2) expression in these cells has little effect on apical FBMN movement, but reduces the fusion of the bilateral FBMN clusters in embryos with strongly diminished NC cohesion. These data provide direct experimental evidence that NC cohesion functions in tangential FBMN migration by restricting their apical movement.},
author = {Stockinger, Petra and Heisenberg, Carl-Philipp J and Maître, Jean-Léon},
journal = {Development},
number = {21},
pages = {4673 -- 4683},
publisher = {Company of Biologists},
title = {{Defective neuroepithelial cell cohesion affects tangential branchiomotor neuron migration in the zebrafish neural tube}},
doi = {10.1242/dev.071233},
volume = {138},
year = {2011},
}
@article{3397,
abstract = {Recent advances in microscopy techniques and biophysical measurements have provided novel insight into the molecular, cellular and biophysical basis of cell adhesion. However, comparably little is known about a core element of cell–cell adhesion—the energy of adhesion at the cell–cell contact. In this review, we discuss approaches to understand the nature and regulation of adhesion energy, and propose strategies to determine adhesion energy between cells in vitro and in vivo.},
author = {Maître, Jean-Léon and Heisenberg, Carl-Philipp J},
journal = {Current Opinion in Cell Biology},
number = {5},
pages = {508 -- 514},
publisher = {Elsevier},
title = {{The role of adhesion energy in controlling cell-cell contacts}},
doi = {10.1016/j.ceb.2011.07.004},
volume = {23},
year = {2011},
}
@article{3399,
abstract = {Context-dependent adjustment of mating tactics can drastically increase the mating success of behaviourally flexible animals. We used the ant Cardiocondyla obscurior as a model system to study adaptive adjustment of male mating tactics. This species shows a male diphenism of wingless fighter males and peaceful winged males. Whereas the wingless males stay and exclusively mate in the maternal colony, the mating behaviour of winged males is plastic. They copulate with female sexuals in their natal nests early in life but later disperse in search for sexuals outside. In this study, we observed the nest-leaving behaviour of winged males under different conditions and found that they adaptively adjust the timing of their dispersal to the availability of mating partners, as well as the presence, and even the type of competitors in their natal nests. In colonies with virgin female queens winged males stayed longest when they were the only male in the nest. They left earlier when mating partners were not available or when other males were present. In the presence of wingless, locally mating fighter males, winged males dispersed earlier than in the presence of docile, winged competitors. This suggests that C. obscurior males are capable of estimating their local breeding chances and adaptively adjust their dispersal behaviour in both an opportunistic and a risk-sensitive way, thus showing hitherto unknown behavioural plasticity in social insect males.},
author = {Cremer, Sylvia and Schrempf, Alexandra and Heinze, Jürgen},
journal = {PLoS One},
number = {3},
publisher = {Public Library of Science},
title = {{Competition and opportunity shape the reproductive tactics of males in the ant Cardiocondyla obscurior}},
doi = {10.1371/journal.pone.0017323},
volume = {6},
year = {2011},
}
@article{3405,
abstract = {Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system and gates non-selective cation channels. The origins of glutamate receptors are not well understood as they differ structurally and functionally from simple bacterial ligand-gated ion channels. Here we report the discovery of an ionotropic glutamate receptor that combines the typical eukaryotic domain architecture with the 'TXVGYG' signature sequence of the selectivity filter found in K+ channels. This receptor exhibits functional properties intermediate between bacterial and eukaryotic glutamate-gated ion channels, suggesting a link in the evolution of ionotropic glutamate receptors.},
author = {Janovjak, Harald L and Sandoz, Guillaume and Isacoff, Ehud},
journal = {Nature Communications},
number = {232},
pages = {1 -- 6},
publisher = {Nature Publishing Group},
title = {{Modern ionotropic glutamate receptor with a K+ selectivity signature sequence}},
doi = {10.1038/ncomms1231},
volume = {2},
year = {2011},
}
@article{3429,
abstract = {Transcription factors are central to sustaining pluripotency, yet little is known about transcription factor dynamics in defining pluripotency in the early mammalian embryo. Here, we establish a fluorescence decay after photoactivation (FDAP) assay to quantitatively study the kinetic behaviour of Oct4, a key transcription factor controlling pre-implantation development in the mouse embryo. FDAP measurements reveal that each cell in a developing embryo shows one of two distinct Oct4 kinetics, before there are any morphologically distinguishable differences or outward signs of lineage patterning. The differences revealed by FDAP are due to differences in the accessibility of Oct4 to its DNA binding sites in the nucleus. Lineage tracing of the cells in the two distinct sub-populations demonstrates that the Oct4 kinetics predict lineages of the early embryo. Cells with slower Oct4 kinetics are more likely to give rise to the pluripotent cell lineage that contributes to the inner cell mass. Those with faster Oct4 kinetics contribute mostly to the extra-embryonic lineage. Our findings identify Oct4 kinetics, rather than differences in total transcription factor expression levels, as a predictive measure of developmental cell lineage patterning in the early mouse embryo.},
author = {Plachta, Nicolas and Bollenbach, Mark Tobias and Pease, Shirley and Fraser, Scott and Pantazis, Periklis},
journal = {Nature Cell Biology},
number = {2},
pages = {117 -- 123},
publisher = {Nature Publishing Group},
title = {{Oct4 kinetics predict cell lineage patterning in the early mammalian embryo}},
doi = {10.1038/ncb2154},
volume = {13},
year = {2011},
}