TY - CONF
AB - Cryptographic e-cash allows off-line electronic transactions between a bank, users and merchants in a secure and anonymous fashion. A plethora of e-cash constructions has been proposed in the literature; however, these traditional e-cash schemes only allow coins to be transferred once between users and merchants. Ideally, we would like users to be able to transfer coins between each other multiple times before deposit, as happens with physical cash. “Transferable” e-cash schemes are the solution to this problem. Unfortunately, the currently proposed schemes are either completely impractical or do not achieve the desirable anonymity properties without compromises, such as assuming the existence of a trusted “judge” who can trace all coins and users in the system. This paper presents the first efficient and fully anonymous transferable e-cash scheme without any trusted third parties. We start by revising the security and anonymity properties of transferable e-cash to capture issues that were previously overlooked. For our construction we use the recently proposed malleable signatures by Chase et al. to allow the secure and anonymous transfer of coins, combined with a new efficient double-spending detection mechanism. Finally, we discuss an instantiation of our construction.
AU - Baldimtsi, Foteini
AU - Chase, Melissa
AU - Fuchsbauer, Georg
AU - Kohlweiss, Markulf
ID - 1651
TI - Anonymous transferable e-cash
VL - 9020
ER -
TY - CONF
AB - We develop new theoretical tools for proving lower-bounds on the (amortized) complexity of certain functions in models of parallel computation. We apply the tools to construct a class of functions with high amortized memory complexity in the parallel Random Oracle Model (pROM); a variant of the standard ROM allowing for batches of simultaneous queries. In particular we obtain a new, more robust, type of Memory-Hard Functions (MHF); a security primitive which has recently been gaining acceptance in practice as an effective means of countering brute-force attacks on security relevant functions. Along the way we also demonstrate an important shortcoming of previous definitions of MHFs and give a new definition addressing the problem. The tools we develop represent an adaptation of the powerful pebbling paradigm (initially introduced by Hewitt and Paterson [HP70] and Cook [Coo73]) to a simple and intuitive parallel setting. We define a simple pebbling game Gp over graphs which aims to abstract parallel computation in an intuitive way. As a conceptual contribution we define a measure of pebbling complexity for graphs called cumulative complexity (CC) and show how it overcomes a crucial shortcoming (in the parallel setting) exhibited by more traditional complexity measures used in the past. As a main technical contribution we give an explicit construction of a constant in-degree family of graphs whose CC in Gp approaches maximality to within a polylogarithmic factor for any graph of equal size (analogous to the graphs of Tarjan et. al. [PTC76, LT82] for sequential pebbling games). Finally, for a given graph G and related function fG, we derive a lower-bound on the amortized memory complexity of fG in the pROM in terms of the CC of G in the game Gp.
AU - Alwen, Joel F
AU - Serbinenko, Vladimir
ID - 1652
T2 - Proceedings of the 47th annual ACM symposium on Theory of computing
TI - High parallel complexity graphs and memory-hard functions
ER -
TY - CONF
AB - HMAC and its variant NMAC are the most popular approaches to deriving a MAC (and more generally, a PRF) from a cryptographic hash function. Despite nearly two decades of research, their exact security still remains far from understood in many different contexts. Indeed, recent works have re-surfaced interest for {\em generic} attacks, i.e., attacks that treat the compression function of the underlying hash function as a black box.
Generic security can be proved in a model where the underlying compression function is modeled as a random function -- yet, to date, the question of proving tight, non-trivial bounds on the generic security of HMAC/NMAC even as a PRF remains a challenging open question.
In this paper, we ask the question of whether a small modification to HMAC and NMAC can allow us to exactly characterize the security of the resulting constructions, while only incurring little penalty with respect to efficiency. To this end, we present simple variants of NMAC and HMAC, for which we prove tight bounds on the generic PRF security, expressed in terms of numbers of construction and compression function queries necessary to break the construction. All of our constructions are obtained via a (near) {\em black-box} modification of NMAC and HMAC, which can be interpreted as an initial step of key-dependent message pre-processing.
While our focus is on PRF security, a further attractive feature of our new constructions is that they clearly defeat all recent generic attacks against properties such as state recovery and universal forgery. These exploit properties of the so-called ``functional graph'' which are not directly accessible in our new constructions.
AU - Gazi, Peter
AU - Pietrzak, Krzysztof Z
AU - Tessaro, Stefano
ID - 1654
TI - Generic security of NMAC and HMAC with input whitening
VL - 9453
ER -
TY - JOUR
AB - Quantifying behaviors of robots which were generated autonomously from task-independent objective functions is an important prerequisite for objective comparisons of algorithms and movements of animals. The temporal sequence of such a behavior can be considered as a time series and hence complexity measures developed for time series are natural candidates for its quantification. The predictive information and the excess entropy are such complexity measures. They measure the amount of information the past contains about the future and thus quantify the nonrandom structure in the temporal sequence. However, when using these measures for systems with continuous states one has to deal with the fact that their values will depend on the resolution with which the systems states are observed. For deterministic systems both measures will diverge with increasing resolution. We therefore propose a new decomposition of the excess entropy in resolution dependent and resolution independent parts and discuss how they depend on the dimensionality of the dynamics, correlations and the noise level. For the practical estimation we propose to use estimates based on the correlation integral instead of the direct estimation of the mutual information based on next neighbor statistics because the latter allows less control of the scale dependencies. Using our algorithm we are able to show how autonomous learning generates behavior of increasing complexity with increasing learning duration.
AU - Martius, Georg S
AU - Olbrich, Eckehard
ID - 1655
IS - 10
JF - Entropy
TI - Quantifying emergent behavior of autonomous robots
VL - 17
ER -
TY - CONF
AB - Recently there has been a significant effort to handle quantitative properties in formal verification and synthesis. While weighted automata over finite and infinite words provide a natural and flexible framework to express quantitative properties, perhaps surprisingly, some basic system properties such as average response time cannot be expressed using weighted automata, nor in any other know decidable formalism. In this work, we introduce nested weighted automata as a natural extension of weighted automata which makes it possible to express important quantitative properties such as average response time. In nested weighted automata, a master automaton spins off and collects results from weighted slave automata, each of which computes a quantity along a finite portion of an infinite word. Nested weighted automata can be viewed as the quantitative analogue of monitor automata, which are used in run-time verification. We establish an almost complete decidability picture for the basic decision problems about nested weighted automata, and illustrate their applicability in several domains. In particular, nested weighted automata can be used to decide average response time properties.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 1656
T2 - Proceedings - Symposium on Logic in Computer Science
TI - Nested weighted automata
VL - 2015-July
ER -
TY - CONF
AB - We consider Markov decision processes (MDPs) with multiple limit-average (or mean-payoff) objectives. There exist two different views: (i) ~the expectation semantics, where the goal is to optimize the expected mean-payoff objective, and (ii) ~the satisfaction semantics, where the goal is to maximize the probability of runs such that the mean-payoff value stays above a given vector. We consider optimization with respect to both objectives at once, thus unifying the existing semantics. Precisely, the goal is to optimize the expectation while ensuring the satisfaction constraint. Our problem captures the notion of optimization with respect to strategies that are risk-averse (i.e., Ensure certain probabilistic guarantee). Our main results are as follows: First, we present algorithms for the decision problems, which are always polynomial in the size of the MDP. We also show that an approximation of the Pareto curve can be computed in time polynomial in the size of the MDP, and the approximation factor, but exponential in the number of dimensions. Second, we present a complete characterization of the strategy complexity (in terms of memory bounds and randomization) required to solve our problem.
AU - Chatterjee, Krishnendu
AU - Komárková, Zuzana
AU - Kretinsky, Jan
ID - 1657
TI - Unifying two views on multiple mean-payoff objectives in Markov decision processes
ER -
TY - CONF
AB - Continuous-time Markov chain (CTMC) models have become a central tool for understanding the dynamics of complex reaction networks and the importance of stochasticity in the underlying biochemical processes. When such models are employed to answer questions in applications, in order to ensure that the model provides a sufficiently accurate representation of the real system, it is of vital importance that the model parameters are inferred from real measured data. This, however, is often a formidable task and all of the existing methods fail in one case or the other, usually because the underlying CTMC model is high-dimensional and computationally difficult to analyze. The parameter inference methods that tend to scale best in the dimension of the CTMC are based on so-called moment closure approximations. However, there exists a large number of different moment closure approximations and it is typically hard to say a priori which of the approximations is the most suitable for the inference procedure. Here, we propose a moment-based parameter inference method that automatically chooses the most appropriate moment closure method. Accordingly, contrary to existing methods, the user is not required to be experienced in moment closure techniques. In addition to that, our method adaptively changes the approximation during the parameter inference to ensure that always the best approximation is used, even in cases where different approximations are best in different regions of the parameter space.
AU - Bogomolov, Sergiy
AU - Henzinger, Thomas A
AU - Podelski, Andreas
AU - Ruess, Jakob
AU - Schilling, Christian
ID - 1658
TI - Adaptive moment closure for parameter inference of biochemical reaction networks
VL - 9308
ER -
TY - CONF
AB - The target discounted-sum problem is the following: Given a rational discount factor 0 < λ < 1 and three rational values a, b, and t, does there exist a finite or an infinite sequence w ε(a, b)∗ or w ε(a, b)w, such that Σ|w| i=0 w(i)λi equals t? The problem turns out to relate to many fields of mathematics and computer science, and its decidability question is surprisingly hard to solve. We solve the finite version of the problem, and show the hardness of the infinite version, linking it to various areas and open problems in mathematics and computer science: β-expansions, discounted-sum automata, piecewise affine maps, and generalizations of the Cantor set. We provide some partial results to the infinite version, among which are solutions to its restriction to eventually-periodic sequences and to the cases that λ λ 1/2 or λ = 1/n, for every n ε N. We use our results for solving some open problems on discounted-sum automata, among which are the exact-value problem for nondeterministic automata over finite words and the universality and inclusion problems for functional automata.
AU - Boker, Udi
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 1659
SN - 1043-6871
T2 - LICS
TI - The target discounted-sum problem
ER -
TY - CONF
AB - We study the pattern frequency vector for runs in probabilistic Vector Addition Systems with States (pVASS). Intuitively, each configuration of a given pVASS is assigned one of finitely many patterns, and every run can thus be seen as an infinite sequence of these patterns. The pattern frequency vector assigns to each run the limit of pattern frequencies computed for longer and longer prefixes of the run. If the limit does not exist, then the vector is undefined. We show that for one-counter pVASS, the pattern frequency vector is defined and takes one of finitely many values for almost all runs. Further, these values and their associated probabilities can be approximated up to an arbitrarily small relative error in polynomial time. For stable two-counter pVASS, we show the same result, but we do not provide any upper complexity bound. As a byproduct of our study, we discover counterexamples falsifying some classical results about stochastic Petri nets published in the 80s.
AU - Brázdil, Tomáš
AU - Kiefer, Stefan
AU - Kučera, Antonín
AU - Novotny, Petr
ID - 1660
TI - Long-run average behaviour of probabilistic vector addition systems
ER -
TY - CONF
AB - The computation of the winning set for one-pair Streett objectives and for k-pair Streett objectives in (standard) graphs as well as in game graphs are central problems in computer-aided verification, with application to the verification of closed systems with strong fairness conditions, the verification of open systems, checking interface compatibility, well-formed ness of specifications, and the synthesis of reactive systems. We give faster algorithms for the computation of the winning set for (1) one-pair Streett objectives (aka parity-3 problem) in game graphs and (2) for k-pair Streett objectives in graphs. For both problems this represents the first improvement in asymptotic running time in 15 years.
AU - Chatterjee, Krishnendu
AU - Henzinger, Monika
AU - Loitzenbauer, Veronika
ID - 1661
T2 - Proceedings - Symposium on Logic in Computer Science
TI - Improved algorithms for one-pair and k-pair Streett objectives
VL - 2015-July
ER -
TY - JOUR
AB - CREB-binding protein (CBP) and p300 are transcriptional coactivators involved in numerous biological processes that affect cell growth, transformation, differentiation, and development. In this study, we provide evidence of the involvement of homeodomain-interacting protein kinase 2 (HIPK2) in the regulation of CBP activity. We show that HIPK2 interacts with and phosphorylates several regions of CBP. We demonstrate that serines 2361, 2363, 2371, 2376, and 2381 are responsible for the HIPK2-induced mobility shift of CBP C-terminal activation domain. Moreover, we show that HIPK2 strongly potentiates the transcriptional activity of CBP. However, our data suggest that HIPK2 activates CBP mainly by counteracting the repressive action of cell cycle regulatory domain 1 (CRD1), located between amino acids 977 and 1076, independently of CBP phosphorylation. Our findings thus highlight a complex regulation of CBP activity by HIPK2, which might be relevant for the control of specific sets of target genes involved in cellular proliferation, differentiation and apoptosis.
AU - Kovács, Krisztián
AU - Steinmann, Myriam
AU - Halfon, Olivier
AU - Magistretti, Pierre
AU - Cardinaux, Jean
ID - 1663
IS - 11
JF - Cellular Signalling
TI - Complex regulation of CREB-binding protein by homeodomain-interacting protein kinase 2
VL - 27
ER -
TY - JOUR
AB - Over a century of research into the origin of turbulence in wall-bounded shear flows has resulted in a puzzling picture in which turbulence appears in a variety of different states competing with laminar background flow. At moderate flow speeds, turbulence is confined to localized patches; it is only at higher speeds that the entire flow becomes turbulent. The origin of the different states encountered during this transition, the front dynamics of the turbulent regions and the transformation to full turbulence have yet to be explained. By combining experiments, theory and computer simulations, here we uncover a bifurcation scenario that explains the transformation to fully turbulent pipe flow and describe the front dynamics of the different states encountered in the process. Key to resolving this problem is the interpretation of the flow as a bistable system with nonlinear propagation (advection) of turbulent fronts. These findings bridge the gap between our understanding of the onset of turbulence and fully turbulent flows.
AU - Barkley, Dwight
AU - Song, Baofang
AU - Vasudevan, Mukund
AU - Lemoult, Grégoire M
AU - Avila, Marc
AU - Hof, Björn
ID - 1664
IS - 7574
JF - Nature
TI - The rise of fully turbulent flow
VL - 526
ER -
TY - JOUR
AB - Which genetic alterations drive tumorigenesis and how they evolve over the course of disease and therapy are central questions in cancer biology. Here we identify 44 recurrently mutated genes and 11 recurrent somatic copy number variations through whole-exome sequencing of 538 chronic lymphocytic leukaemia (CLL) and matched germline DNA samples, 278 of which were collected in a prospective clinical trial. These include previously unrecognized putative cancer drivers (RPS15, IKZF3), and collectively identify RNA processing and export, MYC activity, and MAPK signalling as central pathways involved in CLL. Clonality analysis of this large data set further enabled reconstruction of temporal relationships between driver events. Direct comparison between matched pre-treatment and relapse samples from 59 patients demonstrated highly frequent clonal evolution. Thus, large sequencing data sets of clinically informative samples enable the discovery of novel genes associated with cancer, the network of relationships between the driver events, and their impact on disease relapse and clinical outcome.
AU - Landau, Dan
AU - Tausch, Eugen
AU - Taylor Weiner, Amaro
AU - Stewart, Chip
AU - Reiter, Johannes
AU - Bahlo, Jasmin
AU - Kluth, Sandra
AU - Božić, Ivana
AU - Lawrence, Michael
AU - Böttcher, Sebastian
AU - Carter, Scott
AU - Cibulskis, Kristian
AU - Mertens, Daniel
AU - Sougnez, Carrie
AU - Rosenberg, Mara
AU - Hess, Julian
AU - Edelmann, Jennifer
AU - Kless, Sabrina
AU - Kneba, Michael
AU - Ritgen, Matthias
AU - Fink, Anna
AU - Fischer, Kirsten
AU - Gabriel, Stacey
AU - Lander, Eric
AU - Nowak, Martin
AU - Döhner, Hartmut
AU - Hallek, Michael
AU - Neuberg, Donna
AU - Getz, Gad
AU - Stilgenbauer, Stephan
AU - Wu, Catherine
ID - 1665
IS - 7574
JF - Nature
TI - Mutations driving CLL and their evolution in progression and relapse
VL - 526
ER -
TY - CONF
AB - We consider parametric version of fixed-delay continuoustime Markov chains (or equivalently deterministic and stochastic Petri nets, DSPN) where fixed-delay transitions are specified by parameters, rather than concrete values. Our goal is to synthesize values of these parameters that, for a given cost function, minimise expected total cost incurred before reaching a given set of target states. We show that under mild assumptions, optimal values of parameters can be effectively approximated using translation to a Markov decision process (MDP) whose actions correspond to discretized values of these parameters. To this end we identify and overcome several interesting phenomena arising in systems with fixed delays.
AU - Brázdil, Tomáš
AU - Korenčiak, L'Uboš
AU - Krčál, Jan
AU - Novotny, Petr
AU - Řehák, Vojtěch
ID - 1667
TI - Optimizing performance of continuous-time stochastic systems using timeout synthesis
VL - 9259
ER -
TY - CONF
AB - We revisit the security (as a pseudorandom permutation) of cascading-based constructions for block-cipher key-length extension. Previous works typically considered the extreme case where the adversary is given the entire codebook of the construction, the only complexity measure being the number qe of queries to the underlying ideal block cipher, representing adversary’s secret-key-independent computation. Here, we initiate a systematic study of the more natural case of an adversary restricted to adaptively learning a number qc of plaintext/ciphertext pairs that is less than the entire codebook. For any such qc, we aim to determine the highest number of block-cipher queries qe the adversary can issue without being able to successfully distinguish the construction (under a secret key) from a random permutation.
More concretely, we show the following results for key-length extension schemes using a block cipher with n-bit blocks and κ-bit keys:
Plain cascades of length ℓ=2r+1 are secure whenever qcqre≪2r(κ+n), qc≪2κ and qe≪22κ. The bound for r=1 also applies to two-key triple encryption (as used within Triple DES).
The r-round XOR-cascade is secure as long as qcqre≪2r(κ+n), matching an attack by Gaži (CRYPTO 2013).
We fully characterize the security of Gaži and Tessaro’s two-call
AU - Gazi, Peter
AU - Lee, Jooyoung
AU - Seurin, Yannick
AU - Steinberger, John
AU - Tessaro, Stefano
ID - 1668
TI - Relaxing full-codebook security: A refined analysis of key-length extension schemes
VL - 9054
ER -
TY - CONF
AB - Computational notions of entropy (a.k.a. pseudoentropy) have found many applications, including leakage-resilient cryptography, deterministic encryption or memory delegation. The most important tools to argue about pseudoentropy are chain rules, which quantify by how much (in terms of quantity and quality) the pseudoentropy of a given random variable X decreases when conditioned on some other variable Z (think for example of X as a secret key and Z as information leaked by a side-channel). In this paper we give a very simple and modular proof of the chain rule for HILL pseudoentropy, improving best known parameters. Our version allows for increasing the acceptable length of leakage in applications up to a constant factor compared to the best previous bounds. As a contribution of independent interest, we provide a comprehensive study of all known versions of the chain rule, comparing their worst-case strength and limitations.
AU - Pietrzak, Krzysztof Z
AU - Skórski, Maciej
ID - 1669
TI - The chain rule for HILL pseudoentropy, revisited
VL - 9230
ER -
TY - CONF
AB - Planning in hybrid domains poses a special challenge due to the involved mixed discrete-continuous dynamics. A recent solving approach for such domains is based on applying model checking techniques on a translation of PDDL+ planning problems to hybrid automata. However, the proposed translation is limited because must behavior is only overapproximated, and hence, processes and events are not reflected exactly. In this paper, we present the theoretical foundation of an exact PDDL+ translation. We propose a schema to convert a hybrid automaton with must transitions into an equivalent hybrid automaton featuring only may transitions.
AU - Bogomolov, Sergiy
AU - Magazzeni, Daniele
AU - Minopoli, Stefano
AU - Wehrle, Martin
ID - 1670
TI - PDDL+ planning with hybrid automata: Foundations of translating must behavior
ER -
TY - CONF
AB - This paper studies the concrete security of PRFs and MACs obtained by keying hash functions based on the sponge paradigm. One such hash function is KECCAK, selected as NIST’s new SHA-3 standard. In contrast to other approaches like HMAC, the exact security of keyed sponges is not well understood. Indeed, recent security analyses delivered concrete security bounds which are far from existing attacks. This paper aims to close this gap. We prove (nearly) exact bounds on the concrete PRF security of keyed sponges using a random permutation. These bounds are tight for the most relevant ranges of parameters, i.e., for messages of length (roughly) l ≤ min{2n/4, 2r} blocks, where n is the state size and r is the desired output length; and for l ≤ q queries (to the construction or the underlying permutation). Moreover, we also improve standard-model bounds. As an intermediate step of independent interest, we prove tight bounds on the PRF security of the truncated CBC-MAC construction, which operates as plain CBC-MAC, but only returns a prefix of the output.
AU - Gazi, Peter
AU - Pietrzak, Krzysztof Z
AU - Tessaro, Stefano
ID - 1671
TI - The exact PRF security of truncation: Tight bounds for keyed sponges and truncated CBC
VL - 9215
ER -
TY - CONF
AB - Composable notions of incoercibility aim to forbid a coercer from using anything beyond the coerced parties’ inputs and outputs to catch them when they try to deceive him. Existing definitions are restricted to weak coercion types, and/or are not universally composable. Furthermore, they often make too strong assumptions on the knowledge of coerced parties—e.g., they assume they known the identities and/or the strategies of other coerced parties, or those of corrupted parties— which makes them unsuitable for applications of incoercibility such as e-voting, where colluding adversarial parties may attempt to coerce honest voters, e.g., by offering them money for a promised vote, and use their own view to check that the voter keeps his end of the bargain. In this work we put forward the first universally composable notion of incoercible multi-party computation, which satisfies the above intuition and does not assume collusions among coerced parties or knowledge of the corrupted set. We define natural notions of UC incoercibility corresponding to standard coercion-types, i.e., receipt-freeness and resistance to full-active coercion. Importantly, our suggested notion has the unique property that it builds on top of the well studied UC framework by Canetti instead of modifying it. This guarantees backwards compatibility, and allows us to inherit results from the rich UC literature. We then present MPC protocols which realize our notions of UC incoercibility given access to an arguably minimal setup—namely honestly generate tamper-proof hardware performing a very simple cryptographic operation—e.g., a smart card. This is, to our knowledge, the first proposed construction of an MPC protocol (for more than two parties) that is incoercibly secure and universally composable, and therefore the first construction of a universally composable receipt-free e-voting protocol.
AU - Alwen, Joel F
AU - Ostrovsky, Rafail
AU - Zhou, Hongsheng
AU - Zikas, Vassilis
ID - 1672
TI - Incoercible multi-party computation and universally composable receipt-free voting
VL - 9216
ER -
TY - JOUR
AB - When a new mutant arises in a population, there is a probability it outcompetes the residents and fixes. The structure of the population can affect this fixation probability. Suppressing population structures reduce the difference between two competing variants, while amplifying population structures enhance the difference. Suppressors are ubiquitous and easy to construct, but amplifiers for the large population limit are more elusive and only a few examples have been discovered. Whether or not a population structure is an amplifier of selection depends on the probability distribution for the placement of the invading mutant. First, we prove that there exist only bounded amplifiers for adversarial placement-that is, for arbitrary initial conditions. Next, we show that the Star population structure, which is known to amplify for mutants placed uniformly at random, does not amplify for mutants that arise through reproduction and are therefore placed proportional to the temperatures of the vertices. Finally, we construct population structures that amplify for all mutational events that arise through reproduction, uniformly at random, or through some combination of the two.
AU - Adlam, Ben
AU - Chatterjee, Krishnendu
AU - Nowak, Martin
ID - 1673
IS - 2181
JF - Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences
TI - Amplifiers of selection
VL - 471
ER -
TY - JOUR
AB - We consider N × N random matrices of the form H = W + V where W is a real symmetric Wigner matrix and V a random or deterministic, real, diagonal matrix whose entries are independent of W. We assume subexponential decay for the matrix entries of W and we choose V so that the eigenvalues of W and V are typically of the same order. For a large class of diagonal matrices V, we show that the rescaled distribution of the extremal eigenvalues is given by the Tracy-Widom distribution F1 in the limit of large N. Our proofs also apply to the complex Hermitian setting, i.e. when W is a complex Hermitian Wigner matrix.
AU - Lee, Jioon
AU - Schnelli, Kevin
ID - 1674
IS - 8
JF - Reviews in Mathematical Physics
TI - Edge universality for deformed Wigner matrices
VL - 27
ER -
TY - CONF
AB - Proofs of work (PoW) have been suggested by Dwork and Naor (Crypto’92) as protection to a shared resource. The basic idea is to ask the service requestor to dedicate some non-trivial amount of computational work to every request. The original applications included prevention of spam and protection against denial of service attacks. More recently, PoWs have been used to prevent double spending in the Bitcoin digital currency system. In this work, we put forward an alternative concept for PoWs - so-called proofs of space (PoS), where a service requestor must dedicate a significant amount of disk space as opposed to computation. We construct secure PoS schemes in the random oracle model (with one additional mild assumption required for the proof to go through), using graphs with high “pebbling complexity” and Merkle hash-trees. We discuss some applications, including follow-up work where a decentralized digital currency scheme called Spacecoin is constructed that uses PoS (instead of wasteful PoW like in Bitcoin) to prevent double spending. The main technical contribution of this work is the construction of (directed, loop-free) graphs on N vertices with in-degree O(log logN) such that even if one places Θ(N) pebbles on the nodes of the graph, there’s a constant fraction of nodes that needs Θ(N) steps to be pebbled (where in every step one can put a pebble on a node if all its parents have a pebble).
AU - Dziembowski, Stefan
AU - Faust, Sebastian
AU - Kolmogorov, Vladimir
AU - Pietrzak, Krzysztof Z
ID - 1675
TI - Proofs of space
VL - 9216
ER -
TY - JOUR
AU - Sixt, Michael K
AU - Raz, Erez
ID - 1676
IS - 10
JF - Current Opinion in Cell Biology
TI - Editorial overview: Cell adhesion and migration
VL - 36
ER -
TY - JOUR
AB - We consider real symmetric and complex Hermitian random matrices with the additional symmetry hxy = hN-y,N-x. The matrix elements are independent (up to the fourfold symmetry) and not necessarily identically distributed. This ensemble naturally arises as the Fourier transform of a Gaussian orthogonal ensemble. Italso occurs as the flip matrix model - an approximation of the two-dimensional Anderson model at small disorder. We show that the density of states converges to the Wigner semicircle law despite the new symmetry type. We also prove the local version of the semicircle law on the optimal scale.
AU - Alt, Johannes
ID - 1677
IS - 10
JF - Journal of Mathematical Physics
TI - The local semicircle law for random matrices with a fourfold symmetry
VL - 56
ER -
TY - JOUR
AB - High-throughput live-cell screens are intricate elements of systems biology studies and drug discovery pipelines. Here, we demonstrate an optogenetics-assisted method that avoids the need for chemical activators and reporters, reduces the number of operational steps and increases information content in a cell-based small-molecule screen against human protein kinases, including an orphan receptor tyrosine kinase. This blueprint for all-optical screening can be adapted to many drug targets and cellular processes.
AU - Inglés Prieto, Álvaro
AU - Gschaider-Reichhart, Eva
AU - Muellner, Markus
AU - Nowak, Matthias
AU - Nijman, Sebastian
AU - Grusch, Michael
AU - Janovjak, Harald L
ID - 1678
IS - 12
JF - Nature Chemical Biology
TI - Light-assisted small-molecule screening against protein kinases
VL - 11
ER -
TY - JOUR
AU - Lemoult, Grégoire M
AU - Maier, Philipp
AU - Hof, Björn
ID - 1679
IS - 9
JF - Physics of Fluids
TI - Taylor's Forest
VL - 27
ER -
TY - JOUR
AB - We consider the satisfiability problem for modal logic over first-order definable classes of frames.We confirm the conjecture from Hemaspaandra and Schnoor [2008] that modal logic is decidable over classes definable by universal Horn formulae. We provide a full classification of Horn formulae with respect to the complexity of the corresponding satisfiability problem. It turns out, that except for the trivial case of inconsistent formulae, local satisfiability is eitherNP-complete or PSPACE-complete, and global satisfiability is NP-complete, PSPACE-complete, or ExpTime-complete. We also show that the finite satisfiability problem for modal logic over Horn definable classes of frames is decidable. On the negative side, we show undecidability of two related problems. First, we exhibit a simple universal three-variable formula defining the class of frames over which modal logic is undecidable. Second, we consider the satisfiability problem of bimodal logic over Horn definable classes of frames, and also present a formula leading to undecidability.
AU - Michaliszyn, Jakub
AU - Otop, Jan
AU - Kieroňski, Emanuel
ID - 1680
IS - 1
JF - ACM Transactions on Computational Logic
TI - On the decidability of elementary modal logics
VL - 17
ER -
TY - JOUR
AB - In many social situations, individuals endeavor to find the single best possible partner, but are constrained to evaluate the candidates in sequence. Examples include the search for mates, economic partnerships, or any other long-term ties where the choice to interact involves two parties. Surprisingly, however, previous theoretical work on mutual choice problems focuses on finding equilibrium solutions, while ignoring the evolutionary dynamics of decisions. Empirically, this may be of high importance, as some equilibrium solutions can never be reached unless the population undergoes radical changes and a sufficient number of individuals change their decisions simultaneously. To address this question, we apply a mutual choice sequential search problem in an evolutionary game-theoretical model that allows one to find solutions that are favored by evolution. As an example, we study the influence of sequential search on the evolutionary dynamics of cooperation. For this, we focus on the classic snowdrift game and the prisoner’s dilemma game.
AU - Priklopil, Tadeas
AU - Chatterjee, Krishnendu
ID - 1681
IS - 4
JF - Games
TI - Evolution of decisions in population games with sequentially searching individuals
VL - 6
ER -
TY - JOUR
AB - We study the problem of robust satisfiability of systems of nonlinear equations, namely, whether for a given continuous function f:K→ ℝn on a finite simplicial complex K and α > 0, it holds that each function g: K → ℝn such that ||g - f || ∞ < α, has a root in K. Via a reduction to the extension problem of maps into a sphere, we particularly show that this problem is decidable in polynomial time for every fixed n, assuming dimK ≤ 2n - 3. This is a substantial extension of previous computational applications of topological degree and related concepts in numerical and interval analysis. Via a reverse reduction, we prove that the problem is undecidable when dim K > 2n - 2, where the threshold comes from the stable range in homotopy theory. For the lucidity of our exposition, we focus on the setting when f is simplexwise linear. Such functions can approximate general continuous functions, and thus we get approximation schemes and undecidability of the robust satisfiability in other possible settings.
AU - Franek, Peter
AU - Krcál, Marek
ID - 1682
IS - 4
JF - Journal of the ACM
TI - Robust satisfiability of systems of equations
VL - 62
ER -
TY - JOUR
AB - The 1 MDa, 45-subunit proton-pumping NADH-ubiquinone oxidoreductase (complex I) is the largest complex of the mitochondrial electron transport chain. The molecular mechanism of complex I is central to the metabolism of cells, but has yet to be fully characterized. The last two years have seen steady progress towards this goal with the first atomic-resolution structure of the entire bacterial complex I, a 5 Å cryo-electron microscopy map of bovine mitochondrial complex I and a ∼3.8 Å resolution X-ray crystallographic study of mitochondrial complex I from yeast Yarrowia lipotytica. In this review we will discuss what we have learned from these studies and what remains to be elucidated.
AU - Letts, Jame A
AU - Sazanov, Leonid A
ID - 1683
IS - 8
JF - Current Opinion in Structural Biology
TI - Gaining mass: The structure of respiratory complex I-from bacterial towards mitochondrial versions
VL - 33
ER -
TY - CONF
AB - Given a graph G cellularly embedded on a surface Σ of genus g, a cut graph is a subgraph of G such that cutting Σ along G yields a topological disk. We provide a fixed parameter tractable approximation scheme for the problem of computing the shortest cut graph, that is, for any ε > 0, we show how to compute a (1 + ε) approximation of the shortest cut graph in time f(ε, g)n3.
Our techniques first rely on the computation of a spanner for the problem using the technique of brick decompositions, to reduce the problem to the case of bounded tree-width. Then, to solve the bounded tree-width case, we introduce a variant of the surface-cut decomposition of Rué, Sau and Thilikos, which may be of independent interest.
AU - Cohen Addad, Vincent
AU - De Mesmay, Arnaud N
ID - 1685
TI - A fixed parameter tractable approximation scheme for the optimal cut graph of a surface
VL - 9294
ER -
TY - THES
AB - The human ability to recognize objects in complex scenes has driven research in the computer vision field over couple of decades. This thesis focuses on the object recognition task in images. That is, given the image, we want the computer system to be able to predict the class of the object that appears in the image. A recent succesful attempt to bridge semantic understanding of the image perceived by humans and by computers uses attribute-based models. Attributes are semantic properties of the objects shared across different categories, which humans and computers can decide on. To explore the attribute-based models we take a statistical machine learning approach, and address two key learning challenges in view of object recognition task: learning augmented attributes as mid-level discriminative feature representation, and learning with attributes as privileged information. Our main contributions are parametric and non-parametric models and algorithms to solve these frameworks. In the parametric approach, we explore an autoencoder model combined with the large margin nearest neighbor principle for mid-level feature learning, and linear support vector machines for learning with privileged information. In the non-parametric approach, we propose a supervised Indian Buffet Process for automatic augmentation of semantic attributes, and explore the Gaussian Processes classification framework for learning with privileged information. A thorough experimental analysis shows the effectiveness of the proposed models in both parametric and non-parametric views.
AU - Sharmanska, Viktoriia
ID - 1401
TI - Learning with attributes for object recognition: Parametric and non-parametrics views
ER -
TY - CONF
AB - We present a computer-aided programming approach to concurrency. The approach allows programmers to program assuming a friendly, non-preemptive scheduler, and our synthesis procedure inserts synchronization to ensure that the final program works even with a preemptive scheduler. The correctness specification is implicit, inferred from the non-preemptive behavior. Let us consider sequences of calls that the program makes to an external interface. The specification requires that any such sequence produced under a preemptive scheduler should be included in the set of such sequences produced under a non-preemptive scheduler. The solution is based on a finitary abstraction, an algorithm for bounded language inclusion modulo an independence relation, and rules for inserting synchronization. We apply the approach to device-driver programming, where the driver threads call the software interface of the device and the API provided by the operating system. Our experiments demonstrate that our synthesis method is precise and efficient, and, since it does not require explicit specifications, is more practical than the conventional approach based on user-provided assertions.
AU - Cerny, Pavol
AU - Clarke, Edmund
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
AU - Ryzhyk, Leonid
AU - Samanta, Roopsha
AU - Tarrach, Thorsten
ID - 1729
TI - From non-preemptive to preemptive scheduling using synchronization synthesis
VL - 9207
ER -
TY - GEN
AB - We study conditions under which a finite simplicial complex $K$ can be mapped to $\mathbb R^d$ without higher-multiplicity intersections. An almost $r$-embedding is a map $f: K\to \mathbb R^d$ such that the images of any $r$
pairwise disjoint simplices of $K$ do not have a common point. We show that if $r$ is not a prime power and $d\geq 2r+1$, then there is a counterexample to the topological Tverberg conjecture, i.e., there is an almost $r$-embedding of
the $(d+1)(r-1)$-simplex in $\mathbb R^d$. This improves on previous constructions of counterexamples (for $d\geq 3r$) based on a series of papers by M. \"Ozaydin, M. Gromov, P. Blagojevi\'c, F. Frick, G. Ziegler, and the second and fourth present authors. The counterexamples are obtained by proving the following algebraic criterion in codimension 2: If $r\ge3$ and if $K$ is a finite $2(r-1)$-complex then there exists an almost $r$-embedding $K\to \mathbb R^{2r}$ if and only if there exists a general position PL map $f:K\to \mathbb R^{2r}$ such that the algebraic intersection number of the $f$-images of any $r$ pairwise disjoint simplices of $K$ is zero. This result can be restated in terms of cohomological obstructions or equivariant maps, and extends an analogous codimension 3 criterion by the second and fourth authors. As another application we classify ornaments $f:S^3 \sqcup S^3\sqcup S^3\to \mathbb R^5$ up to ornament
concordance. It follows from work of M. Freedman, V. Krushkal and P. Teichner that the analogous criterion for $r=2$ is false. We prove a lemma on singular higher-dimensional Borromean rings, yielding an elementary proof of the counterexample.
AU - Avvakumov, Sergey
AU - Mabillard, Isaac
AU - Skopenkov, A.
AU - Wagner, Uli
ID - 8183
T2 - arXiv
TI - Eliminating higher-multiplicity intersections, III. Codimension 2
ER -
TY - CONF
AB - We consider the core algorithmic problems related to verification of systems with respect to three classical quantitative properties, namely, the mean-payoff property, the ratio property, and the minimum initial credit for energy property. The algorithmic problem given a graph and a quantitative property asks to compute the optimal value (the infimum value over all traces) from every node of the graph. We consider graphs with constant treewidth, and it is well-known that the control-flow graphs of most programs have constant treewidth. Let n denote the number of nodes of a graph, m the number of edges (for constant treewidth graphs m=O(n)) and W the largest absolute value of the weights. Our main theoretical results are as follows. First, for constant treewidth graphs we present an algorithm that approximates the mean-payoff value within a multiplicative factor of ϵ in time O(n⋅log(n/ϵ)) and linear space, as compared to the classical algorithms that require quadratic time. Second, for the ratio property we present an algorithm that for constant treewidth graphs works in time O(n⋅log(|a⋅b|))=O(n⋅log(n⋅W)), when the output is ab, as compared to the previously best known algorithm with running time O(n2⋅log(n⋅W)). Third, for the minimum initial credit problem we show that (i) for general graphs the problem can be solved in O(n2⋅m) time and the associated decision problem can be solved in O(n⋅m) time, improving the previous known O(n3⋅m⋅log(n⋅W)) and O(n2⋅m) bounds, respectively; and (ii) for constant treewidth graphs we present an algorithm that requires O(n⋅logn) time, improving the previous known O(n4⋅log(n⋅W)) bound. We have implemented some of our algorithms and show that they present a significant speedup on standard benchmarks.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Pavlogiannis, Andreas
ID - 1607
TI - Faster algorithms for quantitative verification in constant treewidth graphs
VL - 9206
ER -
TY - JOUR
AB - Summary: Declining populations of bee pollinators are a cause of concern, with major repercussions for biodiversity loss and food security. RNA viruses associated with honeybees represent a potential threat to other insect pollinators, but the extent of this threat is poorly understood. This study aims to attain a detailed understanding of the current and ongoing risk of emerging infectious disease (EID) transmission between managed and wild pollinator species across a wide range of RNA viruses. Within a structured large-scale national survey across 26 independent sites, we quantify the prevalence and pathogen loads of multiple RNA viruses in co-occurring managed honeybee (Apis mellifera) and wild bumblebee (Bombus spp.) populations. We then construct models that compare virus prevalence between wild and managed pollinators. Multiple RNA viruses associated with honeybees are widespread in sympatric wild bumblebee populations. Virus prevalence in honeybees is a significant predictor of virus prevalence in bumblebees, but we remain cautious in speculating over the principle direction of pathogen transmission. We demonstrate species-specific differences in prevalence, indicating significant variation in disease susceptibility or tolerance. Pathogen loads within individual bumblebees may be high and in the case of at least one RNA virus, prevalence is higher in wild bumblebees than in managed honeybee populations. Our findings indicate widespread transmission of RNA viruses between managed and wild bee pollinators, pointing to an interconnected network of potential disease pressures within and among pollinator species. In the context of the biodiversity crisis, our study emphasizes the importance of targeting a wide range of pathogens and defining host associations when considering potential drivers of population decline.
AU - Mcmahon, Dino
AU - Fürst, Matthias
AU - Caspar, Jesicca
AU - Theodorou, Panagiotis
AU - Brown, Mark
AU - Paxton, Robert
ID - 1855
IS - 3
JF - Journal of Animal Ecology
TI - A sting in the spit: Widespread cross-infection of multiple RNA viruses across wild and managed bees
VL - 84
ER -
TY - JOUR
AB - To prevent epidemics, insect societies have evolved collective disease defences that are highly effective at curing exposed individuals and limiting disease transmission to healthy group members. Grooming is an important sanitary behaviour—either performed towards oneself (self-grooming) or towards others (allogrooming)—to remove infectious agents from the body surface of exposed individuals, but at the risk of disease contraction by the groomer. We use garden ants (Lasius neglectus) and the fungal pathogen Metarhizium as a model system to study how pathogen presence affects self-grooming and allogrooming between exposed and healthy individuals. We develop an epidemiological SIS model to explore how experimentally observed grooming patterns affect disease spread within the colony, thereby providing a direct link between the expression and direction of sanitary behaviours, and their effects on colony-level epidemiology. We find that fungus-exposed ants increase self-grooming, while simultaneously decreasing allogrooming. This behavioural modulation seems universally adaptive and is predicted to contain disease spread in a great variety of host–pathogen systems. In contrast, allogrooming directed towards pathogen-exposed individuals might both increase and decrease disease risk. Our model reveals that the effect of allogrooming depends on the balance between pathogen infectiousness and efficiency of social host defences, which are likely to vary across host–pathogen systems.
AU - Theis, Fabian
AU - Ugelvig, Line V
AU - Marr, Carsten
AU - Cremer, Sylvia
ID - 1830
IS - 1669
JF - Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
SN - 0962-8436
TI - Opposing effects of allogrooming on disease transmission in ant societies
VL - 370
ER -
TY - GEN
AB - Parasitism creates selection for resistance mechanisms in host populations and is hypothesized to promote increased host evolvability. However, the influence of these traits on host evolution when parasites are no longer present is unclear. We used experimental evolution and whole-genome sequencing of Escherichia coli to determine the effects of past and present exposure to parasitic viruses (phages) on the spread of mutator alleles, resistance, and bacterial competitive fitness. We found that mutator alleles spread rapidly during adaptation to any of four different phage species, and this pattern was even more pronounced with multiple phages present simultaneously. However, hypermutability did not detectably accelerate adaptation in the absence of phages and recovery of fitness costs associated with resistance. Several lineages evolved phage resistance through elevated mucoidy, and during subsequent evolution in phage-free conditions they rapidly reverted to nonmucoid, phage-susceptible phenotypes. Genome sequencing revealed that this phenotypic reversion was achieved by additional genetic changes rather than by genotypic reversion of the initial resistance mutations. Insertion sequence (IS) elements played a key role in both the acquisition of resistance and adaptation in the absence of parasites; unlike single nucleotide polymorphisms, IS insertions were not more frequent in mutator lineages. Our results provide a genetic explanation for rapid reversion of mucoidy, a phenotype observed in other bacterial species including human pathogens. Moreover, this demonstrates that the types of genetic change underlying adaptation to fitness costs, and consequently the impact of evolvability mechanisms such as increased point-mutation rates, depend critically on the mechanism of resistance.
AU - Wielgoss, Sébastien
AU - Bergmiller, Tobias
AU - Bischofberger, Anna M.
AU - Hall, Alex R.
ID - 9719
TI - Data from: Adaptation to parasites and costs of parasite resistance in mutator and non-mutator bacteria
ER -
TY - GEN
AB - To prevent epidemics, insect societies have evolved collective disease defences that are highly effective at curing exposed individuals and limiting disease transmission to healthy group members. Grooming is an important sanitary behaviour—either performed towards oneself (self-grooming) or towards others (allogrooming)—to remove infectious agents from the body surface of exposed individuals, but at the risk of disease contraction by the groomer. We use garden ants (Lasius neglectus) and the fungal pathogen Metarhizium as a model system to study how pathogen presence affects self-grooming and allogrooming between exposed and healthy individuals. We develop an epidemiological SIS model to explore how experimentally observed grooming patterns affect disease spread within the colony, thereby providing a direct link between the expression and direction of sanitary behaviours, and their effects on colony-level epidemiology. We find that fungus-exposed ants increase self-grooming, while simultaneously decreasing allogrooming. This behavioural modulation seems universally adaptive and is predicted to contain disease spread in a great variety of host–pathogen systems. In contrast, allogrooming directed towards pathogen-exposed individuals might both increase and decrease disease risk. Our model reveals that the effect of allogrooming depends on the balance between pathogen infectiousness and efficiency of social host defences, which are likely to vary across host–pathogen systems.
AU - Theis, Fabian
AU - Ugelvig, Line V
AU - Marr, Carsten
AU - Cremer, Sylvia
ID - 9721
TI - Data from: Opposing effects of allogrooming on disease transmission in ant societies
ER -
TY - JOUR
AB - Bow-tie or hourglass structure is a common architectural feature found in many biological systems. A bow-tie in a multi-layered structure occurs when intermediate layers have much fewer components than the input and output layers. Examples include metabolism where a handful of building blocks mediate between multiple input nutrients and multiple output biomass components, and signaling networks where information from numerous receptor types passes through a small set of signaling pathways to regulate multiple output genes. Little is known, however, about how bow-tie architectures evolve. Here, we address the evolution of bow-tie architectures using simulations of multi-layered systems evolving to fulfill a given input-output goal. We find that bow-ties spontaneously evolve when the information in the evolutionary goal can be compressed. Mathematically speaking, bow-ties evolve when the rank of the input-output matrix describing the evolutionary goal is deficient. The maximal compression possible (the rank of the goal) determines the size of the narrowest part of the network—that is the bow-tie. A further requirement is that a process is active to reduce the number of links in the network, such as product-rule mutations, otherwise a non-bow-tie solution is found in the evolutionary simulations. This offers a mechanism to understand a common architectural principle of biological systems, and a way to quantitate the effective rank of the goals under which they evolved.
AU - Friedlander, Tamar
AU - Mayo, Avraham
AU - Tlusty, Tsvi
AU - Alon, Uri
ID - 1827
IS - 3
JF - PLoS Computational Biology
TI - Evolution of bow-tie architectures in biology
VL - 11
ER -
TY - JOUR
AB - Evolution of gene regulation is crucial for our understanding of the phenotypic differences between species, populations and individuals. Sequence-specific binding of transcription factors to the regulatory regions on the DNA is a key regulatory mechanism that determines gene expression and hence heritable phenotypic variation. We use a biophysical model for directional selection on gene expression to estimate the rates of gain and loss of transcription factor binding sites (TFBS) in finite populations under both point and insertion/deletion mutations. Our results show that these rates are typically slow for a single TFBS in an isolated DNA region, unless the selection is extremely strong. These rates decrease drastically with increasing TFBS length or increasingly specific protein-DNA interactions, making the evolution of sites longer than ∼ 10 bp unlikely on typical eukaryotic speciation timescales. Similarly, evolution converges to the stationary distribution of binding sequences very slowly, making the equilibrium assumption questionable. The availability of longer regulatory sequences in which multiple binding sites can evolve simultaneously, the presence of “pre-sites” or partially decayed old sites in the initial sequence, and biophysical cooperativity between transcription factors, can all facilitate gain of TFBS and reconcile theoretical calculations with timescales inferred from comparative genomics.
AU - Tugrul, Murat
AU - Paixao, Tiago
AU - Barton, Nicholas H
AU - Tkacik, Gasper
ID - 1666
IS - 11
JF - PLoS Genetics
TI - Dynamics of transcription factor binding site evolution
VL - 11
ER -
TY - JOUR
AB - Deposits of misfolded proteins in the human brain are associated with the development of many neurodegenerative diseases. Recent studies show that these proteins have common traits even at the monomer level. Among them, a polyglutamine region that is present in huntingtin is known to exhibit a correlation between the length of the chain and the severity as well as the earliness of the onset of Huntington disease. Here, we apply bias exchange molecular dynamics to generate structures of polyglutamine expansions of several lengths and characterize the resulting independent conformations. We compare the properties of these conformations to those of the standard proteins, as well as to other homopolymeric tracts. We find that, similar to the previously studied polyvaline chains, the set of possible transient folds is much broader than the set of known-to-date folds, although the conformations have different structures. We show that the mechanical stability is not related to any simple geometrical characteristics of the structures. We demonstrate that long polyglutamine expansions result in higher mechanical stability than the shorter ones. They also have a longer life span and are substantially more prone to form knotted structures. The knotted region has an average length of 35 residues, similar to the typical threshold for most polyglutamine-related diseases. Similarly, changes in shape and mechanical stability appear once the total length of the peptide exceeds this threshold of 35 glutamine residues. We suggest that knotted conformers may also harm the cellular machinery and thus lead to disease.
AU - Gómez Sicilia, Àngel
AU - Sikora, Mateusz K
AU - Cieplak, Marek
AU - Carrión Vázquez, Mariano
ID - 1566
IS - 10
JF - PLoS Computational Biology
TI - An exploration of the universe of polyglutamine structures
VL - 11
ER -
TY - JOUR
AB - Background: Indirect genetic effects (IGEs) occur when genes expressed in one individual alter the expression of traits in social partners. Previous studies focused on the evolutionary consequences and evolutionary dynamics of IGEs, using equilibrium solutions to predict phenotypes in subsequent generations. However, whether or not such steady states may be reached may depend on the dynamics of interactions themselves. Results: In our study, we focus on the dynamics of social interactions and indirect genetic effects and investigate how they modify phenotypes over time. Unlike previous IGE studies, we do not analyse evolutionary dynamics; rather we consider within-individual phenotypic changes, also referred to as phenotypic plasticity. We analyse iterative interactions, when individuals interact in a series of discontinuous events, and investigate the stability of steady state solutions and the dependence on model parameters, such as population size, strength, and the nature of interactions. We show that for interactions where a feedback loop occurs, the possible parameter space of interaction strength is fairly limited, affecting the evolutionary consequences of IGEs. We discuss the implications of our results for current IGE model predictions and their limitations.
AU - Trubenova, Barbora
AU - Novak, Sebastian
AU - Hager, Reinmar
ID - 1809
IS - 5
JF - PLoS One
TI - Indirect genetic effects and the dynamics of social interactions
VL - 10
ER -
TY - JOUR
AB - We present a software platform for reconstructing and analyzing the growth of a plant root system from a time-series of 3D voxelized shapes. It aligns the shapes with each other, constructs a geometric graph representation together with the function that records the time of growth, and organizes the branches into a hierarchy that reflects the order of creation. The software includes the automatic computation of structural and dynamic traits for each root in the system enabling the quantification of growth on fine-scale. These are important advances in plant phenotyping with applications to the study of genetic and environmental influences on growth.
AU - Symonova, Olga
AU - Topp, Christopher
AU - Edelsbrunner, Herbert
ID - 1793
IS - 6
JF - PLoS One
TI - DynamicRoots: A software platform for the reconstruction and analysis of growing plant roots
VL - 10
ER -
TY - JOUR
AB - The fitness effects of symbionts on their hosts can be context-dependent, with usually benign symbionts causing detrimental effects when their hosts are stressed, or typically parasitic symbionts providing protection towards their hosts (e.g. against pathogen infection). Here, we studied the novel association between the invasive garden ant Lasius neglectus and its fungal ectosymbiont Laboulbenia formicarum for potential costs and benefits. We tested ants with different Laboulbenia levels for their survival and immunity under resource limitation and exposure to the obligate killing entomopathogen Metarhizium brunneum. While survival of L. neglectus workers under starvation was significantly decreased with increasing Laboulbenia levels, host survival under Metarhizium exposure increased with higher levels of the ectosymbiont, suggesting a symbiont-mediated anti-pathogen protection, which seems to be driven mechanistically by both improved sanitary behaviours and an upregulated immune system. Ants with high Laboulbenia levels showed significantly longer self-grooming and elevated expression of immune genes relevant for wound repair and antifungal responses (β-1,3-glucan binding protein, Prophenoloxidase), compared with ants carrying low Laboulbenia levels. This suggests that the ectosymbiont Laboulbenia formicarum weakens its ant host by either direct resource exploitation or the costs of an upregulated behavioural and immunological response, which, however, provides a prophylactic protection upon later exposure to pathogens.
AU - Konrad, Matthias
AU - Grasse, Anna V
AU - Tragust, Simon
AU - Cremer, Sylvia
ID - 1993
IS - 1799
JF - Proceedings of the Royal Society of London Series B Biological Sciences
TI - Anti-pathogen protection versus survival costs mediated by an ectosymbiont in an ant host
VL - 282
ER -
TY - GEN
AB - Repeated pathogen exposure is a common threat in colonies of social insects, posing selection pressures on colony members to respond with improved disease-defense performance. We here tested whether experience gained by repeated tending of low-level fungus-exposed (Metarhizium robertsii) larvae may alter the performance of sanitary brood care in the clonal ant, Platythyrea punctata. We trained ants individually over nine consecutive trials to either sham-treated or fungus-exposed larvae. We then compared the larval grooming behavior of naive and trained ants and measured how effectively they removed infectious fungal conidiospores from the fungus-exposed larvae. We found that the ants changed the duration of larval grooming in response to both, larval treatment and their level of experience: (1) sham-treated larvae received longer grooming than the fungus-exposed larvae and (2) trained ants performed less self-grooming but longer larval grooming than naive ants, which was true for both, ants trained to fungus-exposed and also to sham-treated larvae. Ants that groomed the fungus-exposed larvae for longer periods removed a higher number of fungal conidiospores from the surface of the fungus-exposed larvae. As experienced ants performed longer larval grooming, they were more effective in fungal removal, thus making them better caretakers under pathogen attack of the colony. By studying this clonal ant, we can thus conclude that even in the absence of genetic variation between colony members, differences in experience levels of brood care may affect performance of sanitary brood care in social insects.
AU - Westhus, Claudia
AU - Ugelvig, Line V
AU - Tourdot, Edouard
AU - Heinze, Jürgen
AU - Doums, Claudie
AU - Cremer, Sylvia
ID - 9742
TI - Data from: Increased grooming after repeated brood care provides sanitary benefits in a clonal ant
ER -
TY - JOUR
AB - The emergence of drug resistant pathogens is a serious public health problem. It is a long-standing goal to predict rates of resistance evolution and design optimal treatment strategies accordingly. To this end, it is crucial to reveal the underlying causes of drug-specific differences in the evolutionary dynamics leading to resistance. However, it remains largely unknown why the rates of resistance evolution via spontaneous mutations and the diversity of mutational paths vary substantially between drugs. Here we comprehensively quantify the distribution of fitness effects (DFE) of mutations, a key determinant of evolutionary dynamics, in the presence of eight antibiotics representing the main modes of action. Using precise high-throughput fitness measurements for genome-wide Escherichia coli gene deletion strains, we find that the width of the DFE varies dramatically between antibiotics and, contrary to conventional wisdom, for some drugs the DFE width is lower than in the absence of stress. We show that this previously underappreciated divergence in DFE width among antibiotics is largely caused by their distinct drug-specific dose-response characteristics. Unlike the DFE, the magnitude of the changes in tolerated drug concentration resulting from genome-wide mutations is similar for most drugs but exceptionally small for the antibiotic nitrofurantoin, i.e., mutations generally have considerably smaller resistance effects for nitrofurantoin than for other drugs. A population genetics model predicts that resistance evolution for drugs with this property is severely limited and confined to reproducible mutational paths. We tested this prediction in laboratory evolution experiments using the “morbidostat”, a device for evolving bacteria in well-controlled drug environments. Nitrofurantoin resistance indeed evolved extremely slowly via reproducible mutations—an almost paradoxical behavior since this drug causes DNA damage and increases the mutation rate. Overall, we identified novel quantitative characteristics of the evolutionary landscape that provide the conceptual foundation for predicting the dynamics of drug resistance evolution.
AU - Chevereau, Guillaume
AU - Dravecka, Marta
AU - Batur, Tugce
AU - Guvenek, Aysegul
AU - Ayhan, Dilay
AU - Toprak, Erdal
AU - Bollenbach, Mark Tobias
ID - 1619
IS - 11
JF - PLoS Biology
TI - Quantifying the determinants of evolutionary dynamics leading to drug resistance
VL - 13
ER -
TY - JOUR
AB - To reveal the full potential of human pluripotent stem cells, new methods for rapid, site-specific genomic engineering are needed. Here, we describe a system for precise genetic modification of human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). We identified a novel human locus, H11, located in a safe, intergenic, transcriptionally active region of chromosome 22, as the recipient site, to provide robust, ubiquitous expression of inserted genes. Recipient cell lines were established by site-specific placement of a ‘landing pad’ cassette carrying attP sites for phiC31 and Bxb1 integrases at the H11 locus by spontaneous or TALEN-assisted homologous recombination. Dual integrase cassette exchange (DICE) mediated by phiC31 and Bxb1 integrases was used to insert genes of interest flanked by phiC31 and Bxb1 attB sites at the H11 locus, replacing the landing pad. This system provided complete control over content, direction and copy number of inserted genes, with a specificity of 100%. A series of genes, including mCherry and various combinations of the neural transcription factors LMX1a, FOXA2 and OTX2, were inserted in recipient cell lines derived from H9 ESC, as well as iPSC lines derived from a Parkinson’s disease patient and a normal sibling control. The DICE system offers rapid, efficient and precise gene insertion in ESC and iPSC and is particularly well suited for repeated modifications of the same locus.
AU - Zhu, Fangfang
AU - Gamboa, Matthew
AU - Farruggio, Alfonso
AU - Hippenmeyer, Simon
AU - Tasic, Bosiljka
AU - Schüle, Birgitt
AU - Chen Tsai, Yanru
AU - Calos, Michele
ID - 2261
IS - 5
JF - Nucleic Acids Research
TI - DICE, an efficient system for iterative genomic editing in human pluripotent stem cells
VL - 42
ER -
TY - CHAP
AB - Coordinated migration of newly-born neurons to their target territories is essential for correct neuronal circuit assembly in the developing brain. Although a cohort of signaling pathways has been implicated in the regulation of cortical projection neuron migration, the precise molecular mechanisms and how a balanced interplay of cell-autonomous and non-autonomous functions of candidate signaling molecules controls the discrete steps in the migration process, are just being revealed. In this chapter, I will focally review recent advances that improved our understanding of the cell-autonomous and possible cell-nonautonomous functions of the evolutionarily conserved LIS1/NDEL1-complex in regulating the sequential steps of cortical projection neuron migration. I will then elaborate on the emerging concept that the Reelin signaling pathway, acts exactly at precise stages in the course of cortical projection neuron migration. Lastly, I will discuss how finely tuned transcriptional programs and downstream effectors govern particular aspects in driving radial migration at discrete stages and how they regulate the precise positioning of cortical projection neurons in the developing cerebral cortex.
AU - Hippenmeyer, Simon
ED - Nguyen, Laurent
ID - 2265
T2 - Cellular and Molecular Control of Neuronal Migration
TI - Molecular pathways controlling the sequential steps of cortical projection neuron migration
VL - 800
ER -
TY - CONF
AB - Energies with high-order non-submodular interactions have been shown to be very useful in vision due to their high modeling power. Optimization of such energies, however, is generally NP-hard. A naive approach that works for small problem instances is exhaustive search, that is, enumeration of all possible labelings of the underlying graph. We propose a general minimization approach for large graphs based on enumeration of labelings of certain small patches.
This partial enumeration technique reduces complex high-order energy formulations to pairwise Constraint Satisfaction Problems with unary costs (uCSP), which can be efficiently solved using standard methods like TRW-S. Our approach outperforms a number of existing state-of-the-art algorithms on well known difficult problems (e.g. curvature regularization, stereo, deconvolution); it gives near global minimum and better speed.
Our main application of interest is curvature regularization. In the context of segmentation, our partial enumeration technique allows to evaluate curvature directly on small patches using a novel integral geometry approach.
AU - Olsson, Carl
AU - Ulen, Johannes
AU - Boykov, Yuri
AU - Kolmogorov, Vladimir
ID - 2275
TI - Partial enumeration and curvature regularization
ER -
TY - JOUR
AB - GABAergic inhibitory interneurons control fundamental aspects of neuronal network function. Their functional roles are assumed to be defined by the identity of their input synapses, the architecture of their dendritic tree, the passive and active membrane properties and finally the nature of their postsynaptic targets. Indeed, interneurons display a high degree of morphological and physiological heterogeneity. However, whether their morphological and physiological characteristics are correlated and whether interneuron diversity can be described by a continuum of GABAergic cell types or by distinct classes has remained unclear. Here we perform a detailed morphological and physiological characterization of GABAergic cells in the dentate gyrus, the input region of the hippocampus. To achieve an unbiased and efficient sampling and classification we used knock-in mice expressing the enhanced green fluorescent protein (eGFP) in glutamate decarboxylase 67 (GAD67)-positive neurons and performed cluster analysis. We identified five interneuron classes, each of them characterized by a distinct set of anatomical and physiological parameters. Cross-correlation analysis further revealed a direct relation between morphological and physiological properties indicating that dentate gyrus interneurons fall into functionally distinct classes which may differentially control neuronal network activity.
AU - Hosp, Jonas
AU - Strüber, Michael
AU - Yanagawa, Yuchio
AU - Obata, Kunihiko
AU - Vida, Imre
AU - Jonas, Peter M
AU - Bartos, Marlene
ID - 2285
IS - 2
JF - Hippocampus
TI - Morpho-physiological criteria divide dentate gyrus interneurons into classes
VL - 23
ER -
TY - JOUR
AB - We prove the universality of the β-ensembles with convex analytic potentials and for any β >
0, i.e. we show that the spacing distributions of log-gases at any inverse temperature β coincide with those of the Gaussian β-ensembles.
AU - Erdös, László
AU - Bourgade, Paul
AU - Yau, Horng
ID - 2699
IS - 6
JF - Duke Mathematical Journal
TI - Universality of general β-ensembles
VL - 163
ER -
TY - JOUR
AB - Multi-dimensional mean-payoff and energy games provide the mathematical foundation for the quantitative study of reactive systems, and play a central role in the emerging quantitative theory of verification and synthesis. In this work, we study the strategy synthesis problem for games with such multi-dimensional objectives along with a parity condition, a canonical way to express ω ω -regular conditions. While in general, the winning strategies in such games may require infinite memory, for synthesis the most relevant problem is the construction of a finite-memory winning strategy (if one exists). Our main contributions are as follows. First, we show a tight exponential bound (matching upper and lower bounds) on the memory required for finite-memory winning strategies in both multi-dimensional mean-payoff and energy games along with parity objectives. This significantly improves the triple exponential upper bound for multi energy games (without parity) that could be derived from results in literature for games on vector addition systems with states. Second, we present an optimal symbolic and incremental algorithm to compute a finite-memory winning strategy (if one exists) in such games. Finally, we give a complete characterization of when finite memory of strategies can be traded off for randomness. In particular, we show that for one-dimension mean-payoff parity games, randomized memoryless strategies are as powerful as their pure finite-memory counterparts.
AU - Chatterjee, Krishnendu
AU - Randour, Mickael
AU - Raskin, Jean
ID - 2716
IS - 3-4
JF - Acta Informatica
TI - Strategy synthesis for multi-dimensional quantitative objectives
VL - 51
ER -
TY - JOUR
AB - A robust combiner for hash functions takes two candidate implementations and constructs a hash function which is secure as long as at least one of the candidates is secure. So far, hash function combiners only aim at preserving a single property such as collision-resistance or pseudorandomness. However, when hash functions are used in protocols like TLS they are often required to provide several properties simultaneously. We therefore put forward the notion of robust multi-property combiners and elaborate on different definitions for such combiners. We then propose a combiner that provably preserves (target) collision-resistance, pseudorandomness, and being a secure message authentication code. This combiner satisfies the strongest notion we propose, which requires that the combined function satisfies every security property which is satisfied by at least one of the underlying hash function. If the underlying hash functions have output length n, the combiner has output length 2 n. This basically matches a known lower bound for black-box combiners for collision-resistance only, thus the other properties can be achieved without penalizing the length of the hash values. We then propose a combiner which also preserves the property of being indifferentiable from a random oracle, slightly increasing the output length to 2 n+ω(log n). Moreover, we show how to augment our constructions in order to make them also robust for the one-wayness property, but in this case require an a priory upper bound on the input length.
AU - Fischlin, Marc
AU - Lehmann, Anja
AU - Pietrzak, Krzysztof Z
ID - 2852
IS - 3
JF - Journal of Cryptology
TI - Robust multi-property combiners for hash functions
VL - 27
ER -
TY - CONF
AB - Persistent homology is a recent grandchild of homology that has found use in
science and engineering as well as in mathematics. This paper surveys the method as well
as the applications, neglecting completeness in favor of highlighting ideas and directions.
AU - Edelsbrunner, Herbert
AU - Morozovy, Dmitriy
ID - 2905
TI - Persistent homology: Theory and practice
ER -
TY - CONF
AB - Many questions concerning models in quantum mechanics require a detailed analysis of the spectrum of the corresponding Hamiltonian, a linear operator on a suitable Hilbert space. Of particular relevance for an understanding of the low-temperature properties of a system is the structure of the excitation spectrum, which is the part of the spectrum close to the spectral bottom. We present recent progress on this question for bosonic many-body quantum systems with weak two-body interactions. Such system are currently of great interest, due to their experimental realization in ultra-cold atomic gases. We investigate the accuracy of the Bogoliubov approximations, which predicts that the low-energy spectrum is made up of sums of elementary excitations, with linear dispersion law at low momentum. The latter property is crucial for the superfluid behavior the system.
AU - Seiringer, Robert
ID - 8044
SN - 9788961058063
T2 - Proceeding of the International Congress of Mathematicans
TI - Structure of the excitation spectrum for many-body quantum systems
VL - 3
ER -
TY - CONF
AB - In this paper we present INTERHORN, a solver for recursion-free Horn clauses. The main application domain of INTERHORN lies in solving interpolation problems arising in software verification. We show how a range of interpolation problems, including path, transition, nested, state/transition and well-founded interpolation can be handled directly by INTERHORN. By detailing these interpolation problems and their Horn clause representations, we hope to encourage the emergence of a common back-end interpolation interface useful for diverse verification tools.
AU - Gupta, Ashutosh
AU - Popeea, Corneliu
AU - Rybalchenko, Andrey
ID - 1702
T2 - Electronic Proceedings in Theoretical Computer Science, EPTCS
TI - Generalised interpolation by solving recursion free-horn clauses
VL - 169
ER -
TY - CONF
AB - It has been long argued that, because of inherent ambiguity and noise, the brain needs to represent uncertainty in the form of probability distributions. The neural encoding of such distributions remains however highly controversial. Here we present a novel circuit model for representing multidimensional real-valued distributions using a spike based spatio-temporal code. Our model combines the computational advantages of the currently competing models for probabilistic codes and exhibits realistic neural responses along a variety of classic measures. Furthermore, the model highlights the challenges associated with interpreting neural activity in relation to behavioral uncertainty and points to alternative population-level approaches for the experimental validation of distributed representations.
AU - Savin, Cristina
AU - Denève, Sophie
ID - 1708
IS - January
TI - Spatio-temporal representations of uncertainty in spiking neural networks
VL - 3
ER -
TY - JOUR
AB - The classical (boolean) notion of refinement for behavioral interfaces of system components is the alternating refinement preorder. In this paper, we define a distance for interfaces, called interface simulation distance. It makes the alternating refinement preorder quantitative by, intuitively, tolerating errors (while counting them) in the alternating simulation game. We show that the interface simulation distance satisfies the triangle inequality, that the distance between two interfaces does not increase under parallel composition with a third interface, that the distance between two interfaces can be bounded from above and below by distances between abstractions of the two interfaces, and how to synthesize an interface from incompatible requirements. We illustrate the framework, and the properties of the distances under composition of interfaces, with two case studies.
AU - Cerny, Pavol
AU - Chmelik, Martin
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
ID - 1733
IS - 3
JF - Theoretical Computer Science
TI - Interface simulation distances
VL - 560
ER -
TY - CHAP
AB - The generation of asymmetry, at both cellular and tissue level, is one of the most essential capabilities of all eukaryotic organisms. It mediates basically all multicellular development ranging from embryogenesis and de novo organ formation till responses to various environmental stimuli. In plants, the awe-inspiring number of such processes is regulated by phytohormone auxin and its directional, cell-to-cell transport. The mediators of this transport, PIN auxin transporters, are asymmetrically localized at the plasma membrane, and this polar localization determines the directionality of intercellular auxin flow. Thus, auxin transport contributes crucially to the generation of local auxin gradients or maxima, which instruct given cell to change its developmental program. Here, we introduce and discuss the molecular components and cellular mechanisms regulating the generation and maintenance of cellular PIN polarity, as the general hallmarks of cell polarity in plants.
AU - Baster, Pawel
AU - Friml, Jiří
ED - Zažímalová, Eva
ED - Petrášek, Jan
ED - Benková, Eva
ID - 1806
T2 - Auxin and Its Role in Plant Development
TI - Auxin on the road navigated by cellular PIN polarity
ER -
TY - JOUR
AB - Watermarking techniques for vector graphics dislocate vertices in order to embed imperceptible, yet detectable, statistical features into the input data. The embedding process may result in a change of the topology of the input data, e.g., by introducing self-intersections, which is undesirable or even disastrous for many applications. In this paper we present a watermarking framework for two-dimensional vector graphics that employs conventional watermarking techniques but still provides the guarantee that the topology of the input data is preserved. The geometric part of this framework computes so-called maximum perturbation regions (MPR) of vertices. We propose two efficient algorithms to compute MPRs based on Voronoi diagrams and constrained triangulations. Furthermore, we present two algorithms to conditionally correct the watermarked data in order to increase the watermark embedding capacity and still guarantee topological correctness. While we focus on the watermarking of input formed by straight-line segments, one of our approaches can also be extended to circular arcs. We conclude the paper by demonstrating and analyzing the applicability of our framework in conjunction with two well-known watermarking techniques.
AU - Huber, Stefan
AU - Held, Martin
AU - Meerwald, Peter
AU - Kwitt, Roland
ID - 1816
IS - 1
JF - International Journal of Computational Geometry and Applications
TI - Topology-preserving watermarking of vector graphics
VL - 24
ER -
TY - JOUR
AB - We review recent progress towards a rigorous understanding of the Bogoliubov approximation for bosonic quantum many-body systems. We focus, in particular, on the excitation spectrum of a Bose gas in the mean-field (Hartree) limit. A list of open problems will be discussed at the end.
AU - Seiringer, Robert
ID - 1821
IS - 7
JF - Journal of Mathematical Physics
TI - Bose gases, Bose-Einstein condensation, and the Bogoliubov approximation
VL - 55
ER -
TY - JOUR
AU - Jakšić, Vojkan
AU - Pillet, Claude
AU - Seiringer, Robert
ID - 1822
IS - 7
JF - Journal of Mathematical Physics
TI - Introduction
VL - 55
ER -
TY - CHAP
AB - Hitting and batting tasks, such as tennis forehands, ping-pong strokes, or baseball batting, depend on predictions where the ball can be intercepted and how it can properly be returned to the opponent. These predictions get more accurate over time, hence the behaviors need to be continuously modified. As a result, movement templates with a learned global shape need to be adapted during the execution so that the racket reaches a target position and velocity that will return the ball over to the other side of the net or court. It requires altering learned movements to hit a varying target with the necessary velocity at a specific instant in time. Such a task cannot be incorporated straightforwardly in most movement representations suitable for learning. For example, the standard formulation of the dynamical system based motor primitives (introduced by Ijspeert et al (2002b)) does not satisfy this property despite their flexibility which has allowed learning tasks ranging from locomotion to kendama. In order to fulfill this requirement, we reformulate the Ijspeert framework to incorporate the possibility of specifying a desired hitting point and a desired hitting velocity while maintaining all advantages of the original formulation.We show that the proposed movement template formulation works well in two scenarios, i.e., for hitting a ball on a string with a table tennis racket at a specified velocity and for returning balls launched by a ball gun successfully over the net using forehand movements.
AU - Muelling, Katharina
AU - Kroemer, Oliver
AU - Lampert, Christoph
AU - Schölkopf, Bernhard
ED - Kober, Jens
ED - Peters, Jan
ID - 1829
T2 - Learning Motor Skills
TI - Movement templates for learning of hitting and batting
VL - 97
ER -
TY - JOUR
AB - We prove polynomial upper bounds of geometric Ramsey numbers of pathwidth-2 outerplanar triangulations in both convex and general cases. We also prove that the geometric Ramsey numbers of the ladder graph on 2n vertices are bounded by O(n3) and O(n10), in the convex and general case, respectively. We then apply similar methods to prove an (Formula presented.) upper bound on the Ramsey number of a path with n ordered vertices.
AU - Cibulka, Josef
AU - Gao, Pu
AU - Krcál, Marek
AU - Valla, Tomáš
AU - Valtr, Pavel
ID - 1842
IS - 1
JF - Discrete & Computational Geometry
TI - On the geometric ramsey number of outerplanar graphs
VL - 53
ER -
TY - JOUR
AB - Local protein interactions ("molecular context" effects) dictate amino acid replacements and can be described in terms of site-specific, energetic preferences for any different amino acid. It has been recently debated whether these preferences remain approximately constant during evolution or whether, due to coevolution of sites, they change strongly. Such research highlights an unresolved and fundamental issue with far-reaching implications for phylogenetic analysis and molecular evolution modeling. Here, we take advantage of the recent availability of phenotypically supported laboratory resurrections of Precambrian thioredoxins and β-lactamases to experimentally address the change of site-specific amino acid preferences over long geological timescales. Extensive mutational analyses support the notion that evolutionary adjustment to a new amino acid may occur, but to a large extent this is insufficient to erase the primitive preference for amino acid replacements. Generally, site-specific amino acid preferences appear to remain conserved throughout evolutionary history despite local sequence divergence. We show such preference conservation to be readily understandable in molecular terms and we provide crystallographic evidence for an intriguing structural-switch mechanism: Energetic preference for an ancestral amino acid in a modern protein can be linked to reorganization upon mutation to the ancestral local structure around the mutated site. Finally, we point out that site-specific preference conservation naturally leads to one plausible evolutionary explanation for the existence of intragenic global suppressor mutations.
AU - Risso, Valeria
AU - Manssour Triedo, Fadia
AU - Delgado Delgado, Asuncion
AU - Arco, Rocio
AU - Barroso Deljesús, Alicia
AU - Inglés Prieto, Álvaro
AU - Godoy Ruiz, Raquel
AU - Gavira, Josè
AU - Gaucher, Eric
AU - Ibarra Molero, Beatriz
AU - Sánchez Ruiz, Jose
ID - 1844
IS - 2
JF - Molecular Biology and Evolution
TI - Mutational studies on resurrected ancestral proteins reveal conservation of site-specific amino acid preferences throughout evolutionary history
VL - 32
ER -
TY - JOUR
AB - To control morphogenesis, molecular regulatory networks have to interfere with the mechanical properties of the individual cells of developing organs and tissues, but how this is achieved is not well known. We study this issue here in the shoot meristem of higher plants, a group of undifferentiated cells where complex changes in growth rates and directions lead to the continuous formation of new organs [1, 2]. Here, we show that the plant hormone auxin plays an important role in this process via a dual, local effect on the extracellular matrix, the cell wall, which determines cell shape. Our study reveals that auxin not only causes a limited reduction in wall stiffness but also directly interferes with wall anisotropy via the regulation of cortical microtubule dynamics. We further show that to induce growth isotropy and organ outgrowth, auxin somehow interferes with the cortical microtubule-ordering activity of a network of proteins, including AUXIN BINDING PROTEIN 1 and KATANIN 1. Numerical simulations further indicate that the induced isotropy is sufficient to amplify the effects of the relatively minor changes in wall stiffness to promote organogenesis and the establishment of new growth axes in a robust manner.
AU - Sassi, Massimiliano
AU - Ali, Olivier
AU - Boudon, Frédéric
AU - Cloarec, Gladys
AU - Abad, Ursula
AU - Cellier, Coralie
AU - Chen, Xu
AU - Gilles, Benjamin
AU - Milani, Pascale
AU - Friml, Jirí
AU - Vernoux, Teva
AU - Godin, Christophe
AU - Hamant, Olivier
AU - Traas, Jan
ID - 1852
IS - 19
JF - Current Biology
TI - An auxin-mediated shift toward growth isotropy promotes organ formation at the shoot meristem in Arabidopsis
VL - 24
ER -
TY - CONF
AB - Wireless sensor networks (WSNs) composed of low-power, low-cost sensor nodes are expected to form the backbone of future intelligent networks for a broad range of civil, industrial and military applications. These sensor nodes are often deployed through random spreading, and function in dynamic environments. Many applications of WSNs such as pollution tracking, forest fire detection, and military surveillance require knowledge of the location of constituent nodes. But the use of technologies such as GPS on all nodes is prohibitive due to power and cost constraints. So, the sensor nodes need to autonomously determine their locations. Most localization techniques use anchor nodes with known locations to determine the position of remaining nodes. Localization techniques have two conflicting requirements. On one hand, an ideal localization technique should be computationally simple and on the other hand, it must be resistant to attacks that compromise anchor nodes. In this paper, we propose a computationally light-weight game theoretic secure localization technique and demonstrate its effectiveness in comparison to existing techniques.
AU - Jha, Susmit
AU - Tripakis, Stavros
AU - Seshia, Sanjit
AU - Chatterjee, Krishnendu
ID - 1853
TI - Game theoretic secure localization in wireless sensor networks
ER -
TY - JOUR
AB - In this paper, we present a method for non-rigid, partial shape matching in vector graphics. Given a user-specified query region in a 2D shape, similar regions are found, even if they are non-linearly distorted. Furthermore, a non-linear mapping is established between the query regions and these matches, which allows the automatic transfer of editing operations such as texturing. This is achieved by a two-step approach. First, pointwise correspondences between the query region and the whole shape are established. The transformation parameters of these correspondences are registered in an appropriate transformation space. For transformations between similar regions, these parameters form surfaces in transformation space, which are extracted in the second step of our method. The extracted regions may be related to the query region by a non-rigid transform, enabling non-rigid shape matching. In this paper, we present a method for non-rigid, partial shape matching in vector graphics. Given a user-specified query region in a 2D shape, similar regions are found, even if they are non-linearly distorted. Furthermore, a non-linear mapping is established between the query regions and these matches, which allows the automatic transfer of editing operations such as texturing. This is achieved by a two-step approach. First, pointwise correspondences between the query region and the whole shape are established. The transformation parameters of these correspondences are registered in an appropriate transformation space. For transformations between similar regions, these parameters form surfaces in transformation space, which are extracted in the second step of our method. The extracted regions may be related to the query region by a non-rigid transform, enabling non-rigid shape matching.
AU - Guerrero, Paul
AU - Auzinger, Thomas
AU - Wimmer, Michael
AU - Jeschke, Stefan
ID - 1854
IS - 1
JF - Computer Graphics Forum
TI - Partial shape matching using transformation parameter similarity
VL - 34
ER -
TY - JOUR
AB - The prominent and evolutionarily ancient role of the plant hormone auxin is the regulation of cell expansion. Cell expansion requires ordered arrangement of the cytoskeleton but molecular mechanisms underlying its regulation by signalling molecules including auxin are unknown. Here we show in the model plant Arabidopsis thaliana that in elongating cells exogenous application of auxin or redistribution of endogenous auxin induces very rapid microtubule re-orientation from transverse to longitudinal, coherent with the inhibition of cell expansion. This fast auxin effect requires auxin binding protein 1 (ABP1) and involves a contribution of downstream signalling components such as ROP6 GTPase, ROP-interactive protein RIC1 and the microtubule-severing protein katanin. These components are required for rapid auxin-and ABP1-mediated re-orientation of microtubules to regulate cell elongation in roots and dark-grown hypocotyls as well as asymmetric growth during gravitropic responses.
AU - Chen, Xu
AU - Grandont, Laurie
AU - Li, Hongjiang
AU - Hauschild, Robert
AU - Paque, Sébastien
AU - Abuzeineh, Anas
AU - Rakusová, Hana
AU - Benková, Eva
AU - Perrot Rechenmann, Catherine
AU - Friml, Jirí
ID - 1862
IS - 729
JF - Nature
TI - Inhibition of cell expansion by rapid ABP1-mediated auxin effect on microtubules
VL - 516
ER -
TY - CONF
AB - Boolean controllers for systems with complex datapaths are often very difficult to implement correctly, in particular when concurrency is involved. Yet, in many instances it is easy to formally specify correctness. For example, the specification for the controller of a pipelined processor only has to state that the pipelined processor gives the same results as a non-pipelined reference design. This makes such controllers a good target for automated synthesis. However, an efficient abstraction for the complex datapath elements is needed, as a bit-precise description is often infeasible. We present Suraq, the first controller synthesis tool which uses uninterpreted functions for the abstraction. Quantified firstorder formulas (with specific quantifier structure) serve as the specification language from which Suraq synthesizes Boolean controllers. Suraq transforms the specification into an unsatisfiable SMT formula, and uses Craig interpolation to compute its results. Using Suraq, we were able to synthesize a controller (consisting of two Boolean signals) for a five-stage pipelined DLX processor in roughly one hour and 15 minutes.
AU - Hofferek, Georg
AU - Gupta, Ashutosh
ED - Yahav, Eran
ID - 1869
T2 - HVC 2014
TI - Suraq - a controller synthesis tool using uninterpreted functions
VL - 8855
ER -
TY - CONF
AB - We investigate the problem of checking if a finite-state transducer is robust to uncertainty in its input. Our notion of robustness is based on the analytic notion of Lipschitz continuity - a transducer is K-(Lipschitz) robust if the perturbation in its output is at most K times the perturbation in its input. We quantify input and output perturbation using similarity functions. We show that K-robustness is undecidable even for deterministic transducers. We identify a class of functional transducers, which admits a polynomial time automata-theoretic decision procedure for K-robustness. This class includes Mealy machines and functional letter-to-letter transducers. We also study K-robustness of nondeterministic transducers. Since a nondeterministic transducer generates a set of output words for each input word, we quantify output perturbation using setsimilarity functions. We show that K-robustness of nondeterministic transducers is undecidable, even for letter-to-letter transducers. We identify a class of set-similarity functions which admit decidable K-robustness of letter-to-letter transducers.
AU - Henzinger, Thomas A
AU - Otop, Jan
AU - Samanta, Roopsha
ID - 1870
T2 - Leibniz International Proceedings in Informatics, LIPIcs
TI - Lipschitz robustness of finite-state transducers
VL - 29
ER -
TY - CONF
AB - Extensionality axioms are common when reasoning about data collections, such as arrays and functions in program analysis, or sets in mathematics. An extensionality axiom asserts that two collections are equal if they consist of the same elements at the same indices. Using extensionality is often required to show that two collections are equal. A typical example is the set theory theorem (∀x)(∀y)x∪y = y ∪x. Interestingly, while humans have no problem with proving such set identities using extensionality, they are very hard for superposition theorem provers because of the calculi they use. In this paper we show how addition of a new inference rule, called extensionality resolution, allows first-order theorem provers to easily solve problems no modern first-order theorem prover can solve. We illustrate this by running the VAMPIRE theorem prover with extensionality resolution on a number of set theory and array problems. Extensionality resolution helps VAMPIRE to solve problems from the TPTP library of first-order problems that were never solved before by any prover.
AU - Gupta, Ashutosh
AU - Kovács, Laura
AU - Kragl, Bernhard
AU - Voronkov, Andrei
ED - Cassez, Franck
ED - Raskin, Jean-François
ID - 1872
T2 - ATVA 2014
TI - Extensional crisis and proving identity
VL - 8837
ER -
TY - CONF
AB - We present a formal framework for repairing infinite-state, imperative, sequential programs, with (possibly recursive) procedures and multiple assertions; the framework can generate repaired programs by modifying the original erroneous program in multiple program locations, and can ensure the readability of the repaired program using user-defined expression templates; the framework also generates a set of inductive assertions that serve as a proof of correctness of the repaired program. As a step toward integrating programmer intent and intuition in automated program repair, we present a cost-aware formulation - given a cost function associated with permissible statement modifications, the goal is to ensure that the total program modification cost does not exceed a given repair budget. As part of our predicate abstractionbased solution framework, we present a sound and complete algorithm for repair of Boolean programs. We have developed a prototype tool based on SMT solving and used it successfully to repair diverse errors in benchmark C programs.
AU - Samanta, Roopsha
AU - Olivo, Oswaldo
AU - Allen, Emerson
ED - Müller-Olm, Markus
ED - Seidl, Helmut
ID - 1875
TI - Cost-aware automatic program repair
VL - 8723
ER -
TY - JOUR
AB - We study densities of functionals over uniformly bounded triangulations of a Delaunay set of vertices, and prove that the minimum is attained for the Delaunay triangulation if this is the case for finite sets.
AU - Dolbilin, Nikolai
AU - Edelsbrunner, Herbert
AU - Glazyrin, Alexey
AU - Musin, Oleg
ID - 1876
IS - 3
JF - Moscow Mathematical Journal
TI - Functionals on triangulations of delaunay sets
VL - 14
ER -
TY - JOUR
AB - During inflammation, lymph nodes swell with an influx of immune cells. New findings identify a signalling pathway that induces relaxation in the contractile cells that give structure to these organs.
AU - Sixt, Michael K
AU - Vaahtomeri, Kari
ID - 1877
IS - 7523
JF - Nature
TI - Physiology: Relax and come in
VL - 514
ER -
TY - JOUR
AB - Unbiased high-throughput massively parallel sequencing methods have transformed the process of discovery of novel putative driver gene mutations in cancer. In chronic lymphocytic leukemia (CLL), these methods have yielded several unexpected findings, including the driver genes SF3B1, NOTCH1 and POT1. Recent analysis, utilizing down-sampling of existing datasets, has shown that the discovery process of putative drivers is far from complete across cancer. In CLL, while driver gene mutations affecting >10% of patients were efficiently discovered with previously published CLL cohorts of up to 160 samples subjected to whole exome sequencing (WES), this sample size has only 0.78 power to detect drivers affecting 5% of patients, and only 0.12 power for drivers affecting 2% of patients. These calculations emphasize the need to apply unbiased WES to larger patient cohorts.
AU - Landau, Dan
AU - Stewart, Chip
AU - Reiter, Johannes
AU - Lawrence, Michael
AU - Sougnez, Carrie
AU - Brown, Jennifer
AU - Lopez Guillermo, Armando
AU - Gabriel, Stacey
AU - Lander, Eric
AU - Neuberg, Donna
AU - López Otín, Carlos
AU - Campo, Elias
AU - Getz, Gad
AU - Wu, Catherine
ID - 1884
IS - 21
JF - Blood
TI - Novel putative driver gene mutations in chronic lymphocytic leukemia (CLL): results from a combined analysis of whole exome sequencing of 262 primary CLL aamples
VL - 124
ER -
TY - JOUR
AB - Information processing in the sensory periphery is shaped by natural stimulus statistics. In the periphery, a transmission bottleneck constrains performance; thus efficient coding implies that natural signal components with a predictably wider range should be compressed. In a different regime—when sampling limitations constrain performance—efficient coding implies that more resources should be allocated to informative features that are more variable. We propose that this regime is relevant for sensory cortex when it extracts complex features from limited numbers of sensory samples. To test this prediction, we use central visual processing as a model: we show that visual sensitivity for local multi-point spatial correlations, described by dozens of independently-measured parameters, can be quantitatively predicted from the structure of natural images. This suggests that efficient coding applies centrally, where it extends to higher-order sensory features and operates in a regime in which sensitivity increases with feature variability.
AU - Hermundstad, Ann
AU - Briguglio, John
AU - Conte, Mary
AU - Victor, Jonathan
AU - Balasubramanian, Vijay
AU - Tkacik, Gasper
ID - 1886
IS - November
JF - eLife
TI - Variance predicts salience in central sensory processing
ER -
TY - JOUR
AU - Cremer, Sylvia
ID - 1887
JF - Zoologie
TI - Gemeinsame Krankheitsabwehr in Ameisengesellschaften
ER -
TY - CHAP
AB - Im Rahmen meiner Arbeit mit der kollektiven Krankheitsabwehr in Ameisengesellschaften interessiert mich vor allem, wie sich die Kolonien als Ganzes gegen Krankheiten wehren können. Warum ist dieses Thema der Krankheitsdynamik in Gruppen so wichtig? Ein Vergleich von solitär lebenden Individuen mit Individuen, die in sozialen Gruppen zusammenleben, zeigt die Kosten und die Vorteile des Gruppenlebens: Einerseits haben Individuen in sozialen Gruppen aufgrund der hohen Dichte, in der die Tiere zusammenleben, den hohen Interaktionsraten, die sie miteinander haben, und der engen Verwandtschaft, die sie verbindet, ein höheres Ansteckungsrisiko. Andererseits kann die individuelle Krankheitsabwehr durch die kollektive Abwehr in den Gruppen ergänzt werden.
AU - Cremer, Sylvia
ID - 1888
T2 - Soziale Insekten in einer sich wandelnden Welt
TI - Soziale Immunität: Wie sich der Staat gegen Pathogene wehrt Bayerische Akademie der Wissenschaften
VL - 43
ER -
TY - JOUR
AB - We study translation-invariant quasi-free states for a system of fermions with two-particle interactions. The associated energy functional is similar to the BCS functional but also includes direct and exchange energies. We show that for suitable short-range interactions, these latter terms only lead to a renormalization of the chemical potential, with the usual properties of the BCS functional left unchanged. Our analysis thus represents a rigorous justification of part of the BCS approximation. We give bounds on the critical temperature below which the system displays superfluidity.
AU - Bräunlich, Gerhard
AU - Hainzl, Christian
AU - Seiringer, Robert
ID - 1889
IS - 7
JF - Reviews in Mathematical Physics
TI - Translation-invariant quasi-free states for fermionic systems and the BCS approximation
VL - 26
ER -
TY - JOUR
AB - To search for a target in a complex environment is an everyday behavior that ends with finding the target. When we search for two identical targets, however, we must continue the search after finding the first target and memorize its location. We used fixation-related potentials to investigate the neural correlates of different stages of the search, that is, before and after finding the first target. Having found the first target influenced subsequent distractor processing. Compared to distractor fixations before the first target fixation, a negative shift was observed for three subsequent distractor fixations. These results suggest that processing a target in continued search modulates the brain's response, either transiently by reflecting temporary working memory processes or permanently by reflecting working memory retention.
AU - Körner, Christof
AU - Braunstein, Verena
AU - Stangl, Matthias
AU - Schlögl, Alois
AU - Neuper, Christa
AU - Ischebeck, Anja
ID - 1890
IS - 4
JF - Psychophysiology
TI - Sequential effects in continued visual search: Using fixation-related potentials to compare distractor processing before and after target detection
VL - 51
ER -
TY - JOUR
AB - We provide theoretical tests of a novel experimental technique to determine mechanostability of proteins based on stretching a mechanically protected protein by single-molecule force spectroscopy. This technique involves stretching a homogeneous or heterogeneous chain of reference proteins (single-molecule markers) in which one of them acts as host to the guest protein under study. The guest protein is grafted into the host through genetic engineering. It is expected that unraveling of the host precedes the unraveling of the guest removing ambiguities in the reading of the force-extension patterns of the guest protein. We study examples of such systems within a coarse-grained structure-based model. We consider systems with various ratios of mechanostability for the host and guest molecules and compare them to experimental results involving cohesin I as the guest molecule. For a comparison, we also study the force-displacement patterns in proteins that are linked in a serial fashion. We find that the mechanostability of the guest is similar to that of the isolated or serially linked protein. We also demonstrate that the ideal configuration of this strategy would be one in which the host is much more mechanostable than the single-molecule markers. We finally show that it is troublesome to use the highly stable cystine knot proteins as a host to graft a guest in stretching studies because this would involve a cleaving procedure.
AU - Chwastyk, Mateusz
AU - Galera Prat, Albert
AU - Sikora, Mateusz K
AU - Gómez Sicilia, Àngel
AU - Carrión Vázquez, Mariano
AU - Cieplak, Marek
ID - 1891
IS - 5
JF - Proteins: Structure, Function and Bioinformatics
TI - Theoretical tests of the mechanical protection strategy in protein nanomechanics
VL - 82
ER -
TY - JOUR
AB - Behavioural variation among conspecifics is typically contingent on individual state or environmental conditions. Sex-specific genetic polymorphisms are enigmatic because they lack conditionality, and genes causing adaptive trait variation in one sex may reduce Darwinian fitness in the other. One way to avoid such genetic antagonism is to control sex-specific traits by inheritance via sex chromosomes. Here, controlled laboratory crossings suggest that in snail-brooding cichlid fish a single locus, two-allele polymorphism located on a sex-linked chromosome of heterogametic males generates an extreme reproductive dimorphism. Both natural and sexual selection are responsible for exceptionally large body size of bourgeois males, creating a niche for a miniature male phenotype to evolve. This extreme intrasexual dimorphism results from selection on opposite size thresholds caused by a single ecological factor, empty snail shells used as breeding substrate. Paternity analyses reveal that in the field parasitic dwarf males sire the majority of offspring in direct sperm competition with large nest owners exceeding their size more than 40 times. Apparently, use of empty snail shells as breeding substrate and single locus sex-linked inheritance of growth are the major ecological and genetic mechanisms responsible for the extreme intrasexual diversity observed in Lamprologus callipterus.
AU - Ocana, Sabine
AU - Meidl, Patrick
AU - Bonfils, Danielle
AU - Taborsky, Michael
ID - 1892
IS - 1794
JF - Proceedings of the Royal Society of London Series B Biological Sciences
TI - Y-linked Mendelian inheritance of giant and dwarf male morphs in shell-brooding cichlids
VL - 281
ER -
TY - JOUR
AB - Phosphatidylinositol (PtdIns) is a structural phospholipid that can be phosphorylated into various lipid signaling molecules, designated polyphosphoinositides (PPIs). The reversible phosphorylation of PPIs on the 3, 4, or 5 position of inositol is performed by a set of organelle-specific kinases and phosphatases, and the characteristic head groups make these molecules ideal for regulating biological processes in time and space. In yeast and mammals, PtdIns3P and PtdIns(3,5)P2 play crucial roles in trafficking toward the lytic compartments, whereas the role in plants is not yet fully understood. Here we identified the role of a land plant-specific subgroup of PPI phosphatases, the suppressor of actin 2 (SAC2) to SAC5, during vacuolar trafficking and morphogenesis in Arabidopsis thaliana. SAC2-SAC5 localize to the tonoplast along with PtdIns3P, the presumable product of their activity. In SAC gain- and loss-of-function mutants, the levels of PtdIns monophosphates and bisphosphates were changed, with opposite effects on the morphology of storage and lytic vacuoles, and the trafficking toward the vacuoles was defective. Moreover, multiple sac knockout mutants had an increased number of smaller storage and lytic vacuoles, whereas extralarge vacuoles were observed in the overexpression lines, correlating with various growth and developmental defects. The fragmented vacuolar phenotype of sac mutants could be mimicked by treating wild-type seedlings with PtdIns(3,5)P2, corroborating that this PPI is important for vacuole morphology. Taken together, these results provide evidence that PPIs, together with their metabolic enzymes SAC2-SAC5, are crucial for vacuolar trafficking and for vacuolar morphology and function in plants.
AU - Nováková, Petra
AU - Hirsch, Sibylle
AU - Feraru, Elena
AU - Tejos, Ricardo
AU - Van Wijk, Ringo
AU - Viaene, Tom
AU - Heilmann, Mareike
AU - Lerche, Jennifer
AU - De Rycke, Riet
AU - Feraru, Mugurel
AU - Grones, Peter
AU - Van Montagu, Marc
AU - Heilmann, Ingo
AU - Munnik, Teun
AU - Friml, Jirí
ID - 1893
IS - 7
JF - PNAS
TI - SAC phosphoinositide phosphatases at the tonoplast mediate vacuolar function in Arabidopsis
VL - 111
ER -
TY - JOUR
AB - Background: Bacterial Dsb enzymes are involved in the oxidative folding of many proteins, through the formation of disulfide bonds between their cysteine residues. The Dsb protein network has been well characterized in cells of the model microorganism Escherichia coli. To gain insight into the functioning of the Dsb system in epsilon-Proteobacteria, where it plays an important role in the colonization process, we studied two homologs of the main Escherichia coli Dsb oxidase (EcDsbA) that are present in the cells of the enteric pathogen Campylobacter jejuni, the most frequently reported bacterial cause of human enteritis in the world. Methods and Results: Phylogenetic analysis suggests the horizontal transfer of the epsilon-Proteobacterial DsbAs from a common ancestor to gamma-Proteobacteria, which then gave rise to the DsbL lineage. Phenotype and enzymatic assays suggest that the two C. jejuni DsbAs play different roles in bacterial cells and have divergent substrate spectra. CjDsbA1 is essential for the motility and autoagglutination phenotypes, while CjDsbA2 has no impact on those processes. CjDsbA1 plays a critical role in the oxidative folding that ensures the activity of alkaline phosphatase CjPhoX, whereas CjDsbA2 is crucial for the activity of arylsulfotransferase CjAstA, encoded within the dsbA2-dsbB-astA operon. Conclusions: Our results show that CjDsbA1 is the primary thiol-oxidoreductase affecting life processes associated with bacterial spread and host colonization, as well as ensuring the oxidative folding of particular protein substrates. In contrast, CjDsbA2 activity does not affect the same processes and so far its oxidative folding activity has been demonstrated for one substrate, arylsulfotransferase CjAstA. The results suggest the cooperation between CjDsbA2 and CjDsbB. In the case of the CjDsbA1, this cooperation is not exclusive and there is probably another protein to be identified in C. jejuni cells that acts to re-oxidize CjDsbA1. Altogether the data presented here constitute the considerable insight to the Epsilonproteobacterial Dsb systems, which have been poorly understood so far.
AU - Grabowska, Anna
AU - Wywiał, Ewa
AU - Dunin Horkawicz, Stanislaw
AU - Łasica, Anna
AU - Wösten, Marc
AU - Nagy-Staron, Anna A
AU - Godlewska, Renata
AU - Bocian Ostrzycka, Katarzyna
AU - Pieńkowska, Katarzyna
AU - Łaniewski, Paweł
AU - Bujnicki, Janusz
AU - Van Putten, Jos
AU - Jagusztyn Krynicka, Elzbieta
ID - 1894
IS - 9
JF - PLoS One
TI - Functional and bioinformatics analysis of two Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase, DsbA
VL - 9
ER -
TY - JOUR
AB - Major histocompatibility complex class I (MHCI) molecules were recently identified as novel regulators of synaptic plasticity. These molecules are expressed in various brain areas, especially in regions undergoing activity-dependent synaptic plasticity, but their role in the nucleus accumbens (NAc) is unknown. In this study, we investigated the effects of genetic disruption of MHCI function, through deletion of β2-microblobulin, which causes lack of cell surface expression of MHCI. First, we confirmed that MHCI molecules are expressed in the NAc core in wild-type mice. Second, we performed electrophysiological recordings with NAc core slices from wild-type and β2-microglobulin knock-out mice lacking cell surface expression of MHCI. We found that low frequency stimulation induced long-term depression in wild-type but not knock-out mice, whereas high frequency stimulation induced long-term potentiation in both genotypes, with a larger magnitude in knock-out mice. Furthermore, we demonstrated that knock-out mice showed more persistent behavioral sensitization to cocaine, which is a NAc-related behavior. Using this model, we analyzed the density of total AMPA receptors and their subunits GluR1 and GluR2 in the NAc core, by SDS-digested freeze-fracture replica labeling. After repeated cocaine exposure, the density of GluR1 was increased, but there was no change in total AMPA receptors and GluR2 levels in wildtype mice. In contrast, following repeated cocaine exposure, increased densities of total AMPA receptors, GluR1 and GluR2 were observed in knock-out mice. These results indicate that functional deficiency of MHCI enhances synaptic potentiation, induced by electrical and pharmacological stimulation.
AU - Edamura, Mitsuhiro
AU - Murakami, Gen
AU - Meng, Hongrui
AU - Itakura, Makoto
AU - Shigemoto, Ryuichi
AU - Fukuda, Atsuo
AU - Nakahara, Daiichiro
ID - 1895
IS - 9
JF - PLoS One
TI - Functional deficiency of MHC class i enhances LTP and abolishes LTD in the nucleus accumbens of mice
VL - 9
ER -
TY - JOUR
AB - Biopolymer length regulation is a complex process that involves a large number of biological, chemical, and physical subprocesses acting simultaneously across multiple spatial and temporal scales. An illustrative example important for genomic stability is the length regulation of telomeres - nucleoprotein structures at the ends of linear chromosomes consisting of tandemly repeated DNA sequences and a specialized set of proteins. Maintenance of telomeres is often facilitated by the enzyme telomerase but, particularly in telomerase-free systems, the maintenance of chromosomal termini depends on alternative lengthening of telomeres (ALT) mechanisms mediated by recombination. Various linear and circular DNA structures were identified to participate in ALT, however, dynamics of the whole process is still poorly understood. We propose a chemical kinetics model of ALT with kinetic rates systematically derived from the biophysics of DNA diffusion and looping. The reaction system is reduced to a coagulation-fragmentation system by quasi-steady-state approximation. The detailed treatment of kinetic rates yields explicit formulas for expected size distributions of telomeres that demonstrate the key role played by the J factor, a quantitative measure of bending of polymers. The results are in agreement with experimental data and point out interesting phenomena: an appearance of very long telomeric circles if the total telomere density exceeds a critical value (excess mass) and a nonlinear response of the telomere size distributions to the amount of telomeric DNA in the system. The results can be of general importance for understanding dynamics of telomeres in telomerase-independent systems as this mode of telomere maintenance is similar to the situation in tumor cells lacking telomerase activity. Furthermore, due to its universality, the model may also serve as a prototype of an interaction between linear and circular DNA structures in various settings.
AU - Kollár, Richard
AU - Bod'ová, Katarína
AU - Nosek, Jozef
AU - Tomáška, Ľubomír
ID - 1896
IS - 3
JF - Physical Review E Statistical Nonlinear and Soft Matter Physics
TI - Mathematical model of alternative mechanism of telomere length maintenance
VL - 89
ER -
TY - JOUR
AB - GNOM is one of the most characterized membrane trafficking regulators in plants, with crucial roles in development. GNOM encodes an ARF-guanine nucleotide exchange factor (ARF-GEF) that activates small GTPases of the ARF (ADP ribosylation factor) class to mediate vesicle budding at endomembranes. The crucial role of GNOM in recycling of PIN auxin transporters and other proteins to the plasma membrane was identified in studies using the ARF-GEF inhibitor brefeldin A (BFA). GNOM, the most prominent regulator of recycling in plants, has been proposed to act and localize at so far elusive recycling endosomes. Here, we report the GNOM localization in context of its cellular function in Arabidopsis thaliana. State-of-the-art imaging, pharmacological interference, and ultrastructure analysis show that GNOM predominantly localizes to Golgi apparatus. Super-resolution confocal live imaging microscopy identified GNOM and its closest homolog GNOM-like 1 at distinct subdomains on Golgi cisternae. Short-term BFA treatment stabilizes GNOM at the Golgi apparatus, whereas prolonged exposures results in GNOM translocation to trans-Golgi network (TGN)/early endosomes (EEs). Malformed TGN/EE in gnom mutants suggests a role for GNOM in maintaining TGN/EE function. Our results redefine the subcellular action of GNOM and reevaluate the identity and function of recycling endosomes in plants.
AU - Naramoto, Satoshi
AU - Otegui, Marisa
AU - Kutsuna, Natsumaro
AU - De Rycke, Riet
AU - Dainobu, Tomoko
AU - Karampelias, Michael
AU - Fujimoto, Masaru
AU - Feraru, Elena
AU - Miki, Daisuke
AU - Fukuda, Hiroo
AU - Nakano, Akihiko
AU - Friml, Jirí
ID - 1897
IS - 7
JF - Plant Cell
TI - Insights into the localization and function of the membrane trafficking regulator GNOM ARF-GEF at the Golgi apparatus in Arabidopsis
VL - 26
ER -
TY - JOUR
AB - Fast synaptic transmission is important for rapid information processing. To explore the maximal rate of neuronal signaling and to analyze the presynaptic mechanisms, we focused on the input layer of the cerebellar cortex, where exceptionally high action potential (AP) frequencies have been reported invivo. With paired recordings between presynaptic cerebellar mossy fiber boutons and postsynaptic granule cells, we demonstrate reliable neurotransmission upto ~1 kHz. Presynaptic APs are ultrafast, with ~100μs half-duration. Both Kv1 and Kv3 potassium channels mediate the fast repolarization, rapidly inactivating sodium channels ensure metabolic efficiency, and little AP broadening occurs during bursts of up to 1.5 kHz. Presynaptic Cav2.1 (P/Q-type) calcium channels open efficiently during ultrafast APs. Furthermore, a subset of synaptic vesicles is tightly coupled to Ca2+ channels, and vesicles are rapidly recruited to the release site. These data reveal mechanisms of presynaptic AP generation and transmitter release underlying neuronal kHz signaling.
AU - Ritzau Jost, Andreas
AU - Delvendahl, Igor
AU - Rings, Annika
AU - Byczkowicz, Niklas
AU - Harada, Harumi
AU - Shigemoto, Ryuichi
AU - Hirrlinger, Johannes
AU - Eilers, Jens
AU - Hallermann, Stefan
ID - 1898
IS - 1
JF - Neuron
TI - Ultrafast action potentials mediate kilohertz signaling at a central synapse
VL - 84
ER -
TY - JOUR
AB - Asymmetric cell divisions allow stem cells to balance proliferation and differentiation. During embryogenesis, murine epidermis expands rapidly from a single layer of unspecified basal layer progenitors to a stratified, differentiated epithelium. Morphogenesis involves perpendicular (asymmetric) divisions and the spindle orientation protein LGN, but little is known about how the apical localization of LGN is regulated. Here, we combine conventional genetics and lentiviral-mediated in vivo RNAi to explore the functions of the LGN-interacting proteins Par3, mInsc and Gα i3. Whereas loss of each gene alone leads to randomized division angles, combined loss of Gnai3 and mInsc causes a phenotype of mostly planar divisions, akin to loss of LGN. These findings lend experimental support for the hitherto untested model that Par3-mInsc and Gα i3 act cooperatively to polarize LGN and promote perpendicular divisions. Finally, we uncover a developmental switch between delamination-driven early stratification and spindle-orientation-dependent differentiation that occurs around E15, revealing a two-step mechanism underlying epidermal maturation.
AU - Williams, Scott
AU - Ratliff, Lyndsay
AU - Postiglione, Maria P
AU - Knoblich, Juergen
AU - Fuchs, Elaine
ID - 1899
IS - 8
JF - Nature Cell Biology
TI - Par3-mInsc and Gα i3 cooperate to promote oriented epidermal cell divisions through LGN
VL - 16
ER -
TY - JOUR
AB - Epithelial cell layers need to be tightly regulated to maintain their integrity and correct function. Cell integration into epithelial sheets is now shown to depend on the N-WASP-regulated stabilization of cortical F-actin, which generates distinct patterns of apical-lateral contractility at E-cadherin-based cell-cell junctions.
AU - Behrndt, Martin
AU - Heisenberg, Carl-Philipp J
ID - 1900
IS - 2
JF - Nature Cell Biology
TI - Lateral junction dynamics lead the way out
VL - 16
ER -
TY - JOUR
AB - In plants, the patterning of stem cell-enriched meristems requires a graded auxin response maximum that emerges from the concerted action of polar auxin transport, auxin biosynthesis, auxin metabolism, and cellular auxin response machinery. However, mechanisms underlying this auxin response maximum-mediated root stem cell maintenance are not fully understood. Here, we present unexpected evidence that WUSCHEL-RELATED HOMEOBOX 5 (WOX5) transcription factor modulates expression of auxin biosynthetic genes in the quiescent center (QC) of the root and thus provides a robust mechanism for the maintenance of auxin response maximum in the root tip. This WOX5 action is balanced through the activity of indole-3-acetic acid 17 (IAA17) auxin response repressor. Our combined genetic, cell biology, and computational modeling studies revealed a previously uncharacterized feedback loop linking WOX5-mediated auxin production to IAA17-dependent repression of auxin responses. This WOX5-IAA17 feedback circuit further assures the maintenance of auxin response maximum in the root tip and thereby contributes to the maintenance of distal stem cell (DSC) populations. Our experimental studies and in silico computer simulations both demonstrate that the WOX5-IAA17 feedback circuit is essential for the maintenance of auxin gradient in the root tip and the auxin-mediated root DSC differentiation.
AU - Tian, Huiyu
AU - Wabnik, Krzysztof T
AU - Niu, Tiantian
AU - Li, Hongjiang
AU - Yu, Qianqian
AU - Pollmann, Stephan
AU - Vanneste, Steffen
AU - Govaerts, Willy
AU - Rolčík, Jakub
AU - Geisler, Markus
AU - Friml, Jirí
AU - Ding, Zhaojun
ID - 1901
IS - 2
JF - Molecular Plant
TI - WOX5-IAA17 feedback circuit-mediated cellular auxin response is crucial for the patterning of root stem cell niches in arabidopsis
VL - 7
ER -
TY - JOUR
AB - In the 1960s-1980s, determination of bacterial growth rates was an important tool in microbial genetics, biochemistry, molecular biology, and microbial physiology. The exciting technical developments of the 1990s and the 2000s eclipsed that tool; as a result, many investigators today lack experience with growth rate measurements. Recently, investigators in a number of areas have started to use measurements of bacterial growth rates for a variety of purposes. Those measurements have been greatly facilitated by the availability of microwell plate readers that permit the simultaneous measurements on up to 384 different cultures. Only the exponential (logarithmic) portions of the resulting growth curves are useful for determining growth rates, and manual determination of that portion and calculation of growth rates can be tedious for high-throughput purposes. Here, we introduce the program GrowthRates that uses plate reader output files to automatically determine the exponential portion of the curve and to automatically calculate the growth rate, the maximum culture density, and the duration of the growth lag phase. GrowthRates is freely available for Macintosh, Windows, and Linux.We discuss the effects of culture volume, the classical bacterial growth curve, and the differences between determinations in rich media and minimal (mineral salts) media. This protocol covers calibration of the plate reader, growth of culture inocula for both rich and minimal media, and experimental setup. As a guide to reliability, we report typical day-to-day variation in growth rates and variation within experiments with respect to position of wells within the plates.
AU - Hall, Barry
AU - Acar, Hande
AU - Nandipati, Anna
AU - Barlow, Miriam
ID - 1902
IS - 1
JF - Molecular Biology and Evolution
TI - Growth rates made easy
VL - 31
ER -
TY - CONF
AB - We consider two-player zero-sum partial-observation stochastic games on graphs. Based on the information available to the players these games can be classified as follows: (a) general partial-observation (both players have partial view of the game); (b) one-sided partial-observation (one player has partial-observation and the other player has complete-observation); and (c) perfect-observation (both players have complete view of the game). The one-sided partial-observation games subsumes the important special case of one-player partial-observation stochastic games (or partial-observation Markov decision processes (POMDPs)). Based on the randomization available for the strategies, (a) the players may not be allowed to use randomization (pure strategies), or (b) they may choose a probability distribution over actions but the actual random choice is external and not visible to the player (actions invisible), or (c) they may use full randomization. We consider all these classes of games with reachability, and parity objectives that can express all ω-regular objectives. The analysis problems are classified into the qualitative analysis that asks for the existence of a strategy that ensures the objective with probability 1; and the quantitative analysis that asks for the existence of a strategy that ensures the objective with probability at least λ (0,1). In this talk we will cover a wide range of results: for perfect-observation games; for POMDPs; for one-sided partial-observation games; and for general partial-observation games.
AU - Chatterjee, Krishnendu
ID - 1903
IS - PART 1
TI - Partial-observation stochastic reachability and parity games
VL - 8634
ER -
TY - JOUR
AB - We prove a Strichartz inequality for a system of orthonormal functions, with an optimal behavior of the constant in the limit of a large number of functions. The estimate generalizes the usual Strichartz inequality, in the same fashion as the Lieb-Thirring inequality generalizes the Sobolev inequality. As an application, we consider the Schrödinger equation with a time-dependent potential and we show the existence of the wave operator in Schatten spaces.
AU - Frank, Rupert
AU - Lewin, Mathieu
AU - Lieb, Élliott
AU - Seiringer, Robert
ID - 1904
IS - 7
JF - Journal of the European Mathematical Society
TI - Strichartz inequality for orthonormal functions
VL - 16
ER -
TY - JOUR
AB - The unprecedented polymorphism in the major histocompatibility complex (MHC) genes is thought to be maintained by balancing selection from parasites. However, do parasites also drive divergence at MHC loci between host populations, or do the effects of balancing selection maintain similarities among populations? We examined MHC variation in populations of the livebearing fish Poecilia mexicana and characterized their parasite communities. Poecilia mexicana populations in the Cueva del Azufre system are locally adapted to darkness and the presence of toxic hydrogen sulphide, representing highly divergent ecotypes or incipient species. Parasite communities differed significantly across populations, and populations with higher parasite loads had higher levels of diversity at class II MHC genes. However, despite different parasite communities, marked divergence in adaptive traits and in neutral genetic markers, we found MHC alleles to be remarkably similar among host populations. Our findings indicate that balancing selection from parasites maintains immunogenetic diversity of hosts, but this process does not promote MHC divergence in this system. On the contrary, we suggest that balancing selection on immunogenetic loci may outweigh divergent selection causing divergence, thereby hindering host divergence and speciation. Our findings support the hypothesis that balancing selection maintains MHC similarities among lineages during and after speciation (trans-species evolution).
AU - Tobler, Michael
AU - Plath, Martin
AU - Riesch, Rüdiger
AU - Schlupp, Ingo
AU - Grasse, Anna V
AU - Munimanda, Gopi
AU - Setzer, C
AU - Penn, Dustin
AU - Moodley, Yoshan
ID - 1905
IS - 5
JF - Journal of Evolutionary Biology
TI - Selection from parasites favours immunogenetic diversity but not divergence among locally adapted host populations
VL - 27
ER -
TY - JOUR
AB - In this paper, we introduce a novel scene representation for the visualization of large-scale point clouds accompanied by a set of high-resolution photographs. Many real-world applications deal with very densely sampled point-cloud data, which are augmented with photographs that often reveal lighting variations and inaccuracies in registration. Consequently, the high-quality representation of the captured data, i.e., both point clouds and photographs together, is a challenging and time-consuming task. We propose a two-phase approach, in which the first (preprocessing) phase generates multiple overlapping surface patches and handles the problem of seamless texture generation locally for each patch. The second phase stitches these patches at render-time to produce a high-quality visualization of the data. As a result of the proposed localization of the global texturing problem, our algorithm is more than an order of magnitude faster than equivalent mesh-based texturing techniques. Furthermore, since our preprocessing phase requires only a minor fraction of the whole data set at once, we provide maximum flexibility when dealing with growing data sets.
AU - Arikan, Murat
AU - Preiner, Reinhold
AU - Scheiblauer, Claus
AU - Jeschke, Stefan
AU - Wimmer, Michael
ID - 1906
IS - 9
JF - IEEE Transactions on Visualization and Computer Graphics
TI - Large-scale point-cloud visualization through localized textured surface reconstruction
VL - 20
ER -
TY - CONF
AB - Most cryptographic security proofs require showing that two systems are indistinguishable. A central tool in such proofs is that of a game, where winning the game means provoking a certain condition, and it is shown that the two systems considered cannot be distinguished unless this condition is provoked. Upper bounding the probability of winning such a game, i.e., provoking this condition, for an arbitrary strategy is usually hard, except in the special case where the best strategy for winning such a game is known to be non-adaptive. A sufficient criterion for ensuring the optimality of non-adaptive strategies is that of conditional equivalence to a system, a notion introduced in [1]. In this paper, we show that this criterion is not necessary to ensure the optimality of non-adaptive strategies by giving two results of independent interest: 1) the optimality of non-adaptive strategies is not preserved under parallel composition; 2) in contrast, conditional equivalence is preserved under parallel composition.
AU - Demay, Grégory
AU - Gazi, Peter
AU - Maurer, Ueli
AU - Tackmann, Björn
ID - 1907
T2 - IEEE International Symposium on Information Theory
TI - Optimality of non-adaptive strategies: The case of parallel games
ER -
TY - JOUR
AB - In large populations, multiple beneficial mutations may be simultaneously spreading. In asexual populations, these mutations must either arise on the same background or compete against each other. In sexual populations, recombination can bring together beneficial alleles from different backgrounds, but tightly linked alleles may still greatly interfere with each other. We show for well-mixed populations that when this interference is strong, the genome can be seen as consisting of many effectively asexual stretches linked together. The rate at which beneficial alleles fix is thus roughly proportional to the rate of recombination and depends only logarithmically on the mutation supply and the strength of selection. Our scaling arguments also allow us to predict, with reasonable accuracy, the fitness distribution of fixed mutations when the mutational effect sizes are broad. We focus on the regime in which crossovers occur more frequently than beneficial mutations, as is likely to be the case for many natural populations.
AU - Weissman, Daniel
AU - Hallatschek, Oskar
ID - 1908
IS - 4
JF - Genetics
TI - The rate of adaptation in large sexual populations with linear chromosomes
VL - 196
ER -