TY - JOUR
AB - Living cells must control the reading out or "expression" of information encoded in their genomes, and this regulation often is mediated by transcription factors--proteins that bind to DNA and either enhance or repress the expression of nearby genes. But the expression of transcription factor proteins is itself regulated, and many transcription factors regulate their own expression in addition to responding to other input signals. Here we analyze the simplest of such self-regulatory circuits, asking how parameters can be chosen to optimize information transmission from inputs to outputs in the steady state. Some nonzero level of self-regulation is almost always optimal, with self-activation dominant when transcription factor concentrations are low and self-repression dominant when concentrations are high. In steady state the optimal self-activation is never strong enough to induce bistability, although there is a limit in which the optimal parameters are very close to the critical point.
AU - Tkacik, Gasper
AU - Walczak, Aleksandra
AU - Bialek, William
ID - 3262
IS - 4
JF - Physical Review E statistical nonlinear and soft matter physics
TI - Optimizing information flow in small genetic networks. III. A self-interacting gene
VL - 85
ER -
TY - CONF
AB - We propose a mid-level statistical model for image segmentation that composes multiple figure-ground hypotheses (FG) obtained by applying constraints at different locations and scales, into larger interpretations (tilings) of the entire image. Inference is cast as optimization over sets of maximal cliques sampled from a graph connecting all non-overlapping figure-ground segment hypotheses. Potential functions over cliques combine unary, Gestalt-based figure qualities, and pairwise compatibilities among spatially neighboring segments, constrained by T-junctions and the boundary interface statistics of real scenes. Learning the model parameters is based on maximum likelihood, alternating between sampling image tilings and optimizing their potential function parameters. State of the art results are reported on the Berkeley and Stanford segmentation datasets, as well as VOC2009, where a 28% improvement was achieved.
AU - Ion, Adrian
AU - Carreira, Joao
AU - Sminchisescu, Cristian
ID - 3265
TI - Image segmentation by figure-ground composition into maximal cliques
ER -
TY - JOUR
AB - A boundary element model of a tunnel running through horizontally layered soil with anisotropic material properties is presented. Since there is no analytical fundamental solution for wave propagation inside a layered orthotropic medium in 3D, the fundamental displacements and stresses have to be calculated numerically. In our model this is done in the Fourier domain with respect to space and time. The assumption of a straight tunnel with infinite extension in the x direction makes it possible to decouple the system for every wave number kx, leading to a 2.5D-problem, which is suited for parallel computation. The special form of the fundamental solution, resulting from our Fourier ansatz, and the fact, that the calculation of the boundary integral equation is performed in the Fourier domain, enhances the stability and efficiency of the numerical calculations.
AU - Rieckh, Georg
AU - Kreuzer, Wolfgang
AU - Waubke, Holger
AU - Balazs, Peter
ID - 3274
IS - 6
JF - Engineering Analysis with Boundary Elements
TI - A 2.5D-Fourier-BEM model for vibrations in a tunnel running through layered anisotropic soil
VL - 36
ER -
TY - CHAP
AB - The problem of the origin of metazoa is becoming more urgent in the context of astrobiology. By now it is clear that clues to the understanding of this crucial transition in the evolution of life can arise in a fourth pathway besides the three possibilities in the quest for simplicity outlined by Bonner in his classical book. In other words, solar system exploration seems to be one way in the long-term to elucidate the simplicity of evolutionary development. We place these ideas in the context of different inheritance systems, namely the genotypic and phenotypic replicators with limited or unlimited heredity, and ask which of these can support multicellular development, and to which degree of complexity. However, the quest for evidence on the evolution of biotas from planets around other stars does not seem to be feasible with present technology with direct visualization of living organisms on exoplanets. But this may be attempted on the Galilean moons of Jupiter where there is a possibility of detecting reliable biomarkers in the next decade with the Europa Jupiter System Mission, in view of recent progress by landing micropenetrators on planetary, or satellite surfaces. Mars is a second possibility in the inner Solar System, in spite of the multiple difficulties faced by the fleet of past, present and future missions. We discuss a series of preliminary ideas for elucidating the origin of metazoan analogues with available instrumentation in potential payloads of feasible space missions to the Galilean moons.
AU - de Vladar, Harold
AU - Chela Flores, Julian
ID - 3277
T2 - Life on Earth and other planetary bodies
TI - Can the evolution of multicellularity be anticipated in the exploration of the solar system?
VL - 24
ER -
TY - CONF
AB - We show a hardness-preserving construction of a PRF from any length doubling PRG which improves upon known constructions whenever we can put a non-trivial upper bound q on the number of queries to the PRF. Our construction requires only O(logq) invocations to the underlying PRG with each query. In comparison, the number of invocations by the best previous hardness-preserving construction (GGM using Levin's trick) is logarithmic in the hardness of the PRG. For example, starting from an exponentially secure PRG {0,1} n → {0,1} 2n, we get a PRF which is exponentially secure if queried at most q = exp(√n)times and where each invocation of the PRF requires Θ(√n) queries to the underlying PRG. This is much less than the Θ(n) required by known constructions.
AU - Jain, Abhishek
AU - Pietrzak, Krzysztof Z
AU - Tentes, Aris
ID - 3279
TI - Hardness preserving constructions of pseudorandom functions
VL - 7194
ER -
TY - CONF
AB - The (decisional) learning with errors problem (LWE) asks to distinguish "noisy" inner products of a secret vector with random vectors from uniform. The learning parities with noise problem (LPN) is the special case where the elements of the vectors are bits. In recent years, the LWE and LPN problems have found many applications in cryptography. In this paper we introduce a (seemingly) much stronger adaptive assumption, called "subspace LWE" (SLWE), where the adversary can learn the inner product of the secret and random vectors after they were projected into an adaptively and adversarially chosen subspace. We prove that, surprisingly, the SLWE problem mapping into subspaces of dimension d is almost as hard as LWE using secrets of length d (the other direction is trivial.) This result immediately implies that several existing cryptosystems whose security is based on the hardness of the LWE/LPN problems are provably secure in a much stronger sense than anticipated. As an illustrative example we show that the standard way of using LPN for symmetric CPA secure encryption is even secure against a very powerful class of related key attacks.
AU - Pietrzak, Krzysztof Z
ID - 3280
TI - Subspace LWE
VL - 7194
ER -
TY - CONF
AB - We consider the problem of amplifying the "lossiness" of functions. We say that an oracle circuit C*: {0,1} m → {0,1}* amplifies relative lossiness from ℓ/n to L/m if for every function f:{0,1} n → {0,1} n it holds that 1 If f is injective then so is C f. 2 If f has image size of at most 2 n-ℓ, then C f has image size at most 2 m-L. The question is whether such C* exists for L/m ≫ ℓ/n. This problem arises naturally in the context of cryptographic "lossy functions," where the relative lossiness is the key parameter. We show that for every circuit C* that makes at most t queries to f, the relative lossiness of C f is at most L/m ≤ ℓ/n + O(log t)/n. In particular, no black-box method making a polynomial t = poly(n) number of queries can amplify relative lossiness by more than an O(logn)/n additive term. We show that this is tight by giving a simple construction (cascading with some randomization) that achieves such amplification.
AU - Pietrzak, Krzysztof Z
AU - Rosen, Alon
AU - Segev, Gil
ID - 3281
TI - Lossy functions do not amplify well
VL - 7194
ER -
TY - CONF
AB - Traditionally, symmetric-key message authentication codes (MACs) are easily built from pseudorandom functions (PRFs). In this work we propose a wide variety of other approaches to building efficient MACs, without going through a PRF first. In particular, unlike deterministic PRF-based MACs, where each message has a unique valid tag, we give a number of probabilistic MAC constructions from various other primitives/assumptions. Our main results are summarized as follows: We show several new probabilistic MAC constructions from a variety of general assumptions, including CCA-secure encryption, Hash Proof Systems and key-homomorphic weak PRFs. By instantiating these frameworks under concrete number theoretic assumptions, we get several schemes which are more efficient than just using a state-of-the-art PRF instantiation under the corresponding assumption. For probabilistic MACs, unlike deterministic ones, unforgeability against a chosen message attack (uf-cma ) alone does not imply security if the adversary can additionally make verification queries (uf-cmva ). We give an efficient generic transformation from any uf-cma secure MAC which is "message-hiding" into a uf-cmva secure MAC. This resolves the main open problem of Kiltz et al. from Eurocrypt'11; By using our transformation on their constructions, we get the first efficient MACs from the LPN assumption. While all our new MAC constructions immediately give efficient actively secure, two-round symmetric-key identification schemes, we also show a very simple, three-round actively secure identification protocol from any weak PRF. In particular, the resulting protocol is much more efficient than the trivial approach of building a regular PRF from a weak PRF. © 2012 International Association for Cryptologic Research.
AU - Dodis, Yevgeniy
AU - Pietrzak, Krzysztof Z
AU - Kiltz, Eike
AU - Wichs, Daniel
ID - 3282
TI - Message authentication, revisited
VL - 7237
ER -
TY - JOUR
AB - Viral manipulation of transduction pathways associated with key cellular functions such as survival, response to microbial infection, and cytoskeleton reorganization can provide the supportive milieu for a productive infection. Here, we demonstrate that vaccinia virus (VACV) infection leads to activation of the stress-activated protein kinase (SAPK)/extracellular signal-regulated kinase (ERK) 4/7 (MKK4/7)-c-Jun N-terminal protein kinase 1/2 (JNK1/2) pathway; further, the stimulation of this pathway requires postpenetration, prereplicative events in the viral replication cycle. Although the formation of intracellular mature virus (IMV) was not affected in MKK4/7- or JNK1/2-knockout (KO) cells, we did note an accentuated deregulation of microtubule and actin network organization in infected JNK1/2-KO cells. This was followed by deregulated viral trafficking to the periphery and enhanced enveloped particle release. Furthermore, VACV infection induced alterations in the cell contractility and morphology, and cell migration was reduced in the JNK-KO cells. In addition, phosphorylation of proteins implicated with early cell contractility and cell migration, such as microtubule-associated protein 1B and paxillin, respectively, was not detected in the VACV-infected KO cells. In sum, our findings uncover a regulatory role played by the MKK4/7-JNK1/2 pathway in cytoskeleton reorganization during VACV infection.
AU - Pereira, Anna
AU - Leite, Flávia
AU - Brasil, Bruno
AU - Soares Martins, Jamaria
AU - Torres, Alice
AU - Pimenta, Paulo
AU - Souto Padrón, Thais
AU - Tranktman, Paula
AU - Ferreira, Paulo
AU - Kroon, Erna
AU - Bonjardim, Cláudio
ID - 3289
IS - 1
JF - Journal of Virology
TI - A vaccinia virus-driven interplay between the MKK4/7-JNK1/2 pathway and cytoskeleton reorganization
VL - 86
ER -
TY - JOUR
AB - The theory of persistent homology opens up the possibility to reason about topological features of a space or a function quantitatively and in combinatorial terms. We refer to this new angle at a classical subject within algebraic topology as a point calculus, which we present for the family of interlevel sets of a real-valued function. Our account of the subject is expository, devoid of proofs, and written for non-experts in algebraic topology.
AU - Bendich, Paul
AU - Cabello, Sergio
AU - Edelsbrunner, Herbert
ID - 3310
IS - 11
JF - Pattern Recognition Letters
TI - A point calculus for interlevel set homology
VL - 33
ER -
TY - JOUR
AB - We introduce two-level discounted and mean-payoff games played by two players on a perfect-information stochastic game graph. The upper level game is a discounted or mean-payoff game and the lower level game is a (undiscounted) reachability game. Two-level games model hierarchical and sequential decision making under uncertainty across different time scales. For both discounted and mean-payoff two-level games, we show the existence of pure memoryless optimal strategies for both players and an ordered field property. We show that if there is only one player (Markov decision processes), then the values can be computed in polynomial time. It follows that whether the value of a player is equal to a given rational constant in two-level discounted or mean-payoff games can be decided in NP ∩ coNP. We also give an alternate strategy improvement algorithm to compute the value. © 2012 World Scientific Publishing Company.
AU - Chatterjee, Krishnendu
AU - Majumdar, Ritankar
ID - 3314
IS - 3
JF - International Journal of Foundations of Computer Science
TI - Discounting and averaging in games across time scales
VL - 23
ER -
TY - JOUR
AB - The physical distance between presynaptic Ca2+ channels and the Ca2+ sensors that trigger exocytosis of neurotransmitter-containing vesicles is a key determinant of the signalling properties of synapses in the nervous system. Recent functional analysis indicates that in some fast central synapses, transmitter release is triggered by a small number of Ca2+ channels that are coupled to Ca2+ sensors at the nanometre scale. Molecular analysis suggests that this tight coupling is generated by protein–protein interactions involving Ca2+ channels, Ca2+ sensors and various other synaptic proteins. Nanodomain coupling has several functional advantages, as it increases the efficacy, speed and energy efficiency of synaptic transmission.
AU - Eggermann, Emmanuel
AU - Bucurenciu, Iancu
AU - Goswami, Sarit
AU - Jonas, Peter M
ID - 3317
IS - 1
JF - Nature Reviews Neuroscience
TI - Nanodomain coupling between Ca(2+) channels and sensors of exocytosis at fast mammalian synapses
VL - 13
ER -
TY - JOUR
AB - Computing the topology of an algebraic plane curve C means computing a combinatorial graph that is isotopic to C and thus represents its topology in R2. We prove that, for a polynomial of degree n with integer coefficients bounded by 2ρ, the topology of the induced curve can be computed with bit operations ( indicates that we omit logarithmic factors). Our analysis improves the previous best known complexity bounds by a factor of n2. The improvement is based on new techniques to compute and refine isolating intervals for the real roots of polynomials, and on the consequent amortized analysis of the critical fibers of the algebraic curve.
AU - Kerber, Michael
AU - Sagraloff, Michael
ID - 3331
IS - 3
JF - Journal of Symbolic Computation
TI - A worst case bound for topology computation of algebraic curves
VL - 47
ER -
TY - CONF
AB - We consider two-player stochastic games played on a finite state space for an infinite number of rounds. The games are concurrent: in each round, the two players (player 1 and player 2) choose their moves independently and simultaneously; the current state and the two moves determine a probability distribution over the successor states. We also consider the important special case of turn-based stochastic games where players make moves in turns, rather than concurrently. We study concurrent games with \omega-regular winning conditions specified as parity objectives. The value for player 1 for a parity objective is the maximal probability with which the player can guarantee the satisfaction of the objective against all strategies of the opponent. We study the problem of continuity and robustness of the value function in concurrent and turn-based stochastic parity gameswith respect to imprecision in the transition probabilities. We present quantitative bounds on the difference of the value function (in terms of the imprecision of the transition probabilities) and show the value continuity for structurally equivalent concurrent games (two games are structurally equivalent if the support of the transition function is same and the probabilities differ). We also show robustness of optimal strategies for structurally equivalent turn-based stochastic parity games. Finally we show that the value continuity property breaks without the structurally equivalent assumption (even for Markov chains) and show that our quantitative bound is asymptotically optimal. Hence our results are tight (the assumption is both necessary and sufficient) and optimal (our quantitative bound is asymptotically optimal).
AU - Chatterjee, Krishnendu
ID - 3341
TI - Robustness of structurally equivalent concurrent parity games
VL - 7213
ER -
TY - CONF
AB - Many infinite state systems can be seen as well-structured transition systems (WSTS), i.e., systems equipped with a well-quasi-ordering on states that is also a simulation relation. WSTS are an attractive target for formal analysis because there exist generic algorithms that decide interesting verification problems for this class. Among the most popular algorithms are acceleration-based forward analyses for computing the covering set. Termination of these algorithms can only be guaranteed for flattable WSTS. Yet, many WSTS of practical interest are not flattable and the question whether any given WSTS is flattable is itself undecidable. We therefore propose an analysis that computes the covering set and captures the essence of acceleration-based algorithms, but sacrifices precision for guaranteed termination. Our analysis is an abstract interpretation whose abstract domain builds on the ideal completion of the well-quasi-ordered state space, and a widening operator that mimics acceleration and controls the loss of precision of the analysis. We present instances of our framework for various classes of WSTS. Our experience with a prototype implementation indicates that, despite the inherent precision loss, our analysis often computes the precise covering set of the analyzed system.
AU - Zufferey, Damien
AU - Wies, Thomas
AU - Henzinger, Thomas A
ID - 3251
TI - Ideal abstractions for well structured transition systems
VL - 7148
ER -
TY - JOUR
AB - Spontaneous release of glutamate is important for maintaining synaptic strength and controlling spike timing in the brain. Mechanisms regulating spontaneous exocytosis remain poorly understood. Extracellular calcium concentration ([Ca2+]o) regulates Ca2+ entry through voltage-activated calcium channels (VACCs) and consequently is a pivotal determinant of action potential-evoked vesicle fusion. Extracellular Ca 2+ also enhances spontaneous release, but via unknown mechanisms. Here we report that external Ca2+ triggers spontaneous glutamate release more weakly than evoked release in mouse neocortical neurons. Blockade of VACCs has no effect on the spontaneous release rate or its dependence on [Ca2+]o. Intracellular [Ca2+] slowly increases in a minority of neurons following increases in [Ca2+]o. Furthermore, the enhancement of spontaneous release by extracellular calcium is insensitive to chelation of intracellular calcium by BAPTA. Activation of the calcium-sensing receptor (CaSR), a G-protein-coupled receptor present in nerve terminals, by several specific agonists increased spontaneous glutamate release. The frequency of spontaneous synaptic transmission was decreased in CaSR mutant neurons. The concentration-effect relationship for extracellular calcium regulation of spontaneous release was well described by a combination of CaSR-dependent and CaSR-independent mechanisms. Overall these results indicate that extracellular Ca2+ does not trigger spontaneous glutamate release by simply increasing calcium influx but stimulates CaSR and thereby promotes resting spontaneous glutamate release.
AU - Vyleta, Nicholas
AU - Smith, Stephen
ID - 469
IS - 12
JF - European Journal of Neuroscience
TI - Spontaneous glutamate release is independent of calcium influx and tonically activated by the calcium-sensing receptor
VL - 31
ER -
TY - JOUR
AB - BioSig is an open source software library for biomedical signal processing. The aim of the BioSig project is to foster research in biomedical signal processing by providing free and open source software tools for many different application areas. Some of the areas where BioSig can be employed are neuroinformatics, brain-computer interfaces, neurophysiology, psychology, cardiovascular systems, and sleep research. Moreover, the analysis of biosignals such as the electroencephalogram (EEG), electrocorticogram (ECoG), electrocardiogram (ECG), electrooculogram (EOG), electromyogram (EMG), or respiration signals is a very relevant element of the BioSig project. Specifically, BioSig provides solutions for data acquisition, artifact processing, quality control, feature extraction, classification, modeling, and data visualization, to name a few. In this paper, we highlight several methods to help students and researchers to work more efficiently with biomedical signals.
AU - Schlögl, Alois
AU - Vidaurre, Carmen
AU - Sander, Tilmann
ID - 490
JF - Computational Intelligence and Neuroscience
TI - BioSig: The free and open source software library for biomedical signal processing
VL - 2011
ER -
TY - JOUR
AB - In their search for antigens, lymphocytes continuously shuttle among blood vessels, lymph vessels, and lymphatic tissues. Chemokines mediate entry of lymphocytes into lymphatic tissues, and sphingosine 1-phosphate (S1P) promotes localization of lymphocytes to the vasculature. Both signals are sensed through G protein-coupled receptors (GPCRs). Most GPCRs undergo ligand-dependent homologous receptor desensitization, a process that decreases their signaling output after previous exposure to high ligand concentration. Such desensitization can explain why lymphocytes do not take an intermediate position between two signals but rather oscillate between them. The desensitization of S1P receptor 1 (S1PR1) is mediated by GPCR kinase 2 (GRK2). Deletion of GRK2 in lymphocytes compromises desensitization by high vascular S1P concentrations, thereby reducing responsiveness to the chemokine signal and trapping the cells in the vascular compartment. The desensitization kinetics of S1PR1 allows lymphocytes to dynamically shuttle between vasculature and lymphatic tissue, although the positional information in both compartments is static.
AU - Eichner, Alexander
AU - Sixt, Michael K
ID - 491
IS - 198
JF - Science Signaling
TI - Setting the clock for recirculating lymphocytes
VL - 4
ER -
TY - JOUR
AB - Cancer stem cells or cancer initiating cells are believed to contribute to cancer recurrence after therapy. MicroRNAs (miRNAs) are short RNA molecules with fundamental roles in gene regulation. The role of miRNAs in cancer stem cells is only poorly understood. Here, we report miRNA expression profiles of glioblastoma stem cell-containing CD133 + cell populations. We find that miR-9, miR-9 * (referred to as miR-9/9 *), miR-17 and miR-106b are highly abundant in CD133 + cells. Furthermore, inhibition of miR-9/9 * or miR-17 leads to reduced neurosphere formation and stimulates cell differentiation. Calmodulin-binding transcription activator 1 (CAMTA1) is a putative transcription factor, which induces the expression of the anti-proliferative cardiac hormone natriuretic peptide A (NPPA). We identify CAMTA1 as an miR-9/9 * and miR-17 target. CAMTA1 expression leads to reduced neurosphere formation and tumour growth in nude mice, suggesting that CAMTA1 can function as tumour suppressor. Consistently, CAMTA1 and NPPA expression correlate with patient survival. Our findings could provide a basis for novel strategies of glioblastoma therapy.
AU - Schraivogel, Daniel
AU - Weinmann, Lasse
AU - Beier, Dagmar
AU - Tabatabai, Ghazaleh
AU - Eichner, Alexander
AU - Zhu, Jia
AU - Anton, Martina
AU - Sixt, Michael K
AU - Weller, Michael
AU - Beier, Christoph
AU - Meister, Gunter
ID - 518
IS - 20
JF - EMBO Journal
TI - CAMTA1 is a novel tumour suppressor regulated by miR-9/9 * in glioblastoma stem cells
VL - 30
ER -
TY - JOUR
AB - Software transactional memories (STM) are described in the literature with assumptions of sequentially consistent program execution and atomicity of high level operations like read, write, and abort. However, in a realistic setting, processors use relaxed memory models to optimize hardware performance. Moreover, the atomicity of operations depends on the underlying hardware. This paper presents the first approach to verify STMs under relaxed memory models with atomicity of 32 bit loads and stores, and read-modify-write operations. We describe RML, a simple language for expressing concurrent programs. We develop a semantics of RML parametrized by a relaxed memory model. We then present our tool, FOIL, which takes as input the RML description of an STM algorithm restricted to two threads and two variables, and the description of a memory model, and automatically determines the locations of fences, which if inserted, ensure the correctness of the restricted STM algorithm under the given memory model. We use FOIL to verify DSTM, TL2, and McRT STM under the memory models of sequential consistency, total store order, partial store order, and relaxed memory order for two threads and two variables. Finally, we extend the verification results for DSTM and TL2 to an arbitrary number of threads and variables by manually proving that the structural properties of STMs are satisfied at the hardware level of atomicity under the considered relaxed memory models.
AU - Guerraoui, Rachid
AU - Henzinger, Thomas A
AU - Singh, Vasu
ID - 531
IS - 3
JF - Formal Methods in System Design
TI - Verification of STM on relaxed memory models
VL - 39
ER -