TY - JOUR
AB - Gene regulation relies on the specificity of transcription factor (TF)–DNA interactions. Limited specificity may lead to crosstalk: a regulatory state in which a gene is either incorrectly activated due to noncognate TF–DNA interactions or remains erroneously inactive. As each TF can have numerous interactions with noncognate cis-regulatory elements, crosstalk is inherently a global problem, yet has previously not been studied as such. We construct a theoretical framework to analyse the effects of global crosstalk on gene regulation. We find that crosstalk presents a significant challenge for organisms with low-specificity TFs, such as metazoans. Crosstalk is not easily mitigated by known regulatory schemes acting at equilibrium, including variants of cooperativity and combinatorial regulation. Our results suggest that crosstalk imposes a previously unexplored global constraint on the functioning and evolution of regulatory networks, which is qualitatively distinct from the known constraints that act at the level of individual gene regulatory elements.
AU - Friedlander, Tamar
AU - Prizak, Roshan
AU - Guet, Calin C
AU - Barton, Nicholas H
AU - Tkacik, Gasper
ID - 1358
JF - Nature Communications
TI - Intrinsic limits to gene regulation by global crosstalk
VL - 7
ER -
TY - JOUR
AB - The role of gene interactions in the evolutionary process has long
been controversial. Although some argue that they are not of
importance, because most variation is additive, others claim that
their effect in the long term can be substantial. Here, we focus on
the long-term effects of genetic interactions under directional
selection assuming no mutation or dominance, and that epistasis is
symmetrical overall. We ask by how much the mean of a complex
trait can be increased by selection and analyze two extreme
regimes, in which either drift or selection dominate the dynamics
of allele frequencies. In both scenarios, epistatic interactions affect
the long-term response to selection by modulating the additive
genetic variance. When drift dominates, we extend Robertson
’
s
[Robertson A (1960)
Proc R Soc Lond B Biol Sci
153(951):234
−
249]
argument to show that, for any form of epistasis, the total response
of a haploid population is proportional to the initial total genotypic
variance. In contrast, the total response of a diploid population is
increased by epistasis, for a given initial genotypic variance. When
selection dominates, we show that the total selection response can
only be increased by epistasis when s
ome initially deleterious alleles
become favored as the genetic background changes. We find a sim-
ple approximation for this effect and show that, in this regime, it is
the structure of the genotype - phenotype map that matters and not
the variance components of the population.
AU - Paixao, Tiago
AU - Barton, Nicholas H
ID - 1359
IS - 16
JF - PNAS
TI - The effect of gene interactions on the long-term response to selection
VL - 113
ER -
TY - JOUR
AB - We apply the technique of Károly Bezdek and Daniel Bezdek to study billiard trajectories in convex bodies, when the length is measured with a (possibly asymmetric) norm. We prove a lower bound for the length of the shortest closed billiard trajectory, related to the non-symmetric Mahler problem. With this technique we are able to give short and elementary proofs to some known results.
AU - Akopyan, Arseniy
AU - Balitskiy, Alexey
AU - Karasev, Roman
AU - Sharipova, Anastasia
ID - 1360
IS - 10
JF - Proceedings of the American Mathematical Society
TI - Elementary approach to closed billiard trajectories in asymmetric normed spaces
VL - 144
ER -
TY - CONF
AB - We propose a novel surface-only technique for simulating incompressible, inviscid and uniform-density liquids with surface tension in three dimensions. The liquid surface is captured by a triangle mesh on which a Lagrangian velocity field is stored. Because advection of the velocity field may violate the incompressibility condition, we devise an orthogonal projection technique to remove the divergence while requiring the evaluation of only two boundary integrals. The forces of surface tension, gravity, and solid contact are all treated by a boundary element solve, allowing us to perform detailed simulations of a wide range of liquid phenomena, including waterbells, droplet and jet collisions, fluid chains, and crown splashes.
AU - Da, Fang
AU - Hahn, David
AU - Batty, Christopher
AU - Wojtan, Christopher J
AU - Grinspun, Eitan
ID - 1361
IS - 4
TI - Surface only liquids
VL - 35
ER -
TY - CONF
AB - We present a boundary element based method for fast simulation of brittle fracture. By introducing simplifying assumptions that allow us to quickly estimate stress intensities and opening displacements during crack propagation, we build a fracture algorithm where the cost of each time step scales linearly with the length of the crackfront. The transition from a full boundary element method to our faster variant is possible at the beginning of any time step. This allows us to build a hybrid method, which uses the expensive but more accurate BEM while the number of degrees of freedom is low, and uses the fast method once that number exceeds a given threshold as the crack geometry becomes more complicated. Furthermore, we integrate this fracture simulation with a standard rigid-body solver. Our rigid-body coupling solves a Neumann boundary value problem by carefully separating translational, rotational and deformational components of the collision forces and then applying a Tikhonov regularizer to the resulting linear system. We show that our method produces physically reasonable results in standard test cases and is capable of dealing with complex scenes faster than previous finite- or boundary element approaches.
AU - Hahn, David
AU - Wojtan, Christopher J
ID - 1362
IS - 4
TI - Fast approximations for boundary element based brittle fracture simulation
VL - 35
ER -
TY - CONF
AB - When aiming to seamlessly integrate a fluid simulation into a larger scenario (like an open ocean), careful attention must be paid to boundary conditions. In particular, one must implement special "non-reflecting" boundary conditions, which dissipate out-going waves as they exit the simulation. Unfortunately, the state of the art in non-reflecting boundary conditions (perfectly-matched layers, or PMLs) only permits trivially simple inflow/outflow conditions, so there is no reliable way to integrate a fluid simulation into a more complicated environment like a stormy ocean or a turbulent river. This paper introduces the first method for combining nonreflecting boundary conditions based on PMLs with inflow/outflow boundary conditions that vary arbitrarily throughout space and time. Our algorithm is a generalization of stateof- the-art mean-flow boundary conditions in the computational fluid dynamics literature, and it allows for seamless integration of a fluid simulation into much more complicated environments. Our method also opens the door for previously-unseen postprocess effects like retroactively changing the location of solid obstacles, and locally increasing the visual detail of a pre-existing simulation.
AU - Bojsen-Hansen, Morten
AU - Wojtan, Christopher J
ID - 1363
IS - 4
TI - Generalized non-reflecting boundaries for fluid re-simulation
VL - 35
ER -
TY - CONF
AB - We present a computational method for designing wire sculptures consisting of interlocking wires. Our method allows the computation of aesthetically pleasing structures that are structurally stable, efficiently fabricatable with a 2D wire bending machine, and assemblable without the need of additional connectors. Starting from a set of planar contours provided by the user, our method automatically tests for the feasibility of a design, determines a discrete ordering of wires at intersection points, and optimizes for the rest shape of the individual wires to maximize structural stability under frictional contact. In addition to their application to art, wire sculptures present an extremely efficient and fast alternative for low-fidelity rapid prototyping because manufacturing time and required material linearly scales with the physical size of objects. We demonstrate the effectiveness of our approach on a varied set of examples, all of which we fabricated.
AU - Miguel Villalba, Eder
AU - Lepoutre, Mathias
AU - Bickel, Bernd
ID - 1364
IS - 4
TI - Computational design of stable planar-rod structures
VL - 35
ER -
TY - CONF
AB - A memory-hard function (MHF) f is equipped with a space cost σ and time cost τ parameter such that repeatedly computing fσ,τ on an application specific integrated circuit (ASIC) is not economically advantageous relative to a general purpose computer. Technically we would like that any (generalized) circuit for evaluating an iMHF fσ,τ has area × time (AT) complexity at Θ(σ2 ∗ τ). A data-independent MHF (iMHF) has the added property that it can be computed with almost optimal memory and time complexity by an algorithm which accesses memory in a pattern independent of the input value. Such functions can be specified by fixing a directed acyclic graph (DAG) G on n = Θ(σ ∗ τ) nodes representing its computation graph. In this work we develop new tools for analyzing iMHFs. First we define and motivate a new complexity measure capturing the amount of energy (i.e. electricity) required to compute a function. We argue that, in practice, this measure is at least as important as the more traditional AT-complexity. Next we describe an algorithm A for repeatedly evaluating an iMHF based on an arbitrary DAG G. We upperbound both its energy and AT complexities per instance evaluated in terms of a certain combinatorial property of G. Next we instantiate our attack for several general classes of DAGs which include those underlying many of the most important iMHF candidates in the literature. In particular, we obtain the following results which hold for all choices of parameters σ and τ (and thread-count) such that n = σ ∗ τ. -The Catena-Dragonfly function of [FLW13] has AT and energy complexities O(n1.67). -The Catena-Butterfly function of [FLW13] has complexities is O(n1.67). -The Double-Buffer and the Linear functions of [CGBS16] both have complexities in O(n1.67). -The Argon2i function of [BDK15] (winner of the Password Hashing Competition [PHC]) has complexities O(n7/4 log(n)). -The Single-Buffer function of [CGBS16] has complexities O(n7/4 log(n)). -Any iMHF can be computed by an algorithm with complexities O(n2/ log1 −ε(n)) for all ε > 0. In particular when τ = 1 this shows that the goal of constructing an iMHF with AT-complexity Θ(σ2 ∗ τ ) is unachievable. Along the way we prove a lemma upper-bounding the depth-robustness of any DAG which may prove to be of independent interest.
AU - Alwen, Joel F
AU - Blocki, Jeremiah
ID - 1365
TI - Efficiently computing data-independent memory-hard functions
VL - 9815
ER -
TY - CONF
AB - We study the problem of devising provably secure PRNGs with input based on the sponge paradigm. Such constructions are very appealing, as efficient software/hardware implementations of SHA-3 can easily be translated into a PRNG in a nearly black-box way. The only existing sponge-based construction, proposed by Bertoni et al. (CHES 2010), fails to achieve the security notion of robustness recently considered by Dodis et al. (CCS 2013), for two reasons: (1) The construction is deterministic, and thus there are high-entropy input distributions on which the construction fails to extract random bits, and (2) The construction is not forward secure, and presented solutions aiming at restoring forward security have not been rigorously analyzed. We propose a seeded variant of Bertoni et al.’s PRNG with input which we prove secure in the sense of robustness, delivering in particular concrete security bounds. On the way, we make what we believe to be an important conceptual contribution, developing a variant of the security framework of Dodis et al. tailored at the ideal permutation model that captures PRNG security in settings where the weakly random inputs are provided from a large class of possible adversarial samplers which are also allowed to query the random permutation. As a further application of our techniques, we also present an efficient sponge-based key-derivation function (which can be instantiated from SHA-3 in a black-box fashion), which we also prove secure when fed with samples from permutation-dependent distributions.
AU - Gazi, Peter
AU - Tessaro, Stefano
ID - 1366
TI - Provably robust sponge-based PRNGs and KDFs
VL - 9665
ER -
TY - JOUR
AB - Superconductivity in heavy-fermion systems has an unconventional nature and is considered to originate from the universal features of the electronic structure. Here, the Anderson lattice model is studied by means of the full variational Gutzwiller wave function incorporating nonlocal effects of the on-site interaction. We show that the d-wave superconducting ground state can be driven solely by interelectronic correlations. The proposed microscopic mechanism leads to a multigap superconductivity with the dominant contribution due to f electrons and in the dx2−y2-wave channel. Our results rationalize several important observations for CeCoIn5.
AU - Wysokiński, Marcin
AU - Kaczmarczyk, Jan
AU - Spałek, Jozef
ID - 1368
IS - 2
JF - Physical Review B - Condensed Matter and Materials Physics
TI - Correlation driven d wave superconductivity in Anderson lattice model: Two gaps
VL - 94
ER -