TY - JOUR
AB - ATP production requires the establishment of an electrochemical proton gradient across the inner mitochondrial membrane. Mitochondrial uncouplers dissipate this proton gradient and disrupt numerous cellular processes, including vesicular trafficking, mainly through energy depletion. Here we show that Endosidin9 (ES9), a novel mitochondrial uncoupler, is a potent inhibitor of clathrin-mediated endocytosis (CME) in different systems and that ES9 induces inhibition of CME not because of its effect on cellular ATP, but rather due to its protonophore activity that leads to cytoplasm acidification. We show that the known tyrosine kinase inhibitor tyrphostinA23, which is routinely used to block CME, displays similar properties, thus questioning its use as a specific inhibitor of cargo recognition by the AP-2 adaptor complex via tyrosine motif-based endocytosis signals. Furthermore, we show that cytoplasm acidification dramatically affects the dynamics and recruitment of clathrin and associated adaptors, and leads to reduction of phosphatidylinositol 4,5-biphosphate from the plasma membrane.
AU - Dejonghe, Wim
AU - Kuenen, Sabine
AU - Mylle, Evelien
AU - Vasileva, Mina K
AU - Keech, Olivier
AU - Viotti, Corrado
AU - Swerts, Jef
AU - Fendrych, Matyas
AU - Ortiz Morea, Fausto
AU - Mishev, Kiril
AU - Delang, Simon
AU - Scholl, Stefan
AU - Zarza, Xavier
AU - Heilmann, Mareike
AU - Kourelis, Jiorgos
AU - Kasprowicz, Jaroslaw
AU - Nguyen, Le
AU - Drozdzecki, Andrzej
AU - Van Houtte, Isabelle
AU - Szatmári, Anna
AU - Majda, Mateusz
AU - Baisa, Gary
AU - Bednarek, Sebastian
AU - Robert, Stéphanie
AU - Audenaert, Dominique
AU - Testerink, Christa
AU - Munnik, Teun
AU - Van Damme, Daniël
AU - Heilmann, Ingo
AU - Schumacher, Karin
AU - Winne, Johan
AU - Friml, Jirí
AU - Verstreken, Patrik
AU - Russinova, Eugenia
ID - 1346
JF - Nature Communications
TI - Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification
VL - 7
ER -
TY - JOUR
AB - During the past 70 years, the quantum theory of angular momentum has been successfully applied to describing the properties of nuclei, atoms, and molecules, and their interactions with each other as well as with external fields. Because of the properties of quantum rotations, the angular-momentum algebra can be of tremendous complexity even for a few interacting particles, such as valence electrons of an atom, not to mention larger many-particle systems. In this work, we study an example of the latter: A rotating quantum impurity coupled to a many-body bosonic bath. In the regime of strong impurity-bath couplings, the problem involves the addition of an infinite number of angular momenta, which renders it intractable using currently available techniques. Here, we introduce a novel canonical transformation that allows us to eliminate the complex angular-momentum algebra from such a class of many-body problems. In addition, the transformation exposes the problem's constants of motion, and renders it solvable exactly in the limit of a slowly rotating impurity. We exemplify the technique by showing that there exists a critical rotational speed at which the impurity suddenly acquires one quantum of angular momentum from the many-particle bath. Such an instability is accompanied by the deformation of the phonon density in the frame rotating along with the impurity.
AU - Schmidt, Richard
AU - Lemeshko, Mikhail
ID - 1347
IS - 1
JF - Physical Review X
TI - Deformation of a quantum many-particle system by a rotating impurity
VL - 6
ER -
TY - CONF
AB - A drawing in the plane (ℝ2) of a graph G = (V,E) equipped with a function γ : V → ℕ is x-bounded if (i) x(u) < x(v) whenever γ(u) < γ(v) and (ii) γ(u) ≤ γ(w) ≤ γ(v), where uv ∈ E and γ(u) ≤ γ(v), whenever x(w) ∈ x(uv), where x(.) denotes the projection to the xaxis.We prove a characterization of isotopy classes of embeddings of connected graphs equipped with γ in the plane containing an x-bounded embedding.Then we present an efficient algorithm, which relies on our result, for testing the existence of an x-bounded embedding if the given graph is a forest.This partially answers a question raised recently by Angelini et al.and Chang et al., and proves that c-planarity testing of flat clustered graphs with three clusters is tractable when the underlying abstract graph is a forest.
AU - Fulek, Radoslav
ID - 1348
TI - Bounded embeddings of graphs in the plane
VL - 9843
ER -
TY - CONF
AB - Crossing fitness valleys is one of the major obstacles to function optimization. In this paper we investigate how the structure of the fitness valley, namely its depth d and length ℓ, influence the runtime of different strategies for crossing these valleys. We present a runtime comparison between the (1+1) EA and two non-elitist nature-inspired algorithms, Strong Selection Weak Mutation (SSWM) and the Metropolis algorithm. While the (1+1) EA has to jump across the valley to a point of higher fitness because it does not accept decreasing moves, the non-elitist algorithms may cross the valley by accepting worsening moves. We show that while the runtime of the (1+1) EA algorithm depends critically on the length of the valley, the runtimes of the non-elitist algorithms depend crucially only on the depth of the valley. In particular, the expected runtime of both SSWM and Metropolis is polynomial in ℓ and exponential in d while the (1+1) EA is efficient only for valleys of small length. Moreover, we show that both SSWM and Metropolis can also efficiently optimize a rugged function consisting of consecutive valleys.
AU - Oliveto, Pietro
AU - Paixao, Tiago
AU - Heredia, Jorge
AU - Sudholt, Dirk
AU - Trubenova, Barbora
ID - 1349
T2 - Proceedings of the Genetic and Evolutionary Computation Conference 2016
TI - When non-elitism outperforms elitism for crossing fitness valleys
ER -
TY - JOUR
AB - The hippocampal CA3 region plays a key role in learning and memory. Recurrent CA3–CA3
synapses are thought to be the subcellular substrate of pattern completion. However, the
synaptic mechanisms of this network computation remain enigmatic. To investigate these mechanisms, we combined functional connectivity analysis with network modeling.
Simultaneous recording fromup to eight CA3 pyramidal neurons revealed that connectivity was sparse, spatially uniform, and highly enriched in disynaptic motifs (reciprocal, convergence,divergence, and chain motifs). Unitary connections were composed of one or two synaptic contacts, suggesting efficient use of postsynaptic space. Real-size modeling indicated that CA3 networks with sparse connectivity, disynaptic motifs, and single-contact connections robustly generated pattern completion.Thus, macro- and microconnectivity contribute to efficient
memory storage and retrieval in hippocampal networks.
AU - Guzmán, José
AU - Schlögl, Alois
AU - Frotscher, Michael
AU - Jonas, Peter M
ID - 1350
IS - 6304
JF - Science
TI - Synaptic mechanisms of pattern completion in the hippocampal CA3 network
VL - 353
ER -
TY - JOUR
AB - We study the interplay of nematic and superconducting order in the two-dimensional Hubbard model and show that they can coexist, especially when superconductivity is not the energetically dominant phase. Due to a breaking of the C4 symmetry, the coexisting phase inherently contains admixture of the s-wave pairing components. As a result, the superconducting gap exhibits nonstandard features including changed nodal directions. Our results also show that in the optimally doped regime the pure superconducting phase is typically unstable towards developing nematicity (breaking of the C4 symmetry). This has implications for the cuprate high-Tc superconductors, for which in this regime the so-called intertwined orders have recently been observed. Namely, the coexisting phase may be viewed as a precursor to such more involved patterns of symmetry breaking.
AU - Kaczmarczyk, Jan
AU - Schickling, Tobias
AU - Bünemann, Jörg
ID - 1352
IS - 8
JF - Physical Review B - Condensed Matter and Materials Physics
TI - Coexistence of nematic order and superconductivity in the Hubbard model
VL - 94
ER -
TY - JOUR
AB - We characterize absorption in finite idempotent algebras by means of Jónsson absorption and cube term blockers. As an application we show that it is decidable whether a given subset is an absorbing subuniverse of an algebra given by the tables of its basic operations.
AU - Barto, Libor
AU - Kazda, Alexandr
ID - 1353
IS - 5
JF - International Journal of Algebra and Computation
TI - Deciding absorption
VL - 26
ER -
TY - JOUR
AB - Fabrication processes involving anhydrous hydrofluoric vapor etching are developed to create high-Q aluminum superconducting microwave resonators on free-standing silicon membranes formed from a silicon-on-insulator wafer. Using this fabrication process, a high-impedance 8.9-GHz coil resonator is coupled capacitively with a large participation ratio to a 9.7-MHz micromechanical resonator. Two-tone microwave spectroscopy and radiation pressure backaction are used to characterize the coupled system in a dilution refrigerator down to temperatures of Tf=11 mK, yielding a measured electromechanical vacuum coupling rate of g0/2π=24.6 Hz and a mechanical resonator Q factor of Qm=1.7×107. Microwave backaction cooling of the mechanical resonator is also studied, with a minimum phonon occupancy of nm≈16 phonons being realized at an elevated fridge temperature of Tf=211 mK.
AU - Dieterle, Paul
AU - Kalaee, Mahmoud
AU - Fink, Johannes M
AU - Painter, Oskar
ID - 1354
IS - 1
JF - Physical Review Applied
TI - Superconducting cavity electromechanics on a silicon-on-insulator platform
VL - 6
ER -
TY - JOUR
AB - Radiation pressure has recently been used to effectively couple the quantum motion of mechanical elements to the fields of optical or microwave light. Integration of all three degrees of freedom—mechanical, optical and microwave—would enable a quantum interconnect between microwave and optical quantum systems. We present a platform based on silicon nitride nanomembranes for integrating superconducting microwave circuits with planar acoustic and optical devices such as phononic and photonic crystals. Using planar capacitors with vacuum gaps of 60 nm and spiral inductor coils of micron pitch we realize microwave resonant circuits with large electromechanical coupling to planar acoustic structures of nanoscale dimensions and femtoFarad motional capacitance. Using this enhanced coupling, we demonstrate microwave backaction cooling of the 4.48 MHz mechanical resonance of a nanobeam to an occupancy as low as 0.32. These results indicate the viability of silicon nitride nanomembranes as an all-in-one substrate for quantum electro-opto-mechanical experiments.
AU - Fink, Johannes M
AU - Kalaee, Mahmoud
AU - Pitanti, Alessandro
AU - Norte, Richard
AU - Heinzle, Lukas
AU - Davanço, Marcelo
AU - Srinivasan, Kartik
AU - Painter, Oskar
ID - 1355
JF - Nature Communications
TI - Quantum electromechanics on silicon nitride nanomembranes
VL - 7
ER -
TY - JOUR
AU - Barton, Nicholas H
ID - 1356
IS - 1
JF - Genetics
TI - Sewall Wright on evolution in Mendelian populations and the “Shifting Balance”
VL - 202
ER -
TY - JOUR
AU - Barton, Nicholas H
ID - 1357
IS - 3
JF - Genetics
TI - Richard Hudson and Norman Kaplan on the coalescent process
VL - 202
ER -
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 -